Notes

3 brand new polyketides from vasR2 gene over-expressed mutant stress associated with Verrucosispora sp. NS0172.
Peficitinib, a pan-JAK inhibitor, is known to suppress the activation of fibroblast-like synoviocytes (FLSs) and thereby reduces joint inflammation associated with rheumatoid arthritis (RA). However, the effect on osteoporosis in RA remains to be elucidated. In this study, the effect of peficitinib or etanercept on joint inflammation, and consequently decreased bone mineral density (BMD) was evaluated in mice with collagen-induced arthritis (CIA). Additionally, the effect on RANKL production from osteoblasts differentiated from the mesenchymal stem cells of RA patients was evaluated. Administration of peficitinib for established CIA ameliorated arthritis and improved BMD in the femoral metaphysis, but not in the femoral diaphysis. Conversely, etanercept suppressed an increase in synovial inflammatory markers but did not improve arthritic conditions or the reduction of BMD in either region. All elevated bone formation and bone resorption markers were decreased with peficitinib but only partially decreased with etanercept. Furthermore, production of RANKL by human osteoblasts was suppressed by peficitinib but enhanced by etanercept. Unlike etanercept, peficitinib is thought to increase BMD by ameliorating the high bone turnover associated with RA states, resulting in improvement of bone fragility. Our data provide evidence that peficitinib would be expected to show efficacy for osteoporosis associated with RA.Manganese (Mn) is an essential trace element required for various biological processes. However, excess Mn causes serious side effects in humans, including parkinsonism. Thus, elucidation of Mn homeostasis at the systemic, cellular, and molecular levels is important. Many metal transporters and channels can be involved in the transport and homeostasis of Mn, and an increasing body of evidence shows that several zinc (Zn) transporters belonging to the ZIP and ZNT families, specifically, ZNT10, ZIP8, and ZIP14, play pivotal roles in Mn metabolism. Mutations in the genes encoding these transporter proteins are associated with congenital disorders related to dysregulated Mn homeostasis in humans. Moreover, single nucleotide polymorphisms of ZIP8 are associated with multiple clinical phenotypes. In this review, we discuss the recent literature on the structural and biochemical features of ZNT10, ZIP8, and ZIP14, including transport mechanisms, regulation of expression, and pathophysiological functions. Because a disturbance in Mn homeostasis is closely associated with a variety of phenotypes and risk of human diseases, these transporters constitute a significant target for drug development. An understanding of the roles of these key transporters in Mn metabolism should provide new insights into pharmacological applications of their inhibitors and enhancers in human diseases.Rheumatoid arthritis (RA) is an autoimmune disease with increased M1 macrophages. The classical activated M1 macrophages produce various cytokines to control inflammation. Wilforlide A is a natural product that displays anti-inflammatory activities. However, the effect of Wilforlide A on RA progression and the potential mechanisms are unclear. Herein, the collagen-induced arthritis (CIA) mouse was used as an experimental model of RA. The administration of Wilforlide A reduced clinical scores, joint swelling and histological damage in ankle joints of RA mice. The secreted pro-inflammatory factors (MCP1, GM-CSF and M-CSF) and M1 biomarker iNOS in synovium were inhibited by Wilforlide A. In vitro, macrophages deriving from THP-1 cells were stimulated with LPS/IFN-γ to mimic M1 polarization. Similarly, Wilforlide A blocked macrophages polarizing towards M1 subsets. The in vitro results demonstrated that Wilforlide A suppressed LPS/IFN-γ-induced TLR4 upregulation, IκBα degradation and NF-κB p65 activation. In addition, TAK242 (a TLR4 inhibitor) treatment caused a similar inhibitory effect on M1 polarization with Wilforlide A, whereas it was less than the combination of TAK242 and Wilforlide A. Therefore, this work supports that Wilforlide A ameliorates M1 macrophage polarization in RA, which is partially mediated by TLR4/NF-κB signaling pathway inactivation.Brain glycogen metabolism is known to be involved in the learning and memory processes. Protein targeting to glycogen (PTG) is a crucial molecule for glycogenesis, and its expression level is shown to be increased in the dorsal hippocampus during fear memory acquisition and recall, suggesting that PTG may contribute to the memory process. However, its detailed role in the dorsal hippocampus remains unclear. Therefore, we knocked down the expression of PTG in the dorsal hippocampus and attempted to analyze its function behaviorally. PTG expression was found to be enriched in astrocytes. Furthermore, short hairpin RNA against PTG suppressed the expression of PTG in astrocytes. Mice with knockdown of PTG in the dorsal hippocampus showed suppressed alternation behavior in the Y-maze test and reduced memory recall at the first hour after acquisition in the passive avoidance test. Knockdown of mouse dorsal hippocampal astrocyte-specific PTG also impaired working memory in the Y-maze test. GluR1, GluR2, and NR2a subunits expressions were significantly down-regulated in the dorsal hippocampus of mice in which PTG was knocked down. These results indicate that PTG in the dorsal hippocampal astrocytes may contribute to working and short-term memories by maintaining the expression of glutamate receptor subunits.We have reported that nicotine has a neurotrophic action on peripheral adrenergic nerves in vivo, which is mediated by α7 nicotinic acetylcholine receptors (nAChRs). To clarify the possible mechanisms, the present study further investigated the effect of nicotine on neurite outgrowth in tyrosine hydroxylase (TH)-positive superior cervical ganglia (SCG) cells isolated from neonatal rats in vitro. Nicotine at low concentrations (0.01-0.3 mM) increased the number of neurite outgrowths in TH-immunopositive SCG cells, while high concentrations of nicotine (1-10 mM) gradually reduced it, and only 10 mM nicotine was markedly inhibited compared to the control. A 100 μM of nicotine-induced increase in neurite numbers depended on the exposure time and was inhibited by treatment with the nAChR antagonist hexamethonium (Hex) and α7 nAChR antagonist α-bungarotoxin (α-Bgtx). The nicotine (10 mM)-induced a significant decrease in neurite outgrowth in SCG, which was perfectly canceled by Hex to the control level but not by α-Bgtx. These results suggest that nicotine has a regulatory neurotrophic action mediated by both α7 nAChR and other subtypes in TH-positive SCG cells of rats.The KCa3.1 inhibition up-regulates IL-10 expression in regulatory T (Treg) cells in the recovery phase of inflammatory bowel disease (IBD) model mice; however, the underlying signaling pathway remains unclear. We investigated the involvement of AP-1 (Fos/Jun) and NF-κB in the expression of IL-10 and its transcription factors (TFs) in in vitro-induced mouse splenic Treg cells. The pharmacological inhibition of JNK reversed KCa3.1 inhibition-induced increases in the expression of IL-10 and its TFs. The inhibition of KCa3.1 increased phosphorylated JNK and c-Jun levels. Therefore, the JNK/c-Jun signaling pathway may contribute to the KCa3.1 inhibition-induced up-regulation of IL-10 in peripherally-induced Treg cells.
Adolescents involved in the legal system are known to be under elevated risk for repeat offending. There may be many reasons for recidivism. Specifically, we aim to investigate the clinical, socio-demographic, and familial factors and psychopathology among adolescents in a penal institution and to determine risk factors for re-incarceration.

This single-center cross-sectional survey was conducted at Tarsus Closed Penal Institution for Children and Youth. This institution is for males only, and all male adolescents detained at the center within the study period were evaluated with semi-structured interviews (K-SADS-PL). The adolescents completed Meaning and Purpose of Life Scale, The EPOCH measure of Adolescent Well-being, Family Sense of Belonging Scale, Children's Alexithymia Scale, Beck Depression Inventory, and State-Trait Anxiety Inventory for themselves. Descriptive and inferential analyses were used. P was set at 0.05.

Ninety adolescent offenders with a mean age of 16.6years (S·D=0.7) were enrolleychiatric disorders regardless of the individual's request for treatment and refer identified cases to treatment. Integration of child and adolescent psychiatrists with penal institutions serving youth may help in this regard.
Turkish male adolescents in forensic settings may be screened for externalizing disorders and referred for treatment. Re-incarcerated Turkish youth may be more susceptible to peer influence, substance use and externalizing disorders. It may be prudent to systematically screen offending youth for psychiatric disorders regardless of the individual's request for treatment and refer identified cases to treatment. Integration of child and adolescent psychiatrists with penal institutions serving youth may help in this regard.Forensic psychiatric investigations in Sweden can have a major impact on the choice of sentence in criminal cases. Previous research shows that the decisions in several forensic fields, including forensic psychiatry, can be affected in a negative way by factors not relevant to the case. In the present study, the decision-making process of forensic psychiatric investigations was explored by using semi-structured interviews with experts (n = 38) and analyzing these interviews thematically. The results showed that the decision-making process is both complex and iterative, where the experts use and shape a substantial amount of information to reach their decisions. The experts work in teams, which add both benefits and risks to the process, and feel that particularly time constraints may reduce the quality of their decisions. In summary, the decision-making process of Swedish forensic psychiatric investigations creates a potential for high validity, but also contains risks for bias effects that could warrant further mitigation.A 49-year-old female fell from standing. Her right knee extended into the air. She had acute right knee pain preventing weight-bearing. Her knee was most comfortable fully-extended. Vemurafenib order She could not flex it due to pain, nor extend it against resistance. Tenderness and a horizontal defect were noted over the anterior knee. Bedside ultrasound demonstrated a horizontally-fractured patella (confirmed on X-ray) with intact femoral and patellar tendons. She was put in a knee immobilizer and underwent surgery, with return to full function and activities. Ultrasound can identify patella fractures and help with early evaluation, management, and specialty referral, as well as ordering more-focused imaging. In one study, POCUS (point-of-care ultrasound) for patella fracture had 95% sensitivity, 63% specificity, 86% positive predictive value, and 83% negative predictive value. The dynamic nature of ultrasound allows a ruptured patella (87% sensitivity) or quadriceps tendon (100% sensitivity) to be excluded with high certainty.
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