Urinary Paraben Concentrations and Ovarian Aging among Women from a Fertility Center

Background: Parabens are preservatives commonly used in personal care products, pharmaceuticals, and foods. There is documented widespread human exposure to parabens, and some experimental data suggest that they act as estrogenic endocrine disruptors. As far as we are aware, no epidemiologic studies have assessed female reproductive health effects in relation to paraben exposure. Objective: We examined the association of urinary paraben concentrations with markers of ovarian reserve in a prospective cohort study of women seeking fertility treatment at Massachusetts General Hospital, Boston, Massachusetts. Methods: Measures of ovarian reserve were day-3 follicle-stimulating hormone (FSH), antral follicle count (AFC), and ovarian volume. Paraben concentrations [methylparaben (MP), propylparaben (PP), and butylparaben (BP)] were measured in spot urine samples collected prior to the assessment of outcome measures. We used linear and Poisson regression models to estimate associations of urinary paraben concentrations (in tertiles) with ovarian reserve measures. Results: Of the women enrolled in 2004–2010, 192 had at least one ovarian reserve outcome measured (mean age ± SD, 36.1 ± 4.5 years; range, 21.0–46.7 years). MP and PP were detected in > 99% of urine samples and BP in > 75%. We found a suggestive trend of lower AFC with increasing urinary PP tertiles [mean percent change (95% CI) for tertiles 2 and 3 compared with tertile 1, respectively, were –5.0% (–23.7, 18.4) and –16.3% (–30.8, 1.3); trend p-value (ptrend) = 0.07] as well as higher day-3 FSH with higher urinary PP tertiles [mean change (95% CI) for tertiles 2 and 3 compared with tertile 1 were 1.16 IU/L (–0.26, 2.57) and 1.02 IU/L (–0.40, 2.43); ptrend = 0.16]. We found no consistent evidence of associations between urinary MP or BP and day-3 FSH or AFC, or between urinary MP, PP, or BP and ovarian volume. Conclusions: PP may be associated with diminished ovarian reserve. However, our results require confirmation in further studies. Citation: Smith KW, Souter I, Dimitriadis I, Ehrlich S, Williams PL, Calafat AM, Hauser R. 2013. Urinary paraben concentrations and ovarian aging among women from a fertility center. Environ Health Perspect 121:1299–1305; http://dx.doi.org/10.1289/ehp.120535

Delving into instructor‐led feedback interventions informed by learning analytics in massive open online courses

Producción CientíficaBackground:Providing feedback in massive open online courses (MOOCs) is chal-lenging due to the massiveness and heterogeneity of learners' population. Learninganalytics (LA) solutions aim at scaling up feedback interventions and supportinginstructors in this endeavour.Paper Objectives:This paper focuses on instructor-led feedback mediated by LAtools in MOOCs. Our goal is to answer how, to what extent data-driven feedback isprovided to learners, and what its impact is.Methods:We conducted a systematic literature review on the state-of-the-art LA-informed instructor-led feedback in MOOCs. From a pool of 227 publications, weselected 38 articles that address the topic of LA-informed feedback in MOOCs medi-ated by instructors. We applied etic content analysis to the collected data.Results and Conclusions:The results revealed a lack of empirical studies exploring LA todeliver feedback, and limited attention on pedagogy to inform feedback practices. Our find-ings suggest the need for systematization and evaluation of feedback. Additionally, there isa need for conceptual tools to guide instructors' in the design of LA-based feedback.Takeaways:We point out the need for systematization and evaluation of feedback. Weenvision that this research can support the design of LA-based feedback, thus contribut-ing to bridge the gap between pedagogy and data-driven practice in MOOCs.Consejo de Investigación de Estonia (PSG286)Ministerio de Ciencia e Innovación - Fondo Europeo de Desarrollo Regional y la Agencia Nacional de Investigación (grant PID2020-112584RB-C32) and (grant TIN2017-85179-C3-2-R)Junta de Castilla y León - Fondo Social Europeo y el Consejo Regional de Educación (grant E-47-2018-0108488

Strong Carbon Features and a Red Early Color in the Underluminous Type Ia SN 2022xkq

We present optical, infrared, ultraviolet, and radio observations of SN 2022xkq, an underluminous fast-declining type Ia supernova (SN Ia) in NGC 1784 ($\mathrm{D}\approx31$ Mpc), from $<1$ to 180 days after explosion. The high-cadence observations of SN 2022xkq, a photometrically transitional and spectroscopically 91bg-like SN Ia, cover the first days and weeks following explosion which are critical to distinguishing between explosion scenarios. The early light curve of SN 2022xkq has a red early color and exhibits a flux excess which is more prominent in redder bands; this is the first time such a feature has been seen in a transitional/91bg-like SN Ia. We also present 92 optical and 19 near-infrared (NIR) spectra, beginning 0.4 days after explosion in the optical and 2.6 days after explosion in the NIR. SN 2022xkq exhibits a long-lived C I 1.0693 $\mu$m feature which persists until 5 days post-maximum. We also detect C II $\lambda$6580 in the pre-maximum optical spectra. These lines are evidence for unburnt carbon that is difficult to reconcile with the double detonation of a sub-Chandrasekhar mass white dwarf. No existing explosion model can fully explain the photometric and spectroscopic dataset of SN 2022xkq, but the considerable breadth of the observations is ideal for furthering our understanding of the processes which produce faint SNe Ia.Comment: 38 pages, 16 figures, accepted for publication in ApJ, the figure 15 input models and synthetic spectra are now available at https://zenodo.org/record/837925

Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Background: Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Methods: We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515. Findings: Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p&lt;0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (&lt;1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (&lt;1%) deaths in the albiglutide group. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes. Funding: GlaxoSmithKline

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome-Metabolic Disease or Disturbed Homeostasis due to Focal Inflammation in the Hypothalamus?

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex disease characterized by debilitating fatigue, lasting for at least 6 months, with associated malaise, headaches, sleep disturbance, and cognitive impairment, which severely impacts quality of life. A significant percentage of ME/CFS patients remain undiagnosed, mainly due to the complexity of the disease and the lack of reliable objective biomarkers. ME/CFS patients display decreased metabolism and the severity of symptoms appears to be directly correlated to the degree of metabolic reduction that may be unique to each individual patient. However, the precise pathogenesis is still unknown, preventing the development of effective treatments. The ME/CFS phenotype has been associated with abnormalities in energy metabolism, which are apparently due to mitochondrial dysfunction in the absence of mitochondrial diseases, resulting in reduced oxidative metabolism. Such mitochondria may be further contributing to the ME/CFS symptomatology by extracellular secretion of mitochondrial DNA, which could act as an innate pathogen and create an autoinflammatory state in the hypothalamus. We propose that stimulation of hypothalamic mast cells by environmental, neuroimmune, pathogenic and stress triggers activates microglia, leading to focal inflammation in the brain and disturbed homeostasis. This process could be targeted for the development of novel effective treatments

Placental weight in relation to maternal and paternal preconception and prenatal urinary phthalate metabolite concentrations among subfertile couples.

Phthalates are known reproductive toxicants that reduce placental and fetal weight in experimental animal studies. Although phthalate exposure has been associated with reduced birth weight in humans, there is limited epidemiologic evidence on whether the placenta is also affected. To assess whether maternal and paternal preconception and prenatal urinary phthalate metabolite concentrations are associated with placental weight, and the birth weight: placental weight (BW:PW) ratio among singletons conceived by subfertile couples. The present analysis included 132 mothers and 68 fathers, and their corresponding 132 singletons recruited in an academic hospital fertility center in Boston, Massachusetts. Urinary concentrations of eleven phthalate metabolites were measured and averaged in multiple paternal (n = 196) and maternal (n = 596) preconception, and maternal prenatal (n = 328) samples. Placental weight and birth weight (grams) were abstracted from delivery records, and the BW:PW was calculated. We estimated the association of natural log-phthalate metabolite concentrations across windows of exposure with placental weight and the BW:PW ratio using multivariable linear regression models, adjusting for a priori covariates. In adjusted models, each log-unit increase in paternal urinary concentrations of the sum of di-(2-ethylhexyl) phthalate (ΣDEHP) metabolites was associated with a 24 g (95% CI: -48, -1) decrease in placental weight. We also observed a significant negative association between maternal preconception monoethyl phthalate (MEP) metabolite concentrations and the BW:PW ratio (β = -0.26; 95%CI: -0.49, -0.04). Additionally, each log-unit increase in prenatal MEP metabolite concentrations was associated with a 24 g (95% CI: -41, -7) decrease in placental weight. Our results suggest that certain paternal and maternal urinary phthalate metabolites may affect placental weight and the BW:PW ratio. However, given the small sample size within a subfertile cohort and the novelty of these findings, more studies are needed to confirm the present results

Automated smartphone-based system for measuring sperm viability, DNA fragmentation, and hyaluronic binding assay score.

The fundamental test for male infertility, semen analysis, is mostly a manually performed subjective and time-consuming process and the use of automated systems has been cost prohibitive. We have previously developed an inexpensive smartphone-based system for at-home male infertility screening through automatic and rapid measurement of sperm concentration and motility. Here, we assessed the feasibility of using a similar smartphone-based system for laboratory use in measuring: a) Hyaluronan Binding Assay (HBA) score, a quantitative score describing the sperm maturity and fertilization potential in a semen sample, b) sperm viability, which assesses sperm membrane integrity, and c) sperm DNA fragmentation that assesses the degree of DNA damage. There was good correlation between the manual analysis and smartphone-based analysis for the HBA score when the device was tested with 31 fresh, unprocessed human semen samples. The smartphone-based approach performed with an accuracy of 87% in sperm classification when the HBA score was set at manufacturer's threshold of 80. Similarly, the sperm viability and DNA fragmentation tests were also shown to be compatible with the smartphone-based system when tested with 102 and 47 human semen samples, respectively