Teaching Adolescents With Type 1 Diabetes Self-Compassion (TADS) to Reduce Diabetes Distress: Protocol for a Randomized Controlled Trial.

BACKGROUND: Adolescents living with type 1 diabetes (T1D) often experience diabetes distress (DD), a construct distinct from depression or anxiety that refers to the negative emotions that arise from living with and managing diabetes. Self-compassion, which involves being open to one's own suffering and treating oneself with the same care one would show to loved ones, is associated with better psychological and clinical outcomes among individuals with T1D. Self-compassion is a skill that can be taught and therefore represents an opportunity for intervention. OBJECTIVE: The overall aim of this study is to assess the effectiveness of a web-based mindful self-compassion for teens (MSC-T) intervention on improving DD, anxiety, depression, diabetes-related disordered eating, and suicidal ideation experienced by youth with T1D (aged between 12 and 17 years) compared with a waitlist control group (standard of care). We will also explore (1) if the effect of the MSC-T intervention changes over time, (2) if the MSC-T intervention has a positive impact on measures of glycemic control, and (3) if the effect of the MSC-T intervention differs based on self-reported gender. METHODS: We will conduct a single-center, parallel-group randomized controlled trial of 140 adolescents with T1D followed for 12 months. Participants will be randomly allocated (using hidden allocation) in a 1:1 ratio to either the MSC-T intervention or the waitlist control group. Our primary outcome is DD, as measured by the Problem Areas in Diabetes-Teen (PAID-T) version at 3 months. Secondary outcomes, assessed at 3 and 12 months, include anxiety (Generalized Anxiety Disorder 7-item [GAD-7] scale), depression (Patient Health Questionnaire-9 [PHQ-9]), diabetes-related disordered eating (Diabetes Eating Problem Survey-Revised [DEPS-R] version), and suicidal ideation (using 1 question from the PHQ-9). RESULTS: Study recruitment began in October 2022 and was completed in March 2023, with a total of 141 participants enrolling. Data collection will be ongoing until March 2024. The first results are expected in June 2024. CONCLUSIONS: This study will be the first randomized trial to assess the effectiveness of the web-based MSC-T intervention on adolescents with T1D. Given that adolescence is a period where individuals are typically required to assume more responsibility for their diabetes care, providing adolescents with the tools they need to better manage the stress that often accompanies T1D management is paramount. TRIAL REGISTRATION: ClinicalTrials.gov NCT05463874; https://clinicaltrials.gov/study/NCT05463874. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/53935.

Integrated intracellular organization and its variations in human iPS cells.

Understanding how a subset of expressed genes dictates cellular phenotype is a considerable challenge owing to the large numbers of molecules involved, their combinatorics and the plethora of cellular behaviours that they determine1,2. Here we reduced this complexity by focusing on cellular organization-a key readout and driver of cell behaviour3,4-at the level of major cellular structures that represent distinct organelles and functional machines, and generated the WTC-11 hiPSC Single-Cell Image Dataset v1, which contains more than 200,000 live cells in 3D, spanning 25 key cellular structures. The scale and quality of this dataset permitted the creation of a generalizable analysis framework to convert raw image data of cells and their structures into dimensionally reduced, quantitative measurements that can be interpreted by humans, and to facilitate data exploration. This framework embraces the vast cell-to-cell variability that is observed within a normal population, facilitates the integration of cell-by-cell structural data and allows quantitative analyses of distinct, separable aspects of organization within and across different cell populations. We found that the integrated intracellular organization of interphase cells was robust to the wide range of variation in cell shape in the population; that the average locations of some structures became polarized in cells at the edges of colonies while maintaining the 'wiring' of their interactions with other structures; and that, by contrast, changes in the location of structures during early mitotic reorganization were accompanied by changes in their wiring.

Infected abdominal aortic aneurysm graft complicated by lumbar discitis.

We present the case of a 68-year-old male, who underwent open abdominal aortic graft in August 2016 owing to a ruptured large infrarenal abdominal aneurysm. He subsequently presented 6 months later with back pain, general weakness, reduced mobility and cachexia. He underwent CT, MRI and fluorodeoxyglucose (PDG)-PET spinal imaging, all modalities showing signs of aortic graft infection complicated by L4/5 discitis. The patient was treated conservatively with intravenous antibiotics and spinal brace support, as his general condition did not allow for surgery. Although he showed initial clinical improvement allowing plans for supported discharge, his improvement was not sustained and he died 4 months after admission.

Gene set analysis of lung samples provides insight into pathogenesis of progressive, fibrotic pulmonary sarcoidosis.

RATIONALE: Approximately 60 to 70% of patients with pulmonary sarcoidosis have disease that resolves spontaneously; the rest follow a chronic course with varying levels of fibrosis. It is unclear why some patients progress and if treatment affects outcome. OBJECTIVES: To determine differential gene expression profile in lungs of patients with self-limiting sarcoidosis compared to those with progressive-fibrotic disease, and to analyze the biological relevance of these differentially expressed genes. METHODS: We examined microarray expression of 26,626 genes in transbronchial biopsies of granulomatous areas in lungs of patients with active but self-limiting (n = 8) versus those with active, progressive (+/- fibrotic) pulmonary disease (n = 7). MEASUREMENTS AND MAIN RESULTS: Three hundred thirty-four genes were differentially expressed between the two groups (P < 0.01, Bayesian moderated t test). Gene Set Enrichment Analysis showed over-representation of gene-sets (defined by Gene Ontology) related to host immune activation, proliferation, and defense, among genes up-regulated in the progressive-fibrotic group (FDR q < 0.0001 for the top 43 gene sets), and a marked enrichment of, and similarity in gene expression profiles between, progressive-fibrotic sarcoidosis and hypersensitivity pneumonitis (HP), (q < 0.001), but not idiopathic pulmonary fibrosis (IPF). CONCLUSIONS: The findings suggest that patients with progressive/fibrotic pulmonary sarcoidosis have intense immune activity related to host defense in their lungs, with processes more similar to HP than IPF. The study also demonstrates that transbronchial lung biopsy samples can provide good-quality RNA for gene expression profiling, supporting its potential use as a prognostic classifier for pulmonary sarcoidosis.

The interaction between follicular fluid total antioxidant capacity, infertility and early reproductive outcomes during in vitro fertilization.

INTRODUCTION: The objective of this study was to determine whether the relationship between antioxidant capacity of follicular fluid and early reproductive outcomes is influenced by the cause of infertility, polycystic ovarian morphology, age and smoking. PATIENTS AND METHODS: This was a prospective, cross-sectional study performed in an assisted conception unit and a teaching hospital. The study cohort was 34 women undergoing IVF treatment. Interventions included total antioxidant capacity (TAC) measured using ferric reducing/antioxidant power assay in 303 follicular fluid samples. The main outcome measures were follicular fluid TAC, percentage TAC loss after 72 h and early reproductive outcomes. RESULTS: Follicular TAC was elevated in women with infertility of 'unexplained' (UE) or tubal factor (TF) aetiology, relative to those with male factor (MF) infertility, when reproductive outcomes were positive but not when they were negative. In the TF and UE groups, low TAC was associated with ovum fertilization incompetence, whereas TAC was comparable irrespective of embryo viability. Unexplained infertility was associated with significantly elevated follicular TAC. Among women with polycystic ovaries, fertilization incompetence was associated with elevated TAC; the opposite was true in women with normal ovaries. Follicular fluid 72-h TAC consumption > 20% was associated with poorer reproductive performance. CONCLUSIONS: The follicular fluid pro-oxidant-antioxidant balance required for conception in women undergoing IVF is related to the aetiology of infertility, age, the presence of polycystic ovary morphology and smoking.

Vascular dysfunction during pregnancy in women with polycystic ovary syndrome.

BACKGROUND: An association has been proposed between polycystic ovary syndrome (PCOS) and pregnancy-induced hypertensive disorders. Ambulatory blood pressure and carotid artery elasticity were therefore prospectively investigated in matched PCOS and control pregnancies. METHODS: Twenty-two PCOS-control subject pairs with singleton pregnancies, matched for age, body mass index, parity and ethnicity, were recruited in the first trimester (T1, 11-13 weeks). Ambulatory blood pressure recording for 24 h and carotid artery ultrasound for elasticity estimation were performed in T1 and in the second (T2, 22-24 weeks) and third (T3, 32-34 weeks) trimesters. RESULTS: At nearly all time points during gestation, ambulatory systolic, diastolic and mean arterial pressures were elevated in PCOS versus control pregnancies. Carotid artery stiffness index was greater and compliance was less in PCOS pregnancies compared with controls. Differences in night-time systolic pressure and carotid artery elasticity were greatest in T3. PCOS also increased the incidence of pregnancy-induced hypertension (6 of 22 cases versus 0 of 22 in controls; P = 0.011). CONCLUSIONS: Pregnant women with PCOS have higher baseline ambulatory blood pressure and impaired arterial elasticity, suggestive of disturbed vascular adaptation to pregnancy.

Aortic function is compromised in a rat model of polycystic ovary syndrome.

BACKGROUND: Arterial mechanical parameters are modified in women with polycystic ovary syndrome (PCOS), before and during pregnancy. This study tested the hypothesis that aortic mechanics and endothelial function are modified in the mifepristone-treated rat model of PCOS. METHODS: Female rats injected daily with mifepristone or vehicle for 7-9 days were assessed by ultrasound to allow estimation of aortic stiffness index and compliance. The influence of acetylcholine (ACh) and sodium nitroprusside (SNP) on dissected phenylephrine-contracted aortic rings was assessed. RESULTS: Aortic compliance was reduced by 67% in mifepristone-treated rats versus controls (P<0.05), while stiffness index was increased 2.3-fold (P<0.02). ACh-induced dilation was less in aortic rings from mifepristone-treated rats (P=0.022) and was less sensitive to the nitric oxide (NO) synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME) (P<0.001), while SNP-induced dilation was greater (P=0.001). CONCLUSIONS: Aortic mechanics in vivo and endothelial function in vitro were consistently perturbed in mifepristone-treated rats. Aortic ring behaviour suggested that NO release was depressed or degradation elevated, with a compensatory increase in NO sensitivity and/or activation of a non-NO-mediated relaxation mechanism. The mifepristone-treated rat is a valid model for investigation of the vascular deficits seen in PCOS.

The expression of DJ-1 (PARK7) in normal human CNS and idiopathic Parkinson's disease.

Two mutations in the DJ-1 gene on chromosome1p36 have been identified recently to cause early-onset, autosomal recessive Parkinson's disease. As no information is available regarding the distribution of DJ-1 protein in the human brain, in this study we used a monoclonal antibody for DJ-1 to map its distribution in frontal cortex and substantia nigra, regions invariably involved in Parkinson's disease. Western blotting of human frontal cortex showed DJ-1 to be an abundant protein in control, idiopathic Parkinson's disease, cases with clinical and pathological phenotypes of Parkinson's disease with R98Q polymorphism for DJ-1, and in progressive supranuclear palsy (PSP) brains. We also showed that DJ-1 immunoreactivity (IR) was particularly prominent in astrocytes and astrocytic processes in both control and Parkinson's disease frontal cortex, whereas neurons showed light or no DJ-1 IR. Only occasional Lewy bodies (LBs), the pathological hallmarks of Parkinson's disease, showed faint DJ-1 IR, localized to the outer halo. In preclinical studies we showed that DJ-1 is expressed in primary hippocampal and astrocyte cultures of mouse brain. By 2D gel analysis we also showed multiple pI isoforms for DJ-1 ranging between 5.5-6.6 in both control and Parkinson's disease brains, whilst exposure of M17 cells to the oxidizing agent paraquat was manifested as a shift in pI of endogenous DJ-1 towards more acidic isoforms. We conclude that DJ-1 is not an essential component of LBs and Lewy neurites, is expressed mainly by astrocytes in human brain tissue and is sensitive to oxidative stress conditions. These results are consistent with the hypothesis that neuronal-glial interactions are important in the pathophysiology of Parkinson's disease.

Thyroid hormone regulates the expression of alpha-internexin in neurons in culture.

Maternal hypothyroidism in the rat compromises alpha-internexin (alpha-IN) expression in early fetal brain. We have therefore examined whether 3,5,3'-triiodothyronine (T3) regulates alpha-IN expression in fetal brain neurons in culture. Cells expressed transcripts encoding T3 nuclear receptor isoforms in a T3-independent manner. alpha-IN protein abundance was increased in cultures treated with 0.1 and 1 nM T3 for 20 h (177 and 185% control, respectively) and in cultures treated with 1 nM T3 for 40 h (131% control). alpha-IN transcript abundance was unaffected by T3 treatment. In conclusion, T3 at a physiological level, stimulates alpha-IN protein, but not mRNA, levels in early differentiating neurons in culture. This supports the hypothesis that maternal thyroid hormone directly regulates early neuronal differentiation.