Regulation of CLC-1 chloride channel biosynthesis by FKBP8 and Hsp90β.

Mutations in human CLC-1 chloride channel are associated with the skeletal muscle disorder myotonia congenita. The disease-causing mutant A531V manifests enhanced proteasomal degradation of CLC-1. We recently found that CLC-1 degradation is mediated by cullin 4 ubiquitin ligase complex. It is currently unclear how quality control and protein degradation systems coordinate with each other to process the biosynthesis of CLC-1. Herein we aim to ascertain the molecular nature of the protein quality control system for CLC-1. We identified three CLC-1-interacting proteins that are well-known heat shock protein 90 (Hsp90)-associated co-chaperones: FK506-binding protein 8 (FKBP8), activator of Hsp90 ATPase homolog 1 (Aha1), and Hsp70/Hsp90 organizing protein (HOP). These co-chaperones promote both the protein level and the functional expression of CLC-1 wild-type and A531V mutant. CLC-1 biosynthesis is also facilitated by the molecular chaperones Hsc70 and Hsp90β. The protein stability of CLC-1 is notably increased by FKBP8 and the Hsp90β inhibitor 17-allylamino-17-demethoxygeldanamycin (17-AAG) that substantially suppresses cullin 4 expression. We further confirmed that cullin 4 may interact with Hsp90β and FKBP8. Our data are consistent with the idea that FKBP8 and Hsp90β play an essential role in the late phase of CLC-1 quality control by dynamically coordinating protein folding and degradation

Note On Certain Inequalities for Neuman Means

In this paper, we give the explicit formulas for the Neuman means $N_{AH}$, $N_{HA}$, $N_{AC}$ and $N_{CA}$, and present the best possible upper and lower bounds for theses means in terms of the combinations of harmonic mean $H$, arithmetic mean $A$ and contraharmonic mean $C$.Comment: 9 page

Retrospective study of necrotizing fasciitis and characterization of its associated Methicillin-resistant Staphylococcus aureus in Taiwan

<p>Abstract</p> <p>Background</p> <p>Methicillin-resistant <it>Staphylococcus aureus </it>(MRSA) has emerged as a prevalent pathogen of necrotizing fasciitis (NF) in Taiwan. A four-year NF cases and clinical and genetic differences between hospital acquired (HA)- and community-acquired (CA)-MRSA infection and isolates were investigated.</p> <p>Methods</p> <p>A retrospective study of 247 NF cases in 2004-2008 and antimicrobial susceptibilities, staphylococcal chromosomal cassette <it>mec </it>(SCC<it>mec</it>) types, pulsed field gel electrophoresis (PFGE) patterns, virulence factors, and multilocus sequence typing (MLST) of 16 NF-associated MRSA in 2008 were also evaluated.</p> <p>Results</p> <p>In 247 cases, 42 microbial species were identified. <it>S. aureus </it>was the major prevalent pathogen and MRSA accounted for 19.8% of NF cases. Most patients had many coexisting medical conditions, including diabetes mellitus, followed by hypertension, chronic azotemia and chronic hepatic disease in order of decreasing prevalence. Patients with MRSA infection tended to have more severe clinical outcomes in terms of amputation rate (p < 0.05) and reconstruction rate (p = 0.001) than those with methicillin-sensitive <it>S. aureus </it>or non-<it>S. aureus </it>infection. NF patients infected by HA-MRSA had a significantly higher amputation rate, comorbidity, C-reactive protein level, and involvement of lower extremity than those infected by CA-MRSA. In addition to over 90% of MRSA resistant to erythromycin and clindamycin, HA-MRSA was more resistant than CA-MRSA to trimethoprim-sulfamethoxazole (45.8% <it>vs</it>. 4%). ST59/pulsotype C/SCC<it>mec </it>IV and ST239/pulsotype A/SCC<it>mec </it>III isolates were the most prevalent CA- and HA-MRSA, respectively in 16 isolates obtained in 2008. In contrast to the gene for γ-hemolysin found in all MRSA, the gene for Panton-Valentine leukocidin was only identified in ST59 MRSA isolates. Other three virulence factors TSST-1, ETA, and ETB were occasionally identified in MRSA isolates tested.</p> <p>Conclusion</p> <p>NF patients with MRSA infection, especially HA-MRSA infection, had more severe clinical outcomes than those infected by other microbial. The prevalent NF-associated MRSA clones in Taiwan differed distinctly from the most predominant NF-associated USA300 CA-MRSA clone in the USA. Initial empiric antimicrobials with a broad coverage for MRSA should be considered in the treatment of NF patients in an endemic area.</p

Female media use behavior and agreement with publicly promoted agenda-specific health messages.

This study set out to explore the relationship between female media use behavior and agreement with agenda-specific publicly promoted health messages. A random digit dial telephone cross-sectional survey was conducted using a nationally representative sample of female residents aged 25 and over. Respondents' agreement with health messages was measured by a six-item Health Information Scale (HIS). Data were analyzed using chi-square tests and multiple logistic regression. This survey achieved a response rate of 86% (n = 1074). In this study the longest duration of daily television news watching (OR = 2.32), high self-efficacy (OR = 1.56), and greater attention to medical and health news (OR = 5.41) were all correlates of greater agreement with the selected health messages. Surprisingly, Internet use was not significant in the final model. Many women that public health interventions need to be targeting are not receptive to health information that can be accessed through Internet searches. However, they may be more readily targeted by television campaigns. Agenda-specific public health campaigns aiming to empower women to serve as nodes of information transmission and achieve efficient trickle down through the family unit might do better to invest more heavily in television promotion

Existence theorems for a crystal surface model involving the p-Laplace operator

The manufacturing of crystal films lies at the heart of modern nanotechnology. How to accurately predict the motion of a crystal surface is of fundamental importance. Many continuum models have been developed for this purpose, including a number of PDE models, which are often obtained as the continuum limit of a family of kinetic Monte Carlo models of crystal surface relaxation that includes both the solid-on-solid and discrete Gaussian models. In this paper we offer an analytical perspective into some of these models. To be specific, we study the existence of a weak solution to the boundary value problem for the equation - \Delta e^{-\mbox{div}\left(|\nabla u|^{p-2}\nabla u\right)}+au=f, where $p>1, a>0$ are given numbers and $f$ is a given function. This problem is derived from a crystal surface model proposed by J.L.~Marzuola and J.~Weare (2013 Physical Review, E 88, 032403). The mathematical challenge is due to the fact that the principal term in our equation is an exponential function of a p-Laplacian. Existence of a suitably-defined weak solution is established under the assumptions that $p\in(1,2], \ N\leq 4$, and $f\in W^{1,p}$. Our investigations reveal that the key to our existence assertion is how to control the set where -\mbox{div}\left(|\nabla u|^{p-2}\nabla u\right) is $\pm\infty$

Bis(1,3-diethyl­benzimidazolium) tetra­bromidomercurate(II)

In the title compound, (C11H15N2)2[HgBr4], the tetra­coordinated HgII center of the complex anion adopts a distorted tetra­hedral geometry [Hg—Br = 2.5755 (8)–2.623 (11) Å and Br—Hg—Br = 103.78 (19)–116.4 (3)°]. One of the Br atoms is disordered over two sites [site-occupancy factors = 0.51 (6) and 0.49 (6)]. The N—C—N angles in the cations are 110.7 (6) and 111.4 (7)°. In the crystal packing, a supra­molecular chain is formed via both weak inter­molecular C—H⋯Br hydrogen bonds and π–π aromatic ring stacking inter­actions [centroid–centroid separation = 3.803 (1) Å]

Factors associated with the utilization of antenatal care services among pregnant women in Eswatini - A cross-sectional study

The study aimed to assess the utilization of antenatal care services and its associated factors among pregnant women in Eswatini. A cross-sectional study was adopted. Convenience sampling was conducted in a public referral hospital in central Eswatini from 1st of August to the 30 of September 2021. A total of 400 newly delivered women who met the inclusion criteria were recruited. SPSS version 22.0 was used to analyze data including descriptive and bivariate analysis. Results indicated that only 13% of pregnant women booked their first ANC in the first trimester and 24.8% of them attended less than four ANC visits. Maternal education, gestational age, gravity, pregnant-related complications, medical history, and maternal health literacy were significantly associated with the utilization of ANC services (p&lt; .05). To increase the utilization of ANC service, healthcare professionals should pay special attention to pregnant women with tertiary education, gave birth below 38 weeks, multi-gravities, medical history, and poor maternal health literacy. (Afr J Reprod Health 2022; 26[12]: 67-77). L'étude visait à évaluer l'utilisation des services de soins prénatals et ses facteurs associés chez les femmes enceintes en Eswatini. Une étude transversale a été retenue. Un échantillonnage de commodité a été effectué dans un hôpital public de référence du centre d'Eswatini du 1er août au 30 septembre 2021. Un total de 400 femmes nouvellement accouchées qui répondaient aux critères d'inclusion ont été recrutées. La version SPSS 22.0 a été utilisée pour analyser les données, y compris l'analyse descriptive et bivariée. Les résultats ont indiqué que seulement 13 % des femmes enceintes ont réservé leur première CPN au cours du premier trimestre et 24,8 % d'entre elles ont assisté à moins de quatre visites CPN. L'éducation de la mère, l'âge gestationnel, la gravité, les complications liées à la grossesse, les antécédents médicaux et les connaissances en matière de santé maternelle étaient significativement associés à l'utilisation des services de soins prénatals (p &lt; 0,05). Pour accroître l'utilisation des services de soins prénatals, les professionnels de la santé doivent accorder une attention particulière aux femmes enceintes ayant fait des études supérieures, ayant accouché à moins de 38 semaines, multigravités, ayant des antécédents médicaux et une faible littératie en matière de santé maternelle. (Afr J Reprod Health 2022; 26[12]: 67-77)

Methotrexate nanoparticle delivery system for treatment of inflammatory bowel disease in pediatric patients

Purpose: To evaluate the efficacy and safety of methotrexate (MTX) nanoparticles in pediatric patients with inflammatory bowel disease (IBD).Methods: In this randomized, open-label clinical study, 28 pediatric patients with moderate to severe IBD were randomly assigned to treatment (MTX  nanoparticles,15 mg/week) or control (azathioprine, AZA, 2 mg/kg/day) group.  Nanoparticles were synthesized by adding calcium chloride to sodium alginate solution containing MTX, and was further treated with poly-L-lysine aqueous  solution. The nanoparticles were evaluated for particle size, zeta potential and drug encapsulation efficacy. Erythrocyte sedimentation rate, C-reactive protein, aspartate aminotransferase, alanine transaminase, and disease activity scores were used to assess IBD remission.Results: Nanoparticle size, zeta potential and encapsulation efficacy were 164.4 ± 6.9 nm, -32.6 ± 3.7 mV, and 97.8 ± 4.2 %, respectively. After 12 weeks of therapy, the mean Pediatric Crohn's Disease Activity Index (PCDAI) scores for control and treatment groups were 22.3 ± 2.14 and 16.8 ± 1.87, respectively, while mean Pediatric Ulcerative Colitis Activity (PUCAI) Index scores were 24.3 ± 1.47 and18.7 ± 1.92, respectively. Eight patients in the treatment and five patients in the control group achieved remission. Biochemical parameters varied significantly between the groups.Conclusion: MTX nanoparticles are safe and more effective than standard first-line IBD therapy. However, further studies are required to determine the suitability of the formulation for therapeutic use.Keywords: Pediatric patient, Methotrexate nanoparticle, Inflammatory bowel disease, Azathioprin