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☐ ☆ ✇ PLOS ONE Medicine&Health

Prevalence and predictors of viral load non-suppression among adolescents on dolutegravir-based antiretroviral therapy: A cross-sectional study from three urban clinics, Soroti City

by Connie Nait, Simple Ouma, Saadick Mugerwa Ssentongo, Boniface Oryokot, Abraham Ignatius Oluka, Raymond Kusiima, Victoria Nankabirwa, John Bosco Isunju

Background

Despite advances in HIV care, viral load suppression (VLS) among adolescents living with HIV (ALHIV) in Uganda continue to lag behind that of adults, even with the introduction of dolutegravir (DTG)-based regimens, the Youth and Adolescent Peer Supporter (YAPS) model, and community-based approaches. Understanding factors associated with HIV viral load non-suppression in this population is critical to inform HIV treatment policy. This study assessed the prevalence and predictors of viral load non-suppression among ALHIV aged 10–19 years on DTG-based ART in Soroti City, Uganda.

Methods

We conducted a cross-sectional study among 447 ALHIV attending three urban HIV clinics in Soroti City. Data were abstracted using a structured questionnaire and analyzed in STATA 15.0. Modified Poisson regression with robust error variance was used to identify predictors of viral load non-suppression. Adjusted relative risks (aRR) and 95% confidence intervals (CIs) were reported, with statistical significance set at p ≤ 0.05.

Results

Of the 447 participants, 53.5% were female, with a median age of 16 years (IQR: 14.0–17.6). The majority (72.9%) were from Soroti district and had been on DTG-based ART for a median of 42.5 months (IQR: 37.0–48.0). Most were receiving multi-month dispensing (MMD) (75.2%) and were active in care (98%). The prevalence of viral load non-suppression was 19.2% (86/447). Independent predictors of non-suppression included older age (15–19 vs. 10–14 years) (aRR: 1.69; 95% CI: 1.08–2.67), male sex (aRR: 1.48; 95% CI: 1.05–2.11), prior non-suppression before switching to DTG (aRR: 1.76; 95% CI: 1.19–2.59), use of non-fixed dose DTG regimens (aRR: 2.03; 95% CI: 1.23–3.33), history of poor adherence (aRR: 4.36; 95% CI: 2.05–9.26), and not receiving MMD (aRR: 2.83; 95% CI: 1.93–4.15).

Conclusion

Nearly one in five adolescents on DTG-based ART in Soroti City had viral non-suppression, despite optimized treatment regimens. Targeted interventions−particularly enhanced adherence counseling for older and male adolescents, expanding MMD coverage, and provision of fixed-dose regimens−are urgently needed to improve VLS among ALHIV. These findings underscore the need for adolescent-centered HIV care strategies to close the viral suppression gap and advance progress towards epidemic control.

☐ ☆ ✇ PLOS ONE Medicine&Health

Recombinant human alpha-N-acetylglucosamine-6-sulfatase delivered to Sanfilippo D mice with repeated intracerebroventricular injections corrects CNS pathology

by Grant L. Austin, Feng Wang, Steven Q. Le, Alexander Sorensen, Shan Li, Lai C. Foong, Srikanth Singamsetty, Jill Wood, Tsui-Fen Chou, Patricia I. Dickson

Mucopolysaccharidosis type IIID (MPS IIID; Sanfilippo D) is caused by biallelic pathogenic variants in N-acetylglucosamine-6-sulfatase (GNS), which participates in catabolism of heparan sulfate (HS) glycosaminoglycans. Characterization of MPS IIID disease at a cellular level has not been robustly achieved. We used unbiased quantitative proteomics to establish a cellular phenotype for MPS IIID mice. Recombinant human GNS (rhGNS), a variant of which previously demonstrated single dose efficacy in MPS IIID human fibroblasts and in MPS IIID neonatal mice, was used to establish a repeat dosing schedule to treat MPS IIID mice. Adult Gns KO mice or heterozygous carriers were treated via intracerebroventricular (ICV) injections and received 3, 30, or 200 μg rhGNS in 4 doses over 2 weeks or vehicle. Twenty-four hours after the final dose, HS in brain and CSF showed dose-dependent reductions, reaching carrier levels in the higher dose groups. Furthermore, the proteomic perturbations that we described were corrected by rhGNS treatment. Next, Gns KO or carrier adult mice were treated via ICV and received 3, 30 or 200 μg rhGNS or vehicle once every two weeks (Day 1, 15, 29, 43, 57, 71, 85) and were euthanized on day 91. Following treatment, total HS and MPS IIID-specific HS (GlcNAc6S) showed dose-dependent reductions in brain and CSF and markers of neuroinflammation were substantially reduced. ICV enzyme replacement therapy with rhGNS restores CNS pathology of adult MPS IIID mice even with treatment at 14-day intervals, demonstrating preclinical efficacy for MPS IIID.
☐ ☆ ✇ PLOS ONE Medicine&Health

A retrospective single-center pilot study of the genetic background of the transplanted kidney

by Anna Novotna, Klara Horackova, Jana Soukupova, Petra Zemankova, Petr Nehasil, Pavel Just, Ludek Voska, Petra Kleiblova, Silvie Rajnochova Bloudickova

Introduction

Renal cell carcinoma (RCC) is one of the most prevalent cancers in kidney transplant recipients (KTR). The hereditary background of RCC in native kidneys has been determined, implicating its clinical importance.

Materials and methods

This retrospective single-center pilot study aimed to identify a potential genetic predisposition to RCC of the transplanted kidney and outcome in KTR who underwent single kidney transplantation between January 2000 and December 2020 and manifested RCC of the transplanted kidney. Next-generation sequencing (NGS) based germline genetic analysis from peripheral blood-derived genomic DNA (gDNA) was performed in both the recipient and donor using a gene panel targeting 226 cancer predisposition genes.

Results

The calculated incidence of RCC of the transplanted kidney among 4146 KTR was 0.43%. In fifteen KTR and donors, NGS was performed. The mean KTR age at transplantation and the diagnosis of RCC was 50.3 years (median 54; 5–67 years) and 66 years (median 66; 24–79 years), respectively. The mean donor age at transplantation and graft age at RCC diagnosis was 39.7 years (median 42; 7–68 years) and 50.2 years (median 46; 20–83 years), respectively. The mean follow-up after RCC diagnosis was 47 months (median 39.1; 0–112 months). Papillary RCC was the most prevalent (n = 8), followed by clear cell RCC (n = 6) and unspecified RCC (n = 1). Thirteen RCCs were low-stage (pT1a/b) diseases, one was pT3, and one was of unknown stage. Most RCC was higher graded. No germline pathogenic cancer-predisposition variant was found in either KTR or donors except for several variants of uncertain significance.

Conclusion

RCC of the transplanted kidney is very rare. Germline cancer-predisposition testing has identified several variants of uncertain significance, but no germline genetic predisposition to graft RCC in KTR. Further research is needed to assess the clinical relevance of genetic testing for cancer risk in KTR.

☐ ☆ ✇ PLOS ONE Medicine&Health

COVID-19-related research data availability and quality according to the FAIR principles: A meta-research study

Por: Ahmad Sofi-Mahmudi · Eero Raittio · Yeganeh Khazaei · Javed Ashraf · Falk Schwendicke · Sergio E. Uribe · David Moher — Noviembre 18th 2024 at 15:00

by Ahmad Sofi-Mahmudi, Eero Raittio, Yeganeh Khazaei, Javed Ashraf, Falk Schwendicke, Sergio E. Uribe, David Moher

Background

According to the FAIR principles (Findable, Accessible, Interoperable, and Reusable), scientific research data should be findable, accessible, interoperable, and reusable. The COVID-19 pandemic has led to massive research activities and an unprecedented number of topical publications in a short time. However, no evaluation has assessed whether this COVID-19-related research data has complied with FAIR principles (or FAIRness).

Objective

Our objective was to investigate the availability of open data in COVID-19-related research and to assess compliance with FAIRness.

Methods

We conducted a comprehensive search and retrieved all open-access articles related to COVID-19 from journals indexed in PubMed, available in the Europe PubMed Central database, published from January 2020 through June 2023, using the metareadr package. Using rtransparent, a validated automated tool, we identified articles with links to their raw data hosted in a public repository. We then screened the link and included those repositories that included data specifically for their pertaining paper. Subsequently, we automatically assessed the adherence of the repositories to the FAIR principles using FAIRsFAIR Research Data Object Assessment Service (F-UJI) and rfuji package. The FAIR scores ranged from 1–22 and had four components. We reported descriptive analysis for each article type, journal category, and repository. We used linear regression models to find the most influential factors on the FAIRness of data.

Results

5,700 URLs were included in the final analysis, sharing their data in a general-purpose repository. The mean (standard deviation, SD) level of compliance with FAIR metrics was 9.4 (4.88). The percentages of moderate or advanced compliance were as follows: Findability: 100.0%, Accessibility: 21.5%, Interoperability: 46.7%, and Reusability: 61.3%. The overall and component-wise monthly trends were consistent over the follow-up. Reviews (9.80, SD = 5.06, n = 160), articles in dental journals (13.67, SD = 3.51, n = 3) and Harvard Dataverse (15.79, SD = 3.65, n = 244) had the highest mean FAIRness scores, whereas letters (7.83, SD = 4.30, n = 55), articles in neuroscience journals (8.16, SD = 3.73, n = 63), and those deposited in GitHub (4.50, SD = 0.13, n = 2,152) showed the lowest scores. Regression models showed that the repository was the most influential factor on FAIRness scores (R2 = 0.809).

Conclusion

This paper underscored the potential for improvement across all facets of FAIR principles, specifically emphasizing Interoperability and Reusability in the data shared within general repositories during the COVID-19 pandemic.

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