Dahlpickett0531

Phosphodiesterases (PDEs) form a superfamily of enzymes that catalyze the hydrolysis of cyclic nucleotides adenosine 3'5'-cyclic monophosphate (cAMP) and guanosine 3'5'-cyclic monophosphate (cGMP) to their inactive 5' monophosphates. cAMP plays a critical role as a second messenger in endocrine tissues, and activation of cAMP signaling has been reported in endocrine tumors. Germline variants in PDEs have been associated with benign cortisol-secreting adrenocortical adenomas and testicular germ cell cancer but not adrenocortical carcinoma. We performed whole genome sequencing (WGS) and whole exome sequencing (WES) of paired blood and tumor samples from 37 pediatric adrenocortical tumors (ACTs). Germline inactivating variants in PDEs were observed in 9 of 37 (24%) patients. Tumor DNA analysis revealed loss of heterozygosity, with maintenance of the mutated allele in all cases. Our results suggest that germline variants in PDEs and other regulators of the cAMP-signaling pathway may contribute to pediatric adrenocortical tumorigenesis, perhaps by cooperating with germline hypomorphic mutant TP53 alleles and uniparental disomy of chromosome 11p15 (Beckwith-Wiedemann syndrome).Mechanical overload and aging are the main risk factors of osteoarthritis (OA). Galectin 3 (GAL3) is important in the formation of primary cilia, organelles that are able to sense mechanical stress. The objectives were to evaluate the role of GAL3 in chondrocyte primary cilium formation and in OA in mice. Chondrocyte primary cilium was detected in vitro by confocal microscopy. OA was induced by aging and partial meniscectomy of wild-type (WT) and Gal3-null 129SvEV mice (Gal3-/-). Primary chondrocytes were isolated from joints of new-born mice. Chondrocyte apoptosis was assessed by Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), caspase 3 activity and cytochrome c release. Gene expression was assessed by qRT-PCR. GAL3 was localized at the basal body of the chondrocyte primary cilium. Primary cilia of Gal3-/- chondrocytes were frequently abnormal and misshapen. Deletion of Gal3 triggered premature OA during aging and exacerbated joint instability-induced OA. In both aging and surgery-induced OA cartilage, levels of chondrocyte catabolism and hypertrophy markers and apoptosis were more severe in Gal3-/- than WT samples. In vitro, Gal3 knockout favored chondrocyte apoptosis via the mitochondrial pathway. GAL3 is a key regulator of cartilage homeostasis and chondrocyte primary cilium formation in mice. Gal3 deletion promotes OA development.Pigmented villonodular synovitis (PVNS) of the ankle is a very rare, locally aggressive, proliferative disorder. Although surgical excision represents the standard curative treatment, the PVNS relapse rate is high. We present our study of five young athletes (range 20-36 years) with a histopathological diagnosis of PVNS of the ankle, who were treated by surgery and adjuvant radiosynoviorthesis (RSO). The operation involved either arthroscopic (four patients) or open (one patient) debridement, followed by intraarticular RSO with the radiopharmaceutical erbium-169 (169Er). They were evaluated with the Foot Function Index (FFI) and a visual analog scale (VAS) for pain. At a median follow up period of 47 months (range 36-54 months), all five patients reported marked pain relief with improvements in their daily activities. In particular, the median FFI decreased from 77% (range 71.0%-84.5%) pre-treatment, to 0.5% (range 0%-6%) after treatment. selleckchem The median VAS score decreased from 4 (range 3-7) to 0 (range 0-1), respectively. Throughout the follow-up period, there were no major complications regarding either therapeutic intervention (arthroscopic or open debridement, RSO). Based on these results, it can be concluded that adjuvant RSO with 169Er following surgical excision is effective and safe in the treatment of PVNS of the ankle.The ongoing COVID-19 epidemic continues to spread within and outside of China, despite several social distancing measures implemented by the Chinese government. Limited epidemiological data are available, and recent changes in case definition and reporting further complicate our understanding of the impact of the epidemic, particularly in the epidemic's epicenter. Here we use previously validated phenomenological models to generate short-term forecasts of cumulative reported cases in Guangdong and Zhejiang, China. Using daily reported cumulative case data up until 13 February 2020 from the National Health Commission of China, we report 5- and 10-day ahead forecasts of cumulative case reports. Specifically, we generate forecasts using a generalized logistic growth model, the Richards growth model, and a sub-epidemic wave model, which have each been previously used to forecast outbreaks due to different infectious diseases. Forecasts from each of the models suggest the outbreaks may be nearing extinction in both Guangdong and Zhejiang; however, the sub-epidemic model predictions also include the potential for further sustained transmission, particularly in Zhejiang. Our 10-day forecasts across the three models predict an additional 65-81 cases (upper bounds 169-507) in Guangdong and an additional 44-354 (upper bounds 141-875) cases in Zhejiang by February 23, 2020. In the best-case scenario, current data suggest that transmission in both provinces is slowing down.In the dental field, the most common oral diseases include periodontitis, apical periodontitis, abscesses, phlegmons and pulpits, all of which are determined by the same aetiological factor, bacterial infections. For these reasons, it is important to choose the right approach through a target antibiotic therapy against oral bacteria. More specifically, during periodontitis, antibiotics are used, often in association with periodontal debridement, to reduce disease-associated periodontopathogens. However, international guidelines are not unanimous in recommending the use of local and/or systemic antimicrobials to reduce infection by oral bacteria, especially in cases in which there is a danger of spreading systemic infection such as cellulitis, diffuse swelling, and abscesses. The lack of consensus is mainly due to the side effects of antibiotic therapy in dentistry, maybe due to recent scientific evidence regarding the development of bacterial resistance to antibiotics. Therefore, the purpose of this editorial is to analyze the therapeutic effects of antibiotics against the main forms of oral and periodontal diseases, and whether there is a significant clinical benefit, especially in the long term, of antimicrobial therapies in dentistry.