Individuals with diabetes mellitus (DM) have an increased risk of fracture. Glycemic control is crucial to the management of DM, but there are concerns pertaining to hypoglycemia development in the ...course of glycemic control target achievement. The extent to which glycemic control may affect the risk of fracture remains less defined. Hypoglycemia-induced falls have been suggested to contribute to an elevated risk of fracture in DM patients. In this meta-analysis of observational studies, we aimed to investigate the relative contribution of glycemic control, as measured by glycated hemoglobin (HbA1c), and hypoglycemia to the risk of fracture in DM. The PubMed and Web of Science databases were searched for relevant studies. A random-effects model was used to generate summary relative risks (RRs) and 95% confidence intervals (CIs). Both increased HbA1c levels (RR
per 1% increase
1.08, 95% CI 1.03, 1.14;
n
studies
= 10) and hypoglycemia (RR 1.52, 95% CI 1.23, 1.88;
n
studies
= 8) were associated with an increased risk of fracture. The association between HbA1c levels and the risk of fracture was somewhat nonlinear, with a noticeably increased risk observed at an HbA1c level ≥ 8%. The positive associations of HbA1c levels and hypoglycemia with the risk of fracture did not reach statistical significance in the studies that adjusted for insulin use, hypoglycemia, or falls for the former and in those that adjusted for falls for the latter. In summary, both increased HbA1c levels and hypoglycemia may increase the risk of fracture in patients with DM. The positive association between HbA1c levels and the risk of fracture appears to be, in part, explained by hypoglycemia-induced falls, possibly due to insulin use. The avoidance of hypoglycemia in the course of achieving good glycemic control through the careful selection of glucose-lowering medications may contribute to fracture prevention by reducing the risk of falls related to treatment-induced hypoglycemia.
Summary
Epidemiologic evidence has shown inconsistent findings regarding the relationships between abdominal fatness, as measured by waist circumferences (WC) or waist‐to‐hip ratio (WHR), and risks ...of pre‐ and postmenopausal breast cancer (BC). A dose–response meta‐analysis of prospective studies was conducted to address these issues. Potentially eligible studies were identified by searching PubMed and EMBASE databases, and by carefully reviewing the bibliographies of retrieved publications and related reviews. The summary relative risks (RRs) with 95% confidence intervals (CIs) were calculated using a random‐effects model. When the most fully adjusted RRs were combined, both WC (14 studies, RR per 10‐cm increase = 1.06, 95% CI: 1.04–1.09, I2 = 29.9%) and WHR (15 studies, RR per 0.1‐unit increase = 1.07, 95% CI: 1.01–1.14, I2 = 52.9%) were significantly positively associated with postmenopausal BC, but neither WC (eight studies, RR per 10‐cm increase = 1.05, 95% CI: 0.99–1.10, I2 = 0%) nor WHR (11 studies, RR per 0.1‐unit increase = 1.07, 95% CI: 0.95–1.21, I2 = 59.7%) were associated with premenopausal BC. The WHR‐postmenopausal BC association lost statistical significance after correcting publication bias (RR per 0.1‐unit increase = 1.06, 95% CI: 0.99–1.13). When considering BMI‐adjusted RRs, WC was associated with both pre‐ (five studies, RR per 10‐cm increase = 1.09, 95% CI: 1.02–1.16, I2 = 0%) and postmenopausal BC (seven studies, RR per 10‐cm increase = 1.05, 95% CI: 1.02–1.08, I2 = 6.3%), whereas WHR was not associated with either pre‐ (seven studies, RR per 0.1‐unit increase = 1.12, 95% CI: 0.94–1.34, I2 = 70.9%) or postmenopausal BC (eight studies, RR per 0.1‐unit increase = 1.05, 95% CI: 0.98–1.13, I2 = 57.3%). Among non‐current (former or never) users of hormone replacement therapy, the summary RR per 10‐cm increase of postmenopausal BC associated with WC was 1.08 (95% CI: 1.03–1.05, I2 = 69.2%, seven studies; BMI‐adjusted RR = 1.05, 95% CI: 1.02–1.09, I2 = 22.8%, four studies). This meta‐analysis indicates that central obesity measured by WC, but not by WHR, is associated with modestly increased risks of both pre‐ and postmenopausal BC independent of general obesity.
Summary
In the present meta-analysis, reductions in the risk of hip fracture with milk consumption were only observed among American adults, but not among Scandinavian adults, possibly because milk ...products are more commonly fortified with vitamin D in the former population than in Scandinavian countries. The reduction in the risk of hip fracture was also observed with yogurt consumption, which is often associated with healthy lifestyles and dietary patterns that contribute to improved bone health.
Introduction
Although dairy products contain bone-beneficial nutrients, the association between dairy consumption and the risk of hip fracture remains equivocal. Fueling this uncertainty, the elevated risk of hip fracture in association with milk consumption was observed in a cohort of Swedish women. A systematic review and meta-analysis of prospective cohort studies was performed to critically evaluate the association, or lack thereof, between dairy consumption (milk, yogurt, and cheese) and the risk of hip fracture.
Methods
A random effects model was used to generate the summary relative risks (RRs) with their 95% confidence intervals (CIs) for the associations of interest.
Results
In the meta-analysis of the highest versus lowest category of consumption, higher consumption of yogurt (RR 0.78, 95% CI 0.68, 0.90), but not milk (RR 0.86, 95% CI 0.73, 1.02) or cheese (RR 0.85, 95% CI 0.66, 1.08), was associated with a lower risk of hip fracture. For milk, the reduced risk of fracture with higher milk consumption was observed in the USA (RR 0.75, 95% CI 0.65, 0.87), but not in Scandinavian countries (RR 1.00, 95% CI 0.85, 1.17). These findings were further supported by the fact that American studies (RR 0.93, 95% CI 0.88, 0.98; per 1 glass/day), but not Scandinavian studies (RR 1.01, 95% CI 0.95, 1.07; per 1 glass/day), demonstrated a linear association between milk consumption and the risk of hip fracture.
Conclusions
The cumulative evidence from prospective cohort studies reassuringly suggests that the risk of hip fracture may not be elevated among people who consume milk, yogurt, and cheese, and that a greater consumption of milk or yogurt may even be associated with a lower risk of hip fracture depending on the factors that may differ across the population of interest.
Milk intake is widely recommended for a healthy diet. Epidemiological studies have suggested that the consumption of dairy products may be associated with a reduction in type 2 diabetes mellitus ...(T2DM). A meta-analysis was conducted to elucidate the association between dairy products consumption and T2DM.
A systematical literature search was done through the Medline database and seven related cohort studies were identified. The adjusted relative risks (RRs) with the highest and the lowest categories from each study were extracted to calculate the combined RR. A least-square trend estimation was applied to assess the dose-response relationships.
A combined RR of 0.86 (95% confidence interval (CI), 0.79-0.92) was revealed on T2DM risk associated to dairy intake, with little evidence of heterogeneity. For subgroup analysis, a combined RR was 0.82 (95% CI, 0.74-0.90), 1.00 (95% CI, 0.89-1.10), 0.95 (95% CI, 0.86-1.05) and 0.83 (95% CI, 0.74-0.93) for the intake of low-fat dairy, high-fat dairy, whole milk and yogurt, respectively. Dose-response analysis showed that T2DM risk could be reduced 5% for total dairy products and 10% for low-fat dairy products.
An inverse association of daily intake of dairy products, especially low-fat dairy, with T2DM was revealed, indicating a beneficial effect of dairy consumption in the prevention of T2DM development.
This meta‐analysis aimed to assess the gender‐specific differences in the relationship between circulating leptin levels and risk of type 2 diabetes. Published prospective studies that reported the ...association of leptin levels with risk of type 2 diabetes for a certain gender or those that reported gender‐specific associations were considered. Dose‐response relationships were assessed by the generalized least squares trend estimation and summary relative risks (RRs) with 95% confidence interval (CI) were computed with the random‐effects model. Stratified and sensitivity analyses were also performed to investigate potential sources of heterogeneity. Overall, 11 prospective studies were identified. The summary RR for an increment in leptin levels of 1‐log ng mL⁻¹ was 1.37 (95% CI, 1.13–1.66) for men and 0.96 (95% CI, 0.90–1.03) for women. The differences between genders were statistically significant (P for interaction = 0.006). Subgroup and sensitivity analyses generally confirmed the robustness of these findings. Furthermore, the increased risk in men appeared non‐linear, with a tendency to plateau at high levels (P for non‐linearity = 0.03). Little evidence of publication bias was found. Collectively, higher leptin levels were found to be associated with elevated risk of type 2 diabetes in men but not in women.
Objectives
The vicious cycle of dynapenia and abdominal obesity may have synergistic detrimental impacts on health. We aim to investigate the prospective association between dynapenic abdominal ...obesity and the risk of heart disease among middle-aged and older adults.
Design
A prospective cohort study.
Setting
English Longitudinal Study of Ageing, 2002–2019.
Participants
A total of 4734 participants aged 50 years and older were included.
Measurements
Individuals were divided into non-dynapenia/non-abdominal obesity (ND/NAO), non-dynapenia/abdominal obesity (ND/AO), dynapenia/non-abdominal obesity (D/NAO), and dynapenia/abdominal obesity (D/AO) according to grip strength and waist circumference at baseline. The Cox proportional hazards models were used to obtain the hazard ratios (HRs) of incident heart disease associated with dynapenia and abdominal obesity after adjusting for potential confounding factors.
Results
During a median follow-up of 9.5 years, 1040 cases of heart disease were recorded. Compared with ND/NAO group, the multivariable HRs were 1.05 (0.92, 1.21) for ND/AO group, 1.31 (0.96, 1.81) for D/NAO group, and 1.39 (1.03, 1.88) for D/AO group. The significant association of D/AO with incident heart disease was detected in women but not in men HR = 1.55 (1.07, 2.24) and 1.06 (0.60, 1.88), respectively. Among middle-aged adults, significant associations of D/NAO and D/AO with incident heart disease were observed HR = 2.46 (1.42, 4.29) and 1.74 (1.02, 2.97), respectively.
Conclusion
Both D/NAO and D/AO might increase the risk of developing heart disease, highlighting the importance of dynapenia and obesity early screening for heart disease prevention.
Recurrence/persistence of symptoms occurs in approximately 20 % of patients after Heller myotomy for achalasia. Controversy exists regarding the therapy for patients in whom Heller myotomy has ...failed. The aim of the current study was to evaluate the efficacy and feasibility of peroral endoscopic myotomy (POEM), a new endoscopic myotomy technique, for patients with failed Heller myotomy.
A total of 12 patients with recurrence/persistence of symptoms after Heller myotomy, as diagnosed by established methods and an Eckardt score of ≥ 4, were prospectively included. The primary outcome was symptom relief during follow-up, defined as an Eckardt score of ≤ 3. Secondary outcomes were procedure-related adverse events, lower esophageal sphincter (LES) pressure on manometry, reflux symptoms, and medication use before and after POEM.
All 12 patients underwent successful POEM after a mean of 11.9 years (range 2 - 38 years) from the time of the primary Heller myotomy. No serious complications related to POEM were encountered. During a mean follow-up period of 10.4 months (range 5 - 14 months), treatment success was achieved in 11/12 patients (91.7 %; mean score pre- vs. post-treatment 9.2 vs. 1.3; P < 0.001). Mean LES pressure was 29.4 mmHg pre-treatment and 13.5 mmHg post-treatment (P < 0.001). One patient developed mild reflux symptoms and required intermittent medication with proton pump inhibitors.
POEM seems to be a promising new treatment for failed Heller myotomy resulting in short-term symptom relief in > 90 % of cases. Previous Heller myotomy may make subsequent endoscopic remyotomy more challenging, but does not prevent successful POEM.
Vulvovaginal candidiasis (VVC) is an infectious disease caused mainly by Candida albicans. Kangfuxin (KFX) is a traditional Chinese medicine preparation made from Periplaneta americana extracts, ...which promotes wound healing and enhances body immunity and also acts as an antifungal agent. Here, we evaluated the effect of KFX in the treatment of VVC in vitro and in vivo. The minimum inhibitory concentration (MIC50) of KFX against C. albicans ranged from 7·65 to 20·57%. In addition, KFX was more efficient than fluconazole (FLC) in inhibiting the drug‐resistant C. albicans, and the effect was more intense after 8 h. The KFX treatment also exhibited good activity in vivo. It restored the body weight and reduced the vulvovaginal symptoms in mice induced with VVC. It downregulated the expression of the hyphae‐related gene, HWP1, thus inhibiting the growth and development of C. albicans hyphae. It also increased the number of neutrophils and promoted the secretion of interleukin‐17A (IL‐17A); however, the levels of interleukin‐8 (IL‐8) and interleukin‐1β (IL‐1β) decreased in mice with VVC. We deduce that KFX effectively treats vaginal candidiasis in two ways: by inhibiting the growth and development of mycelia to reduce colonization of C. albicans and by promoting the secretion and release of IL‐17A and neutrophils in high numbers to fight C. albicans infection. This study provides a theoretical basis for the use of KFX for the clinical treatment of VVC.
Significance and Impact of the Study: Vulvovaginal candidiasis (VVC) is an infectious disease of the female external reproductive tract, caused by the ecological imbalance in the vagina due to the influence of various pathogenic factors, which brings harm to women's physical and mental health. However, the availability of drugs is limited and the frequency of drug‐resistant Candida isolates is increasing. It is urgent to find new drugs or effective treatment strategies. We found that Kangfuxin liquid (KFX) can be used to treat VVC by reducing mycelial growth and boosting immunity, which presents a new clinical alternative.
Spatially resolved transcriptomic technologies are promising tools to study complex biological processes such as mammalian embryogenesis. However, the imbalance between resolution, gene capture, and ...field of view of current methodologies precludes their systematic application to analyze relatively large and three-dimensional mid- and late-gestation embryos. Here, we combined DNA nanoball (DNB)-patterned arrays and in situ RNA capture to create spatial enhanced resolution omics-sequencing (Stereo-seq). We applied Stereo-seq to generate the mouse organogenesis spatiotemporal transcriptomic atlas (MOSTA), which maps with single-cell resolution and high sensitivity the kinetics and directionality of transcriptional variation during mouse organogenesis. We used this information to gain insight into the molecular basis of spatial cell heterogeneity and cell fate specification in developing tissues such as the dorsal midbrain. Our panoramic atlas will facilitate in-depth investigation of longstanding questions concerning normal and abnormal mammalian development.
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•Stereo-seq enables large field-of-view spatial transcriptomics at cellular resolution•Stereo-seq reveals the spatial cell-type heterogeneity of mouse embryonic tissues•Stereo-seq maps the spatiotemporal transcriptomic dynamics during mouse organogenesis•Stereo-seq defines the spatiotemporal window of developmental disease vulnerability
Stereo-seq combines DNA nanoball-patterned arrays and tissue RNA capture to achieve large field-of-view spatial transcriptomics at cellular resolution, enabling the dissection of spatial cell-type heterogeneity of mouse embryonic tissues.
Objective: To clarify the effects of isoflavone intake on bone resorption and bone formation. Methods: We identified randomized controlled trials related to urinary deoxypyridinoline (Dpyr, a bone ...resorption marker) and serum bone-specific alkaline phosphatase (BAP, a bone formation marker) listed on MEDLINE (January 1966-April 2006), the Cochrane Controlled Trials Register, EMBASE (1985-January 2006), Science Citation Index and PUBMED (updated till April 2006). Results: Nine studies with a total of 432 subjects were selected for meta-analysis. The urinary Dpyr concentration in subjects who consumed isoflavones decreased significantly by -2.08 nmol/mmol (95% confidence interval (CI): -3.82 to -0.34 nmol/mmol) in comparison with that in subjects who did not consume isoflavones. Isoflavone intake vs placebo intake significantly increased serum BAP by 1.48 microgram/l (95% CI: 0.22-2.75 microgram/l). Decreases in the urinary Dpyr concentration with isoflavone intake of <90 mg/day and with treatment lasting less than 12 weeks were -2.34 nmol/mmol (95% CI: -4.46 to -0.22 nmol/mmol) and -2.03 nmol/mmol (95% CI: -3.20 to -0.85 nmol/mmol), respectively. Conclusions: Isoflavone intervention significantly inhibits bone resorption and stimulates bone formation. These favorable effects occur even if <90 mg/day of isoflavones are consumed or the intervention lasts less than 12 weeks.
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