Conectar
by Lauren H. Baker, Terun Desai, Jonathan Sinclair, Amy V. Wells
ObjectivesTo monitor sleep patterns of elite swimmers and explore sleep as a potential risk factor for upper respiratory symptoms (URS) alongside salivary Immunoglobulin A (IgA) in elite swimmers, over an 8-month competitive season.
DesignSecondary analysis of an 8-month longitudinal study in elite international swimmers leading into either the Commonwealth Games 2018 or Swim Cup Eindhoven.
MethodsFourteen elite swimmers (age ± SD = 19.9 ± 0.8 years, height = 178.9 ± 6.3 cm, and mass = 75.0 ± 7.7 kg) were recruited. Self-reported sleep quality, URS data and salivary IgA was obtained weekly on a standardised day. Quantitative sleep parameters were measured using wrist-worn actigraphy four times for two-week bouts; during low, moderate, high training loads and once leading into competition.
ResultsSwimmers waking fatigued was positively associated with frequency (p Conclusions
Perceived fatigue on waking was significantly associated with both frequency and severity of URS, and inversely associated with mucosal immunity (salivary IgA), providing novel insight into the relationship between sleep, fatigue and illness in this cohort. Although causality cannot be established, the high prevalence of inadequate sleep shown in elite swimmers highlights the importance of individual sleep monitoring to support recovery and inform strategies aimed at illness prevention.
The cover image is based on the article Moisture-Responsive Friction Adaptability: Rethinking the Conventional Skin Silicone Interfaces in Pressure Injury Prevention Dressing Designs by Amit Gefen et al., https://doi.org/10.1111/iwj.70860.
The cover image is based on the article Moisture-Responsive Friction Adaptability: Rethinking the Conventional Skin Silicone Interfaces in Pressure Injury Prevention Dressing Designs by Amit Gefen et al., https://doi.org/10.1111/iwj.70860.
The feature cover image is based on the article Intent to treat analysis of the Primary and Secondary Outcomes for the XXX intact fish skin graft for deep diabetic foot wounds trial by John Lantis et al., https://doi.org/10.1111/iwj.70847.
The feature cover image is based on the article Intent to treat analysis of the Primary and Secondary Outcomes for the XXX intact fish skin graft for deep diabetic foot wounds trial by John Lantis et al., https://doi.org/10.1111/iwj.70847.
The COVID-19 pandemic threatened global HIV Test and Treat Efforts. We assessed whether it affected (1) the number of antiretroviral therapy (ART) initiations and (2) the proportion of timely ART initiations in people living with HIV (PLWH) globally.
Quasi-experimental, regression discontinuity design using routinely collected data from HIV clinics.
360 HIV care clinics across primary and secondary levels of care, participating in the International epidemiology Databases to Evaluate AIDS consortium, in 31 countries in Asia, Africa and the Americas.
177 391 PLWH (≥18 years old) who initiated ART 2 years before and 1 year after the onset of the COVID-19 pandemic in their country.
The primary outcome was the number of ART initiations per week; the secondary outcome was the proportion of timely ART initiations (ie, ART initiated within 7 days of enrolment). We assessed changes in these outcomes in the 52 weeks after compared to the 104 weeks before the pandemic onset, defined using each country’s peak Oxford Stringency Index score between January and June 2020.
Among 177 391 newly enrolled PLWH, 129 743 initiated during the pre-pandemic and 47 648 post-pandemic onset. 72.5% of ART initiations were timely pre-pandemic whereas 82.3% were during the pandemic. Absolute number of ART initiations remained stable during the pandemic period in 25 of 31 countries but decreased significantly in six countries: India (–5.0 p, 95% CI –9.2 to –0.7), Rwanda (–10.0 p, –18.6 to –1.4), Malawi (–33.4 p, –54.1 to –12.3), South Africa (–130.8 p, –188.6 to –73.1), Zimbabwe (–12.9 p, –20.0 to –5.8) and Togo (–19.6 p, –39.1 to –0.1). The proportion of timely initiations was stable in all countries except in Kenya (+4.2 pp, 95% CI +0.3 to +8.1) and in Mozambique (+2.7 pp, +0.5 to +4.9), where it increased significantly.
A deeper understanding of the factors that contributed to sustaining ART initiations, particularly in settings with stringent public health and social measures, is needed. These insights should inform preparedness strategies, resource allocation and policy development to ensure continuity of HIV services during future health emergencies, in line with World Health Organisation recommendations.
Multidrug-resistant tuberculosis (MDR-TB) is an urgent public health challenge in Namibia, with profound socioeconomic consequences. The high burden of both tuberculosis and HIV complicates treatment and underscores the need for optimised drug therapies. Precision medicine, which leverages patient-specific genetic and molecular information, offers promise for improving MDR-TB outcomes. However, its effective application relies on population-specific data, particularly understanding how individuals metabolise tuberculosis drugs and how genetic diversity drives variability in treatment response. Currently, no pharmacokinetic (PK) or pharmacogenetic (PG) data on TB treatment exist for Namibian populations. This gap is particularly concerning, given the country’s genetic diversity, environmental factors and comorbidities that may uniquely influence drug metabolism. This study aims to generate PK and PG data to inform dose optimisation and support personalised treatment strategies for MDR-TB in Namibia. The findings will contribute to improved patient care and inform health system strengthening based on locally relevant evidence.
This cross-sectional study will consist of 100 Namibian participants with matched human DNA and PK data of MDR-TB cases receiving isoniazid, clofazimine, bedaquiline and the fluoroquinolones (levofloxacin or moxifloxacin). PK sampling will be divided as follows: 30 individuals will undergo intensive PK sampling, while the remaining (n=70) will undergo sparse PK sampling. DNA will be extracted at Stellenbosch University (SU), and samples will be genotyped using the H3Africa microarray. Sequences will be aligned to the human reference genome, hg38 (GRCh38p13), using the freely available Burrows-Wheeler Aligner. A subset of the samples (n=20–30) will undergo whole genome sequencing (WGS) to verify imputation results and identify novel genetic variants potentially affecting PK in this population.
Quality control and variant call format file generation will be performed using the Genome Analysis Toolkit best practices (V.3.5). Intensive and sparse PK data will be pooled for the development of a population PK (popPK) model using a non-linear mixed-effects modelling approach. The popPK model will characterise the relationship between TB drug dose and exposure, including quantifying covariates, including genetic variation, explaining PK variability, providing a foundation for dose optimisation and personalised treatment strategies.
Ethics approval was obtained from the University of Namibia Human Research Ethics Committee for Health (Ref. SOM18/2024), the Ministry of Health and Social Services (Ref. 22/4/2/3), the SU Health Research Ethics Committee (Ref. N21/11/136) and the University of Cape Town Human Research Ethics Committee (Ref. 500/2022).
There is a significant need for trials that evaluate the treatment of University of Texas (UT) grade 2 and 3 diabetic foot ulcers (bone, joint, or tendon exposed wounds). We undertook a trial looking at the effect of intact fish skin graft (IFSG) on these deep and difficult-to-heal ulcers. 262 patients Intent to Treat (ITT) patients with UT grade 2 and 3 DFUs were randomised to receive intact fish skin graft (IFSG) or a standardised treatment (SOC) that adhered to the International Working Group on the Diabetic Foot (IWGDF) guidelines. The secondary endpoints that were measured included wound area reduction (WAR), healing rates at 20 and 24 weeks; closure rates by UT grade, perfusion, quality of life, pain reduction and IFSG safety. We report ITT (all randomised) (mITT previosly reported) The (WAR) at 12 weeks was 65.53% for IFSG versus 30.82% for SOC (p = 0.007). UT 2 wounds (60% of total) exhibited a closure rate of 47% versus 23% at 16 weeks for IFSG versus SOC (p = 0.0033). Target wound infections were comparable (39 vs. 37) and major outcomes were comparable during the 24 week period (target-limb amputations 8% vs. 7%). Time-to-heal favoured IFSG (restricted mean to 24 weeks 17.31 vs. 19.37 weeks; KM/log-rank significant; Cox HR 1.59). The in the treatment of deep complex diabetic foot wounds the addition of IFSG significantly improved the number of patients with total wound closure as well as the time to wound closure without increased risk of complications. This improvement in total wound closure and time to wound closure was noted across prior amputation status, quality of perfusion, and UT grade.
This study evaluated the frictional properties of the skin-contact interfaces of two multilayer prophylactic dressings under simulated perspiration conditions. The tested dressings were identical except for the skin-contact interface, which was either silicone-made or Hydrofiber-made, that is, AQUACEL Hydrofiber Technology. Using a standardised tribological ‘sled test’ setup and a skin-mimicking polymer substrate, we measured the static and kinetic coefficients of friction for each dressing interface type at varying moisture levels. The dressing with the Hydrofiber interface consistently demonstrated significantly lower static and kinetic coefficients of friction compared to the silicone-based dressing, across all moisture conditions. The Hydrofiber interface exhibited a sharp coefficient of friction reduction with minimal (5%) moisture accumulation, mimicking overnight perspiration under thermoneutral conditions. This dressing maintained the low coefficient of friction levels at a steady level of approximately 0.2 until full saturation. In contrast, the silicone interface retained high (> 1) coefficients of friction regardless of moisture. These findings highlight an important biomechanical advantage of Hydrofiber skin-contact materials in reducing frictional forces at the skin-dressing interface, especially in moisture-prone body areas, in a pressure injury prevention context. Friction-responsive skin-contacting dressing materials with low coefficients of friction, which remain low while they become moist due to perspiration accumulation, should be preferred for preventative dressings.
Effective thermal management at the skin-dressing interface is essential in pressure injury prevention by means of prophylactic dressings. This study quantified the thermal conductivity of AQUACEL Hydrofiber Technology (AHT, hydrofiber) and polyurethane foam dressing materials under normothermic (32°C) and febrile (40°C) conditions across increasing moisture levels. Using a validated custom heat-flow meter system, dry hydrofiber exhibited significantly greater thermal conductivity than the polyurethane foam (0.43 ± 0.01 vs. 0.20 ± 0.01 W/m K at 32°C; p < 0.001). Upon hydration at 32°C, thermal conductivity values increased nonlinearly for both materials but to a much greater extent for the hydrofiber. At 15% moisture, the hydrofiber reached 4.73 ± 0.12 W/m K compared to the polyurethane foam at 1.03 ± 0.02 W/m K. At 40°C, hydrofiber achieved 3.39 ± 0.19 W/m K with only 10% moisture, indicating a temperature-responsive biphasic transformation. Overall, hydrofiber demonstrated a fivefold greater thermal conductivity response to moisture than the polyurethane foam. These findings highlight critical, material-dependent differences in heat dissipation under clinically relevant conditions. The superior moisture-responsive thermal conductivity of hydrofiber highlights its potential to improve heat dissipation at the skin-dressing interface under clinically relevant conditions and thereby mitigate local heat accumulation, contributing to skin protection. Thermal conductivity and thermal adaptability studies should be integrated into dressing efficacy research and be used for selection criteria for pressure injury prevention programs alongside mechanical and absorptive performance.
Clinical trials have produced inconclusive results regarding the optimal glucose range for a patient with sepsis in the intensive care unit (ICU) receiving insulin treatment.
To investigate the optimal glucose range in patients with sepsis in the ICU independent of confounding covariates.
Targeted trial emulation of glucose ranges using causal inference targeted maximum likelihood estimation and longitudinal mixed-effects models combined with survival models.
Single-centre, academic referral hospital in Boston, Massachusetts, USA.
Adults fulfilling sepsis 3 criteria with at least three glucose readings and insulin treatment from the Medical Information Mart for Intensive Care (MIMIC)-IV database (2008–2019).
Five predefined glucose distributions with means at 100, 130, 160 (baseline), 190 and 220 mg/dL mimicking current guidelines’ recommendations (140–180 mg/dL).
The primary outcome was in-hospital mortality. Modified counterfactual treatment-policy risks across distinct time-weighted glucose ranges were estimated.
Of 73 181 eligible patients, 8002 patients with a median age of 66 years (41% women, 67% white ethnicity, 57% diabetes) were included. There was a U-shaped curve between glucose range and mortality in patients without diabetes, but overall, this association was not significant (mean glucose at 100 mg/dL with 21% mortality and mean glucose at 220 mg/dL with 26% mortality, p-for-trend 0.26). Mortality was lowest at 17%, with mean glucose between 130 and 160 mg/dL. Hypoglycaemic events (
Our data suggest a U-shaped association of glucose and mortality with an optimal average glucose between 160 and 190 mg/dL. These results confirm current guideline recommendations. Together with recent results from randomised controlled trials, intensivists should aim for a liberal glucose range in most patients.
A comprehensive skincare regimen involves cleansing, moisturising, and using skin barrier protectants. Cyanoacrylate-based protectants safeguard vulnerable skin from damage caused by moisture, friction, and shear. This research involved two ex vivo and two clinical studies comparing the wear duration and wash-off resistance of a 100% cyanoacrylate and a solvent-cyanoacrylate mixture. Effectiveness was assessed using an ex vivo porcine skin model simulating urinary incontinence, evaluated with Lucifer yellow dye penetration and Corneometry, and a clinical model using Corneometry. Two single-blind clinical studies measured skin surface electrical capacitance in healthy volunteers. Study 1 (n = 42) evaluated the wear duration over 8 days, while Study 2 (n = 52) examined wash-off resistance after nine washes with various cleansers. Ex vivo results showed that both products were effective under repeated moisture and abrasion conditions, with the 100% cyanoacrylate outperforming the solvent-cyanoacrylate mixture. In clinical studies, both products maintained barrier protection throughout Study 1 (p < 0.007) and none of the cleansers significantly degraded either product in Study 2. In conclusion, the 100% cyanoacrylate provided superior protection compared to the solvent-cyanoacrylate mixture. Both products demonstrated comparable wear duration and wash-off resistance in clinical studies, but the 100% cyanoacrylate was more effective in ex vivo testing under harsh conditions.
by Donato Koyalta, Zita Aleyo Nodjikouambaye, Jonathan Muwonga Tukisadila, Hachim Djamal Abdoulaye Bargo, Suitombaye Noubaramadji Yamti, Amine Akouya, Ralph-Sydney Mboumba Bouassa, Laurent Belec
BackgroundHigh-risk (HR) human papillomavirus (HPV) infection remains a great concern in sub-Saharan Africa in men who have sex with men (MSM). The prevalence of anal shedding of HPV and associated risk factors was estimated for the first time in a cross-sectional observational study covering MSM living in N’Djamena, the capital city of Chad.
MethodsMSM were recruited from the community in 21 sites in neighborhoods of 5 districts randomly selected in N’Djamena by respondent-driven sampling (RDS) method. Anal Collector V-Veil UP2™ device was used for anal canal self-sampling. Manual silica-extracted DNA was subjected for HPV detection and genotyping using BMRT Human Papillomavirus Genotyping Real Time PCR assay (Jiangsu Bioperfectus Technologies Co., Ltd., Taizhou, China). HIV serostatus was assessed using two rapid tests in series.
ResultsA total of 70 MSM (mean age: 29.9 years; range, 18–50) were included. The overall acceptability to practice veil-based anal self-sampling was 95.9%. The usability of the veil collector device was high (92.3%), with easy understandable instructions for use and correct placement in the anal canal. Satisfaction questionnaire reported high overall feeling, intimacy respect and lack of shame. The majority of MSM (44/70, 62.8%) showed anal shedding of HPV DNA, with HR-HPV frequently detected (38,70, 54.3%), including HPV-33 (30/70, 42.9%) HPV-68 (16/70, 22.9%), HPV-18 (4/70, 5.7%), HPV-35 (3/70, 4.3%), HPV-58 (2/70, 2.9%), and HPV-45 (1/70, 1.4%). The distribution of genotypes in HR-HPV DNA-positive MSM revealed that HPV-33 (30/70; 42.9%) was the predominant genotype, followed by the HPV-68 (16/70; 22.9%), HPV-18 (4/70; 5.7%), HPV-35 (3/70; 4.3%), HPV-58 (2/70; 2.9%), and HPV-45, HPV-51 and HPV-56 (each type, 1/70;1.4%).Among all HPV detected, only 42 HPV (36.8%) were covered by Gardasil-9® vaccine, including the HR-HPV-33, −18, −58 and −45, and the low risk-HPV-6 (5.7%) and HPV-11 (1.4%). The majority of detected HPV were non-covered by Gardasil-9® vaccine (63.1%). Overall HIV prevalence was 5.7%.
ConclusionsTaken together, these observations point the MSM population in N’Djamena as a very particular core group of HIV and HPV transmission. HIV prevalence was higher than that of general adult population, but limited to only one MSM of twenty. The RDS method of recruitment allowed to include MSM likely belonging to the same sexual network of HPV transmission leading to the selection of an atypical and specific profile of anal HPV distribution. The potential efficacy of HPV prophylactic vaccination in this population can be estimated at relatively weak.
To characterise nurses' perspectives on factors that influence their ability to provide patient-centered nursing care for autistic patients in a large urban hospital setting.
Qualitative exploratory study.
We conducted semi-structured interviews via Zoom with nurses from a large urban hospital serving primarily adult patients. We analysed interviews using codebook/template analysis. Two researchers coded each interview and resolved discrepancies through discussion.
Twelve nurses (3 males) with 2–20 years of professional experience across research, management, and patient care roles were interviewed. Three primary themes were generated: (1) barriers to patient-centered care, including lack of formal autism education, factors related to the hospital setting, and specific nurse characteristics, such as inflexible adherence to care routines; (2) facilitators of patient-centered care, including experiential autism knowledge, caregiver involvement, and specific nurse characteristics, such as showing respect for all patients; and (3) missed opportunities for patient-centered care, including underuse of behavioural care teams, inadequate time for planning and preparation, and reliance upon restraints and security personnel for behaviour management.
Nurses identified several areas where consistent implementation of existing processes could improve care. A key finding was the need to explore more patient-centered alternatives to the use of restraints and security personnel in response to aggressive or self-injurious behaviour. Overall, our results support the need for competency training to facilitate increased nursing comfort and ability to provide patient-centered care for autistic patients.
This work suggests nurses gain much of their autism-related knowledge through patient care experiences. Despite providing the majority of hands-on care, nurses receive little to no formal training about caring for the growing autistic population.
This work has identified targeted areas to improve education and processes in caring for autistic patients.
No patient or public contribution.
by Lauren Riehm, Keean Nanji, Moiz Lakhani, Evelina Pankiv, Dean Hasanee, Wesla Pfeifer
PurposeLarge language models (LLMs) have the potential to change medical education. Whether LLMs can generate multiple-choice questions (MCQs) that are of similar quality to those created by humans is unclear. This investigation assessed the quality of MCQs generated by LLMs compared to humans.
MethodsThis review was registered with PROSPERO (CRD42025608775). A systematic review and frequentist random-effects network meta-analysis (NMA) or pairwise meta-analysis was performed. Ovid MEDLINE, Ovid EMBASE, and Scopus were searched from inception to November 1, 2024. The quality of MCQs was assessed with seven pre-defined outcomes: question relevance, clarity, accuracy/correctness; distractor quality; item difficulty analysis; and item discrimination analysis (point biserial correlation and item discrimination index). Continuous data were transformed to a 10-point scale to facilitate statistical analysis and reported as mean differences (MD). The MERSQI and the Grade of Recommendations, Assessment, Development and Evaluation (GRADE) NMA guidelines were used to assess risk of bias and certainty of evidence assessments.
ResultsFive LLMs were included. NMA demonstrated that ChatGPT 4 generated similar quality MCQs to humans with regards to question relevance (MD −0.13; 95% CI: −0.44,0.18; GRADE: VERY LOW), question clarity (MD −0.03; 95% CI: −0.15,0.10; GRADE: VERY LOW), and distractor quality (MD −0.10; 95% CI: −0.24,0.04; GRADE: VERY LOW); however, MCQs generated by Llama 2 performed worse than humans with regards to question clarity (MD −1.21; 95% CI: −1.60,-0.82; GRADE: VERY LOW) and distractor quality (MD −1.50; 95% CI: −2.03,-0.97; GRADE: VERY LOW). Exploratory post-hoc t-tests demonstrated that ChatGPT 3.5 performed worse than Llama 2 and ChatGPT 4 with regards to question clarity and distractor quality (p Conclusion
ChatGPT 4 may create similar quality MCQs to humans, whereas ChatGPT 3.5 and Llama 2 may be of worse quality. Further studies that directly compare these LLMs to human-generated questions and administer MCQs to students are required.
Patient safety is a central pillar of healthcare quality. However, with repeated examples of failure emerging across healthcare, there is an ongoing need to better understand how the safety of care can be improved for patients. Evidence suggests that some population groups are more likely to inequitably experience healthcare harm. This review will look at what evidence exists on understanding patient safety harm and its causes and impact on different population groups and particularly those from marginalised backgrounds. It will also focus on what actions can be taken to address patient safety disparities and service improvements, including with patient and public involvement.
A scoping review of empirical and grey literature will be conducted following the Joanna Briggs Institute guidance. Medical databases such as Medline, EMBASE, PsycINFO will be searched for peer-reviewed articles and grey literature sources such as BASE, institutional and government repositories will be searched for reports, independent reviews, confidential enquiries, etc. These will be searched from 2001 to present for publications in English. Title and abstract and full text screening will be undertaken by one or more people acting as first reviewers and validated by a second reviewer. A data extraction form will be used to extract data including equity considerations following the PRO EDI framework. Data will be grouped thematically and analysed using a narrative approach.
Ethics approval is not required for this work as the information used is publicly available. The findings of the review will be disseminated through stakeholder meetings, a peer-reviewed publication and conference presentations.
osf.io/4mfus.
This review seeks to explore the illness narratives of children and young people focusing on their healthcare trajectories; the right to health; and the kind of stories told about them.
This scoping review adopts a narrative approach to analyse how the illness experience of Spinal Muscular Atrophy is represented in the literature, moving beyond biomedical descriptions to consider sociocultural and historical dimensions. We explore how global and local forces shape everyday life and therapeutic possibilities for people with this condition.
Four online databases were used to identify papers published between 2014 and 2024 in English and Spanish. The analysis process was guided by the PAGER Framework.
Twenty-one articles met the criteria for the review, mainly published in the Global North. Following organisation of Patterns, findings were categorised into three themes: (1) Parents as storytellers of young people's life trajectories; (2) Tropes about everyday life with Spinal Muscular Atrophy; and (3) The right to health as a narrative terrain. Findings show that access to medical treatment, information, and healthcare coverage poses difficulties when navigating the healthcare system with little institutional support.
The voices of individuals with Spinal Muscular Atrophy are rarely reported, often represented by their parents. There are opportunities to develop strategies that enhance the experiences of children and young people when seeking care, which should have a rights-based, intersectional, and family-centred approach.
This review highlights the need to listen to children and young people's voices, offer support to caregivers, and further explore the right to health in the Global South.
The interpretation of the findings was enriched by the involvement of patients, who participated as advisors for the research team. Their contributions ensured the research remained aligned with concerns and priorities informed by lived experience of the disease.
by Anastasia Topalidou, Lauren Haworth, Raeesa Jassat, Morgan Hawcroft-Hurst
Pregnancy and childbirth involve profound biomechanical transformations, adaptations, and functional demands on the maternal body. Although biomechanical complications have been identified as a major contributor to maternal morbidity and mortality, this remains one of the most under-researched areas in perinatal health. This systematic scoping review aimed to map and synthesise existing literature on the biomechanics of pregnancy and labour. Following Arksey and O’Malley’s framework and PRISMA-ScR guidance, comprehensive searches of MEDLINE, EMBASE, and MIDIRS were conducted up to May 2025. Eligible sources were peer-reviewed empirical studies assessing musculoskeletal, kinematic, kinetic, postural, or dynamic parameters in pregnant or labouring women. Titles, abstracts, and full texts were screened against predefined eligibility criteria. Data were charted using a structured extraction form and synthesised narratively across key biomechanical themes. Eighty-seven studies were included, all of which focused on pregnancy. No studies conducted during labour were identified. Most were observational with small sample sizes and limited diversity. Ethnicity was reported in only one study. Four key themes emerged: (1) Posture and spinal curvature, (2) Gait and locomotor analysis, (3) Functional tasks and interventions, and (4) Balance and stability. Findings showed high individual variability and no consistent biomechanical pattern across pregnancy. Real-world, neuromuscular, and labour-related biomechanics remain largely unexplored. This review underscores a critical gap in perinatal research: while biomechanical adaptations during pregnancy have been increasingly studied, labour remains entirely unexamined from a biomechanical perspective. Current evidence is fragmented, methodologically narrow, and lacks diversity, offering limited clinical relevance. We are effectively operating in a biomechanical vacuum, without empirical data to guide safer, more efficient, and personalised birth practices. Existing clinical approaches rely heavily on tradition, anecdotal experience, and untested theoretical assumptions. Addressing this evidence void, particularly in labour biomechanics and ethnic representation, is essential to improve perinatal outcomes and support equity in maternal care.by Claude Emmanuel Koutouan, Marie Louisa Ramaroson, Angelina El Ghaziri, Laurent Ogé, Abdelhamid Kebieche, Raymonde Baltenweck, Patricia Claudel, Philippe Hugueney, Anita Suel, Sébastien Huet, Linda Voisine, Mathilde Briard, Jean Jacques Helesbeux, Latifa Hamama, Valérie Le Clerc, Emmanuel Geoffriau
Resistance of carrot to Alternaria leaf blight (ALB) caused by Alternaria dauci is a complex and quantitative trait. Numerous QTL for resistance (rQTLs) to ALB have been identified but the underlying mechanisms remain largely unknown. Some rQTLs have been recently proposed to be linked to the flavonoid content of carrot leaves. In this study, we performed a metabolic QTL analysis and shed light on the potential mechanisms underlying the most significant rQTL, located on carrot chromosome 6 and accounting for a large proportion of the resistance variation. The flavonoids apigenin 7-O-rutinoside, chrysoeriol 7-O-rutinoside and luteolin 7-O-rutinoside were identified as strongly correlated with resistance. The combination of genetic, metabolomic and transcriptomic approaches led to the identification of a gene encoding a bHLH162-like transcription factor, which may be responsible for the accumulation of these rutinosylated flavonoids. Transgenic expression of this bHLH transcription factor led to an over-accumulation of flavonoids in carrot calli, together with significant increase in the antifungal properties of the corresponding calli extracts. Altogether, the bHLH162-like transcription factor identified in this work is a strong candidate for explaining the flavonoid-based resistance to ALB in carrot.by Wenshu Li, Jeffrey A. Leibowitz, Shuoguo Wang, Louisa Walker, Chang Xu, Kuei-Ting Chen, Alexa B. Schrock, Jason Hughes, Nimesh Patel, Julia A. Elvin, Lauren L. Ritterhouse, Ethan Sokol, Garrett Frampton, Lucas Dennis, Bahar Yilmazel, Brennan Decker
Homologous recombination repair (HRR) is a cellular pathway for high-fidelity double strand DNA break repair that uses the sister chromatid as a guide to ensure chromosomal integrity and cell viability. Deficiency in the HRR pathway (HRD) can sensitize tumors to poly (ADP-ribose) polymerase inhibitors (PARPi) and platinum-based chemotherapy, offering an avenue to identify patients who may benefit from targeted therapies. HRD signature (HRDsig) is a pan-solid-tumor biomarker on the FoundationOne®CDx (F1CDx®) assay that employs a DNA scar-based approach to calculate a score based on copy number features (e.g., segment size, oscillation patterns, and breakpoints per chromosome arm) and does not rely on HRR gene alterations, enabling detection of genomic and epigenetic mechanisms of HRD. After finalizing the HRDsig algorithm, analytical validation was conducted in a CAP-accredited, CLIA-certified laboratory on 278 solid tumor and normal tissue specimens. HRDsig results were compared with an independent HRD biomarker, defined by the presence of a reversion mutation restoring HRR gene function. In this evaluation, 100 HRD-positive and 126 HRD-negative samples showed a positive percent agreement of 90.00% and a negative percent agreement of 94.44%. The limit of detection (LoD) was estimated at 23.04% tumor purity, with the limit of blank (LoB) confirmed as zero in 60 normal tissue replicates. Reproducibility testing on 11 positive and 11 negative samples across multiple labs, reagent lots, and sequencers yielded agreement in 99.49% of positive and 99.73% of negative replicates. HRDsig status remained consistent in the presence of interfering substances, demonstrating 100% concordance in spiked samples. These validation results underscore the high analytical concordance, low false-positive rate, and overall robustness of HRDsig for reliable assessment of homologous recombination deficiency.by Jack Jefferson, Claire Reigate, Alessandra Giacomini, M. Jordana Rivero, Matthew Hitchings, Tamsyn Uren Webster, Konstans Wells
Livestock grazing in confined pastures often means grazing on a less diverse diet than under more natural conditions and increased exposure to gastrointestinal parasites prevailing in these pastures. However, how sward composition influences gut microbiome (GM) diversity and its relationship with parasite burden remains poorly understood. In this study, we analysed the faecal GM of weaned lambs grazing on two distinct sward types (perennial ryegrass and a mixed-species sward) over three consecutive months using 16S rRNA sequencing, in order to assess how microbial diversity and composition are related to environmental conditions and the gastrointestinal nematode (GIN) burden in naturally infected lambs. Sward type and sampling time explained some of the variation in GM alpha diversity and community composition (beta diversity), whereas individual lamb identity accounted for considerably more variation in microbial assemblages. Shifts in the relative abundance of bacterial genera such as Saccharofermentans, Anaerosporobacter, Butyrivibrio in relation to sward type and sampling time suggest mostly adaptive fluctuations in response to diet and pasture condition. Abundance shifts of Negativibacillus, and Candidatus Saccharimonas were also associated with GIN burden, which, in turn, was higher in lambs grazing on mixed swards compared to ryegrass. Our findings add to the growing understanding of how sheep microbiomes vary with pasture management and changes in parasite burden. We highlight that individual identity may shape gut microbiota, and that potential triadic interactions among gastrointestinal parasites, sward exposure, and the gut microbiome underscore the importance of considering host, parasite, and environmental factors collectively when evaluating microbiome dynamics in grazing livestock.
FreshRSS 