Commentary: Core Descriptor Sets Using Consensus Methods Support 'Table One' Consistency.

Inconsistent reporting of patient characteristics in clinical research hampers reproducibility and limits analysis opportunities. This paper proposes condition-specific 'Core Descriptor Sets'(CDSs) comprising key factors like demographics, disease severity, comorbidities, and prognosis to standardise Table 1 reporting. Development entails stakeholder involvement, systematic identification of descriptors, value rating, and consensus-building using multiple Delphi rounds. Final agreement comes at an expert meeting. Benefits include easier cross-study comparison for example through individual patient meta-analysis, facilitated by comparison of consistently reported individual data rather than group level analysis. This may also support routine data analyses, subgroup and risk identification, and reduced research waste. CDSs describe cohorts thoroughly while minimising research burden. They are intended to enable improved clinical characterisation, personalisation, reproducibility, data sharing and knowledge building.

Longitudinal lung function trajectories in response to azithromycin therapy for chronic lung disease in children with HIV infection: a secondary analysis of the BREATHE trial.

BACKGROUND: Chronic lung disease (CLD) is common among children with HIV (CWH) including in those taking antiretroviral therapy (ART). Azithromycin has both antimicrobial and anti-inflammatory effects and has been effective in improving lung function in a variety of lung diseases. We investigated lung function trajectories among CWH with CLD on ART enrolled in a randomized controlled trial of adjuvant azithromycin. We also investigated factors that modified the effect of azithromycin on lung function. METHODS: The study used data from a double-blinded placebo-controlled trial conducted in Malawi and Zimbabwe of 48 weeks on azithromycin (BREATHE: ClinicalTrials.gov NCT02426112) among CWH aged 6 to 19 years taking ART for at least six months who had a forced expiratory volume in one second (FEV1) z-score <-1.0. Participants had a further follow-up period of 24 weeks after intervention cessation. FEV1, forced vital capacity (FVC) and FEV1/FVC were measured at baseline, 24, 48 and 72-weeks and z-scores values calculated. Generalized estimating equations (GEE) models were used to determine the mean effect of azithromycin on lung-function z-scores at each follow-up time point. RESULTS: Overall, 347 adolescents (51% male, median age 15 years) were randomized to azithromycin or placebo. The median duration on ART was 6.2 (interquartile range: 3.8-8.6) years and 56.2% had an HIV viral load < 1000copies/ml at baseline. At baseline, the mean FEV1 z-score was - 2.0 (0.7) with 44.7% (n = 155) having an FEV1 z-score <-2, and 10.1% had microbiological evidence of azithromycin resistance. In both trial arms, FEV1 and FVC z-scores improved by 24 weeks but appeared to decline thereafter. The adjusted overall mean difference in FEV1 z-score between the azithromycin and placebo arms was 0.004 [-0.08, 0.09] suggesting no azithromycin effect and this was similar for other lung function parameters. There was no evidence of interaction between azithromycin effect and baseline age, lung function, azithromycin resistance or HIV viral load. CONCLUSION: There was no observed azithromycin effect on lung function z-scores at any time point suggesting no therapeutic effect on lung function. TRIAL REGISTRATION: ClinicalTrials.gov NCT02426112. First registered on 24/04/2015.

Leveraging Global Fund's investments to expand innovative public-private provider engagement in TB.

BACKGROUND: TB remains a significant global health threat, claiming 1.3 million lives annually. The COVID-19 pandemic disrupted progress in the global TB response. Most patients with TB initially seek care from private providers, whereas only a small proportion are engaged by national programmes. The Global Fund is the major international source of funding for TB responses and supports the scale-up of innovative private-public mix (PPM) models in TB. METHODS: We collected programmatic and financial data on TB from 11 priority countries implementing PPM activities. Country examples and trends in the budget of Global Fund grants were analysed. RESULTS: These countries account for 60% of the global TB burden and Global Fund TB portfolio. PPM contributed 29% of national TB notifications in 2022 (range: 8% to 49%). During 2021-2023, US$1.4 billion was allocated for TB and US$155 million (11%) for PPM, while PPM contributed to 35% of national TB notification targets. PPM budgets increased over time from US$43 million (2002 to 2014) to US$129 million (2024 to 2026). CONCLUSION: The Global Fund's investments facilitated the expansion of innovative PPM models, improved access, and enhanced TB responses. Our indicative analysis underscores the need for evidence-based planning, collaboration, and increased domestic investment to accelerate the end of TB.

CONTEXTE: La TB reste une menace importante pour la santé mondiale, faisant 1,3 million de morts chaque année. La pandémie de COVID-19 a perturbé les progrès de la riposte mondiale à la TB. La plupart des patients atteints de TB recherchent d'abord des soins auprès de prestataires privés, tandis que seule une petite proportion est engagée par des programmes nationaux. Le Fonds mondial est la principale source internationale de financement de la lutte contre la TB et soutient l'extension de modèles innovants de partenariats public-privé (PPM, pour l'anglais « public-private mix ¼) dans le domaine de la TB. MÉTHODES: Nous avons recueilli des données programmatiques et financières sur la TB dans 11 pays prioritaires mettant en œuvre des activités de PPM. Des exemples de pays et les tendances du budget des subventions du Fonds mondial ont été analysés. RÉSULTATS: Ces pays représentent 60% de la charge mondiale de morbidité de la TB et du portefeuille du Fonds mondial de lutte contre la TB. La PPM a contribué à 29% des notifications nationales de TB en 2022 (fourchette : 8­49%). Au cours de la période 2021­2023, 1,4 milliard de dollars US ont été alloués à la TB et 155 millions de dollars US (11%) à la PPM, tandis que la PPM a contribué à 35% des cibles nationales de notification de la TB. Les budgets PPM ont augmenté au fil du temps, passant de 43 millions de dollars US (2002 à 2014) à 129 millions de dollars américains (2024 à 2026). CONCLUSION: Les investissements du Fonds mondial ont facilité l'expansion de modèles PPM innovants, l'amélioration de l'accès et le renforcement des ripostes à la TB. Notre analyse indicative souligne la nécessité d'une planification fondée sur des données probantes, d'une collaboration et d'une augmentation des investissements nationaux pour accélérer l'éradication de la TB.

High-Order Harmonics Generation Using Spherical and Non-Spherical Nanoparticles.

The conversion efficiency of 800 nm, 65 fs radiation toward high-order harmonic generation (HHG) in laser-induced plasmas containing spherical and non-spherical nanoparticles (NPs) produced during the laser ablation of different metals in water using 1064 nm, 70 ps pulses was analyzed. Non-spherical NPs of different forms (triangle, cubic, bowtie, rod, rectangular, ellipsoid, etc.) were synthesized during the aging of some spherical NPs (In, Al, and Cu) in water. These NPs were then dried on the glass substrates and ablated to produce plasmas comprising nanostructured species of different morphologies. It was shown that harmonic generation in all synthesized non-spherical NPs was less efficient by a factor of at least five than in the initial spherical NP. Meanwhile, the spherical NPs that maintained the morphology state during aging (Ni, Ag, Mn, and Au) showed almost similar HHG conversion efficiency compared to the fresh spherical NPs. In all cases, the HHG conversion efficiency using spherical and non-spherical nanoparticles was notably larger compared to the atomic and ionic single-particle plasmas of the same elemental composition. NP plasmas demonstrated featureless harmonic distributions, contrary to the indium and manganese atomic/ionic plasmas, when the resonance enhancement of harmonics was observed.

Foot and Mouth Disease Vaccine Matching and Post-Vaccination Assessment in Abu Dhabi, United Arab Emirates.

Despite the annual vaccination of livestock against foot and mouth disease (FMD) in the United Arab Emirates (UAE), outbreaks of the disease continue to be reported. The effective control of field outbreaks by vaccination requires that the vaccines used are antigenically matched to circulating field FMD viruses. In this study, a vaccine matching analysis was performed using the two-dimensional virus neutralization test (VNT) for three field isolates belonging to the O/ME-SA/PanAsia-2/ANT-10 and O/ME-SA/SA-2018 lineages collected from different FMD outbreaks that occurred within the Abu Dhabi Emirate in 2021 affecting Arabian oryx (Oryx leucoryx), goat, and sheep. In addition, post-vaccination antibodies in sheep and goats were measured using solid-phase competitive ELISA (SPCE) for FMDV serotypes A and O at five months after a single vaccine dose and a further 28 days later after a second dose of the FMD vaccine. An analysis of vaccine matching revealed that five out of the six vaccine strains tested were antigenically matched to the UAE field isolates, with r1-values ranging between 0.32 and 0.75. These results suggest that the vaccine strains (O-3039 and O1 Manisa) included in the FMD vaccine used in the Abu Dhabi Emirate are likely to provide protection against outbreaks caused by the circulating O/ME-SA/PanAsia-2/ANT-10 and O/ME-SA/SA-2018 lineages. All critical residues at site 1 and site 3 of VP1 were conserved in all isolates, although an analysis of the VP1-encoding sequences revealed 14-16 amino acid substitutions compared to the sequence of the O1 Manisa vaccine strain. This study also reports on the results of post-vaccination monitoring where the immunization coverage rates against FMDV serotypes A and O were 47% and 69% five months after the first dose of the FMD vaccine, and they were increased to 81 and 88%, respectively, 28 days after the second dose of the vaccine. These results reinforce the importance of using a second booster dose to maximize the impact of vaccination. In conclusion, the vaccine strains currently used in Abu Dhabi are antigenically matched to circulating field isolates from two serotype O clades (O/ME-SA/PanAsia-2/ANT-10 sublineage and O/ME-SA/SA-2018 lineage). The bi-annual vaccination schedule for FMD in the Abu Dhabi Emirate has the potential to establish a sufficient herd immunity, especially when complemented by additional biosecurity measures for comprehensive FMD control. These findings are pivotal for the successful implementation of the region's vaccination-based FMD control policy, showing that high vaccination coverage and the wide-spread use of booster doses in susceptible herds is required to achieve a high level of FMDV-specific antibodies in vaccinated animals.

Characterization of bacterial and viral pathogens in the respiratory tract of children with HIV-associated chronic lung disease: a case-control study.

INTRODUCTION: Chronic lung disease is a major cause of morbidity in African children with HIV infection; however, the microbial determinants of HIV-associated chronic lung disease (HCLD) remain poorly understood. We conducted a case-control study to investigate the prevalence and densities of respiratory microbes among pneumococcal conjugate vaccine (PCV)-naive children with (HCLD +) and without HCLD (HCLD-) established on antiretroviral treatment (ART). METHODS: Nasopharyngeal swabs collected from HCLD + (defined as forced-expiratory-volume/second < -1.0 without reversibility postbronchodilation) and age-, site-, and duration-of-ART-matched HCLD- participants aged between 6-19 years enrolled in Zimbabwe and Malawi (BREATHE trial-NCT02426112) were tested for 94 pneumococcal serotypes together with twelve bacteria, including Streptococcus pneumoniae (SP), Staphylococcus aureus (SA), Haemophilus influenzae (HI), Moraxella catarrhalis (MC), and eight viruses, including human rhinovirus (HRV), respiratory syncytial virus A or B, and human metapneumovirus, using nanofluidic qPCR (Standard BioTools formerly known as Fluidigm). Fisher's exact test and logistic regression analysis were used for between-group comparisons and risk factors associated with common respiratory microbes, respectively. RESULTS: A total of 345 participants (287 HCLD + , 58 HCLD-; median age, 15.5 years [IQR = 12.8-18], females, 52%) were included in the final analysis. The prevalence of SP (40%[116/287] vs. 21%[12/58], p = 0.005) and HRV (7%[21/287] vs. 0%[0/58], p = 0.032) were higher in HCLD + participants compared to HCLD- participants. Of the participants positive for SP (116 HCLD + & 12 HCLD-), 66% [85/128] had non-PCV-13 serotypes detected. Overall, PCV-13 serotypes (4, 19A, 19F: 16% [7/43] each) and NVT 13 and 21 (9% [8/85] each) predominated. The densities of HI (2 × 104 genomic equivalents [GE/ml] vs. 3 × 102 GE/ml, p = 0.006) and MC (1 × 104 GE/ml vs. 1 × 103 GE/ml, p = 0.031) were higher in HCLD + compared to HCLD-. Bacterial codetection (≥ any 2 bacteria) was higher in the HCLD + group (36% [114/287] vs. (19% [11/58]), (p = 0.014), with SP and HI codetection (HCLD + : 30% [86/287] vs. HCLD-: 12% [7/58], p = 0.005) predominating. Viruses (predominantly HRV) were detected only in HCLD + participants. Lastly, participants with a history of previous tuberculosis treatment were more likely to carry SP (adjusted odds ratio (aOR): 1.9 [1.1 -3.2], p = 0.021) or HI (aOR: 2.0 [1.2 - 3.3], p = 0.011), while those who used ART for ≥ 2 years were less likely to carry HI (aOR: 0.3 [0.1 - 0.8], p = 0.005) and MC (aOR: 0.4 [0.1 - 0.9], p = 0.039). CONCLUSION: Children with HCLD + were more likely to be colonized by SP and HRV and had higher HI and MC bacterial loads in their nasopharynx. The role of SP, HI, and HRV in the pathogenesis of CLD, including how they influence the risk of acute exacerbations, should be studied further. TRIAL REGISTRATION: The BREATHE trial (ClinicalTrials.gov Identifier: NCT02426112 , registered date: 24 April 2015).

High prevalence and risk of malaria among asymptomatic individuals from villages with high prevalence of artemisinin partial resistance in Kyerwa district of Kagera region, north-western Tanzania.

BACKGROUND: Although Tanzania adopted and has been implementing effective interventions to control and eventually eliminate malaria, the disease is still a leading public health problem, and the country experiences heterogeneous transmission. Recent studies reported the emergence of parasites with artemisinin partial resistance (ART-R) in Kagera region with high prevalence (> 10.0%) in two districts of Karagwe and Kyerwa. This study assessed the prevalence and predictors/risk of malaria infections among asymptomatic individuals living in a hyperendemic area where ART-R has emerged in Kyerwa District of Kagera region, north-western Tanzania. METHODS: This was a community-based cross-sectional survey which was conducted in July and August 2023 and involved individuals aged ≥ 6 months from five villages in Kyerwa district. Demographic, anthropometric, clinical, parasitological, type of house inhabited and socio-economic status (SES) data were collected using electronic capture tools run on Open Data Kit (ODK) software. Predictors/risks of malaria infections were determined by univariate and multivariate logistic regression, and the results were presented as crude (cORs) and adjusted odds ratios (aORs), with 95% confidence intervals (CIs). RESULTS: Overall, 4454 individuals were tested using rapid diagnostic tests (RDTs), and 1979 (44.4%) had positive results. The prevalence of malaria infections ranged from 14.4% to 68.5% and varied significantly among the villages (p < 0.001). The prevalence and odds of infections were significantly higher in males (aOR = 1.28, 95% CI 1.08 -1.51, p = 0.003), school children (aged 5-≤10 years (aOR = 3.88, 95% CI 3.07-4.91, p < 0.001) and 10-≤15 years (aOR = 4.06, 95% CI 3.22-5.13, p < 0.001)) and among individuals who were not using bed nets (aOR = 1.22, 95% CI 1.03-1.46, p = 0.024). The odds of malaria infections were also higher in individuals with lower SES (aOR = 1.42, 95% CI 1.17-1.72, p < 0.001), and living in houses without windows (aOR = 2.08, 95% CI 1.46-2.96, p < 0.001), partially open (aOR = 1.33, 95% CI 1.11-1.58, p = 0.002) or fully open windows (aOR = 1.30, 95%CI 1.05-1.61, p = 0.015). CONCLUSION: The five villages had a high prevalence of malaria infections and heterogeneity at micro-geographic levels. Groups with higher odds of malaria infections included school children, males, and individuals with low SES, living in poorly constructed houses or non-bed net users. These are important baseline data from an area with high prevalence of parasites with ART-R and will be useful in planning interventions for these groups, and in future studies to monitor the trends and potential spread of such parasites, and in designing a response to ART-R.

Understanding the impact of the COVID-19 pandemic and its control measures on women and children: A Zimbabwe case study.

COVID-19 presented countries with unprecedented health policy challenges. For low-income countries in particular, policymakers had to contend with both the direct threats posed by COVID-19 as well as the social, educational, and economic harms associated with lockdown and other infection prevention and control measures. We present a holistic and contextualised case study of the direct and indirect impacts of COVID-19 on women and children, with some assessment of their uneven distribution across socio-economic, age and gender groups. We used different types of primary and secondary data from multiple sources to produce a holistic descriptive analysis. Primary data included: qualitative data obtained from 28 in-depth interviews of key informants, six focus group discussions; and 40 household interviews. We also extracted data from government reports and announcements, the District Health Information Software version 2 (DHIS2), newspaper articles and social media, as well as from published research articles. Our findings show that the direct and indirect adverse impacts of COVID-19 were compounded by many years of severe political economic challenges, and consequent deterioration of the healthcare system. The indirect effects of the pandemic had the most severe impacts on the poorest segment of society and widened age and gender inequalities. The pandemic and its accompanying infection prevention and control measures negatively affected health service delivery and uptake. The management of COVID-19 presented enormous challenges to policymakers and public health specialists. These included managing the greatest tension between direct and indirect harms; short-term and long-term effects; and the unequal distribution of harms across different segments of society.

Risk factors for curable sexually transmitted infections among youth: findings from the STICH population survey in Zimbabwe.

OBJECTIVES: Youth are at high risk of sexually transmitted infections (STIs) in Africa. We aimed to determine the risk factors for curable STIs in youth in Zimbabwe. METHODS: A population-based survey was conducted among randomly selected 18-24 year-olds in 16 communities across two provinces in Zimbabwe to ascertain outcomes for a cluster randomised trial investigating the impact of community-based STI screening for youth on population prevalence of STIs. Participants underwent an interviewer-administered questionnaire, HIV testing and screening for Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG) and Trichomonas vaginalis (TV). Risk factors for curable STIs were explored through multivariable logistic regression. RESULTS: Of the 5601 participants, 62.5% (n=3500) were female, and the median age was 20 (IQR 19-22) years. HIV prevalence was 6.3% (351/5556), and 55.4% (1939/3501) reported condomless sex at last intercourse. Only 7.2% (401/5599) reported STI symptoms, but CT/NG/TV prevalence was 19.8% (1107/5601). On multivariable analysis, factors associated with STI diagnosis included being aged 21-24 years (adjusted OR (aOR) 1.37, 95% CI 1.17 to 1.61); female sex (aOR 2.11, 95% CI 1.76 to 2.53); being unemployed/informally employed (compared with in education/formal employment) (aOR 1.35, 95% CI 1.13 to 1.61); increasing number of sexual partners in the preceding 12 months (one partner: aOR 2.23, 95% CI 1.73 to 2.88; two partners: aOR 2.39, 95% CI 1.69 to 3.39); living with HIV (aOR 1.44, 95% CI 1.07 to 1.94); and previous attempted suicide (aOR 1.58, 95% CI 1.08 to 2.32). CONCLUSIONS: The prevalence of STIs among youth in Zimbabwe is high, particularly among those with HIV. In addition to moving away from syndromic STI management and strengthening implementation of existing prevention tools, there is a need for a more holistic focus on broader risk factors such as mental health and employment opportunities, and of integration of HIV and STI programming. TRIAL REGISTRATION NUMBER: ISRCTN15013425, NCT03719521.

Impact and determinants of door in-door out time for stroke thrombectomy transfers in a large hub-and-spoke network.

INTRODUCTION: The mantra "time is brain" cannot be overstated for patients suffering from acute ischemic stroke. This is especially true for those with large vessel occlusions (LVOs) requiring transfer to an endovascular thrombectomy (EVT) capable center. We sought to evaluate the spoke hospital door in-door out (DIDO) times for patients transferred to our hub center for EVT. METHODS: Individuals who first presented with LVO to a spoke hospital and were then transferred to the hub for EVT were retrospectively identified from a prospectively maintained database from January 2019 to November 2022. DIDO was defined as the time between spoke hospital door in arrival and door out exit. Baseline characteristics, treatments, and outcomes were compared, dichotomizing DIDO at 90 minutes based in the American Heart Association goal for DIDO ≤90 minutes for 50% of transfers. Multivariable regression analyses were performed for determinants of the 90-day ordinal modified Rankin Scale (mRS) and DIDO. RESULTS: We identified 194 patients transferred for EVT with available DIDO. The median age was 67 years (IQR 57-80), and 46% were female. The median National Institutes of Health Stroke Scale (NIHSS) was 16 (10-20), 50% were treated with intravenous thrombolysis at a spoke, and TICI 2B-3 reperfusion was achieved in 87% at the hub. The median DIDO was 120 minutes (97-149), with DIDO ≤90 minutes achieved in 18%. DIDO was a significant determinant of 90-day ordinal mRS (B = 0.007, 95% CI = 0.001-0.012, p = 0.013), even when accounting for the last known well-to-spoke door in, spoke door out-to-hub arrival, hub arrival-to-puncture, puncture-to-first pass, age, NIHSS, intravenous thrombolysis, TICI 2B-3, and symptomatic intracranial hemorrhage. Importantly, determinants of DIDO included Black race or Hispanic ethnicity (B = 0.918, 95% CI = 0.010-1.826, p = 0.048), atrial fibrillation or heart failure (B = 0.793, 95% CI = 0.257-1.329, p = 0.004), and basilar LVO location (B = 2.528, 95% CI = 1.154-3.901, p < 0.001). CONCLUSION: Spoke DIDO was the most important period of time for long-term outcomes of LVO stroke patients treated with EVT. Targets were identified to reduce DIDO and improve patient outcomes.

Higher loss of livelihood and impoverishment in households affected by tuberculosis compared to non-tuberculosis affected households in Zimbabwe: A cross-sectional study.

Tuberculosis (TB) disproportionally affects poor people, leading to income and non-income losses. Measures of socioeconomic impact of TB, e.g. impoverishment and patient costs are inadequate to capture non-income losses. We applied impoverishment and a multidimensional measure on TB and non-TB affected households in Zimbabwe. We conducted a cross-sectional study in 270 households: 90 non-TB; 90 drug-susceptible TB (DS-TB), 90 drug-resistant TB (DR-TB) during the COVID-19 pandemic (2020-2021). Household data included ownership of assets, number of household members, income and indicators on five capital assets: financial, human, social, natural and physical. Households with incomes per capita below US$1.90/day were considered impoverished. We used principal component analysis on five capital asset indicators to create a binary outcome variable indicating loss of livelihood. Log-binomial regression was used to determine associations between loss of livelihood and type of household. TB-affected households were more likely to report episodes of TB and household members requiring care than non-TB households. The proportions of impoverished households were 81% (non-TB), 88% (DS-TB) and 94% (DR-TB) by the time of interview. Overall, 56% (152/270) of households sold assets: 44% (40/90) non-TB, 58% (52/90) DS-TB and 67% (60/90) DR-TB. Children's education was affected in 33% (55/168) of TB-affected compared to 14% (12/88) non-TB households. Overall, 133 (50%) households experienced loss of livelihood, with TB-affected households almost twice as likely to experience loss of livelihood; adjusted prevalence ratio (aPR = 1.78 [95%CI:1.09-2.89]). The effect of TB on livelihood was most pronounced in poorest households (aPR = 2.61, [95%CI:1.47-4.61]). TB-affected households experienced greater socioeconomic losses compared to non-TB households. Multisectoral social protection is crucial to mitigate impacts of TB and other shocks, especially targeting poorest households.

Cardiovascular health in people with perinatally acquired HIV - where do we stand?

PURPOSE OF REVIEW: HIV-associated cardiac disease was well recognized in the preantiretroviral (ART) era among children with perinatally-acquired HIV infection (PHIV). While ART has dramatically improved survival, it has become increasingly apparent that individuals with PHIV continue to experience multisystem co-morbidities. We review the cardiac and vascular manifestations in people growing up with PHIV in the ART era. RECENT FINDINGS: ART has resulted in a drop in incidence of serious cardiac morbidity. However, there is a substantial body of evidence that demonstrates that cardiac and vascular structural and functional abnormalities, mostly subclinical, are common in people with PHIV taking ART. Studies have considerable heterogeneity with respect to types of cardiovascular assessments used. HIV-mediated chronic inflammation and potentially effects of ART contribute to these abnormalities. The long-term clinical significance of these abnormalities remains unknown as studies have mainly been cross-sectional, but it is likely that the burden of cardiovascular disease will grow as individuals with PHIV age and the prevalence of traditional risk factors increases. SUMMARY: Understanding the pathogenesis of cardiovascular disease in PHIV, is critical to inform screening and interventional strategies. Longitudinal studies are also needed to understand the natural history of cardiovascular abnormalities and incidence of clinical outcomes.

Angiotensin II Type 1 receptor blockade attenuates the neuropathological changes in the spinal cords of diabetic rats with modulation of nuclear factor erythroid 2-related factor 2/ heme oxygenase 1 system.

Peripheral and central neuropathies frequently complicate worldwide diabetes. Compared to peripheral neuropathy, central neuropathy didn`t gain a major research interest. Angiotensin II is reported to be involved in diabetic neuropathic pain but its role in the central pathological changes in the spinal cord is not clear. Here, we study the role of Losartan; an Angiotensin II receptor 1 (AT1) antagonist in suppression of the diabetes-induced changes in the spinal cord. Three groups of rats were applied; a negative control group, a streptozotocin (STZ) diabetic group, and a group receiving STZ and Losartan. After two months, the pathological alteration in the spinal cord was investigated, and an immunohistochemical study was performed for neuronal, astrocytic, and microglial markers; nuclear protein (NeuN), Glial fibrillary acidic protein (GFAP), and Ionized calcium-binding adaptor molecule 1 (Iba1), respectively, and for an apoptosis marker; caspase-3, and the inflammatory marker; nuclear factor kappa B (NF-kB) signaling, heme oxygenase-1 (HO-1) and nuclear factor erythroid 2-related factor 2 (Nrf2); physiological antioxidant system. The results showed that Losartan caused recovery of spinal cord changes, by inhibiting the microglial and astrocytic activation, suppressing neuronal apoptosis and NF-kB expression with activation of Nrf2/HO-1 (P<0.0005). It is suggested, herein, that Losartan can suppress diabetes-induced glial activation, inflammation, neuronal apoptosis, and oxidative stress in the spinal cord; the mechanisms that may underlie the role of AT1 antagonism in suppressing diabetic neuropathic pain.

HIV-Associated Cardiovascular Disease Pathogenesis: An Emerging Understanding Through Imaging and Immunology.

Cardiac abnormalities were identified early in the epidemic of AIDS, predating the isolation and characterization of the etiologic agent, HIV. Several decades later, the causation and pathogenesis of cardiovascular disease (CVD) linked to HIV infection continue to be the focus of intense speculation. Before the widespread use of antiretroviral therapy, HIV-associated CVD was primarily characterized by HIV-associated cardiomyopathy linked to profound immunodeficiency. With increasing antiretroviral therapy use, viral load suppression, and establishment of immune competency, the effects of HIV on the cardiovascular system are more subtle. Yet, people living with HIV still face an increased incidence of cardiovascular pathology. Advances in cardiac imaging modalities and immunology have deepened our understanding of the pathogenesis of HIV-associated CVD. This review provides an overview of the pathogenesis of HIV-associated CVD integrating data from imaging and immunologic studies with particular relevance to the HIV population originating from high-endemic regions, such as sub-Saharan Africa. The review highlights key evidence gaps in the field and suggests future directions for research to better understand the complex HIV-CVD interactions.

Phytic acid attenuates acetaminophen-induced hepatotoxicity via modulating iron-mediated oxidative stress and SIRT-1 expression in mice.

Introduction: Administration of high doses of acetaminophen (APAP) results in liver injury. Oxidative stress and iron overload play roles in the pathogenesis of APAP-induced hepatotoxicity. The present study assessed the potential hepatoprotective effects of phytic acid (PA), a natural antioxidant and iron chelator, on APAP-induced hepatotoxicity and the possible underlying mechanism through its effects on CYP2E1 gene expression, iron homeostasis, oxidative stress, and SIRT-1 expression levels. Methods: Twenty-four adult male albino mice were used in this study. Mice were divided into four groups (six mice in each group): control, APAP-treated, PA-treated and APAP + PA-treated groups. Liver function tests, serum and liver tissue iron load were evaluated in all the study groups. Hepatic tissue homogenates were used to detect oxidative stress markers, including malondialdehyde (MDA) and reduced glutathione (GSH). Histological hepatic evaluation and immunohistochemistry of SIRT-1 were performed. Quantitative real-time PCR was used for the assessment of CYP2E1 and SIRT-1 gene expressions. APAP-induced biochemical and structural hepatic changes were reported. Results: PA administration showed beneficial effects on APAP-induced hepatotoxicity through improvements in liver functions, decreased CYP2E1 gene expression, decreased serum and liver iron load, decreased MDA, increased GSH, increased SIRT-1 expression level and improvement in hepatic architecture. Conclusion: Conclusively, PA can be considered a potential compound that can attenuate acetaminophen-induced hepatotoxicity through its role as an iron chelator and antioxidant, as well as the up-regulation of SIRT-1 and down-regulation of CYP2E1.

Fennel seeds extract prevents fructose-induced cardiac dysfunction in a rat model of metabolic syndrome via targeting abdominal obesity, hyperuricemia and NF-κß inflammatory pathway.

BACKGROUND: Metabolic syndrome (MetS) is commonly associated with increased risk of cardiac disease that affects a large number of world populations. OBJECTIVE: This research attempted to investigate the efficacy of fennel seeds extract (FSE) in preventing development of cardiac dysfunction in rats on fructose enriched diet for 3 months, as a model of MetS. MATERIALS & METHODS: Thirty adult Wistar male rats (160-170 g) were assigned into 5 groups including control, vehicle, FSE (200 mg/kg BW) and fructose (60%) fed rats with and without FSE. Following the last treatment, blood pressure, ECG and heart rate were measured. Next, blood and cardiac tissues were taken for biochemical and histological investigations. RESULTS: Feeding fructose exhibited characteristic features of MetS involving, hypertension, abnormal ECG, elevated heart rate, serum glucose, insulin, lipids and insulin resistance, accompanied by abdominal obesity, cardiac hypertrophy and hyperuricemia. Fructose fed rats also showed significant reduction in cardiac antioxidants (GSH, SOD, CAT) with elevation in oxidative stress indices (NADPH oxidase, O2.-, H2O2, MDA, PCO), NF-κß, pro-inflammatory cytokines (TNF-α, IL-1ß, IL-6), adhesion molecules (ICAM-1, VCAM-1) and serum cardiac biomarkers (AST, LDH, CK-MB, cTn-I). Histopathological changes evidenced by destruction of cardiac myofibrils, cytoplasmic vacuolization, and aggregation of inflammatory cells were also detected. Consumption of FSE showed high ability to alleviate fructose-induced hypertension, ECG abnormalities, cardiac hypertrophy, metabolic alterations, oxidative stress, inflammation and histological injury. CONCLUSION: Findings could suggest FSE as a complementary supplement for preventing MetS and associated cardiac outcomes. However, well controlled clinical studies are still needed.

D3/Penta 21 clinical trial design: A randomised non-inferiority trial with nested drug licensing substudy to assess dolutegravir and lamivudine fixed dose formulations for the maintenance of virological suppression in children with HIV-1 infection, aged 2 to 15 years.

BACKGROUND: There is increasing interest in utilising two-drug regimens for HIV treatment with the goal of reducing toxicity and improve acceptability. The D3 trial evaluates the efficacy and safety of DTG/3TC in children and adolescents and includes a nested pharmacokinetics(PK) substudy for paediatric drug licensing. METHODS: D3 is an ongoing open-label, phase III, 96-week non-inferiority randomised controlled trial(RCT) conducted in South Africa, Spain, Thailand, Uganda and the United Kingdom. D3 has enrolled 386 children aged 2- < 15 years, virologically suppressed for ≥6 months, with no prior treatment failure. Participants were randomised 1:1 to receive DTG/3TC or DTG plus two nucleoside reverse transcriptase inhibitors(NRTIs), stratified by region, age (2- < 6, 6- < 12, 12- < 15 years) and DTG use at enrolment (participants permitted to start DTG at enrolment). The primary outcome is confirmed HIV-1 RNA viral rebound ≥50 copies/mL by 96-weeks. The trial employs the Smooth Away From Expected(SAFE) non-inferiority frontier, which specifies the non-inferiority margin and significance level based on the observed event risk in the control arm. The nested PK substudy evaluates WHO weight-band-aligned dosing in the DTG/3TC arm. DISCUSSION: D3 is the first comparative trial evaluating DTG/3TC in children and adolescents. Implications of integrating a PK substudy and supplying data for prompt regulatory submission, were carefully considered to ensure the integrity of the ongoing trial. The trial uses an innovative non-inferiority frontier for the primary analysis to allow for a lower-than-expected confirmed viral rebound risk in the control arm, while ensuring interpretability of results and maintaining the planned sample size in an already funded trial. TRIAL REGISTRATION: International Standard Randomised Clinical Trial Number Register: ISRCTN17157458. European Clinical Trials Database: 2020-001426-57. CLINICALTRIALS: gov: NCT04337450.

microRNA 21 and long non-coding RNAs interplays underlie cancer pathophysiology: A narrative review.

Non-coding RNAs (ncRNAs) are a diverse group of functional RNA molecules that lack the ability to code for proteins. Despite missing this traditional role, ncRNAs have emerged as crucial regulators of various biological processes and have been implicated in the development and progression of many diseases, including cancer. MicroRNAs (miRNAs) and long non-coding RNAs (lncRNAs) are two prominent classes of ncRNAs that have emerged as key players in cancer pathophysiology. In particular, miR-21 has been reported to exhibit oncogenic roles in various forms of human cancer, including prostate, breast, lung, and colorectal cancer. In this context, miR-21 overexpression is closely associated with tumor proliferation, growth, invasion, angiogenesis, and chemoresistance, whereas miR-21 inactivation is linked to the regression of most tumor-related processes. Accordingly, miR-21 is a crucial modulator of various canonical oncogenic pathways such as PTEN/PI3K/Akt, Wnt/ß-catenin, STAT, p53, MMP2, and MMP9. Moreover, interplays between lncRNA and miRNA further complicate the regulatory mechanisms underlying tumor development and progression. In this regard, several lncRNAs have been found to interact with miR-21 and, by functioning as competitive endogenous RNAs (ceRNAs) or miRNA sponges, can modulate cancer tumorigenesis. This work presents and discusses recent findings highlighting the roles and pathophysiological implications of the miR-21-lncRNA regulatory axis in cancer occurrence, development, and progression. The data collected indicate that specific lncRNAs, such as MEG3, CASC2, and GAS5, are strongly associated with miR-21 in various types of cancer, including gastric, cervical, lung, and glioma. Indeed, these lncRNAs are well-known tumor suppressors and are commonly downregulated in different types of tumors. Conversely, by modulating various mechanisms and oncogenic signaling pathways, their overexpression has been linked with preventing tumor formation and development. This review highlights the significance of these regulatory pathways in cancer and their potential for use in cancer therapy as diagnostic and prognostic markers.

Experiences of caring for women with cervical cancer: A qualitative study among male partners in Dar es Salaam, Tanzania.

BACKGROUND: More than three-fourths of cervical cancer cases occur in low- and middle-income countries, with sub-Saharan Africa (SSA) accounting for approximately 25% of global mortality. The significant rise in the prevalence of cervical cancer in SSA amplifies the burden on caregivers, contributing to elevated rates of mental illness, particularly among spouses who provide care. Men who assume the role of caregivers for their partners with cervical cancer encounter unique challenges and substantial adjustments across multiple facets of life, impacting both their own quality of life and that of their partners. Despite this, there is a notable lack of extensive research on the experiences of male partners in caregiving roles, particularly within SSA countries like Tanzania. Therefore, this study aimed to explore the experiences of male partners providing care for women with cervical cancer in Dar es Salaam, Tanzania. METHODS: An exploratory qualitative study was undertaken to explore the experiences of 13 male partners, selected purposively and guided by the principle of saturation. Data gathering employed in-depth interviews utilizing a semistructured interview guide, with subsequent analysis conducted via a thematic analysis approach. RESULTS: Five themes and 13 subthemes were generated, encompassing psychosocial distress, attitudes towards cervical cancer, unity in the provision of care, economic burden, and altered sexual relationships. Participants reported experiencing emotional distress, shifts in social responsibilities, financial challenges, and unfulfilled sexual needs. Moreover, they expressed the need for social, psychological, financial, and sexual and reproductive support. CONCLUSION: This study underscores the numerous challenges encountered by male partners caring for women with cervical cancer, encompassing emotional distress, financial strain, and shifts in social and sexual dynamics. The identified themes and subthemes highlight the intricate interplay of these difficulties and stress the necessity for holistic support systems addressing the social, psychological, financial, and sexual aspects of male partners' experiences. The findings emphasize the importance of designing and implementing comprehensive support programmes tailored to the diverse needs of male partners, ultimately enhancing their quality of life and overall well-being. PATIENT OR PUBLIC CONTRIBUTION: Before the study, the nursing manager assisted in selecting three male partners randomly. These partners were involved in the design of the participants' information sheet, the evaluation of the interview schedule and rooms, and the dissemination of information about the study's purpose to the target population. Their valuable input contributed to improving the participant information sheet, refining data collection procedures and addressing ethical considerations. However, these individuals were not considered study participants. Throughout the study, in-charge nurses in the hospital were informed about the study's goals and helped organize appointments with participants and manage the interview schedule.