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Background/objectives: Qualitative research can be laborious and time consuming, presenting a challenge for practitioners and policymakers seeking rapid, actionable results. Data collection, transcription and analysis are the main contributors to the resource-intensive nature. OpenAI's Chat Generative Pre-trained Transformer (ChatGPT), have demonstrated potential to aid in data analysis. Our study aimed to compare themes generated by ChatGPT (3.5 and 4.0) with traditional human analysis from in-depth interviews., Methods: Three transcripts from an evaluation study to understand patients' experiences at a community eye clinic were used. Transcripts were first analysed by an independent researcher. Next, specific aims, instructions and de-identified transcripts were uploaded to ChatGPT 3.5 and ChatGPT 4.0. Concordance in the themes was calculated as the number of themes generated by ChatGPT divided by the number of themes generated by the researcher. The number of unrelated subthemes and time taken by both ChatGPT were also described., Results: The average time taken per transcript was 11.5 min, 11.9 min and 240 min for ChatGPT 3.5, ChatGPT 4.0 and researcher respectively. Six themes were identified by the researcher: (i) clinic's accessibility, (ii) patients' awareness, (iii) trust and satisfaction, (iv) patients' expectations, (v) willingness to return and (vi) explanation of the clinic by referral source. Concordance for ChatGPT 3.5 and 4.0 ranged from 66 to 100%., Conclusion: Preliminary results showed that ChatGPT significantly reduced analysis time with moderate to good concordance compared with current practice. This highlighted the potential adoption of ChatGPT to facilitate rapid preliminary analysis. However, regrouping of subthemes will still need to be conducted by a researcher., (© 2024. The Author(s), under exclusive licence to The Royal College of Ophthalmologists.)

This study aimed to evaluate the effects of a cafeteria diet and caloric restriction on behavioral and metabolic profiles of adult male Wistar rats. The rats were randomly divided into three groups (n = 12/group) and from 10 weeks of age fed either ad libitum standard rat chow (control group), ad libitum cafeteria diet in addition to standard chow (diet-induced obesity (DIO) group) or kept on caloric restriction (at 85% weight of controls; restricted group) for a period of 12 weeks. Body weight was assessed twice per week and glucose levels were measured at three times during the 12-week period. At week 11 the animals were behaviorally profiled using the multivariate concentric square field™ (MCSF) test. After 12 weeks of diet the animals were euthanized, blood collected, relative organ weights were assessed and plasma or serum levels of insulin, glucose, and lipid profile were measured. The DIO group gained 23% more weight than the control group (p < 0.001) and increased adipose tissue weight in comparison to the control (p < 0.001) and restricted (p < 0.001) groups. Glucose was significantly increased (p < 0.001) only during the second measurement at week 7 and insulin levels were elevated in the DIO group compared to controls and restricted groups (p < 0.01; p < 0.001, respectively). Plasma cholesterol levels were reduced for both DIO (p < 0.01) and restricted (p < 0.001) groups relative to controls. Adiponectin and leptin levels were higher for the DIO group in comparison to both the control (p < 0.001; p < 0.05) and restricted (p < 0.001; p < 0.001) groups. Thus, the two diets led to significant changes in body weight gain, adiposity, and metabolism. However, they did not alter the behavioral profiles in the MCSF test, suggesting that activity, exploration, risk assessment, risk taking or shelter seeking remained unaffected by the dietary interventions. The current findings suggest that an increase or reduction in energy intake resulted in no behavioral effects, despite the accompanying glycemic alterations potentially related to diabetes development., Competing Interests: Declaration of competing interest The authors declare that there are no commercial or financial relationships that could be seen as potential conflicts of interest in conducting this research., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objective: Previous research points to a role of the brain in the regulation of glucose and pathogenesis of type 2 diabetes (T2D) via modulation of counter-regulatory hormone secretion and activity in the autonomic nervous system (ANS). The aim of this study was to investigate glucose-dependent responses of catecholamines and ANS activity in individuals with T2D, prediabetes (PD), and normoglycemia (NG)., Design: Cross-sectional., Methods: Individuals with T2D (n = 19, 7 men, HbA1c 49 mmol/mol), PD (n = 18, 8 men), and NG (n = 17, 3 men) underwent 1 stepwise hyperinsulinemic-euglycemic-hypoglycemic and 1 hyperglycemic clamp with repeated measurements of catecholamines, symptoms, heart rate variability (HRV), and hemodynamics., Results: The hypoglycemic response of adrenaline was augmented in T2D and PD vs NG (both P < .05), and there was a strong association with insulin resistance (P < .05 for M-value). In relation to achieved glucose levels in both clamps, noradrenaline exhibited a steeper rise during hypoglycemia in T2D vs NG and PD (both P < .05). There were trends toward more marked autonomic hypoglycemic symptoms in T2D vs PD and NG. By contrast, insulin resistance was associated with attenuated responses of heart rate and HRV indices PLF and PHF at the target glucose plateau of 2.7 mmol/L (P < .05), independent of BMI and HbA1c., Conclusion: Alterations in glucose-dependent responses of counter-regulatory hormones and the ANS appear before, and probably contribute to, the onset of T2D. Together with other reported alterations in neuroendocrine pathways, the findings suggest that a maladaptation of the brain's responses to glucose fluctuations is important in T2D progression., Competing Interests: Conflict of interest: The authors have no conflicts of interest to declare in relation to the current work., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Society of Endocrinology.)

Retroviruses can be detected by the innate immune sensor cyclic GMP-AMP synthase (cGAS), which recognizes reverse-transcribed DNA and activates an antiviral response. However, the extent to which HIV-1 shields its genome from cGAS recognition remains unclear. To study this process in mechanistic detail, we reconstituted reverse transcription, genome release, and innate immune sensing of HIV-1 in a cell-free system. We found that wild-type HIV-1 capsids protect viral genomes from cGAS even after completing reverse transcription. Viral DNA could be "deprotected" by thermal stress, capsid mutations, or reduced concentrations of inositol hexakisphosphate (IP6) that destabilize the capsid. Strikingly, the capsid inhibitor lenacapavir also disrupted viral cores and dramatically potentiated cGAS activity, both in vitro and in cellular infections. Our results provide biochemical evidence that the HIV-1 capsid lattice conceals the genome from cGAS and that chemical or physical disruption of the viral core can expose HIV-1 DNA and activate innate immune signaling., Competing Interests: Competing interests: The authors declare no competing interests.

Cyanobacteria are photosynthetic prokaryotes that play an important role in the ecology of aquatic ecosystems. However, they can also produce toxins with negative effects on aquatic organisms, wildlife, livestock, domestic animals, and humans. With the increasing global temperatures, urban parks, renowned for their multifaceted contributions to society, have been largely affected by blooms of toxic cyanobacteria. In this work, the toxicity of two different stages of development of a cyanobacterial bloom from a city park was assessed, evaluating mortality, hatching, development, locomotion (total distance, slow and rapid movements, and path angles) and biochemical parameters (oxidative stress, neurological damage, and tissue damage indicators) in zebrafish embryos/larvae ( Danio rerio ). Results showed significant effects for the samples with more time of evolution at the developmental level (early hatching for low concentrations (144.90 mg/L), delayed hatching for high concentrations (significant values above 325.90 mg/L), and delayed development at all concentrations), behavioral level (hypoactivity), and biochemical level (cholinesterase (ChE)) activity reduction and interference with the oxidative stress system for both stages of evolution). This work highlights the toxic potential of cyanobacterial blooms in urban environments. In a climate change context where a higher frequency of cyanobacterial proliferation is expected, this topic should be properly addressed by competent entities to avoid deleterious effects on the biodiversity of urban parks and poisoning events of wildlife, pets and people.

Objective: The objective was to study metabolic characteristics and transcriptome of renal sinus adipose tissue (RSAT) located around renal arteries and veins., Methods: Adipose tissue biopsies from RSAT, omental (OAT), and subcutaneous (SAT) depots were obtained from healthy kidney donors (20 female, 20 male). Adipocyte glucose uptake rate and cell size were measured, and gene expression analyses using transcriptomics were performed., Results: RSAT adipocytes were significantly smaller, with a higher basal glucose uptake rate, than adipocytes from SAT and OAT. Transcriptomic analyses revealed 29 differentially expressed genes between RSAT and OAT (RSAT: 23 lower, 6 higher) and 1214 differentially expressed genes between RSAT and SAT (RSAT: 859 lower, 355 higher). RSAT demonstrated molecular resemblance to OAT, both exhibiting lower metabolic gene expression and higher expression of immune-related pathways, including IL-17, TNFα, and NF-κB signaling than SAT. Weighted gene coexpression network analysis associated RSAT with immune response and nucleic acid transport processes. Despite its location near the renal hilum, RSAT closely resembled OAT and there was a lack of expression in the classical brown adipose tissue genes. Gene enrichment analyses suggest an inflammatory environment in RSAT compared with SAT and, to some extent, OAT., Conclusions: The findings suggest specific RSAT functions that could impact renal function and, possibly, the development of renal and cardiometabolic disorders., (© 2024 The Author(s). Obesity published by Wiley Periodicals LLC on behalf of The Obesity Society.)

T cells play critical roles in adipose tissue (AT) inflammation. The role of CD20 + T cell in AT dysfunction and their contributing to insulin resistance (IR) and type 2 diabetes progression, is not known. The aim was to characterize CD20 + T cells in omental (OAT), subcutaneous (SAT) and peripheral blood (PB) from subjects with obesity (OB, n = 42), by flow cytometry. Eight subjects were evaluated before (T1) and 12 months post (T2) bariatric/metabolic surgery (BMS). PB from subjects without obesity (nOB, n = 12) was also collected. Higher percentage of CD20 + T cells was observed in OAT, compared to PB or SAT, in OB-T1. CD20 expression by PB CD4 + T cells was inversely correlated with adiposity markers, while follicular-like CD20 + T cells were positively correlated with impaired glucose tolerance (increased HbA1c). Notably, among OB-T1, IR establishment was marked by a lower percentage and absolute number of PB CD20 + T cells, compared nOB. Obesity was associated with higher percentage of activated CD20 + T cells; however, OAT-infiltrated CD20 + T cells from OB-T1 with diabetes displayed the lowest activation. CD20 + T cells infiltrating OAT from OB-T1 displayed a phenotype towards IFN-γ-producing Th1 and Tc1 cells. After BMS, the percentage of PB CD4 + CD20 + T cells increased, with reduced Th1 and increased Th17 phenotype. Whereas in OAT the percentage of CD20 + T cells with Th1/17 and Tc1/17 phenotypes increased. Interestingly, OAT from OB pre/post BMS maintained higher frequency of effector memory CD20 + T cells. In conclusion, CD20 + T cells may play a prominent role in obesity-related AT inflammation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

The association of health-related productivity loss (HRPL) with social isolation and depressive symptoms is not well studied. We aimed to examine the association of social isolation and depressive symptoms with productivity loss. Data on employed adults aged 21 years and above were derived from the Population Health Index (PHI) study conducted by the National Healthcare Group (NHG) on community-dwelling adults, residing in the Central and Northern residential areas of Singapore. The severity of depressive symptoms and social isolation were assessed using the 9-item Patient Health Questionnaire (PHQ-9) and Lubben Social Network Scale-6 (LSNS-6) respectively. Productivity loss was assessed using the Work Productivity and Activity Impairment Questionnaire (WPAI). We used Generalised Linear Models, with family gamma, log link for the analysis. Models were adjusted for socio-demographic variables (including age, gender, ethnicity, employment status, housing type) and self-reported chronic conditions (including the presence of diabetes, hypertension, and dyslipidemia). There were 2,605 working (2,143 full-time) adults in this study. The median reported percentage of unadjusted productivity loss was 0.0%, 10.0% and 20.0% for participants with social isolation, depressive symptoms, and both, respectively. In the regression analysis, mean productivity loss scores were 2.81 times (95% Confidence Interval: 2.12, 3.72) higher in participants with depressive symptoms than those without. On the other hand, social isolation was not found to be associated with productivity loss scores (1.17, 95% Confidence Interval: 0.96, 1.42). The interaction term of depressive symptoms with social isolation was statistically significant, with an effect size of 1.89 (95% Confidence Interval: 1.04, 3.44). It appeared that productivity loss was amplified when social isolation and depressive symptoms were concomitant. Our results suggested significant associations of social isolation and depressive symptoms with productivity loss. These findings highlighted the potential impact of social isolation and depressive symptoms on work performance and drew attention to the importance of having a holistic work support system that promotes social connectedness, mental wellbeing and work productivity., (© 2024. The Author(s).)

Background: Diabetes and prediabetes are diagnosed differentially by Western and Chinese medicine. While Western medicine uses objective laboratory analysis of biochemical parameters to define the severity of diabetes and prediabetes, Chinese medicine uses a comprehensive approach that integrates observation, inquiry, pulse palpation, and tongue diagnosis. The medical information collected is then categorized into different syndromes. However, traditional methods of pulse and tongue diagnoses used to determine syndrome differentiation are highly subjective and skill dependent., Objective: This study aims to identify the gap in conventional traditional Chinese medicine (TCM) diagnostic techniques for syndrome differentiation analysis using contemporary diagnostic devices. We devised a protocol for a nonrandomized, exploratory, observational case-control study with equal allocations in 5 arms to investigate the syndrome differentiation of diabetes and prediabetes. We hypothesize that the TCM syndrome differentiation of diabetes and prediabetes in the tropical climate may differ from that defined based on the Chinese demographic. We also speculate that the high-frequency spectral energy may reflect a difference in pulse wave intensity and density between the healthy and diabetes groups., Methods: A total of 250 eligible participants will be equally assigned to 1 of 5 arms (healthy or subhealthy, prediabetes, diabetes, prediabetes with hypertension and dyslipidemia, and diabetes with hypertension and dyslipidemia). Participants aged 21-75 years, of any sex or race, and have been diagnosed with diabetes (fasting plasma glucose [FPG] of 7 mmol/L, or 2-hour plasma glucose [2hPG] of 11.1 mmol/L) or prediabetes (impaired FPG of 6.1-6.9 mmol/L, or impaired glucose tolerance with an 2hPG of 7.8-11 mmol/L) will be included. The Health Evaluation Questionnaire, Physical Activity Questionnaire, sugar intake assessment, Constitution in Chinese Medicine Questionnaire, radial pulse diagnosis, and tongue diagnosis will be performed in a single visit. ANOVA for continuous data and chi-square tests of independence will be used for categorical data assessments, with a level of P<.05 considered significant., Results: The recruitment is in progress. We anticipate that the study will conclude in June 2025. As of July 15, 2024, we have enrolled 140 individuals., Conclusions: To the best of our knowledge, this is the first study to use contemporary TCM diagnostic instruments to map expert and empirical knowledge of TCM to its scientific equivalents for the purpose of evaluating the syndrome differentiation of diabetes. We designed this protocol with the exploratory goal to examine objectively the syndrome differentiation of patients with diabetes and those with prediabetes using TCM diagnostic technologies. The data collected and evaluated under standardized conditions using these contemporary diagnostic devices will exhibit a higher degree of stability, hence yielding dependable and unbiased results for syndrome differentiation. Thus, our findings may potentially increase the accuracy of identification, diagnosis, treatment, and prevention of diabetes and prediabetes through a system of targeted treatment., Trial Registration: ClinicalTrials.gov NCT05563090; https://clinicaltrials.gov/ct2/show/NCT05563090., International Registered Report Identifier (irrid): DERR1-10.2196/56024., (©Hui Ping Ng, Shu Yun Chong, Yi Huan Li, Tong Hwee Goh, Ka Yii Pang, Michelle Jessica Pereira, Chin-Ming Huang. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 12.09.2024.)

Material thermal conductivity is a key factor in various applications, from thermal management to energy harvesting. With microstructure engineering being a widely used method for customizing material properties, including thermal properties, understanding and controlling the role of extended phonon-scattering defects, like grain boundaries, is crucial for efficient material design. However, systematic studies are still lacking primarily due to limited tools. In this study, we demonstrate an approach for measuring grain boundary thermal resistance by probing the propagation of thermal waves across grain boundaries with a temperature-sensitive scanning probe. The method, implemented with a spatial resolution of about 100 nm on finely grained Nb-substituted SrTiO 3 ceramics, achieves a detectability of about 2 × 10 -8 K m 2 W -1 , suitable for chalcogenide-based thermoelectrics. The measurements indicated that the thermal resistance of the majority of grain boundaries in the STiO 3 ceramics is below this value. While there are challenges in improving sensitivity, considering spatial resolution and the amount of material involved in the detection, the sensitivity of the scanning probe method is comparable to that of optical thermoreflectance techniques, and the method opens up an avenue to characterize thermal resistance at the level of single grain boundaries and domain walls in a spectrum of microstructured materials.

Objective: To compare the clinical and cost effectiveness of the Collaborative Model of Care between Orthopaedics and Allied Healthcare Professionals (CONNACT), a community-based, stratified, multidisciplinary intervention consisting of exercise, education, psychological and nutrition delivered through a chronic care model to usual hospital care in adults with knee osteoarthritis (OA)., Methods: Pragmatic, parallel-arm, single-blinded superiority RCT trial. Community-dwelling, ambulant adults with knee OA (Kellgren-Lawrence grade > 1; Knee Injury and OA Outcome Score (KOOS 4 ) ≤75) were enrolled. Primary outcome was KOOS 4 at 12-months; secondary outcomes included: quality of life, physical performance measures, symptom satisfaction, psychological outcomes, dietary habits, and global perceived effect. Intention-to-treat analysis using generalized linear model (GLM) and regression modeling were conducted. Economic evaluation through a societal approach was embedded., Results: 110 participants (55 control, 55 intervention) were randomized. No between-group difference found for the primary outcome (MD [95%CI]: -1.86 [-9.11. 5.38]), although both groups demonstrated within-group improvement over 12-months. Among the secondary outcomes, the CONNACT group demonstrated superior dietary change (12 months) and physical performance measures (3 months), and global perceived effect (6 months). While there was no between-group difference in total cost, significant productivity gains (reduced indirect cost) were seen in the CONNACT group., Conclusion: CONNACT was not superior to usual care at 1 year. Further efforts are needed to understand the underlying contextual and implementation factors in order to further improve and refine such community-based, stratified care models moving forward., Trial Registration: Clinicaltrials.gov Identifier: NCT03809975. Registered January 18, 2019. https://clinicaltrials.gov/ct2/show/NCT03809975., (Copyright © 2024 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

The global prevalence of Type 2 Diabetes (T2D) poses significant public health challenges due to its associated severe complications. Insulin resistance is central to T2D pathophysiology, particularly affecting adipose tissue function. This cross-sectional observational study investigates metabolic alterations in subcutaneous adipose tissue (SAT) associated with T2D to identify potential therapeutic targets. We conducted a comprehensive metabolomic analysis of SAT from 40 participants (20 T2D, 20 ND-T2D), matched for sex, age, and BMI (Body Mass Index). Metabolite quantification was performed using GC/MS and LC/MS/MS platforms. Correlation analyses were conducted to explore associations between metabolites and clinical parameters. We identified 378 metabolites, including significant elevations in TCA cycle (tricarboxylic acid cycle) intermediates, branched-chain amino acids (BCAAs), and carbohydrates, and a significant reduction in the nucleotide-related metabolites in T2D subjects compared to those without T2D. Obesity exacerbated these alterations, particularly in amino acid metabolism. Adipocyte size negatively correlated with BCAAs, while adipocyte glucose uptake positively correlated with unsaturated fatty acids and glycerophospholipids. Our findings reveal distinct metabolic dysregulation in adipose tissue in T2D, particularly in energy metabolism, suggesting potential therapeutic targets for improving insulin sensitivity and metabolic health. Future studies should validate these findings in larger cohorts and explore underlying mechanisms to develop targeted interventions.

Aims/hypothesis: Obesity surgery (OS) and diet-induced weight loss rapidly improve insulin resistance. We aim to investigate the impact of either Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG) surgery compared with a diet low in energy (low-calorie diet; LCD) on body composition, glucose control and insulin sensitivity, assessed both at the global and tissue-specific level in individuals with obesity but not diabetes., Methods: In this parallel group randomised controlled trial, patients on a waiting list for OS were randomised (no blinding, sealed envelopes) to either undergo surgery directly or undergo an LCD before surgery. At baseline and 4 weeks after surgery (n=15, 11 RYGB and 4 SG) or 4 weeks after the start of LCD (n=9), investigations were carried out, including an OGTT and hyperinsulinaemic-euglycaemic clamps during which concomitant simultaneous whole-body [ 18 F]fluorodeoxyglucose-positron emission tomography (PET)/MRI was performed. The primary outcome was HOMA-IR change., Results: One month after bariatric surgery and initiation of LCD, both treatments induced similar reductions in body weight (mean ± SD: -7.7±1.4 kg and -7.4±2.2 kg, respectively), adipose tissue volume (7%) and liver fat content (2% units). HOMA-IR, a main endpoint, was significantly reduced following OS (-26.3% [95% CI -49.5, -3.0], p=0.009) and non-significantly following LCD (-20.9% [95% CI -58.2, 16.5). For both groups, there were similar reductions in triglycerides and LDL-cholesterol. Fasting plasma glucose and insulin were also significantly reduced only following OS. There was an increase in glucose AUC in response to an OGTT in the OS group (by 20%) but not in the LCD group. During hyperinsulinaemia, only the OS group showed a significantly increased PET-derived glucose uptake rate in skeletal muscle but a reduced uptake in the heart and abdominal adipose tissue. Both liver and brain glucose uptake rates were unchanged after surgery or LCD. Whole-body glucose disposal and endogenous glucose production were not significantly affected., Conclusions/interpretation: The short-term metabolic effects seen 4 weeks after OS are not explained by loss of body fat alone. Thus OS, but not LCD, led to reductions in fasting plasma glucose and insulin resistance as well as to distinct changes in insulin-stimulated glucose fluxes to different tissues. Such effects may contribute to the prevention or reversal of type 2 diabetes following OS. Moreover, the full effects on whole-body insulin resistance and plasma glucose require a longer time than 4 weeks., Trial Registration: ClinicalTrials.gov NCT02988011 FUNDING: This work was supported by AstraZeneca R&D, the Swedish Diabetes Foundation, the European Union's Horizon Europe Research project PAS GRAS, the European Commission via the Marie Sklodowska Curie Innovative Training Network TREATMENT, EXODIAB, the Family Ernfors Foundation, the P.O. Zetterling Foundation, Novo Nordisk Foundation, the Agnes and Mac Rudberg Foundation and the Uppsala University Hospital ALF grants., (© 2024. The Author(s).)

Bats are a diverse and ecologically important group of mammals that exhibit remarkable diversity in their feeding habits. These diverse feeding habits are thought to be reflected in the composition and function of their gut microbiota, which plays important roles in nutrient acquisition, immune function, and overall health. Despite the rich biodiversity of bat species in South America, there is a lack of microbiome studies focusing on bats from this region. Such studies could offer major insights into conservation efforts and the preservation of biodiversity in South America. In this work, we aimed to compare the gut microbiota of four bat species with different feeding habits from Southern Brazil, including nectarivorous, frugivorous, insectivorous, and hematophagous bats. Our findings demonstrate that feeding habits can have a significant impact on the diversity and composition of bat gut microbiotas, with each species exhibiting unique metabolic potentials related to their dietary niches. In addition, the identification of potentially pathogenic bacteria suggests that the carriage of microbial pathogens by bats may vary, depending on feeding habits and host-specific factors. These findings provide novel insights into the relationship between bat feeding habits and gut microbiota composition, highlighting the need to promote diverse habitats and food sources to support these ecologically important species.

CD20 + T cells constitute a small subset of T cells. These are found among CD4 + , CD8 + , CD4 + CD8 + , CD4 - CD8 - T, and TCRγδ + T cells, and have been poorly characterized. The aim of this study was to characterize peripheral blood (PB) CD20 + T cells and compare them to their PB CD20 - T cell counterparts. PB from 17 healthy individuals was collected. The distribution of CD20 + T cells among maturation-associated T cells compartments (naïve, central memory, transitional memory, effector memory, and effector T cells), their polarization, activation status, and expression of immune-regulatory proteins were evaluated by flow cytometry. Their function was also assessed, by measuring IFN-γ, TNF-α, and IL-17 production. Compared with CD20 - T cells, CD20 + T cells represent a higher proportion of transitional memory cells. Furthermore, CD20 + T cells display a proinflammatory phenotype, characterized by the expansion of Th1, Th1/17, and Tc1 cell subsets , associated to a high expression of activation (CD25) and exhaustion (PD-1) markers. In addition, the simultaneous production of the proinflammatory cytokines IFN-γ, TNF-α, and IL-17 was also detected in CD4 + CD20 + T cells. Our results show that CD20 + T cells are phenotypically and functionally different from CD20 - T cells, suggesting that these cells are a distinct subset of T cells., (© 2024 The Authors. Cytometry Part B: Clinical Cytometry published by Wiley Periodicals LLC on behalf of International Clinical Cytometry Society.)

Background: Knee osteoarthritis (KOA) is one of most prevalent and fastest-growing causes of pain, impaired mobility, and poor quality of life in the rapidly aging population worldwide. There is a lack of high-quality evidence on the efficacy of traditional Chinese medicine (TCM), particularly acupuncture, and a lack of KOA practice guidelines that are tailored to unique population demographics and tropical climates., Objective: Our HARMOKnee (Heat and Acupuncture to Manage Osteoarthritis of the Knee) trial aims to address these gaps by evaluating the short- and medium-term clinical and cost-effectiveness of acupuncture with heat therapy in addition to standard care, compared to standard care alone. Through a robust process and economic evaluation, we aim to inform evidence-based practice for patients with KOA to facilitate the large-scale implementation of a comprehensive and holistic model of care that harmonizes elements of Western medicine and TCM. We hypothesize that acupuncture with heat therapy as an adjunct to standard care is clinically more effective than standard care alone., Methods: A multicenter, pragmatic, parallel-arm, single-blinded, effectiveness-implementation hybrid randomized controlled trial will be conducted. We intend to recruit 100 patients with KOA randomized to either the control arm (standard care only) or intervention arm (acupuncture with heat therapy, in addition to standard care). The inclusion criteria are being a community ambulator and having primary KOA, excluding patients with secondary arthritis or previous knee replacements. The primary outcome measure is the Knee Osteoarthritis Outcome Score at 6 weeks. Secondary outcome measures include psychological, physical, quality of life, satisfaction, and global outcome measures at 6, 12, and 26 weeks. A mixed method approach through an embedded process evaluation will facilitate large-scale implementation. An economic evaluation will be performed to assess financial sustainability., Results: Patient enrollment has been ongoing since August 2022. The recruitment process is anticipated to conclude by July 2024, and the findings will be analyzed and publicized as they are obtained. As of November 6, 2023, our patient enrollment stands at 65 individuals., Conclusions: The findings of our HARMOKnee study will contribute substantial evidence to the current body of literature regarding the effectiveness of acupuncture treatment for KOA. Additionally, we aim to facilitate the creation of standardized national guidelines for evidence-based practice that are specifically tailored to our unique population demographics. Furthermore, we seek to promote the adoption and integration of acupuncture and heat therapy into existing treatment models., Trial Registration: ClinicalTrials.gov NCT05507619; https://clinicaltrials.gov/study/NCT05507619., International Registered Report Identifier (irrid): DERR1-10.2196/54352., (©Bryan Yijia Tan, Chun Yue Tan, Tong Leng Tan, Su-Yin Yang, Gillian Long Szu Chew, Siang Ing Tan, Yu Chun Chua, Yew Wai Yan, Derrick Bing Quan Soh, Tong Hwee Goh, Pu Jue Ng, Yee Teck Ng, Swee Boey Kuan, Bo Siang Teo, Keng He Kong, Michelle Jessica Pereira, Hui Ping Ng. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 03.04.2024.)

The Serra da Estrela Natural Park (NPSE) in Portugal stands out as a well-preserved region abundant in medicinal plants, particularly known for their pharmaceutical applications in diabetes prevention and treatment. This comprehensive review explores these plants' botanical diversity, traditional uses, pharmacological applications, and chemical composition. The NPSE boast a rich diversity with 138 medicinal plants across 55 families identified as traditionally and pharmacologically used against diabetes globally. Notably, the Asteraceae and Lamiaceae families are prevalent in antidiabetic applications. In vitro studies have revealed their significant inhibition of carbohydrate-metabolizing enzymes, and certain plant co-products regulate genes involved in carbohydrate metabolism and insulin secretion. In vivo trials have demonstrated antidiabetic effects, including glycaemia regulation, insulin secretion, antioxidant activity, and lipid profile modulation. Medicinal plants in NPSE exhibit various activities beyond antidiabetic, such as antioxidant, anti-inflammatory, antibacterial, anti-cancer, and more. Chemical analyses have identified over fifty compounds like phenolic acids, flavonoids, terpenoids, and polysaccharides responsible for their efficacy against diabetes. These findings underscore the potential of NPSE medicinal plants as antidiabetic candidates, urging further research to develop effective plant-based antidiabetic drugs, beverages, and supplements.

Background: Proximal humerus fractures are common osteoporotic fractures. Postinjury outcome measures include objective clinician-measured range of motion (ROM) and subjective patient-reported outcome measures (PROMs), but the relationship between both has not been established. This study aimed to determine the relationship between shoulder ROM and PROMs and establish which ROMs correlated most with PROMs., Methods: A prospective cohort study was conducted on patients with acute proximal humerus fractures. Surgical intervention, open or pathological fractures, neurovascular compromise, polytrauma, or delayed presentations were excluded. Correlation and regression analyses between active ROM and PROMs (Quick Disabilities of Arm, Shoulder and Hand [QuickDASH] and Oxford Shoulder Score [OSS]) at 1-year postinjury were explored. ROM cutoffs predicting satisfactory PROM scores were established., Results: Fifty-five patients were recruited. Moderate correlations were observed between PROMs and flexion, extension, and abduction, but not internal and external rotation. Multivariate analysis showed significant relationships between PROMs and flexion [QuickDASH: adjusted coefficient (AC): -0.135, P  = .013, OSS: AC: 0.072, P  = .002], abduction [QuickDASH: AC: -0.115, P  = .021, OSS: AC: 0.059, P  = .005], and extension [QuickDASH: AC: -0.304, P  = .020] adjusting for age, gender, Neer classification, injury on dominant side, and employment. Achieving 130° flexion, 59° extension, and 124° abduction were correlated with satisfactory OSS/QuickDASH scores, respectively., Conclusion: Overall, holistic assessment of outcomes with both subjective and objective outcomes are necessary, as shoulder flexion, extension, and abduction are only moderately correlated with PROMs. Attaining 130° flexion, 59° extension, and 124° abduction corresponded with satisfactory functional outcomes measured by OSS/QuickDASH and can guide rehabilitation., (© 2024 The Authors.)

Low-grade inflammation is closely linked to obesity and obesity-related comorbidities; therefore, immune cells have become an important topic in obesity research. Here, we performed a deep phenotypic characterization of circulating T cells in people with obesity, using flow cytometry. Forty-one individuals with obesity (OB) and clinical criteria for bariatric surgery were enrolled in this study. We identified and quantified 44 different circulating T cell subsets and assessed their activation status and the expression of immune-checkpoint molecules, immediately before (T1) and 7-18 months after (T2) the bariatric surgery. Twelve age- and sex-matched healthy individuals (nOB) were also recruited. The OB participants showed higher leukocyte counts and a higher percentage of neutrophils. The percentage of circulating Th1 cells were negatively correlated to HbA1c and insulin levels. OB Th1 cells displayed a higher activation status and lower PD-1 expression. The percentage of Th17 and Th1/17 cells were increased in OB, whereas the CD4 + Tregs' percentage was decreased. Interestingly, a higher proportion of OB CD4 + Tregs were polarized toward Th1- and Th1/17-like cells and expressed higher levels of CCR5. Bariatric surgery induced the recovery of CD4 + Treg cell levels and the expansion and activation of Tfh and B cells. Our results show alterations in the distribution and phenotype of circulating T cells from OB people, including activation markers and immune-checkpoint proteins, demonstrating that different metabolic profiles are associated to distinct immune profiles, and both are modulated by bariatric surgery.

Purpose: To evaluate the dopaminergic signaling in human adipose tissue in the context of obesity and type 2 diabetes (T2D) and potential direct implications in adipose tissue metabolism., Methods: mRNA and protein expression of dopamine receptors D1 and D2 (DRD1 and DRD2) were determined in subcutaneous adipose tissue from subjects without or with T2D and with different body weight, and correlated with markers of obesity, hyperglycemia, and insulin resistance. Glucose uptake and lipolysis were measured in adipocytes ex vivo following short-term exposure to dopamine, DRD1 receptor agonist (SKF81297), or DRD2 receptor agonist (bromocriptine)., Results: DRD1 and DRD2 gene expression in subcutaneous adipose tissue correlated positively with clinical markers of insulin resistance (e.g. HOMA-IR, insulin, and triglycerides) and central obesity in subjects without T2D. Protein expression of DRD2 in subcutaneous adipose tissue, but not DRD1, is higher in subjects with impaired fasting glucose and T2D and correlated positively with hyperglycemia, HbA1c, and glucose AUC, independent of obesity status. DRD1 and DRD2 proteins were mainly expressed in adipocytes, compared to stromal vascular cells. Dopamine and dopaminergic agonists did not affect adipocyte glucose uptake ex vivo, but DRD1 and DRD2 agonist treatment inhibited isoproterenol-stimulated lipolysis., Conclusion: The results suggest that protein expression of DRD2 in subcutaneous adipose tissue is up-regulated with hyperglycemia and T2D. Whether DRD2 protein levels contribute to T2D development or occur as a secondary compensatory mechanism needs further investigation. Additionally, dopamine receptor agonists inhibit adipocyte beta-adrenergic stimulation of lipolysis, which might contribute to the beneficial effects in lipid metabolism as observed in patients taking bromocriptine., (© 2023. The Author(s).)

During the SARS-CoV-2 pandemic, governments and public health authorities collected massive amounts of data on daily confirmed positive cases and incidence rates. These data sets provide relevant information to develop a scientific understanding of the pandemic's spatiotemporal dynamics. At the same time, there is a lack of comprehensive approaches to describe and classify patterns underlying the dynamics of COVID-19 incidence across regions over time. This seriously constrains the potential benefits for public health authorities to understand spatiotemporal patterns of disease incidence that would allow for better risk communication strategies and improved assessment of mitigation policies efficacy. Within this context, we propose an exploratory statistical tool that combines functional data analysis with unsupervised learning algorithms to extract meaningful information about the main spatiotemporal patterns underlying COVID-19 incidence on mainland Portugal. We focus on the timeframe spanning from August 2020 to March 2022, considering data at the municipality level. First, we describe the temporal evolution of confirmed daily COVID-19 cases by municipality as a function of time, and outline the main temporal patterns of variability using a functional principal component analysis. Then, municipalities are classified according to their spatiotemporal similarities through hierarchical clustering adapted to spatially correlated functional data. Our findings reveal disparities in disease dynamics between northern and coastal municipalities versus those in the southern and hinterland. We also distinguish effects occurring during the 2020-2021 period from those in the 2021-2022 autumn-winter seasons. The results provide proof-of-concept that the proposed approach can be used to detect the main spatiotemporal patterns of disease incidence. The novel approach expands and enhances existing exploratory tools for spatiotemporal analysis of public health data., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Ribeiro et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Context: Insulin-antagonistic, counter-regulatory hormones have been implicated in the development of type 2 diabetes (T2D)., Objective: In this cross-sectional study, we investigated whether glucose-dependent regulation of such hormones differ in individuals with T2D, prediabetes (PD), and normoglycemia (NG)., Methods: Fifty-four individuals with or without T2D underwent one hyperinsulinemic-normoglycemic-hypoglycemic and one hyperglycemic clamp with repeated hormonal measurements. Participants with T2D (n = 19) were compared with a group-matched (age, sex, BMI) subset of participants without diabetes (ND, n = 17), and also with participants with PD (n = 18) and NG (n = 17)., Results: In T2D vs ND, glucagon levels were higher and less suppressed during the hyperglycemic clamp whereas growth hormone (GH) levels were lower during hypoglycemia (P < .05). Augmented ACTH response to hypoglycemia was present in PD vs NG (P < .05), with no further elevation in T2D. In contrast, glucagon and GH alterations were more marked in T2D vs PD (P < .05).In the full cohort (n = 54), augmented responses of glucagon, cortisol, and ACTH and attenuated responses of GH correlated with adiposity, dysglycemia, and insulin resistance. In multilinear regressions, insulin resistance was the strongest predictor of elevated hypoglycemic responses of glucagon, cortisol, and ACTH. Conversely, fasting glucose and HbA1c were the strongest predictors of low GH levels during hypoglycemia and elevated, i.e. less suppressed glucagon levels during hyperglycemia, respectively. Notably, adiposity measures were also strongly associated with the responses above., Conclusions: Altered counter-regulatory hormonal responses to glucose variations are observed at different stages of T2D development and may contribute to its progression by promoting insulin resistance and dysglycemia., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society.)

The benefits of Pilates have been extensively researched for their impact on muscular, psychological, and cardiac health, as well as body composition, among other aspects. This study aims to investigate the influence of the Pilates method on the learning process, motor control, and neuromuscular trunk stabilization, specifically in both experienced and inexperienced practitioners. This semi-randomized controlled trial compares the level of experience among 36 Pilates practitioners in terms of motor control and learning of two Pilates-based skills: standing plank and side crisscross. Data will be collected using various assessment methods, including abdominal wall muscle ultrasound (AWMUS), shear wave elastography (SWE), gaze behavior (GA) assessment, electroencephalography (EEG), and video motion. Significant intra- and inter-individual variations are expected, due to the diverse morphological and psychomotor profiles in the sample. The adoption of both linear and non-linear analyses will provide a comprehensive evaluation of how neuromuscular structures evolve over time and space, offering both quantitative and qualitative insights. Non-linear analysis is expected to reveal higher entropy in the expert group compared to non-experts, signifying greater complexity in their motor control. In terms of stability, experts are likely to exhibit higher Lyapunov exponent values, indicating enhanced stability and coordination, along with lower Hurst exponent values. In elastography, experienced practitioners are expected to display higher transversus abdominis (TrA) muscle elasticity, due to their proficiency. Concerning GA, non-experts are expected to demonstrate more saccades, focus on more Areas of Interest (AOIs), and shorter fixation times, as experts are presumed to have more efficient gaze control. In EEG, we anticipate higher theta wave values in the non-expert group compared to the expert group. These expectations draw from similar studies in elastography and correlated research in eye tracking and EEG. They are consistent with the principles of the Pilates Method and other scientific knowledge in related techniques.

Background: In spite of new treatments, the incidence of type 2 diabetes (T2D) and its morbidities continue to rise. The key feature of T2D is resistance of adipose tissue and other organs to insulin. Approaches to overcome insulin resistance are limited due to a poor understanding of the mechanisms and inaccessibility of drugs to relevant intracellular targets. We previously showed in mice and humans that CD248, a pre/adipocyte cell surface glycoprotein, acts as an adipose tissue sensor that mediates the transition from healthy to unhealthy adipose, thus promoting insulin resistance., Methods: Molecular mechanisms by which CD248 regulates insulin signaling were explored using in vivo insulin clamp studies and biochemical analyses of cells/tissues from CD248 knockout (KO) and wild-type (WT) mice with diet-induced insulin resistance. Findings were validated with human adipose tissue specimens., Findings: Genetic deletion of CD248 in mice, overcame diet-induced insulin resistance with improvements in glucose uptake and lipolysis in white adipose tissue depots, effects paralleled by increased adipose/adipocyte GLUT4, phosphorylated AKT and GSK3β, and reduced ATGL. The insulin resistance of the WT mice could be attributed to direct interaction of the extracellular domains of CD248 and the insulin receptor (IR), with CD248 acting to block insulin binding to the IR. This resulted in dampened insulin-mediated autophosphorylation of the IR, with reduced downstream signaling/activation of intracellular events necessary for glucose and lipid homeostasis., Interpretation: Our discovery of a cell-surface CD248-IR complex that is accessible to pharmacologic intervention, opens research avenues toward development of new agents to prevent/reverse insulin resistance., Funding: Funded by Canadian Institutes of Health Research (CIHR), Natural Sciences and Engineering Research Council of Canada (NSERC), Canada Foundations for Innovation (CFI), the Swedish Diabetes Foundation, Family Ernfors Foundation and Novo Nordisk Foundation., Competing Interests: Declaration of interests The authors have declared that no conflict of interest exists., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Obesity-related chronic low-grade inflammation may trigger insulin resistance and type 2 diabetes (T2D) development. Cells with regulatory phenotype have been shown to be reduced during obesity, especially CD4 + Treg cells. However, little is known about the CD8 + Treg cells. Therefore, we aim to characterize the CD8 + Treg cells in human peripheral blood and adipose tissue, specifically, to address the effect of obesity and insulin resistance in this regulatory immune cell population. A group of 42 participants with obesity (OB group) were recruited. Fourteen of them were evaluated pre- and post-bariatric surgery. A group of age- and sex-matched healthy volunteers (n = 12) was also recruited (nOB group). CD8 + Treg cell quantification and phenotype were evaluated by flow cytometry, in peripheral blood (PB), subcutaneous (SAT), and visceral adipose tissues (VAT). The OB group displayed a higher percentage of CD8 + Treg cells in PB, compared to the nOB. In addition, they were preferentially polarized into Tc1- and Tc1/17-like CD8 + Treg cells, compared to nOB. Moreover, SAT displayed the highest content of CD8 + Tregs infiltrated, compared to PB or VAT, while CD8 + Tregs infiltrating VAT displayed a higher percentage of cells with Tc1-like phenotype. Participants with pre-diabetes displayed a reduced percentage of TIM-3 + CD8 + Tregs in circulation, and PD-1 + CD8 + Tregs infiltrated in the VAT. An increase in the percentage of circulating Tc1-like CD8 + Treg cells expressing PD-1 was observed post-surgery. In conclusion, obesity induces significant alterations in CD8 + Treg cells, affecting their percentage and phenotype, as well as the expression of important immune regulatory molecules., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

The scarcity on the Atlantic coast of the African sea turtle population and its dynamics data is well known. This article discusses the nesting ecology methods and analysis of a nascent Angolan project aimed at preserving the nesting female population of the Olive Ridley turtle ( Lepidochelys olivacea ) on the coast of Lobito. This study examines the nesting ecology of this species from 2020 to 2023. Females had an average CCL of 70.2 cm and CCW of 68.5 cm. These females laid 127 eggs in nests that averaged 47.0 cm deep. The ex situ nest incubation period averaged 60 days, and the hatchling success was 82.1%. Some techniques used in this project require modifications and enhancements. The utilization of photo identification did not yield the anticipated outcomes, prompting the adoption of passive integrated transponders (PITs) in the last season. However, due to limited funding, the success of this method is contingent upon an augmented field effort, allowing for the recapture of a larger number of females. The continuity of this project hinges upon collaboration between higher authorities and the local community. Together, it is possible to deepen the understanding of the nesting ecology of this species and address pivotal issues for its conservation, thereby implementing the most effective preservation measures.

Cdk5 and Abl enzyme substrate 1 (CABLES1) is a cell cycle regulator that has previously been identified as a candidate gene for obesity-related phenotypes, but little is known about its role in adipose tissue metabolism. In this study, we explore the role of CABLES1 in obesity and type 2 diabetes (T2D) in human subcutaneous adipose tissue (SAT). We performed gene expression analysis of SAT obtained from subjects with and without T2D, and from a second validation cohort consisting of subjects without T2D. We used CRISPR/Cas9 genome editing to perform CABLES1 loss-of-function studies in human primary preadipocytes and assessed them functionally after differentiation. CABLES1 gene expression in SAT was decreased in T2D by almost 25%, and inversely associated with insulin resistance markers and hyperglycaemia. mRNA levels were reduced with increasing BMI and negatively correlated with obesity markers. We found that adipocytes are likely the main CABLES1-expressing cell type in SAT, but CABLES1 depletion in adipocytes caused no phenotypical changes in regards to differentiation, glucose uptake, or expression of key genes of adipocyte function. These findings suggest that CABLES1 gene expression in SAT might be altered in obesity and T2D as a consequence of metabolic dysregulation rather than being a causal factor.

Background: Catecholamine-stimulated lipolysis is reduced with aging, which may promote adiposity and insulin resistance. Organic cation transporter 3 (OCT3), which is inhibited by estradiol (E2), mediates catecholamine transport into adipocytes for degradation, thus decreasing lipolysis. In this study, we investigated the association of OCT3 mRNA levels in subcutaneous adipose tissue (SAT) with aging and markers of insulin resistance in women., Methods: SAT biopsies were obtained from 66 women with (19) or without (47) type 2 diabetes (age 22-76 years, 20.0-40.1 kg/m2). OCT3 mRNA and protein levels were measured for group comparisons and correlation analysis. SAT was incubated with E2 and OCT3 mRNA levels were measured. Associations between OCT3 single nucleotide polymorphisms (SNPs) and diabetes-associated traits were assessed., Results: OCT3 mRNA and protein levels in SAT increased with aging. SAT from postmenopausal women had higher levels of OCT3 than premenopausal women, and there was a dose-dependent reduction in OCT3 mRNA levels in SAT treated with E2. OCT3 mRNA levels were negatively associated with markers of insulin resistance, and ex vivo lipolysis. OCT3 SNPs were associated with BMI, waist to hip ratio, and circulating lipids (eg, triglycerides)., Conclusion: OCT3 mRNA and protein levels in SAT increased with aging, and mRNA levels were negatively associated with markers of insulin resistance. E2 incubation downregulated OCT3 mRNA levels, which may explain lower OCT3 mRNA in premenopausal vs postmenopausal women. High OCT3 protein levels in adipose tissue may result in increased catecholamine degradation, and this can contribute to the reduction in lipolysis observed in women with aging., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society.)