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Summary: West Nile virus (WNV), the most prevalent arthropod-borne virus (arbovirus) in the United States, is maintained in a cycle between Culex spp. mosquitoes and birds. Arboviruses exist within hosts and vectors as a diverse set of closely related genotypes. In theory, this genetic diversity can facilitate adaptation to distinct environments during host cycling, yet host-specific fitness of minority genotypes has not been assessed. Utilizing WNV deep-sequencing data, we previously identified a naturally occurring, mosquito-biased substitution, NS3 P319L. Using both cell culture and experimental infection in natural hosts, we demonstrated that this substitution confers attenuation in vertebrate hosts and increased transmissibility by mosquitoes. Biochemical assays demonstrated temperature-sensitive ATPase activity consistent with host-specific phenotypes. Together these data confirm the maintenance of host-specific minority variants in arbovirus mutant swarms, suggest a unique role for NS3 in viral fitness, and demonstrate that intrahost sequence data can inform mechanisms of host-specific adaptation.

Context: Maxillary expansion is the mainstay therapy for maxillary transverse deficiency. There has been a constant search for the most effective yet biologically friendly method of maxillary expansion, alternatives being, slow, rapid and semi rapid. Aims: The purpose of this study was to explore the outcome of palatal expansion achieved using a removable plate and low continuous forces brought about by a semi rapid screw activation protocol. Settings and Design: Retrospective study. Methods and Material: Plaster models of 56 consecutive patients treated for maxillary expansion were obtained pre-treatment (T0), post-expansion (T1), and post fixed appliance treatment (T2). The radiographic images of the models were traced using Image J software. Linear and angular measurements were evaluated to measure transverse change. Statistical Analysis Used: Interclass Correlation Coefficient [ICC] and Dahlberg's formula were used for reliability test. The differences in the mean values between the three duration groups [T0, T1 and T2] were analysed using Analysis of Variance (ANOVA). For multiple comparisons, a post hoc Tukey honestly significant difference (HSD) test was performed. Results: Significant increase in inter-molar, alveolar and palatal linear widths were observed from T0 to T1 with significant relapses from T1 to T2, with an overall net gain remaining at T2. Similarly, significant increases in all angular measurements were observed from T0 to T1 with significant relapses from T1 to T2 and an overall insignificant change at T2 as compared to T0. Conclusion: The appliance and protocol were effective in producing transverse expansion with minimal molar and alveolar tipping.

Background: The treatment of patients with cholelithiasis with common bile duct (CBD) stones is CBD clearance with cholecystectomy. While traditional teachings advocate waiting for 4–6-week post-endoscopic retrograde cholangiography (ERCP) with CBD clearance, recent studies favour an early laparoscopic cholecystectomy (LC). Hence, this study was conducted to evaluate the optimal timing of LC post-ERCP. Methods: We conducted a prospective observational study between March 2017 and October 2018. Patients diagnosed with cholelithiasis and CBS stones on ultrasonography or computed tomography were included. They were assigned to one of two groups (2 weeks) based on the time interval between ERCP and subsequent LC. Chi-square test was used to analyse the intraoperative and post-operative outcomes between the two study groups, Results: One hundred and forty patients were included in the study of which 69 underwent an early LC (

Summary: Misophonia is a disorder in which certain sounds produced by other people lead to intense negative reactions. It remains unknown how misophonia relates to other psychiatric conditions or impairments. To identify latent constructs underlying symptoms, we conducted a factor analysis consisting of items from questionnaires assessing symptoms of misophonia and other psychiatric conditions. One thousand forty-two participants completed the questionnaires and a social exchange task in which they either could (“controllable”) or could not (“uncontrollable”) influence future monetary offers from other people. Misophonia and obsessive-compulsive (OC) symptoms loaded onto the same factor. Compared with individuals with low Miso-OC factor scores, individuals with high scores reported higher perceived controllability of their social interactions during the uncontrollable condition and stronger aversion to social norm violations in the uncontrollable compared with the controllable condition. Together, these results suggest misophonia, and OC symptoms share a latent psychiatric dimension characterized by aberrant computations of social controllability.

Background Amebic liver abscess (ALA) contributes significantly to morbidity and mortality in patients of the developing world. Even though medical management is the primary modality of treatment, 15% of the cases are refractory and require intervention for drainage. Pigtail catheterization is inefficient and results in a long duration of hospital stay. So, we conducted a prospective observational study to determine the efficacy and safety of drainage of large ALA using a wide bore 24 French (Fr) drain compared with a conventionally used 10 Fr pigtail catheter. Materials and Methods A single center prospective observational study was conducted over a period of 5 years and data of 122 patients was collected. After starting empirical medical therapy, patients underwent drainage of ALA with either a 10 French pigtail or a 24 Fr drain. The primary outcome variables were resolution of clinical symptoms such as fever and pain in abdomen, length of hospital stay, and resolution of abscess on imaging at day 3. Secondary outcome was complications related to the procedures. Results Data of 122 patients was collected. Males constituted a vast majority (96%) of the study population and the fifth decade was the most common age group involved. Alcoholics had a higher chance of developing a large ALA. Sixty-eight patients underwent drainage of the ALA using a 24 Fr drain which resulted in faster resolution of symptoms (2.4 vs. 5.1 days, p-value 0.033), a shorter duration of catheter in situ (6.4 vs. 13.2, p-value 0.011), and a faster drainage of ALA (residual volume at day 3; 177 vs. 212 mL, p-value 0.021). Twenty-eight patients had a biliary communication of which 26 required therapeutic endoscopic retrograde cholangiopancreatography. Conclusion In patients with a large ALA, placement of a wide bore 24 Fr catheter hastens recovery of the patients when compared with drainage with a standard 10 Fr pigtail catheter. Placement of a biliary stent serves as a useful adjunct for their management and it may obliviate the need for a major biliary diversion surgery.

Aims: This study aims to compare clinical outcomes in patients of recurrent implantation failure (RIF), who had embryo transfer (ET) following a receptive (R) endometrial receptivity array (ERA) and a personalized embryo transfer (pET) after a nonreceptive (NR) ERA. Settings and Design: This was a retrospective observational study. Study Period: July 2013–September 2017. Subjects and Methods: Two hundred and forty-eight patients having unexplained RIF who underwent ERA test were included in the study. Clinical outcomes were compared between patients having a receptive (R) ERA and those having a NR ERA who underwent a pET-based on ERA. Statistical Analysis Used: Chi-square and t-test. Results: ERA predicted receptive (R) endometrium at P + 5 in 82.3% (204/248) patients and NR in 17.7% (44/248) patients. Average failed previous in vitro fertilization cycles were 3.67 ± 1.67 among receptive ERA patients and 4.09 ± 1.68 among NR ERA patients. Pregnancy rate (PR), clinical PR, implantation rate (IR), abortion rate (AR), ongoing pregnancy rate (OPR), and cumulative PR were comparable between patients having receptive ERA who had a routine Embryo Transfer (ET) and those with an NR ERA who underwent a pET. Conclusions: ERA is helpful in identifying the window of implantation (WOI) through genetic expressions of the endometrium to pinpoint embryo transfer timing. pET guided by ERA in patients of RIF with displaced WOI improves IRs and OPRs.

β-thalassemia is a common single-gene disorder in India, with hematopoietic stem cell transplantation (HSCT) being the only cure. HSCT with matched unrelated donor is less successful, whereas finding a human leukocyte antigen (HLA)-matched related donor is difficult. Preimplantation genetic testing for monogenic diseases (PGT-M) with HLA matching is a novel option to have a matched sibling for HSCT for couples having an affected child. We present the first such case report in India. A couple, both carriers of β-thalassemia and having an affected son, underwent PGT-M with HLA matching combined with preimplantation genetic testing for aneuploidies of embryos to have a β - thalassemia-free child. This resulted in birth of a 10/10 HLA-matched sibling.

Background Laparoscopic cholecystectomy (LC) is increasingly being used as a first-line treatment for acute cholecystitis. Bile duct injury (BDI) remains the most feared complication of the minimally invasive approach specially in cases with an inflamed calots triangle. While use of indocyanine dye (ICG) to delineate biliary anatomy serves to reduce BDI, the high cost of the technology prohibits its use in the developing world. We propose a novel use of common bile duct (CBD) stenting preoperatively in cases of cholecystitis secondary to choledocholithiasis as a means of identification and safeguarding the CBD. Methods A retrospective review was conducted on 22 patients of Grade 2 or Grade 3 cholecystitis who underwent an early LC at our institution. All patients were stented preoperatively and the stent was used for a much-needed tactile feedback during dissection. A c-arm with intraoperative fluoroscopy was used to identify the CBD prior to clipping of the cystic duct. Results The gall bladder was gangrenous in all the cases while two cases had evidence of end organ damage. This innovative use of CBD stenting allowed us to correctly delineate biliary anatomy in all of the cases and we report no instances of BDI despite a severely inflamed local environment. Conclusion This technique can become a standard of care in all teaching institutions in developing countries further enhancing the safety of cholecystectomy in gangrenous cholecystitis with a distorted biliary anatomy.

Both mosquito species-specific differences and virus strain -specific differences impact vector competence. Previous results in our laboratory with individual populations of N. American mosquitoes support studies suggesting Aedes aegypti are more competent than Ae. albopictus for American Zika virus (ZIKV) strains and demonstrate that U.S. Ae. albopictus have higher competence for an ancestral Asian ZIKV strain. A982V, an amino acid substitution in the NS1 gene acquired prior to the American outbreak, has been shown to increase competence in Ae. aegypti. We hypothesized that variability in the NS1 could therefore contribute to species-specific differences and developed a reverse genetics system based on a 2016 ZIKV isolate from Honduras (ZIKV-WTic) to evaluate the phenotypic correlates of individual amino acid substitutions. In addition to A982V, we evaluated G894A, which was acquired during circulation in the Americas. Reversion of 982 and 894 to ancestral residues increased infectivity, transmissibility and viral loads in Ae. albopictus but had no effect on competence or replication in Ae. aegypti. In addition, while host cell-specific differences in NS1 secretion were measured, with significantly higher secretion in mammalian cells relative to mosquito cells, strain-specific differences in secretion were not detected, despite previous reports. These results demonstrate that individual mutations in NS1 can influence competence in a species-specific manner independent of differences in NS1 secretion and further indicate that ancestral NS1 residues confer increased competence in Ae. albopictus. Lastly, experimental infections of Ifnar1-/- mice demonstrated that these NS1 substitutions can influence viral replication in the host and, specifically, that G894A could represent a compensatory change following a fitness loss from A982V with some viral genetic backgrounds. Together these data suggest a possible role for epistatic interactions in ZIKV fitness in invertebrate and vertebrate hosts and demonstrate that strains with increased transmission potential in U.S. Ae. albopictus could emerge.

The crown form of maxillary central incisor tooth is one of the vital phenomenon for a person's esthetics. Its crown form has been compared with other anatomical parameters such as arch form and facial form. Three different classes of tooth forms which relate to square, tapered, and ovoid forms are identified. The aim of this study was to morphometrically evaluate the correlation between maxillary dental arch form and the maxillary central incisor crown form. Dentate cast models of fifty male and fifty female normal occlusion controls in the age group of 18–23 years were analyzed. The mesiodistal (MD) dimensions of the maxillary central incisors were measured at incisal (MD_I) and at gingival (MD_G) levels. The transverse widths of maxillary casts were measured at the first molar and at the first premolar levels. The measured data were statistically analyzed using the SPSS software. The MD dimensions of maxillary central incisor were significantly greater in males than females. The ratio between the two MD dimensions also varied significantly among genders. The intermolar width (IMW) and inter first premolar width (IPmW) between males and females were highly significant (P < 0.05), whereas the ratio between these two parameters in males and females was not significant (P = 0.43). Eighty-eight percentage of the participants were found to have an ovoid type of maxillary arch, while only 45% of them had the ovoid form of maxillary central incisors. The MD_I and the IMW were found to be in the ratio of 1:5.5 in both genders. The MD_G and the IPmW were in the ratio of 1:4.7 in males and 1:4.5 in females. There was a weak positive correlation between MD_I and IMW (r2 = 0.146) and between MD_G and IPmW (r2 = 0.05). No significant concordance between the maxillary central incisor crown form and the maxillary arch form was found in this study.

Background: Malocclusion in the vertical and sagittal planes is easy to observe whereas it is difficult to diagnose malocclusion in the transverse plane. There are yet no criteria defining a normal transverse occlusion. Aim: The aim of this study was to identify a ratio that defines a normal transverse occlusion. Study Design: This was a retrospective study. Materials and Methods: A total sample of 151 maxillary dental models (M = 55, F = 96) in the age range of 12-16 years were randomly selected, with 73 models in control group and 78 in the study group. All the models were mixed up and given to an operator for the measurement of intercanine width (ICW) and inter-palatal molar width (IPMW). Statistical Analysis Used : The data were statistically analyzed using SPSS software version 16.0. Chi-square test was performed to test the statistical significance difference between the groups at p ≤ 0.05. Results: Nearly 98.60% of normal arches were found to have an IPMW to ICW ratio of 1:1 ± 0.05. On further analysis, it was found that when IPMW ≥37.45 mm, then the case may be considered to have normal arches, and if the ratio between IPMW to ICW is 1.15:1 ± 0.05 or more and IPMW is

Introduction: Epigenetic aging, a marker of biological aging measured by DNA methylation, may be affected by behaviors, including sleep and physical activity. However, investigations of physical activity and sleep with epigenetic aging among pediatric populations are scant and have not accounted for correlated behaviors., Methods: The study population included 472 Mexico City adolescents (52% female). Blood collection and 7-d wrist actigraphy (Actigraph GTX-BT) occurred during a follow-up visit when participants were 14.5 (2.09) yr. Leukocyte DNA methylation was measured with the Infinium MethylationEPIC array after bisulfite conversion, and nine epigenetic clocks were calculated. Sleep versus wake time was identified through a pruned dynamic programing algorithm, and physical activity was processed with Chandler cutoffs. Kmeans clustering was used to select actigraphy-assessed physical activity and sleep behavior clusters. Linear regression analyses were used to evaluate adjusted associations between the clusters and epigenetic aging., Results: There were three unique clusters: "Short sleep/high sedentary behavior," "Adequate sleep duration and late sleep timing/low moderate or vigorous physical activity (MVPA)," and "Adequate sleep duration/high MVPA." Compared with the "Adequate duration/high MVPA," adolescents with "Adequate duration and late sleep timing/low MVPA" had more accelerated aging for the GrimAge clock ( β = 0.63; 95% confidence interval, 0.07-1.19). In pubertal-stratified analyses, more mature adolescents in the "Adequate sleep duration and late sleep timing/low MVPA group" had accelerated epigenetic aging. In contrast, females in the "Short sleep/high sedentary" group had decelerated epigenetic aging for the Wu pediatric clock., Conclusions: Associations between behavior clusters and epigenetic aging varied by pubertal status and sex. Contrary results in the Wu clock suggest the need for future research on pediatric-specific clocks., (Copyright © 2024 by the American College of Sports Medicine.)

Objective: To report utilization, effectiveness, and safety of assisted reproductive technologies in 2015 and 2016., Design: A retrospective, cross-sectional survey of 3,103 assisted reproductive technology clinics in 74 countries in 2015 and 3,249 clinics in 79 countries in 2016 that submitted cycle and pregnancy outcome data through national and regional registries., Setting: Seventy-nine countries and >3,000 assisted reproductive technology clinics., Patient(s): Patients undergoing assisted reproductive technology procedures., Intervention(s): Assisted reproductive technology., Main Outcome Measure(s): Outcomes on country, regional, and global levels., Result(s): Reported for 2015: 2,358,239 cycles with 548,652 infants born; for 2016: 2,807,963 cycles with 647,188 infants born. Estimated in 2015, ≥2,683,677 cycles resulted in >675,134 infants; in 2016, ≥3,100,448 cycles resulted in ≥723,026 infants. Reported cycles represent approximately 80% of global utilization. In 2015 and 2016, 27.6% and 27.8%, respectively, of women undergoing fresh autologous treatment cycles were aged ≥40 years. Frozen-thawed embryo transfer (ET) cycles accounted for 47.0% and 51.9%, respectively, of all ETs in 2015 and 2016. Oocyte donation cycles accounted for 6.7% and 7.1% of all ETs in 2015 and 2016. Intracytoplasmic sperm injection was performed in 57.7% and 56.4% of autologous aspiration cycles in 2015 and 2016, respectively. The cumulative delivery rate per aspiration cycle for fresh and frozen-thawed ET was 32.4% in 2015 and 33.1% in 2016, respectively. The average number of transferred embryos was 1.70 in 2015 and 1.69 in 2016. The proportion of single ETs in fresh autologous cycles increased from 42.1% in 2015 to 44.0% in 2016. The twin delivery rate decreased from 16.0% in 2015 to 14.7% in 2016, and the triplet rate decreased from 0.6% in 2015 to 0.4% in 2016. The proportion of single ETs in frozen-thawed ET autologous treatment cycles was 62.2% in 2015 and 64.2% in 2016, with twin and triplet rates of 10.1% and 0.3% in 2015 and 10.0% and 0.2% in 2016, respectively., Conclusion(s): Utilization of assisted reproductive technology treatment and births per cycle increased from 2015 to 2016, although multiple births were reduced. An increasing proportion of frozen-thawed ET cycles, continuing wide variation in use of intracytoplasmic sperm injection, and an increase in single ET rates are reported., Competing Interests: Declaration of Interests M.S.K. reports travel support from Ferring, IBSA, and Merck, outside the submitted work. G.M.C. reports funding from the International Committee for Monitoring Assisted Reproductive Technologies (ICMART). The National Perinatal Epidemiology and Statistics Unit (NPESU) of the University of New South Wales, Sydney (UNSW) received funding. S.D. has nothing to disclose. F.Z.H. reports travel expenses to give a scientific lecture from Ferring Pharma, Director, responsible for the Latin American Registry of ART, Chair Committee of Ethics and Public Policies; Chilean Society of Obstetrics and Gynecology, Vice Chair ICMART, outside the submitted work. J.D.M. is Chair of Société de Médecine de la Reproduction, France, unpaid, outside the submitted work. O.I. has nothing to disclose. M.B. reports consulting fees from ABBOTT INIDA; honoraria from BAZEL PHARMA and MERCK SPEC; Board of Director, Pacific Rim Society of Reproductive Medicine; Board of Director, POSEIDON Group; Regional Director, IFFS Triennial Report, outside the submitted work. S.C.J. reports travel fee for lectures supported by Ferring; travel support from the Japan Society for Reproductive Medicine for attending meetings, outside the submitted work. B.F. has nothing to disclose. E.E. has nothing to disclose. V.B. reports consulting fees from Organon, Society for Assisted Reproductive Technology Executive Council, not paid, outside the submitted work. G.D.A. reports honoraria from Organon; travel support from ESHRE; Chair, International Committee for Monitoring ART. unpaid; President, World Endometriosis Research Foundation, unpaid; ICMART NGO Liaison Observer, Board of the International Federation of Fertility Societies, unpaid; ASRM: Member, Global Health Committee, American Society for Reproductive Medicine, unpaid; founder and CEO of Advanced Reproductive Care, Inc. (d/b/a ARC®Fertility), outside the submitted work., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Although phthalate exposure has been linked with multiple adverse pregnancy outcomes, their underlying biological mechanisms are not fully understood. We examined associations between biomarkers of phthalate exposures and metabolic alterations using untargeted metabolomics in 99 pregnant women and 86 newborns [mean (SD) gestational age = 39.5 (1.5) weeks] in the PROTECT cohort. Maternal urinary phthalate metabolites were quantified using isotope dilution high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS), while metabolic profiles in maternal and cord blood plasma were characterized via reversed-phase LC-MS. Multivariable linear regression was used in metabolome-wide association studies (MWAS) to identify individual metabolic features associated with elevated phthalate levels, while clustering and correlation network analyses were used to discern the interconnectedness of biologically relevant features. In the MWAS adjusted for maternal age and prepregnancy BMI, we observed significant associations between specific phthalates, namely, di(2-ethylhexyl) phthalate (DEHP) and mono(3-carboxypropyl) phthalate (MCPP), and 34 maternal plasma metabolic features. These associations predominantly included upregulation of fatty acids, amino acids, purines, or their derivatives and downregulation of ceramides and sphingomyelins. In contrast, fewer significant associations were observed with metabolic features in cord blood. Correlation network analysis highlighted the overlap of features associated with phthalates and those identified as differentiating markers for preterm birth in a previous study. Overall, our findings underscore the complex impact of phthalate exposures on maternal and fetal metabolism, highlighting metabolomics as a tool for understanding associated biological processes. Future research should focus on expanding the sample size, exploring the effects of phthalate mixtures, and validating identified metabolic features in larger, more diverse populations.

Objective: The conservative therapy for chronic plantar fasciitis works for a few patients, while surgical options have drawbacks. Before considering surgical options, transcatheter arterial embolization may help patients with plantar fasciitis who are experiencing discomfort resistant to conservative treatment., Methods: We report evaluation data of 10 patients treated with transcatheter arterial embolization using imipenem/cilastatin as embolic agents to relieve chronic pain due to plantar fasciitis. All the patients were refractory to conservative therapy., Results: The technical success of the procedure was found to be 100%. Further, effective pain relief was observed as there was no pain relapse in 6 months, and patients did not require any other form of therapy., Conclusion: This report warrants further adequately designed randomized clinical studies for evaluating the efficacy of transcatheter arterial embolization in plantar fasciitis., Advances in Knowledge: Resorting to surgical option for chronic pain relief in plantar fasciitis might be reconsidered and replaced with arterial embolization. However, adequately designed long-term clinical studies are required to prove its long-term efficacy., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Institute of Radiology.)

Objective: We propose a new health informatics framework to analyze physical activity (PA) from accelerometer devices. Accelerometry data enables scientists to extract personal digital features useful for precision health decision making. Existing methods in accelerometry data analysis typically begin with discretizing summary counts by certain fixed cutoffs into activity categories. One well-known limitation is that the chosen cutoffs are often validated under restricted settings, and cannot be generalizable across populations, devices, or studies., Methods: We develop a data-driven approach to overcome this bottleneck in PA data analysis, in which we holistically summarize a subject's activity profile using Occupation-Time curves (OTCs), which describe the percentage of time spent at or above a continuum of activity count levels. We develop multi-step adaptive learning algorithms to perform supervised learning via a scalar-on-function model that involves OTC as the functional predictor of interest as well as other scalar covariates. Our learning analytic first incorporates a hybrid approach of fused lasso for clustering and Hidden Markov Model for changepoint detection, then executes refinement procedures to determine activity windows of interest., Results: We evaluate and illustrate the performance of the proposed learning analytic through simulation experiments and real-world data analyses to assess the influence of PA on biological aging. Our findings indicate a different directional relationship between biological age and PA depending on the specific outcome of interest., Significance: Our bioinformatics methodology involves the biomedical outcome of interest to detect different critical points, and is thus adaptive to the specific data, study population, and health outcome under investigation.

Background and Aim: Conventional drugs have limitations due to prevalence of contraindications in PCOS patients. To explore the potential effects of swertiamarin, on abrupted insulin and steroidogenic signaling in human luteinized granulosa cells from PCOS patients with or without insulin resistance., Experimental Procedure: hLGCs from 8 controls and 16 PCOS patients were classified for insulin resistance based on down regulation of protein expression of insulin receptor-β (INSR- β) as shown in our previous paper. Cells were grouped as control, PCOS-IR and PCOS-NIR, treated with swertiamarin (66 µM) and metformin (1 mM). Expression of key molecules involved in insulin signaling, fat metabolism, IGF system and steroidogenesis were compared between groups., Results: Swertiamarin significantly (P < 0.05) reversed the expression of INSR-β, PI(3)K, p-Akt, PKC-ζ, PPARγ, (P < 0.01) IRS (Ser 307) and IGF system in PCOS-IR group and was equally potent to metformin. In the same group, candidate genes viz SREBP1c, FAS, ACC-1 and CPT-1 were down regulated by swertiamarin (P < 0.001) and metformin (P < 0.001). Significant upregulation was demonstrated in expression of StAR, CYP19A1, 17β-HSD and 3β-HSD when treated with swertiamarin (P < 0.01) and metformin (P < 0.01) in PCOS-IR followed by increase in 17β-HSD and 3β-HSD enzyme activity along with estradiol and progesterone secretions. However, swertiamarin did not reveal any effect on PCOS-NIR group as compared to metformin that significantly (P < 0.01) reversed all the parameters related to steroidogenesis and down regulated basal expression of insulin signaling genes., Conclusion: Swertiamarin, presents itself as a potential fertility drug in hLGCs from PCOS-IR patients., (© 2023. The Author(s).)

Background: Sedentary behavior is a modifiable risk factor for cardiometabolic health; however, the assessment of total sedentary time may not capture youth's highly active and interrupted activity patterns. This study examined the associations between sedentary activity patterns and cardiometabolic risk factors among Mexican youth, who have a disproportionate burden of metabolic diseases, using a repeated measure design out of a longitudinal data., Methods: 570 subjects in the Early Life Exposure in Mexico to ENvironmental Toxicants (ELEMENT) birth cohort, who were followed up to three-time points during adolescence, were included. Bout duration, and frequency and percentages of waking time spent in specific intensities of activity, were quantified using ActiGraph wGT3X-BT wrist accelerometers. Self-reported questionnaires were used to query the usual duration of different sedentary behaviors. Outcomes were fasting lipid profile, markers for glucose homeostasis, anthropometry, and blood pressure. Associations were modeled using linear mixed-effects models, and isotemporal substitution approach was additionally used to assess the effect of replacing objectively assessed sedentary activity with other activity intensities, adjusting for potential confounders., Results: Each hour of self-reported screen-based time was positively associated with diastolic blood pressure (mm Hg) [β = 0.30, 95% confidence interval (95% CI) = 0.10, 0.51], and an hour of other sedentary time was associated with log serum glucose (mg/dL) [β = 0.01, 95% CI = 0.004, 0.017]. Substitution models showed that replacing 5% of sedentary time with moderate to vigorous physical activity (MVPA) was associated with lower waist circumference (cm) [β = - 1.35, 95% CI = - 1.91, - 0.79] and log serum triglycerides (mg/dL) [β = - 0.11, 95% CI = - 0.18, - 0.03]. Substituting one uninterrupted sedentary bout with light activity was associated with lower insulin (μIU/mL) [β = - 0.06, 95% CI = - 0.10, - 0.02]., Conclusions: Sedentary time was associated with cardiometabolic risk factors in Mexican youth in a context-specific manner. Replacing sedentary time with higher intensities was associated with improvements in some cardiometabolic markers., (© 2022. The Author(s).)

Social distancing reduces the transmission of COVID-19 and other airborne diseases. To test different ways to increase social distancing, we conducted a field experiment at a major US airport using a system that presented color-coded visual indicators on crowdedness. We complemented those visual indicators with nudges commonly used to increase COVID-19-preventive behaviors. Analyzing data from 57,146 travelers, we find that visual indicators and nudges significantly affected social distancing. Introducing visual indicators increased the share of travelers practicing social distancing, and this positive effect was enhanced by introducing nudges focused on personal benefits ("protect yourself") and public benefits ("protect others"). Conversely, an authoritative nudge referencing the Centers for Disease Control and Prevention ("don't break CDC COVID-19 guidelines") did not change social distancing behavior. Our results demonstrate that visual indicators and informed nudges can boost social distancing and potentially curb the spread of contagious diseases.

Background: Alterations in body composition (BC) during adolescence relates to future metabolic risk, yet underlying mechanisms remain unclear., Objectives: To assess the association between the metabolome with changes in adiposity (body mass index [BMI], waist circumference [WC], triceps skinfold [TS], fat percentage [BF%]) and muscle mass (MM)., Methods: In Mexican adolescents (n = 352), untargeted serum metabolomics was profiled at baseline. and data were reduced by pairing hierarchical clustering with confirmatory factor analysis, yielding 30 clusters with 51 singleton metabolites. At the baseline and follow-up visits (1.6-3.5 years apart), anthropometry was collected to identify associations between baseline metabolite clusters and change in BC (∆) using seemingly unrelated and linear regression., Results: Between visits, MM increased in boys and adiposity increased in girls. Sex differences were observed between metabolite clusters and changes in BC. In boys, aromatic amino acids (AAA), branched chain amino acids (BCAA) and fatty acid oxidation metabolites were associated with increases in ∆BMI, and ∆BF%. Phospholipids were associated with decreases in ∆TS and ∆MM. Negative associations were observed for ∆MM in boys with a cluster including AAA and BCAA, whereas positive associations were found for a cluster containing tryptophan metabolites. Few associations were observed between metabolites and BC change in girls, with one cluster comprising methionine, proline and lipids associated with decreases in ∆BMI, ∆WC and ∆MM., Conclusion: Sex-specific associations between the metabolome and change in BC were observed, highlighting metabolic pathways underlying adolescent physical growth., (© 2022 World Obesity Federation.)

Background: The emergence of the COVID pandemic unfolded a series of precautions and dilemmas and the complete suspension of health services. With the gradual emergence of data showing near minimal effects of the virus on pregnancy, Assisted Reproductive Techniques (ART) services were gradually resumed following guidelines and advisories., Aim: The purpose of this study was to detect the COVID positivity rate in women undergoing ART treatment during the COVID pandemic and compare clinical and embryological outcomes to the ART cycles performed in the pre-COVID era., Study Setting and Design: This was a retrospective cohort study of all women undergoing controlled ovarian stimulation, followed by a fresh or frozen embryo transfer (ET) between 1st October 2019 and 31st March 2020 (control group) and between 1st April 2020 and 31st September 2020 (study group) at Nova IVF Fertility Clinic, Ahmedabad., Material and Methods: The study group underwent ART during the first wave of COVID-19 pandemic in India and when gradual unlocking of facilities including ART was advised as per the national ART advisory by the ICMR in December 2020. The outcomes were compared with the control group (cycles in pre-covid time)., Statistical Analysis: Statistical analysis was performed in SPSS (v25.0) and included Mann-Whitney U, Fisher's exact and Pearson Chi-square as appropriate. Values of P < 0.05 were considered statistically significant., Results: A total of 367 in vitro fertilisation (IVF) stimulations were initiated. A total of 342 retrievals and 606 ETs (171 fresh and 435 frozen) were completed during the study period with a COVID positivity rate of 6.8% (25/367) amongst fresh and 3.9% (18/453) amongst frozen ETs, respectively; the PR and IR in the study group was similar to the control group (47.6 vs. 55.1 P = 0.4 and 68.7 vs. 66.4; P = 0.52, respectively). The maternal complication rates were similar in both groups with a COVID positivity rate of 10.2% (23/225) and 1 maternal death in the study group. The live birth rates were similar., Conclusions: We did not find a noteworthy difference in the clinical and embryological outcomes in the IVF cycles conducted in the COVID era as compared to the pre-COVID time. Thus, with adequate precautions and safety measures, ART services conducted during the COVID pandemic have comparable birth outcomes and can be safely advocated., Competing Interests: Dr. Manish Banker is currently an associate editor of the Journal of Human Reproductive Sciences. He has not participated in the blinded external review or the editorial review process., (Copyright: © 2022 Journal of Human Reproductive Sciences.)

Objective/background: Self-reported sleep difficulties, such as insomnia symptoms, have been reported among adolescents. Yet, studies of their prevalence and correlates are scarce among Latin Americans. This study sought (1) to describe associations between sociodemographic and lifestyle factors with self-reported sleep difficulties and (2) to examine associations between self-reported sleep difficulties and actigraphy-based sleep., Participants: Participants included 477 Mexican adolescents from the ELEMENT cohort., Methods: Over 7 days, self-reported sleep measures (hard time falling asleep, overall sleep difficulties, and specific types of sleep difficulties) were obtained from daily sleep diaries. Actigraphy-based sleep measures (duration, i.e. sleep onset to morning wake, midpoint, and fragmentation) were concurrently assessed using a wrist actigraph., Results: Mean (SD) age was 15.9 (2.2) years, and 53.5% were females. Mean (SD) sleep duration was 8.5 (1.2) h/night. Half reported a hard time falling asleep at least 3 days, and 25% had sleep difficulties at least 3 days over 7 days. The 3 types of sleep difficulties commonly reported among the entire cohort were insomnia/restlessness (29%), environmental (27%), and mental/emotional difficulties (19%). Female sex, smoking behavior, and socioeconomic indicators were among the most consistent factors associated with sleep difficulties. Subjective sleep difficulties were associated with shorter sleep duration (β = -20.8 [-35.3, -6.2] min), while subjective hard time falling asleep was associated with longer sleep duration (β = 11.3 [4.6, 27.2] min)., Conclusion: A high proportion of Mexican adolescents in the sample reported sleep difficulties. Findings demonstrate the importance of obtaining subjective and objective sleep measures for a more comprehensive assessment of adolescent sleep.

Context: Adrenal-derived 11-oxygenated androgens (11oAs) are known important contributors to human physiology and disease but have not been studied in pregnancy., Objective: We characterize 11oAs in normal human pregnancy and neonatal period and assess the ratios between 11oAs and compare with ratios of other steroids that undergo placental metabolism., Design: Prospective cohort study, 2010-2018., Setting: Academic institution., Patients: Pairs of pregnant women and newborns (n = 120) were studied. Inclusion criteria were maternal age between 18 and 42 years old, spontaneous singleton pregnancies, and intention to deliver at University of Michigan., Intervention: Maternal venous blood was collected during first trimester and at term. Neonatal cord blood was collected following delivery. Steroids were measured via liquid chromatography-tandem mass spectrometry., Main Outcome Measures: Levels of 11β-hydroxyandrostenedione (11OHA4), 11-ketoandrostenedione (11KA4), 11β-hydroxytestosterone, and 11-ketotestoterone (11KT) in maternal first trimester, maternal term, and neonatal cord blood were compared. 11OHA4-to-11KA4 ratios were correlated with cortisol-to-cortisone ratios., Results: Dominant 11oAs in pregnancy and the cord blood are 11OHA4 and 11KA4, compared to 11OHA4 and 11KT in adult men and nonpregnant women. We found a rise in 11oA concentrations, particularly 11KA4, from first to third trimester. In cord blood, the concentration of 11KA4 exceeded those of both 11OHA4 and 11KT, reflecting placental 11β-hydroxysteroid dehydrogenase type 2 (11βHSD2) and 17β-hydroxysteroid dehydrogenase (17βHSD2) activities, respectively. 11OHA4-to-11KA4 ratios are concordant with cortisol-to-cortisone ratios across all maternal and fetal compartments, reflecting placental 11βHSD2 activity., Conclusions: Placental 17βHSD2 activity defends the fetus against the androgen 11KT. Our normative values may be used in future studies of 11oAs in complicated pregnancies., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: To study the efficacy of estradiol for cycle programming in oocyte donors when administered in the follicular phase only., Design: Prospective interventional study., Setting: Single fertility center., Patients: Ninety-three oocyte donors underwent programmed stimulation using estradiol in the follicular phase. Their previous unprogrammed cycles were used as historical controls., Interventions: Donors received 8 mg of estradiol hemihydrate from day 2 till 1 day before the start of stimulation., Main Outcome Measures: The primary outcome measures studied were the number of oocytes retrieved, duration of stimulation, and total gonadotropin dose. The number of mature oocytes, oocyte maturation rate, fertilization rate, blastulation rate, implantation rate, and pregnancy rate were the secondary outcomes., Results: The average number of oocytes retrieved was higher in the study group (36.4 vs. 32.5). The duration of stimulation (9.22 vs. 9.21 days) and the total gonadotropin dose were similar (3,085.5 vs. 3,026 IU) between both groups. The mean number of mature oocytes retrieved was higher in the study group (30.1 vs. 26.3), but the maturation rate was similar (84.6% vs. 81.2%). The fertilization rate (77.8% vs. 78.7%), number of blastocysts, blastulation rate (32.7% vs. 33.2%), implantation rate (59.3% vs. 66.3%), and pregnancy rate (77.3% vs. 77.1%) showed no statistically significant difference., Conclusions: Estradiol usage in the follicular phase alone is an effective and convenient option for cycle programming in oocyte donors. It can yield similar mature oocytes and does not affect the clinical outcomes. Further larger sample-sized studies may be needed to validate its use which can also be extended to routine in vitro fertilization cycles., Clinical Trials Registration Number: CTRI/2020/09/027815., (© 2022 The Authors.)

The COVID-19 pandemic challenges healthcare services. Concomitantly, this pandemic had a stimulating effect on technological expansions related to telehealth and telemedicine. We sought to elucidate the principal patients' reasons for using telemedicine during the COVID-19 pandemic and the propensity to use it thereafter. Our primary objective was to identify the reasons of the survey participants' disparate attitudes toward the use of telemedicine. We performed an online, multilingual 30-question survey for 14 days during March-April 2021, focusing on the perception and usage of telemedicine and their intent to use it after the pandemic. We analyzed the data to identify the attributes influencing the intent to use telemedicine and built decision trees to highlight the most important related variables. We examined 473 answers: 272 from Israel, 87 from Uruguay, and 114 worldwide. Most participants were women (64.6%), married (63.8%) with 1-2 children (52.9%), and living in urban areas (84.6%). Only a third of the participants intended to continue using telemedicine after the COVID-19 pandemic. Our main findings are that an expected substitution effect, technical proficiency, reduced queueing times, and peer experience are the four major factors in the overall adoption of telemedicine. Specifically, (1) for most participants, the major factor influencing their telemedicine usage is the implicit expectation that such a visit will be a full substitute for an in-person appointment; (2) another factor affecting telemedicine usage by patients is their overall technical proficiency and comfort level in the use of common web-based tools, such as social media, while seeking relevant medical information; (3) time saving as telemedicine can allow for asynchronous communications, thereby reducing physical travel and queuing times at the clinic; and finally (4) some participants have also indicated that telemedicine seems more attractive to them after watching family and friends (peer experience) use it successfully.

Study Question: What were the utilization, effectiveness and safety of practices in assisted reproductive technologies (ART) globally in 2014 and what global trends could be observed?, Summary Answer: The estimated total number of ART cycles conducted in 76 participating countries in 2014 was 1.93 million representing ∼66% of global activity, with 5-year trends including an increase in success rates and proportion of frozen embryo transfer (FET) cycles, improvement in cumulative live birth rates per aspiration, a continued increase in single embryo transfer (SET) and thus a reduction in multiple birth rates, an increase in preimplantation genetic testing and stabilization in the use of intracytoplasmic sperm injection (ICSI)., What Is Known Already: ART is widely practiced throughout the world but continues to be characterized by significant disparities in utilization, practice, effectiveness and safety. The International Committee for Monitoring Assisted Reproductive Technologies (ICMART) annual world report series provides an important instrument for tracking trends in ART treatment and for providing clinical and public health data to ART professionals, health authorities, patients and the general public., Study Design, Size, Duration: A retrospective, cross-sectional survey on ART procedures performed globally during 2014 was carried out. A new method for calculating ART utilization rates and number of babies born was introduced in this latest ICMART world report., Participants/materials, Setting, Methods: Overall, 76 countries and 2 746 ART centres submitted data through national and regional ART registries on ART cycles performed during 2014 and their treatment and pregnancy outcomes. ART cycles and outcomes are described at a country level, regionally and globally. Aggregate country data are processed and analyzed based on methods developed by ICMART., Main Results and the Role of Chance: A total of 1 629 179 ART cycles were reported for the treatment year 2014. After imputing data for missing values and non-reporting centres in reporting countries, an estimated 1 929 905 cycles resulted in >439 039 babies in reporting countries. From 2010 to 2014, the number of reported non-donor aspirations and FET cycles increased by 37.3% and 67.5%, respectively. The proportion of women aged ≥40 years undergoing non-donor ART increased from 23.2% in 2010 to 27.0% in 2014. ICSI, as a percentage of non-donor aspiration cycles, remained relatively stable at 64.8%. The IVF/ICSI combined delivery rates per fresh aspiration and FET cycle were 19.9% and 24.3%, respectively. In fresh non-donor cycles, SET increased from 30.0% in 2010 to 40.0% in 2014, while the average number of transferred embryos decreased from 1.95 to 1.73-but with wide country variation. The rate of twin deliveries following fresh non-donor transfers continued to decrease, from 20.4% in 2010 to 16.2% in 2014, and the triplet rate decreased from 1.1% to 0.5%. In FET non-donor cycles in 2014, the SET rate was 61.6%, with an average of 1.43 embryos transferred, resulting in twin and triplet rates of 10.1% and 0.2%, respectively. The cumulative delivery rate per aspiration increased from 27.1% in 2010 to 32.1% in 2014. The overall perinatal mortality rate per 1 000 births was 19.4 following fresh IVF/ICSI cycles and 9.5 following FET cycles. Among reporting countries, oocyte donation cycles represented 7.3% of all embryo transfers (89 751 transfer cycles) and resulted in 39 278 babies., Limitations, Reasons for Caution: The data presented are dependent on the quality and completeness of data submitted by individual countries to ICMART directly or through regional registries. This report covers approximately two-thirds of world ART activity. China is a major contributor of global cycles missing from this report. Continued efforts to improve the quality and consistency of ART data reported by registries are still needed, including the use of internationally agreed standard definitions (The International Glossary of Infertility and Fertility Care). A new method was introduced in this report to calculate ART utilization and number of babies born following ART; therefore, these results are not directly comparable with previous reports., Wider Implications of the Findings: The ICMART world reports provide the most comprehensive global statistical census and review of ART utilization, effectiveness, safety and quality. While ART treatment effectiveness and safety continue to increase globally, the wide disparities in access to treatment, procedures performed and embryo transfer practices warrant attention by clinicians and policymakers. The new method for estimating ART utilization and number of babies born provided more conservative estimates compared to the previuos method., Study Funding/competing Interest(s): ICMART receives unrestricted grants from Abbott and Ferring Pharmaceuticals. ICMART also acknowledges financial support from the following organizations: American Society for Reproductive Medicine; Asia Pacific Initiative on Reproduction; European Society of Human Reproduction and Embryology; Fertility Society of Australia and New Zealand; Japan Society for Reproductive Medicine; Japan Society of Fertilization and Implantation; Red Latinoamericana de Reproducción Asistida; and the Society for Assisted Reproductive Technology. S.D. reports industry sponsorship for attendance of conference from Ferring, and research grants to support African Network and Registry of ART from Ferring and Merck outside the submitted work. F.Z.-H. reports lectures at organized webinars for Ferring and Merck. O.I. reports honoraria for consulting from Ferring, Merck and ObsEva, as well as honoraria for lectures from Ferring and Merck. G.M.C., J.d.M., M.B., M.S.K. and G.D.A. have nothing to disclose., Trial Registration Number: N/A., (© The Author(s) 2021. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)