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The INDDEX24 Dietary Assessment Platform (INDDEX24) was developed to facilitate the collection of 24-h dietary recall (24HR) data. Alongside validation studies in Viet Nam and Burkina Faso in 2019-2020, we conducted activity-based costing studies to estimate the cost of conducting a 24HR among women of reproductive age using INDDEX24 compared with the pen-and-paper interview (PAPI) approach. We also modelled alternative scenarios in which: (1) 25-75 % of dietary reference data were borrowed from the INDDEX24 Global Food Matters Database (FMDB); (2) all study personnel were locally based and (3) national-scale surveys. In the primary analysis, in Viet Nam, the 24HR cost US $111 004 ($755/respondent, n 147) using INDDEX24 and $120 483 ($820/respondent, n 147) using PAPI. In Burkina Faso, the 24HR cost $78 105 ($539/respondent, n 145) using INDDEX24 and $79 465 ($544/respondent, n 146) using PAPI. In modelled scenarios, borrowing dietary reference data from the FMDB decreased the cost of INDDEX24 by 17-34 % (Viet Nam) and 5-15 % (Burkina Faso). With all locally based personnel, INDDEX24 cost more than PAPI ($498 v. $448 per respondent in Viet Nam and $456 v. $410 in Burkina Faso). However, at national scales (n 4376, Viet Nam; n 6500, Burkina Faso) using all locally based personnel, INDDEX24 was more cost-efficient ($109 v. $137 per respondent in Viet Nam and $123 v. $148 in Burkina Faso). In two countries and under most circumstances, INDDEX24 was less expensive than PAPI. Higher INDDEX24 survey preparation costs (including purchasing equipment) were more than offset by higher PAPI data entry, cleaning and processing costs. INDDEX24 may facilitate cost-efficient dietary data collection.

Effective nutrition policies require timely, accurate individual dietary consumption data; collection of such information has been hampered by cost and complexity of dietary surveys and lag in producing results. The objective of this work was to assess accuracy and cost-effectiveness of a streamlined, tablet-based dietary data collection platform for 24-hour individual dietary recalls (24HR) administered using INDDEX24 platform v. a pen-and-paper interview(PAPI) questionnaire, with weighed food record (WFR) as a benchmark. This cross-sectional comparative study included women 18-49 years old from rural Burkina Faso (n 116 INDDEX24; n 115 PAPI). A WFR was conducted; the following day, a 24HR was administered by different interviewers. Food consumption data were converted into nutrient intakes. Validity of 24HR estimates of nutrient and food group consumption was based on comparison with WFR using equivalence tests (group level) and percentages of participants within ranges of percentage error (individual level). Both modalities performed comparably estimating consumption of macro- and micronutrients, food groups and quantities (modalities' divergence from WFR not significantly different). Accuracy of both modalities was acceptable (equivalence to WFR significant at P < 0·05) at group level for macronutrients, less so for micronutrients and individual-level consumption (percentage within ±20 % for WFR, 17-45 % for macronutrients, 5-17 % for micronutrients). INDDEX24 was more cost-effective than PAPI based on superior accuracy of a composite nutrient intake measure (but not gram amount or item count) due to lower time and personnel costs. INDDEX24 for 24HR dietary surveys linked to dietary reference data shows comparable accuracy to PAPI at lower cost.

PurposeOveractive bladder syndrome is defined as urinary urgency, usually accompanied by frequency and nocturia, with or without urgency urinary incontinence in the absence of urinary tract infection or another obvious pathological condition. Electronic questionnaires have been used in a few specialties with the hope of improving treatment outcomes and patient satisfaction. However, they have not been widely used in the urological field. When treating overactive bladder, the main outcome is to improve patient quality of life. The primary objective of this study was to evaluate whether electronic questionnaires would be equally accepted as or preferred to paper questionnaires. The secondary objective was to look at the preference in relation to patient age, education and iPad® tablet familiarity.Materials and methodsWe prospectively evaluated the iList® electronic questionnaire application using a friendly iPad tablet in patients with overactive bladder who presented to the urology clinic at our institution. Each of the 80 patients who were recruited randomly completed the validated OABSS (Overactive Bladder Symptom Score) and the PPBC (Patient Perception of Bladder Condition) questionnaires in paper and electronic format on the tablet. Variables potentially associated with the outcomes of interest included demographic data, questionnaire method preference, patient response rate and iPad familiarity. We used the 2-sided Z-test to determine whether the proportion of patients who considered the tablet to be the same, better or much better than paper was significantly greater than 50%. The 2-sided chi-square test was applied to assess whether the intervention effect significantly differed among the demographic subgroups.ResultsA total of 80 patients 21 to 87 years old were enrolled in the study from November 2015 to August 2016. Of the patients 53% were female and 49% were 65 years or younger. The incidence of those who considered the tablet to be the same or better than paper was 82.5% (95% CI 74.2-90.8, p

BackgroundBrucellosis, as a serious zoonotic infectious disease, has been recognized as a re-emerging disease in the developing countries worldwide. In china, the incidence of brucellosis is increasing each year, seriously threatening the health of humans as well as animal populations. Despite a quite number of diagnostic methods currently being used for brucellosis, innovative technologies are still needed for its rapid and accurate diagnosis, especially in area where traditional diagnostic is unavailable.Methodology/principal findingsIn this study, a total of 22 B cell linear epitopes were predicted from five Brucella outer membrane proteins (OMPs) using an immunoinformatic approach. These epitopes were then chemically synthesized, and with the method of indirect ELISA (iELISA), each of them displayed a certain degree of capability in identifying human brucellosis positive sera. Subsequently, a fusion protein consisting of the 22 predicted epitopes was prokaryotically expressed and used as diagnostic antigen in a newly established brucellosis testing method, nano-ZnO modified paper-based ELISA (nano-p-ELISA). According to the verifying test using a collection of sera collected from brucellosis and non-brucellosis patients, the sensitivity and specificity of multiepitope based nano-p-ELISA were 92.38% and 98.35% respectively. The positive predictive value was 98.26% and the negative predictive value was 91.67%. The multiepitope based fusion protein also displayed significantly higher specificity than Brucella lipopolysaccharide (LPS) antigen.ConclusionsB cell epitopes are important candidates for serologically testing brucellosis. Multiepitope fusion protein based nano-p-ELISA displayed significantly sensitivity and specificity compared to Brucella LPS antigen. The strategy applied in this study will be helpful to develop rapid and accurate diagnostic method for brucellosis in human as well as animal populations.

Little research has been conducted to examine the influence of various methods of providing nest materials-such as dispersing them, providing them as single units, or clustering them-on the behavior and welfare of group-housed mice. In this study, 6 wk-old C57BL/6NCrl mice were housed 3 per cage and randomized into 1 of 3 nest-material groups: 1) one facial tissue per cage (control; female mice, 3 cages; male mice, 3 cages); 2) an 8-g 'puck' of compressed nesting material and a facial tissue (females, 3 cages; males, 3 cages); or 3) 8 g of dispersed paper strips and a facial tissue (females, 3 cages; males, 3 cages). Mouse behavior (agonistic, stereotypic, nesting), physical examination data, and nest scores were evaluated over 16 d. The results showed that mice in the puck and control groups spent more time manipulating nest materials after cage changes than did mice in the paper-strip group. Average nest scores were highest in the paper-strip group compared with controls and puck cages. Female cages with pucks showed no barbering, whereas all other female mice cages demonstrated barbering. Overall, nest pucks may provide a time-consuming activity for mice and may help protect female C57BL/6 mice from barbering. However, more research is needed to replicate and expand these study results.

The Centers for Medicare & Medicaid Services' Severe Sepsis and Septic Shock Early Management Bundle (SEP-1) measure has appropriately established sepsis as a national priority. However, the Infectious Diseases Society of America (IDSA and five additional endorsing societies) is concerned about SEP-1's potential to drive antibiotic overuse because it does not account for the high rate of sepsis overdiagnosis and encourages aggressive antibiotics for all patients with possible sepsis, regardless of the certainty of diagnosis or severity of illness. IDSA is also concerned that SEP-1's complex "time zero" definition is not evidence-based and is prone to inter-observer variation. In this position paper, IDSA outlines several recommendations aimed at reducing the risk of unintended consequences of SEP-1 while maintaining focus on its evidence-based elements. IDSA's core recommendation is to limit SEP-1 to septic shock, for which the evidence supporting the benefit of immediate antibiotics is greatest. Prompt empiric antibiotics are often appropriate for suspected sepsis without shock, but IDSA believes there is too much heterogeneity and difficulty defining this population, uncertainty about the presence of infection, and insufficient data on the necessity of immediate antibiotics to support a mandatory treatment standard for all patients in this category. IDSA believes guidance on managing possible sepsis without shock is more appropriate for guidelines that can delineate the strengths and limitations of supporting evidence and allow clinicians discretion in applying specific recommendations to individual patients. Removing sepsis without shock from SEP-1 will mitigate the risk of unnecessary antibiotic prescribing for noninfectious syndromes, simplify data abstraction, increase measure reliability, and focus attention on the population most likely to benefit from immediate empiric broad-spectrum antibiotics.

PurposeTo assess time requirements for patient encounters and estimate after-hours demands of paper-based clinical workflows in ophthalmology.DesignTime-and-motion study with a structured survey.MethodsThis study was conducted in a single academic ophthalmology department. A convenience sample consisted of 7 attending ophthalmologists from 6 subspecialties observed during 414 patient encounters for the time-motion analysis and 12 attending ophthalmologists for the survey. Outcome measurements consisted of total time spent by attending ophthalmologists per patient and time spent on documentation, examination, and talking with patients. The survey assessed time requirements of documentation-related activities performed outside of scheduled clinic hours.ResultsAmong the 7 attending ophthalmologists observed (6 men and 1 woman), mean ± SD age 43.9 ± 7.1 years, during encounters with 414 patients (57.8 ± 24.6 years of age), total time spent per patient was 8.1 ± 4.8 minutes, with 2.8 ± 1.4 minutes (38%) for documentation, 1.2 ± 0.9 minutes (17%) for examination, and 3.3 ± 3.1 minutes (37%) for talking with patients. New patient evaluations required significantly more time than routine follow-up visits and postoperative visits. Higher clinical volumes were associated with less time per patient. Survey results indicated that paper-based documentation was associated with minimal after-hours work on weeknights and weekends.ConclusionsPaper-based documentation takes up a substantial portion of the total time spent for patient care in outpatient ophthalmology clinics but is associated with minimal after-hours work. Understanding paper-based clinical workflows may help inform targeted strategies for improving electronic health record use in ophthalmology.

BackgroundRifampicin or rifampin (R) is a common drug used to treat inactive meningitis, cholestatic pruritus and tuberculosis (TB), and it is generally prescribed for long-term administration under regulated dosages. Constant monitoring of rifampicin is important for controlling the side effects and preventing overdose caused by chronic medication. In this study, we present an easy to use, effective and less costly method for detecting residual rifampicin in urine samples using protein (bovine serum albumin, BSA)-stabilized gold nanoclusters (BSA-Au NCs) adsorbed on a paper substrate in which the concentration of rifampicin in urine can be detected via fluorescence quenching. The intensity of the colorimetric assay performed on the paper-based platforms can be easily captured using a digital camera and subsequently analyzed.ResultsThe decreased fluorescence intensity of BSA-Au NCs in the presence of rifampicin allows for the sensitive detection of rifampicin in a range from 0.5 to 823 µg/mL. The detection limit for rifampicin was measured as 70 ng/mL. The BSA-Au NCs were immobilized on a wax-printed paper-based platform and used to conduct real-time monitoring of rifampicin in urine.ConclusionWe have developed a robust, cost-effective, and portable point-of-care medical diagnostic platform for the detection of rifampicin in urine based on the ability of rifampicin to quench the fluorescence of immobilized BSA-Au NCs on wax-printed papers. The paper-based assay can be further used for the detection of other specific analytes via surface modification of the BSA in BSA-Au NCs and offers a useful tool for monitoring other diseases.

BackgroundChronic kidney disease (CKD) is characterized by dysbiosis, elevated levels of uremic toxins, systemic inflammation, and increased markers of oxidative stress. These factors lead to an increased risk of cardiovascular disease (CVD) which is common among CKD patients. Supplementation with high amylose maize resistant starch type 2 (RS-2) can change the composition of the gut microbiota, and reduce markers of inflammation and oxidative stress in patients with end-stage renal disease. However, the impact of RS-2 supplementation has not been extensively studied in CKD patients not on dialysis. Aerobic exercise training lowers certain markers of inflammation in CKD patients. Whether combining aerobic training along with RS-2 supplementation has an additive effect on the aforementioned biomarkers in predialysis CKD patients has not been previously investigated.MethodsThe study is being conducted as a 16-week, double-blind, placebo controlled, parallel arm, randomized controlled trial. Sixty stage 3-4 CKD patients (ages of 30-75 years) are being randomized to one of four groups: RS-2 & usual care, RS-2 & aerobic exercise, placebo (cornstarch) & usual care and placebo & exercise. Patients attend four testing sessions: Two baseline (BL) sessions with follow up visits 8 (wk8) and 16 weeks (wk16) later. Fasting blood samples, resting brachial and central blood pressures, and arterial stiffness are collected at BL, wk8 and wk16. A stool sample is collected for analysis of microbial composition and peak oxygen uptake is assessed at BL and wk16. Blood samples will be assayed for p-cresyl sulphate and indoxyl sulphate, c-reactive protein, tumor necrosis factor α, interleukin 6, interleukin 10, monocyte chemoattractant protein 1, malondialdehyde, 8-isoprostanes F2a, endothelin-1 and nitrate/nitrite. Following BL, subjects are randomized to their group. Individuals randomized to conditions involving exercise will attend three supervised moderate intensity (55-65% peak oxygen uptake) aerobic training sessions (treadmills, bikes or elliptical machine) per week for 16 weeks.DiscussionThis study has the potential to yield information about the effect of RS-2 supplementation on key biomarkers believed to impact upon the development of CVD in patients with CKD. We are examining whether there is an additive effect of exercise training and RS-2 supplementation on these key variables.Trial registrationClinicaltrials.gov Trial registration# NCT03689569 . 9/28/2018, retrospectively registered.

The use of misidentified and contaminated cell lines continues to be a problem in biomedical research. Research Resource Identifiers (RRIDs) should reduce the prevalence of misidentified and contaminated cell lines in the literature by alerting researchers to cell lines that are on the list of problematic cell lines, which is maintained by the International Cell Line Authentication Committee (ICLAC) and the Cellosaurus database. To test this assertion, we text-mined the methods sections of about two million papers in PubMed Central, identifying 305,161 unique cell-line names in 150,459 articles. We estimate that 8.6% of these cell lines were on the list of problematic cell lines, whereas only 3.3% of the cell lines in the 634 papers that included RRIDs were on the problematic list. This suggests that the use of RRIDs is associated with a lower reported use of problematic cell lines.

Human blood is a self-regenerating lipid-rich biological fluid that is routinely collected in hospital settings. The inventory of lipid molecules found in blood plasma (plasma lipidome) offers insights into individual metabolism and physiology in health and disease. Disturbances in the plasma lipidome also occur in conditions that are not directly linked to lipid metabolism; therefore, plasma lipidomics based on MS is an emerging tool in an array of clinical diagnostics and disease management. However, challenges exist in the translation of such lipidomic data to clinical applications. These relate to the reproducibility, accuracy, and precision of lipid quantitation, study design, sample handling, and data sharing. This position paper emerged from a workshop that initiated a community-led process to elaborate and define a set of generally accepted guidelines for quantitative MS-based lipidomics of blood plasma or serum, with harmonization of data acquired on different instrumentation platforms across independent laboratories as an ultimate goal. We hope that other fields may benefit from and follow such a precedent.

The National Institute on Drug Abuse Genetics and Epigenetics Cross-Cutting Research Team convened a diverse group of researchers, clinicians, and healthcare providers on the campus of the University of California, San Diego, in June 2018. The goal was to develop strategies to integrate genetics and phenotypes across species to achieve a better understanding of substance use disorders through associations between genotypes and addictive behaviors. This conference (a) discussed progress in harmonizing large opioid genetics cohorts, (b) discussed phenotypes that are used for genetics studies in humans, (c) examined phenotypes that are used for genetics studies in animal models, (d) identified synergies and gaps in phenotypic analyses of human and animal models and (e) identified strategies to integrate genetics and genomics data with phenotypes across species. The meeting consisted of panels that focused on phenotype harmonization (Dr. Laura Bierut, Dr. Olivier George, Dr. Dan Larach and Dr. Sesh Mudumbai), translating genetic findings between species (Dr. Elissa Chesler, Dr. Gary Peltz and Dr. Abraham Palmer), interpreting and understanding allelic variations (Dr. Vanessa Troiani and Dr. Tamara Richards) and pathway conservation in animal models and human studies (Dr. Robert Hitzemann, Dr. Huda Akil and Dr. Laura Saba). There were also updates that were provided by large consortia (Dr. Susan Tapert, Dr. Danielle Dick, Dr. Howard Edenberg and Dr. Eric Johnson). Collectively, the conference was convened to discuss progress and changes in genome-wide association studies.

The first scientific publication on 'general adaption syndrome', or as we know today 'biologic stress' has been published in Nature in 1936 by the 29-year old Hans Selye. His results in that short publication that contained no references or illustrations, were based on experiments in rats that were exposed to severe insults/ stressors, but his idea about a 'nonspecific bodily response' originated from his observations of sick patients whom he had seen as a medical student and young clinician. Autopsy of stressed rats revealed three major, grossly visible changes: hyperemia and enlargement of the adrenals, atrophy of the thymus and lymph nodes as well as hemorrhagic gastric erosions/ulcers (the "stress triad"). Based on this and additional observations, he concluded that the key master organ in stress reactions is the adrenal cortex (although he also accepted the limited and short lasting effect of catecholamines released from the adrenal medulla) which stimulated by an increased secretion of ACTH, secreted by the anterior pituitary gland. He thus identified the first molecular mediators of the stress reaction, i.e., steroids released from the adrenal cortex that we call today glucocorticoids, based on his classification and naming of steroids. At the end of a very productive life in experimental medicine, Selye recognized that under both unpleasant and demanding stressors as well as positive, rewarding stimuli adrenal cortex releases the same glucocorticoids and only certain brain structures may distinguish the stimuli under distress and eustress - terms he introduced in 1974, that also contained his last definition of stress: the nonspecific response of the body on any demand on it. After brief description of the history of stress research, the rest of this review is focused on one element of stress triad, i.e., gastroduodenal ulceration, especially its pathogenesis, prevention and treatment. Following a short description of acute gastroprotection, discovered by one of Selye's students, we discuss new molecular mediators of gastroduodenal ulceration like dopamine and new drugs that either only heal (very potently, on molar basis) or prevent and heal ulcers like sucralfate derivatives and the relatively new peptide BPC-157. We conclude that despite the extensive and multidisciplinary research on stress during the last 80 years, a lot of basic and clinical research is needed to better understand the manifestations, central and peripheral molecular regulators of stress response, especially the modes of prevention/management of distress or its transformation into eustress and the treatment of stress-related diseases.

Introduction background to metabolomicsMetabolomics is the comprehensive study of the metabolome, the repertoire of biochemicals (or small molecules) present in cells, tissues, and body fluids. The study of metabolism at the global or "-omics" level is a rapidly growing field that has the potential to have a profound impact upon medical practice. At the center of metabolomics, is the concept that a person's metabolic state provides a close representation of that individual's overall health status. This metabolic state reflects what has been encoded by the genome, and modified by diet, environmental factors, and the gut microbiome. The metabolic profile provides a quantifiable readout of biochemical state from normal physiology to diverse pathophysiologies in a manner that is often not obvious from gene expression analyses. Today, clinicians capture only a very small part of the information contained in the metabolome, as they routinely measure only a narrow set of blood chemistry analytes to assess health and disease states. Examples include measuring glucose to monitor diabetes, measuring cholesterol and high density lipoprotein/low density lipoprotein ratio to assess cardiovascular health, BUN and creatinine for renal disorders, and measuring a panel of metabolites to diagnose potential inborn errors of metabolism in neonates.Objectives of white paper—expected treatment outcomes and metabolomics enabling tool for precision medicineWe anticipate that the narrow range of chemical analyses in current use by the medical community today will be replaced in the future by analyses that reveal a far more comprehensive metabolic signature. This signature is expected to describe global biochemical aberrations that reflect patterns of variance in states of wellness, more accurately describe specific diseases and their progression, and greatly aid in differential diagnosis. Such future metabolic signatures will: (1) provide predictive, prognostic, diagnostic, and surrogate markers of diverse disease states; (2) inform on underlying molecular mechanisms of diseases; (3) allow for sub-classification of diseases, and stratification of patients based on metabolic pathways impacted; (4) reveal biomarkers for drug response phenotypes, providing an effective means to predict variation in a subject's response to treatment (pharmacometabolomics); (5) define a metabotype for each specific genotype, offering a functional read-out for genetic variants: (6) provide a means to monitor response and recurrence of diseases, such as cancers: (7) describe the molecular landscape in human performance applications and extreme environments. Importantly, sophisticated metabolomic analytical platforms and informatics tools have recently been developed that make it possible to measure thousands of metabolites in blood, other body fluids, and tissues. Such tools also enable more robust analysis of response to treatment. New insights have been gained about mechanisms of diseases, including neuropsychiatric disorders, cardiovascular disease, cancers, diabetes and a range of pathologies. A series of ground breaking studies supported by National Institute of Health (NIH) through the Pharmacometabolomics Research Network and its partnership with the Pharmacogenomics Research Network illustrate how a patient's metabotype at baseline, prior to treatment, during treatment, and post-treatment, can inform about treatment outcomes and variations in responsiveness to drugs (e.g., statins, antidepressants, antihypertensives and antiplatelet therapies). These studies along with several others also exemplify how metabolomics data can complement and inform genetic data in defining ethnic, sex, and gender basis for variation in responses to treatment, which illustrates how pharmacometabolomics and pharmacogenomics are complementary and powerful tools for precision medicine.Conclusions key scientific concepts and recommendations for precision medicineOur metabolomics community believes that inclusion of metabolomics data in precision medicine initiatives is timely and will provide an extremely valuable layer of data that compliments and informs other data obtained by these important initiatives. Our Metabolomics Society, through its "Precision Medicine and Pharmacometabolomics Task Group", with input from our metabolomics community at large, has developed this White Paper where we discuss the value and approaches for including metabolomics data in large precision medicine initiatives. This White Paper offers recommendations for the selection of state of-the-art metabolomics platforms and approaches that offer the widest biochemical coverage, considers critical sample collection and preservation, as well as standardization of measurements, among other important topics. We anticipate that our metabolomics community will have representation in large precision medicine initiatives to provide input with regard to sample acquisition/preservation, selection of optimal omics technologies, and key issues regarding data collection, interpretation, and dissemination. We strongly recommend the collection and biobanking of samples for precision medicine initiatives that will take into consideration needs for large-scale metabolic phenotyping studies.

ObjectivesPrevious attempts at meta-analysis and systematic review have not provided clear recommendations for the clinical application of thermal ablation in metastatic colorectal cancer. Many authors believe that the probability of gathering randomised controlled trial (RCT) data is low. Our aim is to provide a consensus document making recommendations on the appropriate application of thermal ablation in patients with colorectal liver metastases.MethodsThis consensus paper was discussed by an expert panel at The Interventional Oncology Sans Frontières 2013. A literature review was presented. Tumour characteristics, ablation technique and different clinical applications were considered and the level of consensus was documented.ResultsSpecific recommendations are made with regard to metastasis size, number, and location and ablation technique. Mean 31 % 5-year survival post-ablation in selected patients has resulted in acceptance of this therapy for those with technically inoperable but limited liver disease and those with limited liver reserve or co-morbidities that render them inoperable.ConclusionsIn the absence of RCT data, it is our aim that this consensus document will facilitate judicious selection of the patients most likely to benefit from thermal ablation and provide a unified interventional oncological perspective for the use of this technology.Key points• Best results require due consideration of tumour size, number, volume and location. • Ablation technology, imaging guidance and intra-procedural imaging assessment must be optimised. • Accepted applications include inoperable disease due to tumour distribution or inadequate liver reserve. • Other current indications include concurrent co-morbidity, patient choice and the test-of-time approach. • Future applications may include resectable disease, e.g. for small solitary tumours.

The long-term consequences of exposure to excess stress, particularly during sensitive developmental windows, on the initiation and progression of many complex, common physical and mental disorders that confer a major global burden of disease are well established. The period of intrauterine life represents among the most sensitive of these windows, at which time the effects of stress may be transmitted inter-generationally from a mother to her as-yet-unborn child. As explicated by the concept of fetal or developmental programming of health and disease susceptibility, a growing body of evidence supports the notion that health and disease susceptibility is determined by the dynamic interplay between genetic makeup and environment, particularly during intrauterine and early postnatal life. Except in extreme cases, an adverse intrauterine exposure may not, per se, 'cause' disease, but, instead, may determine propensity for disease(s) in later life (by shaping phenotypic responsivity to endogenous and exogenous disease-related risk conditions). Accumulating evidence suggests that maternal psychological and social stress during pregnancy represents one such condition that may adversely affect the developing child, with important implications for a diverse range of physical and mental health outcomes. In this paper we review primarily our own contributions to the field of maternal stress during pregnancy and child mental and physical health-related outcomes. We present findings on stress-related maternal-placental-fetal endocrine and immune/inflammatory processes that may mediate the effects of various adverse conditions during pregnancy on the developing human embryo and fetus. We enunciate conceptual and methodological issues related to the assessment of stress during pregnancy and discuss potential mechanisms of intergenerational transmission of the effects of stress. Lastly, we describe on-going research and some future directions of our program.

Cancers has instituted a "Best Paper" award to recognize the most outstanding papers in the area of oncology published in Cancers.[...].

The Alzheimer's Disease Neuroimaging Initiative (ADNI) is an ongoing, longitudinal, multicenter study designed to develop clinical, imaging, genetic, and biochemical biomarkers for the early detection and tracking of Alzheimer's disease (AD). The initial study, ADNI-1, enrolled 400 subjects with early mild cognitive impairment (MCI), 200 with early AD, and 200 cognitively normal elderly controls. ADNI-1 was extended by a 2-year Grand Opportunities grant in 2009 and by a competitive renewal, ADNI-2, which enrolled an additional 550 participants and will run until 2015. This article reviews all papers published since the inception of the initiative and summarizes the results to the end of 2013. The major accomplishments of ADNI have been as follows: (1) the development of standardized methods for clinical tests, magnetic resonance imaging (MRI), positron emission tomography (PET), and cerebrospinal fluid (CSF) biomarkers in a multicenter setting; (2) elucidation of the patterns and rates of change of imaging and CSF biomarker measurements in control subjects, MCI patients, and AD patients. CSF biomarkers are largely consistent with disease trajectories predicted by β-amyloid cascade (Hardy, J Alzheimer's Dis 2006;9(Suppl 3):151-3) and tau-mediated neurodegeneration hypotheses for AD, whereas brain atrophy and hypometabolism levels show predicted patterns but exhibit differing rates of change depending on region and disease severity; (3) the assessment of alternative methods of diagnostic categorization. Currently, the best classifiers select and combine optimum features from multiple modalities, including MRI, [(18)F]-fluorodeoxyglucose-PET, amyloid PET, CSF biomarkers, and clinical tests; (4) the development of blood biomarkers for AD as potentially noninvasive and low-cost alternatives to CSF biomarkers for AD diagnosis and the assessment of α-syn as an additional biomarker; (5) the development of methods for the early detection of AD. CSF biomarkers, β-amyloid 42 and tau, as well as amyloid PET may reflect the earliest steps in AD pathology in mildly symptomatic or even nonsymptomatic subjects and are leading candidates for the detection of AD in its preclinical stages; (6) the improvement of clinical trial efficiency through the identification of subjects most likely to undergo imminent future clinical decline and the use of more sensitive outcome measures to reduce sample sizes. Multimodal methods incorporating APOE status and longitudinal MRI proved most highly predictive of future decline. Refinements of clinical tests used as outcome measures such as clinical dementia rating-sum of boxes further reduced sample sizes; (7) the pioneering of genome-wide association studies that leverage quantitative imaging and biomarker phenotypes, including longitudinal data, to confirm recently identified loci, CR1, CLU, and PICALM and to identify novel AD risk loci; (8) worldwide impact through the establishment of ADNI-like programs in Japan, Australia, Argentina, Taiwan, China, Korea, Europe, and Italy; (9) understanding the biology and pathobiology of normal aging, MCI, and AD through integration of ADNI biomarker and clinical data to stimulate research that will resolve controversies about competing hypotheses on the etiopathogenesis of AD, thereby advancing efforts to find disease-modifying drugs for AD; and (10) the establishment of infrastructure to allow sharing of all raw and processed data without embargo to interested scientific investigators throughout the world.

ObjectivesThis article presents an overview of the current literature on biological markers for alcoholism, including markers associated with the pharmacological effects of alcohol and markers related to the clinical course and treatment of alcohol-related problems. Many of these studies are well known, while other studies cited are new and still being evaluated.MethodsIn this paper we first describe known biomarkers of alcohol-related disorders, review their features and the problems involved in their use. We then consider future developments on biomarkers and their possible impact on the field.ResultsMore recent findings cited include the work on type 7 adenylcyclase (AC) polymorphism and its lower expression levels in female alcoholics. Neuroimaging studies involving biomarkers have also reported brain volume reductions of gray and white matter, including amygdala and subcortical regions in alcoholic patients, while a high association between the copy number variations (CNVs) in 6q14.1/5q13.2 and alcohol dependence has more recently been identified in genetic studies.ConclusionsIn addition to their possible importance for diagnosis, biomarkers may have utility for predicting prognosis, progression of the disorder, the development of new treatments, and monitoring treatment effects. Although such findings should be verified in independent studies, the search for new biomarkers is continuing. Several potential candidate biomarkers have been found recently in blood, imaging, and genetic studies with encouraging results.

This review identifies a timeline to nanomedicine anticancer drug approval using the business model of inventors, innovators and imitators. By evaluating the publication record of nanomedicine cancer therapeutics we identified a trend of very few publications prior to FDA approval. We first enumerated the publications related to cancer involving polymers, liposomes or monoclonal antibodies and determined the number of citations per publication as well as the number of published clinical trials among the publications. Combining these data with the development of specific nanomedicines, we are able to identify an invention phase consisting of seminal papers in basic science necessary for the development of a specific nanomedicine. The innovation phase includes the first report, the development and the clinical trials involving that nanomedicine. Finally, the imitation phase begins after approval when others ride the wave of success by using the same formulation for new drugs or using the same drug to validate other nanomedicines. We then focused our analysis on nanomedicines containing camptothecin derivatives, which are not yet approved including two polymers considered innovations and one liposomal formulation in the imitation phase. The conclusion that may be drawn from the analysis of the camptothecins is that approved drugs reformulated in polymeric and liposomal cancer nanomedicines have a more difficult time navigating through the approval process than the parent molecule. This is probably due to the fact that for most currently approved drugs, reformulating them in a nanocarrier provides a small increase in performance that large pharmaceutical companies do not consider being worth the time, effort and expense of development. It also appears that drug carriers have a more difficult path through the clinic than monoclonal antibodies. The added complexity of nanocarriers also deters their use to deliver new molecular entities. Thus, the new drug candidates that might be most improved by drug delivery in nanocarriers are not formulated in this fashion.

Traumatic brain injury (TBI) and post-traumatic stress disorder (PTSD) are signature injuries of the wars in Iraq and Afghanistan and have been linked to an increased risk of Alzheimer's disease (AD) and other dementias. A meeting hosted by the Alzheimer's Association and the Veterans' Health Research Institute (NCIRE) in May 2012 brought together experts from the U.S. military and academic medical centers around the world to discuss current evidence and hypotheses regarding the pathophysiological mechanisms linking TBI, PTSD, and AD. Studies underway in civilian and military populations were highlighted, along with new research initiatives such as a study to extend the Alzheimer's Disease Neuroimaging Initiative (ADNI) to a population of veterans exposed to TBI and PTSD. Greater collaboration and data sharing among diverse research groups is needed to advance an understanding and appropriate interventions in this continuum of military injuries and neurodegenerative disease in the aging veteran.

Building on long-term benefits of early intervention (Paper 2 of this Series) and increasing commitment to early childhood development (Paper 1 of this Series), scaled up support for the youngest children is essential to improving health, human capital, and wellbeing across the life course. In this third paper, new analyses show that the burden of poor development is higher than estimated, taking into account additional risk factors. National programmes are needed. Greater political prioritisation is core to scale-up, as are policies that afford families time and financial resources to provide nurturing care for young children. Effective and feasible programmes to support early child development are now available. All sectors, particularly education, and social and child protection, must play a role to meet the holistic needs of young children. However, health provides a critical starting point for scaling up, given its reach to pregnant women, families, and young children. Starting at conception, interventions to promote nurturing care can feasibly build on existing health and nutrition services at limited additional cost. Failure to scale up has severe personal and social consequences. Children at elevated risk for compromised development due to stunting and poverty are likely to forgo about a quarter of average adult income per year, and the cost of inaction to gross domestic product can be double what some countries currently spend on health. Services and interventions to support early childhood development are essential to realising the vision of the Sustainable Development Goals.

Currently, there are a few detailed guidelines on the overall management of children and adolescents with moderate-severe atopic dermatitis. AD ​​is a complex disease presenting with different clinical phenotypes, which require an individualized and multidisciplinary approach. Therefore, appropriate interaction between primary care pediatricians, pediatric allergists, and pediatric dermatologists is crucial to finding the best management strategy. In this manuscript, members of the Italian Society of Pediatric Allergology and Immunology (SIAIP), the Italian Society of Pediatric Dermatology (SIDerP), and the Italian Society of Pediatrics (SIP) with expertise in the management of moderate-severe atopic dermatitis have reviewed the latest scientific evidence in the field. This narrative review aims to define a pathway to appropriately managing children and adolescents with moderate-severe atopic dermatitis.

ObjectiveElectronic health records (EHRs) are widely adopted, but the time demands of EHR use on ophthalmology trainees are not well understood. This study evaluated ophthalmology trainee time spent on clinical activities in an outpatient clinic undergoing EHR implementation.DesignProspective, manual time-motion observations of ophthalmology trainees in 2018.ParticipantsEleven ophthalmology residents and fellows observed during 156 patient encounters.MethodsProspective time-motion study of ophthalmology trainees 2 weeks before and 6 weeks after EHR implementation in an academic ophthalmology department. Manual time-motion observations were conducted for 11 ophthalmology trainees in 6 subspecialty clinics during 156 patient encounters. Time spent documenting, examining, and talking with patients were recorded. Factors influencing time requirements were evaluated using linear mixed effects models.Main outcome measuresTotal time spent by ophthalmology residents and fellows per patient, time spent on documentation, examination, and talking with patients.ResultsSeven ophthalmology residents and four ophthalmology fellows with mean (standard deviation) postgraduate year of 3.7 (1.2) were observed during 156 patient encounters. Using paper charts, mean total time spent on each patient was 11.6 (6.5) minutes, with 5.4 (3.5) minutes spent documenting (48%). After EHR implementation, mean total time spent on each patient was 11.8 (6.9) minutes, with 6.8 (4.7) minutes spent documenting (57%). Total time expenditure per patient did not significantly change after EHR implementation (+0.17 minutes, 95% confidence interval [CI] for difference in means: -2.78, 2.45; p = 0.90). Documentation time did not change significantly after EHR implementation in absolute terms (+1.42 minutes, 95% CI: -3.13, 0.29; p = 0.10), but was significantly greater as a proportion of total time (48% on paper to 57% on EHR; +9%, 95% CI: 2.17, 15.83; p = 0.011).ConclusionTotal time spent per patient and absolute time spent on documentation was not significantly different whether ophthalmology trainees used paper charts or the recently implemented EHR. Percentage of total time spent on documentation increased significantly with early EHR use. Evaluating EHR impact on ophthalmology trainees may improve understanding of how trainees learn to use the EHR and may shed light on strategies to address trainee burnout.

The 3rd International Consensus Workshop on Research Priorities in Endometriosis was held in São Paulo on May 4, 2014, following the 12th World Congress on Endometriosis. The workshop was attended by 60 participants from 19 countries and was divided into 5 main sessions covering pathogenesis/pathophysiology, symptoms, diagnosis/classification/prognosis, disease/symptom management, and research policy. This research priorities consensus statement builds on earlier efforts to develop research directions for endometriosis. Of the 56 research recommendations from the 2011 meeting in Montpellier, a total of 41 remained unchanged, 13 were updated, and 2 were deemed to be completed. Fifty-three new research recommendations were made at the 2014 meeting in Sao Paulo, which in addition to the 13 updated recommendations resulted in a total of 66 new recommendations for research. The research recommendations published herein, as well as those from the 2 previous papers from international consensus workshops, are an attempt to promote high-quality research in endometriosis by identifying and agreeing on key issues that require investigation. New areas included in the 2014 recommendations include infertility, patient stratification, and research in emerging nations, in addition to an increased focus on translational research. A revised and updated set of research priorities that builds on this document will be developed at the 13th World Congress on Endometriosis to be held on May 17-20, 2017, in Vancouver, British Columbia, Canada.

UnlabelledThis position paper reviews how the National Bone Health Alliance (NBHA) will execute a project to help assure health professionals of the clinical utility of bone turnover markers; the current clinical approaches concerning osteoporosis and the status and use of bone turnover markers in the USA; the rationale for focusing this effort around two specific bone turnover markers; the need to standardize bone marker sample collection procedures, reference ranges, and bone turnover marker assays in clinical laboratories; and the importance of harmonization for future research of bone turnover markers.IntroductionOsteoporosis is a major global health problem, with the prevalence and incidence of osteoporosis for at-risk populations estimated to be 44 million Americans. The potential of bone markers as an additional tool for health care professionals to improve patient outcomes and impact morbidity and mortality is crucial in providing better health care and addressing rising health care costs. This need to advance the field of bone turnover markers has been recognized by a number of organizations, including the International Osteoporosis Foundation (IOF), National Osteoporosis Foundation, International Federation of Clinical Chemistry, and Laboratory Medicine (IFCC), and the NBHA.MethodsThis position paper elucidates how this project will standardize bone turnover marker sample collection procedures in the USA, establish a USA reference range for one bone formation (serum procollagen type I N propeptide, s-PINP) and one bone resorption (serum C-terminal telopeptide of type I collagen, s-CTX) marker, and standardize bone turnover marker assays used in clinical laboratories. This effort will allow clinicians from the USA to have confidence in their use of bone turnover markers to help monitor osteoporosis treatment and assess future fracture risk. This project builds on the recommendations of the IOF/IFCC Bone Marker Standards Working Group by developing USA reference standards for s-PINP and s-CTX, the markers identified as most promising for use as reference markers.ResultsThe goals of this project will be realized through the NBHA and will include its governmental, academic, for-profit, and non-profit sector stakeholders as well as major academic and commercial laboratories. Upon completion, a parallel effort will be pursued to make bone turnover marker measurements reliable and accepted by all health care professionals for facilitating treatment decisions and ultimately be reimbursed by all health insurance payers.ConclusionsSuccessful completion of this project will help assure health professionals from the USA of the clinical utility of bone turnover markers and ties in with the parallel effort of the IOF/IFCC to develop worldwide bone turnover reference ranges.

Family, twin, and adoption studies have documented a strong genetic basis for ADHD/HKD, but these studies do not identify specific genes linked to the disorder. Molecular genetic studies can identify allelic variations of specific genes that are functionally associated with ADHD/HKD, and dopamine genes have been the initial candidates based on the site of action of the stimulants drugs, which for a half century have provided the primary pharmacological treatment for ADHD/HKD. Two candidate dopamine genes have been investigated and reported to be associated with ADHD/HKD: the dopamine transporter (DAT1) gene [Cook et al., American Journal of Human Genetics 1995;56:993-998, Gill et al., Molecular Psychiatry 1997;2:311-313] and the dopamine receptor D4 (DRD4) gene [LaHoste et al., Molecular Psychiatry 1996;1:121-124: Smalley et al., 1998;3:427-430; Swanson et al., Molecular Psychiatry 1998;3:38-41]. Speculative hypotheses [Swanson and Castellanos, NIH Consensus Development Conference: Diagnosis and Treatment of Attention Deficit Hyperactivity Disorder, November 1998. p. 37-42] have suggested that specific alleles of these dopamine genes may alter dopamine transmission in the neural networks implicated in ADHD/HKD (e.g. that the 10-repeat allele of the DAT1 gene may be associated with hyperactive re-uptake of dopamine or that the 7-repeat allele of the DRD4 gene may be associated with a subsensitive postsynaptic receptor). These and other variants of the dopamine hypothesis of ADHD will be discussed.

Engagement is an important component in the advancement of gene-drive vector control research programs as developers look to transition the technology from the laboratory to the field. As research advances and engagement surrounding this novel technology is put into practice, knowledge can be gained from practical experiences and applications in the field. A relationship-based model (RBM) provides a framework for end-user development of engagement programs and strategies. The model places end users at the center of the engagement decision-making processes rather than as recipients of predetermined strategies, methods, and definitions. Successful RBM application for healthcare delivery has previously been demonstrated, and the University of California Malaria Initiative (UCMI) has applied this model to its gene-drive program in the Democratic Republic of São Tomé and Príncipe. The model emphasizes the importance of local leadership in the planning, development, and implementation of all phases of project engagement. The primary aim of this paper is to translate the model from paper to practice and provide a transparent description, using practical examples, of the UCMI program implementation of RBM at its field site. End-user development of the UCMI engagement program provides a unique approach to the development of ethical, transparent, and effective engagement strategies for malaria control programs. This paper may also serve as a reference and example for projects looking to establish an engagement program model that integrates end-user groups in the decision-making processes surrounding engagement.

IntroductionThe analysis of surgical research using bibliometric measures has become increasingly prevalent. Absolute citation counts (CC) or indices are commonly used markers of research quality but may not adequately capture the most impactful research. A novel scoring system, the disruptive score (DS) has been found to identity academic work that either changes paradigms (disruptive (DIS) work) or entrenches ideas (developmental (DEV) work). We sought to analyze the most DIS and DEV versus most cited research in civilian trauma.MethodsThe top papers by DS and by CC from trauma and surgery journals were identified via a professional literature search. The identified publications were then linked to the National Institutes of Health iCite tool to quantify total CC and related metrics. The top 100 DIS and DEV publications by DS were analyzed based on the area of focus, citation, and perceived clinical impact, and compared with the top 100 papers by CC.Results32 293 articles published between 1954 and 2014 were identified. The most common publication location of selected articles was published in Journal of Trauma (31%). Retrospective reviews (73%) were common in DIS (73%) and top CC (67%) papers, while DEV papers were frequently case reports (49%). Only 1 publication was identified in the top 100 DIS and top 100 CC lists. There was no significant correlation between CC and DS among the top 100 DIS papers (r=0.02; p=0.85), and only a weak correlation between CC and DS score (r=0.21; p

In 2019, the National Health Interview survey found that nearly 59% of adults reported pain some, most, or every day in the past 3 months, with 39% reporting back pain, making back pain the most prevalent source of pain, and a significant issue among adults. Often, identifying a direct, treatable cause for back pain is challenging, especially as it is often attributed to complex, multifaceted issues involving biological, psychological, and social components. Due to the difficulty in treating the true cause of chronic low back pain (cLBP), an over-reliance on opioid pain medications among cLBP patients has developed, which is associated with increased prevalence of opioid use disorder and increased risk of death. To combat the rise of opioid-related deaths, the National Institutes of Health (NIH) initiated the Helping to End Addiction Long-TermSM (HEAL) initiative, whose goal is to address the causes and treatment of opioid use disorder while also seeking to better understand, diagnose, and treat chronic pain. The NIH Back Pain Consortium (BACPAC) Research Program, a network of 14 funded entities, was launched as a part of the HEAL initiative to help address limitations surrounding the diagnosis and treatment of cLBP. This paper provides an overview of the BACPAC research program's goals and overall structure, and describes the harmonization efforts across the consortium, define its research agenda, and develop a collaborative project which utilizes the strengths of the network. The purpose of this paper is to serve as a blueprint for other consortia tasked with the advancement of pain related science.

Spastic paraparesis has been described to occur in 13.7% of PSEN1 mutations and can be the presenting feature in 7.5%. In this paper, we describe a family with a particularly young onset of spastic paraparesis due to a novel mutation in PSEN1 (F388S). Three affected brothers underwent comprehensive imaging protocols, two underwent ophthalmological evaluations and one underwent neuropathological examination after his death at age 29. Age of onset was consistently at age 23 with spastic paraparesis, dysarthria and bradyphrenia. Pseudobulbar affect followed with progressive gait problems leading to loss of ambulation in the late 20s. Cerebrospinal fluid levels of amyloid-β, tau and phosphorylated tau and florbetaben PET were consistent with Alzheimer's disease. Flortaucipir PET showed an uptake pattern atypical for Alzheimer's disease, with disproportionate signal in posterior brain areas. Diffusion tensor imaging showed decreased mean diffusivity in widespread areas of white matter but particularly in areas underlying the peri-Rolandic cortex and in the corticospinal tracts. These changes were more severe than those found in carriers of another PSEN1 mutation, which can cause spastic paraparesis at a later age (A431E), which were in turn more severe than among persons carrying autosomal dominant Alzheimer's disease mutations not causing spastic paraparesis. Neuropathological examination confirmed the presence of cotton wool plaques previously described in association with spastic parapresis and pallor and microgliosis in the corticospinal tract with severe amyloid-β pathology in motor cortex but without unequivocal disproportionate neuronal loss or tau pathology. In vitro modelling of the effects of the mutation demonstrated increased production of longer length amyloid-β peptides relative to shorter that predicted the young age of onset. In this paper, we provide imaging and neuropathological characterization of an extreme form of spastic paraparesis occurring in association with autosomal dominant Alzheimer's disease, demonstrating robust diffusion and pathological abnormalities in white matter. That the amyloid-β profiles produced predicted the young age of onset suggests an amyloid-driven aetiology though the link between this and the white matter pathology remains undefined.

Cost-effectiveness analyses of new cancer treatments in real-world settings (e.g., post-clinical trials) inform healthcare decision makers about their healthcare investments for patient populations. The results of these analyses are often, though not always, presented with statistical uncertainty. This paper identifies five ways to characterize statistical uncertainty: (1) a 95% confidence interval (CI) for the incremental cost-effectiveness ratio (ICER); (2) a 95% CI for the incremental net benefit (INB); (3) an INB by willingness-to-pay (WTP) plot; (4) a cost-effectiveness acceptability curve (CEAC); and (5) a cost-effectiveness scatterplot. It also explores their usage in 22 articles previously identified by a rapid review of real-world cost effectiveness of novel cancer treatments. Seventy-seven percent of these articles presented uncertainty results. The majority those papers (59%) used administrative data to inform their analyses while the remaining were conducted using models. Cost-effectiveness scatterplots were the most commonly used method (34.3%), with 40% indicating high levels of statistical uncertainty, suggesting the possibility of a qualitatively different result from the estimate given. Understanding the necessity for and the meaning of uncertainty in real-world cost-effectiveness analysis will strengthen knowledge translation efforts to improve patient outcomes in an efficient manner.

BackgroundUpper extremity (UE) stroke rehabilitation requires patients to perform exercises at home, yet patients show limited benefit from paper-based home exercise programs.ObjectiveTo compare the effectiveness of 2 home exercise programs for reducing UE impairment: a paper-based approach and a sensorized exercise system that incorporates recommended design features for home rehabilitation technology.MethodsIn this single-blind, randomized controlled trial, 27 participants in the subacute phase of stroke were assigned to the sensorized exercise (n = 14) or conventional therapy group (n = 13), though 2 participants in the conventional therapy group were lost to follow-up. Participants were instructed to perform self-guided movement training at home for at least 3 hours/week for 3 consecutive weeks. The sensorized exercise group used FitMi, a computer game with 2 puck-like sensors that encourages movement intensity and auto-progresses users through 40 exercises. The conventional group used a paper book of exercises. The primary outcome measure was the change in Upper Extremity Fugl-Meyer (UEFM) score from baseline to follow-up. Secondary measures included the Modified Ashworth Scale for spasticity (MAS) and the Visual Analog Pain (VAP) scale.ResultsParticipants who used FitMi improved by an average of 8.0 ± 4.6 points on the UEFM scale compared to 3.0 ± 6.1 points for the conventional participants, a significant difference (t-test, P = .029). FitMi participants exhibited no significant changes in UE MAS or VAP scores.ConclusionsA sensor-based exercise system incorporating a suite of recommended design features significantly and safely reduced UE impairment compared to a paper-based, home exercise program.Trial registrationClinicalTrials.gov Identifier: NCT03503617.

BackgroundIndia's recent increase in urbanization alongside with feminization of rural agriculture could increase the existing gender disparities in dietary diversity. With many rural men migrating to urban areas, women have increased domestic burdens as well as productive burdens such as making informed crop production decisions so household members consume a diverse diet. Given the rapid and recent onset of this phenomenon, there is a need to explore gender differentials in diet diversity across urban and rural areas to assess if certain populations are being disproportionately impacted by this trend. There are limited established quantitative studies discussing this gender disparity with respect to urbanization. Therefore, this paper compares dietary diversity among adult men, adult women, adolescent males, and adolescent females in urban and peri-urban locations. The authors also assess if various sociodemographic factors correlate with dietary diversity.MethodsAnalyses were conducted on dietary diversity data collected by the International Crops Research Institute for the Semi-Arid Tropics (ICRISAT) from selected urban (1108 individuals) and peri-urban (808 individuals) locations of Hyderabad, India. The total sample size of the population is n = 1816: 660 adult males, 662 adult females, 205 adolescent males, and 289 adolescent females.ResultsAdult women and adolescent females have a higher diet disparity between peri-urban and urban areas when compared to adult males and adolescent males. Multivariate analyses followed by post hoc multiple comparisons testing further support that peri-urban adult women consume a less diverse diet compared to their urban counterparts and less than other peri-urban adult men and adolescent women. It was also found that marital status, type of household card owned, and the highest degree of education are statistically significant correlators of an individual's dietary diversity.ConclusionsGiven that urbanization could negatively impact already vulnerable populations such as peri-urban adult women, who play a key role in children's nutrition, it is important to provide support to these populations. This paper suggests it is possible to do so through government subsidization of peri-urban farmers to grow more diverse crops, fortifying easily accessible foods with commonly lacking micronutrients, including Vitamin A, folic acid, and iron, market access, and affordable prices.

PurposeEating disorders (EDs) are mental illnesses with severe consequences and high mortality rates. Notwithstanding, EDs are considered a niche specialty making it often difficult for researchers to publish in high-impact journals. Subsequently, research on EDs receives less funding than other fields of psychiatry potentially slowing treatment progress. This study aimed to compare research vitality between EDs and schizophrenia focusing on: number and type of publications; top-cited articles; geographical distribution of top-ten publishing countries; journal distribution of scientific production as measured by bibliometric analysis; funded research and collaborations.MethodsWe used the Scopus database, then we adopted the Bibliometrix R-package software with the web interface app Biblioshiny. We included in the analyses 1,916 papers on EDs and 6491 on schizophrenia.ResultsThe ED field published three times less than schizophrenia in top-ranking journals - with letters and notes particularly lacking-notwithstanding a comparable number of papers published per author. Only 50% of top-cited articles focused on EDs and a smaller pool of journals available for ED research (i.e., Zones 1 and 2 according to Bradford's law) emerged; journals publishing on EDs showed an overall lower rank compared to the schizophrenia field. Schizophrenia research was more geographically distributed and more funded; in contrast, a comparable collaboration index was found between the fields.ConclusionThese data show that research on EDs is currently marginalized and top-rank journals are seldom achievable by researchers in EDs. Such difficulties in research dissemination entail potentially serious repercussions on clinical advancements.Level of evidenceLevel V: opinions of respected authorities, based on descriptive studies, narrative reviews, clinical experience, or reports of expert committees.

BackgroundThe National Cancer Institute (NCI) method has been used widely by researchers to make inferences about usual dietary intake distributions of foods and nutrients based on a limited number of 24-hour dietary recalls (24HRs). Although the NCI method does not provide individual estimates of usual intake, it can be used to address many research questions, including modeling effects of nutrition interventions on population distributions of usual intake. Software for implementing the NCI method and corresponding code examples is publicly available in the form of SAS macros, but little formal guidance exists for conducting advanced analyses.ObjectivesWe aim to present advanced techniques for working with NCI macros to conduct both basic and advanced dietary analyses and modeling.MethodWe first present the three basic building blocks of analyses using the NCI method: 1) dataset preparation; 2) application of the MIXTRAN macro to estimate parameters of the usual intake distribution, including effects of covariates, after transformation of 24HRs to approximate normality; and 3) application of the DISTRIB macro to estimate the distribution of usual nutrient intake. Then, we illustrate how researchers can employ these building blocks to answer questions beyond typical descriptive analyses.ResultsResearchers can adapt the building blocks to 1) account for factors such as demographic changes or nutrition interventions such as food fortification, 2) estimate the prevalence of dietary inadequacy via the full probability method, 3) incorporate nutrient intake from sources not always captured by 24HRs, such as dietary supplements and human milk, and 4) carry out multiple subgroup analyses. This paper describes the theoretical basis and operational guidance for these techniques.ConclusionWith this paper as a detailed resource, researchers can leverage the basic NCI building blocks to investigate a wide range of questions about usual dietary intake distribution.

Cue reactivity is one of the most frequently used paradigms in functional magnetic resonance imaging (fMRI) studies of substance use disorders (SUDs). Although there have been promising results elucidating the neurocognitive mechanisms of SUDs and SUD treatments, the interpretability and reproducibility of these studies is limited by incomplete reporting of participants' characteristics, task design, craving assessment, scanning preparation and analysis decisions in fMRI drug cue reactivity (FDCR) experiments. This hampers clinical translation, not least because systematic review and meta-analysis of published work are difficult. This consensus paper and Delphi study aims to outline the important methodological aspects of FDCR research, present structured recommendations for more comprehensive methods reporting and review the FDCR literature to assess the reporting of items that are deemed important. Forty-five FDCR scientists from around the world participated in this study. First, an initial checklist of items deemed important in FDCR studies was developed by several members of the Enhanced NeuroImaging Genetics through Meta-Analyses (ENIGMA) Addiction working group on the basis of a systematic review. Using a modified Delphi consensus method, all experts were asked to comment on, revise or add items to the initial checklist, and then to rate the importance of each item in subsequent rounds. The reporting status of the items in the final checklist was investigated in 108 recently published FDCR studies identified through a systematic review. By the final round, 38 items reached the consensus threshold and were classified under seven major categories: 'Participants' Characteristics', 'General fMRI Information', 'General Task Information', 'Cue Information', 'Craving Assessment Inside Scanner', 'Craving Assessment Outside Scanner' and 'Pre- and Post-Scanning Considerations'. The review of the 108 FDCR papers revealed significant gaps in the reporting of the items considered important by the experts. For instance, whereas items in the 'General fMRI Information' category were reported in 90.5% of the reviewed papers, items in the 'Pre- and Post-Scanning Considerations' category were reported by only 44.7% of reviewed FDCR studies. Considering the notable and sometimes unexpected gaps in the reporting of items deemed to be important by experts in any FDCR study, the protocols could benefit from the adoption of reporting standards. This checklist, a living document to be updated as the field and its methods advance, can help improve experimental design, reporting and the widespread understanding of the FDCR protocols. This checklist can also provide a sample for developing consensus statements for protocols in other areas of task-based fMRI.

BackgroundThis scoping review reports on studies that collect survey data using quantitative research to measure self-reported oral health status outcome measures. The objective of this review is to categorize measures used to evaluate self-reported oral health status and oral health quality of life used in surveys of general populations.MethodsThe review is guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR) with the search on four online bibliographic databases. The criteria include (1) peer-reviewed articles, (2) papers published between 2011 and 2021, (3) only studies using quantitative methods, and (4) containing outcome measures of self-assessed oral health status, and/or oral health-related quality of life. All survey data collection methods are assessed and papers whose methods employ newer technological approaches are also identified.ResultsOf the 2981 unduplicated papers, 239 meet the eligibility criteria. Half of the papers use impact scores such as the OHIP-14; 10% use functional measures, such as the GOHAI, and 26% use two or more measures while 8% use rating scales of oral health status. The review identifies four data collection methods: in-person, mail-in, Internet-based, and telephone surveys. Most (86%) employ in-person surveys, and 39% are conducted in Asia-Pacific and Middle East countries with 8% in North America. Sixty-six percent of the studies recruit participants directly from clinics and schools, where the surveys were carried out. The top three sampling methods are convenience sampling (52%), simple random sampling (12%), and stratified sampling (12%). Among the four data collection methods, in-person surveys have the highest response rate (91%), while the lowest response rate occurs in Internet-based surveys (37%). Telephone surveys are used to cover a wider population compared to other data collection methods. There are two noteworthy approaches: 1) sample selection where researchers employ different platforms to access subjects, and 2) mode of interaction with subjects, with the use of computers to collect self-reported data.ConclusionThe study provides an assessment of oral health outcome measures, including subject-reported oral health status and notes newly emerging computer technological approaches recently used in surveys conducted on general populations. These newer applications, though rarely used, hold promise for both researchers and the various populations that use or need oral health care.

"Race" and "ethnicity" are socially constructed terms, not based on biology - in contrast to biologic ancestry and genetic admixture - and are flexible, contested, and unstable concepts, often driven by power. Although individuals may self-identify with a given race and ethnic group, as multidimensional beings exposed to differential life influencing factors that contribute to disease risk, additional social determinants of health (SDOH) should be explored to understand the relationship of race or ethnicity to health. Potential health effects of structural racism, defined as "the structures, policies, practices, and norms resulting in differential access to goods, services, and opportunities of society by "race," have been largely ignored in medical research. The Women's Health Initiative (WHI) was expected to enroll a racially and ethnically diverse cohort of older women at 40 U.S. clinical centers between 1993 and 1998; yet, key information on the racial and ethnic make-up of the WHI cohort of 161,808 women was limited until a 2020-2021 Task Force was charged by the WHI Steering Committee to better characterize the WHI cohort and develop recommendations for WHI investigators who want to include "race" and/or "ethnicity" in papers and presentations. As the lessons learned are of relevance to most cohorts, the essence of the WHI Race and Ethnicity Language and Data Interpretation Guide is presented in this paper. Recommendations from the WHI Race and Ethnicity Language and Data Interpretation Guide include: Studies should be designed to include all populations and researchers should actively, purposefully and with cultural-relevance, commit to recruiting a diverse sample; Researchers should collect robust data on race, ethnicity and SDOH variables that may intersect with participant identities, such as immigration status, country of origin, acculturation, current residence and neighborhood, religion; Authors should use appropriate terminology, based on a participant's self-identified "race" and "ethnicity", and provide clear rationale, including a conceptual framework, for including race and ethnicity in the analytic plan; Researchers should employ appropriate analytical methods, including mixed-methods, to study the relationship of these sociocultural variables to health; Authors should address how representative study participants are of the population to which results might apply, such as by age, race and ethnicity.

Recently, we have proposed simple methodology to derive clearance and rate constant equations, independent of differential equations, based on Kirchhoff's Laws, a common methodology from physics used to describe rate-defining processes either in series or parallel. Our approach has been challenged in three recent publications, two published in this journal, but notably what is lacking is that none evaluate experimental pharmacokinetic data. As reviewed here, manuscripts from our laboratory have evaluated published experimental data, demonstrating that the Kirchhoff's Laws approach explains (1) why all of the experimental perfused liver clearance data appear to fit the equation that was previously believed to be the well-stirred model, (2) why linear pharmacokinetic systemic bioavailability determinations can be greater than 1, (3) why renal clearance can be a function of drug input processes, and (4) why statistically different bioavailability measures may be found for urinary excretion versus systemic concentration measurements. Our most recent paper demonstrates (5) how the universally accepted steady-state clearance approach used by the field for the past 50 years leads to unrealistic outcomes concerning the relationship between liver-to-blood Kpuu and hepatic availability FH , highlighting the potential for errors in pharmacokinetic evaluations based on differential equations. The Kirchhoff's Laws approach is applicable to all pharmacokinetic analyses of quality experimental data, those that were previously adequately explained with present pharmacokinetic theory, and those that were not. The publications that have attempted to rebut our position do not address unexplained experimental data, and we show here why their analyses are not valid. SIGNIFICANCE STATEMENT: The Kirchhoff's Laws approach to deriving clearance equations for linear systems in parallel or in series, independent of differential equations, successfully describes published pharmacokinetic data that has previously been unexplained. Three recent publications claim to refute our proposed methodology; these publications only make theoretical arguments, do not evaluate experimental data, and never demonstrate that the Kirchhoff methodology provides incorrect interpretations of experimental pharmacokinetic data, including statistically significant data not explained by present pharmacokinetic theory. We demonstrate why these analyses are invalid.

BackgroundThe purpose of this narrative review was to survey the literature for common complications following treatment of DDH in children less than 4 years old.MethodsThe Pubmed database was queried. Search result titles were reviewed to identify papers that were pertinent to the topic. Abstracts for these papers were obtained and read, and a subset of these were selected for review of the complete manuscript.Results92 manuscripts were reviewed. Residual dysplasia, redislocation, and osteonecrosis are the primary complications of treatment in this age group. In the long term, hips without complications related to DDH treatment tend to do well, although a significant percentage of them will inevitably require joint replacement surgery.ConclusionAlthough there is excellent potential for a good outcome when DDH is diagnosed and treated under age 4 years, osteonecrosis continues to be a concern with all treatment methods. A subset of patients from this young cohort will continue to have residual dysplasia or recurrent dislocation requiring return to the operating room.

This theme issue provides an assessment of the contribution of soils to Nature's Contributions to People (NCP). The papers in this issue show that soils can contribute positively to the delivery of all NCP. These contributions can be maximized through careful soil management to provide healthy soils, but poorly managed, degraded or polluted soils may contribute negatively to the delivery of NCP. Soils are also shown to contribute positively to the UN Sustainable Development Goals. Papers in the theme issue emphasize the need for careful soil management. Priorities for soil management must include: (i) for healthy soils in natural ecosystems, protect them from conversion and degradation, (ii) for managed soils, manage in a way to protect and enhance soil biodiversity, health, productivity and sustainability and to prevent degradation, and (iii) for degraded soils, restore to full soil health. Our knowledge of what constitutes sustainable soil management is mature enough to implement best management practices, in order to maintain and improve soil health. The papers in this issue show the vast potential of soils to contribute to NCP. This is not only desirable, but essential to sustain a healthy planet and if we are to deliver sustainable development in the decades to come. This article is part of the theme issue 'The role of soils in delivering Nature's Contributions to People'.

ContextSodium azide is a highly toxic chemical. Its production has increased dramatically over the last 30 years due to its widespread use in vehicular airbags, and it is available for purchase online. Thus, accidental exposure to azide or use as a homicidal or suicidal agent could be on the rise, and secondary exposure to medical personnel can occur. No antidote exists for azide poisoning. We conducted a systematic review of azide poisoning to assess recent poisoning reports, exposure scenarios, clinical presentations, and treatment strategies.MethodsWe searched both medical and newspaper databases to review the literature between 01/01/2000 and 12/31/2020, pairing the controlled vocabulary and keyword terms "sodium azide" or "hydrazoic acid" with terms relating to exposures and outcomes, such as "ingestion," "inhalation," "exposure," "poisoning," and "death." We included all peer-reviewed papers and news articles describing human azide poisoning cases from English and non-English publications that could be identified using English keywords. Data abstracted included the number, age, and gender of cases, mode of exposure, exposure setting, azide dose and route of exposure, symptoms, outcome, and treatment modalities.ResultsWe identified 663 peer-reviewed papers and 303 newspaper articles. After removing duplicated and non-qualifying sources, 54 publications were reviewed describing 156 cases, yielding an average of 7.8 reported azide poisoning cases per year. This rate is three times higher than in a previous review covering the period of 1927 to 1999. Poisoning occurred most commonly in laboratory workers, during secondary exposure of medical personnel, or from a ripped airbag. Hypotension occurred commonly, in some cases requiring vasopressors and one patient received an intra-aortic ballon pump. Gastric lavage and/or activated charcoal were used for oral azide ingestion, and sodium nitrite, sodium thiosulfate, and/or hydroxocobalamin were used in severely poisoned patients.ConclusionsRecent increases in azide poisoning reports may stem from greater commercial use and availability. Treatment of systemic poisoning may require aggressive hemodynamic support due to profound hypotension. Based on mechanistic considerations, hydroxocobalamin is a rational choice for treating azide poisoning.

IntroductionThe goal of neuromuscular scoliosis (NMS) surgery is to improve sitting balance, facilitate daily care, and alleviate pain. In nonambulatory patients, where sitting balance is key, fusion to the pelvis is usually required. However, in minimally ambulatory patients, fusion to the pelvis remains controversial, and there is considerable practice variability in this patient population. The purpose of this study is to evaluate and summarize the available evidence regarding fusion constructs in minimally ambulatory patients with NMS and to provide expert opinion regarding when fusion to the pelvis should be considered.MethodsA search of the English literature was performed using PubMed to identify papers pertaining to patients with NMS treated with instrumented posterior spinal fusion. Papers published before 2000, case reports, and level V evidence were excluded.ResultsThe authors identified 8 studies for review. The majority included both nonambulatory and minimally ambulatory patients. Structured review of the literature demonstrated fusion to the pelvis may allow for greater curve and pelvic obliquity correction, but it is also associated with increased blood loss and operative time. There is no evidence that fusing to the pelvis decreases ambulatory status in minimally ambulatory patients.ConclusionsIn minimally ambulatory patients with NMS, fusion short of the pelvis may be considered in patients with adequate head control without the presence of hip subluxation or dislocation and when pelvic obliquity is

Cerebrovascular malformations occur in both sporadic and inherited patterns. This paper reviews imaging and clinical features of cerebrovascular malformations with a genetic basis. Genetic diseases such as familial cerebral cavernous malformations and hereditary hemorrhagic telangiectasia often have manifestations in bone, skin, eyes, and visceral organs, which should be recognized. Genetic and molecular mechanisms underlying the inherited disorders are becoming better understood, and treatments are likely to follow. An interaction between the intestinal microbiome and formation of cerebral cavernous malformations has emerged, with possible treatment implications. Two-hit mechanisms are involved in these disorders, and additional triggering mechanisms are part of the development of malformations. Hereditary hemorrhagic telangiectasia encompasses a variety of vascular malformations, with widely varying risks, and a more recently recognized association with cortical malformations. Somatic mutations are implicated in the genesis of some sporadic malformations, which means that discoveries related to inherited disorders may aid treatment of sporadic cases. This paper summarizes the current state of knowledge of these conditions, salient features regarding mechanisms of development, and treatment prospects.