Feldmanmcfarland0399
individualized information regarding the future risk of T2DM can be provided based on the type and number of abnormal OGTT values, as well as the diagnostic criteria used for the diagnosis of GDM.
In women with GDM, individualized information regarding the future risk of T2DM can be provided based on the type and number of abnormal OGTT values, as well as the diagnostic criteria used for the diagnosis of GDM.
To identify predictors of glycemic worsening among youth and adults with impaired glucose tolerance (IGT) or recently diagnosed type 2 diabetes in the Restoring Insulin Secretion (RISE) Study.
A total of 91 youth (10-19 years) were randomized 11 to 12 months of metformin (MET) or 3 months of glargine, followed by 9 months of metformin (G-MET), and 267 adults were randomized to MET, G-MET, liraglutide plus MET (LIRA+MET), or placebo for 12 months. All participants underwent a baseline hyperglycemic clamp and a 3-h oral glucose tolerance test (OGTT) at baseline, month 6, month 12, and off treatment at month 15 and month 21. Cox models identified baseline predictors of glycemic worsening (HbA
increase ≥0.5% from baseline).
Glycemic worsening occurred in 17.8% of youth versus 7.5% of adults at month 12 (
= 0.008) and in 36% of youth versus 20% of adults at month 21 (
= 0.002). In youth, glycemic worsening did not differ by treatment. In adults, month 12 glycemic worsening was less on LIRA+MET versus p.
To determine whether β-cell hyperresponsiveness and insulin resistance in youth versus adults in the Restoring Insulin Secretion (RISE) Study are related to increased glucagon release.
In 66 youth and 350 adults with impaired glucose tolerance (IGT) or recently diagnosed type 2 diabetes (drug naïve), we performed hyperglycemic clamps and oral glucose tolerance tests (OGTTs). From clamps we quantified insulin sensitivity (M/I), plasma fasting glucagon and C-peptide, steady-state glucagon and C-peptide at glucose of 11.1 mmol/L, and arginine-stimulated glucagon (acute glucagon response [AGR]) and C-peptide (ACPRmax) responses at glucose >25 mmol/L.
Mean ± SD fasting glucagon (7.63 ± 3.47 vs. 8.55 ± 4.47 pmol/L;
= 0.063) and steady-state glucagon (2.24 ± 1.46 vs. 2.49 ± 1.96 pmol/L,
= 0.234) were not different in youth and adults, respectively, while AGR was lower in youth (14.1 ± 5.2 vs. 16.8 ± 8.8 pmol/L,
= 0.001). Significant age-group differences in insulin sensitivity, fasting C-peptide, s have hyperresponsive β-cells and lower insulin sensitivity, but their glucagon concentrations are not increased compared with those in adults. Thus, α-cell dysfunction does not appear to explain the difference in β-cell function and insulin sensitivity in youth versus adults.
Women are broadly underrepresented in scientific leadership positions and their accomplishments are not provided equal recognition compared with those of men, but the imbalance in the field of diabetes is unknown. Hence, we analyzed multiple aspects of historical and present-day female representation in the diabetes field.
We quantified gender representation at annual American Diabetes Association (ADA) meetings; editorial board service positions for ADA and the European Association for the Study of Diabetes (EASD) journals; principal investigators for ADA, JDRF, and National Institutes of Health National Institute of Diabetes and Digestive and Kidney Diseases P30 grant funding; and ADA, JDRF, and EASD award recipients.
There are many women in the field of diabetes registration for the ADA Scientific Sessions has been 43% female since 2016, and for over five decades, women comprised 83% of ADA Presidents of Health Care and Education. Yet, only 9% of ADA Presidents of Medicine and Science have been womenment of female investigators and creating environments that promote their retention and equitable recognition for their contributions to the field.
A diverse pediatric workforce reflecting the racial/ethnic representation of the US population is an important factor in eliminating health inequities. Studies reveal minimal improvements over time in the proportions of underrepresented in medicine (URiM) physicians; however, studies assessing trends in pediatric URiM trainee representation are limited. Our objective was to evaluate longitudinal trends in racial/ethnic representation among a cross-section of US pediatric trainees and to compare it to the US population.
Repeated cross-sectional study of graduate medical education census data on self-reported race/ethnicity of pediatric residents and subspecialty fellows from 2007 to 2019. To evaluate trends in URiM proportions over time , the Cochran-Armitage test was performed. Data on self-reported race/ethnicity of trainees were compared with the general population data over time by using US Census Bureau data.
Trends in URiM proportions were unchanged in residents (16% in 2007 to 16.5% in 2019;
= .98) and, overall, decreased for fellows (14.2% in 2007 to 13.5% in 2019;
= .002). URiM fellow trends significantly decreased over time in neonatal-perinatal medicine (
< .001), infectious diseases (
< .001), and critical care (
= .006) but significantly increased in endocrinology (
= .002) and pulmonology (
= .009). Over time, the percentage of URiM pediatric trainee representation was considerably lower compared to the US population.
The continued underrepresentation of URiM pediatric trainees may perpetuate persistent health inequities for minority pediatric populations. There is a critical need to recruit and retain pediatric URiM residents and subspecialty fellows.
The continued underrepresentation of URiM pediatric trainees may perpetuate persistent health inequities for minority pediatric populations. There is a critical need to recruit and retain pediatric URiM residents and subspecialty fellows.
Neoadjuvant chemotherapy with interval debulking surgery represents an alternative treatment for advanced ovarian cancer. Currently, there are few data about the use of poly adenosine diphosphate-ribose polymerase inhibitors in the neoadjuvant setting.
To evaluate whether the administration of olaparib in combination with standard chemotherapy in the neoadjuvant setting can improve tumor response.
The addition of a poly adenosine diphosphate-ribose polymerase inhibitor to standard chemotherapy will achieve a higher response rate in BRCA mutated patients compared with standard chemotherapy TRIAL DESIGN This is a multicenter, phase II, single arm, open label trial. Eligible patients will receive three cycles of weekly carboplatin plus paclitaxel, and intermittent olaparib administration. Responding patients will undergo an interval debulking surgery with pathological evaluation of response to chemotherapy.
Patients must have histologically confirmed International Federation of Gynecology and Obstetrics stages III-IV primary ovarian, peritoneal, or fallopian tube cancers, high grade serous or endometrioid histology, not suitable for primary cytoreductive surgery with a documented BRCA1 or BRCA2 germline and/or somatic mutation.
Rate of complete pathological response after three cycles of the experimental chemotherapy regimen.
A total of 35 patients will be enrolled in the study.
Expected complete 42 accrual in January 2022, with presentation of results by June 2022.
NCT04261465.
NCT04261465.Critical decisions, such as in domains ranging from medicine to finance, are often made under threatening circumstances that elicit stress and anxiety. The negative effects of such reactions on learning and decision-making have been repeatedly underscored. In contrast, here we show that perceived threat alters the process by which evidence is accumulated in a way that may be adaptive. Participants (n = 91) completed a sequential evidence sampling task in which they were incentivized to accurately judge whether they were in a desirable state, which was associated with greater rewards than losses, or an undesirable state, which was associated with greater losses than rewards. Before the task participants in the "threat group" experienced a social-threat manipulation. Results show that perceived threat led to a reduction in the strength of evidence required to reach an undesirable judgment. Computational modeling revealed this was because of an increase in the relative rate by which negative information was accumulated. The effect of the threat manipulation was global, as the alteration to evidence accumulation was observed for information which was not directly related to the cause of the threat. Requiring weaker evidence to reach undesirable conclusions in threatening environments may be adaptive as it can lead to increased precautionary action.SIGNIFICANCE STATEMENT To make good judgments, people gather information. As information is often unlimited, a decision has to be made as to when the data are sufficiently strong to reach a conclusion. selleck chemicals llc Here, we show that this decision is significantly influenced by perceived threat. In particular, under threat, the rate of negative information accumulation increased, such that weaker evidence was required to reach an undesirable conclusion. Such modulation could be adaptive as it can result in enhanced cautious behavior in dangerous environments.The nonpsychoactive phytocannabinoid cannabidiol (CBD) has been shown to have analgesic effects in animal studies but little is known about its mechanism of action. We examined the effects of CBD on intrinsic excitability of primary pain-sensing neurons. Studying acutely dissociated capsaicin-sensitive mouse DRG neurons at 37°C, we found that CBD effectively inhibited repetitive action potential firing, from 15-20 action potentials evoked by 1 s current injections in control to 1-3 action potentials with 2 μm CBD. Reduction of repetitive firing was accompanied by a reduction of action potential height, widening of action potentials, reduction of the afterhyperpolarization, and increased propensity to enter depolarization block. Voltage-clamp experiments showed that CBD inhibited both TTX-sensitive and TTX-resistant (TTX-R) sodium currents in a use-dependent manner. CBD showed strong state-dependent inhibition of TTX-R channels, with fast binding to inactivated channels during depolarizations and slow unbindins. We find that CBD interacts with TTX-resistant sodium channels in a state-dependent manner suggesting particularly tight binding to slow inactivated states of Nav1.8 channels, which dominate the overall inactivation of Nav1.8 channels for small maintained depolarizations from the resting potential. The results suggest that CBD can exert analgesic effects in part by directly inhibiting repetitive firing of primary nociceptors and suggest a strategy of identifying compounds that bind selectively to slow inactivated states of Nav1.8 channels for developing effective analgesics.Functional magnetic resonance imaging (fMRI) is among the foremost methods for mapping human brain function but provides only an indirect measure of underlying neural activity. Recent findings suggest that the neurophysiological correlates of the fMRI blood-oxygen-level-dependent (BOLD) signal might be regionally specific. We examined the neurophysiological correlates of the fMRI BOLD signal in the hippocampus and neocortex, where differences in neural architecture might result in a different relationship between the respective signals. Fifteen human neurosurgical patients (10 female, 5 male) implanted with depth electrodes performed a verbal free recall task while electrophysiological activity was recorded simultaneously from hippocampal and neocortical sites. The same patients subsequently performed a similar version of the task during a later fMRI session. Subsequent memory effects (SMEs) were computed for both imaging modalities as patterns of encoding-related brain activity predictive of later free recall.
