Global metabolomic profiling showed that conventional mice had greater variability in their metabolic response to injury, and a more distinct joint metabolome compared to their corresponding controls. Furthermore, differences in the response to injury in GF compared to conventional mice were linked to mouse metabolic pathways that regulate inflammation associated with the innate immune system. These results suggest that the gut microbiota promote the development of PTOA during the acute phase following joint trauma possibly through the regulation of the innate immune system.These results suggest that the gut microbiota promote the development of PTOA during the acute phase following joint trauma possibly through the regulation of the innate immune system. To estimate the genetic contribution to traumatic and degenerative meniscus tears for men and women across the lifespan. We linked the Swedish Twin Register with individual-level national healthcare data to form a 30-year, population-wide, longitudinal twin cohort. To study genetic contribution to meniscus tears, we estimated the heritability and familial risk using incident traumatic and degenerative tear diagnostic codes in a cohort of 88,414 monozygotic and dizygotic twin-pairs, aged ≥17 years. During follow-up, 3,372 (3.8%) of 88,414 twins were diagnosed with a traumatic or degenerative meniscus tear. The heritability was 0.39 (95% CI=0.32-0.47) for men and 0.43 (95% CI=0.36-0.50) for women, and did not vary by age. Environmental factors that were unique to each twin in a pair explained a greater proportion of the variance than genetic factors, both for men (0.61, 95% CI=0.53-0.68) and women (0.57, 95% CI=0.50-0.64). Separate analyses of traumatic vs degenerative meniscus tears yielded similar results. For the first time, we have estimated the genetic contribution to doctor-diagnosed meniscus tears using a twin study design. We found a relatively low to modest heritability for meniscus tears (∼40%). Lazertinib solubility dmso The heritability was also fairly stable over the lifespan, and equal in both men and women. Our findings suggest that environmental risk factors are a more important contributor to both traumatic and degenerative doctor-diagnosed meniscus tears than genetic factors.For the first time, we have estimated the genetic contribution to doctor-diagnosed meniscus tears using a twin study design. We found a relatively low to modest heritability for meniscus tears (∼40%). The heritability was also fairly stable over the lifespan, and equal in both men and women. Our findings suggest that environmental risk factors are a more important contributor to both traumatic and degenerative doctor-diagnosed meniscus tears than genetic factors. Some studies have examined the association between dietary factors and risk of knee osteoarthritis (OA). We aimed to examine the prospective association of major dietary patterns with the risk of developing knee OA. We followed 2,842 participants in Osteoarthritis Initiative (OAI) aged 45-79 years and with at least one knee free from radiographic knee OA at baseline for up to 72 months. We defined knee OA incidence as Kellgren and Lawrence grade ≥2 during follow-up visits. Using principal component analysis, Western and prudent dietary patterns were derived. Cox proportional hazards models were used to assess the association between dietary patterns and incident knee OA. Among study participants, 385 (418 knees) developed knee OA within 72 months. Following a Western dietary pattern was associated with an increased risk of knee OA (HR =1.69, 95% CI 1.13 to 2.52, p trend 0.03), while adherence to the prudent pattern was associated with a reduced risk of knee OA (HR =0.70, 95% CI 0.50 to 0.98, p trend 0.05). The observed associations attenuated after additionally adjusting for body mass index (BMI). The observed associations were mediated through BMI by approximately 30%. Following a Western diet was associated with increased risk of knee OA, whereas following a prudent pattern was associated with a reduced risk of knee OA. The associations were partially mediated through BMI.Following a Western diet was associated with increased risk of knee OA, whereas following a prudent pattern was associated with a reduced risk of knee OA. The associations were partially mediated through BMI. Osteoarthritis (OA) affects millions of people worldwide. In hand OA, the thumb base is the most affected single joint. The reported radiographic prevalence ranges from 0 to 100%, making the true radiographic prevalence unclear. Hence, we conducted a meta-analysis on the age and sex-specific prevalence of radiographic thumb base OA. We performed a search in Embase, Medline Ovid, Web of Science Core Collection, Cochrane Central Register of Trials, and Google Scholar. We included studies of the general population that reported thumb base OA for males and females separately based on a hand radiograph and reported the age of these groups. Using meta-regression, we estimated the odds ratio (OR) of having radiographic thumb base OA for age and sex, while adjusting for within-study correlation. The initial search yielded 4,278 articles; we finally included 16 studies that reported the age- and sex-stratified prevalence. Taken together, there were 104 age and gender specific-prevalence rates that could be derived from the 16 studies. The prevalence of radiographic OA for the 50-year-old male and female participants was 5.8% and 7.3%, respectively, while the respective prevalence for 80-year-old male and female participants was 33.1% and 39.0%. We found an OR for having radiographic OA of 1.06 (95%CI [1.055-1.065], p<0.001) per increasing year of age, and 1.30 (95%CI 1.05-1.61], p=0.014) for females. In the general population, radiographic thumb base OA is more prevalent in females and is strongly associated with age.In the general population, radiographic thumb base OA is more prevalent in females and is strongly associated with age.Breakthrough cytomegalovirus (CMV) disease during valganciclovir prophylaxis is rare but may cause significant morbidity and even mortality. In order to identify patients at increased risk the incidence of CMV disease was studied in a large population of renal transplant recipients who underwent a kidney transplantation in the Radboud University Medical Center between 2004 and 2015 (n = 1300). CMV disease occurred in 31/1300 patients. Multivariate binary linear regression analysis showed that delayed graft function (DGF) (p = 0.018) and rejection (p = 0.001) significantly and independently increased the risk of CMV disease, whereas CMV status did not. Valganciclovir prophylaxis was prescribed to 281/1300 (21.6%) high-risk patients (defined as CMV IgG-seronegative recipients receiving a kidney from a CMV IgG-seropositive donor (D+/R-)). Of these 281 patients, 51 suffered from DGF (18%). The incidence of breakthrough CMV disease in D + /R- patients with DGF was much higher than in those with immediate function (6/51 (11.