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Background: The differential diagnosis between adult systemic EBV-positive T-cell lymphoproliferative disorders (EBV+ T-LPD) and angioimmunoblastic T-cell lymphoma (AITL) with multiple EBV infections is difficult, and distinguishing between the two has become a diagnostic challenge for pathologists. Given that the clinical treatment plans are different, an accurate diagnosis is a prerequisite to ensure effective treatment, therefore, it is extremely necessary and meaningful to find effective pathological indicators for distinguishing between two diseases. Methods: We present a retrospective study comparing 7 cases of adult EBV+ T-LPD and 16 cases of AITL with multiple EBV infections diagnosed at our institution from 2017 to 2022. Differences in immunophenotype, type of EBV-infected cells, clonality and gene mutations between the two groups of cases were compared by immunohistochemical staining, double-label staining, TCR gene rearrangement and next-generation sequencing analysis. Results: 7 cases of adult EBV+ T-LPD: all cases had no more than 1 T follicular helper (THF) marker was expressed, and there were significantly more EBER+/CD3 + cells than EBER+/CD20 + cells; 5 cases had mutation detection results, in which only 1 had the characteristic KMT2D mutation, 2 had TET2 mutations, and no common mutations such as DDX3X were detected.16 cases of AITL with multiple EBV infections: all cases were found to express at least 2 TFH markers, with 87% of them expressing at least 3 TFH markers., and had significantly more EBER+/CD20 + cells than EBER+/CD3 + cells; 4 cases had mutation test results, with mutated high-frequency genes being TET2 (100%, and all of them had 2 or more TET2 mutations) and RHOA G17V (100%), DNMT3A mutation occurred in 2 cases (50%), and IDH2 R172 mutation occurred in 1 case (25%). Conclusions: We found that the expression pattern of TFH markers, the types of cells predominantly infected by EBV and the different mutations can all be used as effective pathological indicators for distinguishing between two diseases. [ABSTRACT FROM AUTHOR]

Background: Low load resistance training with blood flow restriction (LL-BFRT) has been shown to improve muscle strength and hypertrophic function. The effect of LL-BFRT on lower extremity muscle improvement has been widely discussed. However, no studies have discussed the effect of this training method on the upper extremity muscles until now. This systematic review and meta-analysis focused on the use of LL-BFRT in the upper extremity muscles. Methods: The relevant literature was searched in four major databases including Pubmed, Web of science, the Cochrane Library and Embase from 10 June 2024. The Cochrane Collaboration's tool and GRADE methodology were used to assess the risk of bias and quality in included studies. Results: The meta-analysis included a total of 11 articles with 220 participants. LL-BFRT and high load resistance training (HLRT) produced similar effects in improving upper extremity muscle strength (low certainty evidence, SMD: −0.35; 95%CI: −0.73 to 0.03; p : 0.07; I2: 2%) and hypertrophy (moderate certainty evidence, SMD: −0.36; 95%CI: −0.73 to 0.01; p : 0.05; I2: 0%). Compared with low load resistance training (LLRT), LL-BFRT showed greater advantages in improving upper extremity muscle strength (low certainty evidence, SMD: 0.67; 95%CI: 0.33 to 1.01; p : 0.0001; I2: 0%) and hypertrophy (low certainty evidence, SMD: 0.37; 95%CI: 0.06 to 0.67; p : 0.02; I2: 0%). Conclusion: In general, LL-BFRT can be used as an alternative training method for HLRT to improve upper extremity muscle strength and hypertrophy. Our study shows that the effect of LL-BFRT on upper extremity muscle is limited by age and region. It is necessary to formulate reasonable exercise programs according to the characteristics of different demographic groups. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42024555514. [ABSTRACT FROM AUTHOR]

Background: Childhood obesity is associated with obesity in adulthood, but the consistency between the geographic distributions of obesity among children and adults in China is not fully understood. We aimed to examine the consistency of the geographic distributions of overweight and obesity between adults and children in China. Methods: This was a cross-sectional study including 11,940 adults. Data were from the China Health and Nutrition Survey conducted in 2015. Body mass index (BMI) and waist circumference (WC) were measured. The geographical areas were categorized as low-, middle- or high-epidemic areas according to the prevalence of overweight and obesity in children at the provincial level, based on the classification system determined by the National Health Commission. We examined the differences in adult BMI, WC, prevalence of overweight and obesity, abdominal overweight and obesity across the three classification areas. Results: In this study, the overall prevalence of overweight/obesity and abdominal overweight/obesity were 49.8% and 61.0% respectively. We observed the prevalence of overweight and obesity among adults increased from low- to middle- and high- epidemic areas. Compared with adults from low-epidemic areas, those from middle- and high-epidemic areas had a higher odds of having overweight or obesity (odds ratio [95% confidence interval]: 1.518 [1.362, 1.692] and 2.190 [1.972, 2.433], respectively). Similar results were observed for abdominal overweight and obesity in adults. Conclusion: Our study confirmed the consistency in the geographical clustering of overweight and obesity among adults and children, which suggests that interventions addressing overweight and obesity should be targeted at both local children and adults simultaneously. [ABSTRACT FROM AUTHOR]

Background: Poor quality of life in adults with anorexia nervosa (AN) and persistent high rates of readmission highlight the necessity of developing interventions to optimize treatment outcomes. ECHOMANTRA is a novel online intervention based on interventions for carers (Experienced Carers Helping Others, ECHO) and patients (Maudsley Model of Anorexia Nervosa Treatment for Adults, MANTRA) with anorexia nervosa. The objective of this paper is to describe the study protocol of a randomized control trial (RCT) aimed at evaluating the efficacy of an adaptation of the ECHOMANTRA for adults AN inpatients and outpatients, and their carers, to be implemented as an add-on to treatment-as-usual (TAU). Methods: In a multi − center pilot randomized controlled trial (RCT), 148 adult AN patients, and their carers, will be randomized to receive treatment as usual (TAU) or TAU plus ECHOMANTRA. Assessments will take place at baseline (T0), post-intervention (2-month) (T1), 6-month follow-up (T2), and 12-month follow-up (T3). Primary outcomes will be eating disorder psychopathology and psychological well-being. For carers, outcome variables will include psychological well-being, accommodation and enabling behaviors, expressed emotion, illness burden, quality of life and care skills. Discussion: This study will provide evidence of the efficacy of this novel, online and protocolized intervention in facilitating the recovery of these patients. Trial registration: ISRCTN registry (Identifier: 80253157 https://doi.org/10.1186/ISRCTN80253157). [ABSTRACT FROM AUTHOR]

IntroductionMethodsResultsConclusionsRhabdomyosarcoma (RMS) is a common pediatric orbital malignancy but is extremely rare in adults. This study assesses clinical and radiographic features, management, and outcomes in adult orbital RMS patients with comparison to pediatric patients.A retrospective chart review from 2000–2023 at Bascom Palmer Eye Institute was conducted evaluating patients aged 0 to 100-years-old with biopsy-confirmed orbital RMS. Medical records were reviewed for demographics, clinical features, imaging, histopathology, management, and outcomes. Statistical analysis was conducted with Mann-U Whitney and chi-squared testing.Twenty-four patients were included, 15 children (mean age 6.4 ± 4.4 years) and 9 adults (35.7 ± 12.4 years). Patients in both groups presented with eyelid edema followed by proptosis with similar symptom duration (p = 0.31). Lesions were frequently located medially and inferiorly in both groups. At presentation, adults had significantly more metastatic disease in addition to bone, extraocular muscle, intracranial, and parameningeal involvement. The most common pediatric RMS subtype was embryonal (80%), whereas most adults were alveolar (77.8%, p = 0.001). Treatment in both groups frequently included chemoradiation. Both groups demonstrated similar local recurrence (p = 0.72), overall survival (p = 0.86), and ophthalmologic sequelae (p = 0.45), although pediatric follow-up duration was notably longer.To our knowledge, this study is the largest report of adult orbital RMS from a single institution, highlights key comparisons in features and outcomes between adult and pediatric orbital RMS, and provides an updated literature review. While pediatric and adult orbital RMS clinical presentations are similar, adult disease more often demonstrates aggressive features, including alveolar subtype, local structure involvement, and lower disease-free survival. [ABSTRACT FROM AUTHOR]

Background: Despite advancements in Human Immunodeficiency Virus (HIV) treatment and care, undernutrition remains a significant concern, accelerating disease progression and risk of Acquired Immune Deficiency Syndrome (AIDS)-related deaths. The nutritional status of second-line antiretroviral treatment (SLART) users in Ethiopia has not been thoroughly investigated. So, this study aimed to assess the nutritional status of HIV/AIDS patients who were on SLART and its associated factors in Northern Ethiopia. Methods: A retrospective cross-sectional study was conducted on 366 HIV-infected adults who had been on SLART for at least six months in northern Ethiopia. Clients who had documented Weight and height at six months of therapy were included. Data was entered and cleaned by using EpiDATA version 4.6.0.2 and statistical analysis was done by STATA version 17. Multiple imputation method was applied to manage variables having up to 25% missing values by using R-Version 3.6.2 software. Binary logistic regression was used with P < 0.05 as a significant predictor in the final analysis. Data was collected from February 01 to April 30, 2021. Results: The magnitude of undernutrition among adults who were on SLART in the study area was 38.52% (95%CI: 33.65–43.64). Those populations also had a baseline undernutrition status of 39.1% (95%CI: 34.11–44.15) during their transition to SLART. The risk of being malnourished at six months of SLART initiation was fifteen times higher among those who were undernourished at SLART start (AOR:15.099, 95%CI: 8.532, 26.720) reflecting the high burden of the problem in the advanced courses of HIV/AIDS treatment and care. Conclusions: The proportion of undernutrition among SLART users in Northern Ethiopia is high. During HIV therapy, a client's overall nutritional health is predicted by their prior undernutrition condition. This highlights the need for comprehensive nutritional assessment, counseling, and monitoring of the nutritional status of SLART users in the area with emphasis on an early identification of possible barriers to the improvement of such conditions. Promoting the consumption of nutrient-dense local foods and appropriate food preparation methods in addition to nutritional support are vital in this setting. [ABSTRACT FROM AUTHOR]

Individuals with intellectual disabilities (ID) often exhibit lower levels of physical fitness compared to the general population, including reduced strength, endurance, flexibility, and coordination. Dynamic neuromuscular stabilization (DNS) training can potentially improve the performance of adults with ID caused by weak motor skills due to a lack of desirable nerve growth during childhood and before puberty. Also, DNS training proposed to improve physical fitness in this population, but the effectiveness and durability of DNS training on specific fitness components have not been well-established. This study employed a randomized controlled trial design to investigate the effects of an 8-week DNS training program on the strength, endurance, and flexibility of adults with ID. A total of 31 participants were randomly assigned to either an intervention group (n = 16) or a control group (n = 15). Muscular strength, endurance, and flexibility were assessed at baseline (pre-test), immediately after the intervention (post-test), and 2 months following the intervention (follow-up) using the 30-second chair stand (30sCS) test, sit-ups test, trunk lift test, and chair sit-and-reach test. Participants in the intervention group engaged in the DNS training program for 8 weeks, with 3 sessions per week, while the control group maintained their usual activities. The analysis of the outcome measures revealed significant time, group, and time-group interaction effects. Post-hoc analyses indicated that the DNS group exhibited significantly greater improvements in 30sCS, sit-ups, trunk lift, and chair sit-and-reach compared to the control group (p < 0.01). These improvements were maintained at the 2-month follow-up assessment in the DNS group. This randomized controlled trial demonstrates that an 8-week DNS training program significantly improves muscular strength, endurance, and flexibility in adults with ID, with benefits maintained at a 2 month follow-up. Further research is needed to replicate these findings and investigate underlying mechanisms, but the study highlights the potential of DNS training to promote physical fitness and well-being in individuals with ID. Trial registration RTC, prospectively registered in the Clinical Trial Registry (UMIN000053560) on 24/03/2024. [ABSTRACT FROM AUTHOR]

Background The rising prevalence of pretreatment drug resistance (PDR) to non-nucleoside reverse-transcriptase inhibitors threatens the effectiveness of ART. In response, the WHO recommends dolutegravir-based ART regimens due to their high genetic barrier to resistance and better treatment outcomes. This is expected to contribute to achieving the Joint United Nations Programme on HIV/AIDS (UNAIDS) target of 95% viral suppression in people on ART. Objectives To estimate the prevalence of PDR among adults initiating ART and assess viral suppression and acquired HIV drug resistance (ADR) among individuals receiving ART in Belize. Patients and methods Nationally representative cross-sectional PDR and ADR surveys were conducted between 2021 and 2022. Sixty-seven adults were included in the PDR survey, and 43 children and adolescents and 331 adults were included in the ADR survey. Demographic and clinic data and blood specimens were collected. HIV drug resistance (HIVDR) was predicted using the Stanford HIVdb tool. Results The prevalence of PDR to efavirenz or nevirapine in adults was 49.3% (95% CI 42.2%–56.4%) and was significantly higher in those with previous antiretroviral exposure (OR: 7.16; 95% CI 2.71–18.95; P  = 0.002). Among children and adolescents receiving ART, 50.0% had viral suppression, with better rates for those receiving dolutegravir-based ART (OR: 5.31; 95% CI 3.02–9.34; P  < 0.001). In adults, 79.6% achieved viral suppression. No resistance to integrase inhibitors was observed in those on dolutegravir-based ART. Conclusions Prioritizing dolutegravir-based ART is critical for achieving HIV epidemic control in Belize. Efforts should focus on retention in care and adherence support to prevent HIVDR. [ABSTRACT FROM AUTHOR]

Objective Five Phase 3 bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) clinical studies demonstrated that the efficacy of B/F/TAF was non-inferior to dolutegravir (DTG) + 2 NRTIs. We retrospectively assessed drug adherence and effect on virologic outcomes. Methods Studies (NCT02607930, NCT02607956, NCT03547908, NCT02603120 and NCT03110380) were double-blind, placebo-controlled and enrolled treatment-naïve or virologically suppressed adults. Adherence was calculated by pill count from returned pill bottles; virologic outcome was assessed by last on-treatment HIV-1 RNA. Results Altogether, 2622 participants (B/F/TAF: n  = 1306; DTG + 2 NRTIs: n  = 1316) were categorized as having high (≥95%), intermediate (≥85% to <95%) or low (<85%) adherence. Through Week 48, low adherence was observed in 46 (3.5%) participants in the B/F/TAF group (78% median adherence) and 69 (5.2%) in the DTG + 2 NRTI group (80% median adherence). Overall, 1287 (98.5%) participants in the B/F/TAF group and 1292 (98.2%) in the DTG + 2 NRTI group had virologic suppression (VS; HIV-1 RNA < 50 copies/mL) through Week 48. VS in participants with low adherence versus high or intermediate adherence was similar in the B/F/TAF group, but lower in the DTG + 2 NRTI group (P  ≤ 0.002). Similar results were observed at Weeks 96 and 144. Two participants (<95% adherence) in the DTG + 2 NRTI group receiving DTG and abacavir/lamivudine developed M184V; there was no treatment-emergent resistance to B/F/TAF. Conclusions Participants with suboptimal (<85%) adherence to B/F/TAF maintained high levels of VS, whereas suboptimal DTG + 2 NRTI adherence was associated with lower VS. [ABSTRACT FROM AUTHOR]

To illuminate individual differences in the development of attention-deficit hyperactivity disorder (ADHD) symptoms in the general population, psychometric measures are needed that can capture general population-level symptom variation reliably, validly, and comparably from childhood through to the transition to adulthood. The ADHD subscale of the Social Behavior Questionnaire (SBQ-ADHD) provides a candidate for a measure that can meet this need. We thus evaluate the psychometric properties of the SBQ-ADHD as administered in adulthood (ages 20 and 24) to a large normative sample, as well as the cross-informant (parent-teacher-self-reports) and developmental (ages 7–24) measurement invariance of a core SBQ-ADHD item set. Results support score internal consistency reliability, gender measurement invariance, and criterion validity. Scores from the core item set showed some evidence of non-invariance, providing insights into how ADHD symptoms may manifest and/or be perceived differently by different informants/in different contexts and at different ages. Our findings overall support the use of the SBQ-ADHD items for developmental studies of ADHD symptoms from childhood to adulthood. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Endoscopy, standard-of-care for monitoring eosinophilic esophagitis (EoE), assesses mucosal inflammation. The Esophageal String Test (EST), a minimally invasive swallowed capsule and immunoassays, quantifies EoE inflammation. We determined whether the EST/EoEScore can monitor disease in patients undergoing treatment. METHODS: Thirty-three samples from 14 patients with EoE (7 children, 7 adults) who underwent repeat endoscopies and ESTs were studied. Biopsies were analyzed for peak eosinophil counts; ESTs were analyzed for EoEScores. RESULTS: Eosinophil counts and EoEScores significantly correlated during treatment, distinguishing patients with active EoE from treatment-associated remissions for 93.9% of ESTs performed. DISCUSSION: The EST can be used to longitudinally monitor responses to treatment in EoE. [ABSTRACT FROM AUTHOR]

Over the past two decades there has been increased interest in orphan drug development for rare diseases. However, hurdles to clinical trial design for these disorders remain. This phase 1a/1b study addressed several challenges, while evaluating the safety and tolerability of the novel oral molecule KL1333 in healthy volunteers and subjects with primary mitochondrial disease. KL1333 aims to normalize the NAD+:NADH ratio that is critical for ATP production. The trial incorporated innovative design elements with potential translatability to other rare diseases including patient involvement, adaptive design and exploratory objectives, all of which have subsequently informed the protocol of an ongoing phase 2, pivotal efficacy study of KL1333. Results indicate KL1333 is safe and well tolerated, with dose-dependent gastrointestinal side effects, and validate potential novel outcome measures in primary mitochondrial disease including the 30-s Sit to Stand, and the patient-reported fatigue scales. Importantly, the data from the trial support efficacy of KL1333 based on improvements in fatigue and functional strength and endurance. Furthermore, the study highlights the value in using phase 1 studies to capture data that helps optimize later phase efficacy trial design. [ABSTRACT FROM AUTHOR]

Developmental dyslexia (DD) is one of the most common learning disorders, affecting millions of children and adults worldwide. To date, scientific research has attempted to explain DD primarily based on pathophysiological alterations in the cerebral cortex. In contrast, several decades ago, pioneering research on five post-mortem human brains suggested that a core characteristic of DD might be morphological alterations in a specific subdivision of the visual thalamus—the magnocellular lateral geniculate nucleus (M-LGN). However, due to considerable technical challenges in investigating LGN subdivisions non-invasively in humans, this finding was never confirmed in vivo , and its relevance for DD pathology remained highly controversial. Here, we leveraged recent advances in high resolution MRI at high field strength (7 T) to investigate the M-LGN in DD in vivo. Using a case-control design, we acquired data from a large sample of young adults with DD (n = 26; age 28 ± 7 years; 13 females) and matched control participants (n = 28; age 27 ± 6 years; 15 females). Each participant completed a comprehensive diagnostic behavioural test battery and participated in two MRI sessions, including three functional MRI experiments and one structural MRI acquisition. We measured blood oxygen level-dependent responses and longitudinal relaxation rates to compare both groups on LGN subdivision function and myelination. Based on previous research, we hypothesized that the M-LGN is altered in DD and that these alterations are associated with a key DD diagnostic score, i.e. rapid letter and number naming. The results showed aberrant responses of the M-LGN in DD compared to controls, which was reflected in a different functional lateralization of this subdivision between groups. These alterations were associated with rapid letter and number naming performance, specifically in male DD. We also found lateralization differences in the longitudinal relaxation rates of the M-LGN in DD relative to controls. Conversely, the other main subdivision of the LGN, the parvocellular LGN (P-LGN), showed comparable blood oxygen level-dependent responses and longitudinal relaxation rates between groups. The present study is the first to unequivocally show that M-LGN alterations are a hallmark of DD, affecting both the function and microstructure of this subdivision. It further provides a first functional interpretation of M-LGN alterations and a basis for a better understanding of sex-specific differences in DD with implications for prospective diagnostic and treatment strategies. [ABSTRACT FROM AUTHOR]

Obese adults are often reported to have smaller brain volumes than their non-obese peers. Whether this represents evidence of accelerations in obesity-driven atrophy or is instead a legacy of developmental differences established earlier in the lifespan remains unclear. This study investigated whether early-life differences in adiposity explain differences in numerous adult brain traits commonly attributed to mid-life obesity. We used a two-sample life course Mendelian randomization study in 37 501 adults recruited to UK Biobank (UKB) imaging centres from 2014, with secondary analyses in 6996 children assessed in the Adolescent Brain Cognitive Development Study (ABCD) recruited from 2018. Exposures were genetic variants for childhood (266 variants) and adult (470 variants) adiposity derived from a genome-wide association study (GWAS) of 407 741 UKB participants. Primary outcomes were: adult total brain volume; grey matter volume, thickness and surface area; white matter volume and hyperintensities; and hippocampus, amygdala and thalamus volumes at mean age 55 in the UKB. Secondary outcomes were equivalent childhood measures collected at mean age 10 in ABCD. In the UKB, individuals who were genetically predicted to have had higher levels of adiposity in childhood were found to have multiple smaller adult brain volumes relative to intracranial volume [e.g. z -score difference in normalized brain volume per category increase in adiposity—95% confidence interval (CI) = −0.20 (−0.28, −0.12); P = 4 × 10−6]. These effect sizes remained essentially unchanged after accounting for birthweight or current adult obesity in multivariable models, whereas most observed adult effects attenuated towards null [e.g. adult z -score (95% CI) for total volume = 0.06 (−0.05, 0.17); P = 0.3]. Observational analyses in ABCD showed a similar pattern of changes already present in those with a high body mass index by age 10 [ z -score (95% CI) = −0.10 (−0.13, −0.07); P = 8 × 10−13], with follow-up genetic risk score analyses providing some evidence for a causal effect already at this early age. Sensitivity analyses revealed that many of these effects were likely due to the persistence of larger head sizes established in those who gained excess weight in childhood [childhood z -score (95% CI) for intracranial volume = 0.14 (0.05, 0.23); P = 0.002], rather than smaller brain sizes per se. Our data suggest that the persistence of early-life developmental differences across the life course may underlie numerous neuroimaging traits commonly attributed to obesity-related atrophy in later life. [ABSTRACT FROM AUTHOR]

Case: We present a case of isolated tuberculous osteomyelitis of the calcaneus in an immune-competent adult patient with a 5-year follow-up. The diagnosis was established by core needle aspiration and biopsy. He was treated with antituberculous chemotherapy and immobilization. The lesion healed with collapse of the calcaneal tuberosity that clinically resulted in shortening and heel valgus. A literature review is also presented. Conclusion: Isolated tuberculous osteomyelitis of the calcaneus in an immune-competent adult patient is rare. It may pose diagnostic dilemma, and orthopaedist should work through the differential diagnosis. [ABSTRACT FROM AUTHOR]