North American Specification for Design of Cold-Formed Steel

For over fifty years, the American Iron and Steel Institute has published the widely used Specification for the Design of Cold-Fom1ed Steel Structural Members. Recently, as a result of collaborative efforts with representatives of Canada and Mexico, the AISI Specification was expanded into a new document for use in all three countries. Now known as the North American Specification for the Design of Cold-Formed Steel Structural Members, the new edition supersedes the previous AISI Specification and the Canadian Sl36 Standard. This paper reviews the differences between the previous AISI Specification and the new North American Specification. The basic core document consists of Chapters A through G, while country specific issues are addressed in three separate appendices. The appendices include items of a broad nature, such as provisions for the design method to be used, the reference source for loads and load combinations, and other references that are country specific. The appendices also include country specific technical provisions where full agreement between the three countries was not reached. Efforts will be made to minimize these differences in future editions

Role of Glutathione in the Regulation of Cisplatin Resistance in Cancer Chemotherapy

Three mechanisms have been proposed for the role of glutathione (GSH) in regulating cisplatin (CDDP) sensitivities that affects its ultimate cell-killing ability: (i) GSH may serve as a cofactor in facilitating multidrug resistance protein 2- (MRP2-) mediated CDDP efflux in mammalian cells, since MRP2-transfected cells were shown to confer CDDP resistance; (ii) GSH may serve as a redox-regulating cytoprotector based on the observations that many CDDP-resistant cells overexpress GSH and γ-glutamylcysteine synthesis (γ-GCS), the rate-limiting enzyme for GSH biosynthesis; (iii) GSH may function as a copper (Cu) chelator. Elevated GSH expression depletes the cellular bioavailable Cu pool, resulting in upregulation of the high-affinity Cu transporter (hCtr1) which is also a CDDP transporter. This has been demonstrated that overexpression of GSH by transfection with γ-GCS conferred sensitization to CDDP toxicity. This review describes how these three models were developed and critically reviews their importance to overall CDDP cytotoxicity in cancer cell treatments

Exploring stakeholders' perspectives on the quality of services provided through community pharmacies

Introduction - It is important to understand the factors impacting the quality of services provided through community pharmacies. Exploring how key stakeholders perceive good quality in these services is a logical first step. This could also inform the development of quality measures, such as quality indicators (QIs). Aim - To identify key stakeholders' perspectives on the quality of services provided through community pharmacies in Norway, specifically by exploring their experiences and perceptions about what constitutes good service quality. Methods - A convenient sampling approach was used to recruit participants for five semi-structured focus groups from Facebook, pharmacy chains, and patient organizations. The interviews with twenty-six participants were conducted via Microsoft Teams. Interviews were transcribed verbatim, and an inductive thematic analysis with a reflexive approach was used. Results - Four main themes emerged from the analysis; 1) sufficient and substantively suitable information to cover individual needs, 2) communication skills and relationships with the pharmacy professionals, 3) customer satisfaction with knowledgeable employees and conveniently located pharmacies, and 4) factors that affect the pharmacy working environment. Conclusion - This study has identified areas that pharmacy professionals and customers regard as essential to define good quality of community pharmacy services. Effective communication skills, appropriate provision of information, customer satisfaction, and working environment are all essential factors when developing quality metrics for community pharmacies

Structure-Function Relationships of the Temporomandibular Joint in Response to Altered Loading

Aims: To elucidate the effects of decreased occlusal loading (DOL), with or without reloading (RL), on the structure and bite force function of the mandibular condylar fibrocartilage in skeletally mature male mice. Methods: At 13 weeks old, 30 wild type (WT) male mice were subjected to: (1) 6 weeks normal loading (NL); (2) 6 weeks DOL; or (3) 4 weeks DOL + 2 weeks RL. Histomorphometry, cell metabolic activity, gene expression of chondrogenic markers, and bite force tests were performed. Results: DOL resulted in a significant increase in apoptosis (P .10), apoptosis (P > .999), and bite force (P > .90), but not in mandibular condylar fibrocartilage thickness (P > .05). Conclusions: DOL in skeletally mature mice induces mandibular condylar fibrocartilage atrophy at the hypertrophic cell layer with a corresponding decrease in bite force.R56 DE020097F32 DE026366French Federation of Orthodontic

Duration of untreated bipolar disorder: A multicenter study

Little is known about the demographic and clinical differences between short and long duration of untreated bipolar disorder (DUB) in Chinese patients. This study examined the demographic and clinical features of short (≤2 years) and long DUB (\u3e2 years) in China. A consecutively recruited sample of 555 patients with bipolar disorder (BD) was examined in 7 psychiatric hospitals and general hospital psychiatric units across China. Patients’ demographic and clinical characteristics were collected using a standardized protocol and data collection procedure. The mean DUB was 3.2 ± 6.0 years; long DUB accounted for 31.0% of the sample. Multivariate analyses revealed that longer duration of illness, diagnosis of BD type II, and earlier misdiagnosis of BD for major depressive disorder or schizophrenia were independently associated with long DUB. The mean DUB in Chinese BD patients was shorter than the reported figures from Western countries. The long-term impact of DUB on the outcome of BD is warranted

Influence of the vanilloid receptor TRPV1 on the activation of spinal cord glia in mouse models of pain

Although activation of spinal glia has been implicated in the development of pathological pain, the mechanisms underlying glial activation are not fully understood. One such mechanism may be triggered by reaction to neuroactive substances released from central axons of sensory afferents. The vanilloid receptor TRPV1, a nonselective cation channel in nociceptive sensory afferents, mediates the release of neurotransmitters, such as glutamate and CGRP in the dorsal horn, which can subsequently activate glia. To test the hypothesis that activation of spinal glia is mediated, at least in part, by TRPV1, we studied the expression of markers for microglia (Ionized calcium-binding adapter molecule 1, Iba1) and astrocytes (Glial Fibrillary Acidic Protein, GFAP) in the spinal cord of TRPV1 knockout mice (KO) vs. wild-type mice (WT) in models of acute (intraplantar capsaicin), inflammatory (Adjuvant-Induced Arthritis, AIA), and neuropathic pain (Partial Sciatic Nerve Ligation, PSNL). We found that i) naïve KO mice had denser immunostaining for both Iba1 and GFAP than naïve WT mice, ii) the immunostaining for Iba1 increased significantly in treated mice, compared to naïve mice, 3 days after capsaicin and 7–14 days after AIA or PSNL, and was significantly greater in WT than in KO mice 3 days after capsaicin, 7–14 days after AIA, and 7 days after PSNL, iii) the immunostaining for GFAP increased significantly in treated mice, compared to naïve mice, 3 days after capsaicin and 14–21 days after AIA or PSNL, and was significantly greater in WT than in KO mice 14 days after AIA or PSNL. Our results suggest that TRPV1 plays a role in the activation of spinal glia in mice with nociceptive, inflammatory, and neuropathic pain

Increased expression of CGRP in sensory afferents of arthritic mice – effect of genetic deletion of the vanilloid receptor TRPV1

The neuropeptide calcitonin gene-related peptide (CGRP), expressed by nociceptive sensory afferents in joints, is an important mediator in the pathogenesis of arthritis. Capsaicin causes neurons in the dorsal root ganglia (DRG) to release CGRP from their central and/or peripheral axons, suggesting a functional link between CGRP and the capsaicin receptor TRPV1. The expression of both TRPV1 and CGRP have been reported to increase in several models of arthritis but the specific involvement of TRPV1-expressing articular afferents that can release CGRP remains unclear. We here wanted to ascertain whether the increase in the number of CGRP-positive primary afferents during arthritis may be affected by genetic deletion of TRPV1. For this, we quantified the expression of CGRP in primary afferent neurons in DRG in wild type mice (WT) vs. TRPV1-KO mice with adjuvant-induced arthritis (AIA), using immunohistochemistry. We found that the fraction of DRG neurons that were immunopositive for CGRP 1) was higher in naïve TRPV1-KO mice than in naïve WT mice, 2) increased progressively 3–21 days after induction of AIA, and 3) this increase was bilateral but significantly greater on the CFA-injected side than on the IFA-injected side in TRPV1-KO mice. The increased expression of CGRP in AIA may reflect a phenotypic switch of primary afferents from non-peptidergic to peptidergic and the larger increase in TRPV1-KO mice may represent a plastic change to compensate for the missing receptor in a major sensory circuit