Mccarthymohr1200

Idiopathic pulmonary fibrosis (IPF) is a chronic, fatal lung disease characterized by progressive and non-reversible abnormal matrix deposition in lung parenchyma. check details Myofibroblasts origin mainly from resident fibroblasts via fibroblast-to-myofibroblast transition (FMT) are the dominant collagen-producing cells in pulmonary fibrosis. N6-methyladenosine (m6A) modification has been implicated in various biological process. However, the role of m6A modification in pulmonary fibrosis remains elusive. In this study, we reveal that m6A modification is up-regulated in bleomycin induced pulmonary fibrosis mice model, FMT-derived myofibroblasts and idiopathic pulmonary fibrosis patient lung samples. Lowering m6A level through silencing METTL3 inhibits FMT process in vitro and vivo. Mechanistically, KCNH6 is involved in m6A-regulated FMT process. m6A modification regulates the expression of KCNH6 by modulating its translation in a YTHDF1 dependent manner. Together, our study highlights the critical role of m6A modification in pulmonary fibrosis. Manipulation of m6A modification through targeting METTL3 may become a promising strategy for the treatment of pulmonary fibrosis.A 21-year-old with a history of cyclic abdominal pain beginning at age 13 and a prior diagnosis of a complex Mullerian anomaly represented with abdominal pain and a finding of a right distended hemi-uterus, left hematosalpinx, and cervix separate from the uterine body. After laparoscopic decompression for symptomatic relief at that time, she presented to our center for definitive mangament. After diagnostic vaginoscopy and laparoscopy confirmed the diagnosis of uterine isthmus agenesis, an abdominal approach to utero-cervical anastomosis was planned and undertaken. Post-surgical clinical follow-up the patient reported normal menses and resolution of pain, and imaging confirmed maintenance of anastomotic patency. The diagnosis and classification system of Mullerian anomalies is complex and few reports detail the management of rare Mullerian anomalies. Here, the successful anastomosis of uterus and cervix is reviewed as an approach that can successfully and safely restore normal menses and potentially allow for future fertility in patients with uterine isthmus agenesis.

To compare bone mineral density (BMD) changes after 12 months of treatment with denosumab or bisphosphonates in postmenopausal women with severe osteoporosis after stopping teriparatide therapy.

We retrospectively analyzed 140 postmenopausal women (mean age, 74.2 years) with severe osteoporosis who had been treated with teriparatide for 18 to 24 months at our outpatient clinic in a tertiary endocrine center between 2006 and 2015. After stopping teriparatide therapy, they continued treatment with a bisphosphonate (alendronate, risedronate, ibandronate, or zoledronic acid) or denosumab while receiving daily vitamin D and calcium. BMD at the lumbar spine (LS), total hip (TH), and femoral neck (FN) was measured by dual energy x-ray absorptiometry when teriparatide therapy was discontinued (baseline) and after 12 months of further treatment. Multivariate linear regression models were used to identify the predictors of BMD gain.

After stopping teriparatide therapy, 70 women continued treatment with bisphosphonates and 70 received denosumab. LS, but not TH or FN, BMD gain was significantly greater in the denosumab group than in the bisphosphonates group at 12 months. Multivariate analysis showed that BMD gain at the LS was negatively associated with bisphosphonate versus denosumab treatment and positively associated with baseline serum total procollagen type I N-terminal propeptide. BMD gains at the FN were predicted by higher baseline serum urate levels. BMD gains at the TH and FN were negatively associated with pretreatment BMD gains at the same site.

Twelve months after stopping teriparatide therapy, sequential denosumab treatment appeared to yield higher additional LS BMD gain on average compared with bisphosphonates treatment.

Twelve months after stopping teriparatide therapy, sequential denosumab treatment appeared to yield higher additional LS BMD gain on average compared with bisphosphonates treatment.Adverse Drug Events (ADEs) are prevalent, costly, and sometimes preventable. Post-marketing drug surveillance aims to monitor ADEs that occur after a drug is released to market. Reports of such ADEs are aggregated by reporting systems, such as the Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS). In this paper, we consider the topic of how best to represent data derived from reports in FAERS for the purpose of detecting post-marketing surveillance signals, in order to inform regulatory decision making. In our previous work, we developed aer2vec, a method for deriving distributed representations (concept embeddings) of drugs and side effects from ADE reports, establishing the utility of distributional information for pharmacovigilance signal detection. In this paper, we advance this line of research further by evaluating the utility of encoding orthographic and lexical information. We do so by adapting two Natural Language Processing methods, subword embedding and vector retrofitting, which were developed to encode such information into word embeddings. Models were compared for their ability to distinguish between positive and negative examples in a set of manually curated drug/ADE relationships, with both aer2vec enhancements offering advantages in performances over baseline models, and best performance obtained when retrofitting and subword embeddings were applied in concert. In addition, this work demonstrates that models leveraging distributed representations do not require extensive manual preprocessing to perform well on this pharmacovigilance signal detection task, and may even benefit from information that would otherwise be lost during the normalization and standardization process.The evidence for use of direct oral anticoagulants (DOACs) in the management of post-operative cardiac surgery atrial fibrillation is limited and mostly founded on clinical trials that excluded this patient population. We performed a systematic review and meta-analysis of clinical trials and observational studies to evaluate the hypothesis that DOACs are safe compared to warfarin for the anticoagulation of patients with post-operative cardiac surgery atrial fibrillation. We searched PubMed, EMBASE, Web of Science, clinicaltrials.gov, and the Cochrane Library for clinical trials and observational studies comparing DOAC with warfarin in patients ≥18 years old who had post-cardiac surgery atrial fibrillation. Primary outcomes included stroke, systemic embolization, bleeding, and mortality. We performed a random-effects meta-analysis of all outcomes. The meta-analysis for the primary outcomes showed significantly lower risk of stroke with DOAC use (6 studies, 7143 patients, RR 0.64; 95% CI 0.50-0.81, I2 0.0%) compared to warfarin, a trend towards lower risk of systemic embolization (4 studies, 7289 patients, RR 0.