Healthy Male Subjects Research Articles

Sleep Debt and Insulin Resistance: What's Worse, Sleep Deprivation or Sleep Restriction?

Objective To evaluate which condition of sleep debt has a greater negative impact on insulin resistance: sleep deprivation for 24 hours or 4 hours of sleep restriction for 4 nights. Materials and Methods In total, 28 healthy male subjects aged 18 to 40 years were recruited and randomly allocated to two groups: sleep deprivation (SD) and sleep restriction (SR). Each group underwent two conditions: regular sleep (11 pm to 7 am ) and total sleep deprivation for 24 hours (SD); regular sleep (11 pm to 7 am ) and 4 nights of sleep restriction (SR) (1 am to 5 am ). The oral glucose tolerance test (OGTT) was performed, and baseline glucose, insulin, free fatty acids (FFAs), and cortisol were measured. In addition, the area under the curve (AUC) for glucose and insulin, the homeostasis model assessment of insulin resistance (HOMA-IR), and the Matsuda Index (Insulin Sensitivity Index, ISI) were calculated. Results Glucose and insulin had a similar pattern between groups, except at the baseline, when insulin was higher in the sleep debt condition of the SR when compared with the SD ( p < 0.01). In the comparison between regular sleep and sleep debt, the SD had a higher insulin AUC ( p < 0.01) and FFAs ( p = 0.03) after sleep deprivation, and insulin and the insulin AUC increased ( p < 0.01 for both), while the ISI decreased ( p = 0.02) after sleep restriction in the SR. In baseline parameters covariate by the condition of regular sleep, insulin ( p = 0.02) and the HOMA-IR ( p < 0.01) were higher, and cortisol ( p = 0.04) was lower after sleep restriction when compared with sleep deprivation. Conclusion Sleep restriction for 4 consecutive nights is more detrimental to energy metabolism because of the higher insulin values and insulin resistance compared with an acute period of sleep deprivation of 24 hours.

Degree of serum LDL cholesterol reduction by simvastatin and ezetimibe is dependent on baseline LDL cholesterol concentration but not on baseline values and changes in cholesterol synthesis and absorption parameters.

We questioned whether the baseline status of low-density lipoprotein cholesterol (LDL-C), cholesterol synthesis and absorption, and the changes in these parameters determine the change in serum LDL-C under statin or ezetimibe treatment or under combination treatment. 37 mildly hypercholesterolemic healthy male subjects were studied under placebo, simvastatin (20mg/d), ezetimibe (10mg/d), and combination treatment. We correlated the change of LDL-C (ΔLDL-C) under treatment with the placebo end values of LDL-C (baseline), whole-body cholesterol synthesis, and hepatic cholesterol synthesis (serum lathosterol to cholesterol ratio) as well as fractional absorption rate (FAR) of cholesterol and serum campesterol to cholesterol ratio. The change in serum LDL-C was also correlated with the changes in synthesis and absorption parameters. ΔLDL-C was highly negatively related to baseline LDL-C under ezetimibe (p<0.0001), simvastatin (p<0.0001), and combination treatment (p<0.0001). Under combination treatment, LDL-C lowering appears possible from baseline values of 10 mg/dL upwards, while ΔLDL-C was independent of the baseline value (-50 to -60%). ΔLDL-C was positively associated with placebo FAR under ezetimibe (p=0.0106) and combination treatment (p=0.0457). No associations were found between ΔLDL-C and baseline values for synthesis nor between ΔLDL-C and changes in synthesis and absorption surrogate markers. Under ezetimibe, simvastatin, and combination treatment, ΔLDL-C is predominantly dependent on the baseline LDL-C concentration. We hypothesize that the concentration gradient between serum LDL-C and hepatic cellular cholesterol determines the efficiency of serum LDL-C lowering. Combination treatment is the preferred treatment.

Pioglitazone-induced alterations of purine metabolism in healthy male subjects.

Pioglitazone is class of thiazolidinediones that activates peroxisome proliferator-activated receptors (PPARs) in adipocytes to improve glucose metabolism and insulin sensitivity and has been used as a treatment for type 2 diabetes. However, the underlying mechanisms of associated pioglitazone-induced effects remain unclear. Our study aimed to investigate endogenous metabolite alterations associated with pioglitazone administration in healthy male subjects using an untargeted metabolomics approach. All subjects received 30 mg of pioglitazone once daily in the assigned sequence and period. Urine samples were collected before pioglitazone administration and for 24 h after 7 days of administration. A total of 1465 compounds were detected and filtered using a coefficient of variance below 30% and 108 metabolites were significantly altered upon pioglitazone administration via multivariate statistical analysis. Fourteen significant metabolites were identified using authentic standards and public libraries. Additionally, pathway analysis revealed that metabolites from purine and beta-alanine metabolisms were significantly altered after pioglitazone administration. Further analysis of quantification of metabolites from purine metabolism, revealed that the xanthine/hypoxanthine and uric acid/xanthine ratios were significantly decreased at post-dose. Pioglitazone-dependent endogenous metabolites and metabolic ratio indicated the potential effect of pioglitazone on the activation of PPAR and fatty acid synthesis. Additional studies involving patients are required to validate these findings.

Pharmacokinetic interactions between fexuprazan, a potassium-competitive acid blocker, and nonsteroidal anti-inflammatory drugs in healthy males.

Fexuprazan, a novel potassium-competitive acid blocker, is expected to be used for the prevention of nonsteroidal anti-inflammatory drugs (NSAIDs) induced ulcer. This study aimed to evaluate pharmacokinetic (PK) interactions between fexuprazan and NSAIDs in healthy subjects. A randomized, open-label, multicenter, six-sequence, one-way crossover study was conducted in healthy male subjects. Subjects randomly received one of the study drugs (fexuprazan 40 mg BID, celecoxib 200 mg BID, naproxen 500 mg BID, or meloxicam 15 mg QD) for 5 or 7 days in the first period followed by the combination of fexuprazan and one of NSAIDs for the same days and the perpetrator additionally administered for 1-2 days in the second period. Serial blood samples for PK analysis were collected until 48- or 72-h post-dose at steady state. PK parameters including maximum plasma concentration at steady state (Cmax,ss) and area under plasma concentration-time curve over dosing interval at steady state (AUCτ,ss) were compared between monotherapy and combination therapy. The PKs of NSAIDs were not significantly altered by fexuprazan. For fexuprazan, differences in PK parameters (22% in Cmax, 19% in AUCτ,ss) were observed when co-administered with naproxen, but not clinically significant. The geometric mean ratio (90% confidence interval) of combination therapy to monotherapy for Cmax,ss and AUCτ,ss was 1.22 (1.02-1.46) and 1.19 (1.00-1.43), respectively. There were no significant changes in the systemic exposure of fexuprazan by celecoxib and meloxicam. Fexuprazan and NSAIDs did not show clinically meaningful PK interactions.

Impact of diet and physical activity on reproductive profile: A comparison of middle-aged and elderly men.

Age is a known determinant of reproductive health and fertility in both genders. The present work aims to assess the reproductive hormone profile of a middle-aged and elderly man. For this descriptive cross-sectional study, healthy male subjects (n=77) were recruited from the valley. Any individual suffering from any acute or chronic diseases and on drugs was ruled out from the study. Group A consisted of 40 elderly men between 60-70 years of age, and Group B comprised 37 men between 35-46 years of age. Blood samples were taken to estimate the reproductive hormone profile. Level of oxidant and antioxidant: Malondialdehyde and Glutathione. The demographic variables, which included retrospective and prospective questions, helped to assess the physical activity and diet intake behaviour of all inducted individuals. The analysis of the reproductive profile of both groups was similar and within the normal range of standards. However, the median level of LH was higher in group A than in group B: 6.7 mIU/ml versus 3.4 mIU/ml, respectively, and p<0.003. Both groups showed predominantly involvement in physical activity, >90%. The correlation of biochemical variables gives an insight into the fact that the Mediterranean diet and physical activity help to maintain a normal BMI. These implicate the normal secretion of various hormones, leading to intact spermatogenesis. We can safely deduce from this study that physically active lifestyles and a healthy diet are crucial factors in maintaining an endocrine profile.

Interplay of arsenic exposure and cigarette smoking on oxidative DNA damage in healthy males

BackgroundLong-term exposure to inorganic arsenic (As) and cigarette smoking has been associated with adverse health effects such as cancer, cardiovascular disease, and respiratory disease. Oxidative stress is one of the most well-known damage mechanisms for both. However, studies on the association with induced 8-hydroxy-2-deoxyguanosine (8-OHdG) in Iran are scarce, with no study on the interactive effect of As exposure and smoking in the literature.ObjectiveThis stratified cross-sectional study aimed to assess urinary and serum 8-OHdG levels in the relation to As exposure from drinking water, smoking and their interaction effect.MethodsThis study was based on 132 healthy male subjects living in villages of Hashtroud County, Iran (2021). All participants were categorized into four groups: (i) non-As exposed, never smokers (n = 33); (ii) non-As exposed, active smokers (n = 33); (iii) As exposed, never smokers (n = 33); and (iv) As exposed, active smokers (n = 33). Data on demographic and lifestyle factors were collected, and urinary and serum levels of 8-OHdG were determined by enzyme-linked immunosorbent assay (ELISA). The smoker's daily cigarette consumption and the duration of smoking were self-reported data.ResultsParticipants consuming drinking water with an As concentration > 10 µg/L had significantly higher urinary total arsenic (U-tAs) concentrations (median 26.96, IQR 21.35–37.17) µg/g Cr compared to the reference group (median 19.33, IQR 17.29–23.26) µg/g Cr. There was a significant difference in the serum concentration of 8-OHdG between groups (i) and (iii), (iv) and also between groups (ii) and (iv). We did not find a significant interaction effect of As exposure and smoking on the both urinary and serum 8-OHdG levels (P > 0.05). Serum 8-OHdG (S-8OHdG) was associated with average daily intake of As (As-ADI) (β = 0.32; 95% CI 0.01, 0.04, P-value = 0.001) and cigarettes smoked per day (β = 0.3; 95% CI 0.00, 0.043, P-value = 0.046). While As-ADI (β = 0.16; 95% CI 0.001, 0.004, P-value = 0.01) and U-tAs (β = 0.6; 95% CI 0.006, 0.009, P-value < 0.001) were associated with increased urinary 8-OHdG (U-8OHdG), moderate physical activity (β = − 0.15; 95% CI − 0.07, − 0.008, P-value < 0.015) inversely decreased biomarker levels.ConclusionOur findings suggest that As exposure and smoking are potential risk factors for oxidative DNA damage, and it is strongly recommended to pay more attention to the role of lifestyle factors in future studies.

The Impact of Music Perception on Quantitative Sensory Testing (QST).

Objective: The impact of listening to music on pain perception has been evaluated using questionnaires and numeric/visual analogue scales. In this study, the impact of music perception on sensory pain functions was measured by means of quantitative sensory testing. Methods: We enrolled 10 female and 10 male healthy subjects (10 of them were professional musicians). All subjects underwent, in total, four quantitative sensory testing measures (first: baseline; second: after pleasant music [Johannes Brahms, 3rd symphony, 3rd movement]; third: after unpleasant music [Krzysztof Penderecki, Threnos]; fourth: after a longer break). The pleasantness of music was evaluated using the Ertel differential scale. Results: After the participants listened to pleasant music, an increased sensitivity to cold stimuli (both threshold and pain), to mechanical stimuli (only for threshold), and to repeated stimuli (wind-up reaction) was noted. Listening to unpleasant music was not associated with changes in sensitivity. We did not observe any significant differences between male and female subjects or between musicians and non-musicians. There was no significant correlation between the rating of the music as pleasant/unpleasant and the different quantitative sensory testing measures. Conclusions: Our data show that listening to music inducing a pleasant feeling can increase the sensitivity to stimuli applied during a quantitative sensory testing session. This should be considered when performing or interpreting quantitative sensory testing examinations. Interestingly, this finding is in contrast to the observation that listening to music can decrease pain perception during painful procedures.

Desmin gene expression is not ubiquitous in all upper airway myofibers and the pattern differs between healthy and sleep apnea subjects

BackgroundDesmin is a major cytoskeletal protein considered ubiquitous in mature muscle fibers. However, we earlier reported that a subgroup of muscle fibers in the soft palate of healthy subjects and obstructive sleep apnea patients (OSA) lacked immunoexpression for desmin. This raised the question of whether these fibers also lack messenger ribonucleic acid (mRNA) for desmin and can be considered a novel fiber phenotype. Moreover, some fibers in the OSA patients had an abnormal distribution and aggregates of desmin. Thus, the aim of the study was to investigate if these desmin protein abnormalities are also reflected in the expression of desmin mRNA in an upper airway muscle of healthy subjects and OSA patients.MethodsMuscle biopsies from the musculus uvulae in the soft palate were obtained from ten healthy male subjects and six male patients with OSA. Overnight sleep apnea registrations were done for all participants. Immunohistochemistry, in-situ hybridization, and reverse transcription–quantitative polymerase chain reaction (RT–qPCR) techniques were used to evaluate the presence of desmin protein and its mRNA.ResultsOur findings demonstrated that a group of muscle fibers lacked expression for desmin mRNA and desmin protein in healthy individuals and OSA patients (12.0 ± 5.6% vs. 23.1 ± 10.8%, p = 0.03). A subpopulation of these fibers displayed a weak subsarcolemmal rim of desmin accompanied by a few scattered mRNA dots in the cytoplasm. The muscles of OSA patients also differed from healthy subjects by exhibiting muscle fibers with reorganized or accumulated aggregates of desmin protein (14.5 ± 6.5%). In these abnormal fibers, the density of mRNA was generally low or concentrated in specific regions. The overall quantification of desmin mRNA by RT–qPCR was significantly upregulated in OSA patients compared to healthy subjects (p = 0.01).ConclusionsOur study shows evidence that muscle fibers in the human soft palate lack both mRNA and protein for desmin. This indicates a novel cytoskeletal structure and challenges the ubiquity of desmin in muscle fibers. Moreover, the observation of reorganized or accumulated aggregates of desmin mRNA and desmin protein in OSA patients suggests a disturbance in the transcription and translation process in the fibers of the patients.

Evaluation of Alterations in Basic Cardiac Functions in Operators of Artisanal Refineries in Rivers State, Nigeria

The impact of numerous artisanal refineries on the populace in Niger Delta region has been a great source of mainly health, economic and environmental concerns. Thus, the present study comparatively assessed the alterations of basic cardiac functions that may be associated with the operation of artisanal refineries (OAR) in Rivers State of Nigeria. This cross-sectional survey used a multi-stage sampling technique (including purposive and snowball tools) to recruit 203 (including 120 OAR-exposed and 83 non-OAR exposed) consenting and apparently healthy adult male and female subjects. With the use of the electrocardiographic (ECG) machine, the basic ECG indices were recorded from the study subjects. Quantitative data obtained from the subjects were subjected to statistical analyses using the Statistical Package for Social Sciences (SPSS) version 21.0. The result indicated significantly (P&lt;0.0) elevated heart rates in the OAR-exposed subjects when compared to their non-OAR-exposed counterparts. Amongst the various ECG features, the exposed subjects predominantly presented with left atrial enlargement (LAE) (male exposed=57% and female exposed =46.3%) as against none in the unexposed group. And there was no significant association of the incidences of Abnormal/clinical ECG Features between the actively exposed (OAR operators) and passively exposed (residents in same city who are non-OAR operators) subjects. In conclusion, the operation of artisanal refineries in our locale may potentially predispose its operators to significant elevation of heart rate and incidences of abnormal ECG features.

The mass balance recovery, absorption, metabolism, and excretion of [14C]-orvepitant in healthy male subjects after oral dosing: clinical conduct & mass balance

The mass balance recovery, absorption, metabolism, and excretion of [14C]-orvepitant in healthy male subjects after oral dosing: clinical conduct & mass balance

Experimental assessment of pelvis slipping during postless traction for orthopaedic applications.

The application of lower limb traction during hip arthroscopy and femur fractures osteosynthesis is commonplace in orthopaedic surgeries. Traditional methods utilize a perineal post on a traction table, leading to soft tissue damage and nerve neuropraxia. A postless technique, using high-friction pads, has been considered as a potential damage-free alternative. However, whether these pads sufficiently prevent patient displacement remains unknown. Thus, this study systematically assesses the efficacy of commercial high-friction pads (PinkPad and CarePad) in restraining subject displacement, for progressively increasing traction loads and different Trendelenburg angles. Three healthy male subjects were recruited and tested in supine and Trendelenburg positions (5° and 10°), using a customized boot-pulley system. Ten load disks (5kg) were dropped at 15s intervals, increasing gradually the traction load up to 50kg. Pelvis displacement along the traction direction was measured with a motion capture system. The displacement at 50kg of traction load was analyzed and compared across various pads and bed inclinations. Response to varying traction loads was statistically assessed with a quadratic function model. Pelvis displacement at 50kg traction load was below 60mm for all conditions. Comparing PinkPad and CarePad, no significant differences in displacement were observed. Finally, similar displacements were observed for the supine and Trendelenburg positions. Both PinkPad and CarePad exhibited nearly linear behavior under increasing traction loads, limiting displacement to 60mm at most for 50kg loads. Contrary to expectations, placing subjects in the Trendelenburg position did not increase adhesion.

A pharmacokinetic study comparing the biosimilar HEC14028 and Dulaglutide (Trulicity®) in healthy Chinese subjects.

This study aimed to evaluate the pharmacokinetics (PKs), safety, and immunogenicity of the biosimilar HEC14028 compared to reference Trulicity® (dulaglutide) in healthy male Chinese subjects. This study was a single-center, randomized, open, single-dose, parallel-controlled comparative Phase I clinical trial, including a screening period of up to 14 days, a 17-day observation period after administration, and a 7-day safety follow-up period. A total of 68 healthy male subjects were randomly assigned (1:1) to the test group (HEC14028) and the reference group (dulaglutide) (single 0.75 mg abdominal subcutaneous dose). The primary objective was to evaluate the pharmacokinetic characteristics of HEC14028 and compare the pharmacokinetic similarities between HEC14028 and dulaglutide. The primary PK endpoints were maximum plasma concentration (Cmax) and area under the blood concentration-time curve from zero time to the estimated infinite time (AUC0-∞). The study results showed that HEC14028 and dulaglutide were pharmacokinetically equivalent: 90% confidence interval (CI) of Cmax and AUC0-∞ geometric mean ratios were 102.9%-122.0% and 97.1%-116.9%, respectively, which were both within the range of 80.00%-125.00%. No grade 3 or above treatment emergent adverse events (TEAEs), serious adverse events (SAEs), TEAEs leading to withdrawal from the trial, or TEAEs leading to death were reported in this study. Both HEC14028 and dulaglutide showed good and similar safety profiles, and no incremental immunogenicity was observed in subjects receiving HEC14028 and dulaglutide.

The mass balance recovery, absorption, metabolism, and excretion of [14C]-orvepitant in healthy male subjects after oral dosing: radiosynthesis of [14c]-orvepitant

The mass balance recovery, absorption, metabolism, and excretion of [14C]-orvepitant in healthy male subjects after oral dosing: radiosynthesis of [14c]-orvepitant

Endogenous metabolites change associated with pioglitazone administration in healthy male subjects

Endogenous metabolites change associated with pioglitazone administration in healthy male subjects

The mass balance, recovery, absorption, metabolism, and excretion of [14C]-orvepitant in healthy male subjects after oral dosing: metabolite characterisation

The mass balance, recovery, absorption, metabolism, and excretion of [14C]-orvepitant in healthy male subjects after oral dosing: metabolite characterisation

Assessment of Blood Gas Pattern amongst Artisanal Refinery Operators in Rivers State, Nigeria

Some identified setbacks of the legitimate and illegitimate explorations/exploitations of crude oil and its derivatives in the Niger Delta are degraded environment, weak economy, and deteriorating health of the populace. Therefore, the current study evaluated the effect of artisanal refinery operation on respiratory blood gases and renal functions of its workers in Rivers State. As a cross-sectional investigation with sparse population, the multistage sampling technique (including purposive and snowball tools) was adopted to recruit 203 (including 120 operators of artisanal refinery―OAR-actively exposed and 83 non-OAR- actively exposed) willing and apparently healthy male and female adult subjects. Following receipt of ethical approval and consent, five milliliter of blood was taken from each subject from their antecubital vein after sterilizing the portion of the cubital fossa. The sample was then put into plain sample bottle and centrifuged to recover serum. Thereafter, the automated blood gas analyzer was used to measure the arterial blood gases of the subjects. The result showed marked (P&lt;0.05) reductions in the partial pressure of oxygen (PO2) and oxygen saturation (SO2) levels in artisanal refinery operators (actively exposed) when compared to that of the passively-exposed subjects. Again, there were marked (P&lt;0.05) elevations in the plasma pH and bicarbonate ions (HCO-3) levels in the actively exposed subjects compared to their passively-exposed counterparts. In conclusion, there could be adverse impact on respiratory blood gases and incidences of metabolic alkalosis over chronic exposures to the OAR activities.

Effect of a plant protein-rich diet on postprandial phosphate metabolism in healthy adult men: a randomised controlled trial.

This study examined the effects of animal protein- and plant protein-rich diets on postprandial phosphorus metabolism in healthy male subjects. The study was conducted by randomised parallel-group comparison of healthy men aged 21-24 years. In Study 1, participants were divided into two groups and consumed either a 70% animal protein diet (AD, n = 6) or a 70% plant protein diet (PD, n = 6). In Study 2, participants were divided into three groups and consumed either AD (n = 10), PD (n = 10) or AD + DF, a 70% animal protein diet loaded with the same amount of fibre as PD (n = 9). The phosphorus contents of the diets used in this study were nearly equivalent (AD, 710.1 mg; PD, 709.7 mg; AD + DF, 708.9 mg). Blood and urine samples were collected before, and 2 and 4 h after the meal to measure phosphorus and calcium levels. In Study 1, PD consumption resulted in lower blood and urinary phosphorus concentrations 2 h postprandially compared with AD (p < 0.05). In Study 2, blood phosphorus levels in AD + DF after the diet remained lower, but not significantly so compared with AD, and urinary phosphorus levels were significantly lower 2 h postprandially (p < 0.05). A plant protein-rich diet reduced rapid postprandial increases in blood and urinary phosphorus concentrations compared with the animal protein-rich diets, suggesting that dietary fibre may play a partial role in the postprandial decreases in blood and urinary phosphorus concentrations.

Effects of Simulated Airplane Cabin Noise on In-Flight Meal Perception in the Brain Using Electroencephalography.

Auditory distractions can impair the sensory evaluation of food; however, the specific impact of airplane cabin noise on the sensory perception of in-flight meals remains poorly studied. Here, we investigated the effects of airplane cabin noise on the visual processing of in-flight meal stimuli using electroencephalography (EEG) in twenty healthy male subjects. Resting-state EEG and event-related potential (ERP) responses to in-flight meal images were acquired during quiet and simulated cabin noise conditions. Participants reported mild discomfort and some loss of appetite when exposed to airplane cabin noise. The analysis of resting-state EEG showed an increase in the absolute power of theta and beta frequency bands in the left superior parietal and left frontal/right central regions under simulated cabin noise conditions, compared to quiet conditions. The ERP results showed that the amplitude of responses evoked by visual meal images in the superior parietal area was reduced in the noise condition compared to the quiet condition. Our findings suggest that airplane cabin noise disrupts the visual perception and attentional processing of in-flight food stimuli. These neural changes imply an impact on integrating sensory information, resulting in altered sensory evaluations of food during in-flight dining experiences.

Pharmacokinetics, mass balance, and metabolism of [14C]envonalkib (TQ-B3139), a novel ALK tyrosine kinase inhibitor, in healthy Chinese subjects.

Envonalkib (TQ-B3139) is a novel, potent anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor used to treat ALK-positive non-small cell lung cancer. This phase I mass balance study investigated the pharmacokinetics, metabolism, and excretion of 14C-radiolabeled envonalkib in healthy Chinese male subjects. A single oral dose of 600mg (150µCi) [14C]envonalkib was administered to healthy male subjects under fasted state. Samples of blood, urine and feces were collected for quantitative determination of total radioactivity and unchanged envonalkib, and the metabolites identification. After dosing, the median Tmax of radioactivity was 4h and the mean t1/2 was 65.2h in plasma. The exposure of total radioactivity was much higher than that of unchanged envonalkib in plasma. The mean total recovery of the radiolabeled dose was 93.93% over 504h post-dose, with 15.23% in urine and 78.71% in feces. Envonalkib underwent extensive metabolism and a total of 15 metabolites were identified in plasma, urine, and feces. Unchanged envonalkib and its major metabolite M315 were the main components in plasma, accounting for 20.37% and 33.33% of total plasma radioactivity. In urine, O-dealkylation metabolite M315 was the major component accounted for 7.98% of dose. In feces, 16.01% of dose was excreted as cysteine conjugate M434-1. Envonalkib was well tolerated and there were no serious adverse events observed in the study. Envonalkib was extensively metabolized prior to excretion and eliminated primarily as metabolites via feces.

Coupled effect of load weights and belt use on male shoulder pressure redistribution

Shoulder pressure redistribution is jointly affected by backpack loads and belt support. However, the combined effect of both factors has rarely been fully evaluated. Here, we studied the coupled effect of backpack loads and belt support on shoulder pressure redistribution. All twenty-eight healthy male subjects underwent eight loading conditions with both chest and hip belts fastened (CH) and unfastened (CON) in four conditions where the backpack weighed 7.5, 15, 22.5, and 30% of body weight (BW). Shoulder pressure distribution was quantified through a pressure-sensing vest mat. The results showed that using the hip belt and chest belt was effective in relieving the high pressure in the lateral clavicle and medial trapezius region and strengthening the load-bearing capacity of shoulder. However, the assistance in pressure relief of using belt was weakened when load increased to 30% BW. This study also showed that the belt use can be effective in improving pressure asymmetry on both sides.