• Maternal psychological distress, breast milk extracellular vesicles, and infant immunity: A translational study.
    1 week ago
    Distress during early postnatal life has a potential impact on maternal mental health and related biological systems. However, the potential biological roles of these systems' modifications remain largely unknown. Bronchiolitis represents a life-threatening condition for infants and a possible stressful event for mothers with an impact on maternal breast milk composition and potentially on infants'health. In this framework purposes of the present study were: a) to evaluate the impact of infants' severe bronchiolitis on maternal mental health; b) to examine the correlation between maternal mental health status and extracellular vesicles (EVs) in breast milk; c) to explore the impact of breast milk EVs modification on the infant's innate immunity. We hypothesize that severe infant illness acts as a maternal stressor, which in turn remodels the composition of breast-milk EVs, thereby modulating immune response in the infant affected by bronchiolitis. A prospective, observational study with a case-control design and a longitudinal observation component was conducted. The case group included dyads of mothers and infants, with the infants admitted to the pediatric emergency department for severe bronchiolitis, while the control group consisted of healthy mother-infant dyads. The two groups were evaluated at baseline (admission for bronchiolitis for cases) and after one month. In both the appointments clinical data including mental health status by validated scales and a breast milk sample were collected. Biological analyses included extracellular vesicles (EVs) isolation and characterization, and the use of zebrafish to study the EVs-mediated modulation of innate immunity. Baseline mental health assessment revealed markedly higher scores in the case group for depressive symptoms (p < 0.01) and state anxiety (p < 0.01). These symptoms ameliorated over time in the case group. At baseline, cases showed higher concentrations of CD177+ EVs compared to controls (p = 0.02). Among T cell-derived EVs, CD4+ vesicles were significantly more abundant in cases than controls at follow-up (p = 0.04). At baseline maternal functioning was inversely associated with several EV subtypes. Finally, the treatment of zebrafish embryos with baseline EVs of cases with low level of anxiety resulted in a significant increase in neutrophil recruitment. This study suggests the existence of a complex interplay between stressful events, maternal mental health and innate immune modulation of infants with an acute infectious disease. New studies are needed to confirm the results of the present research.
    Mental Health
    Care/Management
  • Reproducible human reward imaging phenotypes exhibit differential sensitivity to dopamine D2 receptor antagonism.
    1 week ago
    Human reward processing varies along cue-centric and outcome-centric axes, but the mechanistic basis of individual variation in incentive salience attribution remains incompletely characterized. Here we show, using fMRI across five cohorts (N-total = 1251; N1 = 890; N2 = 245; N3 = 34; N4 = 48; N5 = 34), two reproducible imaging phenotypes mirroring sign- and goal-tracking (ST-like, GT-like). ST-like individuals showed dominant ventral striatal responses to reward-anticipation cues and sustained incentive salience attribution; GT-like individuals showed heightened responses to reward outcomes. This distinction was replicable across sites and independent samples. Single-dose and repeated-dose D2/D3 antagonism (risperidone, haloperidol, amisulpride) selectively reduced anticipatory ventral striatal activity in ST, with single-dose antagonism additionally producing a parallel drop in self-reported energy. Instead, D2/D3 partial agonism (aripiprazole) increased anticipatory and reduced outcome-phase responses in GT. In a psychosis cohort, antipsychotic D2 affinity was associated with blunted anticipatory signals and higher negative symptom burden, offering a neuroimaging-driven basis for stratifying patients and predicting response to dopaminergic agents.
    Mental Health
    Care/Management
  • Temporal trend analysis of the global prevalence of vision impairment and blindness attributable to diabetes from 1990 to 2021.
    1 week ago
    This study aimed to systematically assess the burden and temporal patterns of vision impairment due to diabetes mellitus (DM), including moderate vision loss (MVL), severe vision loss (SVL), and blindness, and to identify the demographic drivers of future changes.

    An age-period-cohort (APC) model was used to evaluate the effects of age, period, and birth cohort on diabetes-related vision impairment, with analyses stratified by diabetes type, including type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM). Decomposition analysis was further conducted to quantify the relative contributions of population aging, population growth, and epidemiological changes to projected changes in prevalent case numbers through 2030.

    the age-standardized prevalence rates (ASPRs) of blindness due to type 1 diabetes mellitus (T1DM) continued to rise [males: average annual percentage change (AAPC) = 0.82% (95%CI 0.40-1.23); females: AAPC = 1.31% (95%CI 0.86-1.77)]. The age effect indicated that older populations were at higher risk. Meanwhile, the cohort effect revealed that in regions with high Sociodemographic Index (SDI), high-middle SDI, and middle SDI, later-born cohorts had a significantly higher risk of diabetes-related vision impairment compared to earlier-born cohorts. Globally and in most regions, population growth was the main driver of increased in the number of prevalent MVL and SVL cases, whereas epidemiological change contributed most to increases in prevalent blindness cases. However, population aging had a particularly substantial impact in East Asia, High-income Asia Pacific, Central Europe, Eastern Europe, and Western Europe.

    The global burden of vision impairment due to DM increased continuously. Older populations represented high-risk groups, and the burden varied by sex, diabetes type, and socioeconomic development, with T2DM contributing most to the overall increase in diabetes-related vision impairment. Although population growth and epidemiological changes were major contributors, the impact of population aging in certain regions was also noteworthy.
    Non-Communicable Diseases
    Diabetes
    Diabetes type 1
    Diabetes type 2
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    Policy
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  • Chronic Stress Exacerbates Osteoporosis in Ovariectomized Mice With Anxiety- and Depression-Like Symptoms by Activating Cathepsin K and Impairing Autophagy.
    1 week ago
    Chronic stress (CS) acts as both an initiating and aggravating factor for depression and osteoporosis. Cumulative evidence indicates that Cathepsin K (Cat K), a cysteine protease, is functionally linked to chronic stress and exerts critical regulatory roles in bone metabolism. Nevertheless, the molecular mechanisms whereby CS promotes osteoporosis in the background of mood-related disturbances remain poorly defined. In the present work, we established a combined mouse model of osteoporosis and chronic stress. We evaluated anxiety- and depression-like behaviors, the expression profiles of Cat K, autophagy-, apoptosis-, and inflammation-associated proteins in bone tissue, as well as vascular senescence in experimental animals. Furthermore, we investigated the biological effects of serum collected from chronically-stressed mice on MC3T3-E1 osteoblast-like cells. Following 8-week chronic stress exposure, ovariectomized (OVX) mice developed prominent anxiety- and depression-like behaviors, accompanied by deteriorated osteoporosis and aortic senescence. Meanwhile, bone tissues exhibited elevated levels of Cat K, p62, pro-inflammatory mediators, and apoptosis-related proteins, whereas the autophagy marker LC3B/A was down-regulated. Administration of E64d, a cysteine protease inhibitor, markedly reversed these pathological alterations. In vitro culture revealed that serum from chronically-stressed mice suppressed the viability of MC3T3-E1 osteoblast-like cells. Pharmacological inhibition of Cat K restored autophagic activity, mitigated the overexpression of pro-inflammatory and pro-apoptotic mediators, and rescued MC3T3-E1 cells from stress-triggered injury. Collectively, our findings demonstrate that chronic stress induces anxiety- and depression-like phenotypes in OVX mice and accelerates bone loss, at least partially via Cat K activation and autophagy suppression.
    Non-Communicable Diseases
    Cardiovascular diseases
    Care/Management
  • High Prevalence of Diabetes, Hypertension and Obesity in Guinea-Bissau-Results From a Nationwide Study Carried Out From 2022 to 2024.
    1 week ago
    Non-communicable diseases (NCDs) are rising rapidly in Sub-Saharan Africa. In Guinea-Bissau, nationwide data are scarce. We aimed to estimate the multi-regional prevalence of type 2 diabetes (T2D), obesity, and hypertension and examine associated risk factors within this resource-limited context.

    A multi-regional cross-sectional survey was conducted using a hybrid community- and facility-based sampling approach across urban Bissau, including at the National Diabetes Clinic [CND] and in seven interior regions of the country. Recruitment was conducted between August 3th 2022 and June 8th 2024 across these sites. After a verified 12-h fast, participants underwent capillary glucose, blood pressure, and anthropometric measurements. Diabetes was defined as fasting glucose ≥ 126 mg/dL or previous diagnosis; prediabetes as 110-125 mg/dL; obesity as BMI ≥ 30 kg/m²; and hypertension as blood pressure ≥ 140/90 mmHg. Multivariable logistic regression identified factors associated with diabetes.

    Among 3929 participants, with median age 41 years, the overall raw diabetes prevalence was 20.8% (817/3929), with 30% being newly screen-detected. The T2D prevalence at the specialized CND was 22.8% (342/1502), compared to 18.0% (174/969) in community settings outside health facilities in Bissau. The prediabetes prevalence was 9.1%; while the obesity prevalence was 14.8%, disproportionately affecting more women, at 20.7% vs. 9.1% in men; and the prevalence of hypertension was exceptionally high at 40.4%. In the multivariable model, key risk drivers included age ≥ 55 years (OR 14.0, 95% CI: 8.57-22.9), family history (OR 3.78, 3.02-4.74), Fula ethnicity (OR 2.47, 1.73-3.53), and low physical activity (OR 1.44, 1.17-1.78).

    Guinea-Bissau faces a critical, underreported burden of metabolic and cardiovascular NCDs, particularly T2D and hypertension. Given the recruitment pathways, the overall prevalence reflects a high-risk baseline that warrants cautious national extrapolation. Urgent, context-specific public health strategies and decentralized clinical guidelines are required to manage these chronic conditions amidst severe structural resource constraints.
    Non-Communicable Diseases
    Cardiovascular diseases
    Care/Management
  • Feasibility of measuring walking speed in a diabetes clinic in primary care.
    1 week ago
    Usual walking speed may predict cardiovascular disease in type 2 diabetes, but it is not routinely assessed in UK primary care.

    To examine the feasibility of three methods of assessing walking speed in patients with diabetes in general practice: timed walking, accelerometry, and treadmill walking.

    We approached consecutive mobile patients attending a general practice diabetes clinic. Consenting participants performed a timed 28-m walk (4 × 7 m) at their usual pace in the surgery corridor while wearing an accelerometer, followed by a 3-minute treadmill walk. Measures were repeated after 6 months. Differences in walking speeds between methods and between timepoints were assessed by Bland-Altman limits of agreement.

    Recruitment rate was 91% (30/33). Mean age of participants was 59.6 years (range 37-75), mean body mass index was 30.6 kg/m2 (21.0-46.4), and 17% had a history of cardiovascular disease. Average duration of diabetes was 10 years (range 1-40). Twenty-five participants (83%) repeated assessments at 6-month follow-up.Average (SD) walking speed on the timed walk was similar to both accelerometer and treadmill: 1.12 (0.13), 1.15 (0.16), and 1.01 (0.39) m/s, respectively. Bland-Altman analysis showed good agreement for repeat tests and, on average, between methods. Limits of agreement between timed walk and treadmill were wide. Feedback from seven participants and three practice staff indicated acceptability of all tests, but treadmill testing took longer and least feasible.

    Timed walk was the most feasible and acceptable to patients and staff. Results were similar on average to accelerometry and treadmill.
    Diabetes
    Diabetes type 2
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    Care/Management
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  • The joint association of loneliness, social isolation, and satisfaction with major depressive disorder incidence in individuals with diabetes.
    1 week ago
    To investigate the joint associations of life satisfaction, loneliness and social isolation in relation to the risk of incident major depressive disorder (MDD) in diabetes patients.

    A total of 7712 participants with diagnosed diabetes at baseline from the UK Biobank were included. Cox proportional hazards models and interaction analyses were used to examine associations of loneliness, social isolation, and life satisfaction with MDD.

    During a median follow-up time of 11.1 years, 442 participants developed MDD (incidence rate: 5.73%). Participants with high loneliness, high social isolation, and low life satisfaction were associated with 176%, 82%, and 493% higher risks of MDD compared to those with low loneliness, low social isolation, and high life satisfaction, respectively (all P < 0.001). Several statistically significant interactions between loneliness and different aspects of life satisfaction were identified in relation to incident MDD. Participants with both low life satisfaction and high loneliness were at 8.06 times the risk of MDD than those with high life satisfaction and low loneliness.

    In individuals with diabetes, higher loneliness and social isolation are associated with increased MDD risk, whereas higher life satisfaction was associated with a lower risk. The joint associations varied across levels and domains of life satisfaction, although interaction patterns were not consistent across all measures or statistical scales. These findings may help identify individuals at elevated risk of MDD but should be interpreted cautiously given the observational design, potential residual confounding, and measurement limitations.
    Diabetes
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  • Clinical Burden of Disease and Demographics in Older Adults Hospitalized with RSV Infection in England: A Retrospective Cohort Study.
    1 week ago
    Respiratory syncytial virus (RSV) causes significant disease in older and comorbid adults. Current UK vaccination recommendations restrict eligibility to adults ≥ 75 years, 65-74 years with chronic respiratory disease or immunosuppression, and those in care homes, but evidence on clinical burden in adults < 75 years with comorbidities is limited. This study assessed patient characteristics, healthcare resource utilization (HCRU), and mortality in adults hospitalized with RSV in England.

    Population-based retrospective cohort study using linked Clinical Practice Research Datalink Aurum and Hospital Episode Statistics. Adults ≥ 60 years hospitalized with RSV between October 2014 and March 2019 were included. We defined RSV episodes as 90 days post-diagnosis. We defined cases using diagnosis codes for confirmed RSV (RSV-specific) or acute lower respiratory tract infection with exclusion of other causative pathogens (RSV-possible). All-cause HCRU (hospitalizations, critical care admissions, outpatient attendance, primary care consultations, and prescriptions) and case fatality rates were assessed. Results were stratified by age (60-74 and ≥ 75 years), case definitions (RSV-specific, RSV-possible), and comorbidity profiles (chronic respiratory disease, immunocompromised, cardiovascular disease).

    A total of 97,712 hospitalized episodes in those aged ≥ 60 years were included in the analysis, of which 785 (0.8%) were RSV-specific cases (n = 338 aged 60-74 years, n = 447 aged ≥ 75 years). In RSV-specific cases, median (IQR) cumulative length of stay (LoS) for those ≥ 75 years was 10.00 (6.00-22.00) days, which was equivalent to or lower than each comorbidity subgroup in those aged 60-74 years, with the longest LoS in those immunocompromised (11.50 [7.00-26.00] days). Critical care admissions were more often observed across comorbidity stratifications (13.85-22.34%) compared to those ≥ 75 years (5.03%). All-cause and RSV-related case fatality rates for RSV-specific cases were highest among those ≥ 75 years (all-cause: 19.3%; RSV-related: 10.3%).

    HCRU within RSV episodes in those aged 60-74 years across comorbidity profiles was equal to or greater than that in those aged ≥ 75 years. These findings highlight the need to prioritize consideration of comorbidity groups that could benefit from RSV vaccination.
    Diabetes
    Chronic respiratory disease
    Cardiovascular diseases
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    Care/Management
  • Association between diabetes mellitus and short-term outcomes after transsphenoidal surgery for pituitary tumor: Evidence from the Taiwan Pituitary Tumor Registry 2009-2019.
    1 week ago
    Diabetes mellitus (DM) may affect postoperative recovery, but evidence in pituitary tumor surgery remains limited. We investigated the association between DM and short-term outcomes after transsphenoidal surgery for pituitary tumors.

    We retrospectively analyzed adults in the Taiwan Pituitary Tumor Registry who underwent transsphenoidal surgery for benign pituitary tumors between 2009 and 2019. Patients were categorized into DM and non-DM groups. Associations between DM, prolonged length of hospital stays (LOS), 14-day readmission rate, and complications were determined using regression analyses. Tumor-type stratified analyses and receiver operating characteristic (ROC) analyses of glycated hemoglobin (HbA1c), fasting glucose, and random glucose were also performed.

    Data of 970 patients were analyzed, of whom 144 (15%) had DM. DM was not significantly associated with prolonged LOS or 14-day readmission, but was significantly associated with higher odds of CSF leak (adjusted odds ratio [aOR] = 3.35, 95% confidence interval [CI]: 1.18-9.51, p = 0.023) and antibiotic use for ≥ 7 days (aOR = 5.41, 95% CI: 1.13-25.87, p = 0.034) in age-adjusted analysis. In the non-functioning tumor subgroup, the association with antibiotic use for ≥ 7 days persisted (aOR 7.37, 95% CI 1.46-37.12), whereas the association with CSF leak was not statistically significant. Among patients with DM and non-functioning tumors, glycemic markers showed apparent discrimination for postoperative infection and CSF leak, with area under the curve values ranging from 0.83 to 0.93.

    DM was associated with selected short-term complications after transsphenoidal surgery, particularly CSF leak and prolonged antibiotic use. These exploratory findings require confirmation in larger prospective studies with comprehensive surgical data.
    Diabetes
    Cancer
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    Care/Management
    Advocacy
  • Diagnosis and Management of Adult Type 1 Diabetes Mellitus: Systematic Reviews of Biomarkers, Insulin Regimens and Insulin Delivery Devices Highlighting Evidence Gaps in Emergency and Humanitarian Settings.
    1 week ago
    Supporting the World Health Organization's (WHO) 2021 Global Diabetes Compact's goals, we conducted three systematic reviews on type 1 diabetes (T1D) in adults concerning (1) diagnostic biomarkers, (2) insulin regimens and (3) insulin delivery devices, focusing on emergency and humanitarian settings.

    Multiple databases were searched in October 2024 without language or date restrictions. Two reviewers independently selected studies, extracted data and assessed risk of bias using study-specific tools. Critical outcomes included Haemoglobin A1c (HbA1c), hypoglycaemia, microvascular and macrovascular complications, diabetic ketoacidosis, mortality, adverse events, alongside diagnostic accuracy measures and patient-centred outcomes. Where appropriate, random-effects meta-analyses were performed, and certainty of evidence was assessed using Grading of Recommendations Assessment, Development and Evaluation (GRADE).

    The biomarkers review (n = 15 studies) found C-peptide and other autoantibodies showed high specificity but variable sensitivity for T1DM diagnosis. The insulin regimen review (three reports from one small trial) suggested possible differences in glycaemic control and nephropathy outcomes between multiple daily and twice-daily regimens. The insulin delivery devices review (n = 8 studies) showed strong patient preference for pens; pooled analyses of HbA1c, hypoglycaemia and quality of life demonstrated outcomes comparable to syringes. Overall, the evidence was sparse, low quality and limited to high-income countries, with none of the studies addressing emergency or humanitarian settings. Certainty of evidence was very low for the biomarkers and delivery devices reviews and low for the insulin regimen review.

    Evidence for T1D care in emergency and humanitarian settings remains very limited. Evidence for biomarker use for diagnoses is constrained by very low-certainty evidence and infrastructure barriers. Multiple daily insulin regimens may confer glycaemic benefits, whereas pens and syringes yield similar outcomes despite patients' preference for pens. Evidence gaps underscore the need for pragmatic, context-sensitive guidance balancing clinical and logistical considerations.

    PROSPERO (CRD420250649000).
    Diabetes
    Diabetes type 1
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    Care/Management