Short-term treatment with cholestyramine increases long-acting anticoagulant rodenticide clearance from rabbits without affecting plasma vitamin K1 levels nor blood coagulation.

Administration of high dose vitamin K1 (VK1) overcomes coagulopathy and bleeding elicited by acute poisoning with long-acting anti-coagulant rodenticides (LAARs). However, long-term (months) treatment is required due to long LAAR biological half-lives that may lead to poor compliance and recurrent coagulopathy. The half-lives of LAARs are extended by slow metabolism, and similar to warfarin, are thought to undergo enterohepatic recirculation. We now show that treatment with the bile acid sequestrant cholestyramine (CSA) administered concomitantly with VK1 decreases plasma LAAR levels and increases LAAR fecal excretion. Daily CSA treatment for 14 days did not reduce plasma VK1 levels, nor increase prothrombin time. Collectively, these data show that CSA accelerates LAAR clearance from rabbits without adverse effects on VK1 anti-coagulation, and could provide an additional therapeutic option for treatment of LAAR poisoning.

Sunlight: Time for a Rethink?

UVR is a skin carcinogen, yet no studies link sun exposure to increased all-cause mortality. Epidemiological studies from the United Kingdom and Sweden link sun exposure with reduced all-cause, cardiovascular, and cancer mortality. Vitamin D synthesis is dependent on UVB exposure. Individuals with higher serum levels of vitamin D are healthier in many ways, yet multiple trials of oral vitamin D supplementation show little benefit. Growing evidence shows that sunlight has health benefits through vitamin D-independent pathways, such as photomobilization of nitric oxide from cutaneous stores with reduction in cardiovascular morbidity. Sunlight has important systemic health benefit as well as risks.

Common questions and misconceptions about protein supplementation: what does the scientific evidence really show?

Protein supplementation often refers to increasing the intake of this particular macronutrient through dietary supplements in the form of powders, ready-to-drink shakes, and bars. The primary purpose of protein supplementation is to augment dietary protein intake, aiding individuals in meeting their protein requirements, especially when it may be challenging to do so through regular food (i.e. chicken, beef, fish, pork, etc.) sources alone. A large body of evidence shows that protein has an important role in exercising and sedentary individuals. A PubMed search of "protein and exercise performance" reveals thousands of publications. Despite the considerable volume of evidence, it is somewhat surprising that several persistent questions and misconceptions about protein exist. The following are addressed: 1) Is protein harmful to your kidneys? 2) Does consuming "excess" protein increase fat mass? 3) Can dietary protein have a harmful effect on bone health? 4) Can vegans and vegetarians consume enough protein to support training adaptations? 5) Is cheese or peanut butter a good protein source? 6) Does consuming meat (i.e., animal protein) cause unfavorable health outcomes? 7) Do you need protein if you are not physically active? 8) Do you need to consume protein ≤ 1 hour following resistance training sessions to create an anabolic environment in skeletal muscle? 9) Do endurance athletes need additional protein? 10) Does one need protein supplements to meet the daily requirements of exercise-trained individuals? 11) Is there a limit to how much protein one can consume in a single meal? To address these questions, we have conducted a thorough scientific assessment of the literature concerning protein supplementation.

Effects of Supplementation with Microalgae Extract from Phaeodactylum tricornutum (Mi136) to Support Benefits from a Weight Management Intervention in Overweight Women.

BACKGROUND: Microalgae like Phaeodactylum tricornutum (PT) contain the carotenoid, fucoxanthin, which has been purported to promote fat loss, lower blood lipids, and improve glucose management. This study examined whether dietary supplementation with microalgae extracts from PT containing 4.4 mg/d of fucoxanthin affects changes in body composition or health markers in overweight women during an exercise and diet intervention. MATERIALS AND METHODS: A total of 37 females (28.6 ± 7.9 years, 80.2 ± 14.9 kg, 29.6 ± 3.8 kg/m², 41.4 ± 4.2% fat) fasted for 12 h, donated a fasting blood sample, completed health and mood state inventories, and undertook body composition, health, and exercise assessments. In a counterbalanced, randomized, and double-blind manner, participants ingested a placebo (PL), or microalgae extract of Phaeodactylum tricornutum standardized to 4.4 mg of fucoxanthin (FX) for 12 weeks while participating in a supervised exercise program that included resistance-training and walking (3 days/week) with encouragement to accumulate 10,000 steps/day on remaining days of the week. The diet intervention involved reducing energy intake by about -300 kcal/d (i.e., ≈1400-1600 kcals/d, 55% carbohydrate, 30% fat, 15% protein) to promote a -500 kcal/d energy deficit with exercise. Follow-up testing was performed at 6 and 12 weeks. A general linear model (GLM) with repeated measures statistical analysis was used to analyze group responses and changes from baseline with 95% confidence intervals. RESULTS: Dietary supplementation with microalgae extract from PT containing fucoxanthin for 12 weeks did not promote additional weight loss or fat loss in overweight but otherwise healthy females initiating an exercise and diet intervention designed to promote modest weight loss. However, fucoxanthin supplementation preserved bone mass, increased bone density, and saw greater improvements in walking steps/day, resting heart rate, aerobic capacity, blood lipid profiles, adherence to diet goals, functional activity tolerance, and measures of quality of life. Consequently, there appears to be some benefit to supplementing microalgae extract from PT containing fucoxanthin during a diet and exercise program. Registered clinical trial #NCT04761406.

Projecting the Future Pediatric Subspecialty Workforce: Summary and Recommendations.

This article summarizes the findings of a Pediatrics supplement addressing the United States workforce for 15 pediatric subspecialties. It includes results from a microsimulation model projecting supply through 2040; growth is forecasted to be uneven across the subspecialties with worsening geographic maldistribution. Although each subspecialty has unique characteristics, commonalities include (1) the changing demographics and healthcare needs of children, including mental health; (2) poor outcomes for children experiencing adverse social drivers of health, including racism; and (3) dependence on other subspecialties. Common healthcare delivery challenges include (1) physician shortages for some subspecialties; (2) misalignment between locations of training programs and subspecialists and areas of projected child population growth; (3) tension between increasing subsubspecialization to address rare diseases and general subspecialty care; (4) the need to expand clinical reach through collaboration with other physicians and advanced practice providers; (5) the lack of parity between Medicare, which funds much of adult care, and Medicaid, which funds over half of pediatric subspecialty care; and (6) low compensation of pediatric subspecialists compared with adult subspecialists. Overall, subspecialists identified the lack of a central authority to monitor and inform child healthcare provided by pediatric subspecialists as a challenge. Future research on the pediatric subspecialty workforce and the children it serves will be necessary to ensure these children's needs are met. Together, these articles provide overarching and subspecialty-specific recommendations to improve training, recruitment, and retention of a diverse workforce, implement innovative models of care, drive policy changes, and advise future research.

LIGHTSITE III: 13-Month Efficacy and Safety Evaluation of Multiwavelength Photobiomodulation in Nonexudative (Dry) Age-Related Macular Degeneration Using the Lumithera Valeda Light Delivery System.

PURPOSE: The LIGHTSITE III study evaluated multiwavelength photobiomodulation (PBM) therapy in nonexudative (dry) age-related macular degeneration (AMD) using the LumiThera Valeda Light Delivery System. METHODS: LIGHTSITE III is a randomized, controlled trial to assess the safety and effectiveness of PBM in dry AMD. Subjects were given multiwavelength PBM (590, 660, and 850 nm) or Sham treatment delivered in a series of nine sessions over 3 to 5 weeks every four months over 24 months. Subjects were assessed for efficacy and safety outcomes. Data from the 13-month analysis are presented in this report. RESULTS: A total of 100 subjects (148 eyes) with dry AMD were randomized. LIGHTSITE III met the primary efficacy best-corrected visual acuity endpoint with a significant difference between PBM (n = 91 eyes) and Sham (n = 54 eyes) groups (Between group difference: 2.4 letters (SE 1.15), CI: -4.7 to -0.1, P = 0.02) (PBM alone: 5.4 letters (SE 0.96), CI: 3.5 to 7.3, P < 0.0001; Sham alone: 3.0 letters (SE 1.13), CI: 0.7-5.2, P < 0.0001). The PBM group showed a significant decrease in new onset geographic atrophy ( P = 0.024, Fisher exact test, odds ratio 9.4). A favorable safety profile was observed. CONCLUSION: LIGHTSITE III provides a prospective, randomized, controlled trial showing improved clinical and anatomical outcomes in intermediate dry AMD following PBM therapy.

A Definition of Neuromodulation and Classification of Implantable Electrical Modulation for Chronic Pain.

OBJECTIVES: Neuromodulation therapies use a variety of treatment modalities (eg, electrical stimulation) to treat chronic pain. These therapies have experienced rapid growth that has coincided with escalating confusion regarding the nomenclature surrounding these neuromodulation technologies. Furthermore, studies are often published without a complete description of the effective stimulation dose, making it impossible to replicate the findings. To improve clinical care and facilitate dissemination among the public, payors, research groups, and regulatory bodies, there is a clear need for a standardization of terms. APPROACH: We formed an international group of authors comprising basic scientists, anesthesiologists, neurosurgeons, and engineers with expertise in neuromodulation. Because the field of neuromodulation is extensive, we chose to focus on creating a taxonomy and standardized definitions for implantable electrical modulation of chronic pain. RESULTS: We first present a consensus definition of neuromodulation. We then describe a classification scheme based on the 1) intended use (the site of modulation and its indications) and 2) physical properties (waveforms and dose) of a neuromodulation therapy. CONCLUSIONS: This framework will help guide future high-quality studies of implantable neuromodulatory treatments and improve reporting of their findings. Standardization with this classification scheme and clear definitions will help physicians, researchers, payors, and patients better understand the applications of implantable electrical modulation for pain and guide informed treatment decisions.

Guselkumab-Treated Patients with Plaque Psoriasis Who Achieved Complete Skin Clearance for ≥ 156 Consecutive Weeks: A Post-Hoc Analysis From the VOYAGE 1 Clinical Trial.

BACKGROUND: Treatment of moderate-to-severe plaque psoriasis with biologics, such as guselkumab, has demonstrated greater efficacy over traditional non-biologic treatments. However, given patient diversity, greater understanding of the relationship between patient characteristics, positive clinical outcomes, and long-term response to biologics is crucial for optimizing treatment choices. MATERIALS AND METHODS: This post-hoc analysis of the 5-year VOYAGE 1 clinical trial compares baseline characteristics of patients maintaining a Psoriasis Area and Severity Index (PASI) score of 0 at all visits for ≥ 156 consecutive weeks (PASI = 0 group) with those that never achieve PASI = 0 (comparator group), using descriptive statistics and a multiple logistic regression model. Guselkumab plasma trough concentrations in both response groups were assessed from Weeks 4-156. RESULTS: Of patients who started guselkumab treatment at Week 0 or at Week 16 after switching from placebo, 22.7% (112/494) maintained PASI = 0 for ≥ 156 consecutive weeks. Numerical differences in baseline characteristics, including age, obesity, diabetes, PASI score, disease duration, smoking status, and psoriatic arthritis comorbidity, were identified between the PASI = 0 group and comparator group. Plasma guselkumab levels were consistently higher in the PASI = 0 group. Multiple logistic regression analysis revealed absence of diabetes, lower Dermatology Life Quality Index score at baseline, and higher Week 4 guselkumab plasma concentration as significantly (p < 0.05) associated with the PASI = 0 group. CONCLUSION: A substantial (22.7%) number of guselkumab-treated patients in the VOYAGE 1 clinical trial maintained complete skin clearance for a consecutive period of ≥ 156 weeks. Factors associated with this outcome may suggest clinical benefits of holistic treatment approaches. TRIAL REGISTRATION: NCT02207231.

International Society of Sports Nutrition Position Stand: Effects of essential amino acid supplementation on exercise and performance.

Position Statement: The International Society of Sports Nutrition (ISSN) presents this position based on a critical examination of literature surrounding the effects of essential amino acid (EAA) supplementation on skeletal muscle maintenance and performance. This position stand is intended to provide a scientific foundation to athletes, dietitians, trainers, and other practitioners as to the benefits of supplemental EAA in both healthy and resistant (aging/clinical) populations. EAAs are crucial components of protein intake in humans, as the body cannot synthesize them. The daily recommended intake (DRI) for protein was established to prevent deficiencies due to inadequate EAA consumption. The following conclusions represent the official position of the Society: 1. Initial studies on EAAs' effects on skeletal muscle highlight their primary role in stimulating muscle protein synthesis (MPS) and turnover. Protein turnover is critical for replacing degraded or damaged muscle proteins, laying the metabolic foundation for enhanced functional performance. Consequently, research has shifted to examine the effects of EAA supplementation - with and without the benefits of exercise - on skeletal muscle maintenance and performance. 2. Supplementation with free-form EAAs leads to a quick rise in peripheral EAA concentrations, which in turn stimulates MPS. 3. The safe upper limit of EAA intake (amount), without inborn metabolic disease, can easily accommodate additional supplementation. 4. At rest, stimulation of MPS occurs at relatively small dosages (1.5-3.0 g) and seems to plateau at around 15-18 g. 5. The MPS stimulation by EAAs does not require non-essential amino acids. 6. Free-form EAA ingestion stimulates MPS more than an equivalent amount of intact protein. 7. Repeated EAA-induced MPS stimulation throughout the day does not diminish the anabolic effect of meal intake. 8. Although direct comparisons of various formulas have yet to be investigated, aging requires a greater proportion of leucine to overcome the reduced muscle sensitivity known as "anabolic resistance." 9. Without exercise, EAA supplementation can enhance functional outcomes in anabolic-resistant populations. 10. EAA requirements rise in the face of caloric deficits. During caloric deficit, it's essential to meet whole-body EAA requirements to preserve anabolic sensitivity in skeletal muscle.

Air Medical Transport of a 12-Year-Old Girl With Cerebral Gas Embolism Due to Helium Inhalation.

This case report describes the initial care and transport considerations of a pediatric patient who suffered from cerebral gas embolism sustained after inhalation of helium from a pressurized tank. The patient demonstrated neurologic symptoms necessitating hyperbaric oxygen therapy and required fixed wing air transport across a mountain range from a rural community hospital to a tertiary center for the treatment. We review the pathophysiology of cerebral gas embolism and strategies for transporting patients with cerebral gas embolism and other trapped gas.

Cardio-oncology and Cancer Rehabilitation: Is an Integrated Approach Possible?

With significant improvements in the understanding of cancer biology, improved detection, and the use of novel adjuvant therapies, each year more Canadians are surviving a cancer diagnosis. Despite their effectiveness these therapies often result in short- and long-term deleterious effects to major organ systems, particularly cardiovascular. Cardio-oncology is an emerging field of study with the aim to improve cardiovascular health across the oncology disease spectrum. International guidelines distinguish "cardio-oncology" rehabilitation from "cancer" rehabilitation, but how this is navigated is currently unknown. How such care should be assessed and integrated acutely or in the longer term remains unknown. Accordingly, the aim of this article is to consider the cancer patient's needs beyond the scope of cardio-oncology rehabilitation to holistically integrate cancer rehabilitation across the disease trajectory.

Circulating trans fatty acids are associated with prostate cancer in Ghanaian and American men.

The association between fatty acids and prostate cancer remains poorly explored in African-descent populations. Here, we analyze 24 circulating fatty acids in 2934 men, including 1431 prostate cancer cases and 1503 population controls from Ghana and the United States, using CLIA-certified mass spectrometry-based assays. We investigate their associations with population groups (Ghanaian, African American, European American men), lifestyle factors, the fatty acid desaturase (FADS) genetic locus, and prostate cancer. Blood levels of circulating fatty acids vary significantly between the three population groups, particularly trans, omega-3 and omega-6 fatty acids. FADS1/2 germline genetic variants and lifestyle factors explain some of the variation in fatty acid levels, with the FADS1/2 locus showing population-specific associations, suggesting differences in their control by germline genetic factors. All trans fatty acids, namely elaidic, palmitelaidic, and linoelaidic acids, associated with an increase in the odds of developing prostate cancer, independent of ancestry, geographic location, or potential confounders.

Potential pharmacokinetic interactions with concurrent use of herbal medicines and a ritonavir-boosted COVID-19 protease inhibitor in low and middle-income countries.

The COVID-19 pandemic sparked the development of novel anti-viral drugs that have shown to be effective in reducing both fatality and hospitalization rates in patients with elevated risk for COVID-19 related morbidity or mortality. Currently, nirmatrelvir/ritonavir (Paxlovid™) fixed-dose combination is recommended by the World Health Organization for treatment of COVID-19. The ritonavir component is an inhibitor of cytochrome P450 (CYP) 3A, which is used in this combination to achieve needed therapeutic concentrations of nirmatrelvir. Because of the critical pharmacokinetic effect of this mechanism of action for Paxlovid™, co-administration with needed medications that inhibit or induce CYP3A is contraindicated, reflecting concern for interactions with the potential to alter the efficacy or safety of co-administered drugs that are also metabolized by CYP3A. Some herbal medicines are known to interact with drug metabolizing enzymes and transporters, including but not limited to inhibition or induction of CYP3A and P-glycoprotein. As access to these COVID-19 medications has increased in low- and middle-income countries (LMICs), understanding the potential for herb-drug interactions within these regions is important. Many studies have evaluated the utility of herbal medicines for COVID-19 treatments, yet information on potential herb-drug interactions involving Paxlovid™, specifically with herbal medicines commonly used in LMICs, is lacking. This review presents data on regionally-relevant herbal medicine use (particularly those promoted as treatments for COVID-19) and mechanism of action data on herbal medicines to highlight the potential for herbal medicine interaction Herb-drug interaction mediated by ritonavir-boosted antiviral protease inhibitors This work highlights potential areas for future experimental studies and data collection, identifies herbal medicines for inclusion in future listings of regionally diverse potential HDIs and underscores areas for LMIC-focused provider-patient communication. This overview is presented to support governments and health protection entities as they prepare for an increase of availability and use of Paxlovid™.

Pharmacokinetic Analyses of Liposomal and Non-Liposomal Multivitamin/Mineral Formulations.

Recent research supports previous contentions that encapsulating vitamins and minerals with liposomes help improve overall bioavailability. This study examined whether ingesting a liposomal multivitamin and mineral supplement (MVM) differentially affects the appearance and/or clearance of vitamins and minerals in the blood compared to a non-liposomal MVM supplement. In a double-blind, randomized, and counterbalanced manner, 34 healthy men and women fasted for 12 h. Then, they ingested a non-liposomal (NL) or liposomal (L) MVM supplement and a standardized snack. Venous blood samples were obtained at 0, 2, 4, and 6 h after MVM ingestion and analyzed for a panel of vitamins and minerals. Plasma levels of vitamins and minerals and mean changes from baseline with 95% confidence intervals (CIs) were analyzed using general linear model statistics with repeated measures. The observed values were also entered into pharmacokinetic analysis software and analyzed through univariate analysis of variance with repeated measure contrasts. The results revealed an overall treatment x time interaction effect among the vitamins and minerals evaluated (p = 0.051, ηp2 = 0.054, moderate effect). Differences between treatments were also observed in volume distribution area (vitamin E, iron), median residence time (vitamin E, iron), volume distribution area (iron), volume of distribution steady state (vitamin A, E, iron), clearance rates (vitamin A, E), elimination phase half-life (vitamin E, iron), distribution/absorption phase intercept (vitamin A), and distribution/absorption phase slope and rate (vitamin C, calcium). Vitamin volume distribution was lower with liposomal MVM ingestion than non-liposomal MVM sources, suggesting greater clearance and absorption since similar amounts of vitamins and minerals were ingested. These findings indicate that coating a MVM with liposomes affects individual nutrient pharmacokinetic profiles. Additional research should evaluate how long-term supplementation of liposomal MVM supplements may affect vitamin and mineral status, nutrient function, and/or health outcomes.

International society of sports nutrition position stand: coffee and sports performance.

Based on review and critical analysis of the literature regarding the contents and physiological effects of coffee related to physical and cognitive performance conducted by experts in the field and selected members of the International Society of Sports Nutrition (ISSN), the following conclusions represent the official Position of the Society:(1) Coffee is a complex matrix of hundreds of compounds. These are consumed with broad variability based upon serving size, bean type (e.g. common Arabica vs. Robusta), and brew method (water temperature, roasting method, grind size, time, and equipment).(2) Coffee's constituents, including but not limited to caffeine, have neuromuscular, antioxidant, endocrine, cognitive, and metabolic (e.g. glucose disposal and vasodilation) effects that impact exercise performance and recovery.(3) Coffee's physiologic effects are influenced by dose, timing, habituation to a small degree (to coffee or caffeine), nutrigenetics, and potentially by gut microbiota differences, sex, and training status.(4) Coffee and/or its components improve performance across a temporal range of activities from reaction time, through brief power exercises, and into the aerobic time frame in most but not all studies. These broad and varied effects have been demonstrated in men (mostly) and in women, with effects that can differ from caffeine ingestion, per se. More research is needed.(5) Optimal dosing and timing are approximately two to four cups (approximately 473-946 ml or 16-32 oz.) of typical hot-brewed or reconstituted instant coffee (depending on individual sensitivity and body size), providing a caffeine equivalent of 3-6 mg/kg (among other components such as chlorogenic acids at approximately 100-400 mg per cup) 60 min prior to exercise.(6) Coffee has a history of controversy regarding side effects but is generally considered safe and beneficial for healthy, exercising individuals in the dose range above.(7) Coffee can serve as a vehicle for other dietary supplements, and it can interact with nutrients in other foods.(8) A dearth of literature exists examining coffee-specific ergogenic and recovery effects, as well as variability in the operational definition of "coffee," making conclusions more challenging than when examining caffeine in its many other forms of delivery (capsules, energy drinks, "pre-workout" powders, gum, etc.).

High-Throughput Drug Screening of Primary Tumor Cells Identifies Therapeutic Strategies for Treating Children with High-Risk Cancer.

For one-third of patients with pediatric cancer enrolled in precision medicine programs, molecular profiling does not result in a therapeutic recommendation. To identify potential strategies for treating these high-risk pediatric patients, we performed in vitro screening of 125 patient-derived samples against a library of 126 anticancer drugs. Tumor cell expansion did not influence drug responses, and 82% of the screens on expanded tumor cells were completed while the patients were still under clinical care. High-throughput drug screening (HTS) confirmed known associations between activating genomic alterations in NTRK, BRAF, and ALK and responses to matching targeted drugs. The in vitro results were further validated in patient-derived xenograft models in vivo and were consistent with clinical responses in treated patients. In addition, effective combinations could be predicted by correlating sensitivity profiles between drugs. Furthermore, molecular integration with HTS identified biomarkers of sensitivity to WEE1 and MEK inhibition. Incorporating HTS into precision medicine programs is a powerful tool to accelerate the improved identification of effective biomarker-driven therapeutic strategies for treating high-risk pediatric cancers. SIGNIFICANCE: Integrating HTS with molecular profiling is a powerful tool for expanding precision medicine to support drug treatment recommendations and broaden the therapeutic options available to high-risk pediatric cancers.

Growth rates and histopathological outcomes of small (6-9 mm) colorectal polyps based on CT colonography surveillance and endoscopic removal.

BACKGROUND AND AIMS: The natural history of small polyps is not well established and rests on limited evidence from barium enema studies decades ago. Patients with one or two small polyps (6-9 mm) at screening CT colonography (CTC) are offered CTC surveillance at 3 years but may elect immediate colonoscopy. This practice allows direct observation of the growth of subcentimetre polyps, with histopathological correlation in patients undergoing subsequent polypectomy. DESIGN: Of 11 165 asymptomatic patients screened by CTC over a period of 16.4 years, 1067 had one or two 6-9 mm polyps detected (with no polyps ≥10 mm). Of these, 314 (mean age, 57.4 years; M:F, 141:173; 375 total polyps) elected immediate colonoscopic polypectomy, and 382 (mean age 57.0 years; M:F, 217:165; 481 total polyps) elected CTC surveillance over a mean of 4.7 years. Volumetric polyp growth was analysed, with histopathological correlation for resected polyps. Polyp growth and regression were defined as volume change of ±20% per year, with rapid growth defined as +100% per year (annual volume doubling). Regression analysis was performed to evaluate predictors of advanced histology, defined as the presence of cancer, high-grade dysplasia (HGD) or villous components. RESULTS: Of the 314 patients who underwent immediate polypectomy, 67.8% (213/314) harboured adenomas, 2.2% (7/314) with advanced histology; no polyps contained cancer or HGD. Of 382 patients who underwent CTC surveillance, 24.9% (95/382) had polyps that grew, while 62.0% (237/382) remained stable and 13.1% (50/382) regressed in size. Of the 58.6% (224/382) CTC surveillance patients who ultimately underwent colonoscopic resection, 87.1% (195/224) harboured adenomas, 12.9% (29/224) with advanced histology. Of CTC surveillance patients with growing polyps who underwent resection, 23.2% (19/82) harboured advanced histology vs 7.0% (10/142) with stable or regressing polyps (OR: 4.0; p<0.001), with even greater risk of advanced histology in those with rapid growth (63.6%, 14/22, OR: 25.4; p<0.001). Polyp growth, but not patient age/sex or polyp morphology/location were significant predictors of advanced histology. CONCLUSION: Small 6-9 mm polyps present overall low risk to patients, with polyp growth strongly associated with higher risk lesions. Most patients (75%) with small 6-9 mm polyps will see polyp stability or regression, with advanced histology seen in only 7%. The minority of patients (25%) with small polyps that do grow have a 3-fold increased risk of advanced histology.

Grass flowering times determined using herbarium specimens for modeling grass pollen under a warming climate.

The grass family is responsible for most of peoples pollen allergies, and the severity of pollen-based asthma and allergies is expected to increase with global climate change. Identifying grass species through standard pollen monitoring techniques have limitations due to challenges in species-specific pollen identification. As a result, these monitoring methods end up grouping all Poaceae species together, even though there are hundreds of grass species in Europe with flowering times that may vary drastically among species. Given this lack of specificity, it is hard to know which grass species are responsible for causing allergies over the pollen season, and how different species are affected by climate change. To address these issues, we obtained phenological data from thousands of herbarium specimens collected across Denmark spanning 190 years and used pollen monitoring data collected over the last four decades to determine the response of flowering time to climate change for 12 allergenic grass species, and identify which species are likely the biggest contributors to grass pollen loads throughout the pollen season. We find that pollen season duration is lasting longer and starting earlier, and the maximum pollen loads are occurring earlier in response to climate warming. Herbarium specimens provide taxonomic resolution and reveal that many grass species are flowering earlier in response to warmer spring temperatures. Seven out of the 12 species studied in Denmark are identified as major contributors to airborne pollen based on their flowering times, relative abundance and overlap with the time of the year when maximum pollen loads are detected. Four species (Poa pratensis, Dactylis glomerata, Festuca rubra, Holcus lanatus) significantly shifted their flowering time in response to warming temperatures and are flagged as of particular concern to allergy sufferers. Using data derived from natural history collections can contribute to the advancement of pollen forecasting for asthma and allergy patients under both current conditions and amidst future global changes.

Assessing patient experience of the tenets of osteopathic medicine.

CONTEXT: Previous studies document that both osteopathic physicians and third-party observers identify an approach to the patient that is consistent with the philosophy and tenets of osteopathic medicine, often without investigating whether patients identify or are satisfied with it. Osteopathic physicians and the medical education community understand the distinctiveness of an osteopathic approach to the patient. Understanding the outcomes of an osteopathic approach to patient care includes confirming whether patients experience the tenets of osteopathic medicine in physician visits and, if so, how it relates to their experience of physician empathy and satisfaction with the visit. OBJECTIVES: The objectives of this study were to assess patient experience of the tenets of osteopathic medicine, physician empathy, and satisfaction with the visit and to compare the results for patients who saw DOs with those who saw MD physicians. METHODS: More than 2000 patients at four outpatient clinic facilities were surveyed after a clinical visit on 22 prompts regarding their experiences of physician behaviors, physician empathy, and their own satisfaction with the encounter. Adult patients who were treated by an osteopathic or allopathic physician for a nonemergency encounter and who were not pregnant were included in the analysis. Survey results for 1,330 patient-physician encounters were analyzed utilizing linear regression models comparing constructs representing patient experiences of the tenets of osteopathic medicine (Tenets), physician empathy (Physician Empathy), satisfaction (Satisfaction) with the encounter, as well as additional demographic and encounter variables. RESULTS: Approximately 23.8 % of patients approached during the study period completed a survey (n=2,793), and among those, 54.7 % of patients who consented to the study and who saw a physician provider (n=1,330/2,431) were included. Significant (p≤0.01), positive associations among patient experiences of Satisfaction with the visit and Physician Empathy were observed among those who saw both DO and MD physicians. Patients experienced the Tenets during encounters with both DO and MD physicians, but linear regression showed that their experience of the Tenets was significantly (p≤0.01) and positively explained by their experience of Physician Empathy (ß=0.332, p=0.00, se=0.052) and Satisfaction with the visit (ß=0.209, p=0.01, se=0.081) only when the physician was a DO. CONCLUSIONS: Patients identified physician behaviors consistent with the Tenets and positively associated their experiences of Physician Empathy and Satisfaction with the visit regardless of physician training background. Patient experience of the Tenets significantly explained their experiences of Physician Empathy and Satisfaction after visits with a DO but not after visits with an MD.

International society of sports nutrition position stand: nutritional concerns of the female athlete.

Based on a comprehensive review and critical analysis of the literature regarding the nutritional concerns of female athletes, conducted by experts in the field and selected members of the International Society of Sports Nutrition (ISSN), the following conclusions represent the official Position of the Society: 1. Female athletes have unique and unpredictable hormone profiles, which influence their physiology and nutritional needs across their lifespan. To understand how perturbations in these hormones affect the individual, we recommend that female athletes of reproductive age should track their hormonal status (natural, hormone driven) against training and recovery to determine their individual patterns and needs and peri and post-menopausal athletes should track against training and recovery metrics to determine the individuals' unique patterns. 2. The primary nutritional consideration for all athletes, and in particular, female athletes, should be achieving adequate energy intake to meet their energy requirements and to achieve an optimal energy availability (EA); with a focus on the timing of meals in relation to exercise to improve training adaptations, performance, and athlete health. 3. Significant sex differences and sex hormone influences on carbohydrate and lipid metabolism are apparent, therefore we recommend first ensuring athletes meet their carbohydrate needs across all phases of the menstrual cycle. Secondly, tailoring carbohydrate intake to hormonal status with an emphasis on greater carbohydrate intake and availability during the active pill weeks of oral contraceptive users and during the luteal phase of the menstrual cycle where there is a greater effect of sex hormone suppression on gluconogenesis output during exercise. 4. Based upon the limited research available, we recommend that pre-menopausal, eumenorrheic, and oral contraceptives using female athletes should aim to consume a source of high-quality protein as close to beginning and/or after completion of exercise as possible to reduce exercise-induced amino acid oxidative losses and initiate muscle protein remodeling and repair at a dose of 0.32-0.38 g·kg-1. For eumenorrheic women, ingestion during the luteal phase should aim for the upper end of the range due to the catabolic actions of progesterone and greater need for amino acids. 5. Close to the beginning and/or after completion of exercise, peri- and post-menopausal athletes should aim for a bolus of high EAA-containing (~10 g) intact protein sources or supplements to overcome anabolic resistance. 6. Daily protein intake should fall within the mid- to upper ranges of current sport nutrition guidelines (1.4-2.2 g·kg-1·day-1) for women at all stages of menstrual function (pre-, peri-, post-menopausal, and contraceptive users) with protein doses evenly distributed, every 3-4 h, across the day. Eumenorrheic athletes in the luteal phase and peri/post-menopausal athletes, regardless of sport, should aim for the upper end of the range. 7. Female sex hormones affect fluid dynamics and electrolyte handling. A greater predisposition to hyponatremia occurs in times of elevated progesterone, and in menopausal women, who are slower to excrete water. Additionally, females have less absolute and relative fluid available to lose via sweating than males, making the physiological consequences of fluid loss more severe, particularly in the luteal phase. 8. Evidence for sex-specific supplementation is lacking due to the paucity of female-specific research and any differential effects in females. Caffeine, iron, and creatine have the most evidence for use in females. Both iron and creatine are highly efficacious for female athletes. Creatine supplementation of 3 to 5 g per day is recommended for the mechanistic support of creatine supplementation with regard to muscle protein kinetics, growth factors, satellite cells, myogenic transcription factors, glycogen and calcium regulation, oxidative stress, and inflammation. Post-menopausal females benefit from bone health, mental health, and skeletal muscle size and function when consuming higher doses of creatine (0.3 g·kg-1·d-1). 9. To foster and promote high-quality research investigations involving female athletes, researchers are first encouraged to stop excluding females unless the primary endpoints are directly influenced by sex-specific mechanisms. In all investigative scenarios, researchers across the globe are encouraged to inquire and report upon more detailed information surrounding the athlete's hormonal status, including menstrual status (days since menses, length of period, duration of cycle, etc.) and/or hormonal contraceptive details and/or menopausal status.