Journals
2025 EN
Shattuck Eric C. · Forman Jadyn · Shiju Shilpa
+3 more
ABSTRACT Objectives Vaccines are highly successful in preventing disease, but misinformation has fueled vaccine hesitancy globally, thereby reducing immunization rates and weakening herd immunity. Vaccine knowledge and hesitancy among hunter‐gatherers is a crucial area of research and intervention, as their mobile lifestyle exacerbates other challenges, such as marginalization and medical mistrust. Methods In our exploratory study, we surveyed 91 Hadzabe adults across six camps (mean age = 39, 46% female) about their knowledge of vaccines and their safety and efficacy. Differences between sexes and camps were tested using Fisher's exact tests. Results Half of participants reported not knowing what a vaccine is, while one‐third described vaccines as protecting health or preventing disease. About 32% were unsure about vaccine safety, while most Hadzabe adults strongly agreed vaccines are effective (65.3%). A majority (72%) agreed vaccines are important for children, yet only one‐third strongly agreed on their importance for adults. More females than males expressed uncertainty about the importance of adult vaccines ( p = 0.03). Participants in our sample perceived vaccines as less effective and more safe than the general Tanzanian population, based on 2018 Wellcome data. Discussion In our sample, results indicate that while Hadzabe participants generally agree that vaccines are important, particularly for children, important gaps in vaccine knowledge remain. There is a clear need to communicate vaccine information to the Hadzabe community in a culturally appropriate manner. Such efforts are critical in safeguarding the health of Indigenous populations experiencing greater market integration, thereby supporting access to vaccines against diseases.
Journals
2025 EN
Ibrahim Bakari · Le Moual Nicole · Sit Guillaume
+9 more
ABSTRACT Background Disinfectants and cleaning products (DCPs) are important asthma risk factors among healthcare workers. However, healthcare work involves heterogenous cleaning tasks and co‐exposure to many chemicals. These multidimensional aspects have rarely been considered. We aimed to identify patterns of occupational exposure to DCPs and study their associations with asthma. Methods CONSTANCES is a French population‐based cohort of ≈220,000 adults. Current asthma and asthma symptom score were defined by questionnaire at inclusion (2012–2021). Healthcare workers completed a supplementary questionnaire on their current/last held occupation, workplace, and cleaning activities that were used in unsupervised learning algorithms to identify occupational exposure patterns. Logistic and negative binomial regression models, adjusted for potential confounders, were used to assess associations with asthma outcomes. Results In 5512 healthcare workers, four occupational exposure clusters were identified: Cluster1 (C1, 42%, reference), mainly characterized by low exposed nurses and physicians; C2 (7%), medical laboratory staff moderately exposed to common DCPs (chlorine/bleach, alcohol); C3 (41%), nursing assistants and nurses highly exposed to a few DCPs (mainly quaternary ammonium compounds); and C4 (10%), nurses and nursing assistants highly exposed to multiple DCPs (e.g., glutaraldehyde, hydrogen peroxide, and acids). Among women ( n = 3734), C2 (mean score ratio [95% CI]: 1.31 [1.02; 1.68]) and C3 (1.18 [1.03; 1.36]) were associated with higher asthma symptom score, and an association was suggested between C3 and current asthma (odds ratio 1.22 [0.99; 1.51]). Conclusion In a large population of healthcare workers, four DCP exposure patterns were identified, reflecting the heterogeneity of healthcare jobs. Two patterns, including one characterized by laboratory workers, were associated with greater asthma symptoms in women.
Journals
2025 EN
Quinlan Aisling · Rodan Lance · Barkoudah Elizabeth
+9 more
ABSTRACT Frataxin is an evolutionarily conserved mitochondrial protein responsible for iron homeostasis and metabolism. A deficiency of frataxin (encoded by FXN ) leads to Friedreich's ataxia (FRDA), a progressive disorder that affects both the central and peripheral nervous systems, most commonly via a pathogenic GAA trinucleotide expansion. In contrast, pathogenic variants in ALG1 in humans cause a form of congenital disorder of glycosylation. Here, we present a 15‐year‐old boy with a clinical presentation that raised concern for complex hereditary spastic paraplegia (HSP), with motor features including progressive spastic paraparesis, cervical dystonia, cerebellar dysfunction, and diminished lower extremity reflexes. The proband was initially found to have a novel compound heterozygous variant in ALG1 on exome sequencing, along with N‐glycan profiling revealing evidence of defective mannosylation and Western blot analysis demonstrating an 84% reduction in ALG1 expression. Although several of his clinical features could be explained by the ALG1 variant specifically or considered as part of the presentation of CDGs in general, there were additional phenotypes that suggested an alternative, or additional, genetic diagnosis. Subsequently, he was found to have biallelic pathogenic GAA repeat expansions in FXN on genome sequencing, leading to a diagnosis of FRDA. Given that FRDA explained all his clinical features, the ALG1 variant may have been a hypomorphic form and/or a biochemical phenotype. Our findings underscore the importance of considering FRDA as a differential diagnosis in cases of complex HSP and demonstrate the utility of unbiased genome sequencing approaches that include detection of trinucleotide repeat expansions for progressive motor disorders.
Journals
2025 EN
Elsayed Shaymaa · Elmakkawy Gehad A. · Abdelrazek Ibrahim M.
+5 more
ABSTRACT 3M syndrome is a rare autosomal recessive disorder characterized by short stature and recognizable facial and musculoskeletal features. Pathogenic variants in the CUL7 , OBSL1 , and CCDC8 genes are implicated in the pathogenesis of 3M syndrome. In this review, we discuss the history, epidemiology, molecular basis, clinical features, and management strategies for 3M syndrome. Moreover, we report on 11 new patients (from 9 unrelated families) with short stature and dysmorphic features consistent with 3M syndrome, in whom we identified five novel pathogenic variants expanding the genetic landscape of the syndrome. Finally, we have reviewed the molecularly confirmed cases of 3M published to date.
Journals
2025 EN
Suzer Gamli Ipek · Van Veggel Anne · Karaaslan Rabia Sevcan
+10 more
ABSTRACT Pharmacogenetic studies involving Carboxylesterase 1 (CES1), Latrophilin‐3 (LPHN3), and Catechol‐O‐methyltransferase (COMT) revealed individual differences regarding therapeutic response in children with attention deficit hyperactivity disorder (ADHD) under methylphenidate (MPH) treatment. This study aimed to evaluate MPH's association with the adverse effect status in children and its relationship with CES1, LPHN3, and COMT in the Turkish population. The study included 102 children and adolescents with ADHD, who were categorized as responders, or the adverse effect group based on their treatment response. The Naranjo Adverse Drug Reaction Probability Scale evaluated the presence and severity of adverse effects. Saliva sample was taken from the patients and genotype distribution of CES1 rs3815583, CES1 rs2307227, LPHN3 rs6551665, LPHN3 rs1947274, LPHN3 rs6858066, LPHN3 rs2345039, and COMT rs4680 were examined. In the adverse effect group, instances of carrying the GG genotype in CES1 rs2307227, having G vs. T genotype and GG vs. GT were significantly higher. In LPHN3 rs2345039, carrying the C genotype vs. G was associated with a serious adverse effect. In COMT rs4680, individuals with the AA or GG genotype were significantly higher in the adverse effect group. Our study suggests a relationship between genetic polymorphisms and the side effect status in children receiving MPH.
Journals
2025 EN
Levi Lirit · Yang Angela · Tsai Esmond F.
+8 more
Abstract Introduction Diagnosis of empty nose syndrome (ENS) relies on the ENS six‐item questionnaire (ENS6Q) with a score of ≥11, followed by a “positive” cotton test yielding seven‐point reduction from baseline ENS6Q score via cotton placement to the inferior meatus (IM). Given the intricacies of diagnosing ENS and the propensity for false positives with the standard cotton test, we modified the classic single‐step cotton test into a four‐part Stepwise Empty Nose Syndrome Evaluation (SENSE) cotton test to reduce bias and evaluate the placebo effect. Methods Individuals diagnosed with ENS underwent the SENSE test, a single‐blinded, four‐step, office‐based cotton test, without topical anesthesia or decongestants. Conditions included: (1) placebo/no cotton placed; (2) complete cotton‐blockade of nasal vestibule; (3) cotton placed medially against the nasal septum; and (4) cotton placed laterally in the IM (site of inferior turbinate tissue loss). With each condition, patients completed an ENS6Q. Results Forty‐eight ENS patients were included. Twenty‐nine percent demonstrated a placebo effect ( p < 0.001), 40.4% had a positive response to complete cotton‐blockade ( p < 0.001), 64.4% to septum‐placed cotton, and 79.1% to IM‐placed cotton ( p < 0.001), corresponding to a mean ENS6Q reduction of 11.9 points ( p < 0.001). Notably, the mean difference in ENS6Q scores between septum and IM placement was 1.7 ( p < 0.001). Conclusions The SENSE test offers further insight into subtleties of nasal breathing experienced by ENS patients. The placebo effect can be prominent and important to consider with individual patients. While most ENS patients prefer any intranasal cotton placement over baseline, blinded testing reveals these patients can accurately discriminate minimal changes in nasal aerodynamics.
Journals
2025 EN
Volkmer Anna · Alves Emily Viega · BarZeev Hagit
+63 more
Abstract INTRODUCTION Interventions to treat speech‐language difficulties in primary progressive aphasia (PPA) often use word accuracy as a highly comparable outcome. However, there are more constructs of importance to people with PPA that have received less attention. METHODS Following Core Outcome Set Standards for Development Recommendations (COSSTAD), this study comprised: Stage 1 – systematic review to identify measures; Stage 2 – consensus groups to identify important outcome constructs for people with PPA ( n = 82) and care partners ( n = 91); Stage 3 – e‐Delphi consensus with 57 researchers. RESULTS The systematic review identified 84 Outcome Measurement Instruments. Core outcome constructs identified included: (1) Participate in conversations with family and friends, (2) get words out, (3) be more fluent, (4) convey a message by any means, and (5) understand what others are saying. Researchers were unable to reach a consensus on measurement instruments. DISCUSSION Further work is required to develop appropriate measurement instruments that address all core outcome constructs important to key stakeholders. Highlights We introduce new symptom‐led perspectives on primary progressive aphasia (PPA). The focus is on non‐fluent/agrammatic (nfvPPA) and semantic (svPPA) variants. Foregrounding of early and non‐verbal features of PPA and clinical trajectories is featured. We introduce a symptom‐led staging scheme for PPA. We propose a prototype for a functional impairment scale, the PPA Progression Planning Aid.
Journals
2025 EN
Liou JrJiun · Lou Jerry · FloresAguilar Lisi
+21 more
Abstract INTRODUCTION Aging adults with Down syndrome (DS) accumulate Alzheimer's disease (AD) neuropathology, including amyloid beta plaques and neurofibrillary tangles, by age 40. METHODS We present findings from an individual with DS who remained cognitively stable despite AD neuropathology. Clinical assessments, fluid biomarkers, neuroimaging, and neuropathological examinations were conducted to characterize her condition. RESULTS Her apolipoprotein E was ε2/ε3 and genome‐wide association study data indicated mosaicism. Neuroimaging revealed stable yet elevated amyloid and moderately elevated tau levels, while neuropathology indicated intermediate AD neuropathologic change with Lewy body and cerebrovascular pathologies. The participant demonstrated stable cognitive functioning in her 60s, potentially attributed to genetic variations, cognitive resilience, and environmental enrichment. DISCUSSION These findings emphasize the complexity of AD progression in DS. Further investigation into factors influencing cognitive resilience in individuals with DS is warranted. Understanding the mechanisms underlying cognitive stability in DS could offer insights into resilience to AD neuropathology in people with DS and inform future interventions. Highlights Findings from clinical assessments, fluid biomarkers, genotyping, neuroimaging, and neuropathological examinations of an individual with Down syndrome (DS) who remained cognitively stable despite Alzheimer's disease (AD) neuropathology are presented. Neuroimaging revealed stable yet elevated amyloid profiles and moderately elevated tau levels, while neuropathology indicated intermediate AD neuropathologic change with Lewy body and cerebrovascular pathologies. Despite the presence of AD pathology, the participant demonstrated intact cognitive functioning, potentially attributed to genetic variations, cognitive resilience, and environmental enrichment, emphasizing the complexity of AD progression in DS.
Journals
2025 EN
Wakawa Ibrahim Abdu · Musami Umar Baba · Kwairanga Suleiman Hamidu
+21 more
Abstract INTRODUCTION Dementia prevalence is increasing in sub‐Saharan Africa, potentially due to population growth and aging. Resource‐constrained settings such as Northeastern Nigeria face challenges in dementia management. METHODS We assessed dementia burden and management at the Federal Neuropsychiatric Hospital Maiduguri, the only neuropsychiatric facility in Northeastern Nigeria. This retrospective analysis included patient records from 1999 to 2023 for individuals 60 year of age and older with a dementia diagnosis. RESULTS Of the 1216 cases reported, Alzheimer's disease (60.5%) was the most common subtype, followed by vascular dementia (24.5%). Hypertension (41.6%) was the most frequent comorbidity. Memory loss was present in all cases, whereas behavioral symptoms like agitation presented in some cases. Treatments included cognitive enhancers (donepezil), supplements (gingko biloba), and non‐drug therapies (psychoeducation). DISCUSSION The increasing burden of dementia at this sole facility highlights the urgent need for targeted interventions and further research to understand the underlying factors contributing to dementia in this population. Highlights Dementia trends and management in a neuropsychiatric facility serving over 26 million people in Northeastern Nigeria. Alzheimer's disease accounted for 60.5% of the dementia cases reported, with hypertension as the leading comorbidity. There is an urgent need for improved diagnostic tools and health care infrastructure to address dementia in resource‐constrained settings. The findings lay the foundation for developing a dementia cohort as part of the Northern Nigeria Dementia Research Group.
Journals
2025 EN
Leach Elizabeth M. · Powell David K. · Glueck Amanda C.
+7 more
Abstract INTRODUCTION Individuals with Down syndrome (DS) face a significant risk of neurodegeneration, and gait variability may serve as a clinical biomarker of neurological health. This longitudinal parent substudy aimed to explore relationships between gait, white matter (WM) integrity, and cognitive function in DS. METHODS The associations were investigated between magnetic resonance imaging diffusion tensor imaging (DTI), cognition, and self‐paced gait data from 22 DS participants (mean age ± SD 37 ± 7.5 years). RESULTS DTI measures, such as lower fractional anisotropy (FA) and higher mean diffusivity, were correlated with greater step time variability but not normalized velocities. Lower cognitive scores on the Vineland Adaptive Behavior Composite, Dementia Questionnaire for People with Learning Disabilities, and Motor Skill subscale were correlated with FA. DISCUSSION Gait variability correlates with WM integrity and cognitive function in DS, suggesting that gait and DTI measures may serve as clinical markers of neurological decline. Highlights Gait variability linked to white matter integrity in individuals with Down syndrome (DS). Lower fractional anisotropy and higher mean diffusivity are associated with increased step time variability in DS. Cognitive decline is tied to white matter changes in motor‐related brain regions. Gait analysis alongside diffusion tensor imaging may aid in screening for cognitive impairment in DS.