Encapsidation of Staufen-2 Enhances Infectivity of HIV-1

Staufen, the RNA-binding family of proteins, affects various steps in the Human Immuno-Deficiency Virus (HIV-1) replication cycle. While our previous study established Staufen-2–HIV-1 Rev interaction and its role in augmenting nucleocytoplasmic export of RRE-containing viral RNA, viral incorporation of Staufen-2 and its effect on viral propagation were unknown. Here, we report that Staufen-2 interacts with HIV-1 Gag and is incorporated into virions and that encapsidated Staufen-2 boosted viral infectivity. Further, Staufen-2 gets co-packaged into virions, possibly by interacting with host factors Staufen-1 or antiviral protein APOBEC3G, which resulted in different outcomes on the infectivity of Staufen-2-encapsidated virions. These observations suggest that encapsidated host factors influence viral population dynamics and infectivity. With the explicit identification of the incorporation of Staufen proteins into HIV-1 and other retroviruses, such as Simian Immunodeficiency Virus (SIV), we propose that packaging of RNA binding proteins, such as Staufen, in budding virions of retroviruses is probably a general phenomenon that can drive or impact the viral population dynamics, infectivity, and evolution.

Discovery of Novel Antituberculosis Compounds Using an Intra-Macrophage Assay

<p>The causative agent of tuberculosis (TB) is Mycobacterium tuberculosis, which affects 2 billion of the world population and kills 1.8 million people annually. It is among the top three infectious killers in the world human immuno deficiency virus, TB and Malaria. Every year among 300-400 new cases of TB are reported in New Zealand according to a recent WHO 2008 report. The current treatment regimen for TB is very long and results in significant toxicity, development of resistant strains and is unable to eliminate the latent bacilli. The above reasons demonstrate the growing need of research for novel antimycobacterial compounds and novel targets for the treatment of TB. Many in vitro and biochemical screens are available for testing against different mycobacterium strains but none of these screens can be considered comprehensive. The reason for this can be the lack of resemblance of the in vitro screen model with the biological systems. Hence we chose the intra-macrophage infection screening model to look for novel antimycobacterial prodrugs which are not active in an in vitro screen but selectively active inside macrophage cell lines. We were successful in establishing and validating such an intra-macrophage infection model using the non-pathogenic M. smegmatis. The model was validated using common anti-tuberculosis drugs. A preliminary high throughput screen was then set up using a mini-library demo model, followed by screening with an actual Lopac synthetic library.</p>

Discovery of Novel Antituberculosis Compounds Using an Intra-Macrophage Assay

<p>The causative agent of tuberculosis (TB) is Mycobacterium tuberculosis, which affects 2 billion of the world population and kills 1.8 million people annually. It is among the top three infectious killers in the world human immuno deficiency virus, TB and Malaria. Every year among 300-400 new cases of TB are reported in New Zealand according to a recent WHO 2008 report. The current treatment regimen for TB is very long and results in significant toxicity, development of resistant strains and is unable to eliminate the latent bacilli. The above reasons demonstrate the growing need of research for novel antimycobacterial compounds and novel targets for the treatment of TB. Many in vitro and biochemical screens are available for testing against different mycobacterium strains but none of these screens can be considered comprehensive. The reason for this can be the lack of resemblance of the in vitro screen model with the biological systems. Hence we chose the intra-macrophage infection screening model to look for novel antimycobacterial prodrugs which are not active in an in vitro screen but selectively active inside macrophage cell lines. We were successful in establishing and validating such an intra-macrophage infection model using the non-pathogenic M. smegmatis. The model was validated using common anti-tuberculosis drugs. A preliminary high throughput screen was then set up using a mini-library demo model, followed by screening with an actual Lopac synthetic library.</p>

How do Key Populations Cope their Behaviour Related Stigma? A Qualitative Study in a Province in Sri Lanka

Key populations are at the highest risk of acquiring and transmitting the Human Immuno-deficiency Virus (HIV). Due to the stigma vested upon them, they have become least accessible for preventive and curative services for HIV. Therefore, coping strategies are essential to minimize stigma to end AIDS by 2025, five years ahead of the global target of ending AIDS in 2030. The objective was to describe the coping strategies adopted by key-populations to overcome behavior-related stigma. Data from thirty-two in-depth interviews were analyzed using the thematic analysis method.

Introduction

Women require contraceptive and reproductive/sexual health care from menarche to menopause. An holistic approach to care enables women of all ages to make effective and safe choices regarding contraceptive methods, managing sexually transmitted infections/human immuno–deficiency virus (STI/HIV), unplanned pregnancy care, or pregnancy care within the community and other specialist services provided by health professionals. The multidisciplinary team comprises: Consultants in Reproductive and Sexual Health), GPs, sessional doctors, nurse consultants, Clinical Nurse Specialist and Advanced Nurse Practitioners, nurses, midwives, health visitors, pharmacists, health advisors, associates, healthcare assistants, counsellors, client support workers (CSWs), and receptionists providing client-centred care.

Coexistence of human immuno deficiency virus, diabetes mellitus, epididymal cysts, and Fournier's gangrene: A case report

Fournier's gangrene (FG) is a form of necrotizing fasciitis that is localized in the external genital organs and perianal region and causes skin and subcutaneous tissue gangrene. The clinical picture may vary depending on the patient's comorbidities and the extent of infection; Many predisposing conditions such as immunodeficiency, diabetes, alcoholism encourage the spread of the infection. In this case report, we highlighted the importance of emergency debridement in patients with multiple comorbidities by presenting the Fournier's Gangrene case in a 57-year-old immunosuppressive male patient with cystic lesions in the epididymis, with a history of hypertension, coronary artery disease, diabetes, HIV (human immunodeficiency virus) and a history of bipolar disorder. The patient, who was operated on for debridement by the urology, was given 1x500mg daptomycin, 3x1g meropenem, 3x450mg clindamycin IV treatment. The patient was discharged with full recovery after 17 days of hospitalization. Clinical suspicion in Fournier's gangrene cases, early surgical debridement, and extended-spectrum anti biotherapy are important. with rapid diagnosis and treatment in patients with improvement can also be seen in patients with comorbidities.

γ‑AApeptides as a New Class of Peptidomimetics: Design, Synthesis, and Applications

: Peptidomimetics are studied for medicinal application because of its ability to mimic hierarchical structures of peptides and proteins. To break the limitation and expand the peptidomimetics family, a new class of peptidomimetics based on peptide nucleic acids (PNAs) backbone - “γ-AApeptides” was developed. Compared with previous peptidomimetics, γ-AApeptides possess prominent advantages such as resistance to proteolytic degradation, enhanced chemodiversity, good selectivity and outstanding bioactivity. The synthesis of γ-AApeptides is using a ‘‘monomer building block’’ strategy which is facile and efficient. γ-AApeptides are able to mimic primary and secondary structures of therapeutic peptides which make them promising candidates for molecular probes and potential drug leads. In the past decade, several interesting structures and applications of γ-AApeptides have been developed by different approaches such as structure-based design, combinatorial library screening, and peptides self-assembly and folding. By following the mechanism of host-defense peptides (HDPs), antibiotic γ-AApeptides showed broad-spectrum activity. At the same time, γ-AApeptides can be used for combinatorial library screening because of their structural stability and their chemodiversity. Anti-cancer agents, anti-T2DM (Type 2 diabetes mellitus) agents, anti-HIV (human immuno-deficiency virus) agents and anti-Alzheimer’s disease agents were developed by combinatorial screening and rational deign. Furthermore, γ-AApeptides as biopolymers, nanomaterials, supramolecular structures and self-assembly architectures were studied due to their unique backbone structures. Therefore, γ-AApeptides may play an important role in the development of peptidomimetics.

Ototoxicity: A review of South African studies

Background: Ototoxicity is damage to cells in the inner ear after administering a toxic drug, with a resultant hearing loss. Drugs used to treat illnesses such as cancer, tuberculosis, human immuno-deficiency virus (HIV) and infections are potentially ototoxic. South Africa has one of the highest rates of HIV and tuberculosis, and thus a potentially greater degree of the population is being affected by hearing loss from the medications used to treat these illnesses.Methods: To determine the current status of research in ototoxicity, a systematic literature review was carried out to determine the focus areas of South African studies for the period 1989–2019. From the database search engines used (Science Direct, Ebscohost and Proquest), a total of 33 relevant articles were identified, including the themes of pharmacology, audiology and knowledge.Results: Studies were conducted in the three most resourced provinces in South Africa. Findings indicate that there is a need for educating doctors regarding ototoxicity and a delineation of the role of the audiologist in monitoring and management of ototoxic hearing loss. There is a resultant need for audiology training on the pharmacology of ototoxic medication, otoprotective strategies and adherence to recommended guidelines. This has implications for university audiology training programmes and curriculum planning. The need for development of South Africa-specific audiology guidelines was highlighted.Conclusion: Whilst it is noted that there is a lack of resources for effective implementation of ototoxicity-monitoring protocols, it is also noted that there are measures and otoprotective strategies that can be put in place without additional resources.

Virological Non-Suppression Among HIV-Positive Patients on Antiretroviral Therapy in Northwestern Nigeria: An Eleven-Year Experience of A Tertiary Care Centre, January 2009–December 2019

Background: Human Immuno-Deficiency Virus (HIV) remains one of the world’s significant public health challenges. Viral suppression is the key indicator for treatment success in People living with HIV (PLHIV). We determined the level of viral non-suppression and its associated factors among PLHIV attending Federal Medical Centre Katsina (FMC Katsina), Nigeria. Methods: This retrospective descriptive study was conducted on 913 HIV positive adults enrolled in care between January 2009 and December 2019. Information on socio-demographics, clinical, immunological, Viral Load (VL) and other relevant parameters were extracted from the patients’ care Centre Katsina estimated frequencies/proportions, performed bivariate and multivariate analysis to determine factors associated with VL non-suppression using p<0.05 as significant level. Results: Records of 831 registered patients were analyzed using Epi-info 7. During the period, 751 (90.4%) achieved viral suppression, 426 (51.3%) had CD4 counts of ≥500 and 477 (57.4%) were on HAART for ≥5 years. Majority, 793 (95.4%) were on first-line and 809 (97.4%) in the non-advanced stage (WHO stages 1 and 2). The independent predictors of viral non-suppression included being on the second line HAART [Adjusted OR (AOR) 6.5; 95% CI 3.02-13.89], being employed [AOR 0.26; 95% CI 0.15-0.44] and baseline CD4 count less than 500 [AOR 0.35; 95% CI 0.21-0.61]. Conclusions: Our study demonstrated a good viral suppression among PLHIV on HAART. Low baseline CD4 counts and being on second-line HAART are predictive of viral non-suppression while being unemployed seems to be protective against viral non-suppression.

The Level of Unmet Need for Family Planning and Its Predictors among HIV-Positive Women in Ethiopia: A Systematic Review and Meta-Analysis

Background. Studies indicated that the need for family planning appears to be greater for human immuno-deficiency virus- (HIV-) positive women than the general population to reduce the risk of pediatrics HIV infection and related consequences of unintended pregnancy. We aimed to assess the level of unmet need for family planning and its predictors among HIV-positive women in Ethiopia. Methods. Online databases such as PubMed, SCOPUS, EMBASE, HINARI, Google Scholar, and digital libraries of universities were used to search for studies to be included in this systematic review and meta-analysis. Quality assessment of included studies was conducted using the Newcastle-Ottawa Quality Assessment Scale (NOS). Data were extracted using the format prepared on Excel workbook and analyzed by the Stata 11 software. Cochran ( Q test) and I 2 test statistics were used to assess the heterogeneity of studies. Similarly, the funnel plot and Egger’s regression asymmetry test were used to assess publication bias. Result. This systematic review and meta-analysis was conducted using nine primary studies with a total of 6,154 participants. The pooled prevalence of unmet need for family planning among HIV-positive women was found to be 25.72% (95% CI: 21.63%, 29.81%). Participants age 15-24 years (( OR = 3.12 ; 95% CI: 1.59, 6.11) I 2 = 27.5 %; p = 0.252 ), being illiterate (( OR = 2.69 ; 95% CI: 1.69, 4.26) I 2 = 0.0 % ; p = 0.899 ), failure to discuss FP with partner (( OR = 3.38 ; 95% CI: 2.20, 5.18) I 2 = 0.0 %; p = 0.861 ), and no access to family planning information (( OR = 4.70 ; 95% CI: 2.83, 7.81) I 2 = 0.0 %; p = 0.993 ) were found to be a significant predictors of unmet need for family planning among HIV-positive women. Conclusion. The level of unmet need for family planning among HIV-positive women was found to be high in Ethiopia. Being young age, illiteracy, failed to discuss family planning issues with a partner, and no access to family planning information were found to be the significant predictors of unmet need for family planning among HIV-positive women in Ethiopia. Improving information access and encouraging partners’ involvement in family planning counseling and services could reduce the level of unmet need for family planning.