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Water intake, switching between bites and sips, and drinking behavior are associated with food intake across meals varying in spiciness: A secondary analysis of two randomized crossover studies.

Widespread nutrition advice instructs consumers to drink water with meals to increase fullness and reduce energy intake. However, recent data indicates greater water intake is associated with more food intake at a meal, not less. Switching between meal components (e.g., alternating between food and water), has also been associated with increased food intake at a pasta meal, but it remains unclear whether this applies to other foods. In a secondary analysis, we pooled existing data from 2 crossover experiments (total n&#xa0;=&#xa0;86) where adults ate an ad libitum lunch consisting of 650&#xa0;g of beef chili (n&#xa0;=&#xa0;52) or chicken tikka masala (n&#xa0;=&#xa0;34) with 450&#xa0;g of water twice in the laboratory while being video-recorded. For both experiments, the spiciness of the lunch was varied by adding different ratios of hot:sweet paprika. Videos were coded to measure sip number, sip size (g/sip), drinking rate (g/min), and number of switches between bites of food and sips of water. As we previously reported, increasing spiciness slowed eating rate and reduced food intake; in secondary analyses described here, the reduction in food intake was not moderated by water intake, switching, or drinking behaviors (all p&#xa0;>&#xa0;0.73). Notably, across all meals, greater water intake (p&#xa0;<&#xa0;0.001) and switching (p&#xa0;=&#xa0;0.02) associated with greater food intake. Overall, individuals ate more when they drank more and switched between bites and sips more often, highlighting the potential influence of water and drinking behaviors on food consumption. This finding challenges the widespread dietary advice to drink water with meals to reduce food intake.

Humans

Empathic Accuracy and Behavioral Empathy After a Moderate Dose of Beer.

OBJECTIVES: Empathic accuracy (EA) represents a person's ability to correctly infer the emotions of another person. One past study in men found lower EA for positive emotions after a moderate dose of hard liquor compared to after placebo, particularly among non-hazardous drinkers. The present study aimed to replicate this finding, using a moderate dose of beer and a mixed design. Moreover, we added a novel measure of behavioral empathy. METHODS: Participants (62% men) completed the Alcohol Use Disorders Identification Test, Empathy Quotient, and Revised Drinking Motives Questionnaire. Before and after drinking either beer (6.6% alcohol, n&#xa0;=&#xa0;28) or its 0.0% equivalent (placebo, n&#xa0;=&#xa0;38), they watched videoclips of targets talking about emotional autobiographical events and rated how targets felt while talking. Behavioral empathy was assessed by presenting participants with painful scenarios and asking whether they would help the people in pain. RESULTS: The previous finding of lower EA for positive emotions after alcohol was not replicated. Nonetheless, after alcohol non-hazardous drinkers were less willing to help people in pain. Trait affective empathy (i.e., a person's long-term disposition to experience emotional responses congruent to another's feelings) and the drinking to cope motive did not significantly moderate the findings. CONCLUSIONS: Although alcohol may alter empathy, its effects are not consistent and may depend on the dose and type of alcohol consumed. The moderating roles of trait empathy and trait aggressivity deserves further study.

Humans

Effect of Motor-Control Exercises on Scapulohumeral and Scapulothoracic Muscle Activations in Athletes With Secondary Subacromial Impingement Syndrome.

CONTEXT: Unbalanced or uncoordinated activity across either the scapulohumeral or the scapulothoracic muscle may impair scapulohumeral rhythm during arm elevation. OBJECTIVE: To compare the effects of progressive resistance exercises (PREs), integrated with and without facilitatory motor-control exercises (MCEs), on scapulohumeral and scapulothoracic myoelectric activities in overhead athletes diagnosed with secondary subacromial impingement syndrome (SAIS). DESIGN: Randomized controlled clinical trial. SETTING: Neuromuscular Rehabilitation Research Center. PATIENTS OR OTHER PARTICIPANTS: Overhead athletes diagnosed with secondary SAIS were assigned randomly to 3 parallel groups: 2 intervention groups and 1 control group. INTERVENTIONS: All groups received contemporary physical therapy modalities every other day for 8 weeks. Intervention groups I and II also completed scapulohumeral and scapulothoracic PREs, integrated, respectively, with and without facilitatory MCEs targeting infraspinatus and lower trapezius muscles. MAIN OUTCOME MEASURES: Scapulohumeral and scapulothoracic myoelectric activities were recorded during scapular arm abduction between 80&#xb0; and 110&#xb0; before and after the prescribed treatment protocols. RESULTS: Scapulohumeral and scapulothoracic PREs reduced the corresponding myoelectric activities during scapular arm abduction within the groups (P &#x2264; .02, partial &#x3b7;2 &#x2265; 0.127). Facilitatory biofeedback-guided exercises integrated into PREs preserved scapulohumeral and scapulothoracic myoelectric activities (P &#x2264; .03), excluding teres minor myoelectric activity (P > .99). CONCLUSIONS: Scapulohumeral and scapulothoracic PREs reduced the corresponding muscle activations during scapular arm abduction in overhead athletes with secondary SAIS. Facilitatory MCEs targeting infraspinatus and lower trapezius muscles, integrated into PREs, preserved scapulohumeral and scapulothoracic muscle activations.

Humans

A Randomized Clinical Trial to Compare Moxifloxacin Versus Azithromycin for the Treatment of Mycoplasma genitalium: The FARTHEST Study.

BACKGROUND: Mycoplasma genitalium (MG) is increasingly characterized by high rates of macrolide and fluoroquinolone resistance. International guidelines recommend resistance-guided therapy; however, access to genotypic testing is limited, and randomized trial evidence is lacking. We assessed the efficacy of moxifloxacin and azithromycin without resistance assays. METHODS: This monocentric, open-label, superiority, randomized controlled trial enrolled adults with MG infection detected by multiplex PCR, randomized 1:1 to receive moxifloxacin 400 mg daily for 10 days or azithromycin 500 mg daily for 6 days. A test of cure was performed &#x2265;28 days after treatment completion. The primary endpoint was microbiological cure in the intention-to-treat (ITT) and per-protocol (PP) populations. Subgroup analyses assessed symptomatic versus asymptomatic infections, doxycycline exposure, re-treatment, and sexual behavior. RESULTS: Among 358 randomized participants, 87.0% of those treated with moxifloxacin and 61.2% of those treated with azithromycin achieved microbiological cure in the ITT analysis (absolute risk difference 25.8%, 95% CI 16.5, 35.2). The superiority of moxifloxacin was confirmed in the ITT and PP populations. Moxifloxacin remained superior across most subgroups, whereas azithromycin showed comparable efficacy only among heterosexual individuals. Doxycycline coadministration did not improve outcomes. Both regimens were well tolerated, with only one case of discontinuation. CONCLUSIONS: Moxifloxacin demonstrated superior efficacy compared to azithromycin for treating MG infection in the absence of resistance testing. These randomized data support the use of moxifloxacin as a first-line option when resistance assays are unavailable and may inform treatment strategies.

Humans

Effects of anodal transcranial direct current stimulation over the right primary motor cortex on a sequential motor finger tapping task in developmental stuttering.

INTRODUCTION: This study investigates the impact of anodal transcranial direct current stimulation (tDCS) on non-speech sequential motor practice in adults who stutter (AWS), compared to non-stuttering controls (ANS). Recent research has explored the effects of tDCS on speech fluency in stuttering. However, its effect on non-speech motor tasks has not yet been studied. METHODS: 20 AWS and 30 ANS right-handed participants were randomly assigned to anodal or sham tDCS conditions, performing a sequential finger tapping task. We targeted over the right primary motor cortex, stimulating at 2&#x202f;mA for 20&#x202f;min. Sequence duration and reaction time were analyzed. RESULTS: AWS analysis revealed that the anodal condition had significantly slower reaction times in the second half of the task compared to sham. For sequence durations, AWS in the anodal condition had slower overall sequence durations than the sham condition. However, there were no block-by-block differences in sequence duration. When comparing AWS and ANS, no significant differences were observed for sequence duration. However, there were significant differences in reaction time between AWS and ANS, specifically in earlier blocks. Additionally, there was no significant Group &#xd7;&#x202f;Condition interaction. DISCUSSION: The findings suggest that anodal stimulation impeded finger sequencing in AWS, showing overall slower sequence durations and a diminishing effect on reaction times in the second half of the experiment, suggesting anodal tDCS may interact uniquely with the neural mechanisms in stuttering. Future studies should explore the effects of anodal tDCS on non-speech motor tasks to gain a broader understanding of its impact on motor control and motor learning.

Humans

Silent crises in the COVID-19 pandemic shadow: a six-year medico-legal review of non-lethal intimate partner violence in Morocco.

Intimate partner violence (IPV) is a major global public health concern and one of the most prevalent forms of gender-based violence, with significant consequences. This study analyzes non-lethal IPV cases reported to a medico-legal unit of Casablanca between 2018 and 2023. Data from 4,784 female victims were reviewed, focusing on socio-demographics, violence types, perpetrator relationships, and judicial involvement across the pre-COVID, peak COVID-19, and post-COVID periods. Married women represented 59.2% of victims. Physical violence predominated (83.1%), while sexual violence was underreported (14.7%). The year 2020 marked a sharp increase in reported non-lethal IPV cases (n&#x2009;=&#x2009;1,005), correlating with pandemic confinement. Among married women, judicial requisition (legal request for forensic examination) and medico-legal certification (medical documentation for judicial use) rates were high (81.5% and 81.0%, respectively). Post-pandemic years declined moderately but remained above pre-COVID levels. International comparison confirmed a global rise in IPV during COVID-19, with Morocco displaying comparatively higher rates of medico-legal documentation and judicial involvement. IPV in Morocco is entrenched and intensified by COVID-19. While the medico-legal system is robust in documentation, the system must evolve by integrating systematic psychological assessment into medico-legal evaluations, standardizing certification and referral protocols, and strengthening coordination between medico-legal, health, and social support services to improve victim protection.

Humans

Metabolic Stress Testing Reveals Persistent Lipid-Handling Dysfunction in Women With Polycystic Ovary Syndrome Despite Exercise Training.

AIM: Polycystic ovary syndrome (PCOS) is associated with insulin resistance and metabolic dysfunction, yet baseline metabolomic studies show inconsistent findings. We investigated whether metabolic abnormalities in PCOS emerge under physiological stress and how these responses are modified by exercise training. MATERIALS AND METHODS: Twelve women with PCOS and 10 controls completed hyperinsulinaemic-euglycaemic clamps with randomised saline or lipid infusion, before and after 8&#x2009;weeks of supervised exercise. Plasma metabolomics (163 metabolites) were measured at baseline, post-infusion and post-clamp. Linear mixed-effects models assessed Group&#x2009;&#xd7;&#x2009;Timepoint&#x2009;&#xd7;&#x2009;Intervention interactions. RESULTS: No baseline metabolite differences were observed between groups. A significant three-way interaction (p&#x2009;=&#x2009;0.008) indicated condition-dependent trajectory divergence. Post hoc analysis revealed a specific divergence during post-exercise lipid challenge (p&#x2009;=&#x2009;0.048). Women with PCOS showed reduced suppression of ether-linked phosphatidylcholines during insulin-stimulated lipid loading (PC ae C44:4, p&#x2009;=&#x2009;0.031), despite exercise-induced improvements in fitness and normalisation of amino acid profiles. Exploratory metabolite ratios suggested impaired substrate coordination under stress. CONCLUSIONS: Metabolic defects in PCOS are stress-dependent and not detectable at rest. Exercise training improves resting metabolism but reveals persistent impairment in adaptive lipid handling during combined insulin and lipid challenges, suggesting impaired coordination of substrate supply during metabolic stress. TRIAL REGISTRATION: ClinicalTrials.gov identifier: ISRCTN42448814.

Humans

A clinical study on the efficacy of rectal administration of Tongfu Qinghua decoction combined with external application of Ruyi Jinhuang powder in treating acute pancreatitis.

BACKGROUND: Acute pancreatitis (AP) is a common acute abdominal disease with high mortality in moderate and severe cases. Integrated Chinese and Western medicine therapy has promising clinical application prospects. OBJECTIVES: This study investigated the efficacy and safety of Tongfu Qinghua decoction enema combined with Ruyi Jinhuang powder external application for AP and its therapeutic effects across different age groups. METHODS: A total of 100 AP patients from October 2023 to August 2025 were randomly divided into observation and control groups (50 cases each). The control group received conventional Western medicine and the observation group received additional combined Chinese medicine therapy. Outcomes including hospital stay, symptom relief, inflammatory and pancreatic injury markers, clinical efficacy and adverse reactions were compared, with subgroup analysis of patients aged 18-40, 41-60 and 61-75 years. RESULTS: The observation group had significantly shorter hospital stay, faster symptom relief and gastrointestinal recovery (P<0.05). Post-treatment inflammatory and pancreatic markers improved significantly and the total effective rate was higher (P<0.05), with no significant difference in adverse reactions (P>0.05). Benefits were consistent across all age subgroups, with younger patients recovering faster and elderly patients still achieving significant improvement. CONCLUSION: This combined therapy is effective and safe for AP patients aged 18-75 years, significantly improving clinical outcomes and worthy of clinical promotion.

Humans

Investigation of ACE gene polymorphism and serum ACE activity in relation to alopecia areata among Iraqi patients.

BACKGROUND: Alopecia areata (AA) is a multifactorial disorder with immune dysregulation and genetic susceptibility, affecting 0.5-2% globally. OBJECTIVE: This study investigated angiotensin converting enzyme (ACE) gene insertion /deletion (I/D) polymorphism and serum ACE activity in Iraqi AA patients and their association with inflammatory cytokines (interleukin [IL]-17) and nutritional markers to understand disease progression. METHODS: This case-control study included 50 AA patients (Male and Female) and 35 healthy controls. ACE gene polymorphism (rs1799752) was analyzed using real-time polymerase chain reaction (qPCR) with high-resolution melting (HRM) analysis. Serum IL-17 levels were determined by enzyme-linked immunosorbent assay (ELISA), and biochemical markers were measured using an automated analyzer. RESULTS: ACE gene polymorphism (rs1799752) showed non-significant genotype distribution between patient and control groups (p&#xa0;>&#xa0;0.05), though a trend toward DD genotype enrichment was observed in patients. Serum ACE levels were significantly higher in patients versus controls (p&#xa0;<&#xa0;0.0001) with high diagnostic performance. ACE correlated positively with IL-17 (P&#xa0;<&#xa0;0.0001) and negatively with vitamin D3 and zinc (P&#xa0;<&#xa0;0.0001). Female patients had significantly higher ACE levels than males (P&#xa0;<&#xa0;0.01). CONCLUSIONS: ACE emerges as an immunometabolic hub in AA pathogenesis, integrating inflammation with nutritional deficits, suggesting its potential as a biomarker and therapeutic target.

Humans

Efficacy of a self-guided online resilience intervention for improving mental health among university students: A randomized controlled trial.

Epidemiological data indicates that university students are an at-risk population for the development of mental disorders. Online interventions have been proposed as promising tools for reducing barriers to treatment and establishing easily accessible health-care services promoting mental health and resilience. This study investigated the efficacy of a Learning Management System (LMS)-based self-guided online resilience intervention. 216 university students took part in a randomized controlled trial with an intervention and a waitlist control group and three measurement points (pre, post and follow-up). We conducted per-protocol (PP) and intention-to-treat (ITT) analyses with mental distress as primary outcome, and self-reported resilience and resilience factors as secondary outcomes. Further, attitudes towards online interventions, adherence, satisfaction and possible negative effects were explored. Satisfaction with the intervention was high and PP analyses (n&#x2009;=&#x2009;150) revealed significant improvements in mental distress and self-compassion at post-test and acceptance at follow-up. No favourable effects were found for self-reported resilience and resilience factors. Adherence was low and ITT analyses revealed no significant effects. Overall, the study provides preliminary evidence for the LMS-based self-guided online intervention as a potentially valuable tool for university mental health services under optimal adherence conditions. Further research into determinants of adherence is needed to improve intervention reach.

Humans

Angiotensin II regulates anxiety and social-affective top-down and bottom-up attention control in a sex-dependent manner.

BACKGROUND: The renin-angiotensin system (RAS) has been increasingly recognized as potent modulator of cognitive and affective functions, with angiotensin II type 1 receptor (AT1R) antagonists emerging as repurposing candidate for anxiety and stress-related disorders. However, it remains unclear whether transient AT1R blockade modulates emotional attentional control and whether these effects are sex-dependent. METHODS: We conducted a preregistered, randomized, double-blind, placebo-controlled pharmacological eye-tracking study in 79 healthy adults (males and females) and determined effects of transient AT1R blockade via losartan (50&#xa0;mg) on emotional attention control using a validated anti-saccade paradigm with social (emotional faces) and non-social stimuli. Treatment effects on state anxiety and oculomotor responses were characterized using traditional metrics and a novel trial-history informed dynamic control framework. RESULTS: Losartan reduced state anxiety irrespective of sex but induced sexually dimorphic effects on attentional control. In females, losartan enhanced performance by reducing endpoint error without altering latency. Conversely, in males, losartan increased endpoint error and prolonged latency of the first correct saccade. Trial-history analyses revealed losartan reduced error probabilities following errors and repeat trials in both sexes. Yet, following correct trials, females receiving losartan maintained lower error probabilities, while males exhibited higher errors, potentially reflecting failure to disengage from effortful control. CONCLUSIONS: The RAS modulates anxiety and attentional control, the latter sex-dependently. AT1R blockade reconfigures attentional processing and adaptive control, suggesting sex-specific therapeutic potential in disorders characterized by excessive anxiety and attentional dysregulation. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov; https://clinicaltrials.gov/;NCT06329050.

Humans

Immunomodulatory effects of palm-derived tocotrienol-rich fraction in healthy volunteers following influenza vaccination: A randomised clinical trial.

Most studies on vitamin E and immunity have focused on tocopherols, but the tocotrienol-rich fraction (TRF) from palm oil may exert stronger immunomodulatory effects. This study investigated the effect of various TRF doses on the immune response to influenza immunisation in healthy adults. We hypothesized daily supplementation with lower doses of TRF can boost immune response to the influenza vaccine in healthy Individuals. In a double-blind placebo-controlled trial, 150 participants (&#x2265;18 years) were randomised to receive placebo or TRF (50, 100, 200, or 400 mg) daily for 2 months, with vaccination on day 28. Blood samples collected on days 0, 28, and 56 were analyzed for humoral and cellular immunity, antioxidant status, and plasma concentrations of vitamin E. TRF significantly augmented anti-influenza antibody production across all doses, with the 400 mg group exhibiting the highest titers. A selective Th1-type immune response was observed, characterized by significant IFN-&#x3b3; production upon restimulation in all TRF-supplemented groups compared with placebo. Plasma IL-12 was elevated in the highest dose, whereas the amount of EBI3 produced increased across a broader range of doses compared to placebo. TRF supplementation was associated with increased antioxidant enzyme activities and stable malondialdehyde activity. Elevated &#x3b1;-tocopherol concentrations observed, primarily at higher doses. Supplementation with TRF can enhance immune response to influenza immunisation by modulating humoral, Th1 responses and improving antioxidant status. Critically, antibody production increased similarly across all TRF doses, suggesting that lower doses may offer a cost-effective strategy for supporting humoral immunity, while higher doses provide broader immunomodulatory benefits.

Humans

Pharmacokinetics and safety of TBAJ-587, a novel antimycobacterial diarylquinoline, in healthy participants.

TBAJ-587 is a second-generation diarylquinoline with greater antimycobacterial activity and a potentially better safety profile than the first-generation bedaquiline. It is currently under development for the treatment of drug-susceptible and drug-resistant tuberculosis. A first-in-human trial of TBAJ-587, including single and multiple ascending oral doses and a dedicated food-effect cohort, was conducted in 92 healthy adults. Plasma exposures of TBAJ-587 were generally linear for AUCtau and slightly subproportional for Cmax, with the major circulating active metabolite, M3, remaining low relative to the parent. A high-fat meal increased the mean Cmax and AUClast 3.46- and 2.26-fold, respectively. TBAJ-587 accumulated with multiple dosing over the 28-day period, with mean accumulation ratios across the three tested doses ranging from 1.69 to 2.32 for Cmax and from 2.74 to 3.73 for AUCtau. However, steady-state conditions were not yet reached on day 28. Mean terminal half-lives after 28-day dosing of TBAJ-587 ranged from approximately 80 to 111 days. There were no deaths or serious adverse events, and TBAJ-587 was generally safe and well tolerated at single doses of 25-800 mg under fasting conditions and multiple doses of 50-200 mg once daily for 28 days after a standard breakfast. In addition, no dose- or time-dependent effects were noted for any of the other safety and tolerability parameters, including no clinically significant effects on the QTc interval. These results support further investigation of TBAJ-587 for the treatment of tuberculosis.CLINICAL TRIALSThis study is registered with ClinicalTrials.gov as NCT04890535.

Humans

Cerebellar iTBS enhances gait adaptation by modulating cortical sensorimotor network dynamics: a randomized controlled trial.

Gait adaptation enables individuals to maintain locomotor stability under persistent perturbations. Although the cerebellum is critical for sensory prediction error-based (SPE) adaptation, how cerebellar neuromodulation reshapes cortical sensorimotor networks to enhance gait adaptation remains unclear. This study investigated the behavioral effects and underlying cortical neurodynamic mechanisms of cerebellar intermittent theta-burst stimulation (iTBS) on gait adaptation. Thirty-two healthy adults received either active or sham cerebellar iTBS. Participants performed a split-belt treadmill adaptation task before and after intervention. Cortical responsiveness was evaluated using TMS-evoked EEG over primary motor cortex (M1), while resting-state EEG was analyzed to assess spectral power and directional functional connectivity. Compared to sham, cerebellar iTBS significantly enhanced gait adaptation, evidenced by a faster adaptation rate (p&#x202f;=&#x202f;0.035) and enhanced Early Adaptation SLS (p&#x202f;=&#x202f;0.011), without altering initial perturbation responses or post-adaptation outcomes. The iTBS increased TMS-evoked &#x3b1; (p&#x202f;=&#x202f;0.031) and &#x3b3; (p&#x202f;=&#x202f;0.022) power in M1, while the &#x3b1; power was correlated with faster adaptation (r&#x202f;=&#x202f;0.526, p&#x202f;=&#x202f;0.002). Furthermore, iTBS strengthened PPC-to-M1 directed connectivity in the &#x3b2; (p&#x202f;=&#x202f;0.025) and &#x3b3; (p&#x202f;=&#x202f;0.013) bands. Enhanced parieto-motor directionality were positively associated with adaptation rate (&#x3b2;: r&#x202f;=&#x202f;0.515, p&#x202f;=&#x202f;0.003; &#x3b3;: r&#x202f;=&#x202f;0.463, p&#x202f;=&#x202f;0.009). These findings suggest that cerebellar iTBS facilitates gait adaptation by modulating cortical responsiveness and directional sensorimotor network connectivity, providing multi-level neurodynamic evidence for the cerebello-cortical modulation during gait adaptation and offering a strong physiological rationale for targeted neuromodulation in gait rehabilitation strategies.

Humans

Diurnal differences in the effects of heat exposure on renal function: A randomized controlled crossover trial.

High temperature is a major risk factor for kidney injury, and population exposure to nighttime heat is increasing as the climate warms. However, whether renal responses to heat exposure differ between daytime and nighttime remains unclear. Forty-one healthy adults participated in a randomized crossover experiment conducted in a controlled laboratory setting. Participants were exposed to heat (32&#xb0;C during daytime; 30&#xb0;C during nighttime) and thermoneutral conditions (26&#xb0;C) for 8&#x202f;h. Blood and urine samples were collected before and after each exposure to examine various renal biomarkers reflecting glomerular filtration function, tubular injury, and early kidney stress. Heat exposure affected both blood and urinary biomarkers of kidney function, with notable diurnal differences in renal responses. Daytime heat exposure primarily affected blood markers of glomerular filtration, increasing creatinine by 7.67% (95% CI: 4.73%-10.61%) and cystatin C by 3.05% (95% CI: 0.17%-5.93%), while reducing estimated glomerular filtration rate by 0.05% (95% CI: 0.02%-0.08%). In contrast, nighttime heat exposure predominantly elevated urinary biomarkers of early kidney stress, including insulin-like growth factor-binding protein 7 (58.40%, 95% CI: 27.66%-89.14%), kidney injury molecule-1 (47.25%, 95% CI: 18.91%-75.59%), and tissue inhibitor of metalloproteinases-2 (51.88%, 95% CI: 22.26%-81.51%). Moreover, increases in insulin-like growth factor-binding protein 7 were significantly greater at night than during the day. Sleep-related parameters, including sleep quality, duration, and heart rate variability, partially mediated nighttime heat effects on renal responses. These results indicated that heat exposure induced different diurnal patterns in renal responses.

Humans

A phase I clinical study of the safety, tolerability, pharmacokinetics and pharmacodynamics of SHR-2106, an anti-CD40 antibody, following single intravenous or subcutaneous administration in healthy participants.

BACKGROUND: SHR-2106 is a humanized IgG1 monoclonal antibody that blocks CD40-CD40L interactions and has demonstrated immunosuppressive activity and graft-prolonging effects in preclinical studies. This first-in-human Phase I study evaluated the safety, pharmacokinetics, pharmacodynamics, and immunogenicity of single intravenous or subcutaneous doses of SHR-2106 in healthy adults. METHODS: This randomized, double-blind, placebo-controlled Phase I study enrolled healthy participants. Fifty-one participants were enrolled in seven cohorts and received five intravenous doses (50-1200&#x202f;mg) or two subcutaneous doses (300 and 600&#x202f;mg). Safety, serum pharmacokinetics, CD40 occupancy on B cells, and anti-drug antibodies were assessed using standard clinical and bioanalytical methods. RESULTS: SHR-2106 demonstrated a favorable safety and tolerability profile, and most treatment-emergent adverse events were mild to moderate laboratory abnormalities with incidence rates comparable to placebo. SHR-2106 exhibited nonlinear pharmacokinetics consistent with target-mediated drug disposition, with a dose-dependent increase in geometric mean terminal half-life following intravenous administration (1.83-10.7 days). Absolute bioavailability after subcutaneous administration was approximately 60%. CD40 occupancy exceeded 80% within 24&#x202f;h at all doses, with saturation duration increasing from 7 to 70 days across the intravenous dose range and remaining comparable between routes at matched doses. Anti-drug antibody incidence decreased with increasing intravenous dose and did not significantly affect pharmacokinetics or pharmacodynamics. CONCLUSION: SHR-2106 was well tolerated and achieved rapid and sustained CD40 engagement, supporting dose and route selection for Phase II studies.

Humans

Effects of automated massage chair therapy on mental health and physical health: A comprehensive study.

BACKGROUND AND OBJECTIVE: Automated massage chair therapy is a non-pharmacological intervention widely believed to enhance wellness, yet evidence regarding its effects remains limited. This 3-part study evaluated the effects of automated massage chair therapy on mental and physical health. METHODS: In Part 1, 20 moderately stressed students were randomized to receive a 20-minute automated massage chair therapy session followed by a 20-minute control session, or vice versa, with a 48-hour washout period. Blood pressure (BP), heart rate (HR), electroencephalogram (EEG), State-Trait Anxiety Inventory (STAI), and Visual Analog Scale (VAS) were measured. In Part 2, 20 hypertensive hospital staff received three 20-minute automated massage chair therapy sessions on alternate days. BP, HR, and skin blood flow (SBF) were measured. In Part 3, 20 hospital staff with chronic low back pain received three 20-minute automated massage chair therapy sessions on alternate days. Electromyogram (EMG) and VAS were measured. RESULTS: Automated massage chair therapy significantly reduced diastolic blood pressure (DBP), HR, stress, and anxiety among moderately stressed students. In hospital staff with hypertension, SBF did not change significantly, whereas BP and HR decreased significantly after automated massage chair therapy. In hospital staff with chronic low back pain, low back function improved, and pain was significantly reduced after automated massage chair therapy. CONCLUSION: These findings indicate that automated massage chair therapy may help reduce stress, lower blood pressure, and alleviate low back pain.

Humans

Effect of Music on Pain, Anxiety, and Satisfaction During Intrauterine Device Application: A Randomized Clinical Trial.

This randomized controlled trial aimed to determine the effect of music played during intrauterine device (IUD) insertion on perceived pain, state anxiety, and satisfaction levels. The study was conducted with 70 women who applied to a maternal and child health and family planning center and were randomly assigned to the intervention and control groups using simple randomization. Data were collected using a Demographic Information Form, the State-Trait Anxiety Inventory (STAI-I), and the Visual Analog Scale (VAS), as well as Bluetooth speakers and the musical piece Evgeny Grinko-Valse. Participants in the intervention group listened to music before and during the IUD insertion procedure, whereas the control group received routine care only. Data were analyzed using SPSS version 26 with appropriate descriptive and inferential statistical methods. Women in the music group had significantly lower perceived pain (p&#x2009;<&#x2009;0.001) and state anxiety levels during the procedure (p&#x2009;=&#x2009;0.022), and significantly higher satisfaction levels compared with the control group (p&#x2009;<&#x2009;0.001). In addition, post-procedure state anxiety levels were positively correlated with pain intensity experienced during and after the procedure (r&#x2009;=&#x2009;0.542 and r&#x2009;=&#x2009;0.496, respectively; p&#x2009;<&#x2009;0.001), and negatively correlated with procedural satisfaction (r&#x2009;=&#x2009;-0.652; p&#x2009;<&#x2009;0.001). These findings suggest that listening to music during IUD insertion may help reduce pain and anxiety while potentially enhancing patient satisfaction. Trial Registration: NCT06215183.

Humans