Publications by authors named "Yasmin Mohamed"

24 Publications

  • Page 1 of 1

Operational experiences associated with the implementation of near point-of-care early infant diagnosis of HIV in Myanmar: a qualitative study.

BMC Health Serv Res 2021 Aug 23;21(1):863. Epub 2021 Aug 23.

Burnet Institute, Melbourne, Australia.

Background: Timely diagnosis and early initiation of life-saving antiretroviral therapy are critical factors in preventing mortality among HIV-infected infants. However, resource-limited settings experience numerous challenges associated with centralised laboratory-based testing, including low rates of testing, complex sample referral pathways and unacceptably long turnaround times for results. Point-of-care (POC) HIV testing for HIV-exposed infants can enable same-day communication of results and early treatment initiation for HIV-infected infants. However, complex operational issues and service integration can limit utility and must be well understood prior to implementation. We explored and documented the challenges and enabling factors in implementing the POC Xpert® HIV-1 Qual test (Cepheid, Sunnyvale, CA, USA) for early infant diagnosis (EID) as part of routine services in four public hospitals in Myanmar.

Methods: This sub-study was part of a randomised controlled stepped-wedge trial (Australian and New Zealand Clinical Trials Registry, number 12616000734460) designed to investigate the impact of POC testing for EID in Myanmar and Papua New Guinea. Infants recruited during the intervention phase underwent POC testing at the participating hospitals as part of routine care. Semi-structured interviews with 23 caregivers, 12 healthcare providers and 10 key informants were used to explore experiences of POC-EID testing. The research team and hospital staff documented and discussed implementation challenges throughout the study.

Results: Overall, caregivers and healthcare workers were satisfied with the short turnaround time of the POC test. Occasional delays in POC testing were mostly attributable to late receipt of samples by laboratory technicians and communication constraints among healthcare staff. Hospital staff valued technical assistance from the research group and the National Health Laboratory. Despite staff shortages and infrastructure challenges such as unreliable electricity supply and cramped space, healthcare workers and caregivers found the implementation of the POC test to be feasible at pilot sites.

Conclusions: As plans for national scale-up evolve, there needs to be a continual focus on staff training, communication pathways and infrastructure. Other models of care, such as allowing non-laboratory-trained personnel to perform POC testing, and cost effectiveness should also be evaluated.
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http://dx.doi.org/10.1186/s12913-021-06797-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8383426PMC
August 2021

Protective effects of perindopril against indomethacin-induced gastric mucosal damage through modulation of DDAH-1/ADMA and ACE-2/ANG-(1-7) signaling pathways.

Drug Chem Toxicol 2021 Aug 13:1-10. Epub 2021 Aug 13.

Department of Pharmacology and Toxicology, Faculty of Pharmacy, Beni-Suef University, Beni-Suef, Egypt.

Indomethacin is a widely used nonsteroidal anti-inflammatory drug; however, its clinical utility is accompanied by serious adverse reactions including peptic ulcers. The current study aims to investigate the protective potential of perindopril against indomethacin-induced gastric injury in rats. Perindopril (4 mg/kg) was administered orally for 7 days and indomethacin (60 mg/kg, single oral dose) was administered on the 7 day, 1 h after perindopril administration. Pantoprazole was used as a standard agent. Ulcer index (UI), preventive index ratio (PI), histopathological examination, oxidative stress, and inflammatory biomarkers were investigated. Perindopril significantly decreased UI while increased PI and counteracted histopathological aberrations induced by indomethacin. It alleviated indomethacin-induced oxidative stress by lowering NO while increasing GSH content and superoxide dismutase activity. Perindopril significantly downregulated TNF-α and asymmetric dimethylarginine (ADMA), while significantly upregulated COX-2, PGE-2, dimethylarginine dimethylaminohydrolase-1 (DDAH-1), ANG-(1-7), and ACE-2 expression. Together, these findings suggest the gastroprotective effects of perindopril through modulation of DDAH-1/ADMA and ACE-2/ANG-(1-7) signaling.HIGHLIGHTSPerindopril attenuated gastric histopathological damage.It increased GSH content and SOD activity while decreased NO content.It modulated gastric ADMA and DDAH-1 activity.It reduced TNF-α, while increased COX-2 and PGE-2 expression.It upregulated ACE-2 activity and ANG-(1-7) protein expression.
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http://dx.doi.org/10.1080/01480545.2021.1962672DOI Listing
August 2021

Middle-East OBGYN Graduate Education (MOGGE) Foundation practice guidelines: prevention of group B Streptococcus infection in pregnancy and in newborn. Practice guideline no. 02-O-20.

J Matern Fetal Neonatal Med 2021 Feb 24:1-12. Epub 2021 Feb 24.

Department of Obstetrics and Gynecology, Assiut School of Medicine, Assiut, Egypt.

Rectovaginal colonization with group B streptococcus (GBS) is commonly encountered in pregnancy. GBS is the most common cause of early onset neonatal sepsis, which is associated with 12% case-fatality rate. Although screening protocols and prophylactic treatment are readily available worldwide, practice in low-resource countries is challenged by lack of awareness and limited implementation of these protocols. In addition, antibiotic susceptibility pattern may vary globally owing to different regulations of antibiotic prescription or prevalence of certain bacterial serotypes. This guideline appraises current evidence on screening and management of GBS colonization in pregnancy particularly in low-resource settings.
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http://dx.doi.org/10.1080/14767058.2021.1875211DOI Listing
February 2021

Feasibility and acceptability of implementing early infant diagnosis of HIV in Papua New Guinea at the point of care: a qualitative exploration of health worker and key informant perspectives.

BMJ Open 2020 11 19;10(11):e043679. Epub 2020 Nov 19.

Sexual and Reproductive Health Unit, Papua New Guinea Institute of Medical Research, Goroka, Papua New Guinea.

Introduction: Early infant diagnosis (EID) of HIV and timely initiation of antiretroviral therapy can significantly reduce morbidity and mortality among HIV-positive infants. Access to EID is limited in many low-income and middle-income settings, particularly those in which standard care involves dried blood spots (DBS) sent to centralised laboratories, such as in Papua New Guinea (PNG). We conducted a qualitative exploration of the feasibility and acceptability of implementing a point-of-care (POC) EID test (Xpert HIV-1 Qualitative assay) among health workers and key stakeholders working within the prevention of mother-to-child transmission of HIV (PMTCT) programme in PNG.

Methods: This qualitative substudy was conducted as part of a pragmatic trial to investigate the effectiveness of the Xpert HIV-1 Qualitative test for EID in PNG and Myanmar. Semistructured interviews were undertaken with 5 health workers and 13 key informants to explore current services, experiences of EID testing, perspectives on the Xpert test and the feasibility of integrating and scaling up POC EID in PNG. Coding was undertaken using inductive and deductive approaches, drawing on existing acceptability and feasibility frameworks.

Results: Health workers and key informants (N=18) felt EID at POC was feasible to implement and beneficial to HIV-exposed infants and their families, staff and the PMTCT programme more broadly. All study participants highlighted starting HIV-positive infants on treatment immediately as the main advantage of POC EID compared with standard care DBS testing. Health workers identified insufficient resources to follow up infants and caregivers and space constraints in hospitals as barriers to implementation. Participants emphasised the importance of adequate human resources, ongoing training and support, appropriate coordination and a sustainable supply of consumables to ensure effective scale-up of the test throughout PNG.

Conclusions: Implementation of POC EID in a low HIV prevalence setting such as PNG is likely to be both feasible and beneficial with careful planning and adequate resources.

Trial Registration Number: 12616000734460.
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http://dx.doi.org/10.1136/bmjopen-2020-043679DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7678362PMC
November 2020

Caregiver experience and perceived acceptability of a novel near point-of-care early infant HIV diagnostic test among caregivers enrolled in the PMTCT program, Myanmar: A qualitative study.

PLoS One 2020 30;15(10):e0241245. Epub 2020 Oct 30.

The Kirby Institute for Infection and Immunity in Society, UNSW Sydney, Sydney, Australia.

Background: The majority of HIV infection among children occurs through mother-to-child transmission. HIV exposed infants are recommended to have virological testing at birth or 4-6 weeks of age but challenges with centralized laboratory-based testing in Myanmar result in low testing rates and delays in result communication and treatment initiation. Decentralized point-of-care (POC) testing when integrated in prevention of mother-to-child transmission of HIV (PMTCT) services, can be an alternative to increase coverage of early infant diagnosis (EID) and timely engagement in HIV treatment and care.

Aim: This paper aims to explore experiences of caregivers of HIV-exposed infants enrolled in the PMTCT program in Myanmar and the perceived acceptability of point-of-care EID testing compared to conventional centralised laboratory-based testing.

Methods: This is a sub-study of the cluster randomised controlled stepped-wedge trial (Trial registration number: ACTRN12616000734460) that assessed the impact of near POC EID testing using Xpert HIV-1 Qual assay in four public hospitals in Myanmar. Caregivers of infants who were enrolled in the intervention phase of the main study, had been tested with both Xpert and standard of care tests and had received the results were eligible for this qualitative study. Semi-structured interviews were conducted with 23 caregivers. Interviews were audio recorded, transcribed verbatim and translated into English. Thematic data analysis was undertaken using NVivo 12 Software (QSR International).

Results: The majority of caregivers were satisfied with the quality of care provided by PMTCT services. However, they encountered social and financial access barriers to attend the PMTCT clinic regularly. Mothers had concerns about community stigma from the disclosure of their HIV status and the potential consequences for their infants. While medical care at the PMTCT clinics was free, caregivers sometimes experienced financial difficulties associated with out-of-pocket expenses for childbirth and transportation. Some caregivers had to choose not to attend work (impacting their income) or the adult antiretroviral clinic in order to attend the paediatric PMTCT clinic appointment. The acceptability of the Xpert testing process was high among the caregiver participants and more than half received the Xpert result on the same day as testing. Short turnaround time of the near POC EID testing enabled the caregivers to find out their infants' HIV status quicker, thereby shortening the stressful waiting time for results.

Conclusion: Our study identified important access challenges facing caregivers of HIV exposed infants and high acceptability of near POC EID testing. Improving the retention rate in the PMTCT and EID programs necessitates careful attention of program managers and policy makers to these challenges, and POC EID represents a potential solution.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0241245PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7598472PMC
December 2020

Improving the coverage and accuracy of syphilis testing: The development of a novel rapid, point-of-care test for confirmatory testing of active syphilis infection and its early evaluation in China and South Africa.

EClinicalMedicine 2020 Jul 27;24:100440. Epub 2020 Jun 27.

Burnet Institute, 85 Commercial Road, Melbourne, Victoria 3004, Australia.

Background: Current point-of-care tests (POCT) for syphilis, based on the detection of (TP) total antibodies, have limited capacity in distinguishing between active and past/treated syphilis. We report the development and early evaluation of a new prototype POCT based on the detection of TP-IgA antibodies, a novel biomarker for active syphilis.

Methods: The TP-IgA POCT (index test) was developed in response to the World Health Organisation (WHO) target product profile (TPP) for a POCT for confirmatory syphilis testing. Two sub-studies were conducted consecutively using 458 pre-characterised stored plasma samples in China (sub-study one, addressing the criteria for the WHO TPP), and 503 venous blood samples collected from pregnant/postpartum women in South Africa (sub-study two, addressing potential clinical utility). Performance of the index test was assessed against standard laboratory-based serology using a combination of treponemal (TPHA) and non-treponemal (rapid plasma reagin [RPR]) tests.

Findings: In sub-study one, the index test demonstrated 96·1% (95%CI=91·7%-98·5%) sensitivity and 84·7% (95%CI=80·15-88·6%) specificity for identification of active syphilis (TPHA positive, RPR positive). It correctly identified 71% (107/150) samples of past-treated syphilis (TPHA positive, RPR negative). In sub-study two, the index test achieved 100% (95%CI=59%-100%) sensitivity for active syphilis and correctly identified all nine women with past syphilis.

Interpretation: The TP-IgA POCT has met the WHO TPP for a POCT for diagnosis of active syphilis and demonstrated its potential utility in a clinical setting. Future studies are warranted to evaluate field performance of the final manufactured test.

Funding: Saving Lives at Birth: Grand Challenge for Development, Thrasher Research Fund, and the Victorian Government Operational Infrastructure Scheme.
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http://dx.doi.org/10.1016/j.eclinm.2020.100440DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7327895PMC
July 2020

Regulation of liver regeneration by prostaglandin E and thromboxane A following partial hepatectomy in rats.

Naunyn Schmiedebergs Arch Pharmacol 2020 08 11;393(8):1437-1446. Epub 2020 Mar 11.

Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Kasr El Aini St., Cairo, Egypt.

The implication of prostaglandin E (PGE) and thromboxane A (TXA) in the striking process of liver regeneration has been previously reported. However, their exact roles and downstream signals have not been utterly revealed. Therefore, the present study was conducted to explore whether inhibition of cyclooxygenase-2 (COX-2)-derived PGE by celecoxib and blocking of TXA action by seratrodast could alter the progression of liver regeneration after 70% partial hepatectomy (PHx) in rats. Celecoxib (20 mg/kg/day) and seratrodast (2 mg/kg/day) were given orally 1 h before PHx and then daily till the end of experiment (1, 3, or 7 days after the operation). Interestingly, celecoxib-treated rats showed a further increase in interleukin-6, p65 nuclear factor κB, and phosphorylated signal transducer and activator of transcription 3 as compared with PHx control rats. Furthermore, the liver contents of growth factors as well as β-catenin and cyclin D1protein expressions were also enhanced by celecoxib. Accordingly, celecoxib significantly improved hepatic proliferation as indicated by the increase in Ki67 expression and liver index. Contrariwise, seratrodast hindered the normal regeneration process and completely abolished the proliferative effect of celecoxib. In conclusion, TXA has a major role in liver regeneration that could greatly mediate the triggering effect of celecoxib on hepatocytes proliferation following PHx.
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http://dx.doi.org/10.1007/s00210-020-01848-8DOI Listing
August 2020

Synthesis, Cytotoxicity and Docking Simulation of Novel Annulated Dihydroisoquinoline Heterocycles.

Mini Rev Med Chem 2020 ;20(12):1166-1178

4National Organization for Drug Control and Research, Dokki, Giza, Egypt.

Objective: Coupling of ethyl 2-(6,7-dimethoxy-3,4-dihydroisoquinolin-1-yl)acetate 2 with diazotized anilines in ethanol in the presence of sodium acetate yielded 2-(2-arylhydrazono)-2-(6,7- dimethoxy-3,4-dihydroisoquinolin-1-yl)acetate (4a-f).

Methods: Treatment of 2 with α-bromoketones 6a-f in dry benzene at reflux gave the corresponding isoquinolinium bromides 7a-f. Refluxing of each of the salts 7a-f in dry benzene and in the presence of triethylamine yielded 2-arylpyrrolo-[2,1-a]isoquinoline structures 8a-f, that converted to ethyl (E)-8,9- dimethoxy-3-(phenyldiazen-yl)-2-(aryl)-5,6-dihydropyrrolo[2,1-a]isoquinoline-1-carboxylate (9a-f) upon treatment with diazotized anilines 3 in ethanol in the presence of sodium acetate.

Results And Conclusion: Cytotoxic assay was performed for in vitro antitumor screening against caucasian breast adenocarcinoma (MCF7), hepatocellular carcinoma (HepG2) and colorectal carcinoma (HCT-116) cell lines. The results were compared with the standard anticancer drug (doxorubicin). Molecular docking using MOE 2014.09 software was carried out for the most potent compound 4d, which showed the highest binding affinity towards the four tested proteins and thus initiated apoptosis of cancer cells.
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http://dx.doi.org/10.2174/1389557520666200130104632DOI Listing
February 2021

Type-Specific Human Papillomavirus Prevalence, Incident Cases, Persistence, and Associated Pregnancy Outcomes Among HIV-Infected Women in Kenya.

Sex Transm Dis 2019 08;46(8):532-539

Ghent University, Ghent, Belgium.

Background: Persistent infection with high-risk types of human papillomavirus (HPV) is the preeminent factor driving the development of cervical cancer. There are large gaps in knowledge about both the role of pregnancy in the natural history of HPV infection and the impact of HPV on pregnancy outcomes.

Methods: This single-site prospective cohort substudy, nested within an international multisite randomized controlled trial, assessed prevalence, incident cases, and persistence of type-specific HPV infection, and the association between persistence of high-risk HPV infection with pregnancy outcomes among HIV-infected pregnant women in Kenya, including HIV transmission to infants. Type-specific HPV was assessed using a line probe assay in pregnancy and again at 3 months after delivery. HIV status of children was determined using polymerase chain reaction at 6 weeks.

Results: In total, 84.1% (206/245) of women had a high-risk HPV infection at enrollment. Three quarters (157/206) of these infections persisted postpartum. Persistence of HPV16 and/or HPV18 types was observed in more than half (53.4%; 39/73) of women with this infection at enrollment. Almost two-thirds had an incident high-risk HPV infection postpartum, which was not present in pregnancy (62.5%), most commonly HPV52 (19.0%). After adjustments, no association was detected between persistent high-risk HPV and preterm birth. All mothers of the 7 cases of infant HIV infection had persistent high-risk HPV infection (P = 0.044).

Conclusions: High levels of high-risk HPV infection and type-specific persistence were documented, heightening the urgency of mass role out of HPV vaccination. The association between HPV persistence and HIV transmission is a novel finding, warranting further study.
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http://dx.doi.org/10.1097/OLQ.0000000000001029DOI Listing
August 2019

Outcome predictors of autologous hematopoietic stem cell transplantation in children with relapsed and refractory Hodgkin lymphoma: Single-center experience in a lower-middle-income country.

Pediatr Transplant 2019 09 4;23(6):e13531. Epub 2019 Jul 4.

Department of Pediatric Oncology and Stem Cell Transplantation Unit, Children Cancer Hospital Egypt (CCHE-57357), Cairo, Egypt.

Background: Children and adolescents with HL have excellent long-term survival exceeding 95% after combined modality treatment. However, about 20% will either relapse or have PRF. Salvage HDCT followed by AHSCT is considered to be the preferential treatment.

Objective: To describe the outcome (OS and EFS) and prognostic factors in pediatric patients with relapsed or refractory HL (r/rHL) who underwent AHSCT.

Methods: We retrospectively included 43 pediatric patients with r/rHL who underwent AHSCT from July 1, 2007, till December 31, 2016, at the Children's Cancer Hospital of Egypt. MAC regimen given was CMV.

Results: Of the whole cohort, 88.4% of patients achieved CR, while 11.6% had a positive PET scan prior to transplantation. The 3-year OS and EFS were 85% and 70.6%, respectively. The 3-year OS for patients > 10 years was 94% versus 65.5% for patients 10 years of age or younger (P = 0.046). There is strong tendency toward better 3-year OS for patients with negative PET scan as compared to those with positive PET scan before AHSCT, 89.4% vs 60%, respectively (P = 0.059). This tendency is also applicable when looking at the 3-year EFS for the two groups, 78.3% vs 40%, respectively (P = 0.069).

Conclusion: Poor predictors of OS were younger age and positive PET scan before AHSCT. The latter, along with single modality treatment before AHSCT, were poor predictors of EFS.
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http://dx.doi.org/10.1111/petr.13531DOI Listing
September 2019

Biological Activity, Apoptotic Induction and Cell Cycle Arrest of New Hydrazonoyl Halides Derivatives.

Anticancer Agents Med Chem 2019 ;19(9):1141-1149

Chemistry Department (Biotechnology- Biomolecular Chemistry Program), Faculty of Science, Cairo University, Giza, Egypt.

Background: The hydrazonoyl halides are presently an important target in the field of medicinal chemistry. The interest in the chemistry of hydrazonoyl halides is a consequence of the fact that they undergo a wide variety of reactions which provide routes to a myriad of both heterocyclic and acyclic compounds. In addition, they have diverse biological activities such as antiviral, anthelmintic, antiarthropodal, fungicidal, herbicidal, insecticidal, pesticidal, acaricidal and miticidal Activity correlated to the presence of hydrazonoyl halides. Moreover, many applications in both industrial and pharmaceutical fields have been found to be associated with these halides. Depending on the above facts and continuation to our work, we herein report on the evaluation of the anticancer activity of these two halides prepared according to the published work and trying to know their molecular mechanism that they proceed to stop proliferation and metastasis of tumor cells by molecular tools such as real time PCR using different apoptotic genes, and cell cycle assay.

Objective: The goal of this present study is to bring attention to the biological activities of hydrazonoyl halides and the molecular pathway they follow to exert their role in apoptotic death of cancer cell.

Methods: Synthesis of hydrazonoyl halides 2c and 2f. The cytotoxic effect against different human cancer cell lines PC3, HepG-2, HCT-116, MCF-7 and also on normal human cell lines as MCF-10 and MCF-12 in a monolayer culture model was evaluated. Their mechanism of action inside cancer cell was evaluated using different molecular tools.

Conclusion: Strong and promising chemotherapeutic hydrazonoyl halides (2a-2f) were evaluated for their different biological activities. As antimicrobial agents, results indicated that three compounds 2a, 2e and 2f exhibited high activity against two tested gram positive bacteria Staphylococcus aureus, Bacillus subtilis, and gram negative ones Escherichia coli, and Pseudomonas aeruginosa, the rest of the compounds were found to be moderately active against the tested microorganisms. Regarding their antifungal effect, compound 2c exhibited potent and promising effect against Candida albicans, while 2b was the most potent toward Aspergillus flavus Link. The compound 2f has repellent effect. With respect to the in vitro antitumor screening, this was done on different human cancer cell lines; namely PC3, HepG-2, HCT-116, MCF-7 and also on normal human cell lines; as MCF-10 and MCF-12 (normal breast epithelial cell and non-tumorigenic breast epithelial cell line) in a monolayer culture model where screening has been conducted at 100μg/ml (single dose test). Single dose test (100μg/ml) showed that, in case of PC3, all compounds have cytotoxic activity over 90% inhibition, 4 compounds have cytotoxic activity with 100% inhibition with Human colon cancer cell line, 4 compounds showed over 90% inhibition with MCF7 cell line and 4 compounds showed cytotoxic activity over 90% inhibition with HepG-2. Results of IC50 values for most promising compounds showed compounds with values lower than 20μM for all tested human cancer cell line. The promising hydrazonoyl halide 2c and 2f were selected for molecular study to know how they could act inside cancer cell causing death. Two biochemical tests were performed using the two halides 2c and 2f to predict their mechanism of action against breast carcinoma. Real time PCR analysis indicates that the two compounds induced the apoptosis of MCF7 cells through the up regulation of caspase-3, BAX mediated P53 mechanism but unfortunately, they promote the expression of anti-apoptotic protein BCL2. Also, cell cycle assay was performed using two different cell lines MCF7 and HCT116 and data revealed that the two compounds 2c and 2f induced apoptotic cells death of both lines via cell growth arrest at G2/M phase. In addition, it was noted that 2c induced arrest in the two lines more efficiently than 2f at G2/M phase.
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http://dx.doi.org/10.2174/1871520619666190306123658DOI Listing
April 2020

Qualitative assessment of South African healthcare worker perspectives on an instrument-free rapid CD4 test.

BMC Health Serv Res 2019 Feb 14;19(1):123. Epub 2019 Feb 14.

Wits Reproductive Health and HIV Institute (Wits RHI), Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.

Background: Accurate measurement of CD4 cell counts remains an important tenet of clinical care for people living with HIV. We assessed an instrument-free point-of-care CD4 test (VISITECT® CD4) based on a lateral flow principle, which gives visual results after 40 min. The test involves five steps and categorises CD4 counts as above or below 350 cells/μL. As one component of a performance evaluation of the test, this qualitative study explored the views of healthcare workers in a large women and children's hospital on the acceptability and feasibility of the test.

Methods: Perspectives on the VISITECT® CD4 test were elicited through in-depth interviews with eight healthcare workers involved in the performance evaluation at an antenatal care facility in Johannesburg, South Africa. Audio recordings were transcribed in full and analysed thematically.

Results: Healthcare providers recognised the on-going relevance of CD4 testing. All eight perceived the VISITECT® CD4 test to be predominantly user-friendly, although some felt that the need for precision and optimal concentration in performing test procedures made it more challenging to use. The greatest strength of the test was perceived to be its quick turn-around of results. There were mixed views on the semi-quantitative nature of the test results and how best to integrate this test into existing health services. Participants believed that patients in this setting would likely accept the test, given their general familiarity with other point-of-care tests.

Conclusions: Overall, the VISITECT® CD4 test was acceptable to healthcare workers and those interviewed were supportive of scale-up and implementation in other antenatal care settings. Both health workers and patients will need to be oriented to the semi-quantitative nature of the test and how to interpret the results of tests.
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http://dx.doi.org/10.1186/s12913-019-3948-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6376755PMC
February 2019

A qualitative exploration of menstruation-related restrictive practices in Fiji, Solomon Islands and Papua New Guinea.

PLoS One 2018 3;13(12):e0208224. Epub 2018 Dec 3.

Burnet Institute, Melbourne, Victoria, Australia.

Attitudes and beliefs about menstruation can place restrictions on menstruating women and girls, limiting their ability to fully participate in community life, education and employment. This paper presents evidence on menstruation-related beliefs contributing to restrictive practices in Papua New Guinea (PNG), Solomon Islands (SI) and Fiji. Focus group discussions and interviews were undertaken with 307 adolescent girls, women and men in a rural and urban site in each country. Data were analysed using an inductive thematic approach. Participants described a range of attitudes and beliefs that restrict the behaviour of menstruating women and girls. Themes include the belief that menstrual blood is 'dirty'; that when menstruating, girls and women can bring 'bad luck' to men; secrecy and shame associated with menstruation; and beliefs about the impact of certain behaviours on menstruation and health. Restrictive practices were more frequently reported in PNG and SI than Fiji, and more common in rural compared with urban sites. Some restrictions, such as avoidance of household chores, were perceived as desirable or driven by women themselves. However participants identified other restrictions, such as not being able to attend church or hygienically wash menstrual hygiene materials, as unwanted, in some cases impacting on participation in school, work and community life. Education initiatives guided by women and girls, implemented by local stakeholders and grounded in a sound understanding of specific contexts are needed to address discriminatory attitudes and beliefs that contribute to unwanted restrictions, and to support enabling attitudes and beliefs regarding menstruation.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0208224PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6277107PMC
May 2019

Field Performance and Diagnostic Accuracy of a Low-Cost Instrument-Free Point-of-Care CD4 Test (Visitect CD4) Performed by Different Health Worker Cadres among Pregnant Women.

J Clin Microbiol 2019 02 30;57(2). Epub 2019 Jan 30.

Burnet Institute, Melbourne, Victoria, Australia.

Measuring CD4 counts remains an important component of HIV care. The Visitect CD4 is the first instrument-free low-cost point-of-care CD4 test with results interpreted visually after 40 min, providing a result of ≥350 CD4 cells/mm The field performance and diagnostic accuracy of the test was assessed among HIV-infected pregnant women in South Africa. A nurse performed testing at the point-of-care using both venous and finger-prick blood, and a counselor and laboratory staff tested venous blood in the clinic laboratory (four Visitect CD4 tests/participant). Performance was compared to the mean CD4 count from duplicate flow cytometry tests on venous blood (FACSCalibur Trucount). In 2017, 156 patients were enrolled, providing a total of 624 Visitect CD4 tests (468 venous and 156 finger-prick samples). Of 624 tests, 28 (4.5%) were inconclusive. Generalized linear mixed modeling showed better performance of the test on venous blood (sensitivity = 81.7%; 95% confidence interval [CI] = 72.3 to 91.1]; specificity = 82.6%, 95% CI = 77.1 to 88.1) than on finger-prick specimens (sensitivity = 60.7%; 95% CI = 45.0 to 76.3; specificity = 89.5%, 95% CI = 83.2 to 95.8;  = 0.001). No difference in performance was detected by cadre of health worker ( = 0.113) or between point-of-care versus laboratory-based testing ( = 0.108). Adequate performance of Visitect CD4 with different operators and at the point of care, with no need of electricity or instrument, shows the potential utility of this device, especially for facilitating decentralization of CD4 testing services in rural areas.
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http://dx.doi.org/10.1128/JCM.01277-18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6355532PMC
February 2019

Assessing the operational feasibility and acceptability of an inhalable formulation of oxytocin for improving community-based prevention of postpartum haemorrhage in Myanmar: a qualitative inquiry.

BMJ Open 2018 10 24;8(10):e022140. Epub 2018 Oct 24.

Burnet Institute, Melbourne, Australia.

Objective: This study assessed the potential operational feasibility and acceptability of a heat-stable, inhaled oxytocin (IOT) product for community-based prevention of postpartum haemorrhage in Myanmar.

Methods: A qualitative inquiry was conducted between June 2015 and February 2016 through focus group discussions and in-depth interviews. Research was conducted in South Dagon township (urban setting) and in Ngape and Thanlyin townships (rural settings) in Myanmar. Eleven focus group discussions and 16 in-depth interviews were conducted with mothers, healthcare providers and other key informants. All audio recordings were transcribed verbatim in Myanmar language and were translated into English. Thematic content analysis was done using NVivo software.

Results: Future introduction of an IOT product for community-based services was found to be acceptable among mothers and healthcare providers and would be feasible for use by lower cadres of healthcare providers, even in remote settings. Responses from healthcare providers and community members highlighted that midwives and volunteer auxiliary midwives would be key advocates for promoting community acceptance of the product. Healthcare providers perceived the ease of use and lack of dependence on cold storage as the main enablers for IOT compared with the current gold standard oxytocin injection. A single-use disposable device with clear pictorial instructions and a price that would be affordable by the poorest communities was suggested. Appropriate training was also said to be essential for the future induction of the product into community settings.

Conclusion: In Myanmar, where home births are common, access to cold storage and skilled personnel who are able to deliver injectable oxytocin is limited. Among community members and healthcare providers, IOT was perceived to be an acceptable and feasible intervention for use by lower cadres of healthcare workers, and thus may be an alternative solution for the prevention of postpartum haemorrhage in community-based settings in the future.
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http://dx.doi.org/10.1136/bmjopen-2018-022140DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6224761PMC
October 2018

Synthesis, Cytotoxicity, Antimicrobial and Docking Simulation of Novel Pyrazolo[3,4-d]pyrimidine and pyrazolo[4,3-e][1,2,4]triazolo[3,4-c] pyrimidine Derivatives.

Mini Rev Med Chem 2019 ;19(8):657-670

Department of Chemistry, Faculty of Science, Cairo University, Giza 12613, Egypt.

Background: Isobutyrohydrazonoyl bromide 1 was used as a precursor for the synthesis of 4-imino-3-isopropyl-1-(4-nitrophenyl)-1,4-dihydro-5H-pyrazolo[3,4-d]pyrimidin-5-amine 4, which was converted into hydrazino derivative 5 by heating with hydrazine hydrate at reflux. Hydrazino, as well as imino-amino derivatives, underwent condensation and cyclization reactions to give pyrazolo[ 3,4-d]pyrimidine and pyrazolo[4,3-e][1,2,4]triazolo[3,4-c]pyrimidine derivatives, respectively.

Method: Antimicrobial studies are performed using two-gram positive bacteria and two-gram negative bacteria.

Results: Data revealed that compound 9a is the most promising antibacterial agent with high efficiency (low MIC value (48 μg/ml)). The cytotoxic assay was investigated for in vitro antitumor screening against Caucasian breast adenocarcinoma MCF7, hepatocellular carcinoma HepG2 and colon carcinoma HCT-116 cell lines.

Conclusion: The results are compared with doxorubicin standard anticancer drugs as well as normal cell lines like MCF10 and MCF12. Molecular docking was carried out for the highest potent compound 8c with the binding site of dihydrofolate reductase enzyme DHFR PDB:ID (1DLS).
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http://dx.doi.org/10.2174/1389557518666181017162459DOI Listing
June 2019

Knowledge, perception and practice towards oxytocin stability and quality: A qualitative study of stakeholders in three resource-limited countries.

PLoS One 2018 25;13(9):e0203810. Epub 2018 Sep 25.

Monash Institute of Pharmaceutical Sciences, Monash University, Melbourne, Victoria, Australia.

Background: Oxytocin is the gold standard drug for the prevention of postpartum haemorrhage, but limitations in cold chain systems in resource-constrained settings can severely compromise the quality of oxytocin product available in these environments. This study investigated the perspectives and practices of stakeholders in low and lower-middle income countries towards oxytocin, its storage requirements and associated barriers, and the quality of product available.

Methods: Qualitative inquiries were undertaken in Ethiopia, India and Myanmar, where data was collected through Focus Group Discussions (FGDs) and In-Depth Interviews (IDIs). A total of 12 FGDs and 106 IDIs were conducted with 158 healthcare providers (pharmacists, midwives, nurses, doctors and obstetricians) and 40 key informants (supply chain experts, program managers and policy-makers). Direct observations of oxytocin storage practices and cold chain resources were conducted at 51 healthcare facilities. Verbatim transcripts of FGDs and IDIs were translated to English and analysed according to a thematic content analysis framework.

Findings: Stakeholder awareness of oxytocin heat sensitivity and the requirement for cold storage of the drug was widespread in Ethiopia but more limited in Myanmar and India. A consistent finding across all study regions was the significant barriers to maintaining a consistent cold chain, with the lack of refrigeration facilities and unreliability of electricity cited as major challenges. Perceptions of compromised oxytocin quality were expressed by some stakeholders in each country.

Conclusion: Knowledge of the heat sensitivity of oxytocin and the potential impacts of inconsistent cold storage on product quality is not widespread amongst healthcare providers, policy makers and supply chain experts in Myanmar, Ethiopia and India. Targeted training and advocacy messages are warranted to emphasise the importance of cold storage to maintain oxytocin quality.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0203810PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6156023PMC
February 2019

Role of nitric oxide and KATP channel in the protective effect mediated by nicorandil in bile duct ligation-induced liver fibrosis in rats.

Biochem Pharmacol 2018 05 6;151:135-142. Epub 2018 Mar 6.

Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Cairo, Egypt. Electronic address:

Liver fibrosis is one of the most serious conditions affecting patients worldwide. In the present study, the role of nitric oxide and KATP channel was investigated for the first time in the possible protection mediated by nicorandil in bile duct ligation-induced liver fibrosis in rats. Nicorandil (3 mg/kg/day) was given orally 24 h after bile duct ligation for 14 days till the end of the experiment. Nicorandil group showed marked improvement in liver function tests, hepatic oxidative stress and inflammatory markers as well as inducible and endothelial nitric oxide synthase protein expressions. Furthermore, nicorandil administration led to significant decrement of phosphorylated protein kinase C, fibrosis and hepatic stellate cells activation as indicated by decreased alpha smooth muscle actin expression. Oral co-administration of glibenclamide (5 mg/kg/day) (a KATP channel blocker) with nicorandil mostly showed similar improvement though not reaching to that of nicorandil group. However, co-adminstration of L-NAME (15 mg/kg/day) (an inhibitor of nitric oxide synthase) completely abolished the protective effects of nicorandil and produced more or less similar results to that of untreated bile duct ligated group. In conclusion, nicorandil is an effective therapy against the development of bile duct ligation-induced liver fibrosis in rats where nitric oxide plays a more prominent role in the protective effect of nicorandil than KATP channel opening.
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http://dx.doi.org/10.1016/j.bcp.2018.03.003DOI Listing
May 2018

Prevention of postpartum haemorrhage by community-based auxiliary midwives in hard-to-reach areas of Myanmar: a qualitative inquiry into acceptability and feasibility of task shifting.

BMC Pregnancy Childbirth 2017 May 17;17(1):146. Epub 2017 May 17.

Burnet Institute, Melbourne, Australia.

Background: In Myanmar, postpartum haemorrhage is the leading cause of maternal mortality and contributes to around 30% of all maternal deaths. The World Health Organization recommends training and supporting auxiliary midwives to administer oral misoprostol for prevention of postpartum haemorrhage in resource-limited settings. However, use of misoprostol by auxiliary midwives has not formally been approved in Myanmar. Our study aimed to explore community and provider perspectives on the roles of auxiliary midwives and community-level provision of oral misoprostol by auxiliary midwives.

Methods: A qualitative inquiry was conducted in Ngape Township, Myanmar. A total of 15 focus group discussions with midwives, auxiliary midwives, community members and mothers with children under the age of three were conducted. Ten key informant interviews were performed with national, district and township level health planners and implementers of maternal and child health services. All audio recordings were transcribed verbatim in Myanmar language. Transcripts of focus group discussions were fully translated into English before coding, while key informants' data were coded in Myanmar language. Thematic analysis was done using ATLAS.ti software.

Results: Home births are common and auxiliary midwives were perceived as an essential care provider during childbirth in hard-to-reach areas. Main reasons provided were that auxiliary midwives are more accessible than midwives, live in the hard-to-reach areas, and are integrated in the community and well connected with midwives. Auxiliary midwives generally reported that their training involved instruction on active management of the third stage of labour, including use of misoprostol, but not all auxiliary midwives reported using misoprostol in practice. Supportive reasons for task-shifting administration of oral misoprostol to auxiliary midwives included discussions around the good relationship and trust between auxiliary midwives and midwives, whereby midwives felt confident distributing misoprostol to auxiliary midwives. However, the lack of clear government-level written permission to distribute the drug was perceived as a barrier to task shifting.

Conclusion: This study highlights the acceptability of misoprostol use by auxiliary midwives to prevent postpartum haemorrhage, and findings suggest that it should be considered as a promising intervention for task shifting in Myanmar.
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http://dx.doi.org/10.1186/s12884-017-1324-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5436430PMC
May 2017

Interleukin 10 (- 1082 G/A) and (- 819 C/T) gene polymorphisms in Egyptian women with polycystic ovary syndrome (PCOS).

Meta Gene 2016 Sep 3;9:254-8. Epub 2016 Aug 3.

Molecular Biology Department, Genetic Engineering and Biotechnology Research Institute (GEBRI), University of Sadat City, Egypt.

Cytokines play critical roles in the pathogenesis of Polycystic Ovarian Syndrome (PCOS). This work was designed to study the implication of IL10 gene polymorphisms (- 1082 G/A and - 819 C/T) on the susceptibility of Egyptian women to have PCOS. Rotterdam consensus criteria were used to diagnose PCOS patients. Genotyping was performed by single-stranded polymorphism-polymerase chain reaction (SSP-PCR) in 61 PCOS patients and 80 healthy controls, and IL-10 serum levels were measured using Enzyme linked immunosorbent assay (ELISA). The frequency of IL10 - 1082 G/G (46%) genotype was significantly increased (p < 0.001) while the frequency of - 1082 A/A (16%) genotype was significantly decreased (p < 0.05) in PCOS patients compared to controls (14% and 35% for G/G and A/A genotypes; respectively). G allele (65%) is significantly increased (p < 0.01( in PCOS patients while A allele (61%) is significantly increased (p < 0.001( in control subjects. The distribution of IL10 -819 T/T genotype was significantly increased (p < 0.05) in PCOS group. G/G genotype (odd ratio (OR = 5.322) with confidence interval (CI = 2.364-11.982) and the G allele (OR = 2.828 with CI = 1.73-4.61) of - 1082 G/A and T/T genotype of - 819 C/T (OR = 4.18 with CI = 1.26-13.86) could be considered as risk factors for PCOS. IL-10 levels were significantly lower among PCOS patients (313.42 ± 30.10) compared to normal controls (4914.36 ± 303.72). Depending on our preliminary work, IL10 - 1082 G/G might be considered as a host genetic factor for PCOS susceptibility in Egyptian women. Studies concerning other cytokine gene polymorphisms are required to get a better understanding of the pathogenesis of PCOS disease.
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http://dx.doi.org/10.1016/j.mgene.2016.08.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5006121PMC
September 2016

DNA Methylation Signatures in Vaginal Fluid Samples for Detection of Cervical and Endometrial Cancer.

Int J Gynecol Cancer 2016 Jun 2. Epub 2016 Jun 2.

*Department of Women's Cancer, Elizabeth Garrett Anderson Institute for Women's Health, University College London, London, United Kingdom; †CAS Key Laboratory of Computational Biology, CAS-MPG Partner Institute for Computational Biology, Shanghai; and ‡University of Chinese Academy of Sciences, Beijing, China; and §UCL Cancer Institute, University College London, London, United Kingdom.

Objective: A noninvasive tool that allows individuals to be monitored who are at risk of developing a malignancy is an unmet need. Such a test would need to consist of a molecular signature that allows for gradual judgment to assess the efficacy of preventive strategies. Here we performed a proof-of-principle study to test whether a DNA methylation (DNAme) signature in fluid collected from the vagina is able to identify women with cervical or endometrial cancer.

Materials And Methods: DNA from vaginal fluid samples from 111 women (30, 8, 73 with endometrial cancer, cervical cancer, and benign gynecological conditions, respectively) were analyzed for DNAme using the Illumina 450k DNA methylation bead array assay, which allows the assessment of DNAme at more than 480.000 CpG sites. We developed a cervical and an endometrial cancer DNAme signature by comparing normal and cancerous cervical and endometrial samples from the publicly available The Cancer Genome Atlas data and developed deviation scores to assess the potential of discriminating cancer from a control sample using a vaginal fluid DNAme signature.

Results: More than 60% of variations in DNAme in our vaginal fluid cannot be explained by those clinical or technical factors that we were aware of. Both the cervical and the endometrial cancer DNAme signature resulted in receiver operating characteristic area under the curve between 0.75 and 0.83 to discriminate controls and the cancers for which the signature has been designed for.

Conclusions: Whole DNAme signatures based on array technologies in body fluids are able to discriminate cancer cases from controls.
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http://dx.doi.org/10.1097/IGC.0000000000000739DOI Listing
June 2016

Prevalence and phylogenetic characterization of isolated from processed meat marketed in Egypt.

J Genet Eng Biotechnol 2016 Jun 18;14(1):119-123. Epub 2016 Jun 18.

Department of Zoonoses, National Research Center, El-Behouth St., Giza, Egypt.

Because of its high case fatality rate, listeriosis locates among the most frequent causes of death due to food-borne illness. In this study, a total of 150 processed meat samples were collected from Giza Governorate, Egypt. Phenotypic and genotypic identification of was performed using PCR incorporating listeriolysin O virulence gene hlyA followed by DNA sequence analysis. was confirmed in 4% of each of beef burger, minced meat, and luncheon samples. Phylogenetic analysis showed that all the six Egyptian isolates have high homology with Colombian isolate (EF030606), except one Egyptian isolate which showed high homology with Indian isolate (EU840690). The public health significance of these pathogens as well as recommended sanitary measures were discussed.
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http://dx.doi.org/10.1016/j.jgeb.2016.06.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6299886PMC
June 2016

Listeria monocytogenes: An emerging food-borne pathogen and its public health implications.

J Infect Dev Ctries 2016 Feb 28;10(2):149-54. Epub 2016 Feb 28.

National Research Center, Giza, Egypt.

Introduction: Listeria monocytogenes is considered one of the most important food-borne pathogens transmitted to humans via contaminated food. The aim of the present study was to demonstrate the importance of L. monocytogenes as a food-borne pathogen.

Methodology: A total of 340 samples were collected from different localities in El Giza Governorate, Egypt, to check the occurrence of L. monocytogenes in that area. The collected samples comprised 250 food samples, 40 swabs from food refrigerators, and 50 stool specimens from diarrheic children. L. monocytogenes was isolated from the examined samples according to the International Organization for Standardization. The isolates were tested biochemically using Listeria Microbact 12L and confirmed by polymerase chain reaction.

Results: The isolation rates of L. monocytogenes were 8% in beef burger, 4% in minced meat, 4% in luncheon meat, while sausage samples were all negative. Eight percent of raw milk samples were positive for L. monocytogenes, whereas cheese samples and refrigerator swabs were negative. Only Listeria grayi was isolated from human stools (2.5%).

Conclusion: The high isolation rates of L. monocytogenes among the examined food stuffs highlight the crucial role of food as an important vehicle for this pathogen. More efforts should be made to ensure safe handling and processing of these foods to reduce the transmission of L. monocytogenes to humans.
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http://dx.doi.org/10.3855/jidc.6616DOI Listing
February 2016

Gene-expression patterns in whole blood identify subjects at risk for recurrent tuberculosis.

J Infect Dis 2007 Feb 21;195(3):357-65. Epub 2006 Dec 21.

GlaxoSmithKline, Stevenage, UK.

Background: The majority of patients with tuberculosis who comply with appropriate treatment are cured. However, approximately 5% subsequently have a repeat disease episode, usually within 2 years of successful combination therapy. Presently, there is no way of predicting which patients will experience a relapse.

Methods: We identified 10 subjects who had previously experienced recurrent tuberculosis and carefully matched them to cured subjects who had had only 1 episode of tuberculosis, to patients with active tuberculosis, and to latently infected healthy subjects. We compared their ex vivo whole-blood gene-expression profiles by use of DNA array technology and confirmed the results by use of quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR).

Results: The 4 clinical tuberculosis groups exhibited distinct patterns of gene expression. The gene-transcript profiles of the patients with recurrent tuberculosis were more similar to those of the patients with active tuberculosis than to those of the cured or latently infected subjects. Discriminant analysis of a training data set showed that 9 genes were sufficient to classify the subjects. We confirmed that measurement of the expression of these genes by qRT-PCR can accurately discriminate between subjects in a test set of samples.

Conclusions: A simple test based on gene-expression patterns may be used as a biomarker of cure while identifying patients who are at risk for relapse. This would facilitate the introduction of new tuberculosis drugs.
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http://dx.doi.org/10.1086/510397DOI Listing
February 2007
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