Healthy Female Participants Research Articles

Serum metabolomics analysis of deficiency pattern and excess pattern in patients with rheumatoid arthritis

BackgroundRheumatoid arthritis (RA) is a chronic and refractory autoimmune disease. Deficiency pattern (DP) and excess pattern (EP), as crucial types of Chinese medicine pattern diagnoses published by International Classification of Diseases 11th Revision (ICD-11), could provide new strategies for RA diagnosis. However, the biological basis of DP and EP of RA is not explicit.Methods19 female RA DP patients, 41 female RA EP patients and 30 female healthy participants were included in the study. The serums of participants were collected and analyzed by metabolomics based on ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry to profile metabolic characteristics of RA DP and EP. Furthermore, bioinformatics analysis results were obtained by using Ingenuity Pathway Analysis (IPA) and statistical analysis was performed by SAS version 9.4 for further identification of potential biomarkers.ResultsSerum metabolic profiling revealed 25 and 24 differential metabolites in RA DP and EP respectively, and 19 metabolites were common to RA DP and EP. Compared with DP group, L-Homocysteic acid, LysoPE(P-16:0/0:0), N(omega)-Hydroxyarginine and LysoPC(16:0/0:0) decreased (P < 0.05), and Pyruvic acid, D-Ribose, Gamma-Glutamylserine, PE(22:0/24:1(15Z)), Inosinic acid increased (P < 0.05) in EP group. Menawhile, S-Nitrosoglutathione, 5-Thymidylic acid, SN38 glucuronide, PE(22:0/24:0), PC(24:0/24:1(15Z)) and Bisdiphosphoinositol tetrakisphosphate increased significantly in DP group compared to EP group (P < 0.05). For the unique metabolites, bioinformatics analysis results showed that 5-Methoxytryptamine involved in Melatonin Degradation II and Superpathway of Melatonin Degradation is the key metabolite to RA DP. Meanwhile, GABA is the key metabolite in EP group, which involved in Glutamate Dependent Acid Resistance, GABA Receptor Signaling, Glutamate Degradation III (via 4-aminobutyrate) and 4-aminobutyrate Degradation I. Bioinformatics analysis between unique metabolites of RA DP and EP groups with human target genes for RA showed that 5-methoxytryptamine and LysoPC(18:1(9Z)/0:0), the unique metabolites of RA DP, might participate in colorectal cancer metastasis signaling, tumor microenvironment pathway, apoptosis signaling, MYC mediated apoptosis signaling, erythropoietin signaling pathway and LXR/RXR activation. Simultaneously, GABA, LysoPA(18:1(9Z)/0:0) and L-Targinine, the unique metabolites of RA EP, might participate in neuroinflammation signaling pathway, osteoarthritis pathway, glucocorticoid receptor signaling, ILK signaling, IL-17 signaling and HIF1α signaling.ConclusionsThe study indicates that serum metabolomics preliminarily revealed the biological basis of RA DP and EP. 5-methoxytryptamine, LysoPC(18:1(9Z)/0:0) and GABA, LysoPA(18:1(9Z)/0:0), L-Targinine might be the predictors to distinguish the DP and EP of RA respectively. These interesting results provide thoughts for further study of traditional medicine patterns of ICD-11. It also contributes to provide strategy for personalized precision treatment of RA and further validation is needed.

TMAO Response to a High-Fat High-Sugar Meal Challenge in Generally Healthy United States Adults

ObjectivesTrimethylamine n-oxide (TMAO) is linked to the gut microbiome's metabolism of choline, carnitine, and betaine and is associated with adverse cardiovascular health. In a secondary analysis, we assessed the plasma TMAO response to a high-fat high-sugar meal challenge devoid of choline, carnitine, or betaine in metabolically healthy male (n = 48) and female (n = 49) participants residing near Davis, California, USA.MethodsThe standardized meal challenge was a 3000-gram shake containing 60% kilocalories from fat (shortening and palm oil), 25% kilocalories from carbohydrate (granulated white sugar), and 15% kilocalories from protein (pasteurized egg white). The shake contained limited amounts of direct TMAO-precursors including 2.9 mg of choline and 0.76 mg of betaine. Blood samples were collected at fasting and 0.5, 3, and 6 hours after consuming the meal challenge. TMAO was measured by liquid chromatography-high resolution mass spectrometry using the MxP Quant 500 kit (Biocrates, Innsbruck, Austria). Differences in TMAO concentration by time were assessed by ANOVA and values are means ± standard deviation.ResultsTMAO response demonstrated a post-prandial rise in concentration that peaked at 3 hours and returned to fasting levels by 6 hours. Mean TMAO levels at fasting, 0.5, 3, and 6 hours were 5.27 ± 3.43 μM, 6.09 ± 6.01 μM, 6.87 ± 8.11 μM, 4.76 ± 4.00 μM, respectively. Significant differences were observed between fasting and 3 hours (P = 0.039), and 3 and 6 hours (P = 0.011).ConclusionsPlasma TMAO concentration was affected by a high-fat high-sugar meal challenge despite providing limited amounts of direct TMAO-precursors. The circadian rhythm of the gut microbiome or the host, or the gut microbiome's utilization of phosphatidylcholine from biological sources may contribute to these results. Understanding the regulation of TMAO and its relationship to meals is critical to identifying its role in the etiology of diabetes and cardiovascular disease.Funding SourcesThis work was funded in part by the USDA-Agricultural Research Service (2032–51,530-025–00D) and the National Institute of Health (RO1HL148110).

Detailed evaluation of cognitive performance in idiopathic intracranial hyper- tension and relevance of intracranial pressure

Idiopathic intracranial hypertension (IIH) is an increasingly prevalent disease, characterised by raised intracranial pressure (ICP). Cognitive impairments have been reported in IIH, however evidence support- ing these deficits are scarce and contributing factors have not been defined. Using a bespoke battery of cognitive tests, we identified multiple domains of deficiency in a case-control prospective study of 66 female adult IIH patients. Attention networks (executive function) and sustained attention were impaired compared to a body mass index and age matched control group of 25 healthy female participants. These deficits were not permanent as participants exhibited improvement in several domains over 12 months which were associated with reduction in ICP. Cognition was evaluated before and after a lumbar puncture, with acute reduction in ICP and noted significant improvement in executive function. The impact of comorbidities was explored, with headache severity during cognitive testing, co-morbid depression and markers of obstructive sleep apnoea adversely associated with cognitive performance. Deficits were also significantly associated with impaired reliability to perform visual field tests, the cornerstone of monitoring vision in IIH. Our findings propose that cognitive impairment should be recognised as a clinical manifestation of IIH and treating comorbidities could improve cognitive performance.livgrech@googlemail.com

0111 Effects of Sleep on Working Memory

Abstract Introduction Improvements in working memory (WM) are associated with increased vagal autonomic activity during sleep. Sex hormones, which fluctuate across a menstrual cycle, influence sleep, autonomic activity, and cognitive performance. Given this complex interaction, we examined whether the relation between WM improvement and autonomic activity across a night of sleep was modulated by menstrual phase. Methods Twenty-five healthy female participants with natural, regular menstrual cycles (age = 28.14 ± 4.41 years) were enrolled. We employed a within-subject design to investigate the role of menstrual phase on autonomic activity and sleep-dependent working memory improvement. All participants completed two in-lab visits, with one visit during their low hormones phase (LH: 0 to +2 days from the start of menses) and one visit during their high hormone phase (HH: +1 to +4 days from the start of ovulation). We measured WM with the Operation-Span Task at 9PM and 8AM. Participants’ overnight sleep was monitored with EEG and ECG. We measured parasympathetic activity using the high-frequency heart rate variability (hfHRV) and the root-mean-square of successive differences between normal heartbeats (RMSSD). We used linear-mixed effect models and Pearson’s r. Results No differences in WM were found between menstrual phases (all ps &amp;gt; .223). Interestingly, however, HRV during NREM positively correlated with WM improvement in LH (hfHRV: r = .329, p = .093; RMSSD: r = .327, p = .096), but not during HH (hfHRV: r = -.197, p = .355; RMSSD: r = -.179, p = .402). The differences between correlations were significant (hfHRV: p = .038; RMSSD: p = .045). Conclusion Prior meta-analysis revealed greater vagal autonomic activity during LH (menses), compared with other phases. Though we didn’t replicate this finding, we did show a significantly stronger relation between vagal autonomic activity and overnight WM improvement during this low hormone phase. Our results suggest that menstrual phase shifts the reliance of sleep-dependent WM improvement to vagal autonomic mechanisms. Support (If Any) UCI MIND/WAM 02-2020

Effects of Different Scan Duration on Brain Effective Connectivity among Default Mode Network Nodes.

Background: Resting-state functional magnetic resonance imaging (rs-fMRI) can evaluate brain functional connectivity without requiring subjects to perform a specific task. This rs-fMRI is very useful in patients with cognitive decline or unable to respond to tasks. However, long scan durations have been suggested to measure connectivity between brain areas to produce more reliable results, which are not clinically optimal. Therefore, this study aims to evaluate a shorter scan duration and compare the scan duration of 10 and 15 min using the rs-fMRI approach. Methods: Twenty-one healthy male and female participants (seventeen right-handed and four left-handed), with ages ranging between 21 and 60 years, were recruited. All participants underwent both 10 and 15 min of rs-fMRI scans. The present study evaluated the default mode network (DMN) areas for both scan durations. The areas involved were the posterior cingulate cortex (PCC), medial prefrontal cortex (mPFC), left inferior parietal cortex (LIPC), and right inferior parietal cortex (RIPC). Fifteen causal models were constructed and inverted using spectral dynamic causal modelling (spDCM). The models were compared using Bayesian Model Selection (BMS) for group studies. Result: The BMS results indicated that the fully connected model was the winning model among 15 competing models for both 10 and 15 min scan durations. However, there was no significant difference in effective connectivity among the regions of interest between the 10 and 15 min scans. Conclusion: Scan duration in the range of 10 to 15 min is sufficient to evaluate the effective connectivity within the DMN region. In frail subjects, a shorter scan duration is more favourable.

Decreased Efficiency of Between-Network Dynamics During Early Memory Consolidation With Aging

Aging is associated with memory decline and progressive disabilities in the activities of daily living. These deficits have a significant impact on the quality of life of the aging population and lead to a tremendous burden on societies and health care systems. Understanding the mechanisms underlying aging-related memory decline is likely to inform the development of compensatory strategies promoting independence in old age. Research on aging-related memory decline has mainly focused on encoding and retrieval. However, some findings suggest that memory deficits may at least partly be due to impaired consolidation. To date, it remains elusive whether aging-related memory decline results from defective consolidation. This study examined age effects on consolidation-related neural mechanisms and their susceptibility to interference using functional magnetic resonance imaging data from 13 younger (20–30 years, 8 female) and 16 older (49–75 years, 5 female) healthy participants. fMRI was performed before and during a memory paradigm comprised of encoding, consolidation, and retrieval phases. Consolidation was variously challenged: (1) control (no manipulation), (2) interference (repeated stimulus presentation with interfering information), and (3) reminder condition (repeated presentation without interfering information). We analyzed the fractional amplitude of low-frequency fluctuations (fALFF) to compare brain activity changes from pre- to post-encoding rest. In the control condition, fALFF was decreased in the left supramarginal gyrus, right middle temporal gyrus, and left precuneus but increased in parts of the occipital and inferior temporal cortex. Connectivity analyses between fALFF-derived seeds and network ROIs revealed an aging-related decrease in the efficiency of functional connectivity (FC) within the ventral stream network and between salience, default mode, and central executive networks during consolidation. Moreover, our results indicate increased interference susceptibility in older individuals with dynamics between salience and default mode networks as a neurophysiological correlate. Conclusively, aging-related memory decline is partly caused by inefficient consolidation. Memory consolidation requires a complex interplay between large-scale brain networks, which qualitatively decreases with age.

Hypoxic Vasodilation is Augmented During the High versus Low Estrogen Phase of the Menstrual and Oral Hormonal Contraceptive Pill Cycle

BackgroundHypoxia elicits peripheral vasodilation to preserve oxygen delivery to metabolically active tissue. Hypoxic vasodilation, predominantly mediated by β‐adrenergic and nitric oxide mechanisms, is greater in adult female participants compared to adult male participants. Greater circulating estrogen in adult females has been purported to contribute to observed sex differences in hypoxic vasodilation. Nearly 80% of adult females in the United States will take oral hormonal contraceptive pills (OCPs) in their lifetime. Adult females taking OCPs exhibit greater β‐adrenergic receptor mediated vasodilation and nitric oxide production relative adult females with natural menstrual cycles (NC). Strategically utilizing the fluctuations of circulating estrogen that occur within a NC and OCP cycle, we aimed to examine the contribution of endogenous and exogenous estrogen on hypoxic vasodilation in female participants. We hypothesized female participants taking OCPs would exhibit greater hypoxic vasodilation relative to female participants with a NC. We further hypothesized hypoxic vasodilation would be greatest during the high estrogen (HE) phase of the menstrual or pill cycle compared to the low estrogen (LE) phase.MethodsTen female participants with a NC (25±1 yrs, 23±1 kg/m2) and ten female participants taking monophasic OCPs (24±1 yrs, 21±1 kg/m2) completed two study visits (IRB #2011312, NCT03606434). Participants were studied once during the LE phase of the menstrual or pill cycle (Cycle day: NC 3±1; OCP 5±1) and once during the HE phase of the menstrual or pill cycle (Cycle day: NC 15±1; OCP: 17±1). Forearm blood flow (venous occlusion plethysmography) and blood pressure (BP, finger plethysmography) were measured during normoxia and hypoxia (80% SpO2). Blood flow was normalized for BP and expressed as forearm vascular conductance (FVC).ResultsHypoxia elicited an increase in FVC (% change from baseline) that was greater during the HE phase (NC: 21±10%, OCP: 41±6%) of the menstrual/pill cycle compared to the LE phase (NC: 5±8%, OCP: 10±8%) in both NC and OCP participants (Main effect of phase, p&lt;0.01; Main effect of group, p=0.16; Interaction of phase and group, p=0.30).ConclusionHypoxic vasodilation is augmented in the HE phase of the menstrual and pill cycle in healthy young female participants, independent of whether the hormone is endogenous (NC) or exogenous (OCP). These data further our understanding of the role of estrogen in hypoxic vasodilation. These findings may have clinical implications for the vascular response to hypoxia in conditions of low estrogen (i.e., postmenopause) and/or estrogen excess, and warrant further investigation.

Abstract 336: Comparing Of In-vivo Carnosine Levels In Blood, Urine, And Muscle

Background: Dietary supplementation of carnosine, an endogenously produced antioxidant, can be potentially useful in decreasing oxidative stress in the vasculature. However, a safe and accurate measurement of in-vivo Carnosine levels has not been identified. Methods: We enrolled 28 healthy male (50%) and female participants. In-vivo levels of carnosine were measured in three distinct tissues in all 28 participants - urine, blood red blood cells (RBC), and muscle via proton magnetic resonance spectroscopy (1H-MRS). Generalized Linear Model with gamma-distribution and log-link was adjusted for age, sex, race, and diet. Coefficient of variance (CoV) was calculated for 1H-MRS repeat measurements: single location with multiple measurements and multiple locations with single measurements. Results: Univariate regression analysis showed a significant positive association between RBC and urinary carnosine levels (β=0.02; 95% CI: 0.004-0.03; P=0.01). The adjusted model also showed significant positive association between RBC and urinary carnosine levels (β=0.02; 95% CI: 0.002, 0.03; P=0.03). There was no association between 1H-MRS and RBC carnosine or urinary carnosine or carnosine conjugates in urine. The median CoV for multiple readings at single location were 8% and 1% for C2 and C4 peaks respectively, however 12% and 13% for C2 and C4 peaks respectively for single reading at multiple locations. Conclusions: Even though urine, blood (RBC), and muscle represent in-vivo tissues of the human body, the levels of carnosine pools in these different compartments are not in equilibrium with each other. 1H-MRS is highly sensitive to location of measurement. In-vivo levels of carnosine in urine and blood depot are in synchrony and should be used for large scale clinical and research studies like the NEAT clinical trial (NCT03314987), which studies the use of carnosine dietary supplementation to mitigate harmful cardiovascular effects of PM2.5 air pollution.

Reliability and preliminary reference values for the Total Faulty Breathing Scale (TFBS): A cross-sectional study.

Background and AimsThe evaluation of breathing function is crucial in the clinical examination of the respiratory system. The Total Faulty Breathing Scale (TFBS) could be used in clinical settings to quantify the measurement of breathing dysfunction. Reliability data for the TFBS are available for males, but there is a requirement to determine reliability for females and to develop reference values. The aim of this study, therefore, was to determine the reliability in females and to establish the preliminary reference values for the TFBS.MethodsTwenty‐three healthy female participants for reliability and 44 (7 male and 37 female) participants for preliminary reference values participated in this cross‐sectional study. For both aspects of the study, participants were instructed to breathe at their own pace with no specific instruction. Then each participant was observed carrying out normal breathing for a period of 10 breaths and deep breathing for a period of 10 breaths while being assessed with the TFBS.ResultsIntrarater and interrater reliability of the TFBS showed a kappa value of 0.769 and 0.751, respectively, indicating substantial agreement for female participants. The preliminary reference categories for TFBS were reported to be normal for 20 (45.5%) participants and mild faulty breathing for the remaining 24 (54.4%) participants.ConclusionsThe findings of this study suggested that TFBS was reliable to measure breathing function among female participants, and the reference categories may be helpful in the identification of normal and faulty breathing.

Efficacy of hyaluronic acid gel and spray in healing of extraction wound: a randomized controlled study.

To evaluate the efficacy of 0.2% hyaluronic acid gel and 0.01% hyaluronic acid (HA) spray in the healing of extraction wounds using the ruler and digital planimetry method. 30 systemically healthy female participants aged between 20-60 years requiring extraction were selected. Extraction sockets receiving 0.2% HA gel Gengigel®, 0.01% HA spray Gengigel®, and where hyaluronic acid was excluded were allocated into three groups as test group A (HA gel group), test group B (HA spray group) and control group (without HA). Socket wound closure was measured post-operative on the day of extraction and 1-week post extraction using digital planimetry and ruler method. Patient satisfaction rate was evaluated for both the gel and spray. The wound closure with the ruler method was 43.01% for the control group, 67.01%, and 65.82% for the gel group and spray group respectively. The wound closure with the digital planimetry method was 47.97% for the control group, 69.08% for the gel group, and 66.94% for the spray group. The gel showed better results of wound closure as compared to the spray. However, the results were not statistically significant. Hyaluronic acid offers a beneficial effect in early post-operative healing after extraction.

Acute Effects of Milk vs. Carbohydrate on Bone Turnover Biomarkers Following Loading Exercise in Young Adult Females.

Dairy products and impact exercise have previously been identified to be independently beneficial for bone mineral properties, however, it is unknown how the combination of these two osteogenic interventions may alter acute bone turnover. Using a randomized crossover design, we compared the acute effects of consuming milk vs. an isoenergetic carbohydrate control beverage on bone biomarkers following loading exercise. Thirteen healthy female participants (Age = 20.3 ± 2.3y; BMI = 21.0 ± 1.1 kg/m2) consumed either 550 mL of 0% skim white milk (MILK) or 52.7 g of maltodextrin in 550 mL of water (CHO), both 5 min and 1 h following completion of a combined plyometric (198 impacts) and resistance exercise (3–4 sets/exercise, 8–12 reps/set, ∼75% 1-RM) bout. Venous blood samples were obtained pre-exercise, and 15 min, 75 min, 24 h and 48 h post-exercise to assess serum concentrations of bone resorption biomarkers, specifically carboxyl-terminal crosslinking telopeptide of type I collagen (CTX), receptor activator nuclear factor kappa-β ligand (RANKL), and sclerostin (SOST), as well as bone formation biomarkers, specifically osteoprotegerin (OPG) and osteocalcin (OC). When absolute biomarker concentrations were examined, there were no interaction or group effects for any biomarker, however, there were main time effects (p < 0.05) for RANKL, SOST, and OC, which were lower, and the OPG: OPG/RANKL ratio, which was higher at 75 min post-exercise compared with baseline in both conditions. In addition to assessing absolute biomarker concentrations at specific timepoints, we also evaluated the relative (% change) cumulative post-exercise response (75 min to 48 h) using an area under the curve (AUC) analysis. This analysis showed that the relative post-exercise CTX response was significantly lower in the MILK compared to the CHO condition (p = 0.03), with no differences observed in the other biomarkers. These results show that while milk does not appear to alter absolute concentrations of bone biomarkers compared to CHO, it may attenuate relative post-exercise bone resorption (i.e., blunt the usual catabolic response to exercise).

Aging alters gastrocnemius muscle hemoglobin oxygen saturation (StO2) characteristics in healthy individuals.

Functional limitations during exercise from alterations in the balance of oxygen supply and demand-as reported by lower tissue oxygen saturation and longer recovery time-are well documented in clinical populations. We aimed to assess changes in skeletal muscle hemoglobin oxygen saturation (StO2) characteristics during exercise as a result of aging in otherwise healthy individuals. We recruited healthy male and female participants (n = 101) from three age ranges-young (18-39years), middle age (40-65years), and older (> 65years)-to complete exercise tests commonly used in clinical populations. Using near-infrared spectroscopy (NIRS) we assessed StO2 in the medial gastrocnemius during the Gardner Treadmill Protocol and 6min walk test (6MWT). Minimum StO2 (%) during the treadmill test was significantly lower for both middle-age (36.1 ± 20.6) and older (27.3 ± 19.4) participants compared to young (46.8 ± 14.8) (p < 0.05 and p < 0.01 respectively), and recovery time (minutes) was significantly prolonged (young = 0.22 ± 0.34; middle age = 0.66 ± 0.52; older = 1.04 ± 1.00) (p < 0.001 for both middle age and older compared to young). Similar results were shown during the 6MWT, as minimum StO2 (%) was lower in middle-age (41.7 ± 17.2) and older (40.0 ± 25.9) participants compared to young (53.6 ± 14.5) (p < 0.05), and recovery times (minutes) were prolonged (young: 0.11 ± 0.17; middle age: 0.46 ± 0.42; older: 0.93 ± 0.43) (p < 0.001 for both middle age and older compared to young). Simple linear regression analyses demonstrated that age predicted treadmill recovery and 6MWT recovery. Our study provides evidence that aging, even in otherwise healthy individuals, negatively impacts muscle StO2 characteristics. In older individuals, working muscle tissue may reach lower oxygen saturation during exercise and take longer to return to baseline oxygen saturation post-exercise.

Evaluation of the potential for pharmacokinetic interaction between tirabrutinib and levonorgestrel/ethinyl estradiol in healthy female volunteers.

Tirabrutinib (TIRA), a potent and nonreversible oral Bruton tyrosine kinase inhibitor, is evaluated for treatment of certain hematological malignancies and inflammatory diseases. A drug–drug interaction study to evaluate the effect of TIRA on the pharmacokinetics of the oral contraceptive levonorgestrel (LEVO)/ethinyl estradiol (EE) was conducted in healthy female participants (N = 26). Participants received a single dose of LEVO (150 mcg)/EE (30 mcg) alone (reference), and on day 12 of a 15‐day regimen of TIRA 160 mg once‐daily (test). Intensive blood sampling for determination of LEVO, EE, and TIRA plasma concentrations was conducted, and safety was assessed throughout the study. Pharmacokinetic interactions were evaluated using 90% confidence intervals (CIs) of the geometric least squares mean (GLSM) ratios of the test versus reference treatments. The GLSM (90% CI) ratios of area under the concentration‐time curve from zero to infinity (AUCinf; LEVO: 0.95, 95% CI: 0.88–1.03, EE: 1.10, 95% CI: 1.05–1.16) and maximum plasma concentration (Cmax; LEVO: 0.85, 95% CI: 0.74–0.98, EE: 1.07, 95% CI: 0.98–1.18) were within the prespecified 0.70 to 1.43 no effect bounds; and the AUC ratios met the stricter 0.80 to 1.25 equivalence bounds. Study treatments were generally well‐tolerated. In conclusion, co‐administration with TIRA did not alter the exposure of LEVO/EE, and accordingly LEVO/EE containing oral contraceptives can serve as a contraception method for participants on TIRA 160 mg (or lower) daily doses.

Evaluation of comedogenic potential of a moisturizer venusia max lotion (PAMA free)

: Being commonly used skin care products, comedogenic potential of moisturizers should be assessed. : The aim of the study was to evaluate the comedogenic potential of a moisturizer Venusia Max Lotion (paraben-, alcohol-, mineral oil-, animal origin-(PAMA) free) when applied topically to the skin compared to the controls. : Double-blind, single-center, comparative study conducted at private institute in Mumbai, India: Approximately 0.025 gm of the test product and 0.025 ml of positive control (coconut oil) and negative control (glycerin) were applied and occluded under a patch on the upper back of healthy female participants. Patch application and removal were made 12 consecutive times on alternate days for each participant. On the last day, approximately 2 hours after patch removal, a follicular biopsy was taken for all participants on all product application zones. : Data analyzed with descriptive statistics using the SPSS software version 10.0.: Data from a total of 19 participants was analyzed. The mean age was 35.32 years. The mean comedone grade for Venusia Max Lotion (PAMA free) was significantly lower compared to the positive control (Coconut Oil) (1.00 vs. 2.11, respectively; P=.001). The mean comedone grade was 0.79 for negative control (Glycerine) which is nearly similar to that of the test product. The moisturizer product Venusia Max Lotion (PAMA free) is non-comedogenic as compared to positive control. Thus, it can be considered for moisturizing purposes without the fear of comedogenicity.

In vivo evaluation of topical ascorbic acid application on skin aging by 50MHz ultrasound.

Ascorbic acid (AA) is a powerful antioxidant capable of acting significantly both in the prevention and treatment of the skin aging process. One way to assess the in vivo efficacy of anti-aging treatments is by using the high-frequency ultrasound (HFUS) skin image analysis technique, a non-invasive approach that allows for a new level of evaluating the effectiveness of dermatological and cosmetic products. The aim of the present study was to assess the performance of a topical emulsion of liquid crystalline structures containing AA using the 50MHz HFUS skin image analysis method. Twenty-five healthy female participants between 35 and 60years were included, all of whom randomly applied a placebo formulation and an AA-containing formulation to each forearm, once a day, for 30days. HFUS measurements were performed before using the products (T0), 2h later (T2h), and after 30days of use (T30d). The analyzed parameters included total skin, dermal, and epidermal echogenicity; variation and mean thickness of total skin, the epidermis and dermis; and surface roughness. Statistical analyses were performed using the Friedman test, followed by Dunn's test for comparisons of multiple means (α=0.05). A significant increase in total skin and dermal echogenicity was observed after topical AA application. Our findings suggest that collagen synthesis significantly increased after topical therapy with AA, which was responsible for the increment in dermal echogenicity. This study showed, through the HFUS technique, that the topical use of AA promoted dermal redensification after 30days of application.

Pharmacokinetics of Subcutaneous Dupilumab Injection With an Autoinjector Device or Prefilled Syringe.

Dupilumab, a human monoclonal antibody against interleukin‐4 receptor alpha, has demonstrated efficacy and an acceptable safety profile in adult and pediatric patients with moderate‐to‐severe atopic dermatitis (AD) and other type 2 inflammatory diseases. Dupilumab is available in 200‐ and 300‐mg strengths as a prefilled syringe with a needle shield (PFS‐S), and more recently as an autoinjector (AI) device. This study was designed to assess the pharmacokinetic (PK) comparability of a single subcutaneous (SC) dose of dupilumab 200 mg, delivered by 2 different devices, AI (test) versus PFS‐S (reference). A total of 130 healthy male and female participants were enrolled in this phase 1 parallel design study, with 128 evaluable for PK. Following dupilumab 200‐mg SC injection, dupilumab exposure in serum was similar for both AI and PFS‐S. The geometric mean ratios of PK parameters with 90% confidence intervals were 1.08 (0.97‐1.21) for maximum serum concentration (Cmax) and 1.11 (0.96‐1.28) for area under the serum concentration–time curve until the last quantifiable concentration (AUClast). Dupilumab administration by both devices was well tolerated, and there were no serious adverse events, or severe treatment‐emergent adverse events experienced during the study. Overall, exposure to dupilumab 200 mg was comparable when administered via the AI or PFS‐S devices in healthy male and female study participants.

Neuromuscular recruitment strategies of the vastus lateralis according to sex.

AimDespite males typically exhibiting greater muscle strength and fatigability than females, it remains unclear if there are sex‐based differences in neuromuscular recruitment strategies e.g. recruitment and modulation of motor unit firing rate (MU FR) at normalized forces and during progressive increases in force.MethodsThe study includes 29 healthy male and 31 healthy female participants (18‐35 years). Intramuscular electromyography (iEMG) was used to record individual motor unit potentials (MUPs) and near‐fibre MUPs from the vastus lateralis (VL) during 10% and 25% maximum isometric voluntary contractions (MVC), and spike‐triggered averaging was used to obtain motor unit number estimates (MUNE) of the VL.ResultsMales exhibited greater muscle strength (P < .001) and size (P < .001) than females, with no difference in force steadiness at 10% or 25% MVC. Females had 8.4% and 6.5% higher FR at 10% and 25% MVC, respectively (both P < .03), while the MUP area was 33% smaller in females at 10% MVC (P < .02) and 26% smaller at 25% MVC (P = .062). However, both sexes showed similar increases in MU size and FR when moving from low‐ to mid‐level contractions. There were no sex differences in any near‐fibre MUP parameters or in MUNE.ConclusionIn the vastus lateralis, females produce muscle force via different neuromuscular recruitment strategies to males which is characterized by smaller MUs discharging at higher rates. However, similar strategies are employed to increase force production from low‐ to mid‐level contractions. These findings of similar proportional increases between sexes support the use of mixed sex cohorts in studies of this nature.

Stress dynamically reduces sleep depth: temporal proximity to the stressor is crucial.

The anticipation of a future stressor can increase worry and cognitive arousal and has a detrimental effect on sleep. Similarly, experiencing a stressful event directly before sleep increases physiological and cognitive arousal and impairs subsequent sleep. However, the effects of post- vs. pre-sleep stress on sleep and their temporal dynamics have never been directly compared. Here, we examined the effect of an anticipated psychosocial stressor on sleep and arousal in a 90-min daytime nap, in 33 healthy female participants compared to an anticipated within-subject relaxation task. We compared the results to an additional group (n = 34) performing the same tasks directly before sleep. Anticipating stress after sleep reduced slow-wave activity/beta power ratio, slow-wave sleep, sleep spindles, and slow-wave parameters, in particular during late sleep, without a concomitant increase in physiological arousal. In contrast, pre-sleep psychosocial stress deteriorated the same parameters during early sleep with a concomitant increase in physiological arousal. Our results show that presleep cognitions directly affect sleep in temporal proximity to the stressor. While physiological arousal mediates the effects of presleep stress on early sleep, we suggest that effects during late sleep originate from a repeated reactivation of mental concepts associated with the stressful event during sleep.

Efficacy and Safety of Dietary Undenatured Type II Collagen on Joint and Motor Function in Healthy Volunteers: A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study

Objective: Prevalence of osteoarthritis (OA) is increasing alarmingly worldwide. Slowing down the progression of OA and diverse locomotive organ disorders is gaining interest in improving the quality of life (QOL) and extending healthy life-span. In a pilot study, intake of a small amount of undenatured type II collagen exhibited suppression of damage to the articular cartilage via oral immune tolerance. It also demonstrated improvement of knee and joint flexibility and mobility with continued intake of undenatured type II collagen (NEXT-II®) derived from chicken sternum cartilage. This randomized, double-blind, placebo-controlled, parallel-group clinical investigation (RCT) evaluated the efficacy and safety of 12 weeks of regular intake of NEXT-II® on joint and motor function in healthy Japanese male and female participants (aged 20 to <75 years). Method: Sixty-four participants were randomized to receive either NEXT-II® (undenatured type II collagen 3.2 mg/d) or placebo over a period of 12 consecutive weeks. Efficacy on joint and motor functions were evaluated measuring knee passive range of motion as the primary outcome; the Japan Knee Osteoarthritis Measure (JKOM), Visual Analog Scale (VAS) for knee discomfort, and motor functions (10-meter walking and stair-climbing test) as the secondary outcomes; and Japan Low back pain Evaluation Questionnaire (JLEQ) and VAS for lower back discomfort as the exploratory outcomes. Results: Fifty-eight participants (placebo = 28; NEXT-II® group = 30) completed the study. In the assessment of knee passive range of motion, significant improvements in “flexion” and “flexible angle (range)” were observed in the NEXT-II® group at 4, 8, and 12 weeks of treatment. NEXT-II® induced significant improvements in JKOM, VAS for knee and lower back discomfort, 10-meter walking test, stair-climbing test, and JLEQ. Conclusions: Results demonstrate that undenatured type II collagen is safe and efficacious in improving knee flexibility and mobility, reducing knee and lower back pain, and enhancing motor function.

Ergonomic Risk Assessment of Hairdressers Using Rapid Entire Body Assessment

Work-related musculoskeletal disorders (WRMSDs) are one of the most prevalent causes of occupational injury and disability in both developed and developing nations, affecting a wide range of jobs. Hairdresser in their careers faces many harmful factors, including WRMSDs, especially in the neck, waist and shoulder areas. The study groups comprised 5 healthy males and 8 healthy female participants that work at the hair dresser saloons in Turkey. Hair-coloring and hair-cutting were the most common tasks completed by participants. The population ranged in age from 18 to 45 years old. The respondents' average age, height, and weight, as well as their standard deviations were 33.15 ± 8.97 years, 166.38 ± 8.84 cm, and 68.31 ± 10.14 kg, respectively. The aim of this research was to investigate the individual and occupational risks associated with the tasks on the prevalence and consequence of WRMSDs. In this descriptive analytical study, the risk of WRMSDs was evaluated using the Rapid Entire Body Assessment (REBA) method. The REBA results showed that working postures should be changed as soon as possible