Assessment of causal association between the socio-economic status and osteoporosis and fractures: a bidirectional Mendelian randomization study in European population.

The correlation between socio-economic status (SES) and bone-related diseases garners increasing attention, prompting a bidirectional Mendelian randomization (MR) analysis in this study. Genetic data on SES indicators (average total household income before tax, years of schooling completed, and Townsend Deprivation Index at recruitment), femoral neck bone mineral density (FN-BMD), heel bone mineral density (eBMD), osteoporosis, and five different sites of fractures (spine, femur, lower leg-ankle, foot, and wrist-hand fractures) were derived from genome-wide association summary statistics of European ancestry. The inverse variance weighted method was employed to obtain the causal estimates, complemented by alternative MR techniques, including MR-Egger, weighted median, and MR-pleiotropy residual sum and outlier (MR-PRESSO). Furthermore, sensitivity analyses and multivariable MR were performed to enhance the robustness of our findings. Higher educational attainment exhibited associations with increased eBMD (ß: .06, 95% confidence interval [CI]: 0.01-0.10, P = 7.24 × 10-3), and reduced risks of osteoporosis (OR: 0.78, 95% CI: 0.65-0.94, P = 8.49 × 10-3), spine fracture (OR: 0.76, 95% CI: 0.66-0.88, P = 2.94 × 10-4), femur fracture (OR: 0.78, 95% CI: 0.67-0.91, P = 1.33 × 10-3), lower leg-ankle fracture (OR: 0.79, 95% CI: 0.70-0.88, P = 2.05 × 10-5), foot fracture (OR: 0.78, 95% CI: 0.66-0.93, P = 5.92 × 10-3), and wrist-hand fracture (OR: 0.83, 95% CI: 0.73-0.95, P = 7.15 × 10-3). Material deprivation appeared to increase the risk of spine fracture (OR: 2.63, 95% CI: 1.43-4.85, P = 1.91 × 10-3). A higher FN-BMD level positively affected increased household income (ß: .03, 95% CI: 0.01-0.04, P = 6.78 × 10-3). All these estimates were adjusted for body mass index, type 2 diabetes, smoking initiation, and frequency of alcohol intake. The MR analyses show that higher educational levels is associated with higher eBMD, reduced risk of osteoporosis and fractures, while material deprivation is positively related to spine fracture. Enhanced FN-BMD correlates with increased household income. These findings provide valuable insights for health guideline formulation and policy development.

We conducted stratified analyses to explore the causal links between socio-economic status and osteoporosis and various fractures and observed that education significantly reduced the risk of osteoporosis and lower eBMD. It also lowered the risks of fractures of spine, femur, lower leg-ankle, foot, and wrist-hand, while material deprivation exhibited positive associations with spine fracture risk. Bidirectional MR analysis showed that an elevated score of FN-BMD was associated with a higher income level. Our study shows the importance of conducting routine BMD estimations and osteoporosis screening, to enhance knowledge and awareness among individuals to promote bone health and prevent fractures.

Faster stepping cadence partially explains the higher metabolic cost of walking among females versus males.

The metabolic cost of walking (MCOW), or oxygen uptake normalized to distance, provides information on the energy expended during movement. There are conflicting reports as to whether sex differences in MCOW exist, with scarce evidence investigating factors that explain potential sex differences. This study 1) tested the hypothesis that females exhibit a higher MCOW than males, 2) determined whether normalizing to stepping cadence ameliorates the hypothesized sex difference, and 3) explored whether more habitual step counts and time in intensity-related physical activity, and less sedentary time were associated with a decreased MCOW. Seventy-six participants (42 females, 24 ± 5 yr) completed a five-stage, graded treadmill protocol with speeds increasing from 0.89 to 1.79 m/s (6-min walking stage followed by 4-min passive rest). Steady-state oxygen uptake (via indirect calorimetry) and stepping cadence (via manual counts) were determined. Gross and net MCOW, normalized to distance traveled (km) and step-cadence (1,000 steps) were calculated for each stage. Thirty-nine participants (23 females) wore an activPAL on their thigh for 6.9 ± 0.4 days. Normalized to distance, females had greater gross MCOW (J/kg/km) at all speeds (P < 0.014). Normalized to stepping frequency, females exhibited greater gross and net MCOW at 1.12 and 1.79 m/s (J/kg/1,000 steps; P < 0.01) but not at any other speeds (P < 0.075). Stature was negatively associated with free-living cadence (r = -0.347, P = 0.030). Females expend more energy/kilometer traveled than males, but normalizing to stepping cadence attenuated these differences. Such observations provide an explanation for prior work documenting higher MCOW among females and highlight the importance of stepping cadence when assessing the MCOW.NEW & NOTEWORTHY Whether there are sex differences in the metabolic cost of walking (MCOW) and the factors that may contribute to these are unclear. We demonstrate that females exhibit a larger net MCOW than males. These differences were largely attenuated when normalized to stepping cadence. Free-living activity was not associated with MCOW. We demonstrate that stepping cadence, but not free-living activity, partially explains the higher MCOW in females than males.

Assessment of relationships between frailty and chronic pain: a bidirectional two-sample Mendelian randomisation study.

BACKGROUND: Previous observational studies have indicated a complex association between chronic pain and frailty. This study aimed to examine the bidirectional causal relationship between frailty and chronic pain and to quantify mediating effects of known modifiable risk factors. METHODS: A bidirectional two-sample Mendelian randomisation (MR) analysis was applied in this study. Summary genome-wide association statistics for frailty, as defined by both frailty index (FI) and Fried Frailty Score (FFS), pain at seven site-specific chronic pain (SSCP) (headache, facial, neck/shoulder, stomach/abdominal, back, hip and knee) and multisite chronic pain (MCP) were extracted from populations of European ancestry. Genetic instrumental variables strongly correlated with each exposure were selected. The inverse-variance-weighted method was the primary method used in the MR, supplemented by a range of sensitivity and validation analyses. Two-step MR analysis was undertaken to evaluate the mediating effects of several proposed confounders. RESULTS: Genetically predicted higher FI and FFS were associated with an increased risk of MCP and specific types of SSCP, including neck/shoulder pain, stomach/abdominal pain, back pain, hip pain and knee pain. In the reverse direction analysis, genetic liability to MCP was found to be associated with increased FI and FFS. These results remained consistent across sensitivity and validation assessments. Two-step MR suggested a mediating role for body mass index, smoking initiation, physical inactivity, educational attainment and depression. CONCLUSIONS: Our research provided genetic evidence that the association between frailty and chronic pain was bidirectional where the coexistence of both conditions will exacerbate each other.

A multiplicity of environmental, economic and social factor analyses to understand COVID-19 diffusion.

Research on the impact of the environment on COVID-19 diffusion lacks a full-comprehensive perspective, and neglecting the multiplicity of the human-environment system can lead to misleading conclusions. We attempted to reveal all pre-existing environmental-to-human and human-to-human determinants that influence the transmission of COVID-19. As such, We estimated the daily case incidence ratios (CIR) of COVID-19 for prefectures across mainland China, and used a mixed-effects mixed-distribution model to study the association between the CIR and 114 factors related to climate, atmospheric environmental quality, terrain, population, economic, human mobility as well as non-pharmaceutical interventions (NPIs). Not only the changes in determinants over time as the pandemic progresses but also their lag and interaction effects were examined. CO, O3, PM10 and PM2.5 were found positively linked with CIR, but the effect of NO2 was negative. The temperature had no significant association with CIR, and the daily minimum humidity was a significant negatively predictor. NPIs' level was negatively associated with CIR until with a lag of 15 days. Higher accumulated destination migration scale flow from the epicenter and lower distance to the epicenter (DisWH) were associated with a higher CIR, however, the interaction between DisWH and the time was positive. The more economically developed and more densely populated cities have a higher probability of CIR occurrence, but they may not have a higher CIR intensity.The COVID-19 diffusion are caused by a multiplicity of environmental, economic, social factors as well as NPIs. First, multiple pollutants carried simultaneously on particulate matter affect COVID-19 transmission. Second, the temperature has a limited impact on the spread of the epidemic. Third, NPIs must last for at least 15 days or longer before the effect has been apparent. Fourth, the impact of population movement from the epicenter on COVID-19 gradually diminished over time and intraregional migration deserves more attention.

Aqueous photodegradation of 4-tert-butylphenol: By-products, degradation pathway and theoretical calculation assessment.

4-tert-butylphenol (4-t-BP), an endocrine disrupting chemical, is widely distributed in natural bodies of water but is difficult to biodegrade. In this study, we focused on the transformation of 4-t-BP in photo-initiated degradation processes. The steady-state photolysis and laser flash photolysis (LFP) experiments were conducted in order to elucidate its degradation mechanism. Identification of products was performed using the GC-MS, LC-MS and theoretical calculation techniques. The oxidation pathway of 4-t-BP by hydroxyl radical (HO) was also studied and H2O2 was added to produce HO. 4-tert-butylcatechol and 4-tert-butylphenol dimer were produced in 4-t-BP direct photolysis. 4-tert-butylcatechol and hydroquinone were produced by the oxidation of HO. But the formation mechanism of 4-tert-butylcatechol in the two processes was different. The benzene ring was fractured in 4-t-BP oxidation process and 29% of TOC was degraded after 16h irradiation.