Tolerance, bioavailability, and potential cognitive health implications of a distinct aqueous spearmint extract

Background: Cognitive function can decline during the aging process and significantly reduce quality of life. Although a number of interventions have been investigated for cognitive dysfunction, including antioxidants, this prominent health concern emphasizes a need to explore methods to support cognitive health later in the life span. An aqueous extract from a proprietary spearmint line has been developed which contains a number of antioxidant compounds, including rosmarinic acid, at levels that are higher than found in commercially-bred spearmint. Therefore, this pilot trial assessed the tolerance, bioavailability, and potential cognitive health implications of a proprietary spearmint extract in men and women with self-reported memory impairment. Methods: Subjects consumed 900 mg/day spearmint extract for 30 days. The sample population (N = 11) was 73% female and 27% male with a mean age of 58.7 ± 1.6 y. Tolerability parameters were assessed at baseline and end of treatment visits. Computerized cognitive function tests were completed and blood was drawn at pre- and post-dose (0.5 to 4 h) timepoints during baseline and end of treatment visits. Subjective cognition was also assessed at end of treatment. Results: No serious adverse events or clinically relevant findings were observed in any tolerability parameters. Plasma vanillic, caffeic, and ferulic acid sulfates, rosmarinic acid, and methyl rosmarinic acid glucuronide were detected in plasma following acute administration of the spearmint extract. Computerized cognitive function scores improved in reasoning (P = 0.023) and attention/concentration (P = 0.002) after 30 days of supplementation. After acute administration, subjects had improved attention/concentration in two tests at 2 (P = 0.042 and P = 0.025) and 4 h (P = 0.001 and P = 0.002). Conclusions: The results from this pilot trial suggest that the spearmint extract, which contains higher rosmarinic acid content relative to extracts from typical commercial lines, was welltolerated at 900 mg/day. In addition, the extract was bioavailable and further investigation is warranted regarding its potential for supporting cognitive healt

Sustainability and resilience in midwifery: A discussion paper

Background midwifery workforce issues are of international concern. Sustainable midwifery practice, and how resilience is a required quality for midwives, have begun to be researched. How these concepts are helpful to midwifery continues to be debated. It is important that such debates are framed so they can be empowering for midwives. Care is required not to conceptually label matters concerning the midwifery workforce without judicious scrutiny and diligence. Aim the aim of this discussion paper is to explore the concepts of sustainability and resilience now being suggested in midwifery workforce literature. Whether sustainability and resilience are concepts useful in midwifery workforce development is questioned. Method using published primary midwifery research from United Kingdom and New Zealand the concepts of sustainability and resilience are compared, contrasted and explored. Findings there are obvious differences in models of midwifery care in the United Kingdom and New Zealand. Despite these differences, the concepts of resilience and sustainability emerge as overlapping themes from the respective studies’ findings. Comparison between studies provides evidence of what is crucial in sustaining healthy resilient midwifery practice. Four common themes have been identified that traverse the different models of care; Self-determination, ability to self-care, cultivation of relationships both professionally and with women/families, and a passion, joy and love for midwifery. Conclusions the impact that midwifery models of care may have on sustainable practice and nurturing healthy resilient behaviors remains uncertain. The notion of resilience in midwifery as the panacea to resolve current concerns may need rethinking. Resilience may be interpreted as expecting midwives ‘to toughen up’ in a workplace setting that is socially, economically and culturally challenging. Sustainability calls for examination of the reciprocity between environments of working and the individual midwife. The findings invite further examination of contextual influences that affect the wellbeing of midwives across different models of care

CATMoS: Collaborative Acute Toxicity Modeling Suite.

BACKGROUND: Humans are exposed to tens of thousands of chemical substances that need to be assessed for their potential toxicity. Acute systemic toxicity testing serves as the basis for regulatory hazard classification, labeling, and risk management. However, it is cost- and time-prohibitive to evaluate all new and existing chemicals using traditional rodent acute toxicity tests. In silico models built using existing data facilitate rapid acute toxicity predictions without using animals. OBJECTIVES: The U.S. Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM) Acute Toxicity Workgroup organized an international collaboration to develop in silico models for predicting acute oral toxicity based on five different end points: Lethal Dose 50 (LD50 value, U.S. Environmental Protection Agency hazard (four) categories, Globally Harmonized System for Classification and Labeling hazard (five) categories, very toxic chemicals [LD50 (LD50≤50mg/kg)], and nontoxic chemicals (LD50>2,000mg/kg). METHODS: An acute oral toxicity data inventory for 11,992 chemicals was compiled, split into training and evaluation sets, and made available to 35 participating international research groups that submitted a total of 139 predictive models. Predictions that fell within the applicability domains of the submitted models were evaluated using external validation sets. These were then combined into consensus models to leverage strengths of individual approaches. RESULTS: The resulting consensus predictions, which leverage the collective strengths of each individual model, form the Collaborative Acute Toxicity Modeling Suite (CATMoS). CATMoS demonstrated high performance in terms of accuracy and robustness when compared with in vivo results. DISCUSSION: CATMoS is being evaluated by regulatory agencies for its utility and applicability as a potential replacement for in vivo rat acute oral toxicity studies. CATMoS predictions for more than 800,000 chemicals have been made available via the National Toxicology Program's Integrated Chemical Environment tools and data sets (ice.ntp.niehs.nih.gov). The models are also implemented in a free, standalone, open-source tool, OPERA, which allows predictions of new and untested chemicals to be made. https://doi.org/10.1289/EHP8495

The genomic landscape of balanced cytogenetic abnormalities associated with human congenital anomalies

Despite the clinical significance of balanced chromosomal abnormalities (BCAs), their characterization has largely been restricted to cytogenetic resolution. We explored the landscape of BCAs at nucleotide resolution in 273 subjects with a spectrum of congenital anomalies. Whole-genome sequencing revised 93% of karyotypes and demonstrated complexity that was cryptic to karyotyping in 21% of BCAs, highlighting the limitations of conventional cytogenetic approaches. At least 33.9% of BCAs resulted in gene disruption that likely contributed to the developmental phenotype, 5.2% were associated with pathogenic genomic imbalances, and 7.3% disrupted topologically associated domains (TADs) encompassing known syndromic loci. Remarkably, BCA breakpoints in eight subjects altered a single TAD encompassing MEF2C, a known driver of 5q14.3 microdeletion syndrome, resulting in decreased MEF2C expression. We propose that sequence-level resolution dramatically improves prediction of clinical outcomes for balanced rearrangements and provides insight into new pathogenic mechanisms, such as altered regulation due to changes in chromosome topology

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707

Perceptual changes in place of stimulation with long cochlear implant electrode arrays

Long (31.5 mm) electrode arrays are inserted deeper into the cochlea than the typical 1.25 turn insertion. With these electrode arrays, the apical electrodes are closer to (and possibly extend past) the end of the spiral ganglion. Using multi-dimensional scaling with patients implanted with a 31.5 mm electrode array, the perceptual space between electrodes was measured. The results suggest that deeper insertion increases the range of place pitches, but the perceptual differences between adjacent electrodes become smaller in the apex

The Journal of Nutrition Nutrition and Disease Resistant Starch from High-Amylose Maize Increases Insulin Sensitivity in Overweight and Obese Men 1-3

Abstract This study evaluated the effects of 2 levels of intake of high-amylose maize type 2 resistant starch (HAM-RS2) on insulin sensitivity (S I ) in participants with waist circumference $89 (women) or$102 cm (men). Participants received 0 (control starch), 15, or 30 g/d (double-blind) of HAM-RS2 in random order for 4-wk periods separated by 3-wk washouts. Minimal model S I was assessed at the end of each period using the insulin-modified i.v. glucose tolerance test. The efficacy evaluable sample included 11 men and 22 women (mean 6 SEM) age 49.5 6 1.6 y, with a BMI of 30.6 6 0.5 kg/m 2 and waist circumference 105.3 6 1.3 cm. A treatment main effect (P = 0.018) and a treatment 3 sex interaction (P = 0. Additional research is needed to understand the mechanisms that might account for the treatment 3 sex interaction observed