Planetary Health Diet Index and risk of total and cause-specific mortality in three prospective cohorts.

BACKGROUND: In 2019, the EAT-Lancet Commission proposed a healthy dietary pattern that, along with reductions in food waste and improved agricultural practices, could feed the increasing global population sustainably. We developed a Planetary Health Diet Index (PHDI) to quantify adherence to the EAT-Lancet reference diet. OBJECTIVES: We aimed to assess associations between PHDI and total and cause-specific mortality in 3 prospective cohorts of males and females in the United States. METHODS: We followed 66,692 females from the Nurses' Health Study (1986-2019), 92,438 females from the Nurses' Health Study II (1989-2019), and 47,274 males from the Health Professionals Follow-up Study (1986-2018) who were free of cancer, diabetes, and major cardiovascular diseases at baseline. The PHDI was calculated every 4 y using a semiquantitative food frequency questionnaire. Hazard ratios (HRs) were calculated using multivariable proportional-hazards models. RESULTS: During follow-up, we documented 31,330 deaths among females and 23,206 among males. When comparing the highest with the lowest quintile of PHDI, the pooled multivariable-adjusted HRs were 0.77 [95% confidence interval (CI): 0.75, 0.80] for all-cause mortality (P-trend < 0.0001). The PHDI was associated with lower risk of deaths from cardiovascular diseases (HR: 0.86; 95% CI: 0.81, 0.91), cancer (HR: 0.90; 95% CI: 0.85, 0.95), respiratory diseases (HR: 0.53; 95% CI: 0.48, 0.59), and neurodegenerative diseases (HR: 0.72; 95% CI: 0.67, 0.78). In females, but not males, the PHDI was also significantly associated with a lower risk of deaths from infectious diseases (HR: 0.62; 95% CI: 0.51, 0.76). PHDI scores were also associated inversely with greenhouse gas emissions and other environmental impacts. CONCLUSIONS: In 3 large United States-based prospective cohorts of males and females with up to 34 y of follow-up, a higher PHDI was associated with lower risk of total and cause-specific mortality and environment impacts.

All-cause and cause-specific mortality risk and loss in life expectancy associated with incident type 2 diabetes onset age and duration.

BACKGROUND: Evidence on type 2 diabetes onset age and duration on mortality risk has been limited by short follow-up, inadequate control for confounding, missing repeated measurements, and inability to cover the full range of onset age, duration, and major causes of death. Moreover, scarce data dissect how type 2 diabetes onset age and duration shape life expectancy. METHODS: We evaluate prospectively these topics based on 270,075 eligible participants in the Nurses' Health Studies and Health Professionals Follow-up Study, leveraging repeated measurements throughout up to 40 years of follow-up. Cox models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: In fully adjusted analyses, incident early onset type 2 diabetes (diagnosed <40 years of age) was associated with significantly higher mortality from all-causes (HR, 95% CI was 3.16, 2.64-3.79; vs. individuals without type 2 diabetes), cardiovascular disease (6.56, 4.27-10.1), respiratory disease (3.43, 1.38-8.51), neurodegenerative disease (5.13, 2.09-12.6), and kidney disease (8.55, 1.98-36.9). The relative risk elevations declined dramatically with each higher decade of age at diagnosis for deaths from most of these causes, though the absolute risk difference increased continuously. A substantially higher cumulative incidence of mortality and a greater loss in life expectancy were associated with younger age at type 2 diabetes diagnosis. Longer disease duration was associated with generally higher relative and absolute risk of mortality. CONCLUSION: Early onset of type 2 diabetes and longer disease duration are associated with substantially increased risk of all-cause and cause-specific mortality and greater loss in life expectancy.

A Cadaveric Feasibility Study of the Biportal Endoscopic Transfrontal Sinus Approach: A Minimally Invasive Approach to the Anterior Cranial Fossa.

BACKGROUND AND OBJECTIVES: The trans-sinus transglabellar and bifrontal approaches offer direct access to the anterior cranial fossa. However, these approaches present potential drawbacks. We propose the biportal endoscopic transfrontal sinus (BETS) approach, adapting endoscopic endonasal approach (EEA) techniques for minimally invasive access to the anterior fossa, reducing tissue manipulation, venous sacrifice, and brain retraction. METHODS: Six formalin specimens were used. BETS approach involves 2 incisions over the medial aspect of both eyebrows from the supraorbital notch to the medial end of the eyebrow. A unilateral pedicled pericranial flap is harvested. A craniotomy through the anterior table of the frontal sinus (FS) and a separate craniotomy through the posterior table are performed. Two variants of the approach (preservative vs cranialization) are described for opening and reconstruction of the FS based on the desired pathology to access. Bone flap replacement can be performed with titanium plates and filling of the external table defect with bone cement. RESULTS: Like in EEA, this approach provides access for endoscope and multiple working instruments to be used simultaneously. The approach allows wide access to the anterior cranial fossa, subfrontal, and interhemispheric corridors, all the way up to the suprachiasmatic corridor and through the lamina terminalis to the third ventricle. BETS provides direct access to the anterior fossa, minimizing the level of frontal lobe retraction and providing potentially less tissue disruption and improved cosmesis. Cerebrospinal fluid fistula risk remains one of the major concerns as the narrow corridor limits achieving a watertight closure which can be mitigated with a pedicled flap. Mucocele risk is minimized with full cranialization or reconstruction of the FS. CONCLUSION: The BETS approach is a minimally invasive approach that translates the concepts of EEA to the FS. It allows excellent access to the anterior cranial fossa structures with minimal frontal lobe retraction.

Lipidome changes due to improved dietary fat quality inform cardiometabolic risk reduction and precision nutrition.

Current cardiometabolic disease prevention guidelines recommend increasing dietary unsaturated fat intake while reducing saturated fats. Here we use lipidomics data from a randomized controlled dietary intervention trial to construct a multilipid score (MLS), summarizing the effects of replacing saturated fat with unsaturated fat on 45 lipid metabolite concentrations. In the EPIC-Potsdam cohort, a difference in the MLS, reflecting better dietary fat quality, was associated with a significant reduction in the incidence of cardiovascular disease (-32%; 95% confidence interval (95% CI): -21% to -42%) and type 2 diabetes (-26%; 95% CI: -15% to -35%). We built a closely correlated simplified score, reduced MLS (rMLS), and observed that beneficial rMLS changes, suggesting improved dietary fat quality over 10 years, were associated with lower diabetes risk (odds ratio per standard deviation of 0.76; 95% CI: 0.59 to 0.98) in the Nurses' Health Study. Furthermore, in the PREDIMED trial, an olive oil-rich Mediterranean diet intervention primarily reduced diabetes incidence among participants with unfavorable preintervention rMLS levels, suggestive of disturbed lipid metabolism before intervention. Our findings indicate that the effects of dietary fat quality on the lipidome can contribute to a more precise understanding and possible prediction of the health outcomes of specific dietary fat modifications.

Minimally Invasive Bilateral Duo-Keyhole Approach for Giant Falcine Meningioma: 2 Dimensional Operative Video.

One of the key concepts behind minimally invasive keyhole cranial surgery is that as the operative corridor deepens, it also widens. The corridor should therefore be designed parallel to the long-axis of the tumor to optimize visualization.1 These ideas were applied in a duo-keyhole operation for a falcine meningioma. The patient is a 79-year-old woman diagnosed with a large falcine meningioma compressing both frontal lobes. Her tumor was oriented with the long-axis, perpendicular to the superior sagittal sinus, and has bulbous extensions on both sides of the falx. Incisions on the falx, anterior and posterior to the tumor, in addition to a cut between it and the undersurface of the superior sagittal sinus, would render it practically devascularized and "free-floating.2" One keyhole was insufficient, but one anterior and another posterior to the tumor would make the falcine cuts feasible. The operation was performed with the above scheme and the posterior keyhole to the left and anterior one to the right of midline to facilitate surface vascular detachment on both sides. The patient recovered well and was discharged home after 4 days. This procedure highlights that flexible application of the principles of minimally invasive keyhole. Neurosurgery can tailor-make an operation to precisely fit the unique features of a patient and the tumor. The procedure was performed under the ethical guidelines of our hospital. No Institutional Review Board consent was required or sought because the patient gave specific consent to the procedure and publication of her image.

Total magnesium intake and risk of frailty in older women.

BACKGROUND: An adequate magnesium intake might lower the risk of frailty through its role in muscle function. METHODS: We analysed data from 81 524 women aged ≥60 years participating in the Nurses' Health Study. Total magnesium intake was obtained from repeated food frequency questionnaires administered between 1984 and 2010 and self-reported information on supplementation. Frailty was defined as having at least three of the following five FRAIL scale criteria: fatigue, low strength, reduced aerobic capacity, having ≥5 chronic illnesses and weight loss ≥ 5%. The occurrence of frailty was assessed every 4 years from 1992 to 2018. Cox proportional hazards models adjusted for lifestyle factors, medication use and dietary factors were used to assess the association between magnesium intake and frailty. RESULTS: During a median follow-up of 16 years, we identified 15 477 incident cases of frailty. Women with a higher intake of total energy-adjusted magnesium had a decreased risk of frailty after adjustment for lifestyle factors, medication use and dietary factors. The relative risk (95% confidence interval) for Quintile 5 (Q5) versus Quintile 1 (Q1) was 0.88 (0.82, 0.94) (P-trend < 0.001). When only energy-adjusted magnesium from the diet was considered, the inverse association was stronger (Q5 vs. Q1: 0.68 [0.56, 0.82]; P-trend < 0.001). Those reaching the recommended daily allowance (RDA) of magnesium through diet had a 14% (9%, 19%) lower risk of frailty compared with those not meeting the RDA. CONCLUSIONS: Increased intake of foods rich in magnesium was associated with a decreased risk of frailty.

Sedentary Behaviors, Light-Intensity Physical Activity, and Healthy Aging.

Importance: Sleep duration and moderate-to-vigorous physical activity (MVPA) are associated with healthy aging, but the associations of sedentary behaviors and light-intensity physical activity (LPA) with healthy aging are still unclear. Objective: To examine the independent association of sedentary behaviors and LPA with healthy aging, and to estimate the theoretical association of replacing sedentary behavior with LPA, MVPA, or sleep with healthy aging. Design, Setting, and Participants: In this cohort study using data from the Nurses' Health Study, participants aged 50 years or older and free of major chronic diseases in 1992 were prospectively followed up for 20 years. Data were analyzed from January to May 2022. Exposures: Three measures for sedentary behaviors (hours watching television, sitting at work, and other sitting at home) and 2 measures for LPA (hours of standing or walking around at home [LPA-Home] and at work [LPA-Work]). Main Outcomes and Measures: Healthy aging was defined as survival to at least age 70 years with maintenance of 4 health domains (ie, no major chronic diseases and no impairment in subjective memory, physical function, or mental health). The isotemporal substitution model was used to evaluate the potential impact on healthy aging of replacing 1 hour of 1 behavior with equivalent duration of another. Results: Among 45 176 participants (mean [SD] age, 59.2 [6.0] years), 3873 (8.6%) women achieved healthy aging. After adjustment for covariates including MVPA, each increment of 2 hours per day in sitting watching television was associated with a 12% (95% CI, 7%-17%) reduction in the odds of healthy aging. In contrast, each increase of 2 hours per day in LPA-Work was associated with a 6% (95% CI, 3%-9%) increase in the odds of healthy aging. Replacing 1 hour of sitting watching television with LPA-Home (OR, 1.08; 95% CI, 1.05-1.12), LPA-Work (OR, 1.10; 95% CI, 1.07-1.14), or MVPA (OR, 1.28; 95% CI, 1.23-1.34) was associated with increased odds of healthy aging. Among participants who slept 7 hours per day or less, replacing television time with sleep was also associated with increased odds of healthy aging. Conclusions and Relevance: In this cohort study, longer television watching time decreased odds of healthy aging, whereas LPA and MVPA increased odds of healthy aging and replacing sitting watching television with LPA or MVPA, or with sleep in those who slept 7 hours per day or less, was associated with increased odds of healthy aging, providing evidence for rearranging 24-hour behavior to promote overall health.

Ultra-Processed Food Intake and Risk of Systemic Lupus Erythematosus among Women followed in the Nurses' Health Study Cohorts.

OBJECTIVE: We assessed ultra-processed food (UPF) intake and SLE incidence within the prospective Nurses' Health Study cohorts. METHODS: 204,175 women were followed, NHS: 1984 - 2016; NHSII: 1991 - 2017. Semi-quantitative food frequency questionnaires were completed every 2-4 years. UPF intake was determined as per the Nova classification. Nurses self-reported new doctor-diagnosed SLE, confirmed by medical records. Time-varying Cox regressions estimated hazard ratios (HR, 95% confidence intervals) for incident SLE and SLE by anti-double stranded DNA antibody (dsDNA) at diagnosis, according to cumulatively-updated daily: a) UPF servings, b) total intake (gms + mls), and c) % total intake. Analyses adjusted for age, race, cohort, caloric and alcohol intakes, household income, smoking, body mass index (BMI), physical activity, menarchal age, and oral contraceptive use. We tested for interaction with BMI and examined UPF categories. RESULTS: Mean baseline age was ~50 years (NHS) and ~36 years (NHSII); 93% self-reported White race. 212 incident SLE cases were identified. SLE risk was higher in 3rd vs. 1st UPF tertile (servings/day pooled multivariable [MV] HR 1.56 (1.04-2.32); p trend 0.03). Results were stronger for dsDNA+ SLE (servings/day pooled MV HR 2.05 (1.15-3.65); p trend 0.01), and for absolute (servings or total) than % total intake. Sugar/artificially-sweetened beverages were associated with SLE risk (3rd vs. 1st tertile MV HR 1.45 (1.01-2.09). No BMI interactions were observed. CONCLUSION: Higher cumulative-average daily UPF intake was associated with >50% increased SLE risk, and with doubled risk for anti-dsDNA+ SLE. Many deleterious effects on systemic inflammation and immunity are postulated.

Alcohol intake and endogenous sex hormones in women: Meta-analysis of cohort studies and Mendelian randomization.

BACKGROUND: The mechanisms underlying alcohol-induced breast carcinogenesis are not fully understood but may involve hormonal changes. METHODS: Cross-sectional associations were investigated between self-reported alcohol intake and serum or plasma concentrations of estradiol, estrone, progesterone (in premenopausal women only), testosterone, androstenedione, dehydroepiandrosterone sulfate, and sex hormone binding globulin (SHBG) in 45 431 premenopausal and 173 476 postmenopausal women. Multivariable linear regression was performed separately for UK Biobank, European Prospective Investigation into Cancer and Nutrition, and Endogenous Hormones and Breast Cancer Collaborative Group, and meta-analyzed the results. For testosterone and SHBG, we also conducted Mendelian randomization and colocalization using the ADH1B (alcohol dehydrogenase 1B) variant (rs1229984). RESULTS: Alcohol intake was positively, though weakly, associated with all hormones (except progesterone in premenopausal women), with increments in concentrations per 10 g/day increment in alcohol intake ranging from 1.7% for luteal estradiol to 6.6% for postmenopausal dehydroepiandrosterone sulfate. There was an inverse association of alcohol with SHBG in postmenopausal women but a small positive association in premenopausal women. Two-sample randomization identified positive associations of alcohol intake with total testosterone (difference per 10 g/day increment: 4.1%; 95% CI, 0.6-7.6) and free testosterone (7.8%; 4.1-11.5), and an inverse association with SHBG (-8.1%; -11.3% to -4.9%). Colocalization suggested a shared causal locus at ADH1B between alcohol intake and higher free testosterone and lower SHBG (posterior probability for H4, 0.81 and 0.97, respectively). CONCLUSIONS: Alcohol intake was associated with small increases in sex hormone concentrations, including bioavailable fractions, which may contribute to its effect on breast cancer risk.

Emerging Roles of Exosomes in Stroke Therapy.

Stroke is the number one cause of morbidity in the United States and number two cause of death worldwide. There is a critical unmet medical need for more effective treatments of ischemic stroke, and this need is increasing with the shift in demographics to an older population. Recently, several studies have reported the therapeutic potential of stem cell-derived exosomes as new candidates for cell-free treatment in stoke. This review focuses on the use of stem cell-derived exosomes as a potential treatment tool for stroke patients. Therapy using exosomes can have a clear clinical advantage over stem cell transplantation in terms of safety, cost, and convenience, as well as reducing bench-to-bed latency due to fewer regulatory milestones. In this review article, we focus on (1) the therapeutic potential of exosomes in stroke treatment, (2) the optimization process of upstream and downstream production, and (3) preclinical application in a stroke animal model. Finally, we discuss the limitations and challenges faced by exosome therapy in future clinical applications.

Strain-specific gut microbial signatures in type 2 diabetes identified in a cross-cohort analysis of 8,117 metagenomes.

The association of gut microbial features with type 2 diabetes (T2D) has been inconsistent due in part to the complexity of this disease and variation in study design. Even in cases in which individual microbial species have been associated with T2D, mechanisms have been unable to be attributed to these associations based on specific microbial strains. We conducted a comprehensive study of the T2D microbiome, analyzing 8,117 shotgun metagenomes from 10 cohorts of individuals with T2D, prediabetes, and normoglycemic status in the United States, Europe, Israel and China. Dysbiosis in 19 phylogenetically diverse species was associated with T2D (false discovery rate < 0.10), for example, enriched Clostridium bolteae and depleted Butyrivibrio crossotus. These microorganisms also contributed to community-level functional changes potentially underlying T2D pathogenesis, for example, perturbations in glucose metabolism. Our study identifies within-species phylogenetic diversity for strains of 27 species that explain inter-individual differences in T2D risk, such as Eubacterium rectale. In some cases, these were explained by strain-specific gene carriage, including loci involved in various mechanisms of horizontal gene transfer and novel biological processes underlying metabolic risk, for example, quorum sensing. In summary, our study provides robust cross-cohort microbial signatures in a strain-resolved manner and offers new mechanistic insights into T2D.

24-h urinary sodium and potassium excretions, plasma metabolomic profiles, and cardiometabolic biomarkers in the United States adults: a cross-sectional study.

BACKGROUND: High-sodium and low-potassium intakes are associated with a higher risk of hypertension and cardiovascular disease, but there are limited data on the circulating metabolomics profiles of 24-h urinary sodium and potassium excretions in free-living individuals. OBJECTIVES: We aimed to characterize the metabolomics signatures of a high-sodium and low-potassium diet in a cross-sectional study. METHODS: In 1028 healthy older adults from the Women's and Men's Lifestyle Validation Studies, we investigated the association of habitual sodium and potassium intakes measured by 2 to 4 24-h urine samples with plasma metabolites (quantified using liquid chromatography-tandem mass spectrometry) and metabolomic pathways. Our primary exposures were energy-adjusted 24-h urinary sodium excretion, potassium excretion, and sodium-to-potassium ratio, calculated based on energy expenditure derived from the doubly labeled water method. We then assessed the partial correlations of their metabolomics scores, derived from elastic net regressions, with cardiometabolic biomarkers. RESULTS: Higher sodium excretion was associated with 38 metabolites including higher piperine, phosphatidylethanolamine, and C5:1 carnitine. In pathway analysis, higher sodium excretion was associated with enhanced biotin and propanoate metabolism and enhanced degradation of lysine and branched-chain amino acids (BCAAs). Metabolites associated with higher potassium and lower sodium-to-potassium ratio included quinic acid and proline-betaine. After adjusting for confounding factors, the metabolomics score for sodium-to-potassium ratio positively correlated with fasting insulin (Spearman's rank correlation coefficient ρ = 0.27), C-peptide (ρ = 0.30), and triglyceride (ρ = 0.46), and negatively with adiponectin (ρ = -0.40), and high-density lipoprotein cholesterol (ρ = -0.42). CONCLUSIONS: We discovered metabolites and metabolomics pathways associated with a high-sodium diet, including metabolites related to biotin, propanoate, lysine, and BCAA pathways. The metabolomics signature for a higher sodium low-potassium diet is associated with multiple components of elevated cardiometabolic risk.

Calibration of citrus intake assessed by food frequency questionnaires using urinary proline betaine in an observational study setting.

BACKGROUND: Whether observational study can be employed to establish calibration equations for self-reported dietary intake using food biomarkers is unknown. OBJECTIVES: This study aims to demonstrate the feasibility of obtaining calibration equations based on food biomarkers and 7-d diet records (7DDRs) to correct measurement errors of food frequency questionnaires (FFQs) in an observational study setting. METHODS: The study population consisted of 669 males and 749 females from the Women's and Men's Lifestyle Validation Studies. In the training set, the biomarker-predicted intake derived by regressing 7DDR-assessed intake on urinary proline betaine concentration was regressed on the FFQ-assessed intake to obtain the calibration equations. The regression coefficients were applied to the test set to calculate the calibrated FFQ intake. We examined total citrus as well as individual citrus fruits/beverages. RESULTS: Urinary proline betaine was moderately correlated with orange juice intake (Pearson correlation [r] = 0.53 for 7DDR and 0.48 for FFQ) but only weakly correlated with intakes of orange (r = 0.12 for 7DDR and 0.15 for FFQ) and grapefruit (r = 0.14 for 7DDR and 0.09 for FFQ). The FFQ-assessed citrus intake was systematically higher than the 7DDR-assessed intake, and after calibrations, the mean calibrated FFQ measurements were almost identical to 7DDR assessments. In the test set, the mean intake levels from 7DDRs, FFQs, and calibrated FFQs were 62.5, 75.3, and 63.2 g/d for total citrus; 41.6, 42.5, and 41.9 g/d for orange juice; 11.8, 24.3, and 12.3 g/d for oranges; and 8.3, 9.3, and 8.6 g/d for grapefruit, respectively. We observed larger differences between calibrated FFQ and 7DDR assessments at the extreme ends of intake, although, on average, good agreements were observed for all citrus except grapefruit. CONCLUSIONS: Our 2-step calibration approach has the potential to be adapted to correct systematic measurement error for other foods/nutrients with established food biomarkers in a cost effective way.

Association of ultra-processed food consumption with all cause and cause specific mortality: population based cohort study.

OBJECTIVE: To examine the association of ultra-processed food consumption with all cause mortality and cause specific mortality. DESIGN: Population based cohort study. SETTING: Female registered nurses from 11 US states in the Nurses' Health Study (1984-2018) and male health professionals from all 50 US states in the Health Professionals Follow-up Study (1986-2018). PARTICIPANTS: 74 563 women and 39 501 men with no history of cancer, cardiovascular diseases, or diabetes at baseline. MAIN OUTCOME MEASURES: Multivariable Cox proportional hazard models were used to estimate hazard ratios and 95% confidence intervals for the association of ultra-processed food intake measured by semiquantitative food frequency questionnaire every four years with all cause mortality and cause specific mortality due to cancer, cardiovascular, and other causes (including respiratory and neurodegenerative causes). RESULTS: 30 188 deaths of women and 18 005 deaths of men were documented during a median of 34 and 31 years of follow-up, respectively. Compared with those in the lowest quarter of ultra-processed food consumption, participants in the highest quarter had a 4% higher all cause mortality (hazard ratio 1.04, 95% confidence interval 1.01 to 1.07) and 9% higher mortality from causes other than cancer or cardiovascular diseases (1.09, 1.05 to 1.13). The all cause mortality rate among participants in the lowest and highest quarter was 1472 and 1536 per 100 000 person years, respectively. No associations were found for cancer or cardiovascular mortality. Meat/poultry/seafood based ready-to-eat products (for example, processed meat) consistently showed strong associations with mortality outcomes (hazard ratios ranged from 1.06 to 1.43). Sugar sweetened and artificially sweetened beverages (1.09, 1.07 to 1.12), dairy based desserts (1.07, 1.04 to 1.10), and ultra-processed breakfast food (1.04, 1.02 to 1.07) were also associated with higher all cause mortality. No consistent associations between ultra-processed foods and mortality were observed within each quarter of dietary quality assessed by the Alternative Healthy Eating Index-2010 score, whereas better dietary quality showed an inverse association with mortality within each quarter of ultra-processed foods. CONCLUSIONS: This study found that a higher intake of ultra-processed foods was associated with slightly higher all cause mortality, driven by causes other than cancer and cardiovascular diseases. The associations varied across subgroups of ultra-processed foods, with meat/poultry/seafood based ready-to-eat products showing particularly strong associations with mortality.

Effect of Distal Tibiofibular Destabilization and Syndesmosis Compression on the Flexibility Kinematics of the Ankle Bones: An In Vitro Human Cadaveric Model.

Background: Overcompression of the distal tibiofibular syndesmosis during open reduction and internal fixation of ankle fracture may affect multidirectional flexibility of the ankle bones. Methods: Ten cadaveric lower limbs (78.3±13.0 years, 4 female, 6 male) underwent biomechanical testing in sagittal, coronal, and axial rotation with degrees of motion quantified. The intact force (100%) was the force needed to compress the syndesmosis just beyond the intact position, and overcompression was defined as 150% of the intact force. After intact testing, the anterior inferior tibiofibular ligament (AITFL), interosseus membrane (IOM), and posterior inferior tibiofibular ligament (PITFL) were sectioned and testing was repeated. The IOM and AITFL were reconstructed in sequence and tested at 100% and 150% compression. Results: Overcompression of the syndesmosis did not significantly reduce ROM of the ankle bones for any loading modality (P > .05). IOM+AITFL reconstruction restored distal tibiofibular axial rotation to the intact condition. Axial rotation motion was significantly lower with AITFL fixation compared with IOM fixation alone (P < .05). The proximal tibiofibular syndesmosis demonstrated significantly higher motion in axial rotation with all distal reconstruction conditions. Conclusion: As assessed by direct visualization, overcompression of the distal tibiofibular syndesmosis did not reduce ROM of the ankle bones. Distal tibiofibular axial rotation was significantly lower with IOM+AITFL fixation compared with IOM augmentation alone. Distal tibiofibular axial rotation did not differ significantly from the intact condition after combined IOM+AITFL fixation. Dynamic fixation of the distal tibiofibular syndesmosis resulted in increased axial rotation at the proximal tibiofibular syndesmosis. Clinical Relevance: These biomechanical data suggest that inadvertent overcompression of the distal tibiofibular syndesmosis when fixing ankle fractures does not restrict subsequent ankle bone ROM. The AITFL is an important stabilizer of the distal tibiofibular syndesmosis in external rotation. Level of Evidence: controlled laboratory study.

Effect of standardized patient simulation-based pedagogics embedded with lecture in enhancing mental status evaluation cognition among nursing students in Tanzania: A longitudinal quasi-experimental study.

BACKGROUND: Nurses around the world are expected to demonstrate competence in performing mental status evaluation. However, there is a gap between what is taught in class and what is practiced for patients with mental illness among nursing students during MSE performance. It is believed that proper pedagogics may enhance this competence. A longitudinal controlled quasi-experimental study design was used to evaluate the effect of using standardized patient simulation-based pedagogics embedded with a lecture in enhancing mental status evaluation cognition among nursing students in Tanzania. METHODS: A longitudinal controlled quasi-experimental study design with pre-and post-test design studied 311 nursing students in the Tanga and Dodoma regions. The Standardized Patient Simulation-Based Pedagogy (SPSP) package was administered to the intervention group. Both groups underwent baseline and post-test assessments using a Interviewer-adminstered structured questionnaire as the primary data collection tool, which was benchmarked from previous studies. The effectiveness of the intervention was assessed using both descriptive and inferential statistics, specifically the Difference in Difference linear mixed model, and the t-test was carried out using IBM Statistical Package for Social Science (SPSS) software, version 25. RESULTS: The participant's mean age was 21 years ± 2.69 with 68.81% of the students being female. Following the training Students in the intervention group demonstrated a significant increase in MSE cognition post-test, with an overall mean score of (M ± SD = 22.15 ± 4.42;p = < 0.0001), against (M ± SD = 16.52 ± 6.30) for the control group. CONCLUSION: A significant difference exists in the levels of cognition, among nursing students exposed to Mental Status Evaluation (MSE) materials through Standardized Patient Simulation-Based Pedagogy (SPSP) embeded with lectures. When MSE materials are delivered through SPSP along with lectures, the results are significantly superior to using lectures pedagogy alone.

Knowledge, attitude, intentional practice and individualized determinants of COVID-19 vaccine uptake among adults: A cross-sectional study in Tanzania.

AIM: The study assessed the knowledge, attitude, intentional practice and individualized factors of COVID-19 vaccine uptake among adults in Tanzania. DESIGN: Hospital-based analytical cross-sectional study. METHODS: Quantitative approaches were adopted to study 312 randomly selected adults using an interviewer-administered structured questionnaire. Descriptive analysis established frequencies and percentages of variables at a 95% confidence interval and a 5% significance level. RESULTS: Mean age was 24.66 ± 6.503 of which 61.5% were males. 86.9% of them were not vaccinated. 57.7% of respondents had inadequate knowledge about the COVID-19 vaccine, and 61.5% had negative attitudes towards it. 63.8% of adults demonstrated an unwillingness to be vaccinated. Participants' sociodemographic characteristics profiles were significantly associated with COVID-19 vaccine knowledge, attitude and willingness to uptake it (p < 0.05). Findings highlight the need for large-scale interventions to address the low uptake vaccine. Adults' willingness to get a coronavirus vaccine was comparatively low. Sociodemographic profiles, knowledge and attitude were associated significantly with low uptake of the COVID-19 vaccine among adults in Tanzania.

Use of melatonin supplements and risk of type 2 diabetes and cardiovascular diseases in the USA: insights from three prospective cohort studies.

BACKGROUND: Use of melatonin supplements has been increasing substantially in both children and adults in the USA; however, their long-term cardiometabolic effects remain unclear. We aimed to assess the associations between regular use of melatonin supplements and the risk of developing type 2 diabetes or cardiovascular disease in adults. METHODS: In this study, we included individuals from three US cohorts: the Nurses' Health Study (women only), the Health Professionals Follow-up Study (men only), and the Nurses' Health Study II (women only). Women aged 25-55 years and men aged 45-75 years at baseline, who had no diagnosis of cancer at baseline, and who responded to the question about melatonin supplement use (yes or no) were included. We excluded baseline prevalent cardiovascular disease and baseline prevalent type 2 diabetes for the main analyses. The main outcomes were cardiovascular disease and type 2 diabetes incidence. In secondary analyses, we stratified by duration of rotating night shift work in the Nurses' Health Study and Nurses' Health Study II to examine whether the associations with melatonin supplement use differed by rotating night shift work. FINDINGS: For the cardiovascular disease analysis, we included 67 202 women from the Nurses' Health Study (follow-up 1998-2019, mean age at baseline: 63·6 years [SD 7·1]), 26 629 men from the Health Professionals Follow-up Study (1998-2020, 62·9 years [8·8], and 65 241 women from the Nurses' Health Study II (2003-19, 48·2 years [4·7]). Follow-up for incident type 2 diabetes was from 1998 to June 30, 2021, for the Nurses' Health Study; 2003 to Jan 31, 2023, for the Nurses' Health Study II; and from 1998 to Jan 31, 2020, for the Health Professionals' Follow-up Study. Melatonin supplement use in the study cohorts doubled over recent decades from less than 2% in 1998-2007 to 4% or higher in 2014-15 (4·0% in men and 5·3% in women). We documented 16 917 incident cardiovascular disease events during 2 609 068 person-years of follow-up and 12 730 incident cases of type 2 diabetes during 2 701 830 person-years of follow-up. In a pooled analysis of the three cohorts, comparing users with non-users of melatonin supplements, the pooled multivariable-adjusted hazard ratios were 0·94 (95% CI 0·83-1·06, p=0·32) for cardiovascular disease and 0·98 (0·86-1·12, p=0·80) for type 2 diabetes. In secondary analyses, melatonin supplement use appeared to attenuate the positive association between long-term shift work (>5 years) and risk of cardiovascular disease (pinteraction=0·013) among the female nurses. INTERPRETATION: With up to 23 years of follow-up of three large prospective cohorts of middle-aged and older men and women, self-reported melatonin supplement use was not associated with risk of type 2 diabetes or cardiovascular disease. Further research is warranted to assess if melatonin supplement use could mitigate the potential risks of type 2 diabetes and cardiovascular disease associated with rotating night shift work. FUNDING: US National Institutes of Health.