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isk of pregnancy and did not contribute to the analysis. Some couples may not have recorded all intercourse.

We believe the current balance of evidence does not support a recommendation for avoiding intercourse in the peri-implantation period among couples trying to conceive.

No external funding. The authors have no potential competing interests.

N/A.

N/A.

Fosfomycin is an antibiotic that has seen a revival in use due to its unique mechanism of action and efficacy against isolates resistant to many other antibiotics. In Escherichia coli, fosfomycin often selects for loss-of-function mutations within the genes encoding the sugar importers, GlpT and UhpT. There has, however, not been a genome-wide analysis of the basis for fosfomycin susceptibility reported to date.

Here we used TraDIS-Xpress, a high-density transposon mutagenesis approach, to assay the role of all genes in E. coli involved in fosfomycin susceptibility.

The data confirmed known fosfomycin susceptibility mechanisms and identified new ones. The assay was able to identify domains within proteins of importance and revealed essential genes with roles in fosfomycin susceptibility based on expression changes. Novel mechanisms of fosfomycin susceptibility that were identified included those involved in glucose metabolism and phosphonate catabolism (phnC-M), and the phosphate importer, PstSACB. The impact of these genes on fosfomycin susceptibility was validated by measuring the susceptibility of defined inactivation mutants.

This work reveals a wider set of genes that contribute to fosfomycin susceptibility, including core sugar metabolism genes and two systems involved in phosphate uptake and metabolism previously unrecognized as having a role in fosfomycin susceptibility.

This work reveals a wider set of genes that contribute to fosfomycin susceptibility, including core sugar metabolism genes and two systems involved in phosphate uptake and metabolism previously unrecognized as having a role in fosfomycin susceptibility.

We validated an aging mindset measure that captures beliefs about the process of aging. Specifically, we introduce a brief 4-item and an extended 10-item measure assessing (non)essentialist beliefs about aging.

We report findings from one longitudinal and one cross-cultural study, including young, middle-aged, and older adults between 18 and 88 years. The studies established (retest) reliability and measurement invariance as well as convergent and discriminant validity of the measures.

First, in a longitudinal study (N = 124, 50- 84 years) including 4 measurement occasions, we showed that the 4-item scale assessing (non)essentialist beliefs about aging has good retest-reliability and convergent as well as discriminant validity (e.g., awareness of age-related change, AARC). Second, in a large cross-cultural sample (N = 1,080, 18-82 years) of participants in the US and Germany, we established an extended 10-item measure of (non)essentialist beliefs about aging, providing support for a two-factor structure as well as measurement invariance across samples within and across countries (US and Germany), age groups (young, middle-aged, and older adults), as well as across men and women.

Our results highlight the importance of distinguishing between fixed versus malleable aging beliefs in research on aging and lifespan development.

Our results highlight the importance of distinguishing between fixed versus malleable aging beliefs in research on aging and lifespan development.

The mental and physical health profile of autistic people has been studied in adolescence and adulthood, with elevated rates of most conditions being reported. However, this has been little studied taking a dimensional approach to autistic traits, and in older age.

A total of 20,220 adults aged 50-81 years from the PROTECT study reported whether they experienced persistent socio-communicative traits characteristic of autism. Approximately 1%, 276 individuals, were identified as endorsing elevated autistic traits in childhood and currently, henceforth the 'Autism Spectrum Trait' (AST) group. An age and gender matched comparison group was formed of 10,495 individuals who did not endorse any autistic behavioral traits, henceforth the 'Control Older Adults' (COA) group. Differences between AST and COA groups were explored in self-reported psychiatric diagnoses, self-reported symptoms of current depression and anxiety, and self-reported physical health diagnoses. Associations were also examined between autistidults with elevated autistic traits may be at greater risk of poorer mental, but not physical, health in later life. Future studies should incorporate polygenic scores to elucidate the possible genetic links between propensity to autism/high autistic traits and to psychiatric conditions, and to explore whether those with elevated autistic traits experience particular barriers to mental health care.

Controversy exists regarding if and how body mass index (BMI) impacts antimüllerian hormone (AMH) in women with and without polycystic ovary syndrome (PCOS). Understanding the BMI-AMH relationship has critical implications for clinical interpretation of laboratory values and could illuminate underlying ovarian physiology.

To test the hypotheses that (1) BMI is associated with reduced AMH in PCOS and ovulatory controls (OVAs) and (2) the reduction in AMH is not accounted for by dilutional effects.

Multicenter cohort.

Women aged 25 to 40 years from 2 clinical populations 640 with PCOS, 921 women as OVAs.

Ovarian reserve indices AMH, antral follicle count (AFC), and AMH to AFC ratio (AMH/AFC) as a marker of per-follicle AMH production.

In both cohorts, increasing BMI and waist circumference were associated with reductions in AMH and AMH/AFC, after adjusting for age, race, smoking, and site in multivariate regression models. Increasing BMI was associated with reduced AFC in PCOS but not OVAs. Body surface area (BSA), which unlike BMI is strongly proportional to plasma volume, was added to investigate a potential dilutive effect of body size on AMH concentrations. After controlling for BSA, BMI retained independent associations with AMH in both cohorts; BSA no longer associated with AMH.

In an adjusted analysis, BMI, but not BSA, was associated with reduced AMH; these data do not support a role for hemodilution in mediating the relationship between increased body size and reduced AMH. Staurosporine in vitro Decreased AMH production by the follicle unit may be responsible for reduced AMH with increasing BMI.

In an adjusted analysis, BMI, but not BSA, was associated with reduced AMH; these data do not support a role for hemodilution in mediating the relationship between increased body size and reduced AMH. Decreased AMH production by the follicle unit may be responsible for reduced AMH with increasing BMI.Antibiotic for clinical use lose its effectiveness over time due to bacterial resistance. In this work, four chalcones with modifications in their ligands were synthesized from the natural product 2-hydroxy-3,4,6-trimethoxyacetophenone, characterized by nuclear magnetic resonance (NMR) and infrared spectroscopy, and tested in bacterial models to investigate the direct and modifiers effects of the antibiotic activity of these four novel chalcones. The tests followed the broth microdilution methodology to obtain the Minimum Inhibitory Concentration (MIC). The MIC/8 of the products were used in the resistance reversion test. The chalcone 2 showed the best result in terms of direct activity, with MIC 645 μg/mL for Staphylococcus aureus and 812 μg/mL for Escherichia coli. While, for the bacterial resistance reversal test, the chalcones presented several synergistic interactions, being that chalcone 4 had the best interaction with the tested antibiotics. It was found that the type of ligand, as well as its position in the ring, interferes in the modulation of the antibiotic activity. Our results show that chalcones are strong candidates to be used as antibacterial drug or in combination with antibiotics for the treatment of infections caused by multidrug-resistant (MDR) strains.

In the next few decades, the number of Mexican American older adults with Alzheimer's Disease and Related Disorders (ADRD) will increase dramatically. Given that this population underutilizes formal care services, the degree of care responsibilities in Mexican American families is likely to increase at the same time. However, little is known about the changing need for assistance with instrumental day-to-day activities and emotional support by long-term patterns of cognitive impairment.

We use seven waves of the Hispanic EPESE (1992/1993-2010/2011) and trajectory modeling to describe long-term patterns of perceived emotional and instrumental support, and dementia.

Results revealed two latent classes of both emotional and instrumental support trajectories low and high support. Specifically, those living alone were more likely to belong to the group with low support than to that with high support. Three latent classes for likely dementia were also revealed likely dementia, increasing impairment, and no impairment. Those living alone were more likely to belong to the increasing impairment and likely dementia groups. The dual trajectory of emotional and instrumental support with likely dementia revealed that the probability of belonging to the low support group was highest for those with increasing impairment.

These findings highlight the risk and vulnerability of those who live alone concerning perceived social support and dementia. Implications of the findings for the potential dependency burden on Latino caregivers are discussed.

These findings highlight the risk and vulnerability of those who live alone concerning perceived social support and dementia. Implications of the findings for the potential dependency burden on Latino caregivers are discussed.Graft-versus-host disease (GVHD) remains a major limitation of allogeneic hematopoietic stem cell transplantation. Only half of patients with severe acute GVHD respond to first-line treatment with corticosteroids and, for several decades, there was no optimal second-line treatment of patients with corticosteroid-refractory acute GVHD. Ruxolitinib was recently approved for the treatment of corticosteroid-refractory acute GVHD in adult and pediatric patients 12 years and older. Thus, it is important to define the patient population that would now be considered as refractory to ruxolitinib vs ruxolitinib dependent. Here, we propose to define ruxolitinib-refractory acute GVHD as disease that shows (1) progression of GVHD compared with baseline after at least 5 to 10 days of treatment with ruxolitinib, based either on objective increase in stage/grade, or new organ involvement; (2) lack of improvement in GVHD (partial response or better) compared with baseline after ≥14 days of treatment with ruxolitinib; or (3) loss of response, defined as objective worsening of GVHD determined by increase in stage, grade, or new organ involvement at any time after initial improvement. GVHD manifestations that persist without improvement in patients who had a grade ≥3 treatment-emergent and ruxolitinib-attributed adverse event that did not resolve within 7 days of discontinuing ruxolitinib would serve as a clinical indication for additional treatment. In addition, absence of complete response or very good partial response at day 28 after ruxolitinib could be considered as an eligibility criterion.