Disorders of gallbladder motility can lead to serious pathology. Bitter tastants acting upon bitter taste receptors (TAS2R family) have been proposed as a novel class of smooth muscle relaxants to combat excessive contraction in the airways and other organs. To explore whether this might also emerge as an option for gallbladder diseases, we here tested bitter tastants for relaxant properties and profiled Tas2r expression in the mouse gallbladder. In organ bath experiments, the bitter tastants denatonium, quinine, dextromethorphan, and noscapine, dose-dependently relaxed the pre-contracted gallbladder. Utilizing gene-deficient mouse strains, neither transient receptor potential family member 5 (TRPM5), nor the Tas2r143/Tas2r135/Tas2r126 gene cluster, nor tuft cells proved to be required for this relaxation, indicating direct action upon smooth muscle cells (SMC). Accordingly, denatonium, quinine and dextromethorphan increased intracellular calcium concentration preferentially in isolated gallbladder SMC and, again, this effect was independent of TRPM5. RT-PCR revealed transcripts of Tas2r108, Tas2r126, Tas2r135, Tas2r137, and Tas2r143, and analysis of gallbladders from mice lacking tuft cells revealed preferential expression of Tas2r108 and Tas2r137 in tuft cells. A TAS2R143-mCherry reporter mouse labeled tuft cells in the gallbladder epithelium. An in silico analysis of a scRNA sequencing data set revealed Tas2r expression in only few cells of different identity, and from in situ hybridization histochemistry, which did not label distinct cells. Our findings demonstrate profound tuft cell- and TRPM5-independent relaxing effects of bitter tastants on gallbladder smooth muscle, but do not support the concept that these effects are mediated by bitter receptors.

OBJECTIVE: This single-blind, randomized controlled study aimed to determine the effect of progressive muscle relaxation exercises on sleep quality and fatigue in the postmenopausal period. Progressive muscle relaxation aims to relax the muscles in the body and includes breathing techniques.
METHODS: This study was carried out between January 2022 and July 2022 with 63 postmenopausal women who applied to a district state hospital and had poor sleep quality. The women assigned to the experimental group (EG) (n = 31) applied progressive muscle relaxation exercises every day for 8 weeks. In contrast, the women in the control group (CG) (n = 32) continued their routine coping habits related to sleep problems and fatigue in the postmenopausal period. The EG and CG were reevaluated using the Piper Fatigue Scale and the Pittsburg Sleep Quality Index in the fourth and eighth weeks. The women applied progressive muscle relaxation exercises with a guide prepared by the researchers and the compact disc of the Turkish Psychologists Association. In the data analysis, the independent-samples t test, Fisher\'s exact test, and χ2 test were used to compare individual, obstetric, and medical characteristics between the groups. The difference between dependent groups at different times was evaluated by repeated-measures analysis of variance.
RESULTS: There was an improvement in fatigue symptoms in the progressive muscle relaxation exercises-performing EG at the end of 8 weeks compared with the CG, and fatigue symptoms increased in the CG (P < 0.001). There was a greater improvement in the sleep quality of the progressive muscle relaxation exercises-performing EG at the end of 8 weeks compared with the CG (P < 0.001).
CONCLUSIONS: In our study, it was determined that progressive muscle relaxation exercises had an improving effect on sleep quality and fatigue.

G-protein-coupled receptors (GPCRs) belonging to the type 2 taste receptors (TAS2Rs) family are predominantly present in taste cells to allow the perception of bitter-tasting compounds. TAS2Rs have also been shown to be expressed in human airway smooth muscle (ASM), and TAS2R agonists relax ASM cells and bronchodilate airways despite elevating intracellular calcium. This calcium \"paradox\" (calcium mediates contraction by pro-contractile Gq-coupled GPCRs) and the mechanisms by which TAS2R agonists relax ASM remain poorly understood. To gain insight into pro-relaxant mechanisms effected by TAS2Rs, we employed an unbiased phosphoproteomic approach involving dual-mass spectrometry to determine differences in the phosphorylation of contractile-related proteins in ASM following the stimulation of cells with TAS2R agonists, histamine (an agonist of the Gq-coupled H1 histamine receptor) or isoproterenol (an agonist of the Gs-coupled β2-adrenoceptor) alone or in combination. Our study identified differential phosphorylation of proteins regulating contraction, including A-kinase anchoring protein (AKAP)2, AKAP12, and RhoA guanine nucleotide exchange factor (ARHGEF)12. Subsequent signaling analyses revealed RhoA and the T853 residue on myosin light chain phosphatase (MYPT)1 as points of mechanistic divergence between TAS2R and Gs-coupled GPCR pathways. Unlike Gs-coupled receptor signaling, which inhibits histamine-induced myosin light chain (MLC)20 phosphorylation via protein kinase A (PKA)-dependent inhibition of intracellular calcium mobilization, HSP20 and ERK1/2 activity, TAS2Rs are shown to inhibit histamine-induced pMLC20 via inhibition of RhoA activity and MYPT1 phosphorylation at the T853 residue. These findings provide insight into the TAS2R signaling in ASM by defining a distinct signaling mechanism modulating inhibition of pMLC20 to relax contracted ASM.

OBJECTIVE: This study was carried out to determine the effect of progressive muscle relaxation exercises (PMR) on premenstrual syndrome (PMS) symptoms.
METHODS: The study was designed in a single-blind randomized controlled type. The study was conducted in a hospital in Western Türkiye. Seventy-nine single women who experienced PMS who met the inclusion criteria were randomly assigned to the experimental group in which PMR would be applied, and the control group to continue their routine coping habits regarding PMS. PMR were applied to the experimental group every day for 8 weeks. At the end of 8 weeks, the experimental and control groups were re-evaluated with the Premenstrual Syndrome Scale (PMSS).
RESULTS: At the beginning of the study, it was observed that the individual, health characteristics and PMSS mean scores of the women in the experimental and control groups were similar (p > 0.05). At the end of eight weeks, it was seen that the mean PMSS score of the experimental group was lower than that of the control group, and the difference was statistically significant (p < 0.001). When in-group comparisons were made at the end of the exercise program, no significant difference was found in the mean PMSS score of the control group compared to the beginning (p > 0.05). The PMSS score of the experimental group decreased significantly and the difference was statistically significant (p < 0.001).
CONCLUSIONS: In this study, it was seen that PMR were effective in improving PMS.

Shoulder dislocation, particularly anterior dislocation, is a common orthopedic injury often presenting in emergency care settings, characterized by significant pain and muscle spasms. Prompt reduction is essential to alleviate symptoms and restore function. The Cunningham technique employs gentle pulling and massage motions targeted at the muscles and has emerged as a promising method for reducing anterior shoulder dislocations. However, its reported success rates vary widely across studies, and questions remain regarding its efficacy, particularly in cases of failure. This study aims to evaluate the effectiveness of the Cunningham technique for reducing anterior shoulder dislocations and its potential role in providing analgesia and muscle relaxation as an adjunctive method.
A retrospective study was conducted on patients presenting with acute anterior shoulder dislocation at a single center. Reduction using the Cunningham technique was performed initially, followed by the external rotation technique if unsuccessful. Procedural sedation and analgesia were administered if the reduction was still not achieved, and shoulder dislocation reduction was performed again through the external rotation method. The patients\' VAS scores were recorded and evaluated the Cunningham technique\'s effectiveness in reduction and whether it increases the effectiveness of other techniques applied for reduction by lowering the VAS score, even in cases where it is not effective.
A total of 61 patients were included in the study. The reduction was performed using the Cunningham technique in 34.4% (21/61) patients, the external rotation technique in 47.5% (29/61) patients, and the external rotation technique with PSA in 18% (11/61) patients. Significant differences were observed in the duration of hospital stay among the three techniques, with ER with PSA resulting in the longest stay. VAS scores showed significant improvements from initial presentation to post-reduction in all three groups. A significant decrease in pre-reduction VAS scores was observed during the transition from the Cunningham technique to other techniques.
The Cunningham technique showed effectiveness in reducing anterior shoulder dislocations, providing analgesia, and muscle relaxation. It demonstrated favorable outcomes as an initial reduction technique, with the external rotation technique used as a subsequent option. Further studies comparing the success rates and complications of the Cunningham technique with other reduction methods are warranted to establish its role in clinical practice.

Securing an airway enables the oxygenation and ventilation of the lungs and is a potentially life-saving medical procedure. Adverse and critical events are common during airway management, particularly in neonates and infants. The multifactorial reasons for this include patient-dependent, user-dependent and also external factors. The recently published joint ESAIC/BJA international guidelines on airway management in neonates and infants are summarized with a focus on the clinical application. The original publication of the guidelines focussed on naming formal recommendations based on systematically documented evidence, whereas this summary focusses particularly on the practicability of their implementation.
UNASSIGNED: Die Sicherung der Atemwege ermöglicht die Oxygenierung und Ventilation der Lungen und stellt eine potenziell lebensrettende medizinische Maßnahme dar. Insbesondere bei Neugeborenen und Säuglingen kommt es gehäuft zu unerwünschten und kritischen Ereignissen während des Atemwegsmanagements. Die multifaktoriellen Gründe dafür umfassen patientenabhängige, anwenderabhängige, aber auch externe Faktoren. Im Folgenden wird die neu erschienene internationale Leitlinie zur Atemwegssicherung bei Neugeborenen und Säuglingen fokussierend auf die klinische Anwendung zusammengefasst. Während die Originalpublikation der Leitlinie darauf fokussiert, auf Basis der systematisch erfassten Evidenz formale Empfehlungen zu benennen, stellt diese Zusammenfassung v. a. die Praktikabilität ihrer Umsetzung in den Fokus.

The purpose of this study was to determine the receptor subtype and the underlying mechanisms involved in the relaxant effect to leptin in mid- and late-pregnant mouse uterus. We determined the relative mRNA expression of receptor subtypes, eNOS, and BKCa channel by quantitative PCR and also the overall receptor expression by immunohistochemistry. Isometric tension studies were conducted to evaluate the effects of leptin and to delineate its mechanisms. A selective siRNA for the ObRb receptor was used to determine the participation of the receptor subtype in biochemical and molecular effects of leptin. The relaxant response to leptin was greater in mid-pregnancy compared to late pregnancy and was mediated by the activation of BKCa channels by eNOS-derived nitric oxide in an ObRb receptor-dependent manner. In comparison to mid-pregnancy, expression of short forms (mainly ObRa receptor) of the receptor was significantly increased in late pregnancy, whereas ObRb receptor expression was similar in both phases. The results of the study suggest that ObRb receptor mediates leptin-induced increase in eNOS expression and NO synthesis. Leptin-induced eNOS expression and activation cause cGMP-independent stimulation of BKCa channels causing uterine relaxation. Increased short forms of the receptors and reduced BKCa channels exert a negative effect on uterine relaxation in late pregnancy. Leptin may have a physiological role in maintaining uterine quiescence in mid-pregnancy and its reduced relaxant response in late gestation may facilitate labor. Further, ObRb receptor agonists may be useful in the management of preterm labor.

Multidrug resistance proteins type 4 (MRP4) and 5 (MRP5) play pivotal roles in the transport of cyclic nucleotides in various tissues. However, their specific functions within the lower urinary tract remain relatively unexplored. This study aimed to investigate the effect of pharmacological inhibition of MRPs on cyclic nucleotide signaling in isolated pig bladder. The relaxation responses of the bladder were assessed in the presence of the MRP inhibitor, MK571. The temporal changes in intra- and extracellular levels of cAMP and cGMP in stimulated tissues were determined by mass spectrometry. The gene (ABCC4) and protein (MRP4) expression were also determined. MK571 administration resulted in a modest relaxation effect of approximately 26% in carbachol-precontracted bladders. The relaxation induced by phosphodiesterase inhibitors such as cilostazol, tadalafil, and sildenafil was significantly potentiated in the presence of MK571. In contrast, no significant potentiation was observed in the relaxation induced by substances elevating cAMP levels or stimulators of soluble guanylate cyclase. Following forskolin stimulation, both intracellular and extracellular cAMP concentrations increased by approximately 15.8-fold and 12-fold, respectively. Similarly, stimulation with tadalafil + BAY 41-2272 resulted in roughly 8.2-fold and 3.4-fold increases in intracellular and extracellular cGMP concentrations, respectively. The presence of MK571 reduced only the extracellular levels of cGMP. This study reveals the presence and function of MRP4 transporters within the porcine bladder and paves the way for future research exploring the role of this transporter in both underactive and overactive bladder disorders.NEW & NOTEWORTHY This study investigates the impact of pharmacological inhibition of MRP4 and MRP5 transporters on cyclic nucleotide signaling in isolated pig bladders. MK571 administration led to modest relaxation, with enhanced effects observed in the presence of phosphodiesterase inhibitors. However, substances elevating cAMP levels remained unaffected. MK571 selectively reduced extracellular cGMP levels. These findings shed light on the role of MRP4 transporters in the porcine bladder, opening avenues for further research into bladder disorders.

Urinary bladder dysfunction might be related to disturbances at different levels of the micturition reflex arc. The current study aimed to further develop and evaluate a split bladder model for detecting and analysing relaxatory signalling in the rat urinary bladder. The model allows for discrimination between effects at the efferent and the afferent side of the innervation. In in vivo experiments, the stimulation at a low frequency (1 Hz) of the ipsilateral pelvic nerve tended to evoke relaxation of the split bladder half (contralateral side; -1.0 ± 0.4 mN; n = 5), in contrast to high frequency-evoked contractions. In preparations in which the contralateral pelvic nerve was cut the relaxation occurred at a wider range of frequencies (0.5-2 Hz). In separate experiments, responses to 1 and 2 Hz were studied before and after intravenous injections of propranolol (1 mg/kg IV). The presence of propranolol significantly shifted the relaxations into contractions. Also, electrical stimulation of the ipsilateral pudendal nerve evoked relaxations of similar magnitude as for the pelvic stimulations, which were also affected by propranolol. In control in vitro experiments, substances with β-adrenoceptor agonism, in contrast to a selective α-agonist, evoked relaxations. The current study shows that the split bladder model can be used for in vivo studies of relaxations. In the model, reflex-evoked sympathetic responses caused relaxations at low intensity stimulation. The involvement of β-adrenoceptors is supported by the sensitivity to propranolol and by the in vitro observations.

The purpose of this research was to ascertain how progressive muscle relaxation (PMR) technique affected hip fracture patients\' anxiety, sleep quality, and post-operative pain. This parallel randomized controlled trial was conducted on 100 patients with hip fracture hospitalized in one of the reference orthopedic hospitals in Tehran, Iran who were selected using convenience sampling and randomly were placed in two PMR group (n = 50) and control group (n = 50). Data were collected by Demographic information questionnaire, Visual analogue scale for pain rating, Pittsburgh Sleep Quality Index and State-Trait Anxiety Inventory. The PMR technique was the progressive muscle relaxation technique, which was started the night after the surgery for three nights before going to bed. Data were collected on two occasions, including before the PMR technique and the day after the last stage of the PMR technique. The data were analyzed by SPSS software using descriptive and inferential statistics. The results revealed significant within-group changes in both groups\' post-operative pain, sleep quality, and anxiety scores (P < 0.001). The progressive muscle relaxation group experienced decreased post-operative pain and anxiety scores and increased sleep quality scores (P < 0.001). The linear mixed model showed that the absolute changes in the follow-up post-operative pain, sleep quality, and anxiety scores were 1.19 and 7.94 units, significantly lower than the baseline, respectively. The results revealed significant within-group changes in both groups\' post-operative pain, sleep quality, and anxiety scores (P < 0.001). The progressive muscle relaxation group experienced decreased post-operative pain and anxiety scores and increased sleep quality scores (P < 0.001). The study\'s findings demonstrated the beneficial effects of progressive muscle relaxation on hip fracture patients\' outcomes, such as their level of anxiety, sleep quality, and post-operative pain. The study\'s findings can be applied by medical professionals to improve patient satisfaction and care quality.This clinical trial has been registered with the Iranian Registry of Clinical Trials under the code IRCT20231120060119N1, which was approved on 7/12/2023.