Adult Female Volunteers Research Articles

Normalization technique to build patient specific muscle model in finite element head neck spine.

Finite element models of the head and neck are widely used in automotive and clinical fields to understand spinal biomechanics. These models are developed based on CT and MRI scans of the subjects, but historically the muscle data are obtained from cadaveric specimen. The cadaver data is often obtained from older specimens which commonly have undergone degenerative changes resulting in reduction in muscle cross section area. The objective of the current study is to compare the muscle cross-section area used by various finite element models of neck muscles used in the literature and to develop a normalization technique to scale the MRI muscle cross-section area with those available in the literature. Four male and seven female healthy asymptomatic young adult volunteers enrolled in the study after obtaining necessary approval from Institutional Review Board. T1 and T2 weighted magnetic resonance imaging was performed in neutral upright sitting position wearing military helmet. Muscle cross sectional area was obtained for multifidus muscles from the MRI images. Data was compared with those in the literature. Based on the literature review of prior studies, the cross-sectional area of cadaver specimens was smaller than the MRI obtained muscle area. Multifidus muscle scaling factor was obtained by ratio of sum of MRI cross section area with that of cadaver data. Based on the analysis, the scaling factor for male data is 1.6 and for female data is 1.3. the cadaver data can be multiplied by the scaling factor to obtain the MRI specific cross-sectional area. A Normalization technique was developed for scaling MRI data into finite element model. This technique can be used in developing subject specific finite element model of spine which has applications in clinical, automotive, and military environment.

Vitamin D: Between the brightness of the sun and the darkness of depression

IntroductionThe scientific literature suggests a relationship between vitamin D (VitD) and the onset, treatment and prognosis of depression. However, this line of research continues to be controversial. The aim of the study was to analyse the relationship between depression and VitD values, controlling for the influence of the season. Material and methodsObservational and cross-sectional study. The sample was made up of 150 adult female volunteer participants (aged between 28 and 78 years). The sample was stratified into three groups: a) depression without treatment, b) depression under treatment with antidepressants, and c) without depression (control). VitD values (ng/ml) were compared. ResultsSignificant differences were found between the three groups surveyed. The group of participants with depression without treatment obtained the lowest VitD values (mean 18.62ng/ml; SD 8.42), compatible with severe insufficiency. The group of participants with depression in treatment obtained higher values than the previous group, although in an insufficient range (mean 23.80ng/ml; SD 11.30). The third group (control) obtained the highest values and in accordance with the desirable range (mean 30.19ng/ml; SD 10.21). There were no age differences between the groups. When controlling for possible effects of the season, the previous differences in VitD between the three groups were maintained, with an evident decrease of all the mean levels in the winter period. ConclusionsDepression is associated with insufficient VitD values. Treatment with antidepressants improves these values, although they continue to be insufficient. The findings of this study reinforce the evidence for an association between depression and VitD.

Cognitive function in female patients with chronic functional constipation

IntroductionChronic functional gastro-intestinal disorders can affect cognitive functioning of patients (1). Wong et al (2) showed attentional and executive function impairment, Aizawa et al. (3) found impairment of cognitive plasticity and activity of frontal and temporal arias of brain during performing tests in these patients.ObjectivesAssessing of cognitive functioning of the female patients with chronic functional constipation.Methods42 Rome IV adult female patients with chronic functional constipation and 26 adult normative female volunteers were tested with Brief Assessment of Cognition in Schizophrenia (BACS).ResultsBoth groups were comparable by age (patients’ group 29,5±6,1, volunteers’ group 28,5±9,6, ns) In both groups subjects demonstrated normal level of cognitive functioning but the scores of the patients were closer to the lower level than the scores of the volunteers. The difference was significant in composite scores and in several other scores (Tab.1). Table1.BACSPatients (n=42)Volunteers (n=26)p-levelVerbal Memory49,5± 10,658,8± 7,10,0002Work memory48,2±10,151,7±8,4nsMotor token51,3±10,559,8±10,40,003Verbal fluency52,1±11,556,5±9,9nsSymbol coding45,1±8,454,8±12,70,015Tower of London (planning)50,2±10,757,6±10,20,015Composite scores49,1 ±10,159,9 ±7,40,0001ConclusionsThe findings of the study once more indicate some link between gastrointestinal dysfunction and cognitive functioning. Even these slight decrease in some aspects of cognition from normal population could have negative impact on everyday functioning. The origin of this link is still under question.DisclosureNo significant relationships.

Roles of childhood maltreatment, personality traits, and life stress in the prediction of severe premenstrual symptoms

BackgroundAbout 3% to 8% of women of fertile age are thought to have premenstrual dysphoric disorder (PMDD), which is regarded as a serious form of premenstrual syndrome (PMS), although the details of this common condition remain unclear. The aim of this study was to analyze the interrelations of childhood maltreatment, personality traits, and life stress in the etiology of PMS/PMDD.MethodsA total of 240 adult female volunteers from a community in Japan were investigated, using the following 5 questionnaires: Patient Health Quesstionaire-9, Child Abuse and Trauma Scale, Temperament and Character Inventory (TCI), Life Experiences Survey, and premenstrual dysphoric disorder (PMDD) scale. The questionnaire data were subjected to path analyses to clarify the association between childhood maltreatment and the severity of premenstrual symptoms, mediated by personality traits and life stress.ResultsThe 2 path analysis models showed that high harm avoidance (HA) on the TCI and low self-directedness (SD) on the TCI had significant direct effects on the severity of premenstrual symptoms. Moreover, childhood maltreatment was associated with the severity of premenstrual symptoms, both directly and indirectly through personality traits.ConclusionOur findings suggest that HA on the TCI might be a risk factor for severe premenstrual symptoms among general women and furthermore that SD on the TCI may be a protective factor. In addition, childhood maltreatment is associated with severe premenstrual symptoms both directly and indirectly through personality traits.

Skin occlusive performance: Sustainable alternatives for petrolatum in skincare formulations.

The emollients are important ingredients used in skincare formulations that can act as moisturizing agents through their occlusive potential, preventing skin water loss. Consumer interest in natural and sustainable products has grown considerably in the last few years, requiring efforts from the cosmetic industry to design products with raw materials of natural, organic, and sustainable origin. Thus, it is essential to improve the knowledge about the behavior of cosmetic raw materials that can be used as sustainable alternatives to synthetic ingredients. This work aimed to evaluate the occlusive performance of different vegetable oils used as emollients in skincare cosmetics, through comparative analysis with petrolatum, a synthetic emollient with a high occlusive skin potential. The study included 80 healthy female adult volunteers. TEWL measurements were performed before and after 15min, 2 and 6h of emollients application on the forearms of the research participants. All research participants provided written informed consent. The results obtained showed that the vegetable oils were effective in providing an occlusive effect on the skin. When compared to the petrolatum, the vegetable oils did not provide a high immediate skin occlusion effect. However, most of them showed a skin occlusion performance comparable to petrolatum throughout the 6h time course. Vegetable oils can be used as a sustainable alternative to synthetic emollients, and they are promising in replacing petrolatum in skincare formulations with respect to the occlusion effect of the skin. The vegetable oils did not provide a high immediate skin occlusion effect (15min post-application) as the petrolatum, which is known to have increased occlusion properties. However, most of them showed a skin occlusion performance comparable to petrolatum throughout the 6-hour time course.

Survey of lower urinary tract symptoms in United States women using the new lower urinary tract dysfunction research Network-Symptom Index 29 (LURN-SI-29) and a national research registry.

An online bladder health survey was administered to national registry volunteers to: (1) determine the feasibility of using ResearchMatch for studying lower urinary tract symptoms (LUTS); (2) pilot the new, comprehensive Lower Urinary Tract Dysfunction Research Network Symptom Index-29 (LURN-SI-29) and determine its ability to detect known associations with LUTS; and (3) explore novel areas of bladder health in community-based women. A cross-sectional web-based survey was administered to a random sample of ResearchMatch adult female, transgender and non-binary volunteers. Participant demographics, health characteristics, the LURN-SI-29, and LUTS-related experiences were collected. A total of 1725 ReseachMatch volunteers with a mean age of 44.0 years completed the study and were eligible for the analysis. Participants were primarily white, cisgendered, highly educated, nulliparous, and premenopausal. The median LURN-SI-29 score was 17 (interquartile range: 11-26). More than half the sample reported urinary urgency (71.0%), nocturia (65.7%), and stress incontinence (52.3%) a "few times" or more in the last 7 days. Approximately half reported sensation of incomplete bladder emptying (49.6%) with one-third reporting urgency incontinence (37.6%); notably, 52.6% of respondents reported being at least "somewhat" bothered by LUTS. LURN-SI-29 scores increased with age, body mass index, decrements in self-reported health, medical comorbidity, parity, menopausal status, and urinary symptom bother, providing evidence of convergent validity. LURN-SI-29 scores varied by race and education, with the lowest scores in Asian and highly educated women. Overall, the prevalence and spectrum of LUTS in an online research registry of women volunteers were high and comparable to other population-based samples. The new LURN-SI-29 demonstrated its ability to detect expected associations with demographic and health characteristics in a nonclinical population.

Patients with Chronic Constipation Experience Psychological Stress as Measured By the POMS2 Test and Salivary Stress Markers

Background: Psychological stress is known to lead to the pathogenesis and exacerbation of constipation. Therefore, it is important to understand the stress status in patients with constipation to treat constipation and prevent its exacerbation. Until now, the stress status of patients has been subjectively evaluated mainly by questionnaires, but in recent years it has become possible to objectively evaluate it by measuring stress markers in saliva. This study evaluated the stress status in patients with chronic constipation from both subjective and objective perspectives. Methods: Eighty-four adult females with chronic constipation and 20 healthy adult female volunteers as controls were enrolled in this study. All subjects were subjectively evaluated for their mood using the shortened Profile of Mood StatesSecond Edition (POMS2) and objectively evaluated by measuring salivary stress markers, such as cortisol, chromogen A, oxytocin, and secretory immunoglobulin A (s-IgA) using Enzyme-Linked Immuno Sorbent Assay. Results: In the POMS2 analysis, the T-scores of negative mood subscales, such as Anger–Hostility, Confusion–Bewilderment, Depression–Dejection, Fatigue–Inertia, and Tension–Anxiety were significantly higher in the constipation group than in the control group. In contrast, positive mood subscale scores, such as Vigor–Activity and Friendliness were not significantly different between the two groups. These results significantly increased the total mood disorder score, which comprehensively reflects a negative mood in the constipation group compared to the control group. In the stress marker analyses, cortisol, chromogranin A, and s-IgA concentrations in the constipation group were significantly higher than those in the control group. In contrast, the oxytocin concentration in the constipation group tended to be lower than in the control group. Conclusion: These results suggest that patients with constipation have more stressful negative emotions, such as anxiety, depression, tension, and fatigue than healthy individuals. This study will be important and useful when considering the treatment, exacerbation, or prevention of constipation.

Effects of Ramadan fasting on some biochemical parameters

Introduction: Holy month Ramadan lasts for about 29-30 days. It is mandatory for all adult individuals of the Islamic faith to fast during the holy month of Ramadan. During this period, healthy Muslims do not eat or drink (i.e., total abstinence from food and fluids) and refrain from tobacco, daily from pre‑dawn until dusk. Materials and Methods: The present study included healthy adult male and female Muslim volunteers from different towns in the Republic of North Macedonia. The number of subjects in the study was 195. Blood samples from all subjects were collected twice during the study - once 2-3 days prior to the beginning of Ramadan and then again, the last day of Ramadan fasting. The following biochemical parameters were taken into consideration: total cholesterol, triglycerides, HDL cholesterol, glucose, insulin, total proteins, albumin, total and direct bilirubin, urea, creatinine and uric acid. Results: It was observed that compared to pre‑fasting levels, total cholesterol (TC) and triglycerides (TG) were significantly decreased (P=0.000) and high‑density lipoprotein cholesterol (HDL‑C) level had significantly increased (P=0.000); total proteins were significantly increased (P=0.000); albumins were significantly increased (P=0.004); urea was significantly increased (P=0.004); total and direct bilirubin were significantly increased (P=0.000), glucose was significantly increased (P=0.000); there was no change in insulin levels (P<0.1) Conclusion: This study showed that Ramadan fasting has an effect on biochemical parameters. We can conclude that reduction in total cholesterol and triglycerides along with a rise in levels of HDL‑C have beneficial effects on lipid profile post-Ramadan fasting period.

Influence of facial type on attractiveness of vertical canine position from the perspective of orthodontists and laypeople.

To evaluate the attractiveness of changes in vertical position of maxillary canines in frontal smiles of different facial types, and to evaluate the esthetic perceptions of orthodontists and laypeople, and the influence of facial type on these perceptions. Three adult female volunteers were selected as individuals with normal, vertical, and horizontal growth patterns. Frontal posed smile photographs were digitally altered by adjusting vertical positions of the maxillary canines above, below, or coincident with the incisal line in increments of 0.5 mm within a range of 1 mm of extrusion and intrusion. For assessment, a web-based survey was formed with 18 images (six images for each model). A scale was present underneath each image, graded from 0 to 10 (0: unattractive; 10: the most attractive). Images were rated by 233 participants (105 orthodontists; 128 laypeople). Orthodontists scored 0-mm images significantly as the highest in all groups. Laypeople scored significantly higher for -0.5 mm images regardless of facial type. The lowest scored images were -1 mm (except for horizontal pattern) and +1 mm images. Mean values of scores given by men were higher (P < .05). Orthodontists favored ideal dental alignment and preferred the incisal edges of central and canine teeth to be at the same level. Laypeople preferred a smoother smile arc than orthodontists and found harmony with the soft tissue more attractive. Facial type affected perceptions of the vertical changes of maxillary canines.

Evaluation of Uroflowmetry Curve Patterns and Nomogram Construct in Healthy Nulliparous Female Adults.

The aims of the study were to construct uroflowmetry nomograms, evaluate uroflowmetry flow rate patterns, and graphically illustrate overlaid uroflowmetry curves in nulliparous female adult volunteers. We performed a prospective cross-sectional study evaluating uroflowmetry curve and flow rate patterns on a cohort of nulliparous female adult volunteers. Primary outcome was construction of uroflowmetry maximum and average flow rate nomograms. Secondary outcomes included evaluation of uroflowmetry flow rate patterns and graphical illustrations of overlaid uroflowmetry curves. Uroflowmetry printouts were overlaid and used to create a model of uroflow patterns, and nomogram curves were analyzed in 5 groups based on voided volumes. We enrolled 164 participants and 158 had voided volumes between 50 mL and 800 mL. Participants' mean age and body mass index were 25 years and 23, respectively. Maximum and average flow rate nomograms were created, and analysis of uroflow parameters was performed. Median voided volume was 241 mL (149-431 mL), the median maximum flow was 29 mL/s (20-38 mL/s), and the median average flow was 15 mL/s (10-19 mL/s). Participants were divided into 5 groups based on voided volumes. The nomogram patterns for each voided volume group were visually different from typical nomogram patterns. Uroflowmetry curves and flow rates vary significantly according to voided volume. Our study suggests that in normal healthy nulliparous female adults there is likely a broader range of normal flow rates and uroflowmetry curves than what has been previously reported. Further research is needed to investigate the accuracy of these finding.

Quercetin LipoMicel—A Novel Delivery System to Enhance Bioavailability of Quercetin

Background: Quercetin, a flavonoid found in plant-based foods, has a range of biological activities that may be beneficial for human health. The pharmacokinetic profile of quercetin remains, however, a limiting factor for its use as a nutritional supplement. Quercetin LipoMicel®—a novel delivery system encapsulating quercetin into a liquid micelle matrix—has been designed to address the low bioavailability issue associated with non-conjugated forms by improving the absorption of quercetin. Objective: The purpose of this study was to evaluate the solubility and gastrointestinal absorption of quercetin in a novel Quercetin LipoMicel delivery system in healthy adult volunteers by comparing it with free quercetin and another commercial quercetin product. Several pharmacokinetic parameters were compared between these three formulations. Methods: Twelve healthy adult male and female volunteers aged between 21 and 65, with BMIs under 30, participated in a non-blinded, crossover bioavailability study conducted with three quercetin products. Each treatment contained a total dose of 500 mg quercetin. Capillary whole blood samples from participants were collected serially at intervals from 0–24 hours. Quercetin concentrations were detected and measured by ultra-performance liquid chromatography (UHPLC) coupled to a Thermo QExactive Orbitrap Mass Spectrometer. Solubility of quercetin in water and simulated gastrointestinal media was determined by UHPLC. Results: Oral absorption of quercetin was significantly enhanced with the LipoMicel delivery system compared to free quercetin. Improvements in in vitro gastric stability and intestinal solubility were observed with LipoMicel, leading to significantly higher blood concentration and enhanced duration of a stable concentration of quercetin in the body. Compared to free quercetin, 8- and 9-fold increases in AUC and Cmax were attained with the LipoMicel delivery system, and 10-fold higher quercetin plasma concentrations detected at 12 hours after administration. Conclusions: Quercetin LipoMicel represents an efficient delivery system for augmenting the bioavailability of quercetin in vivo. Significantly higher blood concentrations and a sustained release of quercetin over the study period was achieved following the administration of quercetin via the LipoMicel technology. Optimization in the in vivo bioavailability of quercetin may promote its salutary effects.

Gender Differences in the Extended Theory of Planned Behaviour on Smoking Cessation Intention in Young Soldiers.

Background: The theory of planned behaviour (TPB) explanation of smoking cessation intentions consists of gender differences. The purpose of this study is to adopt the extended TPB to discuss factors influencing the smoking cessation intentions of young adult volunteer soldiers and to further compare the respective factors for both genders. Methods: This is a cross-sectional study. Data were collected from 139 and 165 male and female volunteer soldiers who smoked, respectively. Research participants completed a self-administered questionnaire that comprised items pertaining to the participants’ demographic characteristics, smoking behaviours, smoking cessation experiences, social environments, and TPB variables. Results: Subjective norms (friends) are a positive key factor for young adult male (β = 0.033, p = 0.012) and female (β = 0.076, p < 0.001) volunteer soldiers’ smoking cessation intentions, and perceived behavioural control is a key factor for male young (β = 0.226, p = 0.040) adult volunteer soldiers’ smoking cessation intention. The extended TPB accounted for 27.9% and 53.2% of the variance in the intention to quit smoking in the male and female volunteer soldiers, respectively. Conclusions: We suggest that smoking cessation strategies can reinforce gender-specific intervention strategies to assist young adult volunteer soldiers in smoking cessation.

Safety, pharmacokinetics and pharmacodynamics of TAK-418, a novel inhibitor of the epigenetic modulator lysine-specific demethylase 1A.

AimsDysregulation of histone methylation epigenetic marks may result in intellectual and developmental disability, as seen in Kabuki syndrome. Animal data suggest that increasing histone methylation by inhibiting lysine‐specific demethylase 1A (LSD1) may improve cognitive outcomes in a model of Kabuki syndrome. TAK‐418 is a novel LSD1 inhibitor, developed as a potential therapeutic agent for central nervous system disorders such as Kabuki syndrome. Here, we report safety, tolerability, pharmacokinetic and pharmacodynamic profiles of single and multiple doses of TAK‐418 (ClinicalTrials.gov: NCT03228433, NCT03501069).MethodsTwo randomized, double‐blind, placebo‐controlled, phase 1 studies of oral TAK‐418 were performed, a first‐in‐human single‐rising‐dose (SRD) study (5–60 mg) in healthy adult male and female volunteers (placebo, n = 10; TAK‐418, n = 30), and an SRD (120–160 mg) and multiple‐rising‐dose (MRD) study (20–160 mg once daily for 10 days) in healthy female volunteers (placebo, n = 2 [SRD] and n = 6 [MRD]; TAK‐418, n = 6 [SRD] and n = 18 [MRD]).ResultsTAK‐418 was well tolerated. No clinically significant changes in laboratory test results or vital signs were observed and no serious adverse events were reported. TAK‐418 had a nearly linear pharmacokinetic profile, with rapid absorption and short terminal half‐life across the evaluated dose range. No obvious accumulation was observed after daily administration for 10 days. Administration with food delayed peak plasma concentrations but overall exposure was unaffected. TAK‐418 rapidly crossed the blood–brain barrier and generally showed a dose‐dependent response in the peripheral pharmacodynamic biomarker formyl‐flavin adenine dinucleotide.ConclusionThe brain‐penetrant LSD1 inhibitor TAK‐418 was well tolerated, with pharmacokinetic and pharmacodynamic effects that support further investigation.

MO283IMPACT OF VIS649, AN APRIL-NEUTRALIZING IGG2 MONOCLONAL ANTIBODY, ON TETANUS- AND DIPHTHERIA-TOXOID VACCINATION-ELICITED IMMUNE RESPONSES IN HEALTHY VOLUNTEERS: PHASE 1, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY

Abstract Background and Aims VIS649, a humanized immunoglobulin G (IgG2) monoclonal antibody that binds to and blocks the biological actions of a proliferation-inducing ligand (APRIL), is in clinical development as a potential treatment for immunoglobulin A (IgA) nephropathy (IgAN). In a Phase 1 study, VIS649 was associated with dose-dependent reductions in serum IgA, IgG and IgM, which were reversible and showed a dose-response effect with respect to time-to-recovery. The aim of the present analysis was to determine if VIS649 suppression of APRIL influences antibody responses to tetanus and diphtheria toxoid vaccination. Method This was a Phase 1, randomized, double-blind, placebo-controlled, single ascending dose study of VIS649 in healthy adult male and female volunteers (ClinicalTrials.gov identifier: NCT03719443). In one cohort within the study, participants were randomized in a 2:1 ratio to receive intravenous administration of VIS649 6.0 mg/kg or placebo, followed by a vaccine composed of tetanus and diphtheria toxoids (TENIVAC®, Sanofi Pasteur Limited), in order to evaluate the effect of VIS649 on recipients’ ability to generate a vaccine booster response (exploratory endpoint). Participants received intravenous administration of study drug on Day 1, were discharged from the institution on Day 2, received a single intramuscular dose of vaccine at the Week 4 visit, and were followed for 16 weeks in total on an outpatient basis. Blood samples were taken at regular intervals, and anti-tetanus toxoid and anti-diphtheria toxoid IgG, IgM and IgA quantitative ELISA assays were performed. Tetanus and diphtheria anti-toxoid IgG titers ≥0.1 IU/mL are generally considered to be protective. Results In the vaccination cohort, 15 participants were randomized and dosed with study drug or placebo, of whom 14 completed the study, and one participant who received VIS649 was lost to follow-up prior to receiving the vaccine. Both groups (placebo and VIS649) demonstrated increased tetanus anti-toxoid IgG titers following immunization, with a mean 7.9-fold increase in IU/mL at Week 6 for placebo recipients and a mean 6.4-fold increase in IU/mL for VIS649 recipients (Figure). At visits after Week 6, tetanus anti-toxoid IgG titers declined faster in the VIS649 group than in the placebo group (consistent with the reduction in total IgG associated with VIS649 administration) but remained above the protective threshold of 0.1 IU/mL for all participants throughout the study. Similar trends were observed for diphtheria anti-toxoid IgG titers, with a mean 5.5-fold increase in IU/mL at the Week 6 visit for placebo recipients and a mean 5.1-fold increase for VIS649 recipients (Figure). There was no evidence of tetanus- or diphtheria-toxoid elicited IgM responses in either the placebo or VIS649 groups, consistent with the recall nature of the vaccination. In a post hoc analysis, pre-existing serum tetanus/diphtheria anti-toxoid IgA titers fell between Day 1 and Week 4 in the VIS649 group, consistent with the overall suppression of total serum IgA, were boosted after vaccination in both groups, and declined faster in the VIS649 recipients thereafter. Conclusion VIS649 treatment did not interfere with participants’ ability to mount an antigen-specific serum IgG or IgA boost response to tetanus and diphtheria toxoid vaccination. There was no evidence of tetanus- or diphtheria-specific IgM responses in either the placebo or VIS649 groups, consistent with recall vaccination exposure. These data indicate that qualitative antibody responses are preserved during APRIL suppression.

MO258SAFETY, TOLERABILITY, PHARMACOKINETICS AND PHARMACODYNAMICS OF VIS649, AN APRIL-NEUTRALIZING IGG2 MONOCLONAL ANTIBODY, IN HEALTHY VOLUNTEERS: PHASE 1, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, SINGLE ASCENDING DOSE STUDY

Abstract Background and Aims Immunoglobulin A (IgA) nephropathy (IgAN) is a glomerulonephritis characterized by the presence of circulating and glomerular immune complexes containing galactose-deficient (Gd) IgA1. A proliferation-inducing ligand (APRIL), a member of the tumor necrosis factor superfamily of ligands, is thought to play a key role in the pathogenesis of IgAN by virtue of its role in class-switching to IgA production. VIS649, a humanized immunoglobulin G (IgG2) monoclonal antibody that binds to and blocks the biological actions of APRIL, is in clinical development as a potential treatment for IgAN. The primary objective of this first-in-human study was to evaluate the safety and tolerability of VIS649 in healthy volunteers. Secondary objectives included characterization of the pharmacokinetics (PK) and pharmacodynamics (PD) of VIS649. Method This was a Phase 1, randomized, double-blind, placebo-controlled, single ascending dose study of VIS649 in healthy adult male and female volunteers (ClinicalTrials.gov identifier: NCT03719443). The study was conducted in sequential dosing cohorts. The first four cohorts (0.5, 2.0, 6.0, and 12.0 mg/kg, respectively) each enrolled 9 participants (4 of Japanese descent and 5 of non-Japanese descent) who were randomized to VIS649 or placebo in a ratio of 7:2. In addition, a fifth cohort enrolled 15 adults randomized to receive VIS649 6.0 mg/kg or placebo (10:5), followed by tetanus/diphtheria vaccine challenge after 28 days (TENIVAC®, Sanofi Pasteur Limited; the effect of APRIL inhibition on vaccine response is described in a companion abstract). Participants received intravenous administration of study drug on Day 1, were discharged from the institution on Day 2, and were followed for 16–24 weeks on an outpatient basis. Standard safety assessments and blood sampling for PK and PD were performed at regular intervals. Results 51 participants were randomized and dosed with study drug, of whom 47 (92.2%) completed the study. VIS649 was well tolerated, with no serious adverse events (AEs) or AEs that led to study discontinuation. Most treatment-emergent AEs (TEAEs) were mild; the incidence and severity of TEAEs were not dose dependent. One participant in the 2.0 mg/kg group experienced a severe TEAE of syncope following phlebotomy that the investigator considered unlikely to be related to study drug. There was no clinically relevant effect of treatment on laboratory tests, vital signs, electrocardiogram parameters, or physical examinations. VIS649 had non-linear PK: half-life (t½) increased with dose, while drug exposure (AUC) increased in a greater than dose proportional manner. Serum IgA, Gd-IgA1, IgG, and IgM were reversibly suppressed in a dose-dependent manner following VIS649 administration. The maximum mean percentage reductions from baseline occurred at Week 12 for the 12.0 mg/kg dose: IgA, -57.2% (Figure); Gd-IgA1, -71.6% (Figure); IgG, -33.6%; and IgM, -67.2%. These reductions were reversible and showed a dose-response effect with respect to time-to-recovery. Mean free (non-VIS649 bound) serum APRIL levels decreased to the lower limit of quantification (50 pg/mL) for all VIS649 doses at Week 1, and also showed a dose-response effect with respect to time-to-recovery. No depletions in circulating lymphocyte populations were observed. There were no significant PK or PD differences between Japanese and non-Japanese participants. Conclusion A single dose of VIS649, up to 12.0 mg/kg, was safe and well tolerated in healthy adults and was able to suppress free serum APRIL to the lower level of quantification. Serum Gd-IgA1 decreased in parallel with total serum IgA and recovered in a dose-dependent manner following reappearance of free APRIL in serum. These data support the further clinical development of VIS649 as a potential treatment for IgAN.

Morphological changes in the respiratory system: an MRI investigation of differences between the supine and left lateral decubitus positions

ABSTRACT Preoperative serial imaging of the torso is typically carried out in the supine position (e.g. magnetic resonance imaging [MRI], CT), however, intraoperative patient positioning is often lateral, and for some procedures may involve deflation and/or ventilation of the lungs. This study examined the differences in lung anatomy between the supine and lateral decubitus positions. MRI data for 10 healthy female adult volunteers lying in supine and left lateral decubitus positions were analysed. 2D measurements in coronal, transverse and sagittal planes were used to calculate the cross-sectional area, height and width of the lungs and the shape of the diaphragm. 3D surface reconstructions of the lungs and bronchi were created to determine the volume change between positions. The volume of the right lung was found to increase due to the caudal shift of the insertion points of the right hemidiaphragm (mean volume increase of 25% ± 11, p ≪ 0.05). There was minimal change in the left lung parameters with no significant change in left lung volume between positions (mean volume change = 0% ± 44%, p > 0.05). This study presents new information characterising anatomical changes in the respiratory system when a patient is positioned in the lateral decubitus compared to supine position.

Artocarpus heterophyllus leaves extract improve facial skin in clay mask formulation

Artocarpus heterophyllus (A.heterophyllus) is one of plants that commonly used for skin care. This study aimed to formulate a clay mask preparation with the active ingredient A.heterophyllus 3% leaf extract and evaluating its activities in repairing facial moisture, smoothness, large pores, blemishes and wrinkles. The process of providing clay masks begins with the preparation of Artocarpus heterophyllus leaf etanol extracts with standardized quality, preparation of clay mask bases with guaranteed quality, mixing clay mask bases with extracts, testing the quality and stability and effectiveness of skin care tested. The extract of clay mask formulations were stable in storage, homogeneous, pH 5.6-6.3; drying time is 10-18 minutes, and does not irritate. Effectiveness testing was performed using a skin analyzer for 4 weeks of treatment in adult female volunteers. Test results after 4 weeks of treatment showed that the ethanol extract of A. heterophyllus leaves 3% was able to improve moisture (15.5%), smoothness (33.1%), pore size (60.1%), blemishes (50.2%) and facial wrinkles (61.5%). Statistically, significant effects were found in moisture and smoothnes of the facial skin (p < 0.05). This study concluded that ethanol extract of A. heterophyllus in concentration of 3% have benefit in refining facial skin.

Patients with Chronic Constipation Experience Psychological Stress as Measured by the Poms2 Test and Salivary Stress Markers

Background: Psychological stress is known to lead to the pathogenesis and exacerbation of constipation. Therefore, it is important to understand the stress status in patients with constipation to treat constipation and prevent its exacerbation. Until now, the stress status of patients has been subjectively evaluated mainly by questionnaires, but in recent years it has become possible to objectively evaluate it by measuring stress markers in saliva. This study evaluated the stress status in patients with chronic constipation from both subjective and objective perspectives. Methods: Eighty-four adult females with chronic constipation and 20 healthy adult female volunteers as controls were enrolled in this study. All subjects were subjectively evaluated for their mood using the shortened Profile of Mood States-Second Edition (POMS2) and objectively evaluated by measuring salivary stress markers, such as cortisol, chromogen A, oxytocin, and secretory immunoglobulin A (s-IgA) using Enzyme-Linked Immuno Sorbent Assay. Findings: In the POMS2 analysis, the T-scores of negative mood subscales, such as Anger–Hostility, Confusion–Bewilderment, Depression–Dejection, Fatigue–Inertia, and Tension–Anxiety were significantly higher in the constipation group than in the control group. In contrast, positive mood subscale scores, such as Vigor–Activity and Friendliness were not significantly different between the two groups. These results significantly increased the total mood disorder score, which comprehensively reflects a negative mood in the constipation group compared to the control group. In the stress marker analyses, cortisol, chromogranin A, and s-IgA concentrations in the constipation group were significantly higher than those in the control group. In contrast, the oxytocin concentration in the constipation group tended to be lower than in the control group. Interpretation: These results suggest that patients with constipation have more stressful negative emotions, such as anxiety, depression, tension, and fatigue than healthy individuals. This study will be important and useful when considering the treatment, exacerbation, or prevention of constipation. Funding: None to declare. Declaration of Interest: None to declare. Ethical Approval: This study was approved by the Ethics Committee of Juntendo University Hospital.

Clinical Pharmacokinetic Drug Interaction Potential of MenoAct851 in Adult, Female Healthy Volunteers

MenoAct851 (Varanasi BioResearch Pvt. Ltd., Varanasi, India) is a patented polyherbal formulation developed to manage menopause symptoms that can be taken along with other allopathic medicines. The present study aims to evaluate the drug interaction potential of MenoAct851 to inhibit cytochrome (CY) P450 in vitro in rats, and to measure its effects on simvastatin pharmacokinetic parameters in healthy human volunteers. CYP450-carbon monoxide assay of MenoAct851 was performed in rat liver microsomes to calculate the percentage inhibition. Fluorometric assays of CYP3A4 and CYP2D6 determined half maximal inhibitory concentration value. A double-blind, randomized, placebo-controlled drug interaction study of MenoAct851 was conducted in 24 healthy adult female volunteers aged 25 to 50 years. The selected volunteers were randomized to receive placebo or MenoAct851 500 mg BID PO for 14 days. On the 15th day, each group received 40 mg single-dose simvastatin. Blood samples were drawn at different intervals to measure simvastatin pharmacokinetic parameters. The mean (SD) CYP450 concentration of the diluted microsome sample was calculated and found to be 0.405 (0.12) nmol/mg. The inhibitory potential of MenoAct851 (41.16% [1.24%]) was found to be less than ketoconazole. Half maximal inhibitory concentration values of MenoAct851 on CYP3A4 and CYP2D6 were 11.96 (1.04) µg/mL and 15.24 (0.58) µg/mL, respectively, but they were higher than respective positive controls. There was no statistically significant difference between MenoAct851 and placebo groups concerning the pharmacokinetic parameters such as Cmax, Tmax, t½, and mean residence time of simvastatin; however, AUC showed a significant difference (P < 0.05) between the groups. MenoAct851 produced weaker interaction potential with CYP3A4 and CYP2D6 substrates based on in vitro assays, but the findings of clinical pharmacokinetic analysis indicate that MenoAct851 increased the AUC of simvastatin and simvastatin hydroxy acid. Therefore, coadministration of MenoAct851 might lead to drug-herb interaction, thereby affecting the therapeutic effect of CYP3A4 substrates. (Curr Ther Res Clin Exp. 2020; 81:XXX-XXX).

Efficacy and safety of a cosmeceutical regimen based on a combination of low molecular weight hyaluronic acid, placental peptides and extract of Malus domestica in improving signs of periorbital skin aging

Background: Periorbital wrinkle formation is a relatively early sign of skin aging. The public interest in the reversal of aging has increased significantly among demanding patients and aesthetic practitioners within the past decades. However, many aesthetic patients, whether young or old, prefer to avoid invasive procedures wherever possible, seeking natural-looking results.Therefore, physicians have had to respond to their patient's expectations. Objectives: This study aimed to evaluate whether the synergistic anti-aging activity of MF3 Placenta 3R serum product has an influence towards the treating of wrinkles as well as skin hydration, and skin elasticity in the periorbital area. Methods: 23 healthy adult female volunteers were instructed to apply MF3 Placenta 3R serum containing a mixture of low molecular weight hyaluronic acid (LMWHA), placental peptides and extract of Malus domestica around the eye area twice daily during the study period of eight weeks. The skin measurements were performed in the periorbital area by investigating the skin elasticity (Cutometer) and skin hydration (Corneometer). Patients questionnaires were answered at 59 days. Results: The findings of the study proved a moisturizing impact of MF3 Placenta 3R serum throughout the trial that transformed into significant improvements in periocular skin hydration and elasticity. Conclusion: The tested formulation of MF3 Placenta 3R serum appears to be effective and may stimulate the periorbital skin rejuvenation in a women 44 – 52 years, resulting in the clinical appearance of smoother skin with less visible wrinkling. Further randomized, controlled studies have to be done to confirm these results.