Genetic Analysis of an F2 Population Derived from the Cotton Landrace Hopi Identified Novel Loci for Boll Glanding.

Landraces are an important reservoir of genetic variation that can expand the narrow genetic base of cultivated cotton. In this study, quantitative trait loci (QTL) analysis was conducted using an F2 population developed from crosses between the landrace Hopi and inbred TM-1. A high-density genetic map spanning 2253.11 and 1932.21 cM for the A and D sub-genomes, respectively, with an average marker interval of 1.14 cM, was generated using the CottonSNP63K array. The linkage map showed a strong co-linearity with the physical map of cotton. A total of 21 QTLs were identified, controlling plant height (1), bract type (1), boll number (1), stem color (2), boll pitting (2), fuzz fiber development (2), boll shape (3), boll point (4), and boll glanding (5). In silico analysis of the novel QTLs for boll glanding identified a total of 13 candidate genes. Analysis of tissue-specific expression of the candidate genes suggests roles for the transcription factors bHLH1, MYB2, and ZF1 in gland formation. Comparative sequencing of open reading frames identified early stop codons in all three transcription factors in Hopi. Functional validation of these genes offers avenues to reduce glanding and, consequently, lower gossypol levels in cottonseeds without compromising the defense mechanisms of the plant against biotic stresses.

Chemotherapy medication errors.

Although chemotherapy is a well established treatment modality, chemotherapy errors represent a potentially serious risk of patient harm. We reviewed published research from 1980 to 2017 to understand the extent and nature of medication errors in cancer chemotherapy, and to identify effective interventions to help prevent mistakes. Chemotherapy errors occur at a rate of about one to four per 1000 orders, affect at least 1-3% of adult and paediatric oncology patients, and occur at all stages of the medication use process. Oral chemotherapy use is a particular area of growing risk. Our knowledge of chemotherapy errors is drawn primarily from single-institution studies at university hospitals and referral centres, with a particular focus on prescription orders and pharmacy practices. Although the heterogeneity of research methods and measures used in these studies limits our understanding of this issue, the rate of chemotherapy error-related injuries is generally lower than those seen in comparable studies of general medical patients. Although many interventions show promise in reducing chemotherapy errors, most have little empirical support. Additional research is needed to understand and to mitigate the risk of chemotherapy medication errors.

The perplexing links between contraceptive sterilization and (dis)advantage in ten low-fertility countries.

This study investigated the association between contraceptive sterilization and socio-economic status (measured by educational attainment) in ten countries, using data from the 2006-10 National Survey of Family Growth and the 2004-10 Generations and Gender Surveys. The findings confirm that a long-standing association between socio-economic status and sterilization persists in the contemporary United States: female sterilization is associated with economic disadvantage, whereas male sterilization is associated with economic advantage. The latter association is found to be unique to the United States, but female sterilization is associated with disadvantage in most of the other countries studied. While basic demographic background factors such as early childbearing and parity can explain the observed associations in most of the countries, a strong gendered association between sterilization and socio-economic status remains in the United States and Belgium even after adjusting for these factors.

Effects of osteopathic manipulative treatment on children with plagiocephaly in the context of current pediatric practice: a retrospective chart review study.

CONTEXT: Deformational plagiocephaly (DP) is on the rise in pediatric patients. The current standard of care recommended for management is repositioning with possible addition of cranial orthoses. However, strong data are lacking to support these recommendations. Osteopathic manipulative treatment (OMT) is another treatment option for DP that is also lacking evidential support. OBJECTIVES: This retrospective chart review study investigated the effects of OMT at restoring a more symmetrical cranial bone configuration in children with DP. METHODS: A retrospective chart review was performed on medical records of patients with a diagnosis of DP from three private practices over a 4-year period from September 2017 to December 2021. Inclusion criteria were diagnoses of DP by a referring physician and aged 10 months or less at the time of initial evaluation and treatment. Patients were excluded if they had confounding diagnoses such as genetic syndromes or severe torticollis. A total of 26 patients met these criteria, and their records were reviewed. The main outcome reviewed was anthropometric assessment of the cranium, mainly the cranial vault asymmetry index (CVAI). RESULTS: Participants demonstrated a mean CVAI - a measure that determines the severity of DP - of 6.809 (±3.335) (Grade 3 severity) at baseline, in contrast to 3.834 (±2.842) (Grade 2 severity) after a series of OMT treatments. CVAI assessment after OMT reveals statistically significant (p≤0.001) decreases in measurements of skull asymmetry and occipital flattening. No adverse events were reported throughout the study period. CONCLUSIONS: The application of OMT has shown potential benefit for reducing cranial deformity in patients with DP.

Case Report: Initial Successful Treatment of Migraine and Irritable Bowel Syndrome With a Low-FODMAP Diet.

OBJECTIVE: Migraine and irritable bowel syndrome (IBS) can be difficult-to-treat comorbidities that may be driven by underlying gut-brain axis dysfunction. This report describes utilization of a low-FODMAP (fermentable oligosaccharides, disaccharides, monosaccharides, and polyols) diet (LFD) in a patient with refractory migraine and co-occurring IBS. METHODS: After unremarkable physical and neurological examinations, a 57-year-old woman with IBS and chronic migraine was started on a LFD under the guidance of a registered dietician. Psychometrically validated surveys administered at baseline and initial follow-up assessed patient-reported outcomes related to migraine and IBS symptoms. RESULTS: At baseline, the patient reported 80/90 migraine days with average pain of 8/10, a Migraine Disability Assessment (MIDAS) score of 33, and Headache Impact Test-6 (HIT-6) score of 64, the latter 2 scores indicating severe disability. Baseline IBS symptom severity was noted at 9/10. Within 1 week on a LFD, the patient's IBS symptoms and migraines improved in both frequency and intensity of episodes. After 5 weeks on a LFD elimination, the patient's clinical improvement continued and she reported significant reduction in migraines, with average pain of 1/10 and IBS severity of 3/10. The patient also improved from severe to minimal levels of disability on validated measures (MIDAS, HIT-6, and IBS Patient Global Impression of Change). CONCLUSION: This is the first case report detailing successful initial treatment of migraine and co-occurring IBS utilizing a dietician-guided LFD. There are a number of important reasons for potential improvement in these gut-brain axis disorders which are reviewed as well as an implication for long-term management and food reintroduction. Larger, randomized trials evaluating a LFD in diverse individuals with migraine and co-occurring IBS are warranted to help confirm these results.

Evaluating Mobile Apps Targeting Older Adults: Descriptive Study.

BACKGROUND: Smartphone use has increased dramatically and, in parallel, a market for mobile apps, including health apps, has emerged. The business model of targeted mobile app advertisements allows for the collection of personal and potentially sensitive information, often without user knowledge. Older adults comprise a rapidly growing demographic that is potentially vulnerable to exploitation by those accessing data collected via these apps. OBJECTIVE: This research examined apps that claimed to be useful to older adults with a goal of (1) classifying the functionality of each app, (2) identifying whether a privacy policy existed and was accessible, and (3) evaluating evidence that could support claims of value to older adults. METHODS: An environmental scan was conducted using the Google search engine and typing "apps for older adults." The first 25 sites that this search returned comprised the primary data for this study. Data were organized by descriptive features of purpose (eg, health, finance, and utility), the existence of an electronically accessible privacy policy, price, and evidence supporting each recommended mobile app. RESULTS: A total of 133 mobile apps were identified and promoted as being the best "apps for older adults." Of these 133 mobile apps, 83% (n=110) included a privacy policy. Fewer apps designated in the "medical" category included a privacy policy than those classified otherwise. CONCLUSIONS: The results suggest that most mobile apps targeting older adults include a privacy policy. Research is needed to determine whether these privacy policies are readable, succinct, and incorporate accessible data use and sharing practices to mitigate potential risks, particularly when collecting potentially sensitive health information.

Academic and Employment Status in Patients With Generalized Myasthenia Gravis Treated With Eculizumab: A Case Series.

OBJECTIVES: To evaluate the impact of treatment with eculizumab, a terminal complement inhibitor, on academic and employment status in patients with refractory generalized myasthenia gravis (MG). METHODS: Case review of 7 US patients. RESULTS: Six patients were aged ≤65 years; one was a full-time student and the remainder were in employment before MG diagnosis. After diagnosis, all patients gave up work (n = 3) or reduced their study/working hours (n = 4). In the 12 months after eculizumab initiation, patients who had stopped work resumed working in some capacity, whereas those who had changed their work/study hours returned to their original work/study pattern. Patients also experienced a reduction in the number of MG exacerbations, and a clinically significant improvement in MG-Activities of Daily Living scores, and were able to reduce other MG medications. CONCLUSIONS: These results suggest that treatment with eculizumab may help maintain education/employment activity in patients with refractory generalized MG.

Urinoma formation following renal mass cryoablation treated with nephroureteral stent placement.

Renal cryoablation (CA) has become an accepted treatment option for patients with small renal tumors and co-morbidities that make them less favorable for surgical intervention. Complications from renal CA have been previously reported and are generally associated with increasing size and central location of the tumor. Ureteral injury from renal CA, although rare, can be difficult to manage and may require complex surgeries in patients who are poor surgical candidates to begin with. We report a case of a renal mass CA complicated by proximal ureteral necrosis and transection, treated with multiple minimally invasive procedures ultimately resulting in successful bridging of the necrotic segment with nephroureteral stent and thus avoiding major surgery.

COVID-19 Vaccination Might Induce Postural Orthostatic Tachycardia Syndrome: A Case Report.

We report a case of new-onset postural orthostatic tachycardia syndrome in a healthy 46-year-old female after a single dose of the BNT162b2 (Pfizer-BioNTech) SARS-CoV-2 vaccine. There have been three prior reports of new-onset postural orthostatic tachycardia syndrome after COVID-19 vaccination. Predominant symptoms noted included fatigue, brain fog, headache, sinus tachycardia, and dizziness. Management includes noninvasive therapies, behavioral approaches, and pharmacologic regimens. Here, the patient presented with fatigue, palpitations, dizziness, and presyncope, with symptoms beginning 7 days after vaccination. Presenting vitals included temperature within normal limits, inappropriate tachycardia, up to 120 beats per minute, blood pressure of 128/87 mm of mercury, and 100% saturation in room air. Her management included lifestyle changes, dietary supplements, and ivabradine. Further studies are needed to evaluate prevalence, etiology, and optimal management.

Teamwork Among Medicine House Staff During Work Rounds: Development of a Direct Observation Tool.

OBJECTIVE: Teamwork is integral to effective health care but difficult to evaluate. Few tools have been tested outside of classroom or medical simulation settings. Accordingly, we aimed to develop and pilot test an easy-to-use direct observation instrument for measuring teamwork among medical house staff. METHODS: We performed direct observations of 18 inpatient medicine house staff teams at a teaching hospital using an instrument constructed from existing teamwork tools, expert panel review, and pilot testing. We examined differences across teams using the Kruskal-Wallis statistic. We examined interrater reliability with the κ statistic, domain scales using Cronbach α, and construct validity using correlation and multivariable regression analyses of quality and utilization metrics. Observers rated team performance before and after providing feedback to 12 of the 18 team leaders and assessed changes in team performance using paired two-tailed t tests. RESULTS: We found variation in team performance in the situation monitoring, mutual support, and communication domains. The instrument evidenced good interrater reliability among concurrent, independent observers (κ = 0.7, P < 0.001). It had satisfactory face validity based on expert panel review and the assessments of resident team leaders. Construct validity was supported by a positive correlation between team performance and the Hospital Consumer Assessment of Healthcare Providers and Systems physician communication score (r = 0.6, P = 0.03). Providing resident physicians with information about their teams' performance was associated with improved mean performance in follow-up observations (3.6-3.8/4.0, P = 0.001). CONCLUSIONS: Direct observation of teamwork behaviors by medicine house staff on ward rounds is feasible and feedback may improve performance.

Late Testicular Yolk Sac Tumor With Cerebellar Metastasis and a Rapid Recurrence After a Gross Total Resection: A Case Report.

Yolk sac tumor (YST) is the most common prepubertal testicular tumor. It is considered a subtype of non-seminoma germ cell tumor (NSGCT) that is presumed to have an aggressive behavior with high malignant potential, thus requiring multimodality treatment with resection and chemotherapy. Treatment is curative for the majority of patients, even the ones with relapse after a few years. Here, we describe for the first time an atypical case of YST recurrence 17 years after primary treatment of YST. This is a case of YST in a 32-year-old man who presented with a large cerebellar mass consistent with YST recurrence after being in remission for 17 years. He underwent suboccipital craniotomy and complete excision of the tumor, as evident on postoperative MRI with a plan for stereotactic radiosurgery with dose and fractionation determined by MRI at four weeks postoperatively. However, the four-week MRI postoperatively revealed a large mass that was engulfing the prior resection cavity, indicative of unusual rapid tumor recurrence despite evidence of complete resection. The highly aggressive nature of this tumor should prompt clinicians to consider chemotherapy and radiation earlier than four weeks postoperatively.

Sublethal, Behavioral, and Developmental Effects of the Neonicotinoid Pesticide Imidacloprid on Larval Wood Frogs (Rana sylvatica).

Imidacloprid, a neonicotinoid pesticide, is used to prevent the spread of the hemlock woolly adelgid, currently affecting Eastern Hemlock trees across North America. When the pesticide is sprayed directly onto soil around infested trees (soil drenching), it can run off into aquatic systems, with potential negative effects on biota. Simultaneously, climate change may lead to faster pool drying, which acts as an additional stressor for sensitive species such as amphibians. We evaluated the sublethal effects of imidacloprid (10 ppb), and interaction with shorter hydroperiods on the larval behavior, growth, and survival of a model organism, the wood frog (Rana sylvatica). We performed 3 behavioral experiments evaluating swimming speed, time spent swimming, and distance the larvae swam. We found that larvae raised in 10 ppb imidacloprid or shorter hydroperiod did not differ in their swimming time, distance, and speed from nonexposed larvae. Naïve larvae exposed for 20 min to 10- to 500-ppb concentrations also showed similar performance to nonexposed larvae. However, when we applied a stimulus halfway through each experiment, we found that larvae exposed to 10 ppb imidacloprid (short and long term) swam shorter distances and spent less time swimming, suggesting that imidacloprid exposure may slow reaction time, potentially increasing the risk of predation. To minimize impacts on pool-breeding amphibians, imidacloprid application to combat the invasive hemlock woolly adelgid should use trunk injection and avoid soil drenching. Environ Toxicol Chem 2021;40:1840-1849. © 2021 SETAC.

Current and Upcoming Treatment Modalities in Myasthenia Gravis.

ABSTRACT: Myasthenia gravis (MG) is one of the extensively studied autoimmune disorder. There has been a dramatic increase in research to further understand molecular pathogenesis of MG and clinical trials for new drugs in MG treatment in the past decade. This review article is to consolidate the available information in simple terms with students, residents, and fellows as target audience for easy learning and help application of this knowledge to clinical practice.

Natural Supplements for COVID19-Background, Rationale, and Clinical Trials.

Worldwide, the turmoil of the SARS-CoV-2 (COVID-19) pandemic has generated a burst of research efforts in search of effective prevention and treatment modalities. Current recommendations on natural supplements arise from mostly anecdotal evidence in other viral infections and expert opinion, and many clinical trials are ongoing. Here the authors review the evidence and rationale for the use of natural supplements for prevention and treatment of COVID-19, including those with potential benefit and those with potential harms. Specifically, the authors review probiotics, dietary patterns, micronutrients, antioxidants, polyphenols, melatonin, and cannabinoids. Authors critically evaluated and summarized the biomedical literature published in peer-reviewed journals, preprint servers, and current guidelines recommended by expert scientific governing bodies. Ongoing and future trials registered on clinicaltrials.gov were also recorded, appraised, and considered in conjunction with the literature findings. In light of the controversial issues surrounding the manufacturing and marketing of natural supplements and limited scientific evidence available, the authors assessed the available data and present this review to equip clinicians with the necessary information regarding the evidence for and potential harms of usage to promote open discussions with patients who are considering dietary supplements to prevent and treat COVID-19.

New insights into the history of rice domestication.

The history of rice domestication has long been a subject of debate. Recently obtained genetic evidence provides new insights into this complex story. Genome-wide studies of variation demonstrate that the two varietal groups in Oryza sativa (indica and japonica) arose from genetically distinct gene pools within a common wild ancestor, Oryza rufipogon, suggesting multiple domestications of O. sativa. However, the evolutionary history of recently cloned domestication genes adds another layer of complexity to the domestication of rice. Although some alleles exist only within specific subpopulations, as would be expected if the domestications occurred independently, other major domestication alleles are common to all cultivated O. sativa varieties. Our current view of rice domestication supports multiple domestications coupled with limited introgression that transferred key domestication alleles between divergent rice gene pools.

Global dissemination of a single mutation conferring white pericarp in rice.

Here we report that the change from the red seeds of wild rice to the white seeds of cultivated rice (Oryza sativa) resulted from the strong selective sweep of a single mutation, a frame-shift deletion within the Rc gene that is found in 97.9% of white rice varieties today. A second mutation, also within Rc, is present in less than 3% of white accessions surveyed. Haplotype analysis revealed that the predominant mutation originated in the japonica subspecies and crossed both geographic and sterility barriers to move into the indica subspecies. A little less than one Mb of japonica DNA hitchhiked with the rc allele into most indica varieties, suggesting that other linked domestication alleles may have been transferred from japonica to indica along with white pericarp color. Our finding provides evidence of active cultural exchange among ancient farmers over the course of rice domestication coupled with very strong, positive selection for a single white allele in both subspecies of O. sativa.

Divorce, Repartnering, and Stepfamilies: A Decade in Review.

This article reviews key developments in the past decade of research on divorce, repartnering, and stepfamilies. Divorce rates are declining overall, but they remain high and have risen among people older than age 50. Remarriage rates have declined, but the overall proportion of marriages that are remarriages is rising. Transitions in parents' relationships continue to be associated with reduced child well-being, but shifting patterns of divorce and repartnering during the past decade have also reshaped the family lives of older adults. We review research on the predictors and consequences of these trends and consider what they reveal about the changing significance of marriage as an institution. Overall, recent research on divorce, repartnering, and stepfamilies points to the persistence of marriage as a stratified and stratifying institution and indicates that the demographic complexity of family life is here to stay.

Networks of Physiological Adjustments and Defenses, and Their Synergy With Sodium (Na+) Homeostasis Explain the Hidden Variation for Salinity Tolerance Across the Cultivated Gossypium hirsutum Germplasm.

The abilities to mobilize and/or sequester excess ions within and outside the plant cell are important components of salt-tolerance mechanisms. Mobilization and sequestration of Na+ involves three transport systems facilitated by the plasma membrane H+/Na+ antiporter (SOS1), vacuolar H+/Na+ antiporter (NHX1), and Na+/K+ transporter in vascular tissues (HKT1). Many of these mechanisms are conserved across the plant kingdom. While Gossypium hirsutum (upland cotton) is significantly more salt-tolerant relative to other crops, the critical factors contributing to the phenotypic variation hidden across the germplasm have not been fully unraveled. In this study, the spatio-temporal patterns of Na+ accumulation along with other physiological and biochemical interactions were investigated at different severities of salinity across a meaningful genetic diversity panel across cultivated upland Gossypium. The aim was to define the importance of holistic or integrated effects relative to the direct effects of Na+ homeostasis mechanisms mediated by GhHKT1, GhSOS1, and GhNHX1. Multi-dimensional physio-morphometric attributes were investigated in a systems-level context using univariate and multivariate statistics, randomForest, and path analysis. Results showed that mobilized or sequestered Na+ contributes significantly to the baseline tolerance mechanisms. However, the observed variance in overall tolerance potential across a meaningful diversity panel were more significantly attributed to antioxidant capacity, maintenance of stomatal conductance, chlorophyll content, and divalent cation (Mg2+) contents other than Ca2+ through a complex interaction with Na+ homeostasis. The multi-tier macro-physiological, biochemical and molecular data generated in this study, and the networks of interactions uncovered strongly suggest that a complex physiological and biochemical synergy beyond the first-line-of defense (Na+ sequestration and mobilization) accounts for the total phenotypic variance across the primary germplasm of Gossypium hirsutum. These findings are consistent with the recently proposed Omnigenic Theory for quantitative traits and should contribute to a modern look at phenotypic selection for salt tolerance in cotton breeding.

Detoxification Enhanced Lifestyle Intervention Targeting Endotoxemia (DELITE) in the Setting of Obesity and Pain: Results of a Pilot Group Intervention.

BACKGROUND: Obesity is a complex multifactorial disorder affecting a growing proportion of the population. While therapeutic lifestyle change (TLC) is foundational, results of interventional programs are often inconsistent. Factors related to systemic inflammation, toxin load and endotoxemia have been postulated to play a contributory role. This pilot study sought to evaluate the role of TLC with enhanced laboratory evaluation and interventions to address these emerging therapeutic targets. METHODS: Twelve participants with a body mass index (BMI) greater than 30 (or 27 with metabolic co-morbidities) were recruited from an outpatient clinic for participation with a primary outcome of pre/post changes in body composition. Participants completed a 12-week program involving weekly group and individualized dietary, exercise, and behavioral support, supplemented with a commercial, 30-day dietary detoxification intervention and ongoing nutritional counseling. All participants completed baseline and post-intervention evaluation including metabolic, toxin load, endotoxin, body composition and functional fitness profiles. RESULTS: After 12-weeks, participants as a group significantly improved body composition parameters including BMI, body fat, fat mass, and waist and hip circumference (P < .01). Significant improvement in several secondary outcomes including levels of lipopolysaccharide, zonulin and leptin were noted. Additionally, results demonstrate substantial improvements in pain, pain interference and functional fitness. Upon completion, all participants rated the program favorably with a high likelihood of continuing or recommending participation to others. CONCLUSIONS: Obesity remains a challenging and often refractory clinical scenario with emerging evidence indicating the potential role of systemic inflammation, toxin load and endotoxemia. A group therapeutic lifestyle change program enhanced with a detoxification component is feasible and may provide a promising intervention for achieving weight loss while also addressing functional and pain related co-morbidities. Future randomized trials evaluating the components of such a program are needed to better delineate the role of specific interventions in the complex setting of obesity.

Analysis of State Insurance Coverage for Nonpharmacologic Treatment of Low Back Pain as Recommended by the American College of Physicians Guidelines.

BACKGROUND: In 2017, the American College of Physicians (ACP) released guidelines encouraging nonpharmacologic treatment of chronic low back pain (LBP). These guidelines recommended utilization of treatments including multidisciplinary rehabilitation, acupuncture, mindfulness-based stress reduction (MBSR), tai chi, yoga, progressive relaxation, biofeedback, cognitive behavioral therapy (CBT), and spinal manipulation. OBJECTIVE: We aimed to determine status of insurance coverage status for multiple nonpharmacological pain therapies based on the 2017 Essential Health Benefits (EHB) benchmark plans across all states. METHODS: The 2017 EHB benchmark plans represent the minimum benefits required in all new policies in the individual and small group health insurance markets and were reviewed for coverage of treatments for LBP recommended by the ACP guidelines. Additionally, plans were reviewed for limitations and exclusionary criteria. RESULTS: In nearly all state-based coverage policies, chronic pain management and multidisciplinary rehabilitation were not addressed. Coverage was most extensive (supported by 46 states) for spinal manipulation. Acupuncture, massage, and biofeedback were each covered by fewer than 10 states, while MBSR, tai chi, and yoga were not covered by any states. Behavioral health treatment (CBT and biofeedback) coverage was often covered solely for mental health diagnoses, although excluded for treating LBP. CONCLUSION: Other than spinal manipulation, evidence-based, nonpharmacological therapies recommended by the 2017 ACP guidelines were routinely excluded from EHB benchmark plans. Insurance coverage discourages multidisciplinary rehabilitation for chronic pain management by providing ambiguous guidelines, restricting ongoing treatments, and excluding behavioral or complementary therapy despite a cohesive evidence base. Better EHB plan coverage of nondrug therapies may be a strategy to mitigate the opioid crisis. Recommendations that reflect current research-based findings are provided to update chronic pain policy statements.