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Osteoporotic vertebral fractures adversely impact quality of life and also increase the risk of infection and mortality. Alendronate treatment increases bone mass and reduces the risk of fractures in patients with osteoporosis by suppressing bone resorption. We investigated the relationship between alendronate treatment and infection-related death in patients with osteoporotic vertebral fractures. We retrospectively reviewed patients with osteoporosis and vertebral fractures from January 2001 to December 2007. The use of alendronate, glucocorticoid and medical factors including smoking, alcohol consumption, diabetes, hypertension, stroke, liver disease, heart disease, and pulmonary disease were analyzed. Cox regression was used to analyze the factors associated with life-threatening infections. A total of 210 patients (161 females and 49 males) were included with a mean age of 74.06±7.43 years. Among them, 87 had life-threatening infections and 123 did not. In Cox regression analysis, the patients who used alendronate had a significantly lower risk of life-threatening infections (p = 0.006, HR = 0.845, 95% CI 0.750-0.954), while glucocorticoid users had higher risk of death (p = 0.010, HR = 2.037, 95% CI 1.187-3.498). Osteoporosis was associated with a high rate of life-threatening infections, and the use of alendronate had a lower rate of infection-related death. Therefore, we suggest that alendronate be used after vertebral fractures in these patients.

This study investigated the effects of home-based nutritional and telemedicine-based resistance exercise interventions on improving body composition, blood biochemistry, and lower-limb functional performance. In total, 66 obese patients with mild-to-moderate knee osteoarthritis were randomly divided into a diet control group (D), elastic band resistance exercise group (E), and diet control plus elastic band exercise group (D + E). Each group was supervised by a clinical dietitian and follow-up was conducted via telephone calls or a communication application to track the participants’ progress. After 12 weeks of intervention, the D (p < 0.001) and D + E (p < 0.001) groups achieved significant weight loss. The D + E group exhibited a significant reduction in body fat relative to the D (p = 0.019) and E (p = 0.012) groups. Compared with the D (p = 0.002) and E (p = 0.019) groups, the D + E group achieved significant improvements in the timed up-and-go test and Western Ontario and McMaster Universities Osteoarthritis total scale. The D + E group experienced significant improvements in total cholesterol (p = 0.001), low-density lipoprotein cholesterol (p = 0.01), and triglyceride levels (p = 0.007) relative to other groups. In conclusion, individual diet control intervention combined with telemedicine-based resistance exercise intervention significantly improved the body composition, blood biochemistry, and lower-limb functional performance of the investigated population with comorbid conditions.

Precise, scalable, and sustainable control of genetic and cellular activities in mammalian cells is key to developing precision therapeutics and smart biomanufacturing. Here we create a highly tunable, modular, versatile CRISPR-based synthetic transcription system for the programmable control of gene expression and cellular phenotypes in mammalian cells. Genetic circuits consisting of well-characterized libraries of guide RNAs, binding motifs of synthetic operators, transcriptional activators, and additional genetic regulatory elements express mammalian genes in a highly predictable and tunable manner. We demonstrate the programmable control of reporter genes episomally and chromosomally, with up to 25-fold more activity than seen with the EF1α promoter, in multiple cell types. We use these circuits to program the secretion of human monoclonal antibodies and to control T-cell effector function marked by interferon-γ production. Antibody titers and interferon-γ concentrations significantly correlate with synthetic promoter strengths, providing a platform for programming gene expression and cellular function in diverse applications. Precise and scalable regulation of gene expression in mammalian cells is challenging. Here, the authors created a highly tunable CRISPR-based synthetic transcription system for programmable control of mammalian gene expression and cellular activity.

To explore the risk factors for fragility fractures in rheumatoid arthritis (RA) patients using a 3-year longitudinal, observational cohort study. This RA registry study included consecutive RA patients in the outpatient clinic of Chang Gung Memorial Hospital since September 1, 2014. The demographics, clinical characteristics, lifestyle, evidence of previous fracture, risk factors according to the Fracture Risk Assessment Tool (FRAX.sup.® ), and the FRAX score of each participant were recorded. The participants were categorized into the new incident fracture (group A) and no incident fracture (group B) groups based on evidence or absence of new incident fractures and propensity score matching (age and gender, 1:2). Overall, 477 participants completed the 3-year observation period. After matching, 103 and 206 participants were allocated to groups A and B, respectively. The non-adjusted model revealed, presented as hazard ratio (HR) (95% confidence interval [CI]), that the presence of co-morbidity (1.80 [1.17-2.78], p = 0.008), Health Assessment Questionnaire Disability Index (1.35 [1.07-1.69], p = 0.010), lower baseline hip bone mineral density (0.11 [0.02-0.48], p = 0.004), longer disease duration (1.02 [1.00-1.04], p = 0.026), higher FRAX score of major fracture (1.03 [1.02-1.04], p<0.001) or hip fracture (1.03 [1.02-1.04], p<0.001), and previous fracture history (2.65 [1.79-3.94], p<0.001) were associated with new incident fracture. After adjustment, it was disclosed that a previous fracture is an independent risk factor for fragility fractures in RA patients (2.17 [1.20-3.90], p = 0.010). In addition to aging and disease-related factors, previous fracture history is the most important risk factor for fragility fractures in RA patients.

Schistosoma mansoni infection leads to chronic schistosomiasis and severe hepatic fibrosis. We designed a liver-targeted lipid nanoparticle (LNP) carrying siRNA against type I TGF-β receptor (TGFβRI) mRNA to treat schistosomiasis-induced liver fibrosis in BALB/c mice. Knockdown of TGFβRI by LNP-siTGFβRI reduced LX-2 cell activation in vitro and alleviated liver fibrosis in S . mansoni -infected mice. αSMA and Col1a1 fibrotic markers in the liver tissues of infected mice were significantly suppressed in the treatment groups. In the serum of the LNP-siTGFβRI-treated groups, cytokines IFNγ, IL-1α, IL-6, IL-12, RANTES (CCL5), and TNFα increased, while GM-CSF, IL-2, IL-4, IL-10, IL-13, and KC (CXCL1) decreased compared to the control. Cell proportions were significantly altered in S . mansoni -infected mice, with increased CD56d NK cells and decreased CD19 + B cells and CD4 + T cells compared to naïve mice. Following LNP-siTGFβRI treatment, CD56d NK cells were downregulated, while B and memory Th cell populations were upregulated. The density of fibrotic regions significantly decreased with LNP-siTGFβRI treatment in a dose-dependent manner, and no systemic toxicity was observed in the major organs. This targeted siRNA delivery strategy effectively reduced granulomatous lesions in schistosomiasis-induced liver fibrosis without detectable side effects.

Background Primary Sjögren’s syndrome (pSS) is associated with dental caries. Pilocarpine, a salivary stimulant, can improve the amount and flow rate of saliva in patients with pSS. This study aimed to assess whether the risk of dental caries decreases with the use of pilocarpine in patients with pSS. Methods For this prospective cohort study, we identified pSS patients from the catastrophic illnesses registry of the National Health Insurance Research Database of Taiwan between 2009 and 2013. We divided participants into pilocarpine and non-user groups based on the pilocarpine prescriptions available during the first 3-month follow-up. The primary endpoint was dental caries. The secondary endpoints were periodontitis and oral candidiasis. We compared the risk of these oral manifestations using the Cox proportional hazard model. Results A total of 4973 patients with new-onset pSS were eligible for analysis. After propensity score matching, we included 1014 patients in the pilocarpine group and 2028 patients in the non-user group. During the mean follow-up of 2.6 years, the number of events was 487 in the pilocarpine group (48.0%) and 1047 in the non-user group (51.6%); however, the difference was not significant (hazard ratio [HR] 0.93, 95% confidence interval [CI] 0.82 to 1.06). Furthermore, there was no significant difference between groups regarding risk of periodontitis (HR 0.91, 95% CI 0.81 to 1.03) and oral candidiasis (HR 1.16, 95% CI 0.70 to 1.94). Conclusion Pilocarpine may have no protective effect on dental caries, periodontitis, or oral candidiasis in patients with pSS.

Background To evaluate the factors to predict subclinical inflammation of wrist joints in patients with RA who are in clinical remission or low disease activity. Methods Gray scale and power Doppler ultrasound were performed on the dorsal radio-lunate of both wrists. The presence of synovitis, comorbidities, and use of disease modifying anti-rheumatic drugs were recorded. A Multivariable forward logistical regression model was used to identify factors associated with subclinical inflammation. Results There were 1248 patients (1010 females, 238 males; mean age: 60.0 ± 10.5 years ). 57.4% of patients in complete remission and low disease activity had sonographic inflammation. Multivariable forward logistic regression analysis indicated that male sex, smoking are positively associated with inflammation and that age, alcohol consumption, and use of methotrexate, glucocorticoid, or a biological therapy are negatively associated with inflammation. Use of biological agents decreased the risk of inflammation by 40.9%. Conclusions There was evidence of subclinical inflammation in most patients who were in low or no disease activity, those with biological therapy had lower risk of subclinical inflammation.

Migraine is a prevalent neurological disorder characterized by significant disability and triggered by various factors, including dietary habits. This review explores the complex relationship between diet and migraine, highlighting both triggering and protective roles of dietary patterns and specific nutrients. Evidence suggests that certain foods, such as alcohol, caffeine, chocolate, MSG, nitrates, and tyramine, can trigger migraines in susceptible individuals. Conversely, dietary interventions, including carbohydrate-restricted diets, ketogenic diets, vitamin D3 supplementation, omega-3 fatty acids, Mediterranean dietary patterns, and increased water intake, have shown potential in reducing migraine frequency and severity. Observational studies also indicate that maintaining a healthy diet, rich in fruits and vegetables and low in processed foods, is associated with better migraine outcomes. The effectiveness of these interventions varies among individuals, underscoring the importance of personalized approaches. Future studies should further explore the role of diet in migraine management, focusing on randomized trials to establish causality and refine dietary recommendations for patients.

Background Adjacent fracture of the cemented vertebrae result from crushed fragile trabeculae during follow-up, suggesting impaired bone marrow integrity. This study aimed to determine if anti-osteoporotic therapy can decrease the risk of adjacent fracture in patients after vertebroplasty. Methods This retrospective study reviewed of cases of osteoporotic patients with magnetic resonance imaging (MRI)-proven acute vertebral fractures between 2001 and 2007. Osteoporotic patients were investigated as determined by pre-operative MRI with subsequent adjacent fracture of the cemented vertebrae and for the possibility of anti-osteoporotic therapy decreasing the progression of collapse after a minimum of 6 months follow-up. All associated co-morbidities were recorded, as well as the use of anti-osteoporotic drugs (i.e., bisphosphonate, raloxifen, calcitonin, and teriparatide). Cox regression analysis was also performed. Results The 192 vertebral fractured patients who underwent vertebroplasty and anti-osteoporotic therapy had a mean age of 74.40 ± 6.41. The basic characteristics of patients with and without adjacent fracture differed in age, body mass index, rheumatoid arthritis, and use of glucocorticoids and anti-osteoporotic drugs (Table 1). Using the Kaplan-Meier curve, anti-osteoporotic therapy after vertebroplasty had a significant effect on adjacent fracture ( p  = 0.037, by log rank text). After adjusting for potential confounders, patients with anti-osteoporotic therapy still had a lower adjacent fracture rate than patients without anti-osteoporotic therapy ( p  = 0.006; HR: 2.137, 95 % CI: 1.1238–3.690). The adjacent fracture rate also increased in old age ( p  = 0.019; HR: 1.049; 95 % CI:1.008–1.039) and among smokers ( p  = 0.026; HR: 3.891; 95 % CI: 1.175–12.890). Conclusions In this study, adjacent fracture of cemented vertebrae is inevitable after vertebroplasty but can be mitigated by anti-osteoporotic therapy to increase bone mass.

To compare changes in bone mineral density (BMD) in rheumatoid arthritis (RA) patients receiving three-year conventional synthetic disease-modifying anti-rheumatic drugs (csDMARD), tumor necrosis factor-α inhibitors (TNFi), and abatacept. Patients with RA were recruited from September 2014 to February 2021. Dual-energy X-ray absorptiometry was used to measure BMD at the femoral neck (FN), total hip (TH), and lumbar spine (L1-4) at enrollment and three years later. Changes in the BMD of each regimen group were analyzed. Multiple ordinary least squares regression was used with the dependent variables to develop a model to predict the change in BMD. A total of 752 participants were enrolled and 485 completed the three-year follow-up period. Of these, 375 (Group I), 84 (Group II), and 26 (Group III) participants received csDMARDs, TNFi, and abatacept therapy, respectively. Considering both type of therapy and completion of the follow-up period, participants were divided into groups A (csDMARDs, n = 104), B (TNFi, n = 52), and C (abatacept, n = 26). Compared to baseline, BMD decreased significantly at FN (p = 0.003) and L1-4 (p = 0.002) in Group A and at L1-4 (p = 0.005) in Group B, but remained stable at all sites in Group C. In terms of regression-adjusted percent change in BMD, there was a significant difference seen at all measured sites between group C compared to both groups A and B (+0.8%, -2.7%, -1.8% at FN; +0.5%, -1.1%, -1.0% at TH; +0.8%, -2.0%, -3.5% at L1-4, respectively; all p < 0.05). Anti-osteoporosis therapy had a BMD-preserving effect in RA. Compared with csDMARDs and TNFi, abatacept may have a better BMD-preserving effect in RA. Anti-osteoporosis therapy can prevent systemic bone loss irrespective of RA therapy.