College of Health Sciences

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Acceptability and effectiveness of rapid ART initiation: patients’ and healthcare workers’ perspectives.
(2022) Govere, Sabina May.; Chimbari, Moses John.
The Joint United Nations Programme on HIV/AIDS is leading the global effort to end AIDS as a public health threat by 2030. In achieving these goals, emphasis has been on the 95–95–95 targets that by 2030, 95% of people living with HIV know their HIV status. However, the focus is on achieving the second 95 and third 95; having 95% of people diagnosed with HIV initiating on treatment within the expected timeframe and 95% of those on treatment obtaining a suppressed viral load. Commendable efforts have been made in increasing HIV testing numbers however, same day initiation on treatment and achieving viral load suppression remains a challenge. According to the WHO recommendations; same day (ART) initiation should be offered to all people living with HIV following a confirmed diagnosis. This study determined the factors influencing the acceptability and implementation of Universal Test and Treat by both patients and healthcare workers. Universal Test and Treat is a prevention strategy encourages that if a person tests HIV positive, irrespective of the persons CD4 count and clinical staging at the time of testing they will have to begin treatment immediately. Furthermore, patient’s clinical outcomes following test and treat in eThekwini municipality in KwaZulu-Natal were determined. This study was cross-sectional and used prospective - mixed methodology to collect data from 403 patients who either accepted or deferred same day ART initiation from June 2020 to May 2021. A structured questionnaire was used to collect demographic information, sexual behaviour, acceptance of same day ART initiation and knowledge of Universal Test and Treat on the day of HIV diagnosis. Key informant in-depth interviews were conducted with healthcare workers and patients were followed up at 6 months after HIV diagnosis to determine clinical outcomes for both groups, rapid and deferred ART initiators using medical charts and electronic databases. Two different analysis univariate and multivariate logistic regression were performed to examine associations between same day ART initiation and several explanatory factors. Logistic regression was performed to examine associations between same day ART initiation and several explanatory factors, retention in care, clinical outcomes and facility related factors. Thematic analysis was used to assess experiences, knowledge and observations of healthcare workers in implementing the Universal Test and Treat policy. Among the 403 participants same-day initiation was 69.2% (n=279). In an adjusted analysis (age, gender, level of education were adjusted at 0.5 significance level in univariate level) number of sexual partners (aOR: 0.35; 95% CI: 0.15-0.81), HIV status of the partner (aOR: 5.03; 95% CI: 2.74-9.26), knowledge of universal test and treat (aOR: 1.97; 95% CI: 1.34-2.90), support from non-governmental organizations (chi-square = 10.18; p-value= 0.015 and provision of clinic staff (chi-square = 7.51; p value = 0.006) were identified as major factors influencing uptake of same-day ART initiation. In the bivariate analysis; gender (OR: 1.672; 95% CI: 1.002–2.791), number of sexual partners (OR: 2.092; 95% CI: 1.07–4.061), age (OR: 0.941; 95% CI: 0.734–2.791), ART start date (OR: 0.078; 95% CI: 0.042–0.141) and partner HIV status (OR: 0.621; 95% CI: 0.387–0.995) were significantly associated with viral load detection and retention in care. (All variables that were significant at e.g. 0.5 level in univariate). Our results suggest a steady increase in uptake of same day ART initiation with poor retention in care. The results also emphasise a vital need to not only streamline processes to increase immediate ART uptake further but also ensure retention in care in order to meet the 95-95-95 targets. The findings of the study contribute to knowledge useful for strengthening rapid ART initiation implementation by considering individual patient factors, healthcare workers’ perspectives and facility level factors. The qualitative findings revealed variations in UTT knowledge, experiences and observations among diverse healthcare workers from the four clinics in different geographical settings. While training on UTT and SDI of ART initiation was conducted at the inception of the implementation phase, the understanding and interpretation varied especially between clinicians and non-clinical healthcare providers. Denial, feeling healthy, fear of disclosure, limited knowledge about ART, fear of ART side effects, fear of stigma and discrimination were some of the factors HCW observed as hindering uptake of SDI. These findings relate to some of the reasons given by patients with fear of disclosure frequently mentioned by those who deferred SDI of ART.
An investigation into kojic acid-associated mitochondrial toxicity and inflammation in melanoma cells (SK-MEL-1) = Uphenyo ku-esidi yekojiki ehlobaniswa nokukhinyabezeka kwemayithokhondriya nokuvuvukala ezinhlayiyeni zemelanoma (SK-MEL-1).
(2023) Suritham, Tamzin Kimera.; Chuturgoon, Anil Amichund.; Ghazi, Terisha.
ojic acid (KA), 5-hydroxy-2-(hydroxymethyl)-4H-pyran-4-one, is used in agriculture, food, and cosmetics. KA is known to have antimicrobial, antifungal, antioxidant, and anti-inflammatory properties. The cosmetic industry's increasing interest in KA is due to its ability to inhibit tyrosinase activity resulting in skin lightening. The mitochondria play a key role in maintaining homeostasis and ensuring efficient melanin production. Therefore, mitochondrial dysfunction has severe effects on the skin. This study investigates mitochondrial stress, antioxidant responses, protein kinase signalling and inflammation in human melanoma (SK-MEL-1) cells. The mitochondria are important in processing metabolites and supplying the cell with energy in the form of ATP. KA interacts with key mitochondrial homeostasis proteins. Our results found an increase in macromolecule damage specifically lipid peroxidation and protein oxidation. Due to oxidative conditions, increased Nrf2 expression was observed. LON protease is ATP-dependent and regulated by Sirtuin 3 expression. Mitochondrial function was affected illustrated by decreased ATP production leading to decreased LON protease and Sirtuin 3 protein expression. Following increased oxidative stress, KA suppressed the expression of protein kinases but increased inflammatory mediators. There was decreased expression of phospho-Akt, Akt, phospho-GSK3β, p38 and ERK1/2. The mediation of the NLRP3 inflammasome involves priming and activation. At concentrations with high proliferation, NFκB gene and protein expression was activated. The protein kinase signalling pathways are known as mediators of inflammation; however, protein and gene expression of inflammatory mediators was increased following KA treatment. The inflammasome was subsequently activated as shown by an increase in intracellular caspase 1 levels as well as NLRP3, ILβ and IL-6 expression. KA induced mitochondrial stress and suppressed mitochondrial homeostasis proteins. The increased Nrf2 expression could have further downregulated LON protease expression and increased macromolecule damage. Oxidative conditions could have activated the inflammasome pathway independent of protein kinase signalling. In conclusion, KA displayed mitochondrial toxicity following acute exposure by suppressing mitochondrial homeostasis, protein kinase pathways and initiating inflammation. Iqoqa. I-esidi yeKojic (KA), 5-hydroxy-2-(hydroxymethyl)-4H-pyran-4- eyodwa, iyasetshenziswa kwezolimo, ekudleni nasezimonyweni. I-KA yaziwa ngokuba ne-antimicrobial, antifungal, antioxidant, nezinto ezibanga ukuvuvukala. Luyakhula uthando lwezimboni zezimonyo ekuthandeni i-KA ngenxa yobukhona bayo ukuphazamisa ukusebenza kwetyrosinase okuholela ekutheni isikhumba sibe mhlophe. Kunokumqoka kakhulu okwenziwa imayithokhondriya ekugcineni usimamisoluzinzo lobunjalomzimba nokuqinisekisa ukukhiqizwa okwanele kwemvikelambala, imelanin. Ngakho ke, ukungasebenzi kwemayithokhondriya kunemithelela emibi esikhunjeni. Lolu cwaningo luphenya ngengcindezi yemayithokhondriya, ukusebenza kwe-antioxidant, ukukhombisa iphrotheyini khinasi nokuvuvukala kwezinhlayiya (SK-MEL-1) zemelanoma yomuntu. Imayithokhondriya ibalulekile ekuqhubeni umsebenzi wokugaya ukudla nokunika inhlayiya amandla ayisimo se-ATP. I-KA iyahlangana namaphrotheyini asemqoka osimamisoluzinzo lobunjalomzimba bemayithokhondriya. Imiphumela yethu yathola kukhula ukulimala emolekhiyulini enkulu okuyiliphidi iphreroksideyishini nokuncipha kwezinhlayiyabugesi ezihambayo zamaphrotheyini. Ngenxa yezimo zokuncipha kwezinhlayiyabugesi ezihambayo, kwabhekwa ukukhula kokuziveza kweNrf2. Okubalulekile empilweni nasekusebenzeni kwezinhlayiya, kuyi-LON, I-LON phrothizi kuncike kuyi-ATP futhi kulawulwa ukuziveza kweSirtuin 3. Umsebenzi wemayithokhondriya kwaphazamiseka kwaboniswa ukuncipha komkhiqizo we-ATP okwaholela ekuncipheni kweLON phrothizi nokuziveza kwephrotheyini iSirtuin 3. Ukulandela ukukhula kwengcindezi yokuncipha kwezinhlayiyabugesi zamaphrotheyini, i-KA yacindezela ukuziveza kwephrotheyini yekinases kodwa kwakhulisa ukuvuvukala kwezixhumanisi zengxube ezihlanganisayo. Kwaba nokuncipha kokuziveza kwephospho-Akt, i-Akt, i-phospho-GSK3β, i-p38 a ne-ERK1/2. Isihlanganisi seNLRP3 inflammasome sibandakanya ukulungiselela nokukhuthaza. Kusilinganisobungako esineproliferation ephezulu, ukuziveza kofuzo lweNFκB kanye nephrotheyini kwakhuthazeka. Ukukhombisa izindlela kwephrotheyini ikinase kwaziwa ngokuthi ukuvuvukala kwezixhumanisi; nokho, ukuziveza kwezixhumanisi zamaphrotheyini nawofuzo avuvukele kwakhula kulandela ukwelashwa kweKA. I-inflammasome yakhuthazwa njengoba yayiboniswa ngokukhula kwamazinga loku-1 lezinhlayiya zokufanayo kwecaspase nokuziveza kweNLRP3, i--β ne- IL-6. I-KA iletha ingcindezi yemayithokhondriya ibuye icindezele amaphrotheyini osimamisoluzinzo lobunjalomzimba bemayithokhondriya. Ukukhula kokuziveza kweNrf2 bekungeza ukwehlisa ukulawulwa kokuziveza kweLON phrothizi nokukhula kokulimala kwemolekhiyuli enkulu. Izimo zokuncipha kwezinhlayiyabugesi ezihambayo ngabe kukhuthaze izindlela ze-inflammasome ezizimele ezikhombisa iphrotheyini yekhinasi. Ucwaningo lwaphetha ngokuthi i-KA yabonisa ubuthi bemayithokhondriya kulandela ukungavimbeki kwabo okunamandla ngokuthi bucindezele usimamisoluzinzo lobunjalomzimba lwemayithokhondriya, izindlela zephrotheyini khinasi nokuqala kokuvuvukala.
An investigation on the effects of a rhenium (V) compound with uracil-derived ligands on markers associated with hepatic, cardiovascular and renal complications in diet-induced prediabetic rats = Ucwaningo ngemiphumela yerhenium (V) compound ene-uracil ezifweni eziyamene nesibindi, inhliziyo kanye nezinso emagundaneni ayedla kodwa esengcupheni yesifo sikashukela.
(2023) Siboto, Angezwa.; Khathi, Andile.; Ngubane, Phikelelani Siphosethu.; Sibiya, Ntethelelo Hopewell.
Prediabetes is a metabolic disorder that often precedes the onset of type 2 diabetes mellitus. This development of this asymptomatic condition is associated with chronic consumption of high calorie diets and sedentary lifestyles. Prediabetes results in decreased insulin sensitivity in the peripheral tissues resulting in elevated blood glucose levels that are not high enough for a diagnosis of type 2 diabetes. This moderate hyperglycaemia has been shown to lead to trigger complications such as non-alcoholic fatty liver disease, renal dysfunction and cardiovascular disease which are generally only diagnosed during type 2 diabetes. The current management strategy for prediabetes consists of a combination of pharmacological and lifestyle intervention. The pharmacological agents such as metformin while lifestyle intervention involves dietary modification to lower calorie diets. Studies show that prediabetic patients tend to be more dependent pharmacological intervention and struggle with changing diets thus lowering the efficacy of drugs such as metformin. This often leads to the eventual development of prediabetes. Therefore, there is a need for new pharmacological agents that can remain effective in both the presence and absence of dietary intervention. In our laboratory we have synthesised a novel rhenium (v) compound with uracil-derived ligands that has shown promising biological activities that include anti-hyperglycaemic effects in diet-induced prediabetic rats. This compound was shown to improve insulin sensitivity in peripheral tissues in prediabetic rats. To advance from this knowledge, this study sought to investigate the effects of the rhenium (V) compound with uracil-derived ligands on markers associated with hepatic, cardiovascular and renal complications in diet induced prediabetic rats model. Iqoqa. Isendlalelo: Iziguli ezisengcupheni yokungenwa yisifo sikashukela zibhekene nokuba sengcupheni yokungenwa yizifo ezinhlobonhlobo, okubalwa kuzo isifo sesibindi, isifo senhliziyo, kanye nokulimala kwezinso ngenxa yesifo sikashukela. Uma sesihlahliwe isifo, indlela ephakanyiswayo ibandakanya ukuxutshwa kokwelapha ngemithi kanye nokushintsha indlela yokuphila. Kodwa-ke, kunenkinga eqoshwe phansi yokwahluleka kweziguli ezihluphekayo ukugcina imithetho eyamene nendlela yokudla, bagxile kakhulu ekusebenziseni imithi, okuholela ekutheni imithi ingasebenzi kahle. Ngenxa yalokhu, kunesidingo semithi emisha ezokwazi ukwelapha ngempumelelo ngisho indlela yokudla ingashintshiwe. Lolu cwaningo luhlose ukuhlola umthelela werhenium (V) compound ene-uracil-derived ligands kwabaqokiwe asebecishe bangenwe ushukela, kubhekwa kokubili ukuba khona nokungabi khona kokungenelela ngokudla. Izindlela zokuqhuba ucwaningo: Amagundane ajovwa ngeprediabetes ewuhlobo oluhlala amasonto angama-20 anomsoco wamafutha kanye nezinikamandla. Emuva kokujovwa, amagundane aqokwa ngokuwola afakwa ekulashweni ngemithi ehlukahlukene. Ajovwa ngerhenium (V) compound elinganiselwa ku-15 mg/kg kanye ngosuku, njalo ngosuku lwesithathu Isikhathi esingamasonto ayi-12, kunganakwa ukuthi uhlobo lokudla kunjani. Imiphumela: Engxenyeni yokuqala (1), ukujovwa ngerhenium (V) compound kwadala ukulapheka kwesibindi, ukunonophala komzimba kanye nokwakheka kwamafutha. Okokugcina, lokhu kwelashwa kwavimbela ukonakala kwesibindi okwafakazelwa ukwehla kwama-enzyme biomarkers esibindi. Engxenyeni yesibili (2), ukusebenzisa irhenium (V) compound kwadala ukwehla kokhwantalala kanye namapro-inflammatory cytokines markers. Lokhu kwehla kwayamaniswa nokwehla kwamazinga amatriglycerides anesisindo samafutha esiphansi. Ngaphezu kwalokho, kwaba nokubuyela esimweni kokukhiqizwa kwamafutha anesisindo esiphezulu kulawo magundane afakwa irhenium (V) compound. Engxenyeni yesithathu (3), ukusebenza kwezinso kwabuyela esimweni, okwabonakala ngokwenyuka kweGRF nokwehla kweKIM 1, ipodocin ne-aldosterone. Irhenium (V) compound yathuthukisa ukusebenza kwezinso ngokuvimbela ukhwantalala oluyamene nokwehla kukashukela ezinsweni kukona kokubili ukuba khona nokungabi bikho kokushintsha indlela yokudla. Isiphetho: Imiphumela yakhombisa ukuthi irhenium (V) compound yaphumelela ukuvikela isibindi nezinso, kanti yathuthukisa ukusebenza kwenhliziyo kulawo magundane ayejovwe ngeprediabetic enokudla. Yize kunjalo, lusadingeka ucwaningo oluzocacisa kabanzi ngokusebenza nokulethwa kwemiphumela yalo muthi.
Analyzing and strengthening the clinical support of undergraduate midwifery students and developing a mentorship training program at a higher education institution in KwaZulu-Natal, South Africa: a mixed method and action research design.
(2022) Amod, Hafaza Bibi.; Mkhize, Sipho Wellington.
The competence of midwifery students is highly dependent on the quality of clinical support they receive during clinical placement. Offering support and training to midwifery practitioners, who supervise students during placement, is necessary in South Africa. This study aimed to analyze and strengthen the clinical support of undergraduate midwifery students, and develop a mentorship-training program. This study adopted a mixed-method and action research approach incorporating a descriptive and exploratory design. A convenient and purposive sampling technique, multiple research tools (systematic scoping review protocol, questionnaires, interviews and focus groups), and three different study populations (60 midwifery students, 28 practitioners and 10 educators) complimented the aim of conducting a mixed-methods study. Data collection commenced for Cycle 1 in May 2019 and concluded with Cycle 4 in April 2022. Quantitative data was inserted into SPSS version 27 for descriptive and comparative analysis whilst qualitative data used a thematic content analysis approach. Cycle 1 results highlighted that 93% of students had support from midwifery practitioners and found that the clinical placement benefitted their learning outcomes. Although students received three types of clinical support, namely clinical supervision, mentorship and preceptorship, 80% of clinical support was clinical supervision. Postclinical placement, students were incompetent in 11.4% of their clinical requirements. In Cycle 2, a two-round Delphi method evaluated the quality of a mentorship-training program using midwifery experts in round 1 and midwifery practitioners in round 2. There was an overall quality score achieved of 81% round 1 and 96% in round 2. In Cycle 3, three themes emanated from the focus group discussions. Mentorship training was a new phenomenon, empowered mentorship abilities, and an investment toward midwifery leadership. Interview results showed that the mentorship training program was a new, well-structured and valuable program; a refresher course for midwifery clinical practitioners and educators, adequate to support midwifery practitioners in their mentorship roles and responsibilities, and produced recommendations for midwifery practice and education. Mentorship during clinical placement is likely to strengthen the clinical support of midwifery students. A mentorship training program for midwifery practitioners developed in this study is valuable to midwifery educators and practitioners in South Africa.
Challenges in developing and integrating community clinical psychology services in non-urban areas of KwaZulu-Natal = Izinselelo ekuthuthukiseni kanye nokuhlanganisa imisebenzi yesayikholoji yezifo zengqondo emphakathi osezindaweni zasemakhaya KwaZulu Natali.
(2023) Siyothula , Evy-Terressah Busisiwe.; Pillay , Anthony Lingum.
The World Health Organization continues to encourage the integration of mental health services into primary health care. Primary health care was identified as a means to facilitate community access to health services closer to where people live. In this thesis, the researcher explores the progress (or lack of progress) in developing and integrating community clinical psychology services in the non-urban areas of KwaZulu-Natal (KZN), South Africa, in response to the World Health Organization’s call to invest in the integration of mental health services into primary health care. The researcher explored the clinical psychology integration process from different perspectives, namely, the distribution of clinical psychology services in non-urban areas of KwaZulu-Natal and the clinical psychologist-population ratio, the experiences and views of clinical psychologists and health care providers working in non-urban areas, as well as non-urban service users' mental health knowledge and preferences when they receive clinical psychology services. A mixed-method study design using quantitative and qualitative research approaches was utilised to provide a broader perspective of integrating clinical psychology services in non-urban areas of KZN. The first two studies of the present research were published in the local psychology journal. The third study, which documented the experiences of clinical psychology services by other health professionals working in KZN non-urban areas, was submitted for publication, and the last study, which documented mental health knowledge and clinical service preferences of KZN non-urban service users, is in manuscript format, ready for journal submission. The first three studies highlighted inequitable distribution and inadequate mental health resources, particularly focusing on clinical psychology services, between the urban and non-urban areas of KZN. Both the clinical psychologists and other health care providers expressed the need for training and access to information that empowers them to work confidently in resource-constrained settings. The fourth study highlighted service users’ priority focus on receiving clinical psychology services with less concern over demographic preferences (in terms of the clinical psychologists’ age, gender or language) when consulting clinical psychologists. Iqoqa. Inhlangano yezizwe yezempilo iyaqhubeka nokugqugquzela ukuhlanganiswa kwemisebenzi ephathelene nempilo yengqondo ukuba inikezwe usizo lokuqala. Unakekelo lokuqala lwezempilo lwahlonzwa njengento yokwenza ukuba umphakathi uhlomule emisebenzini yezempilo eseduze lapho behlala khona. Kulo mqulucwaningo, umcwaningi uphenya inqubekela phambili ekuthuthukiseni nokuhlanganisa imisebenzi yesayikholoji yezifo zengqondo emphakathini ezindaweni zasemakhaya KwaZulu-Natali, eNingizimu Afrika, ukuphendula okucelwa inhlangano yezizwe kwezempilo ngokuba kutshalwe ekuhlanganisweni kwemisebenzi yezengqondo ukuba usizo lokuqala lokunakekela kwezempilo. Umcwaningi uphenya indlela okuhlanganiswa ngayo imisebenzi yesayikholoji yezifo zengqondo ngokwemibono eyahlukene, njengokuhanjiswa kwemisebenzi yesayikholoji yezifo zengqondo ezindaweni ezisemakhaya KwaZulu-Natali kanye nenani lomphakathi wezazi zesayikholoji, ulwazi lwakamuva kanye nemibono yochwepheshe balo mkhakha wobusayikholoji kanye nabahlinzeka ngonakekelo lwezempilo abasebenza ezindaweni zasemakhaya, kanye nabasemakhaya abasebenzisa ulwazi lwengqondo ngezempilo kanye nokukhetha ngesikhathi bethola imisebenzi yesayikholoji yezifo zengqondo. Ucwaningo oluyisifanekisomumo esindlelangxube olusebenzisa Izindlelakwenza zocwaningo oluyikhwantithethivu kanye noluyikhwalithethivu lwasetshenziswa ukunikeza umbono obanzi ekuhlangnisweni kwemisebenzi yesayikholoji yezifo zengqondo ezindaweni zasemakhaya KwaZulu-Natali. Ucwaningo olubili lokuqala lwalolu cwaningo lwashicilelwa ejenelini yesayikholoji. Ucwaningo lwesithathu, olwaqopha ulwazi lwakamuva lemisebenzi yesayikholoji yezifo zengqondo ngabanye bezisebenzi bezempilo abasebenza emakhaya aKwaZulu-Natali, kwahanjiswa ukuze kushicilelwe, kanye nocwaningo lokugcina olwaqapha ulwazi ngezempilo zengqondo kanye nemisebenzi yesayikholoji yezifo zengqondo okukhethwe abantu abalusebenzisayo basemakhaya aKwaZulu-Natali isesesimweni somqulu ongakashicilelwa. Izifundo ezintathu zokuqala zigqamisa ukungasatshalaliswa ngokulinganayo kanye nokunganeli kokusetshenziswa kwezempilo ezithinta ingqondo, ikakhulukazi okubhekene ngqo nemisebenzi yesayikholoji, phakathi kwabasezindaweni zasemadolobheni nezasemakhaya KwaZulu-Natali. Kokubili izifundangqondo zezifo zengqondo kanye nabahlinzeka ngonakekelo lwezempilo, baphefumula ngesidingo soqeqesho kanye nokuthola ulwazi olubanikeza amandla okuba basebenze ngokuzethemba ezizindeni ezintula izinsizakusebenza. Ucwaningo lwesine lugqamisa abamukela usizo ngokugxila ekutholeleni imisebenzi yesayikholoji yezifo zengqondo ngaphandle kokunaka izibalo ezincamela (ikakhulukazi ubuchwepheshe bengqondo ngokweminyaka yokuzalwa, ubulili nolimi) ngesikhathi bebonana nezifundangqondo zezifo zengqondo.
Coevolution of mutations in HIV-1 ENV and GAG-PR genes: implications for the development of protease inhibitors resistance.
(2023) Maphumulo, Ntombikhona Fortunate.; Gordon, Michelle Lucille.
Cross-resistance in PIs-exposure has been reported to be driven by Gag, however recent studies suggest Env also contributes to PIs resistance. Although studies have reported gp41 mutations in PI failures, the impact of the full-length Env on PI resistance remains unclear. We investigate the prevalence of subtype C Env mutations in patients failing PIs, the coevolution of Env mutations with Gag-PR mutations and determine whether mutations in gp120 as a result of PI resistance, affect coreceptor usage. Lastly, determine the structural changes in the Env during PI failure. The study used generated sequences from subtype C infected patients failing LPV/r inclusive treatment and HIV-1 subtype C drug-naïve sequences downloaded from the Los Alamos HIV database to compare the frequency of Env mutations in patients failing LPV/r. Bayesian network probability was applied to determine the relationship between mutations occurring within the Env and Gag-PR regions and LPV/r treatment. Furthermore, Los Alamos sequence database tools, Geno2Pheno[coreceptor], and Molecular dynamics simulations were used to demonstrate structural changes and to understand how gp120 mutations affect co-receptor usage. Lastly, Molecular dynamics simulation followed by Ring server was used to determine the structural changes caused by mutations in gp41, and gag mutations, and to look for interaction (hydrogen bond contact and VDW) between mutations and the nearby residues. Thirty-five mutations in the Env region had significantly higher frequencies in LPV/r treated patients. Env mutations were shown to coevolve with Gag-PR and they form a potential pathway to LPV/r resistance. Gp120 sequences from the PIs treated patients showed to modulate viral entry by protecting the virus from antibody recognition through the increased length in V1/V2 and V5 variable loops and the number of N-glycosylation sites observed in VI/V2. Results further showed that gp120 mutations could modulate viral entry through coreceptor switching induced by a higher charge in the V3 region, mutations in coreceptor-specific sites, and those that interact with the coreceptor binding site. Three mutations in gp41 (D632E-HR2, I688-TM, and P724Q/S-CT) were shown to influence folding by stabilizing the β-turns in their respective regions. Env coevolution with Gag-PR (mainly MA and CA) was shown through the pathway to LPV/r resistance. The gp120 mutations were also shown to contribute to viral entry through coreceptor usage and immune escape, while gp41 and Gag mutations played a role in stabilizing the α-helices which might influence the fusion of the virus. Further investigations using site-directed mutagenesis are needed to determine the effect of mutations on replication capacity. Iqoqa. Isingeniso Ukungezweli okuthelelanayo ekuvezekeni kwama-PIs kwabikwa ukuthi kuphushwa yi-Gag, kodwa ucwaningo olusanda kwenziwa luphakamisa ukuthi i-Env inomthelela ekungazweleni kwama-PIs. Nakuba ucwaningo lubike izinhlobo ze-gp41 ekwehlulekeni kwe-PI, umthelela wobude obuphelele be-Env ekungezwelini kwe-PI kuhlezi kungacacile. Siphenya ukwanda kwezinhlobo eziyisubtype C envelope nezinhlobo ze-Gag-PR nokuhlonza ukuthi izinhlobo kwi-gp120 njengomphumela wokungezweli kwe-PI, okunomthelela wokusetshenziswa kwesisizisemukeli. Okokugcina, ukuhlonza ushintsho lwesakhiwo emvilophini ngesikhathi sokwehluleka kwe-PI. Izindlelakwenza zocwaningo Ucwaningo lwasebenzisa ukulandelana okwenziwe lususelwa ezigulini ezitheleleke ngesubtype C okwehluleka kokwelapha okufaka konke kwe-LPV/r kanye ne-HIV-1 subtype C nokulandelana okungezwani nemithi yokwelapha okudawunilodwe kwisizindalwazi seLos Alamos HIV ukuqhathanisa nezikhawu zezinhlobo ze-Env ezigulini ze-LPV/r eyehlulekayo. Ukuba khona kobuxhakaxhaka beBayesian basetshenziswa ukuhlonza ubudlelwane phakathi kwezinhlobo ezenzeka kwi-Env nezindawo ze-gag-PR nemithi yokwelapha i-LPV/r. Ngaphezu kwalokho, izisetshenziswa zesizindalwazi zokulandela zeLos Alamos, i-Geno2Pheno[coreceptor], nezinhlobo zamadayinamikhi amamolekhyuli asetshenziswa ukuveza ushintsho lomumo nokuqonda ukuthi izinhlobo zama-gp120 nokunomthelela ekusetshenzisweni kwesisizisemukeli. Okokugcina, uhlobo lokwehluka kwamamolekhyuli lulandelwa yi-Ring server yasetshenziswa ukuhlonza ushintsho lomumo oludalwe yizinhlobo zakwi- gp41, nezinhlobo ze-gag, nokubheka ukuxhumana (ukuthintana nokuxhumana nehayidrojini ne-VDW) phakathi kwezinhlobo nezinsalela eziseduze. Imiphumela Izinhlobo ezingamashumi amathathu nanhlanu esifundeni se-Env yaba nezivuvabakwenzeka eziphezulu ezigulini ezelashelwa i-LPV/r. Izinhlobokuxetshulwa ze-Env zakhonjiswa njengeziguquke ne-Gag-PR nokwakha indlela engaba khona ukumelana ne-LPV/r. Ukulandelana kwe-Gp120 ezigulini ezelashelwa ama-PIs kwakhombisa ukuguqulela ukungena kwegciwane ngokuvikela igciwane ekubonakaleni emasosheni omzimba ngobude obunwetshiwe kumavariyebhuli e- V1/V2 ne-V5 kanye nenombolo yezindawo ze-N-glycosylation ezibhekwe kwi-VI/V2. Imiphumela iphinde yakhombisa ukuthi izinhlobo ze-gp120 engaguqula ukungena kwegciwane ngokuguqula okudalwa yisisizisemukeli equbuka kakhulu endaweni eyi-V3, izinhlobo zezindawo yezisizizemukeli eziqondile, nalezo ezisebenzisana nendawo efaka nesisizisemukeli. Izinhlobo ezintathu kwi-gp41 (D632E-HR2, I688-TM, ne-P724Q/S-CT) zakhombisa ukuba nomthelela ngokusimamisa ama-β-turns ezindaweni zawo. Isiphetho Lolu cwaningo luphakamisa ukuthi i-gp120 iqhube ngendlela engaqondile ukusebenza ngokungezweli kwe-PI ngokuthola izinhlobo eziphakamisa ubude be-V1/V2, njengomphumela yenyusa inani jikelele lezindawo ze-N-glycosylation, kanjalo nokwenyuka nokushaja okuphelele kwi-V3. Ngale ndlela, lezi zinhlobo zenza ukungena kwegciwane ngokuputshuka kwamasosha, nokuhambisa uguquko emagciwaneni e-CXCR4 okungaphucula ukuziphindaphinda kwegciwane. Ngaphezu kwalokho, izinhlobo ze-gp41 ezibikwe kulolu cwaningo zithinta ukuziguquguqukela kwephrotheyni. Ekugcineni, izinhlobo ze-Env zifaka isandla ekungezwelini komuthi we-PI ngokuguquka nezinhlobo kwi-Gag ezaziwa ngokufaka isandla ekwehlulekeni kwe-PI nokuchibiyela ukulahlekelwa amandla kwegciwane, okuveza ukuthi kunokusebenzisana phakathi kwamasosha nokuphakama kokungezweli komuthi.
Comparative study of covalent & non-covalent drug inhibitory mechanism investigation: targeting HSP72 protein in cancer therapy using molecular modelling techniques.
(2021) Aljoundi, Aimen Khalefa Misbah.; Soliman, Mahmoud Elsayed Soliman.
Cancer is the most complicated and diverse disease that has been menacing human beings worldwide. Up to date, important advancement has been done to improve the existing therapeutic interventions in the treatment and management of cancer. However, the side effect of these drugs that are mostly associated with the “off-target” effects is a perpetual failure in cancer drug development. Therefore, efficient regimen with minimal toxicities and high drug target selectivity should be achieved. Covalent inhibition is an emerging field in drug discovery and a very distinct category of therapeutics that reduces adverse side effects and possible interactions that lead to drug resistance due to its attainable reactivity and high selectivity. The Heat shock proteins (HSPs) play a crucial role in the clearance of damaged proteins by encouraging proteotoxicity and proteins acclamation. This process occurs by avoiding unsuitable stress-induced protein aggregation, ensure suitable refolding of denatured proteins, and promoting their degradation; thus, the involvement of this enzyme in many human diseases, including cancer. In this study, we delve into the structural features of one of the most crucial enzymatic targets of the stress proteins, the Heat shock proteins72. In drug development, the integration of computational techniques including molecular dynamic simulations, docking and molecular modelling has allowed drug developers to screen and syntheses millions of compounds and thus screen out possible lead drugs. Computer-Aided Drug Design has been validated as a cost-effective strategy to fast trace the drug discovery process due to these in silico methods. One of the characteristics of the HSP72 is its ability to be targeted either covalently or non-covalently through small drug molecules. Therefore, the above-mentioned methods, amongst several other computational tools were employed out in this study to provide insights into conformational changes that explain potential covalent and non-covalent inhibitory mechanisms, binding sites assessment features leading to promising small molecule inhibitor candidates. These combinatorial computational studies offer an inclusive in silico perspective to fill the gap in drug design studies about targeting protein degradation, thus providing insights toward the structural characteristics of the pivotal target and describing promising drug developments.
Concurrent treatment of in vitro cell lines with uthuli lwezichwe™, an African traditional medicine used in the management of diabetes mellitus in KwaZulu-Natal, with conventional treatments and their effects on glucose uptake and insulin secretion.
(2022) Hlatshwayo, Sphamandla.; Ngcobo, Mlungisi.; Gqaleni, Nceba.
Background: By the year 2025, prevalence of diabetes mellitus is estimated to reach 300 million globally; with type 2 diabetes mellitus comprising more than 90% of these cases. Due to the side effects which are sometimes adverse and gradual loss of efficacy with time, presented by conventional regimens; a number of diabetic patients have been reported to be using both traditional medicines and conventional regimens concurrently. Experimental and clinical experiments have yielded positive results on studies performed on conventional treatments in combination with traditional medicines and medicinal plant extracts. Most these studies have been performed using a single medical plant, whilst African traditional medicine (ATM) products constitute of a variety of medical plants. Aim: This study aimed to investigate the concurrent treatment of in vitro cell lines with Uthuli Lwezichwe™, an African traditional medicine used in the management of diabetes mellitus in KwaZulu-Natal, in combination with conventional treatments and their effects on glucose uptake and insulin secretion. Methods: Cell viability was used to establish the IC50 doses of Uthuli Lwezichwe™ for HepG2 liver, C2C12 muscle and RIN-5 pancreatic beta cell lines. The IC50 doses were used in combination with known effective doses of metformin, insulin and tolbutamide to treat liver, skeletal muscle and beta cells, respectively. Glucose uptake was monitored at 0, 6, 12 and 24 h time intervals. Changes in glycogen and glutathione (GSH) levels in treated liver cells were evaluated using a glycogen assay kit (MAK0160) and GSH Glo glutathione kits, respectively. Insulin secretion in treated pancreatic cells was assessed using an ultra-sensitive rat insulin ELISA kit. Results: In comparison to the untreated control, treatment with Uthuli LwezichweTM in combination with conventional drugs significantly increased (p<0.05) increased insulin secretion in comparison to all treatment groups. Conclusion: Interaction of anti-diabetic agents studied, resulted in ameliorated glucose metabolism, both via glucose uptake and insulin secretion. This could be beneficial both in modulating diabetes mellitus and its comorbidities.
Contraceptive use among adolescent girls in Zambia: a study on adolescents’ needs, preferences and perspectives on contraception methods=Ukusetshenziswa kwezivimbelakukhulelwa ngamantombazane angamatshitshi eZambia: Ucwaningo ngezidingo zamatshitshi, okukhethwayo nemibomo kwezindlela zezivimbelakukhulelwa.
(2023) Chola, Mumbi.; Ginindza, Themba Geoffrey.; Hlongwana, Khumbulani Welcome.
The fertility rate in Africa is among the highest in the world, and this trend is projected to continue unless drastic interventions are put in place to avert the situation. Contraceptive use among adolescents in sub-Saharan Africa remains very low despite various interventions to improve the uptake. The study aimed to examine the key determinants of contraceptive use among adolescent girls in Zambia; specifically, i) examining patterns, trends and factors that drive poor usage of contraceptives; ii) exploring the motivators and influencers of decision-making regarding contraceptive use among adolescent girls; and finally, iii) understanding their perspectives on existing contraceptive methods. The study examined patterns, trends and factors associated with contraceptive use among adolescents in Zambia, using data from 1996, 2001/2, 2007 and 2013/14 Zambia Demographic and Health Surveys. Qualitative data was collected through focus group discussions and analysed using thematic analysis. Permission to conduct the study was obtained from the Ministry of Health and the National Health Research Authority. Ethical approvals were provided by the Biomedical Research Ethics Committees (BRECs) of the University of Zambia and the University of KwaZulu-Natal in South Africa. Results revealed that contraceptive use among adolescent girls in Zambia remained low over the 18 years and increased by only 3%, particularly among younger, uneducated, and unmarried sexually active adolescent girls. Marriage or living with a partner contributed the most to the change in contraceptive use (44%), while living in a rural area accounted for approximately 20%. Adolescent girls' experience with contraceptives was affected by various factors such as knowledge of contraceptives, including sources of information and contraceptives, experience with using contraceptives, challenges with access to contraceptives, and misconceptions about contraceptives. The interaction of factors related to their personal experience, their community and the environment in which they access contraceptive services all contribute to the overall patient experience and influence the adolescent girls’ contraceptive decision. Most of the motivators for the use and/or non-use of contraceptives are intrapersonal and interpersonal. Contraceptive use among adolescent girls remains low and is determined by various factors. Key influencers and motivators for contraceptive use involve people in their lives, such as partners, family and community members. Interventions targeting increasing demand, access and use of contraceptives among adolescents must be innovative, participatory and implemented within the context of local cultural norms. IQOQA Izinga lokuvunda e-Afrika libalelwa kweliphezulu emhlabeni wonke, futhi le nkombamvama ihlelelwe ukuqhubeka ngaphandle uma kunokungenelela okunamandla okumele kufakwe ukuze kugwenywe isimo. Izimvimbelakukhulelwa ezisetshenziswa phakathi kwamatshitshi ase-Saharan Africa ziyohlala ziphansi ngale kokungenelela okwahlukene ukuze kuthuthukiswe lokho okukhona okuzosetshenziswa. Ucwaningo lwaluhlose ukuhlola izinkombamthelela ezisemqoka zokusetshenziswa kwezivimbelakukhulelwa phakathi kwamantombazane eZambia; ngokucacile i) ukuhlola izinhlelo, izinkombamvama noma izinto eziqhuba ukusetshenziswa kabi kwezivimbelakukhulelwa; ii) ukuhlola abagqugquzeli nabanomthelela ekuthathweni kwezinqumo ezimayelana nokusetshenziswa kwezivimbelakukhulelwa phakathi kwamantombazane angamatshitshi; ekugcineni, iii) ukuqonda imicabango yabo mayelana nezindlela ezikhona zezivimbelakukhulelwa. Ucwaningo lwahlola izinhlelo, izinkombamvama nezici ezihlobene nezivimbelakukhulelwa ezisetshenziswa phakathi kwamantombazane eZambia, lusebenzisa imininingo esukela onyakeni wowe-1996, 2001/2, 2007 kanye nowezi-2013/14 eZambia Demographic and Health Surveys. Kwaqoqwa imininingo yocwaningo lobunjalo botho kugxilwe ezingxoxweni zeqoqo okwakucwaningwa ngalo lahlaziywa kusetshenziswa uhlaziyongqikithi. Imvume yokwenza ucwaningo yatholakala kuNgqongqoshe WeZempilo kanye NeZiphathimandla Zocwaningo LweZempilo KuZwelonke. Isiqinisekiso SeNqubonhle sanikezelwa Amakomidi eBiomedical Research Ethics (BRECs) aseNyuvesi yaseZambia kanye neNyuvesi YakwaZulu-Natali eNingizimu Afrika. Imiphumela yocwaningo yaveza ukuthi ukusetshenziswa kwezivimbelakukhulelwa phakathi kwamantombazane angamatshitshi aseZambia kwahlala kuphansi esikhathini esingaphezu kweminyaka eyi-18 kwase kukhula ngama-3%, kwabancane, abangafundile kanye nakumantombazane abangamatshitshi angaganile kodwa alwenzayo ucansi. Umshado noma ukuhlala nomlingani wakho kube neqhaza elikhulu ezinguqukweni ezisetshenziswayo zokuvimbela ukukhulelwa (44%), ngenkathi ukuhlala endaweni yasemakhaya kubalelwa esilinganisweni esingama-20%. Lokho amantombazane asengamatshitshi aseke edlula kukho mayelana nokusetshenziswa kwezivimbelakukhulelwa kwaphazanyiswa yizinto eziningi njengolwazi lwezivimbelakukhulelwa kubandakanya nemithombo yolwazi nezivimbelakukhulelwa, odlula kukho uma usebenzisa izivikelakukhelwa, izingqinamaba zokusebenzisa izivimbelakukhulelwa kanye nemibono engemihle ngezivimbelakukhulelwa. Ukuxhumanakunikezelana kwezinto ezihlobene kulokho umuntu nomuntu adlule kukho, umphakathi wabantu kanye nendawo lapho abakwazi ukuthola khona izivimbelakukhulelwa konke kunomthelela kukho lokho isiguli esedlule kukho nalokho okuthinta izinqumo zokuvimbela ukukhulelwa ezithathwa ngamantombazane angamatshitshi. Abagqugquzeli abaningi bokusetshenziswa nokungasetshenziswa kwezivimbelakukhulelwa banobudlelwane bomuntu kanye nobudlelwane kubantu. Ukusetshenziswa kwezivimbelakukhulelwa amantombazane angamatshitshi kuhlale kuphansi futhi lokhu kudalwa yizinto ezahlukene. Abagqugquzeli nabakhuthaza ukusetshenziswa kwezivikelakukhulelwa basemqoka kufaka abantu ezimpilweni zabo, njengabalingani, umndeni namalunga omphakathi. Ukungenelela okuqonde ekukhuliseni isidingo, ukufinyelela nokusetshenziswa kwezivimbelakukhulelwa phakathi kwamatshitshi kumele kufake izindlela ezintsha, kubambe iqhaza futhi kuqaliswe engqikithini yenkambisonqubo yokuyisiko endaweni.
Critical care nurses’ perceptions of caring for patients at a selected hospital in KwaZulu-Natal.
(2022) Jugroop, Merashni.; Emmamally, Waheedha.
Background: Caring in a critical care setting requires a holistic process of individualised, patient-focused, and specialised care within a work intensive and technologically focused environment. These are what have an impact on how caring unfolds within a critical care environment. The COVID-19 pandemic has further altered the care relationship between critical care nurses, critically ill patients and their families. Aim: To determine critical care nurse’s perceptions of caring for patients at a selected hospital in KwaZulu-Natal Methods: A quantitative, descriptive, cross-sectional study was conducted on 139 participants in a tertiary quaternary hospital. Data collection used the Caring Assessment for Caregivers questionnaire, and analysis was with descriptive statistics. Results: Results revealed that most of the participants were females above 30 years, holding a Diploma in Nursing and had > 10 years of work experience. Participants had an overall high perception of caring, with a total mean score of 116.01 (range of 25- 125). Of the five subscales, the subscale of “Maintaining belief,” had the highest mean composite score 24.25(range of 5-25) and the subscale of “Being with,” had the lowest mean composite score 22.70. There was no significant relationship found between the critical care nurses’ socio-demographic characteristics, the overall score and the total scores of each of the five subscales. Conclusion: Whilst critical care nurses reported a high overall perception of caring, lower mean scores on the subscale “Being with” suggest that there areas for critical care nurses to grow in their role as carers. Further research is necessary for replication of the study using qualitative approaches to bring forth valuable findings on how the critical care environment has an impact on the caring experiences of critical care nurses.
Defining HIV persistence and host immune responses in lymph nodes of combined antiretroviral therapy (cART) suppressed individuals and the determination of the impact of HIV infection on SARS-COV-2 specific t cell responses in South Africa = Ukuchazwa kokuphikelela kwe-HIV kanye nokulwisana nayo kwamasosha okwelashwa ngemishanguzo exubile eyaziwa nge-cART okubonakala ezimbilaphweni kubantu abangakhombisi ukuthi banegciwane le-HIV, kanye nokuvela kwemithelela yokutheleleka ngegciwane le-HIV ekulweni kwamaseli awuhlobo lwe-T kwi-SARS-CoV-2 eNingizimu Afrikha.
(2023) Chasara, Caroline.; Ndhlovu, Zaza Mtine.
Abstract 1 People living with HIV (PLWH) who have unsuppressed HIV are at a greater risk of acquiring infectious diseases such as Coronavirus disease of 2019 (COVID-19). More recent data has shown that unsuppressed HIV is associated with severe COVID-19 symptoms, but the mechanisms underpinning this susceptibility are still unclear. In our study we used flow cytometry and culture T lymphocyte expansion to assess the impact of HIV infection on the quality and epitope specificity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) T cell responses in the first wave and second wave of the COVID-19 epidemic in South Africa. We observed that HIV-seronegative individuals had significantly greater CD4+ T cell responses against the Spike protein compared to the viremic individuals living with HIV. In addition, there was diminished T cell cross-recognition between the two waves, which was more pronounced in individuals with unsuppressed HIV infection. Importantly, we identified four mutations in the Beta variant that resulted in the abrogation of T cell recognition. These findings partly explain the increased susceptibility of PLWH to diseases such as COVID-19 and highlight their vulnerability to emerging SARS-CoV-2 variants of concern. Abstract 2 The major keys to developing an HIV cure is through understanding HIV reservoir dynamics. The role of tissue macrophages in HIV reservoirs is complex and not yet fully understood. However, their ability to support viral replication, longevity, localization in immune sanctuaries, and potential for viral latency all contribute to the persistence and resilience of HIV reservoirs in various tissues throughout the body. Understanding and targeting these reservoirs is a critical area of research in the quest for an HIV cure. To gain insight into the macrophage reservoir, we used a combination of flow cytometry and immunofluorescence microscopy to characterize and investigate HIV persistence in lymph node (LN) macrophages. We detected pro-inflammatory (CD68+ ) macrophages harboring HIV Gag p24 and HIV1 RNA in the germinal centers of HIV positive early and late treated individuals suggesting their potential role as an HIV reservoir. In contrast, anti-inflammatory (CD206+ ) macrophages were localized along lymphatic vessels and outside the germinal centers. Importantly, we show the presence of longlived CD4+ TIM-4+ macrophages in LNs. The data reported in this thesis will go a long way in furthering our understanding of macrophage HIV reservoirs in lymph node macrophages. Iqoqa 1. Abantu abaphila ne-HIV (PLWH) abakhombisayo ukuthi bane-HIV basengozini enkulu yokuthola izifo ezithathelwanayo njenge-Coronavirus ka-2019 (COVID-19). Imininingo yakamuva ibonise ukuthi i-HIV ebonakalayo ihlotshaniswa nezimpawu ezinzima ze-COVID-19, kodwa izindlela ezisekela lokhu kuba sengozini azikacaci. Ocwaningweni lwethu siqale sasebenzisa i-flow cytometry kanye nokwandiswa kokuhlolwa kwamaseli egazini angamasosha okulwisana nezifo ukuze kubonakale umthelela wokuchaphazeleka nge-HIV kwikhwalithi nokucaciswa kokuvela kwezimpawu zezinkinga zokuphefumula kanzima ze-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) kanye nendlela amaseli ayi-T cell alwa ngayo ekugaseleni kuqala kanye nokwesibili kobhubhane lwe-COVID-19 eNingizimu Afrika. Siqaphele ukuthi abantu abangenalo igciwane le-HIV, amaseli abo ayi- CD4+ T ayelwa ngendlela enamandla amakhulu ngokumelene ne-Spike protein uma kuqhathaniswa nabantu abanegciwane egazini abaphila ne-HIV. Ukwengeza, kube nokuncipha kokuqashelwa kwe-T cell phakathi kwalezi ziwombe zokugasela ezimbili, okwakubonakala kakhulu kubantu abane-HIV engacashile. Okubalulekile, sihlonze izinguquko ezine kwi-DNA yo hlobo lwe-Beta okuholele ekucindezelekeni kokusebenza kweseli ye-T. Imiphumela ichazile nakuba kungaphelele ukuhlaseleka kwe-PLWH ezifweni ezinjenge-COVID-19 kanti futhi kugqamisa nokuba sengozini kwabo kwezinye izinhlobo ze-SARS-CoV-2 ezisaqubuka ngendlela eyethusayo. Iqoqa 2. Izindlela ezinqala zokuthuthukisa ikhambi lokwelapha i-HIV zisekuqondeni iziguquguquli zesidlekemagciwane se-HIV. Iqhaza lamaseli ayi-macrophage ezicutshini zesidlekemagciwane se-HIV liyinkimbinkimbi futhi alikaqondakali ngokugcwele. Kodwa-ke, amandla awo okusekela ukuphindaphindeka kwegciwane, ukuphila isikhathi eside, ukutholakala kwawo ezindaweni ezivikela amasosha omzimba, kanye nokukwazi ukungazivezi njengegciwane, konke kunomthelela ekuphikeleleni nasekuqineni kwesidlekemagciwane se-HIV ezicutshini ezihlukahlukene emzimbeni wonke. Ukuqonda kanye nokuhlasela lezi zidlekemagciwane kuyingxenye ebaluleke kakhulu kulolu cwaningo emizamweni yokuthola ikhambi lokwelapha i-HIV. Ukuthola ukuqonda ngesidlekemagciwane se-macrophage sisebenzise inhlanganisela yeqhinga elaziwa nge-flow cytometry kanye ne-immunofluorescence microscopy ukuze kutholakale futhi kuphenywe ukuphikelela kwe-HIV kuma-macrophage asezimbilaphweni. Sithole ama-macrophage avunana nokuvuvukala i-(CD68+) okucashe kuwo i-HIV-Gag p24 kanye ne-HIV-1 RNA ezindaweni la kumila khona igciwane le-HIV kubantu abane-HIV abasaqala ukwelashwa nalabo asebenesikhathi eside belashwa, okukhombisa indima angayidlala njengesidlekemagciwane se-HIV. Ngokuphambene nalokho, ama-macrophage alwa nokuvuvukala i-(CD206+) atholakala emithanjeni yezimbilapho kanye nangaphandle kwezindawo okumila kuzo igciwane. Okubalulekile ukuthi sibonisa ukuba khona kwama-macrophage CD4+TIM-4+ asemadala ezimbilaphweni. Imininingo ebikwe kulo mqingo izohamba ibanga elide ekuqhubekiseleni phambili ukuqonda kwethu izidlekemagciwane zama-macrophage e-HIV kuma-macrophage atholakala ezimbilaphweni.
Design of advanced multifunctional biomaterial-based biomimetic and pH-responsive hybrid nanocarriers for antibiotic delivery against bacterial infections and sepsis = Ukwakhiwa kwama-haybridiangezona izedlulisela asebenza ngezindlela ezahlukahlukene enziwe nge-biomimetic eyakhiwe ngezinto eziphilayo abe ezwana futhi ne-pH. Lawa angezona izedluliseli ahambisa izinqindimagciwane ezilwisana nokutheleleka kwegciwane kanye nokudlanga kwekhovidi-19.
(2023) Elhassan, Eman Hussain Elmubarak.; Govender, Thirumala.; Omolo, Calvin Andeve.
Despite the notable improvements in the management of bacterial infections and sepsis, the mounting threat of antibiotic resistance on a global scale is leading towards a post-antibiotic era. Nano-drug delivery systems have improved the delivery and efficacy of various antibiotics. Biomimicry and stimuli-responsiveness have recently been used to improve the targetability of these nanocarriers, and enhance their localization at infected sites, thus improving overall therapeutic outcomes and reducing toxicity. Strategies such as targeting bacterial biofilms and efflux pumps can further enhance the delivery and effectiveness of antibiotics. Developing smart biomaterials with multifunctional properties to confer biomimetic, stimuli-responsive and antivirulence properties to antibiotic nanocarriers is the focus of ongoing research. Therefore, the general aim of this study was to investigate the potential of various novel multifunctional biomaterial-based hybrid nanocarriers (HNs), including biomimetic and/or pH-responsive HNs in enhancing the targeted delivery of antibiotics and modulating the proinflammatory response against bacterial infections and sepsis. In this study, two biomaterials with multifunctional activities, hyaluronic acid-lysine conjugate (HA-Lys) and tannic acid (TA), were employed to design, formulate, and extensively characterize innovative biomimetic and pH-responsive HNs for efficient and targeted delivery of antibiotics. The novel HA-Lys was synthesized and fully characterized using proton nuclear magnetic resonance (1H NMR) spectroscopy and Fourier-transform infrared spectroscopy (FT-IR). Then it was successfully employed with tocopherol succinate (TS) and Oleylamine (OLA) to fabricate biomimetic pH-responsive vancomycin-loaded hybrid nanostructured lipid carriers (VCM-HNLCs). The prepared VCM-HNLCs were spherical and had average diameters, zeta potential, polydispersity index, drug encapsulation efficiency and loading capacity of 110.77  1.69 nm, 0.11  0.02, -2.92  0.21 mV, 76.27  1.20 % and 8.36  0.25 %, respectively. Both HA-Lys conjugate and its respective nanoformulations had excellent biosafety profiles (>70 % cell viability and ˂ 1 % hemolytic effect). Possible VCM-HNLCs competitive inhibition activity to toll-like receptors 2 and 4 (TLR2 and TLR4) was demonstrated via microscale thermophoresis (MST) analysis, which showed a 5-times and 16-times lower Kd values than their natural substrates peptidoglycan (PGN) and lipopolysaccharide (LPS), respectively. VCM-HNLCs exhibited a pH-responsive drug release profile under acidic conditions, higher bacterial killing kinetics, enhanced antibacterial, anti-biofilm, and efflux pump inhibition activities over bare VCM. Also, they showed an improved activity in neutralizing reactive oxygen species (ROS) and modulating the inflammatory response induced by LPS. On the other hand, tannic acid (TA) and Oleylamine (OLA) were successfully employed to formulate biomimetic ciprofloxacin-loaded tannic acid hybrid nanoparticles (CIP-loaded TAH-NPs) to enhance the efficacy of CIP against bacterial infections and sepsis. The prepared HNs had onion-shaped morphology, with average diameters, zeta potential, polydispersity index, drug encapsulation efficiency and loading capacity of 85.65 ± 0.89 nm, 0.126 ± 0.01, +16.3 ± 0.23 mV, 68.73 ± 0.54 % and 6.86 ± 0.09 %, respectively. The hemolysis and MTT assays confirmed the biosafety and non-hemolytic activity of CIP-loaded TAH-NPs formulations (>70 % cell viability and ˂ 1 % hemolytic effect). The results of MST investigations and in-silico simulations demonstrated that TA and its nanoformulation (CIP-loaded TAH-NPs) competitively inhibited TLR4 compared to its natural substrate LPS. CIP-loaded TAH-NPs showed a diffusion-based sustained release profile at physiological pH 7.4. Also, in comparison to bare CIP, the hybrid nanovesicles demonstrated improved antibacterial, anti-biofilm and efflux pump inhibition properties, as well as faster bacterial killing kinetics. Moreover, they showed a significant neutralization of ROS and the ability to control the inflammatory responses brought on by LPS. In summary, VCM-HNLCs and CIP-loaded TAH-NPs were successfully formulated and showed significant improvement in antibiotics efficacy and overall therapeutic outcomes. This study confirmed the potential of biomimetic stimuli-responsive antibiotic hybrid nanocarriers for enhancing antibiotic efficacy against bacterial sepsis and addressing the antimicrobial resistance crisis. The data from this study has resulted in one first-authored review article, two first-authored research publications and one co-authored review article. Iqoqa. Nakuba kubonakala ukuba ngcono ukwelashwa kokutheleleka ngamagciwane kanye nokudlanga kwekhovidi-19 ukuqina kokuphikisana nokusebenza kwezinqandimagciwane emhlabeni jikelele kuholela ekuthi kubhekwe esikhathini lapho kuzobe kungasasetshenziswa izinqandimagciwane. Izindlela zokuhanjiswa kwemithi eyizinhlayiya ezincane kakhulu ezaziwa ngama-nano-drug zenze kusheshe ukuhanjiswa kanye nokusebenza ngendlela efanele kwezinqandimagciwane ezihlukahlukene. Sekusetshenziswe indlela yokubukela emvelweni kanye nokubheka ukusebenza kwezikhuthazi ukuze kuthuthukiswe ukufinyelela lapho kufanele khona kwalawa ma-nano-carrier, futhi kuthuthukiswe nokuzinza kwawo ezingxenyeni zomzimba ezitheleleke ngegciwane okwenza kusheshe kubonakale ukuphola ngokushesha kunciphe noshevu emithini. Amasu afana nokuhlasela ungwengwezi olwemboze amagciwane kanye namaphrotheyni akhipha ubuthi kumaseli aziwa ngama-efflux pump angaphinde athuthukise ukuhanjiswa kanye nokusebenza kahle kwezinqandimagciwane. Ucwaningo oluqhubekayo lusekuthuthukiseni izinto zokusebenza ezakhiwe ngemvelo zibe zinezimo ezisebenza ngokuhlukahlukana ukuze zinikeze amandla okumelana nezikhuthazi kanye nokulwisana namagciwane kuma-nanocarrier. Ngakho-ke, inhloso yalolu cwaningo ukuhlola ukuthi ama-nanocarrier ayizinhlobo ezintsha ezisebenza ngezindlela ezihlukahlukene abe eyingxubevange enziwe ngokususelwe emvelweni (HNs) okuhlanganiswa kuwo ama-HNs akopela ekusebenzeni kwemvelo kanye/noma asebenzisana ne-pH angasebenza kangakanani noma kanjani ukuthwala izinqandimagciwane ziye ngqo lapho okumele ziye khona kanye nokulawula ukungavuvukali uma kunokutheleleka ngegciwane noma kune-sepsisi. Kulolu cwaningo kwasetshenziswa izinto zokusebenza ezakhiwe ngemvelo ezimbili ezenza imisebenzi ehlukahlukene i-hyaluronic acid-lysine conjugate (HA-Lys) kanye ne-tannic acid (TA) ukuze kwakhiwe futhi kucatshangwe kabanzi ama-HNs aphambili ngokubukela emvelweni futhi asebenzisanayo ne-pH ukuze kuthwaleke izinqandimagciwane ngendlela efanele nezifika kahle lapho kumele ziyosebenza khona. Kwahlanganiswa i-HA-Lys entsha yahlolisiswa kusetshenziswa i-spectroscopy esiyi- proton nuclear magnetic resonance (1H NMR) kanye ne- Fourier-transform infrared spectroscopy (FT-IR). Yase isetshenziswa ngempumelelo isetshenziswa ne- tocopherol succinate (TS) kanye ne- Oleylamine (OLA) ekwenzeni izithuthi ezisamafutha ezisebenza njengokwasemvelweni futhi okusebenzisanayo ne-pH kube kuyingxubevange egcwele i-vancomycin (VCM-HNLC). Ama-VCM-HNLC akhiwa ayeyimbulunga enobubanzisiyingi obuyisilinganisomaphakathi, i-zeta potential, i-polydispersity index, ukugcineka ngokufanele kobungako bomuthi ozinze lapho okumele uhlasele khona , okwaziwa nge- drug encapsulation efficiency, kanye nobungako bomuthi ongafakwa oyi- 110.77  1.69 nm, 0.11  0.02, -2.92  0.21 mV, 76.27  1.20 % and 8.36  0.25 %, ngokulandelana. Kokubili ukuhlangana kwesikhashana kwe-HA-Lys kanye nama-nanoformulation ayo alandelayo kwakhombisa isimo esihle sokuphepha (>70 % ukusebenza kwamaseli kanye nemithelela kulokho okuhlangene nokuqhuma kwemithambo yegazi ˂ 1 %). Kwavela ukuthi kungenzeka kube nokuncintisana nezithiyo ze-VCM-HNLC kuma-receptor 2 kanye no-4(TLR2 kanye ne-TLR4) asebenza njengabalindisango. Lokhu kwakhonjiswa uhlaziyo lwe-microscale thermophoresis (MST) olwakhombisa ukwehla kwama-K value ngokuphindwe ka-5 kanye naka-16 uma kuqhathaniswa nama- natural substrates peptidoglycan (PGN) kanye nama- lipopolysaccharide (LPS)awo, ngokulandelana. Ama-VCM-HNLC akhombisa ukukwazi ukukhipha umuthi osebenzisana ne-pH ngaphansi kwezimo ezine-esidi, uhlololumbanozithako oluphezulu ekubulaleni amagciwane, amandla aphezulu okulwisana namgciwane, ukulwisana nongwengwezi lokuphilayo, kanye nokusebenza kwezithibi ze-efflux pump kuma-VCM ahlezi obala. Okunye futhi, akhombisa ukusebenza kangcono ekudambiseni ama-reactive oxygen species (ROS) kanye nasekwenyuseni izinga lokulwa nokuvuvukala okudalwa yi-LPS. Ngakolunye uhlangothi, kwasetshenziswa ngempumelelo i-tannic acid (TA) kanye ne-Oleylamine (OLA) ukwakha ama- ciprofloxacin-loaded tannic acid hybrid nanoparticle (CIP-loaded TAH-NP) akhiwe njengokwemvelo ukwenyusa izinga lokusebenza ngendlela efanele kwama-CIP ekulwisaneni nokutheleleka ngegciwane kanye ne-sepsisi. Ama-HN alungiselelwe ayenesimo esifana no-anyanisi enobubanzisiyingi obuyisilinganisomaphakathi, i-zeta potential, i-polydispersity index, ukugcineka ngokufanele kobungako bomuthi ozinze lapho okumele uhlasele khona , okwaziwa nge- drug encapsulation efficiency, kanye nobungako bomuthi ongafakwa oyi-85.65 ± 0.89 nm, 0.126 ± 0.01, +16.3 ± 0.23 mV, 68.73 ± 0.54 % and 6.86 ± 0.09 %, ngokulandelana. Ama-aseyi aqondene nokuqhuma kwemithambo yegazi kanye ne-MTT akuqinisekisa ukuphepha emzimbeni kanye nokusebenza kwama-TAH-NP afakwe i-CIP angayiqhumisi imithambo yegazi ((>70 % ukusebenza kwamaseli kanye nemithelela kulokho okuhlangene nokuqhuma kwemithambo yegazi ˂ 1 %). Imiphumela yokuhlola kwe-MST kanye nokulingiswa okwenziwa yikhompyutha yaveza ukuthi i-TA kanye nokwakheka kwayo (CIP-loaded TAH-NP) kwakhombisa ukuthiba i-TLR4 ngempumelelo uma kuqhathaniswa neLPS ewuhlobo lwemvelo. Ama-TAH-NP afakwe i-CIP akhombisa ukuthi ayakwazi ukukhipha ngokusabalalisa okunganqamukiyo ezingeni le-pH 7.4. Okunye futhi, uma kuqhathaniswa ne-CIP engamboziwe izikhwanyana ezincane ezaziwa nge-hybrid nanovesicles emzimbeni zakhombisa ukulwisana namagciwane okungcono, kanjalo nasongwengwezini kanye nokuthiba i-efflux pump, kanye nhlololumbanozithako lokubulala amagciwane ngokushesha. Kanti futhi zakhombisa amandla amakhulu okunciphisa i-ROS kanye nokukwazi ukulawula ukuvuvukala okudalwa yi-LPS. Kafushane, ama-VCM-HNLC kanye namaTAH-NP afakwe i-CIP akhiwa ngempumelelo futhi akhombisa ubungcono obukhulu ekusebenzeni kwezinqandimagciwane kanye nemiphumela yokwelapha ngobubanzi. Lolu cwaningo lwaqinisekisa amandla ama-nanocarrier ayi-haybhridi athwala izinqandimagciwane abe ekwazi ukusebenzisana nezikhuthazi ekuthuthukiseni ukusebenza ngendlela efanele kwenqandamagciwane ezilwa ne-sepsisi enamagciwane kanye nokubhekana nokuphikisana kwezinto ezilwisana namamaykhrobhu. Imininingo etholakala kulolu cwaningo igcine ngokuthi kukhishwe i-athikhili eyodwa ebuyekezayo okokuqala, imibhalo yocwaningo emibili ebhalwe okokuqala, kanye ne-athikhili eyodwa ebhalwe ngokuhlanganyela ebuyekezayo.
Developing a competence-based framework for theprovision of mental healthcare in patients with mental health problems and HIV in primary healthcare in Maseru, Lesotho = Ukuthuthukisa uhlaka olususelwa ekukwazini ukuhlinzekela iziguli ezigula ngokomqondo eziphinde zibe negciwane le-HIV ezelashwa ngonakekelo oluphezulu eMaseru, eLesotho.
(2023) Posholi, Malerotholi Thabida.; Ngcobo, Winnie Baphumelele.
In 2017 there were approximately 792 million people with mental health problems globally. mental health problems are increasing rapidly globally but mental health services are lacking. Approximately 80% of people living with Human immunodeficiency virus have mental health problems yet these disorders have been absent from the global health agenda. Around 90% of people who require MHS do not obtain them in Low and middle-income countries. The aim of the study was to develop a competence-based framework for mental health provision in people living with Human immunodeficiency virus in primary Health Care in Lesotho. A mixed method study was used. In total, 88 questionnaires were returned by the respondents and 50 interviews were conducted. The findings from the quantitative and qualitative study were supportive and used to develop a competence-based framework that would facilitate the provision of mental health services for people presenting with mental health problems and Human immunodeficiency virus in primary health care. The quantitative data was analysed using an appropriate software package, in this case SPSS version 26. Qualitative data was analysed using the software called Nvivo and thematic framework analysis. 92 % of the participants needed competence-based frame work to enable them to successfully manage mental health problems in people presenting with mental health problems and Human immunodeficiency virus however the majority (69.7%) of the participants had inadequate knowledge regarding mental health. Competence-based frame work was developed to enable health professional to successfully manage people with mental health problems and Human immunodeficiency virus. Currently, mental health services are lacking in primary health cares in Lesotho. There was lack of knowledge regarding mental health in health professionals, mental health was also not an in-country priority as the professionals are taught about mental health in colleges, but do not practice it in their professional work. Availability of competence-based framework was seen as a great need by health professionals to manage mental health problems. Many studies emphasized the need to integrate mental health services with Human immunodeficiency virus services as they are related. However, in Lesotho it was still a serious problem during the time of the study. Iqoqa. Enyakeni wezi-2017 kwakunabantu abacishe babe yizigidi ezingama-792 abanenkinga yokugula ngokomqondo emhlabeni jikelele. Izinkinga zokugula ngokomqondo zikhula ngesivinini esikhulu emhlabeni jikelele kodwa izindawo zokwelapha ukugula ngokomqondo azanele. Cishe abantu abangama-80% abaphila negciwane lesandulela ngculazi banezinkinga zokugula ngokomqondo nakuba lezi zifo kade zingekho ohlelweni lwezempilo yomhlaba. Abantu abacishe babe ama-90% abadinga i-MHS abayitholi emazweni anengenisomali eliphansi nelimaphakathi. Inhloso yocwaningo wukuphucula uhlaka olugxiliswe ekukwazini ukuhlinzekela impilo yangokomqondo kubantu abaphila negciwane lesandulela ngculazi kweZempilo ezihamba Phambili eLesotho. Kusetshenziswe indlelakwenza engxube. Sekukonke, izinhlumibuzo ezingama-88 ezabuyiswa ababephendula nezimposamibuzo ezingama-50 zenziwa. Okutholakele ocwaningweni lwekhwantithethivu nowekhwalithethivu kweseka kwaphinda kwasetshenziselwa ukuthuthukisa uhlaka olugxile ekukwazini, okuzokwenza kwenzeke ukuhlinzeka izinsiza zokugula ngokomqondo kubantu abanezinkinga zokugula ngokomqondo kanye negciwane lesandulela ngculazi abasonakekelweni oluphambili. Imininingo yekhwantithethivu yacutshungulwa kusetshenziswa iphakheji yesofthiwe eyiyo, okuyi-SPSS uhlobo 26. Imininingo yekhwalithethivu yahluzwa kusetshenziswa uhlelokusebenza olubizwa nge-Nvivo nokuhluza uhlaka lwezindikimba. Ama-92 % ababambiqhaza babedinga uhlaka olugxiliswe ekukwazini ukuze bakwazi ukulawula ngempumelelo izinkinga zokugula ngokomqondo kubantu ababonakala benezinkinga ngokomqondo kanye negciwane lesandulelangculazi kodwa iningi (69.7%) lababambiqhaza banolwazi olungenele olumayelana nempilo yokomqondo. Uhlaka olugxile ekukwazini lwathuthukiswa ukusiza abasebenzi bezempilo ukuba balawule ngempumelelo abantu abanenkinga yokugula ngokomqondo nabanegciwane lesandulelangculazi. Njengamanje, izinsizakusebenza zempilo yokomqondo ezindaweni zokunakekela eziphambili eLesotho zisaswelekile. Kunokuntuleka kolwazi olumayelana nempilo yokomqondo ezisebenzini zezempilo, impilo yokomqondo yayingeyona into ephambili ezweni njengoba izisebenzi bezifundiswa ngezempilo yokomqondo emakolishi, kodwa zingasebenzi ngalokho emsebenzini wabo wansuku zonke. Ukuba khona kohlaka olugxiliswe ekukwazini kwabonakala kuyisidingo esikhulu kubasebenzi bezempilo ukulawula izinkinga zokugula ngokomqondo. Ucwaningo oluningi lugcizelele isidingo sokudidiyela imisebenzi yokwelapha ukugula ngokomqondo nezinsizakusebenza zokwelapha igciwane lesandulela ngculazi njengoba kuhlobene. Kodwa, eLesotho bekuseyinkinga enkulu lokhu ngesikhathi sokwenziwa kocwaningo.
Differential effects of early life stress and schizophrenia on the development of impulse control disorder = Imiphumela ehlukene yengcindezi yempilo engasekuqaleni kanye nokusangana ekuthuthukiseni ukulawula isifo esivumbuka kungahlelekile.
(2024) Oginga, Fredrick.; Mpofana, Thabisile.
Background: Early life stress (ELS) and parental psychopathology, such as schizophrenia, have profound effect on neurobiological and behavioral outcomes in later life. While previous studies in human have explored the individual effects of ELS and parental schizophrenia (PSZ), this study investigates their interactive effects. Objectives: This study aimed to comprehensively examine the impact of ELS and schizophrenia like symptoms on locomotion, anxiety and depressive like behavior, spatial memory, social interaction and neuro-inflammation in Sprague-Dawley rats. Methods: Male and female Sprague-Dawley pups were randomly assigned to eight groups: control, ELS, Ketamine to induce schizophrenia like symptoms (KSZ), and ELS + KSZ. ELS was induced through prenatal stress and maternal separation (MS), while schizophrenia-like behaviour was induced by ketamine administration (KSZ). Ketamine was administered intraperitoneal to the dams, while subcutaneous to the pups as per previously published studies. Behavioral assay, including open field, Morris water maze, social interaction behaviour, and sucrose preference test, was conducted. Neuro-inflammation was through quantification of glial fibrillary acidic protein astrocytes density and inflammatory biomarkers. Results: ELS and KSZ on dams exhibited enduring effects on particularly psychomotor retardation (p < 0.05). Anxiety and depressive like behavior was elevated in the ELS (p = 0.023) and KSZ on dams (p =0.017) groups compared to controls. The combined ELS and KSZ groups showed the highest anxiety and depressive like outcomes (p = 0.006). Additionally, spatial memory and cognitive impairment in pups were observed due to the combined impact of ELS and KSZ, which was associated with a decrease in astrocyte density and dysregulation of neuro-inflammatory markers (p < 0.05). Conclusion: This study highlights the interactive effects of ELS and KSZ on behavior, neurodevelopment, and neuro-inflammation in rats. Both ELS and KSZ in parents were linked to anhedonia, subsequently anxiety-like behavior, and ultimately psychomotor, spatial memory, and cognitive decline in rats. Positive parenting was associated with astrocyte regeneration (p < 0.05) and cognitive improvement. Understanding these complex interactions provides insights into the challenges associated with these stressors and offers potential therapeutic avenues. Iqoqa. Isendlalelo: ingcindezi ekuqaleni kwempilo kanye nobuzali ekuziphatheni kwesifo sengqondo, njengokusangana, kuba nomphumela omkhulu ohlelwenimizwa kanye nemiphumela yokuziphatha ngokuhamba kwesikhathi empilweni. Izifundo ezedlule ngomuntu ziyiphenyile imiphumela ngomuntu mayelana nengcindezi ekuqaleni kwempilo kanye nobuzali ekuphazamisekeni kwengqondo (PSZ). Lolu cwaningo luphenya imiphumela ethelelanayo. Izinhloso: lolu cwaningo luhlose ngokubanzi ukucwaninga imiphumela yengcindezi ekuqaleni kwempilo kanye nokusangana njengezimpawu zokudlathuzela, ixhala kanye nokuziphatha okunobukhwantalala, ukugcinwa kolwazi engqondweni, ukuphilisana ngokwenhlalo kanye nokuvuvukala kwemizwa yengqondo ngokukaSprague-Dawley emagundaneni. Izindlelakwenza: imidlwane yenduna neyensikazi kaSprague-Dawley yakhethwa ngokungahlelekile yanikezwa amaqoqa ayisishiyagalombili: ukulawulwa, i-ELS, Ketamine ukulandela ukusangana njengezimpawu i-KSZ, kanye ne-ELS+KSZ. I-ELS yalandelwa ngokwengcindezi engaphambi kokuzalwa ngesikhathi sokumitha nokuhlukaniswa nonina (MS), ngesikhathi ukuziphatha okusakusangana kwalandelwa ukusetshenziswa kweketamine (KSZ). Iketamine yafakwa ngaphakathi ontwentwesini lwenxasisu yemidlwane esemadamini, ngesikhathi futhi ifakwe ngaphansi kwesikhumba semidlwane njengokusho kocwaningo olushicilelwe ngokwedlule. Ukuziphatha ngokuhlola ingqondo, kufaka insimu evulekile, amanzi amazombe ngokukaMorris, ukuziphatha ngokwenhlalo, kanye nesivivinyo esikhethekile sikashukela, kwenziwa. Ukuvuvukala kwaba ngenxa yequantification yeglial fibrillary yensiza zakhamzimba nokugqishelana kwe-astrocytes kanye nokuvuvukala kwebiomarkers. Imiphumela: Ixhala kanye nengcindezi njengokuziphatha kwaphakanyiswa kuyo i-ELS (p=0.023) and KSZ emadamini (p=0.017) yamaqoqo yaqhathaniswa nabaqashelwe. Ukuhlanganiswa kwe-ELS kanye neKSZ kwatshengisa ixhala elikhulu kanye nengcindezi njengemiphumela (p=0.006). Ngokunezezela, isikhala ngokukhumbula kanye nokulimaza umqondo kwafakelwa izibuko ngenxa yokuhlangana kwesisindo se-ELS kanye neKSZ, okumataniswa nekwehla kwesisindo se-astrocyte kanye nokungalawulwa kwezinkomba zokuvuvukala ngokomqondo (p<0,05). Isiphetho: lolu cwaningo lugqamisa imiphumela ethelelanayo ye-ELS kanye ne-KSZ ekuziphatheni, ukuthuthuka ngokwasengqondo, nokuvuvukala kwengqondo emagundaneni. Kokubili i-ELS kanye ne-KSZ kubazali kwaxhunyaniswa ne-anhedonia, kwalandela ukuziphatha okusaxhala, kwasekuthi ekugcineni ubudlelwanokusebenza kwengqondo nomzimba, ukugcinwa kolwazi engqondweni, nokufadalala kwenqubokucabanga emagundaneni. Ubuzali obuhle kwamataniswa nokuvuselelwa kwe-astrocyte (p<0,005) kanye nokubangcono komqondo. Ukuqonda ukuthelelana okudidayo kokuphilisana kwanikeza ulwazi mayelana nezinselelo ezimataniswa nezimbangangcindezi kwanikeza namathuba okwelapha okungase kwenziwe.
Drug transporter expression and genetic polymorphisms in HIV endemic settings = Indlela yokuthutheka kwemithi emzimbeni nesakhiwo esingxube sofuzo ezimweni zokubhebhetheka kwesandulela ngculazi.
(2023) Zondo, Nomusa Margaret.; Archary, Derseree.; Sobia, Parveen.
Pre-exposure prophylaxis (PrEP) in the form of oral Truvada® remains the standard of care for HIV prevention in South Africa. Despite the availability of PrEP, HIV infections continue in young women significantly more than in men. Clinical trials testing antiretrovirals containing tenofovir as topical or oral PrEP formulations in African women, produced inconsistent patterns of efficacies against HIV. Effectiveness of oral and topical PrEP is dependent on adequate drug delivery and availability to cells and tissues targeted by HIV. Our study, therefore, focused on how different biological factors: drug transporter expression, single nucleotide polymorphisms (SNPs) in drug transporter genes and genital inflammation modulate PrEP disposition in African women. We characterized drug transporter mRNA expression in two compartments, the female genital tract (FGT) and blood, at baseline, 3 and 6 months in 45 women taking oral PrEP-Truvada®. Additionally, the impact of SNPs in 393 women and genital inflammation in 45 women on circulating tenofovir and drug transporter mRNA expression were determined. SNPs in drug transporter genes: ABCB1 3435G>A; ABCC1 198217T>C; ABCC2 1249G>A; ABCC4 3463T>C; ABCC4 4131A>C and ABCC4 4976A>G were evaluated using real-time PCR. mRNA expression of efflux P-gp, MRP-2, MRP-4, MATE-1 and influx OAT-1 and OAT-3 drug transporters was evaluated using quantitative real-time PCR. Genital inflammation was measured in cervicovaginal specimens using a 28-cytokine multiplexed platform. Results showed that ABCC4 4976A>G and ABCC4 3463T>C SNPs alter circulating tenofovir differently. While the ABCC4 4976A>G SNP significantly increased the mRNA expression of the ABCC4 gene (p=0.0132), there was inverse association with circulating tenofovir (p=0.018). In contrast, although the ABCC4 3463T>C SNP did not significantly impact mRNA expression of the ABCC4 gene, it was significantly and directly associated with circulating tenofovir (p<0.05). Correlation analyses showed moderately significant associations between the mRNA expression of the influx drug transporter OAT-1 in the FGT and blood pre- and post- PrEP exposure (rs<1, p<0.05). In contrast efflux drug transporters P-gp, MATE-1, MRP-2 and MRP-4 showed significance after PrEP initiation (3 and 6 months) (rs<1, p<0.05). For pro-inflammatory cytokines, linear mixed models showed negatively correlated trends between IL-1β and MCP-1 and influx drug transporter OAT-1 and OAT-3 (p<0.1), while IL1Rα and TNF-α showed these correlations with efflux drug transporters MRP-2 and MRP-4 (p<0.1). Collectively our results suggested that PrEP disposition can be modified through a convergence of host genetics and different biological factors: drug transporter expression, SNPs in drug transporter genes and inflammation. Findings from such studies may be used to better understand PrEP pharmacokinetics and aid in the implementation of optimal PrEP dosages. This 14 will ultimately inform on effective and safe PrEP for HIV prevention especially in vulnerable and at-risk African women. Iqoqa. ENingizimu Afrika ipre-exposure prophylaxis (PrEP) oral-Truvada® kuseyiyona ndlela yokunakekela ekuvimbeleni isandulela ngculazi, i-HIV. Kodwa ukutheleleka nge-HIV kuyaqhubeka kakhulu kwabesifazane abasebancane. Ukuvivinywa kwemithi lapho kuhlolwa i-PrEP egcotshwayo/neyasemlonyeni kulabo besifazane abangama-Afrika kuveza izimo ezingazinzile ekulweni ne-HIV. Ukuphumelela kwale mithi egcotshwayo/neyasemlonyeni kuncike kakhulu ekuhambisekeni komuthi okwanele nasebukhoneni bama-cells aqondwe ngqo yi-HIV; izinto ezihambisana nomzimba ezibalulekile zibonakele ekulawuleni ukusebenza kwe-PrEP ezindaweni ezithelelekile. Lolu cwaningo, lwabheka ukuthi izimo zomzimba: indlela yokuthuthwa komuthi emzimbeni, isakhiwo esisodwa ekuthuthweni komuthi emzimbeni isingle nucleotide polymorphisms (SNPs) kanye nokuvuvukala kwezitho zangasese kunomthelela muni ekusebenzeni kwePrEP kwabesifazane abangama-Afrika. Kwakhethwa isithuthi semithi i-mRNA-expression ngezindlela ezimbili: umgudu wezitho zangasese kwabesifazane, ifemale genital tract (FGT) kanye negazi, ekuqaleni kocwaningo, izinyanga ezi-3 neziyi- 6 kwabesifazane abangama-N=45 abathatha i-PrEP-Truvada® ngomlomo. Kwabe sekubhekwa i-mRNA-expression ye-P-gp, MRP-2, MRP-4, MATE-1 kanye ne-OAT-1 kanye ne-OAT-3 okuyizithuthi zemithi ezahlolwa kusetshenziswa ucwaningozibalo lwereal-time-PCR. Umthelela we-SNPs (N=393) kanye nokuvuvukala kwezitho zangasese (N=45) ekuzungeziseni i-tenofovir kanye nesithuthimithi i-mRNA-expression kwabonakala. Ukubonakala kwe-SNPs kwizithuthimithi zofuzo: ABCB1[3435G>A]; ABCC1[198217T>C]; ABCC2[1249G>A]; ABCC4[3463T>C]; ABCC4[4131A>C] kanye ne-ABCC4[4976A>G] kwahlolwa kusetshenziswa ireal-time-PCR. Ukuvuvukala kwezitho zangasese kwakalwa kumasampula ayethathwe ebuntwini babesifazane kusetshenziswa indlela ye-28-cytokine-multiplexed platform. Imiphumela yakhombisa ukuthi i-ABCC4[4976A>G] kanye ne-ABCC4[3463T>C] SNP ishintsha ukuzungeza kwetenofovir ngendlela ehlukile. I-ABCC4[4976A>G] SNP yakhulisa kakhulu i-mRNA-expression ye-ABCC4 gene (p=0.0132), kodwa yanomthelela ophambene ekuzungezeni kwetenofovir (p=0.018). Uma kuqhathaniswa, yize i-ABCC4[3463T>C] SNP ingabanga namthelela otheni kwi-mRNA-expression yofuzo i-ABCC4, yayamana kakhulu nokukhula ekuzungeziseni itenofovir (p<0.05). Ukuhlaziya kwalokhu kuhlobana kwakhombisa ukuhambisana okubalulekile phakathi kwe-mRNA-expression ye-OAT-1 kwiFGT kanye negazi ngaphambi nangemuva kokusetshenziswa kwe-PrEP. Kanti i-P-gp, MATE-1, MRP-2 kanye ne-MRP-4 kwakhombisa ukubaluleka emuva kokuqalwa kwe-PrEP ezinyangeni ezi-3 kuya kweziyi-6 (rs<1, p<0.05). Ekuvuvukaleni kwezitho zangasese, izindlela eziqondile ezingxube zakhombisa ukungahlobani phakathi kwe-IL-1β kanye ne-MCP-1 ene-OAT-1 kanye ne-OAT-3; IL-1Rα kanye ne-TNF-α ene-MRP-2 kanye ne-MRP-4 (p<0.1). Seyihlangene yonke le miphumela yakhombisa ukuthi ukusebenza kwe-PrEP kuyashintshashintsha ngokubambisana kwezimo ezahlukene emzimbeni: yindlela umuthi othutheka ngayo, ama-SNPs, kanye nokuvuvukala kwezitho zangasese. Imiphumela yalolu cwaningo ingasetshenziselwa ukuba kuqondwe kangcono amandla okusebenza kwe-PrEP kanye nokuqalwa kokukala ubungako bomuthi we-PrEP ngendlela efanele. Ngaleyo ndlela, kungaba nokusebenziseka ngempumelelo nangendlela ephephile kwe-PrEP ukuze kunqandwe isandulela ngculazi kwabesifazane bama-Afrika abasengcupheni.
Effect of HIV-1 subtype C Transactivator of transcription (Tat) A21P variant on TAR binding ability, nuclear levels of active positive transcription elongation factor b (P-TEFb) and viral latency = Umthelela we-HIV-1 subtype C Transactivator of transcription (Tat) A21P okuhlukile ekhonweni lokubopha i-TAR, amazinga enyukliya we-active transcription elongation factor b (P-TEFb) kanye neviral latency.
(2023) Mkhize, Zakithi Zinhle.; Madlala, Paradise Zamokuhle.
The HIV-1 Transactivator of transcription (Tat) enhances the ability of the viral promoter 5’ long terminal repeat (LTR) to drive viral gene transcription and is important for HIV-1 pathogenesis. Tat binds to the transactivator RNA (TAR) element of the 5’LTR and subsequently recruits the host positive transcription elongation factor b (P-TEFb) for efficient viral gene transcription. Inter- and intra-subtype Tat genetic variation that translates to functional differences has been reported. Specifically, HIV-1 subtype C (HIV-1C) exhibiting Alanine at position 21 of the Tat protein (TatA21) was reported to be associated with reduced LTR transcriptional activity compared to Tat exhibiting Proline at position 21 mutation (TatP21). However, the effect of Tat variation on its ability to recruit P-TEFb is unknown. Therefore, this study seek to determine the effect of HIV-1 subtype C TatA21 mutant on the ability of Tat to recruit P-TEFb to 5’ LTR to enhance viral gene transcription. To this effect, site-directed mutagenesis (SDM) was performed on the Plasmid pcDNA3.1(+) HIV-1C BL43/02 TatA21 to introduce TatP21 alone or together with other mutations using designed primers and the Q5 DNA polymerase kit. The effect of Tat mutations was measured using Tat transactivation assay where the luciferase activity was the measured output in TZM-bl cell lines and the impact of TatA21 was further assessed on ability of the LTR to drive GFP and Gag expression in Jurkat and A72 cells respectively. Next, protein modelling was performed using Hdock software, followed by RNA immunoprecipitation (RNA IP) was performed using stably expressing TatA21 and TatP21 in Jurkat cells. Lastly, co-immunoprecipitation of TatA21 and associated with significantly reduced LTR transcription activity compared to TatP21 (p = 0.0004). TatA21 resulted in had significantly lower GFP expression Jurkat cells (p = 0.0439) and lower Gag expression in A72 cells compared to TatP21. Although TatA21 reduced the LTR transcription activity compared to TatP21, protein modelling using Hdock software revealed that TatA21 and TatP21 protein structures were the same. Consistently, molecular docking showed that TatA21 had a lower binding affinity than TatP21. The RNA IP showed that TatA21 had significantly reduced affinity to bind to TAR compared to TatP21 (p = 0.0151). Moreover, TatA21 and TatP21 formed a complex with cycT1 and CDK9. Taken together, our data shows that HIV-1C TatA21 significantly reduced its transactivation activity but does not affect its ability to recruit P-TEFb. Interestingly, TatP21 is able to bind TAR more efficiently than TatA21 thus revealing a possible mechanism but which the reduced functionality of SDMs and patient derived TatA21 variants was observed. The effect of TatA21 and TatP21 on the propensity of HIV-1 latency development or reversal. To this effect, a recombinant viral vector exhibiting either TatA21 (C731CTatA21C) or TatP21 (C731CTatP21C) were generated. The C731CTatA21C or C731CTatP21C were separately co-transfected together with VSV-G and R8.91 into Jurkat cells for virus production. This virus was then used to infect Jurkat cells for 3 days. Followed by cell sorting of GFP- cells, which represented either truly negative or latently infected cells was then performed. We were able to successfully generate C731CTatA21C virus and characterized it to a 1.2% reactivation. However, the generation of C731CTatP21C recombinant viral vector was unsuccessful and thus could not be used for comparison. Future studies should involve the characterization of TatP21 in the propensity of latency development and/ or reactivation. Iqoqa. Iphrotheni eyaziwa ngeTransactivator of transcription (Tat) le-HIV-1 inamandla okuthuthukisa amandla egciwane 5’ le-LTR ukulawula ukuhlonzwa kofuzo lwegciwane futhi ibalulekile ekwelashweni kokukhula kwe-HIV-1. I-Tat ihlanganisa izinhlasiyana ze-RNA (TAR) ye-5'LTR futhi ikwazi ukudonsa i-P-TEFb ukuze ihlonze ngempumelelo isakhi sofuzo. Ukuhlukahluka kofuzo kwangaphakathi nokwangaphandle ekuhlonzweni komehluko nakho kuveziwe. Ngokukhethekile, uhlobo C lwe-HIV-1 (HIV-1C) ebonisa i-alanine endaweni engu-21 yephrotheni i-Tat (TatA21) kubikwe ukuthi ihlotshaniswa nomsebenzi wokuhlonza oncishisiwe we-LTR uma kuqhathaniswa ne-Tat ebonisa iproline ekuguqulweni kwe-21ye-Tat (TatP21). Nokho, umthelela wokuhluka kwe-Tat ekuphumeleni kwayo ukudonsa i-P-TEFb awaziwa. Ngakho-ke, lolu cwaningo beluhlose ukuhlonza umthelela we-HIV-1 lohlobo C lwe-TatA21 eguquguqukayo emandleni e-Tat okuhlonza i-P-TEFb kuya ku-5’ LTR ukuze kuthuthukiswe ukuhlonzwa kofuzo lwegciwane. Kulokhu, isite-directed mutagenesis (SDM) yenziwa kwiPlasmid pcDNA3.1(+) HIV-1C BL43/02 TatA21 ukwethula i-TatP21 iyodwa noma kanye nezinye izinguquko kusetshenziswa amathuluzi aklanyelwe kanye neDNA ye-Q5. Umthelela wokuguqulwa kwe-Tat ukalwe kusetshenziswa i-Tat lapho umsebenzi weluciferase wawungumphumela olinganiselwe emigqeni yenhlasiya ye-TZM-bl futhi umthelela we-TatA21 wabuye wahlolwa mayelana nokuphumelela kwe-LTR uhlonza i-GFP ne-Gag ezinhlasiyeni zeJurkat nama-A72 ngokulandelanayo. Okulandelayo, ukubheka amaprotheni kwenziwa kusetshenziswa isofthiwe ye-Hdock, kwalandelwa yi-RNA immunoprecipitation (RNA IP) kwenziwa kusetshenziswa okuveza ngokuzinzile i-TatA21 ne-TatP21 ezinhlasiyeni zeJurkat. Okokugcina, ico-immunoprecipitation ye-TatA21 ne-TatP21 yenziwe nge-cycT1 ne-CDK9. Imiphumela yethu ibonisa i-TatA21 eguquguqukayo iyodwa ihlotshaniswe nomsebenzi wokuhlonzwa kwe-LTR owehliswe kakhulu uma kuqhathaniswa ne-TatP21 (p = 0.0004). I-TatA21 iholele ekutheni ibe nezinhlasiya ze-GFP yeJurkat ephansi kakhulu (p = 0.0439) kanye ne-Gag ephansi ezinhlasiyeni ze-A72 uma kuqhathaniswa ne-TatP21. Nakuba i-TatA21 yehlise umsebenzi wokuhlonzwa kwe-LTR uma kuqhathaniswa ne-TatP21, ukubhekwa kwamaprotheni kusetshenziswa isofthiwe i-Hdock kuveze ukuthi izakhiwo ze-TatA21 ne-TatP21 zazifana. Ngokuvumelanayo, ukuhlonzwa kwezinhlasiya kubonise ukuthi i-TatA21 inobudlelwane obubophezelayo obuphansi kune-TatP21. I-RNA IP ibonise ukuthi i-TatA21 inciphise kakhulu ukuhambisana ukuze izibophezele kwi-TAR uma kuqhathaniswa ne-TatP21 (p = 0.0151). Ngaphezu kwalokho, i-TatA21 ne-TatP21 bakhe inkimbinkimbi ene-cycT1 ne-CDK9. Sekuhlangene, imiphumela yethu ibonisa ukuthi i-HIV-1C TatA21 iwunciphise kakhulu umsebenzi wayo wokwenza izinto kodwa ayithinti impumelelo yayo yokuhlonza i-P-TEFb. Kuyajabulisa ukuthi i-TatP21 iyakwazi ukuhlanganisa i-TAR kahle kakhulu kune-TatA21, ngaleyo ndlela iveze indlela engase ibe khona kodwa okuye kwabonwa ukusebenza okuncishisiwe kwama-SDM kanye nokuhluka okutholwe esigulini se-TatA21. Umthelela we-TatA21 kanye ne-TatP21 ekuthembekeni kokuthuthukiswa kokubambezeleka kwe-HIV-1 noma ukuguqulwa. Kulokhu, inhlanganisela yegciwane ekhombisa i-TatA21 (C731CTatA21C) noma i-TatP21 (C731CTatP21C) yenziwe. I-C731CTatA21C noma i-C731CTatP21C yadluliselwa ngokuhlukana ndawonye ne-VSV-G kanye ne-R8.91 kuzinhlasiya zeJurkat ukuze kukhiqizwe igciwane. Leli gciwane labe selisetshenziselwa ukuthelela izinhlasiya zeJurkat izinsuku ezi-3. Kulandelwa ukuhlungwa kwezinhlasiya ze-GFP, okwakumele izinhlasiya ezingezinhle ngempela noma ezisanda kungenwa amagciwane kwase kwenziwa. Sikwazile ukukhiqiza ngempumelelo igciwane le-C731CTatA21C futhi silibeke ku-1.2%. Nokho, ukukhiqizwa kwe-C731CTatP21C akuphumelelanga, ngakho-ke akukwazanga ukusetshenziselwa ukuqhathanisa. Ucwaningo lwangomuso kufanele luhlonze ubunjalo be-TatP21 ekuthambekeni kokuthuthukiswa kokubambezeleka nokusebenza kohlelo lokwelapha.
Effective coverage of emergency obstetric and newborn care services in Wolaita Zone, Southern Ethiopia=Ukubhekana nesimo esiphuthumayo sokubelethisa nezinsiza zokunakekela izinsana endaweni iWolaita eNingizimu ye-Etopiya.
(2023) Arba, Mihiretu Alemayehu.; Khuzwayo, Nelisiwe.; Yota, Bereket Yakob.
Background: Despite the significant improvement in the availability and access of facilities in low and middle-income countries, a considerable burden of maternal and child morbidity and mortality exists, further suggesting the need for effective coverage of EmONC services. Understanding the extent to which the health system delivers quality service and the factors that predict the gap in providing the services are vital to evidence-based decisions at the local, national, and global levels. However, evidence is lacking on the effective coverage of EmONC services and factors influencing quality service provision. Objective: This study aimed to understand, explore, and describe the contexts, correlates, and levels of effective coverage of EmONC services in the Wolaita Zone, southern Ethiopia, and develop a model for effective coverage of EmONC services. Methods: After mapping the evidence for effective coverage of EmONC services in Africa, the study employed an explanatory sequential mixed-method approach. The quantitative study applied a cross148 sectional design, including 414 (facility-based survey) and 402 (house-to-house survey) study participants. The quantitative data were collected using an Open Data Kit (ODK) tablet phone software and exported to Stata version 17 for analysis. Simple and multiple linear regressions, along with p151 values, coefficients, and 95% confidence intervals, were used to declare the statistical significance and strength of the association. The qualitative study employed a case-study research design including 37 participants (selected using maximum variation sampling) to explore the barriers and enablers of EmONC services utilization. The coding and thematic analysis of the qualitative study were assisted by NVIVO version 12 software. The qualitative study assured trustworthiness by establishing credibility, transferability, conformability, and dependability. Result: The scoping review showed a paucity of evidence on the effective coverage of EmONC services in Africa. It also provided a summary of existing evidence on the crude coverage, quality of EmONC services assessed through diverse indicators, and factors linked with the quality of EmONC services. The household survey identified 72.1% crude coverage of EmONC services. The facility-based survey of EmONC services revealed that the indices of structural, process, and output quality were 74.2%, 69.4%, and 79.6%, respectively. Overall, 59.2% of women with EmONC service-need received poor quality services. Women’s education grade 1–8 (B=5.35, 95% C.I: 0.56, 10.14), and grade 9–12 (B=8.38, 95% C.I: 2.92, 13.85), age (B= 3.86, 95% C.I: 0.39, 7.33), length of stay at health facility (B= 3.58, 95% C.I: 2.66, 4.9), crowding in the delivery room (B= -4.14, 95% C.I: -6.14, -2.13), and health professional’s experience (B= 1.26, 95% C.I: 0.83, 1.69) were statistically significant predictors of observed EmONC service quality. Overall, the effective coverage (the crude coverage adjusted by the observed quality of care) of EmONC services in the Wolaita Zone was 50%, indicating half of the potential health gain loss in EmONC services. The qualitative study of barriers and facilitators of EmONC services utilization identified five themes that interacted at different levels. Theme one was women’s perceptions and experiences with EmONC services, including their knowledge and awareness of the availability of services, perception of the quality of care, reputation, respectful care, and care providers’ gender. Theme two was community-related factors encompassing misconceptions, traditional management of obstetric complications, the role of traditional birth attendants, and family and peer influence on EmONC services utilization. Theme three was the accessibility and availability of EmONC services, including infrastructure and delays in transportation. Theme four was healthcare financing which focused on drugs and supplies, out-of-pocket expenses, and service fee exemption. Theme five was the health facility-related factors related to the care provider, referral system, waiting time, and leadership. Conclusion: The study showed that the effective coverage of EmONC services in the Wolaita Zone (Southern Ethiopia) was low, where half of the potential health gain was lost due to barriers centered on the women, community, access and accessibility, healthcare financing, and health facility linked factors. The quality of EmONC services was sub-optimal, where women and newborns received inadequate services, and the care providers poorly adhered to the standard clinical actions. The study also underlined that the care providers’ adherence to the standard clinical actions was poor and is significantly associated with the age and education of women, length of stay in the facility, crowding of the delivery room, and health professionals’ experience. The inequitable effective coverage of EmONC services implied loose emphasis and suggested an urgent need for the health system’s intervention. Therefore, interventions directed at the identified bottlenecks can improve the utilization and quality of care, ultimately enhancing effective coverage. Furthermore, the model developed by the study can be utilized to enhance maternal and newborn health. Iqoqa Isingeniso: Nakuba kubonakala ukuthuthuka ekutholakaleni nasekufinyeleleni kwezikhungo emazweni anengenisomali ephansi nemaphakathi, kusenomthwalo omkhulu wokugula komama nokufa kwezingane okukhona, futhi kuphakamisa isidingo sokuhlinzekwa ngempumelelo kwezinsiza eziphuthumayo zokubelethisa nokunakekela izinsana (Emergency Obstetric and Newborn Care - EmONC) nezinto ezinomthelela ekuhlinzekeni ngensiza yezingabunjalo. Lolu cwaningo, lwaluhlose ukuqonda, ukuhlola nokuchaza ingqikithi, ukuhambisa, namazinga okufaka ngempumelelo izinsiza ze-EmONC endaweni iWolaita, eNingizimu ye-Etopiya. Izindlelakwenza: emva kokwenza inkombandlela yobufakazi yobungako bokusebenza kwezinsiza ze–EmONC e-Afrika, ucwaningo lusebenzise indlela echazayo ngokulandelanayo kwendlelakwenza eyingxube. Ucwaningo lwekhwantithethivu lusebenzise umklamomumo wocwaningo oyimpambanazigaba (isikhungo sezempilo nenhlwayalwazi yomuzi nomuzi) ngokuqoqa imininingo kusetshenziswa iOpen Data Kit yethabhulethi foni softhiwe nokuyihlaziya kusetshenziswa uhlobo lwe-17 software. Ucwaningo lwekhwalithathivu lusebenzise umklamomumo wocwaningo, futhi ukuhlaziya kulekelelwe ngeNVIVO yohlobo lwe-12 lwesofthiwe. Umphumela: ukubuyekezwa kokuhloliwe kukhombise ukuswelakala kobufakazi ngokufaka okusebenzayo kwezinsiza ze-EmONC e-Afrika. kuphinde kwabeka ngamafuphi ubufakazi obukhona nokwenza obala, ubunjalozinga bezinsiza nezinto ezihlobene. Kukho konke, ukufaka okusebenzayo kwezinsiza ze-EmONC. Inhlwayalwazi ebizinze esikhungweni idalule ukuthi izinkomba zesakhiwo, inqubo nezingabunjalo lokuphumayo kube ngama-74.2%, 69.4%, nama-79.6%, ngokulandelana. Imfundo yabesifazane, iminyaka yobudala, isikhathi sokuhlala esikhungweni sezempilo, ukuminyana endlini yokubeletha nolwazi lwabezempilo abangongoti kwakuqagula okubalulekile ngokwezibalo zezingabunjalo lokunakekelwa. Ucwaningo lwekhwalithethivu luhlonze izingqikithi ezinhlanu: imibono yabesifazane nolwazi oluhambisana nezinsiza ze-EmONC, izinto ezihambisana nomphakathi, ukufinyelela nokutholakala kwezinsiza ze-EmONC, ukufaka imali kwezempilo nezinto ezihlobene nesikhungo sezempilo. Isiphetho: Lolu cwaningo luhlonze ukubika okuphansi kokusebenza kwezinsiza ze-EmONC, ekubeni yingxenye yenzuzo yezempilo eyayingaba khona yalahleka ngenxa yemigoqo eyimixhantela. Ubunjalozinga bensiza belisezingeni eliphansi, lapho abesifazane nezinsana bethole izinsiza ezingenele, futhi abahlinzeka ngonakekelo bengagxilisisi kahle ezenzweni ezejwayelekile emtholampilo. Ukusatshalaliswa kokufaka okusebenzayo okungalingani kukhomba ukuyekethisa nokuphakamisa isidingo esiphuthumayo sohlelo lwezempilo ukuba lubhekane nezithiyo ezihlonziwe.
The effects of a lung cancer awareness intervention in KwaZulu-Natal (KZN): a stratified cluster based study in five representative communities=Imithelela yokungenelela ngokuqwashisa mayelana nomdlavuza wamaphaphu KwaZulu-Natali (KZN): Ucwaningo lwamaqoqo ngokohlelomikhakha emiphakathini emihlanu eqokelwe ucwaningo.
(2022) Dlamini, Siyabonga Blessing.; Ginindza, Bonginkosi Mfundza.
Abstract Background Lung cancer is the leading cause of cancer mortality worldwide, accounting for approximately 1.8 million cancer deaths in 2020. In South Africa, lung cancer is among the top four ranking cancers in terms of morbidity and mortality after breast, prostate, and cervical cancers. The objective of the study was, therefore, to investigate the level of awareness about lung cancer and its screening among communities in KZN, in an attempt to increase awareness of this disease across the province. Methodology A quasi-experiment study was conducted among the selected communities in KZN. In total, forty out of 879 clusters were selected, where a comparison between two cross-sectional surveys was done. An intervention employing community health workers aimed at raising awareness of lung cancer was developed, implemented and evaluated in these communities. A binary logistic regression model was used to measure the effects of the intervention. Results At baseline, approximately 59.9% (95% CI 52.0 - 67.3) of the participants had heard of lung cancer. About 5.7% (95% CI 3.9 - 8.1) were screened for lung cancer at the time. Coughing up blood was the most recognised symptom (61.0%, 95% CI 52.1 - 69.1). Post-intervention, the mean knowledge score increased to 59.9 (95% CI 53.8 – 66.0) (p<0.001). There was a reduction in the number of cigarettes smoked per day (p<0.001) and the number of packs smoked per week (p=0.026). However, the prevalence of smoking remained relatively the same before and after the intervention, at approximately 18% (p=0.958). The intervention had a statistically significant effect (aOR 4.370, 95% CI 1.477-12.928) on lung cancer knowledge in these communities (p<0.001). Conclusion The intervention in this study demonstrated the ability to raise awareness of lung cancer at a community level. It also reduced the number of cigarettes smoked among smokers. Therefore, integration into smoking cessation programmes should be explored. A national lung cancer screening programme should be introduced to encourage health-seeking behaviour. The integration of a lung cancer awareness intervention into the already existing community health worker programmes, such as the tuberculosis response strategy, is recommended. Iqoqa Isendlalelo Umdlavuza wamaphaphu ungenye yezimbangela eziphambili zokubulawa umdlavuza emhlabeni wonke jikelele. Kubantu ababulawa umdlavuza ngonyaka wezi-2020, bayi-1.8 wezigidi zabantu ababulawa umdlavuza wamaphaphu. ENingizimu Afrika umdlavuza wamaphaphu ungolunye lwezinhlobo ezine zomdlavuza ezihamba phambili eziphatha abantu futhi zibabulale emva komdlavuza webele, umdlavuza wamankwahlwa (iprostate), kanye nowesibeletho. Inhloso yalolu cwaningo kwakunguphenya ngamazinga olwazi mayelana nomdlavuza wamaphaphu kanye nokuhlolwa kwawo emiphakathini yaKwaZulu-Natali ngenjongo yokuqwashisa kabanzi ngalesi sifo esifundazweni jikelele. Indlelakwenza Kwenziwa ucwaningo oluyisingalinge emiphakathini eqokelwe ucwaningo KwaZulu-Natali. Esewonke kwakhethwa amaqoqwana angama-879 lapho kwaqhathaniswa khona amasaveyi amabili across-sectional. Kwathuthukiswa, kwasetshenziswa kwaphinda kwahlolwa ukungenelela konompilo ngenhloso yokuqwashisa ngomdlavuza wamaphaphu kule miphakathi. Kwasetshenziswa imodeli yesilinganisobudlelwane ukulinganisa imithelela yalokhu kungenelela. Imiphumela Ukusuka phansi, bangacishe babe ngama-59.9% (95% CI 52.0 - 67.3)kubabambiqhaza abake bezwa ngomdlavuza wamaphaphu. Okungenani u-5.7% (95% CI 3.9 - 8.1) wahlolwa umdlavuza wamaphaphu ngaleso sikhathi. Ukukhwehlela igazi yikhona okwakuyinkomba eyaziwayo (61.0%, 95% CI 52.1 - 69.1). Emva kokungenelela, imini yobungako bolwazi yanyukela ku-59.9% (95% CI 53.8 – 66.0) (p<0.001). Kwaba nokuncipha kwesibalo sosikilidi ababhenywa ngosuku (p<0.001) kanye namaphakethe abhenywa ngesonto (p=0.026). Kodwa-ke, ukuvama kokubhema akuzange kwehle ngaphambi kanye nasemuva kokungenelela; kwakumi ku-18% (p=0.958). Ukungenelela kwaba nomthelela omkhulu ngokwezibalomidanti (aOR 4.370, 95% CI 1.477-12.928)maqondana nolwazi ngomdlavuza wamaphaphu kule miphakathi (p<0.001). Isiphetho Ukungenelela kulolu cwaningo kwakhombisa okungenzeka uma kuqwashiswa abantu ngomdlavuza wamaphaphu ezigabeni semiphakathi. Kwaphinda kwanciphisa isibalo sikasikilidi obhenywayo kubantu ababhemayo. Ngakho-ke kumele kuhlolwe izindlela zokuhlanganiswa kwezinhlelo zokuyekiswa ukubhema. Kumele kuqaliswe ngohlelo lukazwelonke lokuhlola umdlavuza wamaphaphu kubantu ukuze kukhuthazwe umkhuba wokufuna usizo lwezempilo. Kuphakanyiswa ukuthi kuhlanganiswe ukungenelela ngokuqwashisa abantu ngomdlavuza wamaphaphu ezinhlelweni zonompilo ezikhona emiphakathini ezifana namaqhinga okuhlangabezana nesifo sofuba.
Evaluation of laboratory tests for COVID-19 in South Africa = Ukuhlaziya iZivivinyo zaseLabhorethri ze-COVID-19 eNingizimu Afrika
(2023) Samsunder, Natasha.; Kharsany, Ayesha Bibi Mahomed.; Sivro, Aida.
The emergence of SARS-CoV-2 prompted urgent needs for accurate diagnosis, management, and containment strategies. This study evaluated diagnostic tests, including point-of-care (POC) tests, to aid in rapid diagnosis across different stages of COVID-19 in South Africa. A scoping review highlighted the variability in test performance, with no single assay achieving optimal sensitivity and specificity simultaneously. Sensitivity was influenced by the timing of sample collection, emphasizing the importance of early sampling. Rapid antigen tests were evaluated against RT-PCR, revealing reasonable sensitivity, especially in samples with lower Ct values and within the first week of symptom onset. However, performance varied across SARS-CoV-2 variants. Notably, PanbioTM and SD Biosensor tests maintained high sensitivity and specificity across different variants, including Omicron sub-lineages. Additionally, the study explored alternative sample types, such as saliva, finding comparable results to nasopharyngeal swabs. Serological tests were also assessed, with the Orient Gene Rapid test showing comparable performance to standard assays, while the MILLIPLEX® MAP Kit demonstrated higher detectability. Overall, despite extensive testing efforts, the sensitivity of diagnostic tests remained limited, underscoring the need for improved performance to effectively diagnose and manage SARS-CoV-2 infections and limit transmission. These findings provide valuable insights for enhancing testing strategies in South Africa and globally amidst evolving pandemic challenges. Iqoqa. Ukuqubuka kwe-SARS-CoV-2 kwaphusha izidingo eziphuthumayo zamasu okuhlonza isifo okuyikho, ukulawula nokunqanda. Lolu cwaningo lwahlola izivivinyo, okufaka nezivivinyo ezaziwa ngelepoint-of-care (POC), ukusiza ukuhlonza isifo ngokushesha ezigabeni ezehlukene ze-COVID-19 eNingizimu Afrika. Ukubuyekeza umumo kwagqamisa ukwehlukahlukana ekuhloleni ukusebenza, kungekho neyodwa i-asayi efikisa ekuzweleni okukhulu nasekuqondeni kanyekanye. Ukuzwela kwakudalwa yisikhathi sokuqoqwa kwesampula, kugcizelelwa ukubaluleka kokuqoqwa kwamasampula kwasekuqaleni. Izivivinyo eziningi zedalasihlungu zahlaziywa ziqhathaniswa ne-RT-PCR, okuveza ukuzwela okuzwakalayo, ikakhulukazi emasampuleni ane-Ct ephansi esontweni lokuqala lokubonakala kwezimpawu. Kodwa, ukusebenza kwehlukana ngokwezinhlobo ze-SARS-CoV-2. Okuqaphelekayo, yi-v Notably, PanbioTM nezivivinyo ze-SD Biosensor ezasimama ngokuzwela okukhulu namavariyenti ehlukene, okufaka nama-Omicron sub-lineages. Ukwengeza, ucwaningo lubheke ezinye izinhlobo zamasampula, njengamathe, ukuthola imiphumela eqhathaniseka nemisubelo yenasopharyngeal. Izivivinyo zeseroloji nazo zahlolwa, kanye nesivivinyo se-Orient Gene Rapid okukhombisa ukusebenza okuqhathanisekayo nama-asayi asezingeni, nakuba i-MILLIPLEX® MAP Kit yakhombisa ukutholakala ngezinga eliphezulu. Ngaphezu kwalokho, nakuba kunemizamo yokuhlola okunzulu, ubuthaka bezivivinyo eziyinhlonzasifo zazilokhu zincane, ukuthola okungaphansi isidingo sokusebenza okuphuculiwe ukuze kuhlonzwe ngendlela futhi kulawulwe ukutheleleka nge-SARS-CoV-2 bese kunqanda ukwedluliseka. Lokhu okutholakele kuhlinzeka imibono enesisindo ukuphucula amasu okuhlola eNingizimu Afrika nasemhlabeni jikelele ezinselelweni zobhubhane eziguquguqukayo.
Evaluation of the addition of moringa oleifera as a nutritional supplement on the anthropometric, viral load, and cd4 counts of adult hiv patients on antiretroviral therapy.
(2022) Gambo, Aisha.; Gqaleni, Nceba.
Background: This thesis reports on studies conducted at the S. S Wali virology centre, Aminu Kano Teaching Hospital (AKTH), Kano State, Nigeria. The studies aimed to evaluate the addition of Moringa oleifera Lam. leaves powder as a nutritional supplement on the anthropometric and immune status of adult HIV patients on antiretroviral therapy (ART). The studies further assessed the quality of life (QoL) and dietary diversity of PLHIV. Method: The study was a six months double-blind randomized controlled trial conducted from December 2017 to November 2018. Two hundred consented patients on ART were randomly allocated to either Moringa oleifera Lam. group (MOG) or the control group (COG). The participants were followed for six months. The outcomes assessed were changes in anthropometric parameters (weight, body mass index [BMI], and mid-upper-arm circumference [MUAC], changes in immune status (CD4 cell count and viral load), and the impact of the intervention on quality of life (QoL) using the WHOQOLHIV-Bref questionnaire. Additionally, the dietary diversity of the patients was assessed using the FAO 24-hour dietary recall questionnaire. Results: One hundred and seventy-seven patients completed the six-month follow-up (89 MOG versus 88 COG). At study inception, both groups had similar socio-demographic, socioeconomic, nutritional status, and immunological characteristics. At both baseline and sixth month, a poor dietary diversity pattern was observed. The food groups most commonly consumed in both MOG and COG were cereals, spices and condiments, oils, fats and palm oil, and dark green vegetables. In both groups, participants were in the medium or low dietary diversity tercile. Over the study period, Moringa oleifera Lam. leaf supplementation did not have an impact on any of the anthropometric parameters measured. However, Moringa oleifera Lam. leaf supplementation intervention and ART were effective in improving the CD4 cell counts of the study participants. No effect was observed in the viral loads in both study groups. Supplementation with Moringa oleifera Lam. leaf for PLHIV that are on ART improves the quality of life (QoL) domains of physical, psychological, level of independence, and social relationships. Conclusion: The study suggests that nutritional supplementation with Moringa oleifera Lam. leaf has a beneficial effect among adult HIV patients on ART in a limited resource setting. In low-income settings like Nigeria, programs should consider nutritional supplementation as part of a comprehensive approach to ensure optimal treatment outcomes in people living with HIV and AIDS.

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