TRPM4 channels couple purinergic receptor mechanoactivation and myogenic tone development in cerebral parenchymal arterioles

Cerebral parenchymal arterioles (PAs) have a critical role in assuring appropriate blood flow and perfusion pressure within the brain. They are unique in contrast to upstream pial arteries, as defined by their critical roles in neurovascular coupling, distinct sensitivities to chemical stimulants, and enhanced myogenic tone development. The objective of the present study was to reveal some of the unique mechanisms of myogenic tone regulation in the cerebral microcirculation. Here, we report that in vivo suppression of TRPM4 (transient receptor potential) channel expression, or inhibition of TRPM4 channels with 9-phenanthrol substantially reduced myogenic tone of isolated PAs, supporting a key role of TRPM4 channels in PA myogenic tone development. Further, downregulation of TRPM4 channels inhibited vasoconstriction induced by the specific P2Y4 and P2Y6 receptor ligands (UTPγS and UDP) by 37% and 42%, respectively. In addition, 9-phenanthrol substantially attenuated purinergic ligand-induced membrane depolarization and constriction of PAs, and inhibited ligand-evoked TRPM4 channel activation in isolated PA myocytes. In concert with our previous work showing the essential contributions of P2Y4 and P2Y6 receptors to myogenic regulation of PAs, the current results point to TRPM4 channels as an important link between mechanosensitive P2Y receptor activation and myogenic constriction of cerebral PAs.     

Evaluation and validation of the Core Lower Urinary Tract Symptom Score as an outcome assessment tool for the treatment of benign prostatic hyperplasia: Effects of the α1‐adrenoreceptor antagonist silodosin

We investigated the Core Lower Urinary Tract Symptom Score as an outcome assessment tool for the treatment of lower urinary tract symptoms using silodosin. In addition, the ability of the Core Lower Urinary Tract Symptom Score to detect overactive bladder in male patients with lower urinary tract symptoms was examined. The present study included 241 males with benign prostatic hyperplasia treated at 31 medical facilities between June 2009 and December 2010. All patients were given silodosin, and the effects of silodosin intake were measured using four questionnaires: the Core Lower Urinary Tract Symptom Score, International Prostate Symptom Score, Overactive Bladder Symptom Score and Quality‐of‐Life index. The efficacy of silodosin for treating lower urinary tract symptoms was validated according to the total scores of all four questionnaires weighted equally (P < 0.05). Spearman's ρ among the Core Lower Urinary Tract Symptom Score, International Prostate Symptom Score and Overactive Bladder Symptom Score showed a mild‐high correlation. However, the correlation between the baseline values of the Core Lower Urinary Tract Symptom Score and Quality‐of‐Life index was low in the groups with benign prostatic hyperplasia (ρ = 0.314) and benign prostatic hyperplasia/overactive bladder (ρ = 0.244). Our findings showed the Core Lower Urinary Tract Symptom Score, both its total score and each subscore, is able to show the efficacy of silodosin, similar to other questionnaires. The Core Lower Urinary Tract Symptom Score is also useful for identifying overactive bladder symptoms in patients with benign prostatic hyperplasia. As the Core Lower Urinary Tract Symptom Score does not correlate well with the Quality‐of‐Life index, these two questionnaires might be better used in combination to assess treatment outcomes.     

Removal of forearm plate leads to a high risk of refracture: decision regarding implant removal after fixation of the forearm and analysis of risk factors of refracture

Introduction

Plate fixation is the gold standard for the treatment of forearm fractures at present, and whether or not to remove the implant after bone union remains controversial. This study demonstrated some cases of refracture in adult forearm fractures after bone union and discussed the risk factors for decision-making regarding implant removal.

Methods

We reviewed patients with forearm diaphyseal fractures (including the radius, ulna, or both bones) who received open reduction and internal fixation (ORIF) from January 2008 to May 2011 in our institute. Fracture type was classified according to the AO/OTA system. All patients were fixed with a 3.5-mm dynamic compression plate. The patients were divided into two main groups: group A received implant removal after bone union, and group B retained the implant.

Results

There were 122 patients (170 bones) included in this study (40 females and 82 males). In group A, 7/51 patients (8/62 bones; 12.9 %) had refracture. As classified by the AO/OTA classification, one patient was classified as type A1, one patient as type A2, two patients as type A3, and three patients as type B3. All patients suffered refracture without high-energy trauma. In group B, the refracture rate was 2.77 %, and all were caused by high-energy trauma. Patients with refracture had a shorter time interval between ORIF and implant removal. The possible risk factors of refracture in this study included a wedge bone defect on plain film, implant removal performed after less than 18 months, and AO/OTA type B fracture.

Conclusion

The incidence of refracture was significantly lower in the group that retained the implant. Routine implant removal after bone union in adult forearm fractures is not recommended due to the higher refracture rate.     

体脂量是绝经后女性股骨近端骨强度的决定因素

正Lower body weight or body mass index(BMI)has been known to be higher risk of developing osteoporosis and low-energy fractures via mechanical loading and other factors in both men and women[1].Recently,there have been new insights into the relationships between body composition and bone health.However,most of the previous studies regarding the relative effect of body composition on bone mass yielded inconsistent     

The Utilization of Quality KPIs in the Pharmaceutical Industry

Purpose

The overall aim of this study was to investigate the significance of quality key performance indicators (KPIs) and how comprehensively they are used in the pharmaceutical industry. A specific aim was to find which KPIs were relevant to personnel from the perspective of their own work responsibilities. A further aim was to determine which factors motivate personnel enough to respond to improve KPIs.

Methods

Qualitative theme interviews of ten staff from one case company were conducted to study the impact of KPIs. Interview data were analyzed using qualitative content analysis and reductive analysis.

Results

Personnel considered deviations in manufacturing and packaging to be the most important quality KPI when they considered their own work responsibilities. The quality indicators data were utilized quite efficiently, for example, in complaint and deviation handling processes, and they provided useful information for corrective and preventive actions (CAPA)-reporting. The most important factors that motivated supervisors, managers, and experts regarding KPIs were those that affected interviewees own particular work responsibilities, the cooperation within the operators own departments, and the cooperation between different departments. The interviewees opined that the production bonus was the most important motivational factor for production operators to improve upon quality indicator performance.

Conclusions

Quality indicator feedback data were utilized widely by the case company and were considered to be a useful tool to guide personnel in ensuring or potentially improving the quality of operations.     

Chemically Accessible Hsp90 Inhibitor That Does Not Induce a Heat Shock Response

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Field applicable detection of hepatitis B virus using internal controlled duplex recombinase-aided amplification assay and lateral flow dipstick assay

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Patient follow-up after discharge after COVID-19 pneumonia: Considerations for infectious control

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