Alopecia areata is characterized by expansion of circulating Th2/Tc2/Th22, within the skin-homing and systemic T-cell populations.

BACKGROUND: Characterizing blood profile of alopecia areata (AA) is important not only for treatment advancements, but also for possibly identifying peripheral biomarkers that will eliminate the need for scalp biopsies. We aimed to compare frequencies of skin homing (CLA+ ) vs systemic (CLA- ) "polar" CD4+ and CD8+ and activated T-cell subsets in AA vs atopic dermatitis (AD) and control blood. METHODS: Flow cytometry was used to measure IFN-γ, IL-13, IL-9, IL-17, and IL-22 cytokines in CD4+ and CD8+ T cells. Inducible co-stimulator molecule (ICOS) and HLA-DR were used to define mid- and long-term T-cell activation. We compared peripheral blood from 32 moderate-to-severe AA adults with 43 moderate-to-severe AD patients and 30 age-matched controls. RESULTS: AA patients had increased CLA+ /CLA- Th2 (P < .007), CLA+ Tc2 (P = .04), and CLA+ Th22 (P < .05) frequencies than controls. Except of CLA- Tc1 cells (P = .03), IFN-γ levels were mostly similar between AA, AD, and controls (P > .1). ICOS and HLA-DR activation were significantly higher in AA than controls (P < .05). T regulatory cells were significantly decreased in AA patients than controls (P < .01) and were correlated with activated CD8+ T cells and with multiple cytokine subsets (P < .05). While Th2 and Tc2 clustered with disease severity, IFN-γ producing cells were linked with AA duration. CONCLUSIONS: Alopecia areata is accompanied by Th2/Tc2 activation in skin-homing and systemic subsets, correlating with disease severity, while IFN-γ is linked to disease chronicity. These data hint for a possible role of diverse T-cells subsets in disease pathogenesis and emphasize the systemic nature of AA supporting the need for systemic therapeutic strategies in severe patients.

Risk factors of involuntary referral by police to ER psychiatric services for patients with a severe mental illness: A GEE analysis.

This study aimed to identify risk factors for involuntary referral by police to emergency room (ER) psychiatric services for community-based patients with a mental illness via a generalized estimating equation (GEE) analysis. The analysis was based on data from the Management Information System of Psychiatric Care (MISPC) system for patients with a severe mental illness in Taipei, Taiwan and registered referral records of the police. Data on 6378 patients aged ≥20 years were used in this study, including 164 patients who were involuntarily referred to the ER by the police and 6214 patients who were not during the period of January 1, 2018 to December 31, 2020. GEEs were utilized to explore possible risk factors of repeated involuntary referral to ER psychiatric services for patients with a severe mental illness. The logistic regressions indicated that patients defined as "severe" according to the Mental Health Act of Taiwan (crude odds ratio (OR): 3.840, 95 % confidence interval (CI): 2.407-6.126), with a disability (crude OR: 3.567, 95 % CI: 1.339-9.501), with two or more family members with a psychiatric disorder (crude OR: 1.598, 95 % CI: 1.002-2.548), with a history of a suicide attempt (crude OR: 25.582, 95 % CI: 17.608-37.167), and with a history of domestic violence (crude OR: 16.141, 95 % CI: 11.539-22.579) were positively associated with involuntary referral to ER psychiatric services. However, age (crude OR: 0.971, 95 % CI: 0.960-0.983) and the MISPC score (crude OR: 0.834, 95 % CI: 0.800-0.869) were inversely associated with involuntary referral to ER psychiatric services. After adjusting for demographics and potential confounders, we found that patients defined as "severe" (Exp (ß): 3.236), with a disability (Exp (ß): 3.715), with a history of a suicide attempt (Exp (ß): 8.706), and with a history of domestic violence (Exp (ß): 8.826), as well as age (Exp (ß): 0.986) and the MISPC score (Exp (ß): 0.902) remained significantly associated with repeated involuntary referral to ER psychiatric services. In conclusion, community-based mentally ill patients with a history of a suicide attempt, with a history of domestic violence, with a severe illness, and with a profound level of disability were highly associated with involuntary referral to ER psychiatric services. We suggest that community mental health case managers identify significant factors associated with involuntary referral to ER psychiatric services to accordingly arrange case management plans.

[Research advances on platelet-rich blood products combined with biological materials in wound repair].

The efficient management of wounds is the focus of current research. In addition to conventional wound management and necessary surgery, the role of pro-healing drugs in wound treatment has gradually been emphasized. Platelet-rich blood products that is rich in a variety of biologically active molecules are considered as a low-cost and safe therapy in promoting tissue healing, and have great development prospects in the field of regenerative medicine. However, due to the lack of standard preparation and management and the unstable activities of the biomolecules in them, the therapeutic effects of platelet-rich blood products are uneven. In order to solve these problems, researches related to the protection and delivery of biologically active molecules in platelet-rich blood products by biomaterials have gradually increased in recent years, which is also one of the latest trends in wound treatment research. This article first briefly introduces the types of platelet-rich blood products, then outlines the latest research progress achieved by their combination with biomaterials, and finally summarizes the research progress and future research directions of the combination approach in wound treatment.

Heat shock protein 72 overexpression protects against hyperthermia, circulatory shock, and cerebral ischemia during heatstroke.

This study extends our earlier studies in rats by applying our heatstroke model to a new species. Additionally, transgenic mice are used to examine the role of heat shock protein (HSP) 72 in experimental heatstroke. Transgenic mice that were heterozygous for a porcine HSP70i gene ([+]HSP72), transgene-negative littermate controls ([-]HSP72), and normal Institute of Cancer Research strain mice (ICR) under pentobarbital sodium anesthesia were subjected to heat stress (40 degrees C) to induce heatstroke. In [-]HSP72 or ICR, the values for mean arterial pressure, the striatal blood flow, and the striatal PO2 after the onset of heatstroke were significantly lower than those in preheat controls. The core and brain temperatures, the extracellular concentrations of ischemic and injury markers in the striatum, and the striatal neuronal damage scores were significantly greater than those in the preheat controls. In [-]HSP72 or ICR, the body temperatures, cell ischemia content, and injury marker in the striatum were significantly higher, and the mean arterial pressure, striatal blood flow, and striatal PO2 concentration were significantly lower during heatstroke than in [+]HSP72. Accordingly, the latency and the survival times for [+]HSP72 significantly exceeded those of [-]HSP72 or ICR. These results demonstrate that the overexpression of HSP72 in multiple organs improves survival during heatstroke by reducing hyperthermia, circulatory shock, and cerebral ischemia and damage in mice.

Stress signaling and the shaping of the mammary tissue in development and cancer.

The postnatal mammary gland develops extensively through cycles of proliferation, branching, involution and remodeling. We review recent advances made in the field of stress signaling pathways and its roles in mammary gland organogenesis, how they contribute to normal organ specification and homeostasis and how its subversion by oncogenes leads to cancer. We analyze stress signaling in mammary gland biology taking into account the interrelationship with the extracellular matrix and adhesion signaling during morphogenesis. By integrating the information gathered from in vivo and three dimensional in vitro organogenesis studies, we review the novel contribution of p38(SAPK), c-Jun NH2-terminal kinase and PKR-like endoplasmic reticulum kinase (PERK) signaling pathways to the timely activation of cell death, correct establishment of polarity and growth arrest and autophagy, respectively. We also review the evidence supporting that the activation of the aforementioned stress kinases maintain breast acinar structures as part of a tumor suppressive program and that its deregulation is commonplace during breast cancer initiation.

Optimal design of integrally gated CNT field-emission devices using a genetic algorithm.

A method to optimize the focusing quality of integrally gated CNT field-emission (FE) devices by combining field-emission modeling and a computational intelligence technique, genetic algorithm (GA), is proposed and demonstrated. In this work, the e-beam shape, as a characteristic parameter of electron-optical properties, is calculated by field-emission simulation modeling. Using a design tool that combines GA and physical modeling, a set of structural and electrical parameters for four FE device groups, including double-gate, triple-gate, quadruple-gate and quintuple-gate type, were optimized. The resultant FE devices exhibit satisfactory e-beam focusabilities and the extracted parameters with the best performance for each type of FE device were represented to be fabricated by a VLSI technique. The GA-based automatic design parameter extraction will significantly benefit the design of integrated electron-optical systems for versatile vacuum micro- and nano-electronic applications.

Basal cPLA(2) phosphorylation is sufficient for Ca(2+)-induced full activation of cPLA(2) in A549 epithelial cells.

The release of [(3)H] arachidonic acid (AA) and its connection with the triggering of the MAP kinase cascade were studied in the human A549 epithelial cell line upon stimulation with thapsigargin. Thapsigargin can increase AA release along with the increase of intracellular calcium concentration, phosphorylation, and activation of extracellular regulated kinase (ERK) and cytosolic phospholipase A(2) (cPLA(2)). Both ERK and cPLA(2) phosphorylation in response to thapsigargin were inhibited by PD 98059, a specific inhibitor of MAP kinase kinase of the ERK group (MEK), and EGTA. cPLA(2) phosphorylation was not affected by Ro 31-8220 (an inhibitor of all PKC isoforms) or LY 379196 (a PKCbeta selective inhibitor), while both of them indeed attenuated ERK activation. On the other hand, rottlerin (the selective PKCdelta inhibitor), SB 203580 (the selective p38 MAPK inhibitor), and wortmannin (the PI 3-kinase inhibitor) can affect neither cPLA(2) nor ERK phosphorylation. In A549 cells, PKC activator PMA cannot increase either the basal or thapsigargin-induced (3)H-AA release, while it can induce the phosphorylation of ERK and cPLA(2.) The PMA-induced ERK phosphorylation was inhibited by Ro 31-8220, LY 379196, rottlerin, and PD 98059, but unaffected by SB 203580 and wortmannin. Moreover, the phosphorylation by PMA was non-additive with that of thapsigargin. This implies that intracellular Ca(2+) level is the key factor for induction of cPLA(2) activity and thapsigargin-elicited ERK activation itself is substantially sufficient for cPLA(2) activation upon intracellular Ca(2+) increase.