Subset Of Individuals Research Articles

Effects of behavioural types on the problem‐solving performance of wild house mice under controlled and semi‐natural conditions

Animals often face challenges that require them to come up with solutions to novel problems or to find new solutions to existing ones; i.e. they need to innovate. However, not all individuals in a population are equally likely to solve novel problems, and it is unclear which individual characteristics make a successful innovator. Theoretical frameworks suggest the importance of intrinsic (e.g. individual characteristics) and extrinsic (e.g. study condition) factors on problem‐solving performance. Such frameworks have been empirically tested in model, highly neophobic species, leaving the generality of these processes unclear. We examined whether behavioural traits such as exploration and risk‐taking are linked to problem‐solving behaviour, using two replicated populations (n = 121) of wild house mice Mus musculus domesticus living under semi‐natural conditions. There, we presented a battery of four problem‐solving setups that individuals could access voluntarily, and we tested the mice for risk‐taking and exploration. Furthermore, after acclimatising to cages, we tested a subset (n = 50) of the same individuals in controlled conditions, to validate the cross‐context stability of cognitive performance and potential influences of behaviours. We placed single individuals overnight in arenas containing another four novel problem‐solving setups. Contrasting most existing literature, we found no direct effects of behavioural type on the likelihood to problem‐solve in either condition. However, there was an indirect effect, with shyer individuals visiting the problems more, which improved their likelihood of solving them. Additionally, mice were more likely to solve alone, and individuals were not consistent across conditions. Our findings suggest that exploration and risk‐taking do not affect the ability to problem‐solve across different conditions, but impact the non‐cognitive steps that lead to the final performance. Also, individuals did not perform consistently across conditions, questioning the ecological validity of measures taken under controlled, artificial conditions when they do not reflect the animals' natural experience.

The Role of the Immune Response to Helicobacter pylori Antigens and Its Relevance in Gastric Disorders

Helicobacter pylori (H.p.) is a Gram-negative bacterium endowed with gastric tropism. H.p. infection is widely spread throughout the world, accounting for various pathologies, such as peptic ulcer, gastric cancer, mucosa-associated lymphoid tissue lymphoma, and extra-gastric manifestations. This bacterium possesses several virulence factors, e.g., lipopolysaccharides (LPS), the toxins CagA and VacA, and adhesins, which elicit a robust immune response during the initial phase of the infection. Of note, the lipid A moiety of the LPS exhibits a lower endotoxic potency than that of other LPSs, thus facilitating infection through a mechanism of immune escape. H.p. colonization of the gastric mucosa induces an initial protective immune response with innate immune cells, e.g., neutrophils, monocytes, and macrophages, which engulf and kill bacteria. Moreover, the same cells, along with gastric epithelial cells, secrete cytokines and chemokines, which recruit T cells [T helper (h)1 and Th17 cells] to the site of infection, thus leading to H.p. eradication. In a large subset of individuals, the perturbation of such an immune equilibrium leads to a harmful response, with an expansion of T regulatory (TREG) cells, which suppress the protective immune response. In fact, TREG cells, via the production of interleukin (IL)-10, downregulate Th1- and Th17-related cytokines, thus allowing H.p. survival and the perpetuation of inflammation. As far as the humoral immune response is concerned, B cells, upon H.p. stimulation, produce autoreactive antibodies, and IgG anti-Lex antibodies are harmful to the gastric mucosa. In this review, the structure and function of H.p. antigenic components and immune mechanisms elicited by this bacterium will be described in relation to gastric damage.

Monoclonal gammopathy of undetermined significance and the risk of thrombotic events: Results from iStopMM, a prospective population-based screening study.

Monoclonal gammopathy of undetermined significance (MGUS) is the asymptomatic precursor of multiple myeloma and related diseases but has also been associated with thrombosis. Prior studies have not been based on screened cohorts leading to bias. We assessed the risk of thrombosis in a cohort of 75 422 individuals over 40 years old who were screened for MGUS in Iceland. We also evaluated the association of M protein concentration with thrombotic risk. A total of 3668 participants had MGUS. After a median follow-up of ~3.7 years, 124 venous and 252 arterial thrombotic events (10.3 and 21.0 per 1000 person years respectively) were observed in the MGUS group, compared to 1509 and 3471 in the non-MGUS group (6.0 and 13.8 per 1000 person years respectively). After adjusting for multiple confounders, MGUS was associated with an increased risk of venous thrombosis (hazard ratio [HR] = 1.43; 95% confidence interval [CI]: 1.19-1.73) but not arterial thrombosis (HR = 0.96; 95% CI: 0.87-1.13). M protein concentration was not associated with venous (p = 0.72) or arterial (p = 0.95) thrombosis. The findings show, in a screened cohort, that MGUS is associated with venous, but not arterial, thrombosis. Furthermore, they suggest that there is a subset of individuals with MGUS with subclinical monoclonal gammopathy of thrombotic significance.

Physiological, biochemical and genome-wide expression patterns during graded normobaric hypoxia in healthy individuals

The regulation of oxygen homeostasis is critical in physiology and disease pathogenesis. High Altitude environment or hypoxia (lack of oxygen) can lead to adverse health conditions such as HAPE despite initial adaptive physiological responses. Studying genetic, hematological and biochemical, and the physiological outcomes of hypoxia together could yield a comprehensive understanding and potentially uncover valuable biomarkers for predicting responses. To this end, healthy individuals (n=51) were recruited and exposed to graded normobaric hypoxia. Physiological parameters such as Heart Rate(HR), Heart Rate Variability(HRV), oxygen saturation(SpO2), and Blood Pressure(BP) were constantly monitored, and a blood sample was collected before and after the hypoxia exposure for the haematological and gene-expression profiles. HR was elevated, and SpO2 and HRV were significantly reduced in a FiO2-dependent manner. After exposure to hypoxia, there was a minimal decrease in HCT, RDW-CV, MPV, Platelet Distribution Width, Plateletcrit, Eosinophils, Lymphocytes and HDL-Cholesterol. Additionally, there was a marginal increase observed in Neutrophils. The effect of hypoxia was further assessed at the genome-wide expression level in a subset of individuals. 82 genes significantly differed after hypoxia exposure, with 46 up-regulated genes and 36 down-regulated genes (p ≤ 0.05 and log2 fold change > ± 0.5). We also conducted an integrative analysis of global gene expression profiles linked with physiological parameters, and we uncovered numerous reliable gene signatures associated with BP, SpO2, HR, and HRV in response to graded normobaric hypoxia.

PINK1 is a target of T cell responses in Parkinson's disease.

Parkinson's disease (PD) is the second most prevalent neurodegenerative disorder. While there is no curative treatment, the immune system's involvement with autoimmune T cells that recognize the protein alpha-synuclein (α-syn) in a subset of individuals suggests new areas for therapeutic strategies. As not all patients with PD have T cells specific for α-syn, we explored additional autoantigenic targets of T cells in PD. We generated 15-mer peptides spanning several PD-related proteins implicated in PD pathology, including Glucosylceramidase Beta 1 (GBA), Superoxide dismutase 1 (SOD1), PTEN Induced Kinase 1 (PINK1), Parkin RBR E3 Ubiquitin Protein Ligase (parkin), Oxoglutarate Dehydrogenase (OGDH), and Leucine Rich Repeat Kinase 2 (LRRK2). Cytokine production (IFNγ, IL-5, IL-10) against these proteins was measured using a fluorospot assay and PBMCs from patients with PD and age-matched healthy controls. We identified PINK1, a regulator of mitochondrial stability, as an autoantigen targeted by T cells, as well as its unique epitopes, and their HLA restriction. The PINK1-specific T cell reactivity revealed sex-based differences as it was predominantly found in male patients with PD, which may contribute to the heterogeneity of PD. Identifying and characterizing PINK1 and other autoinflammatory targets may lead to antigen-specific diagnostics, progression markers, and/or novel therapeutic strategies for PD.

A Cost-effective, High-throughput, Highly Accurate Genotyping Method for Outbred Populations.

Affordable sequencing and genotyping methods are essential for large scale genome-wide association studies. While genotyping microarrays and reference panels for imputation are available for human subjects, non-human model systems often lack such options. Our lab previously demonstrated an efficient and cost-effective method to genotype heterogeneous stock rats using double-digest genotyping-by-sequencing. However, low-coverage whole-genome sequencing offers an alternative method that has several advantages. Here, we describe a cost-effective, high-throughput, high-accuracy genotyping method for N/NIH heterogeneous stock rats that can use a combination of sequencing data previously generated by double-digest genotyping-by-sequencing and more recently generated by low-coverage whole-genome-sequencing data. Using double-digest genotyping-by-sequencing data from 5,745 heterogeneous stock rats (mean 0.21x coverage) and low-coverage whole-genome-sequencing data from 8,760 heterogeneous stock rats (mean 0.27x coverage), we can impute 7.32 million bi-allelic single-nucleotide polymorphisms with a concordance rate >99.76% compared to high-coverage (mean 33.26x coverage) whole-genome sequencing data for a subset of the same individuals. Our results demonstrate the feasibility of using sequencing data from double-digest genotyping-by-sequencing or low-coverage whole-genome-sequencing for accurate genotyping, and demonstrate techniques that may also be useful for other genetic studies in non-human subjects.

Data Measurement, Instruments and Sampling.

Data measurement, instrument selection, and sampling are fundamental elements in quantitative research and data collection. Data measurement is the systematic assignment of numeric values or categories to variables to permit measurement with precision and accuracy. Instrument selection involves selecting the right tool or method to collect data effectively and accurately and ensure the reliability and validity of the data. Sampling is the process of selecting a subset of individuals or items from a larger population to best represent that population, free of bias and generalizable. Understanding these key terms ensures that data collected is valid, reliable, and appropriate for future statistical analysis and interpretation.

The Evolution and Role of Molecular Tools in Measuring Diversity and Genomic Selection in Livestock Populations (Traditional and Up-to-Date Insights): A Comprehensive Exploration.

Distinctive molecular approaches and tools, particularly high-throughput SNP genotyping, have been applied to determine and discover SNPs, potential genes of interest, indicators of evolutionary selection, genetic abnormalities, molecular indicators, and loci associated with quantitative traits (QTLs) in various livestock species. These methods have also been used to obtain whole-genome sequencing (WGS) data, enabling the implementation of genomic selection. Genomic selection allows for selection decisions based on genomic-estimated breeding values (GEBV). The estimation of GEBV relies on the calculation of SNP effects using prediction equations derived from a subset of individuals in the reference population who possess both SNP genotypes and phenotypes for target traits. Compared to traditional methods, modern genomic selection methods offer advantages for sex-limited traits, low heritability traits, late-measured traits, and the potential to increase genetic gain by reducing generation intervals. The current availability of high-density genotyping and next-generation sequencing data allow for genome-wide scans for selection. This investigation provides an overview of the essential role of advanced molecular tools in studying genetic diversity and implementing genomic selection. It also highlights the significance of adaptive selection in light of new high-throughput genomic technologies and the establishment of selective comparisons between different genomes. Moreover, this investigation presents candidate genes and QTLs associated with various traits in different livestock species, such as body conformation, meat production and quality, carcass characteristics and composition, milk yield and composition, fertility, fiber production and characteristics, and disease resistance.

Functional Neurological Disorder and Autism Spectrum Disorder: A Complex and Potentially Significant Relationship.

Functional neurological disorder (FND) and autism spectrum disorder (ASD) are two complex neuropsychiatric conditions that have been historically classified within psychiatric domains, resulting in a lack of extensive research, insufficient clinical recognition, and persistent societal stigma. In recent years, there has been an increasing recognition among professionals and affected individuals of their possible overlap. This review explores the potential clinical and mechanistic overlap between FND and ASD, with particular attention to shared symptoms across sensory, motor, and psychiatric domains. We conducted a narrative analysis utilizing the PubMed, CINAHL, MEDLINE, and ScienceDirect databases from inception to June 2024. The search employed specific MeSH terms related to ASD and FND. Given the limited data availability, we included all relevant articles that explored the potential connections between FND and ASD, focusing on established findings and theoretical hypotheses areas. Scientific evidence indicates that FND and ASD may co-occur more frequently than previously acknowledged and with notable overlaps in their clinical presentations and pathophysiology. Theoretical models that have been applied to FND and ASD, such as the Bayesian brain theory and the tripartite model of autism, may provide valuable insights into the intersection of these conditions. Although much of the current evidence remains speculative, it underscores the need for hypothesis-driven research to investigate these potential connections further. ASD and FND are heterogeneous conditions that appear to co-occur in a subset of individuals, with overlapping symptomatology and possibly shared underlying mechanisms. This hypothesis-generating review emphasizes the need for further research to better understand these links, ultimately aiming to improve clinical recognition and develop targeted interventions that enhance the quality of life for affected individuals.

Clinic evaluation of cognitive impairment in post-COVID syndrome: Performance on legacy pen-and-paper and new digital cognitive tests

BackgroundCognitive impairment, colloquially termed “brain fog”, is one of the most prevalent manifestations of post-Covid syndrome and a major contributor to impaired daily function and reduced quality of life. However, despite the high numbers of affected individuals presenting to clinical services with cognitive impairment, little work has been undertaken to date on the suitability of current memory clinic tests for identifying the cognitive deficits in this new acquired cognitive disorder.The aim of this study was therefore to determine the performance of people with post-Covid syndrome presenting with cognitive impairment on the Addenbrooke's Cognitive Examination-III (ACE-III), a cognitive test used widely in memory clinics. A subset of individuals also underwent testing on a novel battery of short digital tests assessing attention, speed of information processing and executive function, representing the domains primarily implicated in post-Covid cognitive dysfunction. Methods102 individuals with post-Covid syndrome presenting with subjective cognitive complaints were recruited from a specialist cognitive long Covid clinic at University Hospitals Sussex NHS Trust. All participants completed self-report questionnaires on depression, anxiety, sleep and fatigue. Cognitive performance was assessed using the ACE-III, with 20 participants also being tested on the digital Long COVID Assessment Battery (LCCAB) (N = 20). ResultsThe overall sample had a mean ACE-III score of 91/100 (SD 6) with 15.7% (16/102) scoring at or below the cut-off score considered to represent objective cognitive impairment. Of the 20 individuals who also completed the LCCAB, 89.47% were impaired on at least one task, primarily in the domains of attention, executive function and processing speed. Cognitive performance was not associated with depression, anxiety, sleep quality or fatigue. ConclusionThe vast majority of individuals with post-Covid syndrome presenting with subjective cognitive complaints do not exhibit impaired performance on the ACE-III. This likely reflects the historical use of ACE-III and other pen and paper cognitive tests to detect cognitive impairment in diseases causing dementia, but they are ill-equipped to identify impairment in those cognitive domains affected in post-Covid syndrome. The LCCAB detected cognitive impairments in nearly 90% of participants, primarily affecting attention, executive function, and processing speed. These observations highlight the need for alternative cognitive tests for use in routine clinical practice to detect the impairments in new acquired cognitive disorders that are not adequately captured by legacy tests.

Lung Clearance Index Improves in People with Cystic Fibrosis not Achieving a Clinical Important Difference in Forced Expiratory Volume in One Second After Elexacaftor/Tezacaftor/Ivacaftor Therapy.

In people with cystic fibrosis (pwCF), elexacaftor/tezacaftor/ivacaftor (ETI) therapy is associated with an average improvement in FEV1 of 10-14%. However, a subset of individuals fails to achieve a clinically meaningful increase in spirometric indicators. In this study, we aimed to assess whether the lung clearance index (LCI2.5), a more sensitive indicator of lung involvement, improves following ETI initiation in this population. We conducted a prospective observational study in a specialized CF center in Italy. PwCF performed a spirometry and a multiple breath nitrogen washout test the day they initiated ETI therapy and after 6 and 12months. They were grouped according to the 12-month change in FEV1 into two groups: Individuals who experienced a change in FEV1 ≥ a minimal clinically important difference (MCID) of 3% and those who did not. Mean changes in LCI2.5 were estimated using generalized estimating equations. The study included 129 pwCF who initiated ETI at our center (Age Range: 12-36years). In 20 subjects (15.5%), the FEV1 change was < MCID. These individuals had better baseline pulmonary function than those with FEV1 changes ≥ MCID (Median FEV1: 102.5 vs 87.0%), with the majority (90%) having FEV1 values ≥ 90%. Mean changes in LCI2.5 at 12-month follow-up visit were -1.44 units (95% CI: -2.12; -0.75) in individuals with changes in FEV1 < MCID and -2.64 units (95% CI: -3.05; -2.23) in those with values ≥ MCID. LCI2.5 is a useful measure to monitor the effectiveness of ETI in pwCF with normal spirometry and limited FEV1 change following treatment initiation.

"I Felt Supported, Empowered, and Encouraged": Early Findings from a Community Initiative to Strengthen and Support Families Through the First 1,000 Days of Life.

Evaluation of the First 1,000 Days Suncoast Family Navigation program aimed to (1) describe the social needs of families in Southwest Florida and (2) measure the program's impact on client-reported mental health and social support outcomes. A multi-method design was employed, including quantitative data collected through an online social care referral network and longitudinal surveys, supplemented by qualitative key informant interview data. A convenience sample of 538 parents who submitted online assistance request forms to First 1,000 Days between August 2020 and January 2024 were included. Phone surveys were conducted from October 2022 to October 2023 with a subset of individuals (n=33) at three timepoints: (1) initial intake; (2) 30 days; and (3) 60 days after receiving assistance. Key informant interviews were conducted (n = 20) to explore the themes of parental coping and resilience. Parents reported statistically significant improvements in concrete and social support networks. We observed an average reduction in perceived stress scores of 3.88 points by 30 days and of 4.82 points by 60 days post intervention. The number of unhealthy mental health days per month was reduced from 9.9 to 6.0 days per month. Social care technology paired with family navigation support demonstrates the potential for long-term impact on the quality of life, well-being, and self-sufficiency. These early results make a compelling case for incorporating social care coordination services into clinical practice to achieve improved patient outcomes.

Abnormal spirometry in individuals with a smoking history and no known obstructive lung disease: current understanding and clinical implications.

Recent recognition of the importance of abnormal spirometry without obstruction has generated interest in its epidemiology, risk factors, longitudinal outcomes, and clinical implications. Preserved ratio impaired spirometry (PRISm), defined as an forced expiratory volume in 1 s (FEV1)/ forced vital capacity (FVC) ≥0.7 with an FEV1 <80% predicted, has a high prevalence globally (2.4-16.7%) and is more common in individuals with metabolic comorbidities, smoking history, female sex, and higher BMI. PRISm is associated with increased respiratory symptoms and poor clinical outcomes such as increased all-cause mortality and cardiovascular events compared to normal spirometry. Longitudinal studies show substantial subsets of individuals with PRISm will transition to other spirometric categories, including progression to obstruction. Individuals with PRISm are heterogeneous; recent investigations have focused on subtyping PRISm based on spirometric features or pathobiologically-based phenotypes. PRISm is a common spirometric abnormality which is robustly associated with negative outcomes. However, current knowledge gaps with respect to heterogeneity, specific etiologies, and longitudinal progression preclude the development of universal evidence-based diagnostic and management strategies. At present, clinicians are advised to focus on risk factor modification (e.g., diabetes, obesity) and the identification of actionable traits (e.g. emphysema, interstitial lung abnormalities) among patients with PRISm.

Exploring the impact of 3,3’-diindolylmethane on the urinary estrogen profile of premenopausal women

Background3,3’-diindolylmethane (DIM) is a phytonutrient derived from cruciferous vegetables that is an often-used supplement in the complementary and alternative medicine space. The most common goal for providers when recommending DIM to their patients is to alter estrogen metabolism, yet research into DIM’s effect on the estrogen profile is lacking in the published literature. The objective of this study was to comprehensively evaluate DIM’s effect on the urinary estrogen profile.MethodsIn this retrospective cohort study, we analyzed data from a clinical laboratory, including urinary estrogen and estrogen metabolite concentrations. Analyte concentrations were determined from dried urine samples using a gas chromatography-tandem mass spectrometry assay. Individuals were separated into two groups, either reporting taking DIM (N = 909) or reporting not taking DIM (N = 18,385). Comparisons between individuals in these two groups were made using the Wilcoxon rank sum test. Additionally, we were also able to explore a subset of women who had laboratory results in the database before and after initiating DIM treatment (N = 53). In this subset, differences were assessed with Wilcoxon signed rank tests.ResultsIn the larger group that was separated into women reporting either DIM use or no use, significant differences were observed in the concentrations of almost every urinary estrogen and estrogen metabolite (with the only exception being 2-methoxyestrone) in the urinary estrogen profiles of those taking DIM compared to those not taking DIM (all P values < 0.001). In the smaller subset of individuals with results before and after initiating DIM use, differences were only seen in 4 of the urinary estrogens and estrogen metabolites (P < 0.001 for estrone, estradiol, estriol, and 16-hydroxyestrone). Differences in total estrogens were significant in both the larger group and the smaller subset (both with P < 0.001). Additionally, observed differences in the ratios of metabolites followed a similar trend with more significant differences observed in the larger group. Notably, the 2-hydroxyestrone:16-hydroxyestrone ratio increased significantly in both the larger group and the smaller subset with results before and after DIM use.ConclusionsThe results of this study provide the most comprehensive evaluation to date of DIM’s effect on the urinary estrogen profile. Additionally, the results demonstrate that the dried urine collection and accompanying assay used capture changes that are similar in direction, but not necessarily magnitude, to previous reports in the literature. Considered together, these two things highlight the clinical validity and utility of this approach to the evaluation of DIM supplementation and suggest the need for additional studies using this approach to fully understand the potential clinical utility of DIM.

HIV-1 low-level viremia predicts viral failure in participants on antiretroviral therapy in the Swiss HIV Cohort Study.

Most individuals on combination antiretroviral therapy (ART) have HIV plasma viral loads below the limit of detection. However, episodes of low-level viremia (LLV) are observed in subsets of individuals, risk factors and clinical significance of which remain debated. We included participants enrolled in the Swiss HIV Cohort Study, starting ART between July 1999 and April 2023, with HIV RNA <200 copies/ml six months post ART initiation. Using longitudinally collected data, we applied a time-updated Cox proportional hazards model to determine the association of LLV with the risk of subsequent viral failure, defined as ≥200 copies/ml. LLV was quantified by the time-updated area under the curve (AUC) of HIV RNA values, segmented into categories undetectable, and based on AUC tertiles into low, intermediate, and high. We included 8'132 participants with a total of 49'579 person-years of follow-up. Median follow-up time was 4.7 years, and median number of HIV RNA measurements was 16. Participants had a median age of 38 years, 75.9% were male, 74.4% had white ethnicity, and 45.9% had HIV-1 subtype B. LLV was associated with an increased risk for subsequent viral failure, with the highest LLV category showing the strongest association (hazard ratio = 3.3 compared to undetectable viral load) among all included variables including ethnicity, age, and ART. LLV was strongly associated with the risk for subsequent viral failure, even after adjusting for demographic and clinical characteristics, including adherence and treatment regimen. The detection of LLV should prompt appropriate measures to decrease the risk of subsequent viral failure.

Acceptability of multi-level sexual health interventions and sexually transmitted infection screening and testing among persons with HIV across three clinical sites in Florida

Introduction: The US state of Florida has the third highest rate of HIV as well as high rates of sexually transmitted infections (STIs) indicating critical HIV and STI prevention needs remain unmet. To address gaps in the STI care continuum in people with HIV (PWH), evidence-based interventions were implemented across three Ryan White HIV/AIDS Program (RWHAP) funded clinics in Florida between August 2020–August 2021. Interventions included comprehensive sexual health history (SHH) taking using audio computer-assisted self-interview (ACASI) software, self-collected extragenital gonorrhea and chlamydia testing, and the introduction of a lesbian, gay, bisexual, transgender, and queer (LGBTQ+) welcoming environment. Methods: We 1) assessed the acceptability of these interventions and examined if acceptability differed among youth and sexual, racial and ethnic minorities, 2) determined the proportion of appropriate STI testing completed based on the SHH assessment, 3) examined whether STI at-risk individuals underwent STI screening 3-6 months after initial evaluation, and 4) determined the proportion of positive STI test results among priority intervention groups in Florida. Results: Acceptability of all interventions was high. Youth, lesbian, gay, and bisexual, and Hispanic individuals were significantly more likely to notice and like LGTBQ+ welcoming measures. The proportion of recommended tests completed was high, although only a subset of at-risk individuals completed re-screening. 11.9% of rectal samples were positive for chlamydia and 6.5% of pharyngeal samples were positive for gonorrhea. Conclusions: Our study highlights the importance of incorporating comprehensive sexual health care protocols, including extragenital STI testing, into the overall care of PWH.

Traumatic Brain Injury and Risk of Incident Dementia: Forensic Applications of Current Research.

Traumatic Brain Injury (TBI) has been identified as a risk factor for later developing neurodegenerative disorders, and there has been significant attention on this association in forensic settings. As a result, forensic neuropsychologists are frequently asked to comment on risk for dementia after an alleged TBI in litigation and criminal cases. This article provides an evidence-based foundation to aid forensic practice by synthesizing comprehensive information pertaining to: (i) the role of the neuropsychologist in TBI-related litigation, (ii) the complexities associated with identifying TBIs in forensic cases, (iii) the science of TBI in relation to incident dementia, and (iv) current scientific evidence for chronic traumatic encephalopathy. Developing a neurodegenerative disorder after TBI is the exception rather than the rule. Prevalence rates suggest that only a small subset (< 5%) of individuals with moderate-to-severe TBI, and even fewer (< 1%) with mild TBI (mTBI), appear to develop certain neurodegenerative diseases, and the characteristics that place some at risk remain unclear. The literature is mixed in terms of identifying a relationship between mTBI and later-in-life dementia risk. Also, the quality of positive evidence for risk of dementia after mTBI is weak and mostly consists of observational studies characterized by methodological limitations. Methods used to establish the likely occurrence of a TBI in a forensic context are typically more extensive than those used in a routine clinical evaluation. Research methodology to define TBI is often even more rudimentary and inconsistent. Applying clinical research results of TBI and dementia outcomes to forensic cases at an individual level carries significant limitations. Estimating the contribution of remote head hits or concussion in a causal manner to dementia is a challenge forensic experts sometimes face, yet at present, the task is impossible beyond correlations and speculation.

COVID-19 vaccination survey and anti-SARS-CoV-2 IgG responses in a human cohort from Schistosoma mansoni-endemic villages in Mayuge District, Uganda: a cross-sectional study.

The coronavirus disease 2019 (COVID-19) pandemic has resulted in devastating health and economic consequences worldwide. Vaccination has been a central pillar for COVID-19 prevention and control. Understanding the immunomodulatory effects of helminth infections on COVID-19 vaccine-induced immune responses and vaccine efficacy is crucial to the development and deployment of effective vaccination strategies in low- and middle-income countries with a high prevalence of worms. In September 2022, we conducted a cross-sectional, population-based survey in five Schistosoma mansoni endemic villages in Mayuge District, Uganda (n = 450). The prevalence of schistosomiasis and soil-transmitted helminths was determined by the Kato-Katz (KK) technique on two stool samples collected from each participant. A subset of individuals (n = 204) were interviewed in a COVID-19 vaccination survey. IgG levels against the SARS-CoV-2 spike S1 subunit (anti-S1 IgG) were measured by enzyme-linked immunosorbent assay (ELISA) in collected serum samples. The overall schistosomiasis and hookworm prevalence rates in the five villages were 36.4% (166/450) and 36.9% (168/450), respectively. Within the cohort, 69.78% (314/450) of the subjects had a positive anti-S1 IgG response. COVID-19 vaccination coverage among the interviewed participants was 93.14% (190/204; 95% CI, 88.8% - 95.9%). However, 81% (154/190) of COVID-19 vaccinees had an anti-S1 IgG titre ≤200. In an adolescent group receiving a single dose of the BNT162b2 mRNA vaccine (n = 23), an inverse correlation was observed between anti-S1 IgG antibody level/titre and faecal egg count. Within the above group, anti-S1 IgG levels/titres were significantly lower in subjects with moderate or heavy S. mansoni infection (n = 5) than those in KK-negative individuals (n = 9). Although the acceptance rate of COVID-19 vaccination was high, the majority of participants received only a single vaccine dose and the overall anti-S1 IgG titres in confirmed vaccinees were low. Moderate-to-heavy schistosome infections blunted the antibody responses following vaccination with a single dose of BNT162b2. These observations confirm the necessity for a second COVID-19 vaccine dose for two-dose primary immunization series and call for implementation research that may inform the development of a 'treat and vaccinate' policy during vaccination roll-out in regions with heavy worm burdens.

Morphological and molecular data demonstrate the existence of Betula fruticosa and B. middendorffii and the absence of B. ovalifolia in northeastern China

Abstract Shrub birches are important components of massive wetlands in Northeast China, although much of these habitats have been lost over the past two decades. However, the taxonomy of shrub birches has been ambiguous owing to their morphological variation. In this study, we incorporated morphological and molecular data to address the taxonomic challenges associated with shrub birches. We characterized the morphological variation in the leaves, seeds, and bracts of 11 shrub birch populations in Northeast China and a population of Betula ovalifolia in northern Japan. We genotyped birch individuals from Northeast China at 15 microsatellite loci as well as a subset of individuals, using restriction site-associated DNA sequencing (RAD-seq). The populations in Northeast China consisted of B. fruticosa and B. middendorffii. These two species and B. ovalifolia differ in the width of their seed wings and the angle between the side lobes of their bracts, despite substantial intraspecific variation. Our genetic data revealed two distinct clusters, corresponding to B. fruticosa and B. middendorffii. Ploidy level assessment via RAD-seq revealed that B. fruticosa is diploid and B. middendorffii is tetraploid. Phylogenetic analysis revealed that B. fruticosa formed a sister clade to diploid B. humilis, and B. middendorffii formed a clade with diploid B. nana. Our results indicate the existence of B. fruticosa and B. middendorffii and the probable absence of B. ovalifolia in the northern Daxing’an Range, as all the tetraploid individuals sampled there represented B. middendorffii. In addition, our results suggest that B. humilis and B. nana may have served as diploid parents of the tetraploid species B. ovalifolia and B. middendorffii, respectively.

Investigating frank autism: clinician initial impressions and autism characteristics

Background“Frank autism,” recognizable through the first minutes of an interaction, describes a behavioral presentation of a subset of autistic individuals that is closely tied to social communication challenges, and may be linked to so-called “prototypical autism.” To date, there is no research on frank autism presentations of autistic adolescents and young adults, nor individuals diagnosed with autism spectrum disorder (ASD) in childhood who do not meet diagnostic criteria during or after adolescence (loss of autism diagnosis, LAD). In addition, there are currently no data on the factors that drive frank autism impressions in these adolescent groups.MethodsThis study quantifies initial impressions of autistic characteristics in 24 autistic, 24 LAD and 26 neurotypical (NT) individuals ages 12 to 39 years. Graduate student and expert clinicians completed five-minute impressions, rated confidence in their own impressions, and scored the atypicality of behaviors associated with impressions; impressions were compared with current gold-standard diagnostic outcomes.ResultsOverall, clinicians’ impressions within the first five minutes generally matched current gold-standard diagnostic status (clinical best estimate), were highly correlated with ADOS-2 CSS, and were driven primarily by prosodic and facial cues. However, this brief observation did not detect autism in all cases. While clinicians noted some subclinical atypicalities in the LAD group, impressions of the LAD and NT groups were similar.LimitationsThe brief observations in this study were conducted during clinical research, including some semi-structured assessments. While results suggest overall concordance between initial impressions and diagnoses following more thorough evaluation, findings may not generalize to less structured, informal contexts. In addition, our sample was demographically homogeneous and comprised only speaking autistic participants. They were also unmatched for sex, with more females in the non-autistic group. Future studies should recruit samples that are diverse in demographic variables and ability level to replicate these findings and explore their implications.ConclusionsResults provide insights into the behavioral characteristics that contribute to the diagnosis of adolescents and young adults and may help inform diagnostic decision making in the wake of an increase in the demand for autism evaluations later than childhood. They also substantiate claims of an absence of apparent autistic characteristics in individuals who have lost the diagnosis.