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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.

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.

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.

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.

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

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.)

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.)

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.)

Objective: To report the utilization, effectiveness, and safety of practices in assisted reproductive technology (ART) globally in 2013 and assess global trends over time., Design: Retrospective, cross-sectional survey on the utilization, effectiveness, and safety of ART procedures performed globally during 2013., Setting: Seventy-five countries and 2,639 ART clinics., Patient(s): Women and men undergoing ART procedures., Intervention(s): All ART., Main Outcome Measure(s): The ART cycles and outcomes on country-by-country, regional, and global levels. Aggregate country data were processed and analyzed based on methods developed by the International Committee for Monitoring Assisted Reproductive Technology (ICMART)., Result(s): A total of 1,858,500 ART cycles were conducted for the treatment year 2013 across 2,639 clinics in 75 participating countries with a global participation rate of 73.6%. Reported and estimated data suggest 1,160,474 embryo transfers (ETs) were performed resulting in >344,317 babies. From 2012 to 2013, the number of reported aspiration and frozen ET cycles increased by 3% and 16.4%, respectively. The proportion of women aged >40 years undergoing nondonor ART increased from 25.2% in 2012 to 26.3% in 2013. As a percentage of nondonor aspiration cycles, intracytoplasmic sperm injection (ICSI) was similar to results for 2012. The in vitro fertilization (IVF)/ICSI combined delivery rates per fresh aspiration and frozen ET cycles were 24.2% and 22.8%, respectively. In fresh nondonor cycles, single ET increased from 33.7% in 2012 to 36.5% in 2013, whereas the average number of transferred embryos was 1.81-again with wide country variation. The rate of twin deliveries after fresh nondonor transfers was 17.9%; the triplet rate was 0.7%. In frozen ET cycles performed in 2013, single ET was used in 57.6%, with an average of 1.49 embryos transferred and twin and triplet rates of 10.8% and 0.4%, respectively. The cumulative delivery rate per aspiration was 30.4%, similar to that in 2012. Perinatal mortality rate per 1,000 births was 22.2% after fresh IVF/ICSI and 16.8% after frozen ET. The data presented depended on the quality and completeness of the data submitted by individual countries. This report covers approximately two-thirds of world ART activity. Continued efforts to improve the quality and consistency of reporting ART data by registries are still needed., Conclusion(s): Reported ART cycles, effectiveness, and safety increased between 2012 and 2013 with adoption of a better method for estimating unreported cycles., (Copyright © 2021 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Improvements in stimulation protocols, introduction of vitrification, and changes in clinical practices have contributed to improved efficacy and safety of assisted reproductive technology (ART) procedures. This has also led to a concomitant increase in number of cycles requiring hormone replacement therapy (HRT) protocol for performing an embryo transfer. Successful implantation is dependent on endometrial thickness which in turn is regulated by temporal regulation of hormones. Careful control of estrogen levels determines uterine receptivity. One of the most used drugs for achieving appropriate endometrial lining of >7 mm in HRT is estradiol valerate. Although different estrogen formulations with varying physicochemical properties exist, there is not enough literature to support if the differences translate into a discernible clinical outcome in an in vitro fertilization (IVF) setting. Objective and Method . In this study, retrospective in nature, we compare the efficacy of oral estradiol hemihydrate with estradiol valerate in HRT cycles in 2,529 Indian women, undergoing treatment at a center in India between Jan 2017 and May 2019. Results . Our results primarily indicate that between the estradiol valerate and estradiol hemihydrate treatment groups, the implantation rate (IR) was 47.42% and 49.07%, respectively ( P value 0.284), and the endometrial thickness (mean ± SEM in mm) that was achieved was 9.25 ± 0.038 mm and 9.57 ± 0.058 mm ( P value < 0.001), respectively. There were no significant differences observed in the secondary outcome measures including clinical pregnancy rate, abortion rate, ectopic pregnancy, and live birth rate. Conclusions . Hence, this study concludes that oral estradiol hemihydrate and estradiol valerate are therapeutically equivalent and provide similar clinical outcomes in an IVF setting., Competing Interests: The authors declare that they have no conflict of interest. All authors declare no support, either financial or other activities, from any organization that could appear to have influenced the submitted work., (Copyright © 2021 Manish Banker et al.)

Background: There is no consensus regarding optimal endometrial thickness and duration of estrogen supplementation in embryo transfer cycles, at present., Aims: To observe the effect of endometrial thickness and/or duration of estrogen supplementation on in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) outcomes in fresh ovum/embryo donation cycles., Settings and Design: This was a retrospective observational study. The study was conducted from January 2015 to November 2017., Subjects and Methods: Nine hundred and fifty seven fresh blastocyst transfer cycles in the recipients of oocyte/embryo donation regardless of reproductive history and diagnosis conducted at Nova IVF Fertility, Ahmedabad, Gujarat, India. Of these, 315 women had single embryo transfer (SET), while 642 had double embryo transfer (DET). Only fresh blastocysts derived from oocytes of young donors (≤30 years) and transferred in a uniform hormone replacement therapy (HRT) cycle were included. The effect of endometrial thickness and duration of estrogen on live birth rate (LBR) and other IVF/ICSI outcomes were analyzed., Statistical Analysis: Univariate logistic regression., Results: A significant improvement in LBR was noted in the recipients with each millimeter increase in endometrial thickness starting from 6 mm after transfer of either single (odds ratio [OR] = 1.3, P = 0.003) or double (OR = 1.14, P = 0.0218) blastocysts. Lower LBR was observed in recipients having SET and who received estrogen supplementation of <10 days (OR = 0.72; P = 0.02). Implantation rate and clinical pregnancy rate also improved significantly with endometrial thickness, but there was no change in clinical abortion rate and ectopic pregnancy rate., Conclusions: After minimizing the possible oocyte factor by including only donor oocytes and that of COH using a uniform HRT protocol, LBR improved with each millimeter increase in endometrial thickness starting from 6 mm. Shorter duration of estrogen supplementation (<10 days) reduced the chances of live birth in recipients after transfer of a single blastocyst., Competing Interests: Dr. MB is the Senior Associate Editor of JHRS but was not involved in the editorial or review process of the article., (Copyright: © 2021 Journal of Human Reproductive Sciences.)

Context: Steroids play an important role in fetal development and parturition. Gestational exposures to endocrine-disrupting chemicals (EDCs) affect steroidal milieu and pregnancy outcomes, raising the possibility of steroids serving as biomarkers. Most studies have not addressed the impact of EDC mixtures, which are reflective of real life scenarios., Objective: Assess the association of maternal and neonatal steroids with pregnancy outcomes and early pregnancy EDC levels., Design: Prospective analysis of mother-infant dyads., Setting: University hospital., Participants: 121 mother-infant dyads., Main Outcome Measures: The associations of maternal and neonatal steroidal hormones from 121 dyads with pregnancy outcomes, the associations of first trimester EDCs individually and as mixtures with maternal and neonatal steroids in a subset of 56 dyads and the influence of body mass index (BMI), age, and offspring sex in modulating the EDC associations with steroids were determined., Results: Steroid-specific positive or negative associations with pregnancy measures were evident; many maternal first trimester EDCs were negatively associated with estrogens and positively with androgen/estrogen ratios; EDC-steroid associations were influenced by maternal age, pre-pregnancy BMI, and fetal sex; and EDCs individually and as mixtures showed direct and inverse fetal sex-dependent associations with maternal and neonatal steroids., Conclusions: This proof-of-concept study indicates association of steroids with pregnancy outcomes depending on maternal age, prepregnancy BMI, and fetal sex, with the effects of EDCs differing when considered individually or as mixtures. These findings suggest that steroidal hormonal measures have potential to serve as biomarkers of impact of EDC exposures and pregnancy outcome., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Improvement in cancer treatments has allowed more women to plan a pregnancy once the disease is cured. The effects of chemotherapy on ovaries are well proven but those on the uterus, especially the endometrium and embryo implantation are still unknown. Usage of newer tyrosine kinase inhibitors such as nilotinib has revolutionized the management of leukemias. Although nilotinib has been reported to be safe in pregnancy, further studies are needed to evaluate its effect on the process of embryo implantation, especially in women undergoing in-vitro fertilization. We report a case where successful pregnancy outcome was achieved after stoppage of nilotinib before embryo transfer in a woman who had previous four failed attempts while on nilotinib and no other obvious cause of implantation failure. Despite optimal endometrial thickness and receptivity, the pale appearance of endometrium on hysteroscopy was attributed to be a possible effect of nilotinib and prompted us to withhold it., Competing Interests: There are no conflicts of interest., (Copyright: © 2021 Journal of Human Reproductive Sciences.)

Human liver microsomes (HLM) and human hepatocytes (HHEP) are two common in vitro systems used in metabolic stability and inhibition studies. The comparison between the assays using the two systems can provide mechanistic insights on the interplay of metabolism, passive permeability and transporters. This study investigated the critical factors impacting the unbound intrinsic clearance (CL int,u ) and IC 50 of CYP3A inhibition between HLM and HHEP. The HLM/HHEP CL int,u ratio and HHEP/HLM IC 50 ratio are inversely correlated to passive permeability, but have no correlation with P-gp efflux ratio. Cofactor-supplemented permeabilized HHEP (MetMax™) collapses the IC 50 differences between HHEP and HLM. P-gp inhibitor, encequidar, shows minimal impact on CL int,u and IC 50 in HHEP. This is the first study that is able to separately investigate the effects of passive permeability and efflux transport. These data collectively show that passive permeability plays a critical role in metabolism and enzyme inhibition in HHEP, while P-gp efflux has a minor role. This may be due to low functional P-gp activity in suspension HHEP under the assay conditions. Low passive permeability may limit metabolism and enzyme inhibition in HHEP, leading to lower CL int,u and higher IC 50 in HHEP compared to HLM. When liver microsomes give higher CL int,u than hepatocytes, microsomes are more predictive of in vivo clearance than hepatocytes., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Study Question: What was the utilization, effectiveness and safety of practices in ART globally in 2012 and what global trends could be observed?, Summary Answer: The total number of ART cycles increased by almost 20% since 2011 and the main trends were an increase in frozen embryo transfers (FET), oocyte donation, preimplantation genetic testing and single embryo transfers (SET), whereas pregnancy and delivery rates (PR, DR) remained stable, and multiple deliveries decreased., What Is Known Already: ART is widely practiced throughout the world, but continues to be characterized by significant disparities in utilization, availability, practice, effectiveness and safety. The International Committee for Monitoring Assisted Reproductive Technologies (ICMART) annual world report provides a major tool for tracking trends in ART treatment for over 25 years and gives important data to ART professionals, public health authorities, patients and the general public., Study Design, Size, Duration: A retrospective, cross-sectional survey on the utilization, effectiveness and safety of ART procedures performed globally during 2012 was carried out., Participants/materials, Setting, Methods: Sixty-nine countries and 2600 ART clinics submitted data on ART cycles performed during the year 2012, and their pregnancy outcome, through national and regional ART registries. ART cycles and outcomes are described at country, regional and global levels. Aggregate country data were processed and analyzed based on methods developed by ICMART., Main Results and Role of Chance: A total of 1 149 817 ART cycles were reported for the treatment year 2012. After imputing data for missing values and non-reporting clinics in reporting countries, 1 948 898 cycles (an increase of 18.6% from 2011) resulted in >465 286 babies (+17.9%) in reporting countries. China did not report and is not included in this estimate. The best estimate of global utilization including China is ∼2.8 million cycles and 0.9 million babies. From 2011 to 2012, the number of reported aspirations and FET cycles increased by 6.9% and 16.0%, respectively. The proportion of women aged 40 years or older undergoing non-donor ART increased from 24.0% in 2011 to 25.2% in 2012. ICSI, as a percentage of non-donor aspiration cycles, increased from 66.5% in 2011 to 68.9% in 2012. The IVF/ICSI combined delivery rates per fresh aspiration and FET cycles were 19.8% and 22.1%, respectively. In fresh non-donor cycles, SET increased from 31.4% in 2011 to 33.7% in 2012, while the average number of transferred embryos decreased from 1.91 to 1.88, respectively-but with wide country variation. The rates of twin deliveries following fresh non-donor transfers decreased from 19.6% in 2011 to 18.0% in 2012, and the triplet rate decreased from 0.9% to 0.8%. In FET non-donor cycles, SET was 54.8%, with an average of 1.54 embryos transferred and twin and triplet rates of 11.1% and 0.4%, respectively. The cumulative DR per aspiration increased from 28.0% in 2011 to 28.9% in 2012. The overall perinatal mortality rate per 1000 births was 21.4 following fresh IVF/ICSI and 15.9 per 1000 following FET., Limitations, Reasons for Caution: The data presented depend 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, with a major missing country, China. Continued efforts to improve the quality and consistency of reporting ART data by registries are still needed, including the use of internationally agreed standard definitions (International Glossary of Infertility and Fertility Care)., 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 continues to increase globally, the wide disparities in access to treatment, procedures performed and embryo transfer practices warrant attention by clinicians and policy makers. With the increasing practice of SET and of freeze all and resulting increased proportion of FET cycles, it is clear that PR and DR per aspiration in fresh cycles do not give an overall accurate estimation of ART efficiency. It is time to use cumulative live birth rate per aspiration, combining the outcomes of FET cycles with the associated fresh cycle from which the embryos were obtained, and to obtain global consensus on this approach., Study Funding/competing Interest(s): The authors declare no conflict of interest and no specific support from any organizations in relation to this manuscript. ICMART gratefully acknowledges financial support from the following organizations: American Society for Reproductive Medicine; European Society for Human Reproduction and Embryology; Fertility Society of Australia; Japan Society for Reproductive Medicine; Japan Society of Fertilization and Implantation; Red Latinoamericana de Reproduccion Asistida; Society for Assisted Reproductive Technology; Ferring Pharmaceuticals and Abbott (both providing ICMART unrestricted grants unrelated to world reports)., Trial Registration Number: NA., (© The Author(s) 2020. 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.)

This commentary outlines the importance of utilizing assisted reproductive technology (ART) as an indicator of access to infertility care and provides a standard way of reporting utilization to facilitate international comparisons. Factors that influence ART utilization as well as underlying inequalities and inequities in access to care are discussed. The relevance of a marker that can inform and evaluate policy initiatives, monitor progress and document change is emphasized., (Copyright © 2020 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Objective: The primary objective is to compare live birth rates (LBRs) following frozen embryo transfer (FET) of euploid day 5 with day 6 blastocysts. We also compared LBRs following FET of untested blastocysts vitrified on day 5 and day 6 in self-oocyte and ovum donation (OD) cycles., Design: This was a retrospective observational study., Setting: Nova IVF Fertility, Ahmedabad., Materials and Methods: Ninety-seven FET using self-oocytes following preimplantation genetic testing A (PGT-A), 464 FET following OD, and 907 FET using self-oocytes without PGT-A testing between January 2016 and December 2017 were included in this study., Main Outcome Measures: LBR following FET in day 5 versus day 6 blastocysts in euploid embryos using self-oocytes and in untested embryos using both self and donor oocytes., Results: In PGT-A cycles, no statistically significant difference was observed in LBRs following transfer of euploid blastocysts developed on day 5 or day 6 (D5: 53%; D6:40%, P = 0.83). However, the LBRs with day 5 blastocysts were higher compared with day 6 group in untested group using both self and donor oocytes (self D5: 52.7%; D6: 38.2%; P = 0.001 and OD D5: 44.7%; D6: 29.8%; P = 0.001). Miscarriage rates were comparable in both the groups., Conclusions: The present study demonstrated comparable pregnancy outcomes following FET of euploid embryos vitrified on day 5 and day 6. However, higher LBRs were reported in day 5 group in untested embryos., Competing Interests: There are no conflicts of interest., (Copyright: © 2020 Journal of Human Reproductive Sciences.)

Lab experiments disagree on the efficacy of disclosure as a remedy to conflicts of interest (COIs). Some experiments suggest that disclosure has perverse effects, although others suggest these are mitigated by real-world factors (eg, feedback, sanctions, norms). This article argues that experiments reporting positive effects of disclosure often lack external validity: disclosure works best in lab experiments that make it unrealistically clear that the one disclosing is intentionally lying. We argue that even disclosed COIs remain dangerous in settings such as medicine where bias is often unintentional rather than the result of intentional corruption, and we conclude that disclosure might not be the panacea many seem to take it to be., (© 2020 American Medical Association. All Rights Reserved.)

Introduction/purpose: Limited studies have examined the association of physical activity with reproductive hormones, DNA methylation, and pubertal status among adolescents., Methods: Among 248 boys and 271 girls, we estimated daily physical activity levels based on 7 d of wrist-worn accelerometer data. We used an isotemporal substitution paradigm and sex-stratified regression models to examine the association of physical activity levels with 1) testosterone, cortisol, progesterone, and androstenedione concentrations; 2) DNA methylation of long interspersed nucleotide (LINE-1) repeats and the genes H19, hydroxysteroid (11-Beta) dehydrogenase 2 (HSD11B2), and peroxisome proliferator-activated receptor alpha (PPARA) from blood leukocytes; and 3) Tanner stages, adjusted for age, BMI, and socioeconomic status., Results: In boys, substituting 30 min of moderate physical activity for 30 min of sedentary behavior per day was associated with 29% (-49%, 0%) of lower testosterone and 29% (4%, 61%) of higher progesterone. Substituting 30 min of light physical activity for sedentary behavior was associated with 13% (-22%, -2%) of lower progesterone. Among girls, 30 min of additional sedentary behavior was associated with 8% (-15%, 0%) of lower testosterone and 24% (8%, 42%) of higher progesterone concentrations. Substituting 30 min of moderate physical activity for sedentary behavior was associated with 15% (0%, 31%) of higher cortisol, whereas substituting the same amount of light physical activity for sedentary behavior was associated with 22% (-39%, 0%) of lower progesterone. Substituting 30 min of vigorous physical activity for sedentary behavior per day was associated with almost six times higher levels (5.83, 95% confidence interval = 1.79-9.86) of HSD11B2 methylation in boys., Conclusions: Accelerometer-measured daily physical activity was associated with reproductive hormones and HSD11B2 DNA methylation, differed by sex and activity intensity levels.

Context: Early pregnancy exposure to endocrine disrupting chemicals (EDCs) may contribute to poor birth outcomes through oxidative stress (OS)-mediated disruption of the maternal and fetal milieu. Most studies have investigated the effect of single EDC exposures on OS., Objective: Assess the association of uniquely weighted mixtures of early pregnancy exposures with the maternal and neonatal OS markers., Design: Prospective analysis of mother-infant dyads., Setting: University hospital., Participants: 56 mother-infant dyads., Main Outcome Measures: The association of OS markers (nitrotyrosine, dityrosine, chlorotyrosine) in maternal first trimester and term, and cord blood plasma with maternal first trimester exposure levels of each of 41 toxicants (trace elements, metals, phenols, and phthalates) from 56 subjects was analyzed using Spearman correlations and linear regression. The association of OS markers with inflammatory cytokines and birth outcomes were analyzed by Spearman correlation and linear regression analysis, respectively. Weighted mixtures of early pregnancy exposures were created by principal component analysis and offspring sex-dependent and independent associations with oxidative stress markers were assessed., Results: (1) An inverse relationship between levels of maternal/cord OS markers and individual EDCs was evident. In contrast, when assessed as EDC mixtures, both direct and inverse associations were evident in a sex-specific manner; (2) the maternal term OS marker, nitrotyrosine, was inversely associated with gestational age, and (3) both direct and inverse associations were evident between the 3 OS markers and individual cytokines., Conclusions: Provides proof of concept that effects of exposures on OS varies when assessed as EDC mixtures versus individually., (© Endocrine Society 2019. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Twin pregnancy is an iatrogenic complication following in vitro fertilization (IVF) that can be decreased using elective single-embryo transfer. However, the risks associated with twin pregnancy following IVF as compared to singleton IVF pregnancy need to be further evaluated., Aim: This study aims to compare the maternal, perinatal, and neonatal complications in singleton and twin pregnancies following IVF-intracytoplasmic sperm injection (ICSI). Settings and Design: Retrospective observational cohort study using previously collected routine patient data., Materials and Methods: Singleton and twin deliveries following IVF/ICSI from January 2014 to August 2015 were included. Data were collected from patient records and the obstetricians of the patients., Statistical Analysis Used: SPSS was used for analysis. Student's t -test and Fisher's exact test were used for continuous and categorical data, respectively. Significance was kept at 0.05., Results: There were 897 singleton and 382 twin deliveries (total of 1661 babies). The mean gestational age at delivery was lower in twin deliveries (34.9 ± 3.1 weeks) as compared to singleton deliveries (36.8 ± 3.2 weeks, P < 0.001). The overall incidence of maternal complications was higher in twin pregnancies (29.3% vs. 21.3%, odds ratio = 1.53, 95% confidence interval = 1.17-2.01; P = 0.003). The mean birth weight of babies was significantly lower (2.02 ± 0.58 kg vs. 2.71 ± 0.68 kg; P < 0.001) and the incidence of stillbirth plus neonatal death was higher (7.5% vs. 4.6%, P = 0.01) in the twin group as compared to the singleton group., Conclusion: Twin deliveries, following IVF/ICSI deliver at lower gestational age, have lower birth weight and have higher odds of stillbirth plus neonatal death as compared to singleton deliveries following IVF/ICSI., Competing Interests: There are no conflicts of interest., (Copyright: © 2020 Journal of Human Reproductive Sciences.)

This article represents a viewpoint on the POSEIDON criteria by a group of clinicians and embryologists. Its primary objective is to contextualize the Poseidon criteria and their metric of success for the relevant Frontiers Research Topic "POSEIDON's Stratification of Low Prognosis Patients in ART: The WHY, the WHAT, and the HOW". "Low prognosis" relates with reduced oocyte number, which can be associated with low or sometimes a normal ovarian reserve and is aggravated by advanced female age. These aspects will ultimately affect the number of embryos generated and consequently, the cumulative live birth rate. The novel system relies on female age, ovarian reserve markers, ovarian sensitivity to exogenous gonadotropin, and the number of oocytes retrieved, which will both identify the patients with low prognosis and stratify such patients into one of four groups of women with "expected" or "unexpected" impaired ovarian response to exogenous gonadotropin stimulation. Furthermore, the POSEIDON group introduced a new measure of clinical success in ART, namely, the ability to retrieve the number of oocytes needed to obtain at least one euploid blastocyst for transfer in each patient. Using the POSEIDON criteria, the clinician can firstly identify and classify patients who have low prognosis in ART, and secondly, aim at designing an individualized treatment plan to maximize the chances of achieving the POSEIDON measure of success in each of the four low prognosis groups. The novel POSEIDON classification system is anticipated to improve counseling and management of low prognosis patients undergoing ART, with an expected positive effect on reproductive success and a reduction in the time to live birth., (Copyright © 2019 Esteves, Alviggi, Humaidan, Fischer, Andersen, Conforti, Bühler, Sunkara, Polyzos, Galliano, Grynberg, Yarali, Özbek, Roque, Vuong, Banker, Rienzi, Vaiarelli, Cimadomo and Ubaldi.)

Background: Lymphedema of limbs is caused by partial or total obstruction of lymphatic collectors. In advanced cases all main lymphatics are obstructed and tissue fluid accumulates in the interstitial spaces. The microsurgical lympho-venous shunts cannot be performed. We propose in such cases drainage of fluid accumulations by creating artificial flow pathways to the nonobstructed regions by implantation of silicone tubes. Aim: To present the 3 to over 6 year follow-up results of therapy by subcutaneous implantation of silicone tubes. Methods: In 150 patients with obstructive limb lymphedema after pelvic or axillary lymphadenectomy and irradiation in uterine or breast cancer or following soft tissue inflammation silicone tubes were implanted subcutaneously. Results: There was (1) immediate decrease of limb circumference within days after implantation; (2) in lower limbs in a 3-year follow-up a decrease in mid-calf circumference by a mean -8.7% ( p  < 0.05) with range of -3.2% to -31.0% corresponding to 90-900 mL volume and in the mid-thigh a mean -1.8% ( p  < 0.05) with range of -9.3% to +3% equal to 0-900 mL. In the upper limb in the 2-year follow-up the decrease in the mid-forearm was -8.5% ( p  < 0.01) with a range of -3.0% to -22.0% and in the mid-arm a mean -12% ( p  < 0.05) with a range of -7% to -22%. That corresponded to 180-700 mL volume for the limb; (3) decreased tissue stiffness; (4) maintenance of tubes patency on control lymphoscintigraphy, contrast opacification, and ultrasonography; and (5) lack of reaction to foreign body and effective control of inflammation at the site of implantation using low doses of benzathine penicillin. Conclusions: The technical simplicity of the surgical procedure, fast decrease of limb edema, and lack of tissue reaction to the implant make the method worth applying in advanced stages of lymphedema.

Study Objectives: Sleep deprivation and low sleep quality are widespread among adolescents, and associate with obesity risk. Plausible mediators include diet and physical activity. Another potential interrelated pathway, as yet unexplored in adolescents, could involve epigenetic modification of metabolism genes., Methods: In a cohort of 351 Mexico City adolescents (47% male; mean [SD] age = 14 [2] years), 7-day actigraphy was used to assess average sleep duration, sleep fragmentation, and movement index. DNA isolated from blood leukocytes was bisulfite-converted, amplified, and pyrosequenced at four candidate regions. Linear mixed models evaluated sex-stratified associations between sleep characteristics (split into quartiles [Q]) and DNA methylation of each region, adjusted for potential confounders., Results: Mean sleep duration was 8.5 [0.8] hours for boys and 8.7 [1] hours for girls. There were sex-specific associations between sleep duration and LINE-1 (long interspersed nuclear element) methylation. Boys with longer sleep duration (Q4) had lower LINE-1 methylation than boys in the 3rd quartile reference category, while girls with both longer and shorter sleep duration had higher LINE-1 methylation compared to Q3. Longer sleep duration was associated with higher H19 methylation among girls (comparing highest to third quartile, -0.9% [-2.2, 0.5]; p, trend = 0.047). Sleep fragmentation was inversely associated with peroxisome proliferator-activated receptor alpha (PPARA) methylation among girls (comparing highest to lowest fragmentation quartile, 0.9% [0.1 to 1.8]). Girls also showed an inverse association between sleep fragmentation and hydroxysteroid (11-beta) dehydrogenase 2 (HSD11B2; Q4 to Q1, 0.6% [-1.2%, 0%])., Conclusions: Sleep duration and fragmentation in adolescents show sex-specific associations with leukocyte DNA methylation patterns of metabolism genes., (© Sleep Research Society 2019. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Introduction: This study was conducted to evaluate and compare the incidence of birth defects in In-Vitro Fertilization-Intra Cytoplasmic Sperm Injection (IVF-ICSI) pregnancies with autologous and donor oocytes. As a secondary outcome, the prevalence of birth defects in IVF-ICSI pregnancies was compared with those from spontaneous conceptions in India., Material and Methods: This retrospective study included 2444 births resulting from IVF-ICSI cycles from autologous (n = 1743) and donor oocytes (n = 701) during a 3-year period in an Indian infertility center. Birth defects, if any, were noted antenatally and followed till the neonatal period, in case of live birth., Results: The overall prevalence of birth defects in IVF-ICSI pregnancies in this study was 29/2444 (118.6/10 000 births) and the most common congenital anomaly was cardiac malformation (32.7/10 000 births) followed by genitourinary (28.6/10 000 births). The risks of birth defects resulting from autologous and donor oocytes did not differ (114.7/10 000 vs 128.38/10 000; P > 0.05). However, pregnancies resulting from autologous oocytes had a higher trend of gastrointestinal birth defects (20.5/10 000 births vs 0), though not statistically significant. The risk of cardiovascular birth defects resulting from IVF-ICSI pregnancies was much higher compared with the natural conceptions in India (32.7/10 000 vs 12.7/10 000 births; P = 0.03), whereas the risk of central nervous system malformations was much lower (8.1/10 000 vs 60.18/10 000 births; P = 0.005)., Conclusions: Overall, there was no significant difference in birth defects resulting from IVF-ICSI with autologous or donor oocytes. The births resulting from IVF-ICSI pregnancies did not tend to have a higher rate of birth defects a compared with natural conceptions. The differences in the prevalence of certain birth defects (cardiovascular or central nervous system) reported in IVF-ICSI pregnancies may be due to improved surveillance modalities and early detection in pregnancies following IVF-ICSI. A study with larger number of sample size will give us better understanding of the prevalence of reported incidence in this study., (© 2019 Nordic Federation of Societies of Obstetrics and Gynecology.)

Endocrine disrupting chemicals (EDCs) are ubiquitous, and pregnancy is a sensitive window for toxicant exposure. EDCs may disrupt the maternal immune system, which may lead to poor pregnancy outcomes. Most studies investigate single EDCs, even though "real life" exposures do not occur in isolation. We tested the hypothesis that uniquely weighted mixtures of early pregnancy exposures are associated with distinct changes in the maternal and neonatal inflammasome. First trimester urine samples were tested for 12 phthalates, 12 phenols, and 17 metals in 56 women. Twelve cytokines were measured in first trimester and term maternal plasma, and in cord blood after delivery. Spearman correlations and linear regression were used to relate individual exposures with inflammatory cytokines. Linear regression was used to relate cytokine levels with gestational age and birth weight. Principal component analysis was used to assess the effect of weighted EDC mixtures on maternal and neonatal inflammation. Our results demonstrated that maternal and cord blood cytokines were differentially associated with (1) individual EDCs and (2) EDC mixtures. Several individual cytokines were positively associated with gestational age and birth weight. These observed associations between EDC mixtures and the pregnancy inflammasome may have clinical and public health implications for women of childbearing age.