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Forty percent of the US population and 1 in 6 individuals worldwide are obese, and the incidence of this disease is surging globally1,2. Various dietary interventions, including carbohydrate and fat restriction, and more recently amino acid restriction, have been explored to combat this epidemic3-6. We sought to investigate the impact of removing individual amino acids on the weight profiles of mice. Compared to essential amino acid restriction, induction of conditional cysteine restriction resulted in the most dramatic weight loss, amounting to 20% within 3 days and 30% within one week, which was readily reversed. This weight loss occurred despite the presence of substantial cysteine reserves stored in glutathione (GSH) across various tissues7. Further analysis demonstrated that the weight reduction primarily stemmed from an increase in the utilization of fat mass, while locomotion, circadian rhythm and histological appearance of multiple other tissues remained largely unaffected. Cysteine deficiency activated the integrated stress response (ISR) and NRF2-mediated oxidative stress response (OSR), which amplify each other, leading to the induction of GDF15 and FGF21, hormones associated with increased lipolysis, energy homeostasis and food aversion8-10. We additionally observed rapid tissue coenzyme A (CoA) depletion, resulting in energetically inefficient anaerobic glycolysis and TCA cycle, with sustained urinary excretion of pyruvate, orotate, citrate, α-ketoglutarate, nitrogen rich compounds and amino acids. In summary, our investigation highlights that cysteine restriction, by depleting GSH and CoA, exerts a maximal impact on weight loss, metabolism, and stress signaling compared to other amino acid restrictions. These findings may pave the way for innovative strategies for addressing a range of metabolic diseases and the growing obesity crisis.
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Introduction: It is unknown how intestinal B cell populations and B cell receptor (BCR) repertoires are established and maintained over time in humans. Following intestinal transplantation (ITx), surveillance ileal mucosal biopsies provide a unique opportunity to map the dynamic establishment of recipient gut lymphocyte populations in immunosuppressed conditions. Methods: Using polychromatic flow cytometry that includes HLA allele group-specific antibodies distinguishing donor from recipient cells along with high throughput BCR sequencing, we tracked the establishment of recipient B cell populations and BCR repertoire in the allograft mucosa of ITx recipients. Results: We confirm the early presence of naïve donor B cells in the circulation (donor age range: 1-14 years, median: 3 years) and, for the first time, document the establishment of recipient B cell populations, including B resident memory cells, in the intestinal allograft mucosa (recipient age range at the time of transplant: 1-44 years, median: 3 years). Recipient B cell repopulation of the allograft was most rapid in infant (<1 year old)-derived allografts and, unlike T cell repopulation, did not correlate with rejection rates. While recipient memory B cell populations were increased in graft mucosa compared to circulation, naïve recipient B cells remained detectable in the graft mucosa for years. Comparisons of peripheral and intra-mucosal B cell repertoires in the absence of rejection (recipient age range at the time of transplant: 1-9 years, median: 2 years) revealed increased BCR mutation rates and clonal expansion in graft mucosa compared to circulating B cells, but these parameters did not increase markedly after the first year post-transplant. Furthermore, clonal mixing between the allograft mucosa and the circulation was significantly greater in ITx recipients, even years after transplantation, than in deceased adult donors. In available pan-scope biopsies from pediatric recipients, we observed higher percentages of naïve recipient B cells in colon allograft compared to small bowel allograft and increased BCR overlap between native colon vs colon allograft compared to that between native colon vs ileum allograft in most cases, suggesting differential clonal distribution in large intestine vs small intestine. Discussion: Collectively, our data demonstrate intestinal mucosal B cell repertoire establishment from a circulating pool, a process that continues for years without evidence of stabilization of the mucosal B cell repertoire in pediatric ITx patients.
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Mucosa Intestinal , Receptores de Antígenos de Linfocitos B , Humanos , Niño , Preescolar , Adolescente , Lactante , Mucosa Intestinal/inmunología , Masculino , Femenino , Receptores de Antígenos de Linfocitos B/genética , Receptores de Antígenos de Linfocitos B/inmunología , Adulto , Linfocitos B/inmunología , Adulto Joven , Intestinos/inmunología , Intestinos/trasplante , Trasplante de Órganos , Rechazo de Injerto/inmunologíaRESUMEN
Introduction: Unmanaged hypertension in pregnancy is the second most common cause of direct maternal death and disproportionately affects women in rural areas. While telehealth technologies have worked to reduce barriers to healthcare, lack of internet access has created new challenges. Cellular-enabled remote patient monitoring devices provide an alternative option for those without access to internet. Objective: This study aimed to assess maternal and neonatal clinical outcomes and patient acceptability of an integrated model of cellular-enabled remote patient monitoring devices for blood pressure supported by a 24/7 nurse call center. Methods: In a mixed-methods study, 20 women with hypertension during pregnancy were given a cellular-enabled BodyTrace blood pressure cuff. Participants' blood pressures were continuously monitored by a nurse call center. Participants completed a baseline survey, post-survey, and semi-structured interview after 8 weeks of device use. Results: Participants reported a significant decrease in perceived stress after device use (P = .0004), high satisfaction with device usability (mean = 78.38, SD = 13.68), and high intention to continue device use (mean = 9.05, SD = 1.96). Relatively low hospitalization and emergency department rates was observed (mean = 0.35, SD = 0.59; mean = 0.75, SD = 0.91). Participant-perceived benefits of device use included convenience, perceived better care owing to increased monitoring, and patient empowerment. Perceived disadvantages included higher blood pressure readings compared to clinical readings and excessive calls from call center. Conclusion: Remote patient monitoring for women whose pregnancies are complicated by hypertension can reduce barriers and improve health outcomes for women living in rural and low-health-resource areas.
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To ensure timely duplication of the entire eukaryotic genome, thousands of replication machineries (replisomes) act on genomic DNA at any time during S phase. In the final stages of this process, replisomes are unloaded from chromatin. Unloading is driven by polyubiquitylation of MCM7, a subunit of the terminated replicative helicase, and processed by p97/VCP segregase. Most of our knowledge of replication termination comes from model organisms, and little is known about how this process is executed and regulated in human somatic cells. Here we show that replisome disassembly in this system requires CUL2LRR1-driven MCM7 ubiquitylation, p97, and UBXN7 for unloading and provide evidence for "backup" mitotic replisome disassembly, demonstrating conservation of such mechanisms. Finally, we find that small-molecule inhibitors against Cullin ubiquitin ligases (CULi) and p97 (p97i) affect replisome unloading but also lead to induction of replication stress in cells, which limits their usefulness to specifically target replisome disassembly processes.
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Hypoxia represents one of the key factors that stimulates the growth of leukemic cells in their niche. Leukemic cells in hypoxic conditions are forced to reprogram their original transcriptome, miRNome, and metabolome. How the coupling of microRNAs (miRNAs)/mRNAs helps to maintain or progress the leukemic status is still not fully described. MiRNAs regulate practically all biological processes within cells and play a crucial role in the development/progression of leukemia. In the present study, we aimed to uncover the impact of hsa-miR-155-5p (miR-155, MIR155HG) on the metabolism, proliferation, and mRNA/miRNA network of human chronic lymphocytic leukemia cells (CLL) in hypoxic conditions. As a model of CLL, we used the human MEC-1 cell line where we deleted mature miR-155 with CRISPR/Cas9. We determined that miR-155 deficiency in leukemic MEC-1 cells results in lower proliferation even in hypoxic conditions in comparison to MEC-1 control cells. Additionally, in MEC-1 miR-155 deficient cells we observed decreased number of populations of cells in S phase. The miR-155 deficiency under hypoxic conditions was accompanied by an increased apoptosis. We detected a stimulatory effect of miR-155 deficiency and hypoxia at the level of gene expression, seen in significant overexpression of EGLN1, GLUT1, GLUT3 in MEC-1 miR-155 deficient cells. MiR-155 deficiency and hypoxia resulted in increase of glucose and lactate uptake. Pyruvate, ETC and ATP were reduced. To conclude, miR-155 deficiency and hypoxia affects glucose and lactate metabolism by stimulating the expression of glucose transporters as GLUT1, GLUT3, and EGLN1 [Hypoxia-inducible factor prolyl hydroxylase 2 (HIF-PH2)] genes in the MEC-1 cells.
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INTRODUCTION: Solving disparities in assessments is crucial to a successful surgical training programme. The first step in levelling these inequalities is recognising in what contexts they occur, and what protected characteristics are potentially implicated. METHODS: This scoping review was based on Arksey & O'Malley's guiding principles. OVID and Embase were used to identify articles, which were then screened by three reviewers. RESULTS: From an initial 358 articles, 53 reported on the presence of differential attainment in postgraduate surgical assessments. The majority were quantitative studies (77.4%), using retrospective designs. 11.3% were qualitative. Differential attainment affects a varied range of protected characteristics. The characteristics most likely to be investigated were gender (85%), ethnicity (37%) and socioeconomic background (7.5%). Evidence of inequalities are present in many types of assessment, including: academic achievements, assessments of progression in training, workplace-based assessments, logs of surgical experience and tests of technical skills. CONCLUSION: Attainment gaps have been demonstrated in many types of assessment, including supposedly "objective" written assessments and at revalidation. Further research is necessary to delineate the most effective methods to eliminate bias in higher surgical training. Surgical curriculum providers should be informed by the available literature on inequalities in surgical training, as well as other neighbouring specialties such as medicine or general practice, when designing assessments and considering how to mitigate for potential causes of differential attainment.
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Competencia Clínica , Educación de Postgrado en Medicina , Evaluación Educacional , Cirugía General , Humanos , Cirugía General/educación , Factores Socioeconómicos , FemeninoRESUMEN
The eukaryotic replicative helicase (CMG complex) is assembled during DNA replication initiation in a highly regulated manner, which is described in depth by other manuscripts in this Issue. During DNA replication, the replicative helicase moves through the chromatin, unwinding DNA and facilitating nascent DNA synthesis by polymerases. Once the duplication of a replicon is complete, the CMG helicase and the remaining components of the replisome need to be removed from the chromatin. Research carried out over the last ten years has produced a breakthrough in our understanding, revealing that replication termination, and more specifically replisome disassembly, is indeed a highly regulated process. This review brings together our current understanding of these processes and highlights elements of the mechanism that are conserved or have undergone divergence throughout evolution. Finally, we discuss events beyond the classic termination of DNA replication in S-phase and go over the known mechanisms of replicative helicase removal from chromatin in these particular situations.
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OBJECTIVE: To report the use of a Lateral Epicondylar Anatomical Plate for the management of humeral condylar fractures (HCF) in dogs. STUDY DESIGN: Medical records of dogs with HCF stabilized using the Lateral Epicondylar Anatomical Plate at six UK veterinary referral centres between April 2018 and February 2021 were reviewed. Long-term follow-up (>6 months) was obtained via owner questionnaire, which incorporated the Liverpool Osteoarthritis in Dogs clinical metrology instrument. RESULTS: Sixty-two HCF were treated in 61 dogs (44 lateral condylar fractures [LCF] and 18 intracondylar (T/Y) fractures [ICF]). Fifty-one dogs were Spaniels or Spaniel crossbreeds. Intraoperative contouring of the plate was required for one dog-a French Bulldog. Postoperative complications occurred in 14/42 LCF and 6/18 ICF; overall there were 14 minor, 8 major, and 2 catastrophic complications. On final follow-up imaging, there was evidence of partial or complete osseous continuity of the condylar part of the fracture 32/53 HCF (24/39 LCF and 8/14 ICF) and lateral epicondylar part of the fracture in 53/53 HCF (39/39 LCF and 14/14 ICF). At final reexamination, 20/28 dogs with LCF and 5/13 dogs with ICF were not lame and the remaining dogs demonstrated mild lameness. According to the owner questionnaire, 17/17 dogs with LCF and 8/10 dogs with ICF returned to full limb use and median Liverpool Osteoarthritis in Dogs scores were 2/52 for LCF and 6.5/52 for ICF. CONCLUSION: The Lateral Epicondylar Anatomical Plate can be used successfully for the surgical stabilization of HCF in dogs.
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Primary biliary cholangitis (PBC) is a chronic cholestatic liver disease. The management landscape was transformed 20 years ago with the advent of ursodeoxycholic acid. Up to 40% of patients do not, however, respond adequately to ursodeoxycholic acid and therefore still remain at risk of disease progression to cirrhosis. The introduction of obeticholic acid as a second-line therapy for patients failing ursodeoxycholic acid has improved outcomes for patients with PBC. There remains, however, a need for better treatment for patients at higher risk. The greatest threat facing our efforts to improve treatment in PBC is, paradoxically, the regulatory approval model providing conditional marketing authorization for new drugs based on biochemical markers on the condition that long-term, randomized placebo-controlled outcome trials are performed to confirm efficacy. As demonstrated by the COBALT confirmatory study with obeticholic acid, it is difficult to retain patients in the required follow-on confirmatory placebo-controlled PBC outcome trials when a licensed drug is commercially available. New PBC therapies in development, such as the peroxisome proliferator-activated receptor agonists, face even greater challenges in demonstrating outcome benefit through randomized placebo-controlled studies once following conditional marketing authorization, as there will be even more treatment options available. A recently published EMA Reflection Paper provides some guidance on the regulatory pathway to full approval but fails to recognize the importance of real-world data in providing evidence of outcome benefit in rare diseases. Here we explore the impact of the EMA reflection paper on PBC therapy and offer pragmatic solutions for generating evidence of long-term outcomes through real-world data collection.
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INTRODUCTION: Improved outcomes of liver disease in childhood and young adulthood have resulted in an increasing number of young adults (YA) entering adult liver services. The adult hepatologist therefore requires a working knowledge in diseases that arise almost exclusively in children and their complications in adulthood. AIMS: To provide adult hepatologists with succinct guidelines on aspects of transitional care in YA relevant to key disease aetiologies encountered in clinical practice. METHODS: A systematic literature search was undertaken using the Pubmed, Medline, Web of Knowledge and Cochrane database from 1980 to 2023. MeSH search terms relating to liver diseases ('cholestatic liver diseases', 'biliary atresia', 'metabolic', 'paediatric liver diseases', 'autoimmune liver diseases'), transition to adult care ('transition services', 'young adult services') and adolescent care were used. The quality of evidence and the grading of recommendations were appraised using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. RESULTS: These guidelines deal with the transition of YA and address key aetiologies for the adult hepatologist under the following headings: (1) Models and provision of care; (2) screening and management of mental health disorders; (3) aetiologies; (4) timing and role of liver transplantation; and (5) sexual health and fertility. CONCLUSIONS: These are the first nationally developed guidelines on the transition and management of childhood liver diseases in adulthood. They provide a framework upon which to base clinical care, which we envisage will lead to improved outcomes for YA with chronic liver disease.
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Colestasis , Hepatopatías , Trasplante de Hígado , Adolescente , Niño , Humanos , Adulto Joven , Hepatopatías/diagnóstico , Hepatopatías/terapia , Reino UnidoRESUMEN
The Department of Defense has mandated combat and operational stress control (COSC) efforts for the Services since 1999. Although several COSC-related programs have been implemented, few have undergone evaluation, and no standardized metrics have been established to assess their effectiveness and utility. The purpose of this review was to characterize the content and psychometrics of measures that have been utilized as outcome metrics in evaluations of COSC-related programs and interventions. Systematic literature searches were conducted for publications that: a) evaluated at least one measure from U.S. service members who participated in a program or intervention to prevent or reduce the adverse effects of combat and operational stress; and b) reported U.S. data on the internal consistency, test-retest reliability, convergent validity, and sensitivity/specificity of the identified measures. This process identified 15 measures for which psychometric properties were reviewed for acceptability based on recommended criteria. Identified measures varied from well-validated measures to newer instruments for which more data is needed on one or more of the target psychometric properties. Aside from internal consistency, psychometric data from U.S. military samples were sparse. Results further suggested that some measures might have reduced sensitivity in service members under certain conditions, such as large-scale screening. Additional studies are needed to validate COSC-relevant measures in service members. Future evaluations of programs and interventions for combat and operational stress should select measures that will increase the consistency of the literature, allow comparisons across studies, and ensure alignment with the objectives of identified programs.
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Personal Militar , Psicometría , Psicometría/métodos , Humanos , Personal Militar/psicología , Estados Unidos , Reproducibilidad de los Resultados , Estrés Psicológico/terapia , Evaluación de Programas y Proyectos de Salud , Evaluación de Resultado en la Atención de Salud , Trastornos de Combate/terapia , Trastornos de Combate/psicología , Estrés Laboral/prevención & control , Estrés Laboral/terapiaRESUMEN
BACKGROUND: Understanding formation of the human tissue resident memory T cell (TRM) repertoire requires longitudinal access to human non-lymphoid tissues. METHODS: By applying flow cytometry and next generation sequencing to serial blood, lymphoid tissue, and gut samples from 16 intestinal transplantation (ITx) patients, we assessed the origin, distribution, and specificity of human TRMs at phenotypic and clonal levels. FINDINGS: Donor age ≥1 year and blood T cell macrochimerism (peak level ≥4%) were associated with delayed establishment of stable recipient TRM repertoires in the transplanted ileum. T cell receptor (TCR) overlap between paired gut and blood repertoires from ITx patients was significantly greater than that in healthy controls, demonstrating increased gut-blood crosstalk after ITx. Crosstalk with the circulating pool remained high for years of follow-up. TCR sequences identifiable in pre-Tx recipient gut but not those in lymphoid tissues alone were more likely to populate post-Tx ileal allografts. Clones detected in both pre-Tx gut and lymphoid tissue had distinct transcriptional profiles from those identifiable in only one tissue. Recipient T cells were distributed widely throughout the gut, including allograft and native colon, which had substantial repertoire overlap. Both alloreactive and microbe-reactive recipient T cells persisted in transplanted ileum, contributing to the TRM repertoire. INTERPRETATION: Our studies reveal human intestinal TRM repertoire establishment from the circulation, preferentially involving lymphoid tissue counterparts of recipient intestinal T cell clones, including TRMs. We have described the temporal and spatial dynamics of this active crosstalk between the circulating pool and the intestinal TRM pool. FUNDING: This study was funded by the National Institute of Allergy and Infectious Diseases (NIAID) P01 grant AI106697.
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Células T de Memoria , Receptores de Antígenos de Linfocitos T , Humanos , Íleon , Aloinjertos , Memoria Inmunológica , Linfocitos T CD8-positivosRESUMEN
The oyster toadfish (Opsanus tau) is an ideal model to examine the effects of anthropogenic noise on behavior because they rely on acoustic signals for mate attraction and social interactions. We predict that oyster toadfish have acclimated to living in noise-rich environments because they are common in waterways of urban areas, like New York City (NYC). We used passive acoustic monitoring at two locations to see if calling behavior patterns are altered in areas of typically high boat traffic versus low boat traffic (Pier 40, NYC, NY, and Eel Pond, Woods Hole, MA, respectively). We hypothesized that toadfish in NYC would adjust their circadian calling behavior in response to daily anthropogenic noise patterns. We quantified toadfish calls and ship noise over three 24-h periods in the summer reproductive period at both locations. We observed an inverse relationship between the duration of noise and the number of toadfish calls at Pier 40 in comparison to Eel Pond. Additionally, toadfish at Pier 40 showed significant differences in peak calling behavior compared to Eel Pond. Therefore, oyster toadfish may have acclimated to living in an urban environment by potentially altering their communication behavior in the presence of boat noise.
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Batrachoidiformes , Ostreidae , Animales , Batrachoidiformes/fisiología , Ruido/efectos adversos , Vocalización Animal/fisiología , Ciudad de Nueva YorkRESUMEN
OBJECTIVE: Heart failure remains a key public health priority across the globe. The median age of people with heart failure admitted to hospital in the UK is 81 years old. Many such patients transcend the standard interventions that are well characterised and evidenced in guidelines, into holistic aspects surrounding frailty, rehabilitation and social care. Previous published competency frameworks in heart failure have focused on the value of doctors, nurses and pharmacists. We aimed to provide an expert consensus on the minimum heart failure-specific competencies necessary for multiple different healthcare professionals, including physiotherapists, occupational therapists, dietitians and cardiac physiologists. METHODS: The document has been developed focussing on four main parts, (1) establishing a project working group of expert professionals, (2) a literature review of previously existing published curricula and competency frameworks, (3) consensus building, which included developing a structure to the framework with ongoing review of the contents to adapt and be inclusive for each specialty and (4) write up and dissemination to widen the impact of the project. RESULTS: The final competency framework displays competencies across seven sections; knowledge (including subheadings on heart failure syndrome, diagnosis and clinical management); general skills; heart failure-specific skills; clinical autonomy; multidisciplinary team working; teaching and education; and research and development. CONCLUSION: People with heart failure can be complex and have needs that require input from a broad range of specialties. This publication focuses on the vital impact of wider multidisciplinary groups and should help define the generic core heart failure-specific competencies needed to support future pipelines of professionals, who regularly interact with and deliver care for patients with heart failure.
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Personal de Salud , Insuficiencia Cardíaca , Humanos , Anciano de 80 o más Años , Personal de Salud/educación , Curriculum , Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/terapiaRESUMEN
BACKGROUND: Poor mental health is associated with obesity, but existing studies are either cross-sectional or have long time periods between measurements of mental health and weight. It is, therefore, unclear how small fluctuations in mental wellbeing within individuals predict bodyweight over short time periods, e.g. within the next month. Studying this could identify modifiable determinants of weight changes and highlight opportunities for early intervention. METHODS: 2,133 UK adults from a population-based cohort completed monthly mental health and weight measurements using a mobile app over a period of 6-9 months. We used random intercept regression models to examine longitudinal associations of depressive symptoms, anxiety symptoms and stress with subsequent weight. In sub-group analyses, we included interaction terms of mental health variables with baseline characteristics. Mental health variables were split into "between-individual" measurements (= the participant's median score across all timepoints) and "within-individual" measurements (at each timepoint, the difference between the participant's current score and their median). RESULTS: Within-individual variation in depressive symptoms predicted subsequent weight (0.045kg per unit of depressive symptom severity, 95% CI 0.021-0.069). We found evidence of a moderation effect of baseline BMI on the association between within-individual fluctuation in depressive symptoms and subsequent weight: The association was only apparent in those with overweight/obesity, and it was stronger in those with obesity than those with overweight (BMI<25kg/m2: 0.011kg per unit of depressive symptom severity [95% CI -0.017 to 0.039]; BMI 25-29.9kg/m2: 0.052kg per unit of depressive symptom severity [95%CI 0.010-0.094kg]; BMI≥30kg/m2: 0.071kg per unit of depressive symptom severity [95%CI 0.013-0.129kg]). We found no evidence for other interactions, associations of stress and anxiety with weight, or for a reverse direction of association. CONCLUSION: In this exploratory study, individuals with overweight or obesity were more vulnerable to weight gain following higher-than-usual (for that individual) depressive symptoms than individuals with a BMI<25kg/m2.
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Salud Mental , Sobrepeso , Adulto , Humanos , Sobrepeso/complicaciones , Sobrepeso/epidemiología , Estudios Transversales , Estudios Longitudinales , Obesidad/complicaciones , Obesidad/epidemiologíaRESUMEN
Awareness and knowledge of national movement behaviour guidelines are needed to influence individual behaviour and public health policies. This study assessed the awareness and knowledge of the Canadian 24-Hour Movement Guidelines for Adults Aged 18-64 Years and Adults Aged 65 Years or Older (24HMG) recommendations among adults living in Canada across three timepoints. Online surveys were distributed to representative samples of adults living in Canada over a 6-month period. Findings suggest that short-term dissemination efforts were successful in increasing awareness of the 24HMG following guideline release. However, other strategies, such as education, may be needed to influence knowledge of guideline recommendations.
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Ejercicio Físico , Canadá , Encuestas y Cuestionarios , EscolaridadRESUMEN
PURPOSE: This study examined the acute effects of interrupting sitting with light-intensity walking on postprandial cardiometabolic risk markers in South Asian adults. METHODS: South Asians with overweight/obesity (n = 19; body mass index [BMI] > 23 kg·m-2) and normal-weight (n = 8; BMI 18.0-22.9 kg·m-2) aged 48.8 ± 5.6 years completed two, 5-h conditions: (1) prolonged sitting (SIT), and (2) interrupted sitting with 5-min bouts of light-intensity walking every 30-min (INT-SIT). Blood samples and resting expired air samples were collected throughout each condition. Statistical analyses were completed using linear mixed models. RESULTS: In participants with overweight/obesity, postprandial glucose, triglycerides (TAG) and metabolic load index (MLI) over time were lower, whereas resting substrate utilisation and resting energy expenditure (REE) were higher, in INT-SIT than SIT (all p ≤ 0.05). Compared with SIT (0.18 [95% CI 0.13, 0.22] kcal.min-1), INT-SIT (0.23 [95% CI 0.18, 0.27] kcal.min-1) increased postprandial REE iAUC in participants with overweight/obesity (p = 0.04, d = 0.51). Postprandial TAG concentrations over time were lower in INT-SIT versus SIT (p = 0.01, d = 30) in normal-weight participants, with no differences in any other outcomes for this sample group. CONCLUSION: These findings suggest that interrupting sitting with 5-min bouts of light walking every 30-min acutely attenuates cardiometabolic risk markers among South Asians living with overweight/obesity, whereas limited effects may be seen in individuals with normal-weight.
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Enfermedades Cardiovasculares , Sobrepeso , Adulto , Humanos , Glucemia/metabolismo , Insulina , Estudios Cruzados , Obesidad/metabolismo , Caminata , Periodo PosprandialRESUMEN
BACKGROUND: Emotional eating is a barrier to weight management. Interventions based on Acceptance and Commitment Therapy (ACT) promote the acceptance of uncomfortable feelings, which can reduce the urge to use food as a coping mechanism. We aimed to explore how participants of an ACT-based weight management intervention (WMI) experience emotional eating and relevant intervention content. METHODS: We conducted semi-structured telephone interviews with participants of a digital ACT-based guided self-help WMI. Fifteen participants were purposefully selected to represent a range of demographic characteristics and emotional eating scores. We used reflexive thematic analysis to explore experiences of emotional eating. RESULTS: We generated five themes. Participants improved emotional eating by disconnecting emotions from behaviours though increased self-awareness (theme 1) and by implementing alternative coping strategies, including preparation, substitution, and acceptance (theme 2). Most participants maintained improvements in emotional eating over time but wished for more opportunities to re-engage with intervention content, including more immediate support in triggering situations (theme 3). Participants who struggled to engage with emotional eating related intervention content often displayed an external locus of control over emotional eating triggers (theme 4). The perceived usefulness of the intervention depended on participants' prior experiences of emotional eating, and was thought insufficient for participants with complex emotional experiences (theme 5). DISCUSSION: This ACT-based WMI helped participants with emotional eating by improving self-awareness and teaching alternative coping strategies. Intervention developers may consider adding ongoing forms of intervention that provide both real-time and long-term support. Additionally, a better understanding of how to support people with an external locus of control and people with complex experiences of emotional eating is needed. Future research may explore ways of personalising WMIs based on participants' emotional needs.
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Terapia de Aceptación y Compromiso , Humanos , Emociones , Conductas Relacionadas con la SaludRESUMEN
The site of transition between tissue-resident memory (TRM) and circulating phenotypes of T cells is unknown. We integrated clonotype, alloreactivity, and gene expression profiles of graft-repopulating recipient T cells in the intestinal mucosa at the single-cell level after human intestinal transplantation. Host-versus-graft (HvG)-reactive T cells were mainly distributed to TRM, effector T (Teff)/TRM, and T follicular helper compartments. RNA velocity analysis demonstrated a trajectory from TRM to Teff/TRM clusters in association with rejection. By integrating pre- and post-transplantation (Tx) mixed lymphocyte reaction-determined alloreactive repertoires, we observed that pre-existing HvG-reactive T cells that demonstrated tolerance in the circulation were dominated by TRM profiles in quiescent allografts. Putative de novo HvG-reactive clones showed a transcriptional profile skewed to cytotoxic effectors in rejecting grafts. Inferred protein regulon network analysis revealed upstream regulators that accounted for the effector and tolerant T cell states. We demonstrate Teff/TRM interchangeability for individual T cell clones with known (allo)recognition in the human gut, providing novel insight into TRM biology.
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Tolerancia Inmunológica , Linfocitos T , Humanos , Trasplante Homólogo , Células Clonales , Memoria InmunológicaRESUMEN
Basement membranes (BMs) are specialized sheets of extracellular matrix that underlie epithelial and endothelial tissues. BMs regulate the traffic of cells and molecules between compartments, and participate in signaling, cell migration, and organogenesis. The dynamics of mammalian BMs, however, are poorly understood, largely due to a lack of models in which core BM components are endogenously labeled. Here, we describe the mTurquoise2-Col4a1 mouse in which we fluorescently tag collagen IV, the main component of BMs. Using an innovative planar-sagittal live imaging technique to visualize the BM of developing skin, we directly observe BM deformation during hair follicle budding and basal progenitor cell divisions. The BM's inherent pliability enables dividing cells to remain attached to and deform the BM, rather than lose adhesion as generally thought. Using FRAP, we show BM collagen IV is extremely stable, even during periods of rapid epidermal growth. These findings demonstrate the utility of the mTurq2-Col4a1 mouse to shed new light on mammalian BM developmental dynamics.