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Introduction High-grade serous ovarian cancer (HGSOC) is characterized by high mortality and prevalent recurrences. This study investigates the prognostic value of phosphoglycerate dehydrogenase (PHGDH) in HGSOC which has been linked to metabolic reprogramming and recurrences in other cancers. Methods Data from 306 patients with advanced-stage HGSOC treated between 2008 and 2015 were analyzed. PHGDH expression levels were determined using immunohistochemistry and categorized as "low" or "high." Results PHGDH-high was associated with higher FIGO stage and increased use of neoadjuvant chemotherapy. Patients with PHGDH-high tumors had significantly worse survival than PHDH-low, even after adjusting for confounding factors. [ABSTRACT FROM AUTHOR]

Background: Ovarian granulosa cells (GCs) are essential for follicular development. Ovarian advanced glycation endproducts (AGEs) accumulation is related to GCs dysfunction. Alpha-lipoic acid (ALA) illustrates therapeutic capabilities for infertility-related disorders. Therefore, this study assessed the effects of ALA on AGEs-induced GCs hormonal dysfunction. Methods: The study was conducted from October 2021 to September 2022 at the Department of Medical Genetics, Shiraz University of Medical Sciences. Isolated GCs (n=50) were divided into control, human glycated albumin (HGA), HGA+ALA, and ALA treatments. Steroidogenic enzymes and AGE receptor (RAGE) genes were assessed by qRT-PCR. Steroid hormones and RAGE protein were evaluated using ELISA and Western blotting. Data were analyzed using GraphPad Prism software (ver. 9), and P<0.05 was considered significant. Results: Our findings showed that HGA treatment significantly (P=0.0001) increased RAGE (by 140.66%), STAR (by 117.65%), 3β-HSD (by 165.68%), and 17β-HSD (by 122.15%) expression, while it decreased CYP19A1 (by 68.37%) expression. RAGE protein level (by 267.10%) was also increased in HGA-treated GCs. A significant decrease in estradiol (by 59.66%) and a slight and sharp elevation in progesterone (by 30.40%) and total testosterone (by 158.24%) levels was also observed. ALA treatment ameliorated the HGA-induced changes in steroidogenic enzyme mRNA levels (P=0.001) and steroid hormone secretion (P=0.010). Conclusion: This work shows that ALA therapy likely corrects hormonal dysfunctions caused by AGEs in luteinized GCs. This effect is probably achieved by decreased RAGE expression. Clinical research is needed to understand how AGEs and ALA interact in the ovary, which might lead to a more targeted ovarian dysfunction therapy. [ABSTRACT FROM AUTHOR]

Purpose: To compare the difference in analgesic effect between femoral triangle block (FTB) and adductor canal block (ACB) during arthroscopic knee surgery. Methods: Patients who underwent arthroscopic knee surgery were randomized preoperatively to FTB group or ACB group. For each group, 20 mL of 0.1% ropivacaine was injected. Primary outcomes: The numeric rating score (NRS) at 12 h after surgery at rest and during movement. Secondary outcome: (1) The NRS at post anesthesia care unit (PACU) and 2, 24 h after surgery at rest and during movement; (2) The quadriceps muscle strength at PACU and 2, 12, 24 h after surgery; (3) Consumption of Rescue analgesia; (4) Incidence of adverse reactions. Results: The NRS at 12 h after surgery at rest and during movement of ACB group were higher than FTB group. Among secondary outcomes, the NRS at PACU at rest and during movement, 2 h after surgery during movement of FTB group lower than ACB group; the quadriceps muscle strength at 2 h after surgery of FTB group stronger than ACB group. After multiple linear regression model analysis, the data showed additional statistically significant reduction NRS at 24 h after surgery at rest (0.757, p = 0.037) in FTB group. Other outcomes were similar between two groups. Conclusions: The FTB appears to provide superior pain control after knee arthroscopy than ACB, the FTB is superior to the ACB in quadriceps muscle strength at 2 h after surgery. Trial registration: The trial was registered in the Chinese Clinical Trial Registry (ChiCTR2300068765). Registration date: 28/02/2023. [ABSTRACT FROM AUTHOR]

BACKGROUND: Increasing medical school faculty diversity is an urgent priority. National Institutes of Health (NIH) diversity supplements, which provide funding and career development opportunities to individuals underrepresented in research, are an important mechanism to increase faculty diversity. OBJECTIVE: Analyze diversity supplement utilization by medical schools. DESIGN: Retrospective cohort study. PARTICIPANTS: All R01 grant-associated diversity supplements awarded to medical schools from 2005 to 2020. Diversity supplements were identified using the publicly available NIH RePORTER database. MAIN MEASURES: Main measures were the number of R01-associated diversity supplements awarded to medical schools each year by medical school NIH funding status and the number of R01-associated diversity supplements awarded to individual medical schools in the NIH top 40 by funding status. We also examined the percentage of R01 grants with an associated diversity supplement by NIH funding status and individual medical school in the NIH top 40. KEY RESULTS: From 2005 to 2020, US medical school faculty received 1389 R01-associated diversity supplements. The number of diversity supplements awarded grew from 2012 to 2020, from ten to 187 for top 40 schools, and from seven to 83 for non-top 40 schools. The annual growth rate for diversity supplement awards at NIH top 40 schools (44.2%) was not significantly different than the annual growth rate among non-top 40 schools (36.2%; p = 0.68). From 2005 to 2020, the highest number of diversity supplements that an individual medical school received was 56 and the lowest number was four (mean = 24.6, SD = 11.7). The highest percentage of R01 grants with an associated diversity supplement received by a school was 4.5% and the lowest percentage was 0.79% (mean = 2.3%, SD = 0.98). CONCLUSION: Medical schools may be missing an opportunity to address the continuing shortage of individuals historically underrepresented in biomedical science and should consider additional mechanisms to enhance diversity supplement utilization.

Background: Over the past decade, Iranian households have experienced a decline in dairy product consumption. This study aimed to evaluate the population-attributable risk of prevalent non-communicable diseases related to dairy product consumption. Methods: This cross-sectional analytical study involved 628 adults over 18 years old in Hamadan City in 2021. Clusters were selected based on comprehensive urban health centers. The standardized Iranian version of the food frequency questionnaire was used. Participants were categorized into 3 levels of dairy product consumption: >1 serving per day, 1-2 servings per day, and ≥3 servings per day. Results: The mean age of the 628 participants was 38.05 (SD: 12.5), with 42.36% being male. Cheese (54.5%), yogurt (39.7%), and milk (30.4%) were consumed most frequently. The prevalence of insufficient dairy product consumption was 48.6%, higher than that reported in previous studies. Insufficient dairy product consumption was associated with hypertension (9.3%), cardiovascular disease (5.6%), and osteoporosis (5.1%). Conclusion: Individuals with lower education levels, female gender, lowest quartile of socioeconomic status, and those diagnosed with cardiovascular disease were more likely to have insufficient dairy product consumption. Insufficient dairy product consumption was associated with hypertension, cardiovascular disease, and osteoporosis. [ABSTRACT FROM AUTHOR]

Background: Patients who had left atrial enlargement (LAE) with atrial fibrillation (AF) had an increased risk of LA dysfunction. However, there were few reports about the relationship between apolipoprotein B (apo B) and LAE or the association between low-density lipoprotein cholesterol (LDL-C) and LAE. We aimed to evaluated the above relationships in patients with non-valvular atrial fibrillation (NVAF). Methods: A total of 170 subjects were consecutively enrolled from December 2012 to July 2015. 87 subjects were retrospectively enrolled as control group. 83 patients were retrospectively included in NVAF group. Heart color Doppler ultrasound examination of all the study subjects were diagnosed by medical specialists. Routine biochemical indicators of hematology were tested in clinical laboratory. Results: There were significant differences between the control and the NVAF group in terms of α- Hydroxybutyrate dehydrogenase (α-HBDH), triglyceride (TG), total cholesterol (TC) and LDL-C. In total NVAF patients, both the CHADS2 (r = 0.578, P = 0.000) and CHA2DS2-VASc (r = 0.632, P = 0.000) scores were positively correlated with age. The CHADS2 score was negatively correlated with apo B (r = -0.217, P = 0.049), and the CHA2DS2-VASc score was negatively correlated with TG (r = -0.256, P = 0.019) and calcium ion (CA) (r = -0.285, P = 0.009). In Pearson correlation analysis, LA diameter was negatively correlated with LDL-C (r = -0.425, P = 0.001), apo B (r = -0.407, P = 0.001) and TC (r = -0.378, P = 0.002) in patients with total NVAF accompanied by LAE. Multiple stepwise regression analysis revealed that LDL-C was an important factor influencing LA size in patients with NVAF. Conclusion: In conclusion, apo B and LDL-C was associated with LAE in patients with NVAF, and LDL-C was an important factor influencing LA size in patients with NVAF. [ABSTRACT FROM AUTHOR]

The Dietary Guidelines for Americans, 2020-2025, included guidelines for pregnancy, lactation, and children from birth to age 24 mo (B-24) to reflect the growing body of evidence about appropriate nutrition during the earliest stages of life. Guidelines were based on a thorough review of the existing scientific evidence by the 2020 Dietary Guidelines Advisory Committee (DGAC). This studys objective was to enumerate early-life (pregnancy, lactation, and B-24) nutrition research needs that are already being addressed by the scientific community and to identify remaining research gaps. The Scientific Report of the 2020 Dietary Guidelines Advisory Committee was reviewed, and 138 research gaps relevant to early life were identified. Research gaps were consolidated into 13 topic areas. A total of 1632 nutrition- and early-life-focused research projects funded by the NIH between 2018 and 2020 were manually coded using title, abstract, and public health relevance statement available on NIH RePORTER. Projects were coded as affirmative if they addressed a research gap within 1 of the 13 research gap topic areas. Of coded projects, 235 (14.4%) addressed any early-life nutrition research gap. Between fiscal years 2018 to 2020, total costs of projects addressing any gap represented only 15% of total costs for all projects reviewed. Complementary foods, breastfeeding (never vs. ever), and frequency of eating were research gap areas most frequently coded as being addressed by a funded project. Iron supplementation, seafood consumption, and maternal diet food allergens were research gap areas least frequently coded as being potentially addressed by a funded project. This analysis highlights opportunities for changes in the federal government investment in maternal and child nutrition research to support development of effective, evidence-based dietary guidelines for improvement in early-life nutrition practices and overall public health.

Lung cancer is the leading cause of mortality and person‐years of life lost from cancer among US men and women. Early detection has been shown to be associated with reduced lung cancer mortality. Our objective was to update the American Cancer Society (ACS) 2013 lung cancer screening (LCS) guideline for adults at high risk for lung cancer. The guideline is intended to provide guidance for screening to health care providers and their patients who are at high risk for lung cancer due to a history of smoking. The ACS Guideline Development Group (GDG) utilized a systematic review of the LCS literature commissioned for the US Preventive Services Task Force 2021 LCS recommendation update; a second systematic review of lung cancer risk associated with years since quitting smoking (YSQ); literature published since 2021; two Cancer Intervention and Surveillance Modeling Network‐validated lung cancer models to assess the benefits and harms of screening; an epidemiologic and modeling analysis examining the effect of YSQ and aging on lung cancer risk; and an updated analysis of benefit‐to‐radiation‐risk ratios from LCS and follow‐up examinations. The GDG also examined disease burden data from the National Cancer Institute's Surveillance, Epidemiology, and End Results program. Formulation of recommendations was based on the quality of the evidence and judgment (incorporating values and preferences) about the balance of benefits and harms. The GDG judged that the overall evidence was moderate and sufficient to support a strong recommendation for screening individuals who meet the eligibility criteria. LCS in men and women aged 50–80 years is associated with a reduction in lung cancer deaths across a range of study designs, and inferential evidence supports LCS for men and women older than 80 years who are in good health. The ACS recommends annual LCS with low‐dose computed tomography for asymptomatic individuals aged 50–80 years who currently smoke or formerly smoked and have a ≥20 pack‐year smoking history (strong recommendation, moderate quality of evidence). Before the decision is made to initiate LCS, individuals should engage in a shared decision‐making discussion with a qualified health professional. For individuals who formerly smoked, the number of YSQ is not an eligibility criterion to begin or to stop screening. Individuals who currently smoke should receive counseling to quit and be connected to cessation resources. Individuals with comorbid conditions that substantially limit life expectancy should not be screened. These recommendations should be considered by health care providers and adults at high risk for lung cancer in discussions about LCS. If fully implemented, these recommendations have a high likelihood of significantly reducing death and suffering from lung cancer in the United States. [ABSTRACT FROM AUTHOR]

Simple Summary: Theranostic robot-assisted radical prostatectomy (T-RARP) means adopting RARP as an integration of diagnosis and therapy, and this concept has rarely been discussed. Before the advancement of imaging technologies, the diagnosis of prostate cancer (PCa) needed to rely on systematic biopsies, which had certain limitation of sensitivity and specificity. In our previous reports, even with preoperative benign biopsies, there were still large portions of incidental PCa in specimens of simple prostatectomies. We first introduced the feasibility of T-RARP in 2016 in patients with clinically highly suspected prostate cancer. In 2020, we developed a nomogram to identify the potential groups. With the advantages of imaging technologies, potential groups can be more easily identified, and the concept of T-RARP can be more widely adopted. However, no studies have discussed the benefits of T-RARP in these patients. Herein, we conducted this cohort study to explore the benefits of T-RARP for such patients and topics of T-RARP that are unclear and need to be unveiled in future studies. Objective: This study aimed to explore the benefits of theranostic robot-assisted radical prostatectomy (T-RARP) for clinically highly suspicious prostate cancer (PCa) without proven biopsies. Material and Methods: Between February 2016 and December 2020, we included men with clinically highly suspicious PCa in this study. They were assessed to have possible localized PCa without any initial treatments, and were categorized into previous benign biopsies or without biopsies. Furthermore, another group of malignant biopsies with RARP in the same time frame was adopted as the control group. The endpoints were to compare the oncological outcome and functional outcome between malignant biopsies with RARP and T-RARP. p < 0.05 was considered to be significant. Results: We included 164 men with proven malignant biopsies treated with RARP as the control group. For T-RARP, we included 192 men. Among them, 129 were preoperatively benign biopsies, and 63 had no biopsies before T-RARP. Approximately 75% of men in the T-RARP group had malignant pathology in their final reports, and the other 25% had benign pathology. T-RARP provides several oncological advantages, such as a higher initial pathological T stage, lower Gleason grade, and lower odds of positive surgical margins. However, the biochemical recurrence rates were not significantly decreased. From our cohort, T-RARP (odds ratio with 95% confidence interval; erectile recovery: 3.19 (1.84–5.52), p < 0.001; continence recovery: 2.25 (1.46–3.48), p < 0.001) could result in better recovery of functional outcomes than malignant biopsies with RARP. Conclusions: For clinically highly suspicious PCa, T-RARP was able to detect around 75% of PCa cases and preserved their functional outcomes maximally. However, in 25% of men with benign pathology, approximately 6% would have incontinence and 10% would have erectile impairment. This part should be sufficiently informed of the potential groups considering T-RARP. [ABSTRACT FROM AUTHOR]

Background: Sorghum is the fifth most consumed cereal grain but limiting in the indispensable amino acid lysine. Complementing sorghum with lentils can improve the quality of sorghum-based diets. However, knowledge of lysine bioavailability in sorghum is lacking.Objectives: The study objectives were to determine the bioavailability of lysine in sorghum and to assess the effect of complementation of sorghum and lentils in a mixed-meal format.Methods: We studied 5 healthy young men (≤30 years; BMI <25 kg/m2) in a repeated-measure design using the indicator amino acid oxidation (IAAO) method, with L-[1-13C] phenylalanine as the indicator. Each subject participated in 8 determinations in random order. On the reference diet, subjects received 4 amounts of L-lysine (5, 8, 12, and 15 mg. kg-1 . d-1) from a crystalline amino acid mixture patterned after egg protein. On the test diet, they received 3 levels of lysine (8.2, 12.5, and 15.7 mg. kg-1 . d-1) from sorghum, and on the complementation diet they received 1 level of lysine from a mixed meal of sorghum and lentils. The bioavailability of lysine in sorghum was estimated by comparing the IAAO response to the test diet with the IAAO response to the reference diet using the slope-ratio method. Effectiveness of complementation was assessed by comparing the IAAO response to the mixed meal to the IAAO response to the test protein.Results: The bioavailability of lysine from sorghum was 94%. Upon complementation with lentils, there was a decline in the oxidation of L-[1-13C] phenylalanine by 19% (P < 0.0495), reflecting an improvement in available lysine in the mixed meal due to increased lysine intake.Conclusions: Although the bioavailability of lysine in sorghum is high, its lysine content is limiting. Complementation with lentils in a 1:1 ratio is recommended to achieve the lysine requirement for adult men consuming a sorghum-based diet. This trial was registered at clinicaltrials.gov as NCT03411005. [ABSTRACT FROM AUTHOR]

Purpose: This study aims to apply the yes/no Angoff and Hofstee methods to actual Korean Medical Licensing Examination (KMLE) 2022 written examination data to estimate cut scores for the written KMLE. Methods: Fourteen panelists gathered to derive the cut score of the 86th KMLE written examination data using the yes/no Angoff method. The panel reviewed the items individually before the meeting and shared their respective understanding of the minimum-compatibility physician. The standard setting process was conducted in 5 rounds over a total of 800 minutes. In addition, 2 rounds of the Hofstee method were conducted before starting the standard setting process and after the second round of yes/no Angoff. Results: For yes/no Angoff, as each round progressed, the panel's opinion gradually converged to a cut score of 198 points, and the final passing rate was 95.1%. The Hofstee cut score was 208 points out of a maximum 320 with a passing rate of 92.1% at the first round. It scored 204 points with a passing rate of 93.3% in the second round. Conclusion: The difference between the cut scores obtained through yes/no Angoff and Hofstee methods did not exceed 2% points, and they were within the range of cut scores from previous studies. In both methods, the difference between the panelists decreased as rounds were repeated. Overall, our findings suggest the acceptability of cut scores and the possibility of independent use of both methods. [ABSTRACT FROM AUTHOR]

We detected Rift Valley fever virus (RVFV) IgM and IgG in human serum samples collected during 2018-2019 in northern KwaZulu-Natal Province, South Africa. Our results show recent RVFV circulation and likely RVFV endemicity in this tropical coastal plain region of South Africa in the absence of apparent clinical disease. [ABSTRACT FROM AUTHOR]

Background: Heart failure (HF) with preserved ejection fraction (HFpEF) constitutes half of all HF but lacks effective therapy. Understanding of its myocardial biology remains limited because of a paucity of heart tissue molecular analysis.Methods: We performed RNA sequencing on right ventricular septal endomyocardial biopsies prospectively obtained from patients meeting consensus criteria for HFpEF (n=41) contrasted with right ventricular septal tissue from patients with HF with reduced ejection fraction (HFrEF, n=30) and donor controls (n=24). Principal component analysis and hierarchical clustering tested for transcriptomic distinctiveness between groups, effect of comorbidities, and differential gene expression with pathway enrichment contrasted HF groups and donor controls. Within HFpEF, non-negative matrix factorization and weighted gene coexpression analysis identified molecular subgroups, and the resulting clusters were correlated with hemodynamic and clinical data.Results: Patients with HFpEF were more often women (59%), African American (68%), obese (median body mass index 41), and hypertensive (98%), with clinical HF characterized by 65% New York Heart Association Class III or IV, nearly all on a loop diuretic, and 70% with a HF hospitalization in the previous year. Principal component analysis separated HFpEF from HFrEF and donor controls with minimal overlap, and this persisted after adjusting for primary comorbidities: body mass index, sex, age, diabetes, and renal function. Hierarchical clustering confirmed group separation. Nearly half the significantly altered genes in HFpEF versus donor controls (1882 up, 2593 down) changed in the same direction in HFrEF; however, 5745 genes were uniquely altered between HF groups. Compared with controls, uniquely upregulated genes in HFpEF were enriched in mitochondrial adenosine triphosphate synthesis/electron transport, pathways downregulated in HFrEF. HFpEF-specific downregulated genes engaged endoplasmic reticulum stress, autophagy, and angiogenesis. Body mass index differences largely accounted for HFpEF upregulated genes, whereas neither this nor broader comorbidity adjustment altered pathways enriched in downregulated genes. Non-negative matrix factorization identified 3 HFpEF transcriptomic subgroups with distinctive pathways and clinical correlates, including a group closest to HFrEF with higher mortality, and a mostly female group with smaller hearts and proinflammatory signaling. These groupings remained after sex adjustment. Weighted gene coexpression analysis yielded analogous gene clusters and clinical groupings.Conclusions: HFpEF exhibits distinctive broad transcriptomic signatures and molecular subgroupings with particular clinical features and outcomes. The data reveal new signaling targets to consider for precision therapeutics. [ABSTRACT FROM AUTHOR]

Background: Ventricular tachyarrhythmias and sudden cardiac death show a circadian pattern of occurrence in patients with heart failure. In the rodent ventricle, a significant portion of genes, including some ion channels, shows a circadian pattern of expression. However, genes that define electrophysiological properties in failing human heart ventricles have not been examined for a circadian expression pattern.Methods: Ventricular tissue samples were collected from patients at the time of cardiac transplantation. Two sets of samples (n=37 and 46, one set with a greater arrhythmic history) were selected to generate pseudo-time series according to their collection time. A third set (n=27) of samples was acquired from the nonfailing ventricles of brain-dead donors. The expression of 5 known circadian clock genes and 19 additional ion channel genes plausibly important to electrophysiological properties were analyzed by real-time polymerase chain reaction and then analyzed for the percentage of expression variation attributed to a 24-hour circadian pattern.Results: The 5 known circadian clock gene transcripts showed a strong circadian expression pattern. Compared with rodent hearts, the human circadian clock gene transcripts showed a similar temporal order of acrophases but with a ≈7.6 hours phase shift. Five of the ion channel genes also showed strong circadian expression. Comparable studies of circadian clock gene expression in samples recovered from nonheart failure brain-dead donors showed acrophase shifts, or weak or complete loss of circadian rhythmicity, suggesting alterations in circadian gene expression.Conclusions: Ventricular tissue from failing human hearts display a circadian pattern of circadian clock gene expression but phase-shifted relative to rodent hearts. At least 5 ion channels show a circadian expression pattern in the ventricles of failing human hearts, which may underlie a circadian pattern of ventricular tachyarrhythmia/sudden cardiac death. Nonfailing hearts from brain-dead donors show marked differences in circadian clock gene expression patterns, suggesting fundamental deviations from circadian expression. [ABSTRACT FROM AUTHOR]

Background: Abdominal aortic aneurysm (AAA) is an important cause of cardiovascular mortality; however, its genetic determinants remain incompletely defined. In total, 10 previously identified risk loci explain a small fraction of AAA heritability.Methods: We performed a genome-wide association study in the Million Veteran Program testing ≈18 million DNA sequence variants with AAA (7642 cases and 172 172 controls) in veterans of European ancestry with independent replication in up to 4972 cases and 99 858 controls. We then used mendelian randomization to examine the causal effects of blood pressure on AAA. We examined the association of AAA risk variants with aneurysms in the lower extremity, cerebral, and iliac arterial beds, and derived a genome-wide polygenic risk score (PRS) to identify a subset of the population at greater risk for disease.Results: Through a genome-wide association study, we identified 14 novel loci, bringing the total number of known significant AAA loci to 24. In our mendelian randomization analysis, we demonstrate that a genetic increase of 10 mm Hg in diastolic blood pressure (odds ratio, 1.43 [95% CI, 1.24-1.66]; P=1.6×10-6), as opposed to systolic blood pressure (odds ratio, 1.06 [95% CI, 0.97-1.15]; P=0.2), likely has a causal relationship with AAA development. We observed that 19 of 24 AAA risk variants associate with aneurysms in at least 1 other vascular territory. A 29-variant PRS was strongly associated with AAA (odds ratioPRS, 1.26 [95% CI, 1.18-1.36]; PPRS=2.7×10-11 per SD increase in PRS), independent of family history and smoking risk factors (odds ratioPRS+family history+smoking, 1.24 [95% CI, 1.14-1.35]; PPRS=1.27×10-6). Using this PRS, we identified a subset of the population with AAA prevalence greater than that observed in screening trials informing current guidelines.Conclusions: We identify novel AAA genetic associations with therapeutic implications and identify a subset of the population at significantly increased genetic risk of AAA independent of family history. Our data suggest that extending current screening guidelines to include testing to identify those with high polygenic AAA risk, once the cost of genotyping becomes comparable with that of screening ultrasound, would significantly increase the yield of current screening at reasonable cost. [ABSTRACT FROM AUTHOR]

During the last decade, there have been several publications highlighting the need for consistent terminology in breastfeeding research. Standard terms and definitions are essential for the comparison and interpretation of scientific studies that, in turn, support evidence‐based education, consistency of health care, and breastfeeding policy. Inconsistent advice is commonly reported by mothers to contribute to early weaning. A standard language is the fundamental starting point required for the provision of consistent advice. LactaPedia (www.lactapedia.com) is a comprehensive lactation glossary of over 500 terms and definitions created during the development of LactaMap (www.lactamap.com), an online lactation care support system. This paper describes the development of LactaPedia, a website that is accessible free of charge to anyone with access to the Internet. Multiple methodological frameworks were incorporated in LactaPedia's development in order to meet the needs of a glossary to support both consistent health care and scientific research. The resulting LactaPedia methodology is a six‐stage process that was developed inductively and includes framework to guide vetting and extension of its content using public feedback via discussion forums. The discussion forums support ongoing usability and refinement of the glossary. The development of LactaPedia provides a fundamental first step towards improving breastfeeding outcomes that are currently well below World Health Organisation recommendations globally. [ABSTRACT FROM AUTHOR]

Background: Arginine vasopressin has complex actions in critically ill patients, involving vasoregulatory status, plasma volume, and cortisol levels. Copeptin, a surrogate marker for arginine vasopressin, has shown promising prognostic features in small observational studies and is used clinically for early rule out of acute coronary syndrome. The objective of this study was to explore the association between early measurements of copeptin, circulatory status, and short-term survival after out-of-hospital cardiac arrest.Methods: Serial blood samples were collected at 24, 48, and 72 h as part of the target temperature management at 33 °C versus 36 °C after cardiac arrest trial, an international multicenter randomized trial where unconscious survivors after out-of-hospital cardiac arrest were allocated to an intervention of 33 or 36 °C for 24 h. Primary outcome was 30-day survival with secondary endpoints circulatory cause of death and cardiovascular deterioration composite; in addition, we examined the correlation with extended the cardiovascular sequential organ failure assessment (eCvSOFA) score.Results: Six hundred ninety patients were included in the analyses, of whom 203 (30.3%) developed cardiovascular deterioration within 24 h, and 273 (39.6%) died within 30 days. Copeptin measured at 24 h was found to be independently associated with 30-day survival, hazard ratio 1.17 [1.06-1.28], p = 0.001; circulatory cause of death, odds ratio 1.03 [1.01-1.04], p = 0.001; and cardiovascular deterioration composite, odds ratio of 1.05 [1.02-1.08], p < 0.001. Copeptin at 24 h was correlated with eCvSOFA score with rho 0.19 [0.12-0.27], p < 0.001.Conclusion: Copeptin is an independent marker of severity of the post cardiac arrest syndrome, partially related to circulatory failure.Trial Registration: Clinical Trials, NCT01020916. Registered November 26, 2009. [ABSTRACT FROM AUTHOR]

Emergency vaccination programs often are needed to control outbreaks of meningococcal disease caused by Neisseria meningitidis serogroup B (MenB) on college campuses. Such campaigns expend multiple campus and public health resources. We conducted a randomized, controlled, multicenter, observer-blinded trial comparing immunogenicity and tolerability of an accelerated vaccine schedule of 0 and 21 days to a longer interval of 0 and 60 days for 4-component MenB vaccine (MenB-4C) in students 17-25 years of age. At day 21 after the first MenB-4C dose, we observed protective human serum bactericidal titers >4 to MenB strains 5/99, H44/76, and NZ 98/254 in 98%-100% of participants. Geometric mean titers increased >22-fold over baseline. At day 180, >95% of participants sustained protective titers regardless of their vaccine schedule. The most common adverse event was injection site pain. An accelerated MenB-4C immunization schedule could be considered for rapid control of campus outbreaks. [ABSTRACT FROM AUTHOR]

Emergency vaccination programs often are needed to control outbreaks of meningococcal disease caused by Neisseria meningitidis serogroup B (MenB) on college campuses. Such campaigns expend multiple campus and public health resources. We conducted a randomized, controlled, multicenter, observer-blinded trial comparing immunogenicity and tolerability of an accelerated vaccine schedule of 0 and 21 days to a longer interval of 0 and 60 days for 4-component MenB vaccine (MenB-4C) in students 17-25 years of age. At day 21 after the first MenB-4C dose, we observed protective human serum bactericidal titers >4 to MenB strains 5/99, H44/76, and NZ 98/254 in 98%-100% of participants. Geometric mean titers increased >22-fold over baseline. At day 180, >95% of participants sustained protective titers regardless of their vaccine schedule. The most common adverse event was injection site pain. An accelerated MenB-4C immunization schedule could be considered for rapid control of campus outbreaks. [ABSTRACT FROM AUTHOR]

Ebola virus disease (EVD) is associated with elevated cytokine levels, and hypercytokinemia is more pronounced in fatal cases. This type of hyperinflammatory state is reminiscent of 2 rheumatologic disorders known as macrophage activation syndrome and hemophagocytic lymphohistiocytosis, which are characterized by macrophage and T-cell activation. An evaluation of 2 cohorts of patients with EVD revealed that a marker of macrophage activation (sCD163) but not T-cell activation (sCD25) was associated with severe and fatal EVD. Furthermore, substantial immunoreactivity of host tissues to a CD163-specific antibody, predominantly in areas of extensive immunostaining for Ebola virus antigens, was observed in fatal cases. These data suggest that host macrophage activation contributes to EVD pathogenesis and that directed antiinflammatory therapies could be beneficial in the treatment of EVD. [ABSTRACT FROM AUTHOR]

Ebola virus disease (EVD) is associated with elevated cytokine levels, and hypercytokinemia is more pronounced in fatal cases. This type of hyperinflammatory state is reminiscent of 2 rheumatologic disorders known as macrophage activation syndrome and hemophagocytic lymphohistiocytosis, which are characterized by macrophage and T-cell activation. An evaluation of 2 cohorts of patients with EVD revealed that a marker of macrophage activation (sCD163) but not T-cell activation (sCD25) was associated with severe and fatal EVD. Furthermore, substantial immunoreactivity of host tissues to a CD163-specific antibody, predominantly in areas of extensive immunostaining for Ebola virus antigens, was observed in fatal cases. These data suggest that host macrophage activation contributes to EVD pathogenesis and that directed antiinflammatory therapies could be beneficial in the treatment of EVD. [ABSTRACT FROM AUTHOR]

Background: The mechanisms by which persistent atrial fibrillation (AF) terminates via localized ablation are not well understood. To address the hypothesis that sites where localized ablation terminates persistent AF have characteristics identifiable with activation mapping during AF, we systematically examined activation patterns acquired only in cases of unequivocal termination by ablation.Methods and Results: We recruited 57 patients with persistent AF undergoing ablation, in whom localized ablation terminated AF to sinus rhythm or organized tachycardia. For each site, we performed an offline analysis of unprocessed unipolar electrograms collected during AF from multipolar basket catheters using the maximum -dV/dt assignment to construct isochronal activation maps for multiple cycles. Additional computational modeling and phase analysis were used to study mechanisms of map variability. At all sites of AF termination, localized repetitive activation patterns were observed. Partial rotational circuits were observed in 26 of 57 (46%) cases, focal patterns in 19 of 57 (33%), and complete rotational activity in 12 of 57 (21%) cases. In computer simulations, incomplete segments of partial rotations coincided with areas of slow conduction characterized by complex, multicomponent electrograms, and variations in assigning activation times at such sites substantially altered mapped mechanisms.Conclusions: Local activation mapping at sites of termination of persistent AF showed repetitive patterns of rotational or focal activity. In computer simulations, complete rotational activation sequence was observed but was sensitive to assignment of activation timing particularly in segments of slow conduction. The observed phenomena of repetitive localized activation and the mechanism by which local ablation terminates putative AF drivers require further investigation. [ABSTRACT FROM AUTHOR]

Background: The VANISH trial (Ventricular Tachycardia Ablation Versus Escalated Antiarrhythmic Drug Therapy in Ischemic Heart Disease) compared the effectiveness of escalated antiarrhythmic drug therapy to catheter ablation in patients with prior myocardial infarction, an implanted defibrillator, and ventricular tachycardia (VT). The effectiveness of these interventions in patients on sotalol versus amiodarone was compared.Methods and Results: Analysis was conducted based on whether patients had recurrent VT, despite amiodarone (amio-refractory) or nonamiodarone drugs (sotalol-refractory). Outcomes included death, VT storm, appropriate implantable cardioverter defibrillator shock, and any ventricular arrhythmia. At baseline, 169 (65.2%) were amio-refractory, and 90 (34.7%) were sotalol-refractory (1 patient on procainamide rather than sotalol). Amio-refractory patients had more renal insufficiency (23.7% versus 10%; P=0.0008), worse New York Heart Association class (82.3% II/III versus 65.5%; P=0.0003), and lower ejection fraction (29±9.7% versus 35.2±11%; P<0.0001). Within the amio-refractory group, ablation resulted in reduction of any ventricular arrhythmia compared with escalated drug therapy (hazard ratio, 0.53; 95% confidence interval, 0.31-0.9), P=0.020). Sotalol-refractory patients had trends toward higher mortality and VT storm with ablation, with no effect on implantable cardioverter defibrillator shocks. Within the escalated drug therapy arm, amio-refractory patients had a higher rate of the composite outcome (hazard ratio, 1.94; 95% confidence interval, 1.14-3.29; P=0.0144) and a trend to higher mortality (hazard ratio, 2.40; 95% confidence interval, 0.93-6.22; P=0.07), whereas mortality was not different between amio- and sotalol-refractory patients within the ablation treatment group.Conclusions: Patients with amio-refractory VT have a higher rate of ventricular arrhythmia and mortality than those with sotalol-refractory VT and derive greater benefit of catheter ablation than for patients with sotalol-refractory VT who are switched to amiodarone.Clinical Trial Registration: URL: https://clinicaltrials.gov. Unique identifier: NCT00905853. [ABSTRACT FROM AUTHOR]

Preventing emergence of new zoonotic viruses depends on understanding determinants for human risk. Nipah virus (NiV) is a lethal zoonotic pathogen that has spilled over from bats into human populations, with limited person-to-person transmission. We examined ecologic and human behavioral drivers of geographic variation for risk of NiV infection in Bangladesh. We visited 60 villages during 2011-2013 where cases of infection with NiV were identified and 147 control villages. We compared case villages with control villages for most likely drivers for risk of infection, including number of bats, persons, and date palm sap trees, and human date palm sap consumption behavior. Case villages were similar to control villages in many ways, including number of bats, persons, and date palm sap trees, but had a higher proportion of households in which someone drank sap. Reducing human consumption of sap could reduce virus transmission and risk for emergence of a more highly transmissible NiV strain. [ABSTRACT FROM AUTHOR]

Background: Among individuals without hypertension based on clinic blood pressure (BP), it is unclear who should be screened for masked hypertension, defined as having hypertension based on out-of-clinic BP. We hypothesized that individuals with a higher 10-year predicted atherosclerotic cardiovascular disease (ASCVD) risk, calculated using the pooled cohort risk equations, have a higher prevalence of masked hypertension.Methods and Results: We analyzed data from the Jackson Heart Study-a population-based cohort of blacks-to determine the association of predicted ASCVD risk with masked hypertension. The sample included 644 participants, 40 to 79 years of age, with clinic systolic/diastolic BP <140/90 mm Hg, who completed ambulatory BP monitoring, were free of cardiovascular disease, and had data on factors needed to calculate ASCVD risk. Ten-year predicted ASCVD risk was calculated using the pooled cohort risk equations. Any masked hypertension was defined as masked daytime hypertension (mean daytime systolic/diastolic BP ≥135/85 mm Hg), masked nighttime hypertension (mean nighttime systolic/diastolic BP ≥120/70 mm Hg), or masked 24-hour hypertension (mean 24-hour systolic/diastolic BP ≥130/80 mm Hg). The prevalence of any masked hypertension was 54.0%. Compared with participants in the lowest (<5%) predicted ASCVD risk category, multivariable-adjusted prevalence ratios (95% confidence interval) for any masked hypertension were 1.36 (1.03-1.79), 1.62 (1.22-2.16), and 1.91 (1.47-2.48) for those with ASCVD risk of 5% to <7.5%, 7.5% to <10%, and ≥10%, respectively. The C statistic for discriminating between participants with versus without any masked hypertension was 0.681 (95% confidence interval, 0.640-0.723) for ASCVD risk and 0.703 (95% confidence interval, 0.663-0.744) for clinic systolic BP and diastolic BP.Conclusions: Higher ASCVD risk was associated with an increased prevalence of masked hypertension. Although the discrimination of ASCVD risk for masked hypertension was not superior to clinic BP, risk prediction equations may be useful for identifying the subgroup of individuals with both masked hypertension and high predicted ASCVD risk. [ABSTRACT FROM AUTHOR]

Background: Zinc and copper have many physiologic functions and little or no functional storage capability, so persistent losses of either element present health concerns, especially during extended-duration space missions.Objectives: We evaluated the effects of short-term bed rest (BR), a spaceflight analog, on copper and zinc metabolism to better understand the role of these nutrients in human adaptation to (simulated) spaceflight. We also investigated the effect of artificial gravity on copper and zinc homeostasis.Methods: Zinc and copper balances were studied in 15 men [mean ± SD age: 29 ± 3 y; body mass index (in kg/m2): 26.4 ± 2.2] before, during, and after 21 d of head-down tilt BR, during which 8 of the participants were subjected to artificial gravity (AG) by centrifugation for 1 h/d. Control subjects were transferred onto the centrifuge but were not exposed to centrifugation. The study was conducted in a metabolic ward; all urine and feces were collected. Data were analyzed by 2-factor repeated-measures ANOVA.Results: Urinary zinc excretion values for control and AG groups were 33% and 14%, respectively, higher during BR than before BR, and fecal zinc excretion values for control and AG groups were 36% and 19%, respectively, higher during BR, resulting in 67% and 82% lower net zinc balances for controls and AG, respectively (both P < 0.01), despite lower nutrient intake during BR. Fecal copper values for control and AG groups were 40% and 33%, respectively, higher during BR than before BR (P < 0.01 for both). Urinary copper did not change during BR, but a 19% increase was observed after BR compared with before BR in the AG group (P < 0.05).Conclusions: The increased fecal excretion of copper and zinc by men during BR suggests that their absorption of these minerals from the diet was reduced, secondary to the release of minerals from bone and muscle. These findings highlight the importance of determining dietary requirements for astronauts on space missions and ensuring provision and intake of all nutrients. [ABSTRACT FROM AUTHOR]

Background: Chronic headache (CrH) occurs commonly in the population, and chronic migraine (CM) accounts for much of the CrH. Diagnostic criteria for CM remain controversial, and this could lead to undertreatment of CM. The purpose of this study was to analyze the clinical profiles of CM and to field test the International Classification of Headache Disorders-3β criteria (ICHD-3β) and Expert Opinion criteria (EO) for CM application. Methods: We retrospectively reviewed the medical records of CrH patients in our headache clinic during the period. Eligible patients were selected from CrH population based on Silberstein and Lipton criteria (S-L) for CM, and meanwhile fulfilled with migraine days at least 8 days/month. Then we evaluated the characteristics of clinic profiles and outcomes between patients diagnosed CM using ICHD-3β and EO criteria. Field tested the CM criteria Of ICHD-3β and EO. Results: In a total of 710 CrH patients , 261 (36.8 %) were recruited with CM based on both S-L criteria and fulfilled at least 8 migraine days/month. Be understandable, all the 261 patients met the EO criteria, and only 185 (70.9 %) met ICHD-3β for CM. For the 76 patients who met EO but not ICHD-3β, 70 had atypical migraine attacks (probable migraine, PM), and another 6 had typical migraine attacks but less than a total history of 5 attacks. Although 173 (66.3 %) were concurrent with medication overuse, just one patient overused triptans and none used ergot agents. Clinical features were not significantly different between the ICHD-3β and EO criteria groups (P > 0.05), and neither were outcomes of prophylaxis (P = 0.966). Total migraine prophylaxis effectiveness was 73 %. Conclusion: Migraine-specific analgesics are rarely used in China, permitting patients with PM to avail themselves of “migraine days” is a reasonable accommodation for this difficult condition. In our hands, use of the new EO criteria for diagnosis of CM increases the sensitivity and maintains the specificity of decision making, and therefore should be adopted in CM management practice. [ABSTRACT FROM AUTHOR]

Background: The branched-chain amino acids leucine and isoleucine lower blood glucose after oral glucose ingestion, and the intraduodenal infusion of leucine decreases energy intake in healthy, lean men. Objective: We investigated the effects of the intragastric administration of leucine and isoleucine on the gastric emptying of, and blood glucose responses to, a physiologic mixed-macronutrient drink and subsequent energy intake. Design: In 2 separate studies, 12 healthy, lean subjects received on 3 separate occasions an intragastric infusion of 5 g leucine (leucine-5g) or an intragastric infusion of 10 g leucine (leucine-10g), an intragastric infusion of 5 g isoleucine (isoleucine-5g) or an intragastric infusion of 10 g isoleucine (isoleucine-10g), or a control. Fifteen minutes later, subjects consumed a mixed-nutrient drink (400 kcal, 56 g carbohydrates, 15 g protein, and 12 g fat), and gastric emptying (13C-acetate breath test) and blood glucose, plasma insulin, C-peptide, glucagon, glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), and cholecystokinin (leucine study only) were measured for 60 min. Immediately afterward, energy intake from a cold, buffet-style meal was assessed. Results: Compared with the control, leucine-10g decreased the blood glucose area under the curve (AUC) (P < 0.05) and tended to reduce peak blood glucose (P = 0.07), whereas effects of leucine-5g were NS. Leucine-10g, but not leucine-5g, increased plasma insulin and C-peptide AUCs (P < 0.01 for both), but neither dose affected glucagon, GLP-1, GIP, cholecystokinin, gastric emptying, or energy intake. Compared with the control, isoleucine-10g reduced the blood glucose AUC and peak blood glucose (P < 0.01), whereas effects of isoleucine-5g were NS. Neither load affected insulin, C-peptide, glucagon, GLP-1, or GIP. Isoleucine-10g, but not isoleucine-5g, slowed gastric emptying (P < 0.05), but gastric emptying was not correlated with the blood glucose AUC. Isoleucine did not affect energy intake. Conclusions: In healthy subjects, both leucine and isoleucine reduced blood glucose in response to a mixed-nutrient drink but did not affect subsequent energy intake. The mechanisms underlying glucose lowering appear to differ; leucine stimulated insulin, whereas isoleucine acted insulin independently. These trials were registered at www.anzctr.org.au as 12613000899741 and 12614000837628. [ABSTRACT FROM AUTHOR]

Background: Model-based compartmental analysis of data on plasma retinol kinetics after administration of labeled retinol provides unique information about whole-body vitamin A metabolism. If labeled β-carotene is coadministered, its bioefficacy relative to the retinol reference dose can also be estimated.Objectives: The objectives were to model plasma retinol kinetics after administration of labeled preformed vitamin A and provitamin A β-carotene and to determine relative β-carotene bioefficacy.Methods: We used the Simulation, Analysis and Modeling software (WinSAAM version 3.0.8; http://www.WinSAAM.org) to analyze previously collected data on plasma [13C10]- and [13C5]retinol kinetics for 14 d after oral administration of 1 mg [13C10]retinyl acetate and 2 mg [13C10]β-carotene in oil to 30 healthy young adults of European ancestry [13 men, 17 women; mean ± SD age: 24.5 ± 4.2 y; mean ± SD body weight: 65.2 ± 10 kg; mean ± SD body mass index (in kg/m2): 22.5 ± 1.9] with moderate vitamin A intakes.Results: A 6-component model provided the best fit to the data, including compartments for initial metabolism of vitamin A, plasma retinol, and extravascular vitamin A storage. The disposal rate was 6.7 ± 3.1 μmol/d, fractional catabolic rate was 6.0% ± 2.3%/d, and vitamin A stores were 123 ± 71 μmol. Relative β-carotene bioefficacy, based on the ratio of the areas under the fraction of dose curves calculated by WinSAAM, averaged 13.5% ± 6.02% (retinol activity equivalents = 7.7:1.0 μg). Interindividual variation in relative β-carotene bioefficacy was high (CV: 44%).Conclusions: Vitamin A kinetics in these young adults were best described by essentially the same model that had been previously developed by using data for older adults with higher vitamin A stores; differences in parameter values reflected differences in vitamin A status. Estimated β-carotene bioefficacy was relatively low but similar to previously reported estimates obtained by graphical methods. This trial was registered at the UK Clinical Research Network as UKCRN 7413. [ABSTRACT FROM AUTHOR]

Background: Resistant starch (RS) and whey protein are thought to be effective nutrients for reducing glycemic responses. Objective: We aimed to determine the effect of varying the sucrose, RS, and whey protein content of cereal bars on glucose and insulin responses. Esign: Twelve healthy subjects [mean ± SD age: 36 ± 12 y; mean ± SD body mass index (in kg/m²): 24.9 ± 2.7] consumed 40 g available-carbohydrate (avCHO) portions of 5 whole-grain cereal bars that contained varying amounts of RS and whey protein concentrate [WPC; 70% protein; RS:WPC, %wt:wt: 15:0 (Bar15/0); 15:0, low in sucrose (Bar15/0LS); 15:5 (Bar15/5); 10:5 (Bar10/5); and 10:10 (Bar10/10)] and 2 portion sizes of a control bar low in whole grains, protein, and RS [control 1 contained 40 g avCHO (Control1); control 2 contained total carbohydrate equal to Bar15/0LS (Control2)] on separate days by using a randomized crossover design. Glucose and insulin responses in vivo and carbohydrate digestibility in vitro were measured over 3 h. Results: Incremental area under the curve (iAUC) over 0-3 h for glucose (min × mmol/L) differed significantly between treatments (P < 0.001) [Bar15/0LS (mean ± SEM), 169 ± 14; Control2, 164 ± 20; Bar15/0, 144 ± 15; Control1, 140 ± 17; Bar10/5, 117 ± 12; Bar15/5, 116 ± 9; and Bar10/10, 100 ± 9; Tukey's least significant difference = 42, P < 0.05], but insulin iAUC did not differ significantly. Higher protein content was associated with a lower glucose iAUC (P = 0.028) and a higher insulin-to-glucose iAUC ratio (P = 0.002) All 5 RS-containing bars were digested in vitro ~30% more slowly than the control bars (P < 0.05); however, in vivo responses were not related to digestibility in vitro. Glucose and insulin responses elicited by high-RS, whey protein-free bars were similar to those elicited from control bars. Conclusions: The inclusion of RS in cereal bar formulations did not reduce glycemic responses despite slower starch digestion in vitro. Thus, caution is required when extrapolating in vitro starch digestibility to in vivo glycemic response. The inclusion of whey protein in cereal bar formulations to reduce glycemic response requires caution because this may be associated with a disproportionate increase in insulin as judged by an increased insulin-to-glucose iAUC ratio. [ABSTRACT FROM AUTHOR]