Search

The incidence of Parkinson's disease (PD) in sub-Saharan Africa (SSA) is greater than thought however, is largely undiagnosed and untreated. This study aimed to evaluate a nonpharmacological approach using cueing therapy to improve gait in drug-naïve PD and the feasibility of delivering rehabilitation in northern Tanzania. In this study, twenty-one people with PD aged 76.4 years (12.9 SD) with varying disease severity participated. They received 9 x 30 min sessions of cueing therapy for gait problems over 3 weeks from a trained therapist delivered in their home environment. Cueing therapy consisted of walking in time to a metronome beat to correct step amplitude and step frequency during a range of functional activities. Gait was recorded on video before and after therapy, and videos were analyzed in the UK by an assessor not involved in data collection. Disease severity (UPDRS) and balance were also measured. Patients were assessed in their nearest clinic. Data were analyzed in Minitab and a P value of 0.05 was considered significant. Cueing therapy significantly improved single and dual task walking speed, step amplitude, and single task step frequency. There was also a significant improvement in motor impairment (UPDRS III) and activities of daily living (UPDRS II). The results provide promising evidence for the role of cueing therapy in PD for symptom management to reduce or delay medication onset. This study also supports the feasibility of rehabilitation in PD in community environments in SSA, which may be applicable to other developing regions. [ABSTRACT FROM AUTHOR]

BACKGROUND: Cognitive impairment is well recognised in Parkinson's Disease (PD) but few studies have examined cognitive decline over time in such subjects. Standard clinical assessments of cognitive function, such as the MMSE, do not measure all cognitive domains and often have a ceiling effect. CAMCOG-R provides a more comprehensive cognitive assessment allowing several different domains of cognition to be compared. It also features the ability to test 'executive function'. CAMCOG-R has only been reported on one previous occasion in PD subjects and this is the first study to report a follow-up CAMCOG-R to assess cognitive decline. METHODS: In a previously published study CAMCOG-R was administered to a prevalent community-based population of 94 subjects with PD with a MMSE of 25 or above. In this subsequent study 85 of the subjects (two declined and seven were deceased) underwent a follow-up CAMCOG-R after a mean delay of 13.1 months. RESULTS: The initial, and follow-up mean total CAMCOG-R scores were 88.65/104 and 84.75/104 respectively, demonstrating a significant decline (p < 0.05). Significant cognitive decline (p < 0.05) was also seen across every CAMCOG-R cognitive domain and in the executive function scores. CONCLUSIONS: A wide range of cognitive ability was again demonstrated using CAMCOG-R in this PD population. The decline of 3.9 CAMCOG-R points over the 13-month period compares to other previous studies showing an annual decline of 1.6 CAMCOG points in normal elderly individuals and 12 CAMCOG points annually in those with established dementia. This study suggests that CAMCOG-R is a useful and appropriate tool for use in follow-up cognitive screening in PD subjects. [ABSTRACT FROM AUTHOR]

CONTEXT: While there has been considerable research on prenatal alcohol use, there have been limited studies focused on women in rural and small-town environments. PURPOSE: This 2-part study examines gender differences in attitudes and perceived barriers to intervention in large community sample of persons living in rural and small-town environments in Kentucky (n = 3,346). The study also examines rural/small-town prenatal service providers' perceptions of barriers to assessment and intervention with pregnant substance abusers (n = 138). METHODS: Surveys were administered to a convenience sample of employees and customers from 16 rural and small-town community outlets. There were 1503 males (45%) and 1843 females (55%) ranging in age from under 18 years old to over 66 years old. Surveys also were mailed to prenatal providers in county health departments of the 13-county study area, with 138 of 149 responding. FINDINGS: Overall results of the community sample suggest that neither males nor females were knowledgeable about the harmful effects of alcohol use during pregnancy. Results also indicate substantial gender differences in alcohol attitudes, knowledge, and perceived barriers. Further, prenatal care providers identified several barriers in assessment and treatment of pregnant women with alcohol use problems in rural and small-town communities, including lack of knowledge and comfort with assessment as well as a lack of available and accessible treatment for referrals. [ABSTRACT FROM AUTHOR]

Objectives: To accurately establish the incidence of falls in Parkinson's disease (PD) and to investigate predictive risk factors for fallers from baseline data.Methods: 109 subjects with idiopathic PD diagnosed according to the brain bank criteria underwent a multidisciplinary baseline assessment comprising demographic and historical data, disease specific rating scales, physiotherapy assessment, tests of visual, cardiovascular and autonomic function, and bone densitometry. Patients were then prospectively followed up for one year using weekly prepaid postcards along with telephone follow up.Results: Falls occurred in 68.3% of the subjects. Previous falls, disease duration, dementia, and loss of arm swing were independent predictors of falling. There were also significant associations between disease severity, balance impairment, depression, and falling.Conclusions: Falls are a common problem in PD and some of the major risk factors are potentially modifiable. There is a need for future studies to look at interventions to prevent falls in PD. [ABSTRACT FROM AUTHOR]

Dementia with Lewy bodies (DLB) is part of the spectrum of Lewy body disorders. However, it may be difficult to diagnose patients who have dementia but no Parkinsonism. Visual and semiquantitative assessment of the nigrostriatal dopaminergic nerve terminals in the putamen and caudate nuclei can be obtained with single photon emission computerized tomography (SPECT) using ligands that bind to the dopamine transporter molecule in the membranes of the nigrostriatal nerve terminals. This can be employed as a means of identifying subclinical degeneration of nigrostriatal neurones in patients with suspected DLB, increasing the probability of the diagnosis. In several studies, the sensitivity and specificity of abnormal dopamine transporter scans with regard to diagnosing probable DLB are better than 75 and 90%, respectively. This communication outlines the evidence for this and discusses some of the advantages, potential disadvantages, and areas of uncertainty with regard to the use of dopamine transporter SPECT in DLB diagnosis. [ABSTRACT FROM AUTHOR]

Background Mucous membrane pemphigoid (MMP) is a rare subepidermal autoimmune blistering disorder. The clinical and demographic parameters of this disease in Indian patients have not yet been elucidated in detail. Objective We aimed to study the clinical and demographic characteristics, disease course, and treatment aspects of MMP patients. Methods The data for this study were obtained by reviewing the case record forms of patients registered in the Autoimmune Bullous Disease (AIBD) Clinic of the Department of Dermatology, Venereology & Leprology, Postgraduate Institute of Medical Education and Research, Chandigarh, a tertiary care centre in India. The diagnosis of MMP was established on the basis of clinical and immune-histopathological features which are consistent with standard diagnostic criteria for the disease. Results A total of 52 patients with MMP registered in the AIBD clinic were included. The mean age at disease onset was 50 years and the average age at presentation was 56 years. Females outnumbered males in the study with a ratio of 1.36:1. The oral and ocular mucosae were the most commonly affected sites (82.6% and 63.4% respectively). Visual difficulty was reported by half the patients (26 of 52 patients). IgG, C3, and IgA deposits were detected on direct immunofluorescence (DIF) in 29, 21, and 11 patients, respectively. Serologic analysis was performed in only 7 of the patients and of these, just 1 exhibited a positive result on multivariant ELISA and epidermal pattern of binding on salt split skin indirect immunofluorescence. Most patients were treated with prednisolone (44 of 52). Steroid-sparing adjuvants were used in combination including cyclophosphamide, azathioprine, methotrexate, dapsone, and colchicine. Rituximab was administered in 7 patients with severe or refractory disease. Limitations This is a retrospective analysis of data available from a clinic registry. In patients with negative direct immunofluorescence on biopsy, the diagnosis was based on clinico-pathologic consensus. Conclusion MMP is not as uncommon in India as the paucity of reports suggest. Visual complications are frequent in Indian MMP patients. A high index of suspicion is required for early diagnosis and appropriate treatment to prevent ocular complications.

Objective: To assess chemokine receptor CXCR4 expression in lung parenchyma and on peripheral immune cells in systemic sclerosis-related interstitial lung disease (SSc-ILD) patients., Methods: SSc-ILD patients underwent 68Ga- CPCR4 Trifluoroacetate positron emission tomography (PET) scan, SUVmean in different lung regions and architecturally abnormal areas, and receiver operating characteristic (ROC) curves were analyzed. CXCR4 expression on peripheral immune cells using flow cytometer was studied and correlated with the different lung regions. In addition, subset analysis of CXCR4 expression by clinical subset (early, progressive, stable), ILD pattern and anti-Scl-70 positivity were done., Results: On PET, SSc-ILD patients showed higher median SUVmean uptake of CXCR4 in the whole lung (0.56; p< 0.0001), different lung regions and architecturally abnormal areas than controls. Highest area under curve (AUC) were observed in dorsobasal regions (AUC-0.91; p< 0.0001) and reticular with architecturally distorted areas (AUC-0.95; p< 0.0001). Progressive subset had higher whole lung median SUVmean (0.73) than early (0.49; p< 0.0001) and stable (0.45; p< 0.0001) subsets, and AUC than early and stable subsets. Usual interstitial pneumonia pattern ILD showed higher CXCR4 uptake compared with non-specific interstitial pneumonia (p= 0.0032). Additionally, a trend for higher uptake was noted in anti-Scl70 positive patients as compared with anti-Scl70 negative ones. SSc-ILD patients had higher CD4+CXCR4+T cells (p= 0.0003), and CD8+CXCR4+T cells (p= 0.0013), and showed moderate to strong association on correlation with the lung parenchymal regions., Conclusion: In SSc-ILD, CXCR4 expression is upregulated in both lung parenchyma and peripheral T cells, significantly in progressive and UIP subsets. CXCR4 expression is a potential tool for activity assessment and prognostication., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objective: Human immunodeficiency virus (HIV)-associated neurocognitive disorder (HAND) prevalence is expected to increase in East Africa as treatment coverage increases, survival improves, and this population ages. This study aimed to better understand the current cognitive phenotype of this newly emergent population of older combination antiretroviral therapy (cART)-treated people living with HIV (PLWH), in which current screening measures lack accuracy. This will facilitate the refinement of HAND cognitive screening tools for this setting., Method: This is a secondary analysis of 253 PLWH aged ≥50 years receiving standard government HIV clinic follow-up in Kilimanjaro, Tanzania. They were evaluated with a detailed locally normed low-literacy neuropsychological battery annually on three occasions and a consensus panel diagnosis of HAND by Frascati criteria based on clinical evaluation and collateral history., Results: Tests of verbal learning and memory, categorical verbal fluency, visual memory, and visuoconstruction had an area under the receiver operating characteristic curve >0.7 for symptomatic HAND (s-HAND) (0.70-0.72; p < 0.001 for all tests). Tests of visual memory, verbal learning with delayed recall and recognition memory, psychomotor speed, language comprehension, and categorical verbal fluency were independently associated with s-HAND in a logistic mixed effects model ( p < 0.01 for all). Neuropsychological impairments varied by educational background., Conclusions: A broad range of cognitive domains are affected in older, well-controlled, East African PLWH, including those not captured in widely used screening measures. It is possible that educational background affects the observed cognitive impairments in this setting. Future screening measures for similar populations should consider assessment of visual memory, verbal learning, language comprehension, and executive and motor function.

Background and Aims: Scarce knowledge about the impact of metabolism-disrupting chemicals (MDCs) on liver injury limits opportunities for intervention. We evaluated pregnancy MDC-mixture associations with liver injury and effect modification by folic acid (FA) supplementation in mother-child pairs., Methods: We studied ∼200 mother-child pairs from the Mexican PROGRESS cohort, with measured 43 MDCs during pregnancy (estimated air pollutants, blood/urine metals or metalloids, urine high- and low-molecular-weight phthalate [HMWPs, LMWPs] and organophosphate-pesticide [OP] metabolites), and serum liver enzymes (ALT, AST) at ∼9 years post-parturition. We defined liver injury as elevated liver enzymes in children, and using established clinical scores for steatosis and fibrosis in mothers (i.e., AST:ALT, FLI, HSI, FIB-4). Bayesian Weighted Quantile Sum regression assessed MDC-mixture associations with liver injury outcomes. We further examined chemical-chemical interactions and effect modification by self-reported FA supplementation., Results: In children, many MDC-mixtures were associated with liver injury outcomes. Per quartile HMWP-mixture increase, ALT increased by 10.1% (95%CI: 1.67%, 19.4%) and AST by 5.27% (95% CI: 0.80%, 10.1%). LMWP-mixtures and air pollutant-mixtures were associated with higher AST and ALT, respectively. Air pollutant and non-essential metal/element associations with liver enzymes were attenuated by maternal cobalt blood concentrations ( p -interactions<0.05). In mothers, only the LMWP-mixture was associated with liver injury [OR=1.53 (95%CI: 1.01, 2.28) for HSI>36, and OR=1.62 (95%CI: 1.05, 2.49) for AST:ALT<1]. In mothers and children, most associations were attenuated (null) at FA supplementation≥600mcg/day ( p -interactions<0.05)., Conclusions: Pregnancy MDC exposures may increase liver injury risk, particularly in children. These associations may be attenuated by higher FA supplementation and maternal cobalt levels.

Two of every three persons living with dementia reside in low- and middle-income countries (LMICs). The projected increase in global dementia rates is expected to affect LMICs disproportionately. However, the majority of global dementia care costs occur in high-income countries (HICs), with dementia research predominantly focusing on HICs. This imbalance necessitates LMIC-focused research to ensure that characterization of dementia accurately reflects the involvement and specificities of diverse populations. Development of effective preventive, diagnostic, and therapeutic approaches for dementia in LMICs requires targeted, personalized, and harmonized efforts. Our article represents timely discussions at the 2022 Symposium on Dementia and Brain Aging in LMICs that identified the foremost opportunities to advance dementia research, differential diagnosis, use of neuropsychometric tools, awareness, and treatment options. We highlight key topics discussed at the meeting and provide future recommendations to foster a more equitable landscape for dementia prevention, diagnosis, care, policy, and management in LMICs. HIGHLIGHTS: Two-thirds of persons with dementia live in LMICs, yet research and costs are skewed toward HICs. LMICs expect dementia prevalence to more than double, accompanied by socioeconomic disparities. The 2022 Symposium on Dementia in LMICs addressed advances in research, diagnosis, prevention, and policy. The Nairobi Declaration urges global action to enhance dementia outcomes in LMICs., (© 2024 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

HIV-associated neurocognitive disorders (HAND) are highly prevalent in those ageing with HIV. High-income country data suggest that vascular risk factors (VRFs) may be stronger predictors of HAND than HIV-disease severity, but data from sub-Saharan Africa are lacking. We evaluated relationships of VRFs, vascular end-organ damage and HAND in individuals aged ≥ 50 in Tanzania. c-ART-treated individuals were assessed for HAND using consensus criteria. The prevalence of VRFs and end organ damage markers were measured. The independent associations of VRFs, end organ damage and HAND were examined using multivariable logistic regression. Data were available for 153 individuals (median age 56, 67.3% female). HAND was highly prevalent (66.7%, 25.5% symptomatic) despite well-managed HIV (70.5% virally suppressed). Vascular risk factors included hypertension (34%), obesity (10.5%), hypercholesterolemia (33.3%), diabetes (5.3%) and current smoking (4.6%). End organ damage prevalence ranged from 1.3% (prior myocardial infarction) to 12.5% (left ventricular hypertrophy). Measured VRFs and end organ damage were not independently associated with HAND. The only significant association was lower diastolic BP ( p 0.030, OR 0.969 (0.943-0.997). Our results suggest that vascular risk factors are not major drivers of HAND in this setting. Further studies should explore alternative aetiologies such as chronic inflammation.

Skin is now emerging as a complex realm of three chief systems viz. immune system, nervous system, and endocrine system. The cells involved in their intricate crosstalk, namely native skin cells, intra-cutaneous immune cells and cutaneous sensory neurons have diverse origin and distinct functions. However, recent studies have explored their role beyond their pre-defined functional boundaries, such that the cells shun their traditional functions and adopt unconventional roles. For example, the native skin cells, apart from providing for basic structural framework of skin, also perform special immune functions and participate in extensive neuro-endocrine circuitry, which were traditionally designated as functions of cutaneous resident immune cells and sensory neurons respectively. At the cellular level, this unique collaboration is brought out by special molecules called neuromediators including neurotransmitters, neuropeptides, neurotrophins, neurohormones and cytokines/chemokines. While this intricate crosstalk is essential for maintaining cutaneous homeostasis, its disruption is seen in various cutaneous diseases. Recent study models have led to a paradigm shift in our understanding of pathophysiology of many such disorders. In this review, we have described in detail the interaction of immune cells with neurons and native skin cells, role of neuromediators, the endocrine aspect in skin and current understanding of cutaneous neuro-immuno-endocrine loop in one of the commonest skin diseases, psoriasis. An accurate knowledge of this unique crosstalk can prove crucial in understanding the pathophysiology of different skin diseases and allow for generation of targeted therapeutic modalities., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Populations are ageing globally and Low- and Middle-Income Countries (LMICs) are experiencing the fastest rates of demographic change. Few studies have explored the burden of frailty amongst older people in hospital in LMICs, where healthcare services are having to rapidly adapt to align with the needs of older people. This study aimed to measure the prevalence of frailty amongst older people admitted to hospital in Tanzania and to explore their demographic and clinical characteristics., Methods: This study had a prospective observational design. Over a six-month period, all adults ≥ 60 years old admitted to medical wards in four hospitals in northern Tanzania were invited to participate. They were screened for frailty using the Clinical Frailty Scale (CFS) and the Frailty Phenotype (FP). Demographic and clinical characteristics of interest were recorded in a structured questionnaire. These included the Barthel Index, the Identification of Elderly Africans Instrumental Activities of Daily Living (IADEA-IADL) and Cognitive (IDEA-Cog) screens, the EURO-D depression scale and Confusion Assessment Method., Results: 540 adults aged ≥ 60 were admitted, and 308 completed assessment. Frailty was present in 66.6% using the CFS and participants with frailty were significantly older, with lower levels of education and literacy, greater disability, greater comorbidity, poorer cognition and higher levels of delirium. Using the FP, 57.0% of participants were classed as frail though a majority of participants (n = 159, 51.6%) could not be classified due to a high proportion of missing data., Conclusions: This study indicates that the prevalence of frailty on medical wards in northern Tanzania is high according to the CFS. However, the challenges in operationalising the FP in this setting highlight the need for future work to adapt frailty screening tools for an African context. Future investigations should also seek to correlate frailty status with long-term clinical outcomes after admission in this setting., (© 2024. The Author(s).)

Introduction: musculoskeletal (MSK) disorders account for approximately 20% of all years lived with disability worldwide however studies of MSK disorders in Africa are scarce. This pilot study aimed to estimate the community-based prevalence of MSK disorders, identify predictors, and assess the associated disability in a Tanzanian population., Methods: a cross-sectional study was conducted in one village in the Kilimanjaro region from March to June 2019. The Gait, Arms, Legs, Spine (GALS) or paediatric GALS (pGALS) examinations were used during household and school visits. Individuals positive in GALS/pGALS screening were assessed by the regional examination of the musculoskeletal system (REMS) and Modified Health Assessment Questionnaire (MHAQ)., Results: among the 1,172 individuals enrolled in households, 95 (8.1%, 95% CI: 6.6 - 9.8) showed signs of MSK disorders using the GALS/pGALS examination and 37 (3.2%, 95% CI: 2.2 - 4.3) using the REMS. Among 682 schools enrolled children, seven showed signs of MSK disorders using the GALS/pGALS examination (1.0%, 95% CI: 0.4 - 2.1) and three using the REMS (0.4%, 95% CI: 0.0 - 1.3). In the household-enrolled adult population, female gender and increasing age were associated with GALS and REMS-positive findings. Among GALS-positive adults, increasing age was associated with REMS-positive status and increasing MHAQ score., Conclusion: this Tanzanian study demonstrates a prevalence of MSK disorders and identifies predictors of MSK disorders comparable to those seen globally. These findings can inform the development of rheumatology services and interventions in Tanzania and the design of future investigations of the determinants of MSK disorders, and their impacts on health, livelihoods, and well-being., Competing Interests: The authors declare no competing interests., (Copyright: Nateiya Mmeta Yongolo et al.)

Background: Few studies have compared gait speed and its correlates among different ethnogeographic regions. The goals of this study were to describe usual and rapid gait speed, and identify their correlates across Australian, Asian, and African countries., Methods: We used data from 6 population-based cohorts of adults aged 65+ from 6 countries and 3 continents (N = 6 472), with samples ranging from 231 to 1 913. All cohorts are members of the Cohort Studies of Memory in an International Consortium collaboration. We investigated whether clinical (body mass index [BMI], hypertension, stroke, apolipoprotein status), psychological (cognition, mood, general health), and behavioral factors (smoking, drinking, physical activity) correlated with usual (N = 4 cohorts) and rapid gait speed (N = 3 cohorts) similarly across cohorts. Regression models were controlled for age, sex, and education, and were sex-stratified., Results: Age- and sex-standardized usual gait speed means ranged from 0.61 to 1.06 m/s and rapid gait speed means ranged from 1.16 to 1.64 m/s. Lower BMI and better cognitive function consistently correlated with faster gait speed in all cohorts. Less consistently, not having hypertension and greater physical activity engagement were associated with faster gait speed. Associations with mood, smoking, and drinking were largely nonsignificant. These patterns were not attenuated by demographics. There was limited evidence that the associations differed by sex, except physical activity, where the greater intensity was associated with usual gait among men but not women., Conclusions: This study is among the first to describe the usual and rapid gait speeds across older adults in Africa, Asia, and Australia., (© The Author(s) 2023. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background and Aims: Ectopic lipid storage is implicated in type 2 diabetes pathogenesis; hence, exercise to deplete stores (i.e., at the intensity that allows for maximal rate of lipid oxidation; MLO) might be optimal for restoring metabolic health. This intensity ("Fat max ") is estimated during incremental exercise ("Fat max test"). However, in "the field" general recommendations exist regarding a range of percentages of maximal heart rate (HR) to elicit MLO. The degree to which this range is aligned with measured Fat max has not been investigated. We compared measured HR at Fat max , with maximal HR percentages within the typically recommended range in a sample of 26 individuals (Female: n = 11, European ancestry: n = 17)., Methods and Results: Subjects completed a modified Fat max test with a 5-min warmup, followed by incremental stages starting at 15 W with work rate increased by 15 W every 5 min until termination criteria were reached. Pulmonary gas exchange was recorded and average values for V˙ o 2 and V˙ co 2 for the final minute of each stage were used to estimate substrate-oxidation rates. We modeled lipid-oxidation kinetics using a sinusoidal model and expressed MLO relative to peak V˙ o 2 and HR. Bland-Altman analysis demonstrated lack of concordance between HR at Fat max and at 50%, 70%, and 80% of age-predicted maximum with a mean difference of 23 b·min -1 ., Conclusion: Our results indicate that estimated "fat-burning" heart rate zones are inappropriate for prescribing exercise to elicit MLO and we recommend direct individual exercise lipid oxidation measurements to elicit these values., Competing Interests: Declaration of competing interest No conflicts of interest, financial or otherwise, are declared by the authors., (Copyright © 2023 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

To identify and evaluate differentially expressed plasma proteins in biliary atresia (BA), we performed plasma proteome profiling using liquid chromatography with tandem mass spectrometry (LC-MS/MS) in 20 patients with BA and 10 control children. Serological assays validated the most significant and highly upregulated proteins in a cohort of 45 patients and 15 controls. Bioinformatics tools were used for functional classification and protein-protein interactions of differentially expressed proteins (DEPs). Of 405 proteins detected in patients and 360 in controls, 242 proteins, each with ≥2 unique peptides (total of 3230 peptides), were common in both groups. Compared to controls, 90 proteins in patients were differentially expressed and were dysregulated. Twenty-five were significantly upregulated with polymeric immunoglobulin receptor (PIgR), galectin-3-binding protein (Gal-3BP), complement C2, the most prominent, and 15 had low expression. The bioinformatic analysis revealed functional interaction between DEPs and their role in an inflammatory immune response. Enzyme immunoassay for PIgR and Gal-3BP in patients' plasma showed their levels raised significantly (p = 0.0021 and p = 0.0369, respectively). The PIgR and Gal-3BP are novel proteins upregulated in BA and may be tested further for their utility as potential circulating disease biomarker(s). SIGNIFICANCE: The study shows that plasma PIgR and GAL-3BP levels are significantly raised in infants with BA within the first 3 months of life. If tested in a larger cohort, these proteins may be found to have their diagnostic potential and utility as disease biomarkers. The study also provides valuable information on the involvement of several DEPs in innate immune response, chronic inflammation, and fibrosis. This strengthens the hypothesis that the immune-mediated inflammatory processes are responsible for the progressive nature of BA., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Introduction: Systemic sclerosis (SSc) is a chronic multisystem autoimmune rheumatic disease of unknown etiology. Several studies have established that SSc is triggered by a dynamic interplay between genetic factors and environmental stimuli. In the present study, we aimed to study the association of human leukocyte antigen (HLA) with familial and non-familial SSc patients [limited cutaneous SSc (lcSSc) and diffuse cutaneous SSc (dcSSc)] from North India., Methods: The HLA-A, B, DRB1, and DQB1 genotyping of 150 (70 lcSSc and 80 dcSSc) adult-onset SSc patients and 150 age-gender-matched healthy controls were performed with sequence-specific oligonucleotide (SSO) typing kits using the luminex platform. HLA typing for HLA class I (A, B, and C) and II (DRB1, DQB1, and DPB1) in five North Indian families consisting of parent-child/sibling pairs affected with SSc or overlap syndrome was performed by Next Generation Sequencing (NGS) with Illumina MiniSeq., Rseults: Among the non-familial SSc patients, HLA- DRB1*11 ( P = 0.001, OR: 2.38, P c = 0.01) was identified as a risk allele, and DRB1*12 ( P = .0001, OR: 0.00, P c = 0.001) as a protective allele. There was no statistical association found with HLA-DQB1*. Also, no significant association was observed between HLA antigens and different clinical subsets (lcSSc and dcSSc) of SSc. Two cases of familial SSc patients had the DRB1*11 allele. The DRB1*12 allele was absent in all the familial SSc patients., Discussion: HLA DRB1*11 (risk allele) and DRB1*12 (protective allele) were found to be strongly associated with non-familial SSc patients and partially explain the disease's familial clustering, supporting the susceptible genetic background theory for SSc development. The study also indicates the HLA allele as a common genetic risk factor in distinct autoimmune diseases contributing to overlap syndrome or polyautoimmunity., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Machhua, Sharma, Kumar, Singh, Aggarwal, Anand, Kumar, Singh and Minz.)

ANCA-associated vasculitis (AAV) is a life-threatening disease characterized by small vessel inflammation and pathogenic self-directed antibodies. Programmed death-ligand 1 receptor (PD-1) and programmed cell death ligand-1 (PD-L1) are immune checkpoint molecules crucial for maintaining tolerance and immune homeostasis. After checkpoint inhibition therapy, development of various autoimmune diseases and immune-related adverse events (irAEs) have been observed. Here, we investigated the immunomodulatory roles of neutrophils through the expression of immune checkpoint molecule (PD-L1), migratory molecules (CXCR2), chemotactic chemokines (CXCL5) and other important molecules (BAFF and HMGB1) in development of AAV. We also scrutinized the immune mechanism responsible for development of pauci-immune crescentic GN (PICGN). We demonstrate for the first time that the frequency of PD-L1 expressing neutrophils was significantly reduced in AAV patients compared to healthy controls and correlated negatively with disease severity (BVASv3). Further, in renal biopsy, reduced PD-L1 immune checkpoint expression provides a microenvironment that unleashes uncontrolled activated CD4 + T cells, B cells, neutrophils and macrophages and ultimately causes engulfment of immune complexes leading to PICGN. Furthermore, during remission, reduced neutrophils PD-L1 and CXCR2 expression, increased neutrophils CXCL5 expression and increased peripheral effector memory T cells and increased HMGB1 and BAFF levels in serum, demonstrate the propensity for the persistence of sub-clinical inflammation, which could explain relapse, in this group of diseases., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Purpose of Review: There is a growing interest in understanding the health effects of exposure to per- and polyfluoroalkyl substances (PFAS) through the study of the human metabolome. In this systematic review, we aimed to identify consistent findings between PFAS and metabolomic signatures. We conducted a search matching specific keywords that was independently reviewed by two authors on two databases (EMBASE and PubMed) from their inception through July 19, 2022 following PRISMA guidelines., Recent Findings: We identified a total of 28 eligible observational studies that evaluated the associations between 31 different PFAS exposures and metabolomics in humans. The most common exposure evaluated was legacy long-chain PFAS. Population sample sizes ranged from 40 to 1,105 participants at different stages across the lifespan. A total of 19 studies used a non-targeted metabolomics approach, 7 used targeted approaches, and 2 included both. The majority of studies were cross-sectional ( n = 25), including four with prospective analyses of PFAS measured prior to metabolomics., Summary: Most frequently reported associations across studies were observed between PFAS and amino acids, fatty acids, glycerophospholipids, glycerolipids, phosphosphingolipids, bile acids, ceramides, purines, and acylcarnitines. Corresponding metabolic pathways were also altered, including lipid, amino acid, carbohydrate, nucleotide, energy metabolism, glycan biosynthesis and metabolism, and metabolism of cofactors and vitamins. We found consistent evidence across studies indicating PFAS-induced alterations in lipid and amino acid metabolites, which may be involved in energy and cell membrane disruption., Competing Interests: Conflict of Interest The authors declared no conflicts of interest.

Studies of depression and its outcomes in older people living with HIV (PLWH) are currently lacking in sub-Saharan Africa. This study aims to investigate the prevalence of psychiatric disorders in PLWH aged ≥ 50 years in Tanzania focussing on prevalence and 2-year outcomes of depression. PLWH aged ≥ 50 were systematically recruited from an outpatient clinic and assessed using the Mini-International Neuropsychiatric Interview (MINI). Neurological and functional impairment was assessed at year 2 follow-up. At baseline, 253 PLWH were recruited (72.3% female, median age 57, 95.5% on cART). DSM-IV depression was highly prevalent (20.9%), whereas other DSM-IV psychiatric disorders were uncommon. At follow-up (n = 162), incident cases of DSM-IV depression decreased from14.2 to 11.1% (χ 2 : 2.48, p = 0.29); this decline was not significant. Baseline depression was associated with increased functional and neurological impairment. At follow-up, depression was associated with negative life events (p = 0.001), neurological impairment (p < 0.001), and increased functional impairment (p = 0.018), but not with HIV and sociodemographic factors. In this setting, depression appears highly prevalent and associated with poorer neurological and functional outcomes and negative life events. Depression may be a future intervention target., (© 2023. The Author(s).)

Objective: The burden of stroke has increased in recent years worldwide, particularly in low-income and middle-income countries. In this study we aim to determine the number of stroke admissions, and associated comorbidities, at a referral hospital in Northern Tanzania., Design: This was a retrospective observational study., Setting: The study was conducted at a tertiary referral hospital, Kilimanjaro Christian Medical Centre (KCMC), in the orthern zone of Tanzania., Participants: The study included adults aged 18 years and above, who were admitted to the medical wards from 2017 to 2019., Outcome: The primary outcome was the proportion of patients who had a stroke admitted in the medical ward at KCMC and the secondary outcome was clinical outcome such as mortality., Methods: We conducted a retrospective audit of medical records from 2017 to 2019 for adult patients admitted to the medical ward at KCMC. Data extracted included demographic characteristics, previous history of stroke and outcome of the admission. Factors associated with stroke were investigated using logistic regression., Results: Among 7976 patients admitted between 2017 and 2019, 972 (12.2%) were patients who had a stroke. Trends show an increase in patients admitted with stroke over the 3 years with 222, 292 and 458 in 2017, 2018 and 2019, respectively. Of the patients who had a stroke, 568 (58.4%) had hypertension while 167 (17.2%) had diabetes mellitus. The proportion of admitted stroke patients aged 18-45 years, increased from 2017 (n=28, 3.4%) to 2019 (n=40, 4.3%). The in-hospital mortality related to stroke was 229 (23.6%) among 972 patients who had a stroke and female patients had 50% higher odds of death as compared with male patients (OR:1.5; CI 1.30 to 1.80)., Conclusion: The burden of stroke on individuals and health services is increasing over time, which reflects a lack of awareness on the cause of stroke and effective preventive measures. Prioritising interventions directed towards the reduction of non-communicable diseases and associated complications, such as stroke, is urgently needed., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)

Objectives: The burden of dementia is increasing in sub-Saharan Africa (SSA), but there are limited epidemiological data on dementia in SSA. This study investigated the prevalence and associations of dementia in older adults (less than 60 y) attending the outpatient department of Mount Meru Hospital in Tanzania., Methods: This one-phase cross-sectional study screened a sample using the Identification of Dementia in Elderly Africans (IDEA) cognitive screening tool. Those that screened as having possible and probable dementia were further assessed, and diagnosis of dementia was made according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV). Demographic and risk factor data were collected., Results: Within those screened, 57/1141 (5.0%) (95% CI: 3.7-6.3) had dementia. Female sex [odds ratio (OR)=2.778, 95% CI: 1.074-7.189], having never attended school (OR=6.088, 95% CI: 1.360-27.256), alcohol (U/wk) (OR=1.080, 95% CI: 1.016-1.149), uncorrected visual impairment (OR=4.260, 95% CI: 1.623-11.180), body mass index <18.5 kg/m 2 (OR=6.588, 95% CI: 2.089-20.775), and stroke (OR=15.790, 95% CI: 3.48-74.475) were found to be significantly, independently associated with dementia., Conclusions: The prevalence of dementia in this population is similar to a recent community-based rate in Tanzania and lower than a hospital-based rate in Senegal. This is the first time the association between visual impairment and dementia has been reported in SSA. Other associations are in keeping with previous literature., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: HIV-associated neurocognitive disorders (HANDs) are prevalent in older people living with HIV (PLWH) worldwide. HAND prevalence and incidence studies of the newly emergent population of combination antiretroviral therapy (cART)-treated older PLWH in sub-Saharan Africa are currently lacking. We aimed to estimate HAND prevalence and incidence using robust measures in stable, cART-treated older adults under long-term follow-up in Tanzania and report cognitive comorbidities., Design: Longitudinal study., Participants: A systematic sample of consenting HIV-positive adults aged ≥50 years attending routine clinical care at an HIV Care and Treatment Centre during March-May 2016 and followed up March-May 2017., Measurements: HAND by consensus panel Frascati criteria based on detailed locally normed low-literacy neuropsychological battery, structured neuropsychiatric clinical assessment, and collateral history. Demographic and etiological factors by self-report and clinical records., Results: In this cohort (n = 253, 72.3% female, median age 57), HAND prevalence was 47.0% (95% CI 40.9-53.2, n = 119) despite well-managed HIV disease (Mn CD4 516 (98-1719), 95.5% on cART). Of these, 64 (25.3%) were asymptomatic neurocognitive impairment, 46 (18.2%) mild neurocognitive disorder, and 9 (3.6%) HIV-associated dementia. One-year incidence was high (37.2%, 95% CI 25.9 to 51.8), but some reversibility (17.6%, 95% CI 10.0-28.6 n = 16) was observed., Conclusions: HAND appear highly prevalent in older PLWH in this setting, where demographic profile differs markedly to high-income cohorts, and comorbidities are frequent. Incidence and reversibility also appear high. Future studies should focus on etiologies and potentially reversible factors in this setting.

Background: Celiac disease (CD) is frequently associated with type I diabetes mellitus (T1D), where its diagnosis may be a challenging task. This study aims to test the usefulness of the double staining immunofluorescence (dsIF) technique for the detection of intestinal anti-tissue transglutaminase specific IgA antibody (tTG-IgA) deposits in CD and T1D children with coexisting CD., Methods: A total of 46 patients (30 cases of CD and 16 cases of T1D with CD) and 16 non-diabetic, non-celiac children were recruited. Endoscopic biopsies were taken and analyzed by light microscopy, quantitative histology (QH), and a dsIF technique., Results: Histologically, villous atrophy was most severe in CD, followed by T1D with CD, while all control biopsies except 1 were normal. QH showed a statistically significant difference in villous height (Vh), crypt depth (CrD), and Vh:CrD ratio between diabetic and non-diabetic patients with CD. dsIF technique could detect tTG-IgA deposits in 85.7% of cases of CD alone and 93.8% of biopsies from diabetic children. Surprisingly, deposits were more extensive in biopsies with minimal villous shortening. Also, all 5 biopsies from T1D patients with normal histology were dsIF positive., Conclusion: In-situ analysis of tTG-IgA immune deposits facilitates the detection of positive serology early-onset CD. Quantitative analysis may be used as an ancillary tool to increase the reliability of histological findings in these patients., Competing Interests: Declaration of competing interest None of the authors has any conflict of interest to disclose., (Copyright © 2023 Taiwan Pediatric Association. Published by Elsevier B.V. All rights reserved.)

Background: Metal exposures are associated with gut microbiome (GM) composition and function, and exposures early in development may be particularly important. Considering the role of the GM in association with many adverse health outcomes, understanding the relationship between prenatal metal exposures and the GM is critically important. However, there is sparse knowledge of the association between prenatal metal exposure and GM later in childhood., Objectives: This analysis aims to identify associations between prenatal lead (Pb) exposure and GM composition and function in children 9-11 years old., Methods: Data come from the Programming Research in Obesity, Growth, Environment and Social Stressors (PROGRESS) cohort based in Mexico City, Mexico. Prenatal metal concentrations were measured in maternal whole blood drawn during the second and third trimesters of pregnancy. Stool samples collected at 9-11 years old underwent metagenomic sequencing to assess the GM. This analysis uses multiple statistical modeling approaches, including linear regression, permutational analysis of variance, weighted quantile sum regression (WQS), and individual taxa regressions, to estimate the association between maternal blood Pb during pregnancy and multiple aspects of the child GM at 9-11 years old, adjusting for relevant confounders., Results: Of the 123 child participants in this pilot data analysis, 74 were male and 49 were female. Mean prenatal maternal blood Pb was 33.6 (SE = 2.1) ug/L and 34.9 (SE = 2.1) ug/L at second and third trimesters, respectively. Analysis suggests a consistent negative relationship between prenatal maternal blood Pb and the GM at age 9-11, including measures of alpha and beta diversity, microbiome mixture analysis, and individual taxa. The WQS analysis showed a negative association between prenatal Pb exposure and the gut microbiome, for both second and third trimester exposures (2Tβ = -0.17, 95%CI = [-0.46,0.11]; 3Tβ = -0.17, 95%CI = [-0.44,0.10]). Ruminococcus gnavus , Bifidobacterium longum , Alistipes indistinctus , Bacteroides caccae , and Bifidobacterium bifidum all had weights above the importance threshold from 80% or more of the WQS repeated holdouts in association with both second and third trimester Pb exposure., Discussion: Pilot data analysis suggests a negative association between prenatal Pb exposure and the gut microbiome later in childhood; however, additional investigation is needed., Competing Interests: MA is an employee and equity holder of Linus Biotechnology Inc., a start-up company of Mount Sinai Health System. The company develops tools for the detection of autism spectrum disorder and related conditions. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Eggers, Midya, Bixby, Gennings, Torres-Olascoaga, Walker, Wright, Arora and Téllez-Rojo.)

Objectives: To characterise mortality and functional outcome and their relationships with socioeconomic deprivation for women and men in Zanzibar., Materials and Methods: Participants in ZanStroke, a prospective observational study of patients admitted to hospital with a diagnosis of acute stroke, were followed up until one year after the stroke. The modified National Institute of Health Stroke Scale was used to assess initial stroke severity, while modified Rankin Scale (mRS) was used to assess disability at 12 months post-stroke. A multidimensional poverty index was created using individual-level data. Kaplan-Meier analysis and Cox regression model were used to examine associations of socioeconomic deprivation and death at 28 days and 12 months after stroke onset, while logistic regression analysis was used to examine associations between deprivation and functional outcome., Results: Overall mortality rate was 38.2% (CI 34.8-41.9) at 28 days, rising to 59.0% (CI 55.2-62.8) at 12 months. When adjusted for other variables, survival was higher among the least deprived (HR 0.60 CI 0.45-0.80), an association that was strongly significant for women (HR 0.46 CI 0.29-0.74). Among 12-month survivors 45.1% (n = 122) had no/low level of disability (mRS 0-2), while 22.9% (n = 62) were unable to walk independently or at all. No difference between socioeconomic deprivation and outcome was seen at one year., Conclusion: Case-fatality rates were high, and socioeconomic disparities were evident even during the acute stroke phase. Policies are needed to reduce significant health disparities, adapt evidence-based interventions, and promote equitable access to stroke care and rehabilitation., Competing Interests: Declaration of Competing Interest KKN is employed at Steno Diabetes Center Copenhagen, a public hospital and research institution under the Capital Region of Denmark, which is partly funded by a grant from the Novo Nordisk Foundation. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Autoimmune hepatitis (AIH) is a chronic and progressive disease of the liver. This is a multifactorial autoimmune disease with both environmental factors and genetic factors playing a role in its pathogenesis. Certain environmental agents like viruses, drugs, etc., can trigger the disease in a genetically susceptible individual. The present study was aimed to explore the distribution of human leukocyte antigen (HLA)-DRB1, Protein tyrosine phosphatase non-receptor type 22 (PTPN22) and Cytotoxic T-Lymphocyte-associated protein 4 (CTLA-4) polymorphisms in North Indian adult AIH patients and their associations with clinical and pathological characteristics associated with the disease. A total of 147 subjects with 47 cases and 100 healthy controls were enrolled. Diagnosis of AIH was made by Revised International Autoimmune Hepatitis Group scoring system. HLA-DRB1 Typing was done by Luminex-based reverse Sequence-Specific Oligonucleotide Probing (SSOP). Single nucleotide variant (SNV) genotyping for CTLA-4 and PTPN22 was done by simple probe-based SNP arrays. Results indicated SLA positive AIH patients are poor responders to therapy. A significant predispositional association of HLA-DRB1*03 was observed in AIH patients from the North Indian population (p= 0.0001, OR=4.83 (2.30-10.15). The frequency of the GG genotype of CTLA-4 CT 60 was significantly increased in AIH patients compared to controls. Multinomial analysis showed that CTLA-4 CT 60 is an independent predictor for cases., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Ahuja, Singh, Minz, Anand, Das and Taneja.)