Search

The incidence of deterioration and associated characteristics are largely unknown for children transported for admission from referring emergency departments (EDs) to general inpatient units. This study describes this population and identifies associated preadmission characteristics.This single-center cohort study included children ≤ 18 years old transferred from an ED and directly admitted to general inpatient units from 2016 to 2019. Deterioration was defined as 1 or more of the following occurring within 24 hours of admission: rapid response team activation, transfer to the intensive care unit (ICU), or cardiac or respiratory arrest. ICU transfer was the secondary outcome. Logistic regression was performed.One thousand nine hundred eighty-eight patients were included; the median age was 4.2 years, 53.9% were male, and 44.1% had respiratory diagnoses. Deterioration occurred in 135 (6.8%) children overall and in 10.1% of children with respiratory complaints. Deterioration was associated with ≥ 2 complex chronic conditions (adjusted odds ratio [aOR] = 2.09; 95% confidence interval [CI], 1.04-4.19) and a longer stabilization time (per 10 minutes) (aOR = 1.17; 95% CI, 1.01-1.36). ICU transfer was associated with ≥ 2 complex chronic conditions (aOR = 2.33; 95% CI, 1.13-4.80), supplemental oxygen via nasal cannula (aOR = 2.13; 95% CI, 1.18-3.85), and nebulizer treatment (aOR = 2.77; 95% CI, 1.21-6.35).Deterioration was experienced by 7% of children admitted to a general unit, with the majority having respiratory complaints. Transport teams should consider the potential for increased risk of deterioration among children with respiratory disease, multiple complex chronic conditions, and a nasal cannula or nebulizer therapy. The clinical significance of marginally longer stabilization times is unclear and warrants further investigation.

Medicare/Medicaid dual-eligible patients who undergo primary total knee arthroplasty (TKA) demonstrate poor outcomes when compared to patients with other payers. We compare Medicare/Medicaid dual-eligible patients vs Medicare and Medicaid only patients at a single hospital center.All patients who underwent TKA for aseptic arthritis between August 9, 2016 and December 30, 2020 with either Medicare or Medicaid insurance were retrospectively reviewed. 4599 consecutive TKA (3749 Medicare, 286 Medicare/Medicaid dual eligibility, and 564 Medicaid) were included. Groups were compared using appropriate tests for direct comparisons and regression analysis.Patients with dual eligibility and Medicaid insurance were less likely to be white and married, more likely to be female and current smokers, and more likely to have COPD, mild liver disease, diabetes mellitus, malignancy, and HIV/AIDS, but had a lower age-adjusted Charleson Comorbidity Index when compared to Medicare patients. When controlling for smoking status and medical comorbidities, patients with dual eligibility and Medicaid insurance stayed in the hospital 0.64 and 0.39 additional days (P.001), respectively, were more likely to be discharged to subacute rehab (RR 2.01, 1.49, P.001) and acute rehab (RR 2.22, 2.46, P = .007,.001), and were 2.14 and 1.73 times more likely to return to the ED within 90 days (P.001) compared to Medicare patients.Value-based healthcare may disincentivize treating patients with low socioeconomic status, represented by Medicaid and dual-eligible insurance status, by their association with increased postoperative healthcare utilization, and less risky patients may be prioritized.

Comparing twins from same- and opposite-sex pairs can provide information on potential sex differences in a variety of outcomes, including socioeconomic-related outcomes such as educational attainment. It has been suggested that this design can be applied to examine the putative role of intrauterine exposure to testosterone for educational attainment, but the evidence is still disputed. Thus, we established an international database of twin data from 11 countries with 88,290 individual dizygotic twins born over 100 years and tested for differences between twins from same- and opposite-sex dizygotic pairs in educational attainment. Effect sizes with 95% confidence intervals (CI) were estimated by linear regression models after adjusting for birth year and twin study cohort. In contrast to the hypothesis, no difference was found in women (β = −0.05 educational years, 95% CI −0.11, 0.02). However, men with a same-sex co-twin were slightly more educated than men having an opposite-sex co-twin (β = 0.14 educational years, 95% CI 0.07, 0.21). No consistent differences in effect sizes were found between individual twin study cohorts representing Europe, the USA, and Australia or over the cohorts born during the 20th century, during which period the sex differences in education reversed favoring women in the latest birth cohorts. Further, no interaction was found with maternal or paternal education. Our results contradict the hypothesis that there would be differences in the intrauterine testosterone levels between same-sex and opposite-sex female twins affecting education. Our findings in men may point to social dynamics within same-sex twin pairs that may benefit men in their educational careers. CC BY 4.0Correspondence Address: Silventoinen, K.; University of Helsinki, P.O. Box 18, Finland; email: karri.silventoinen@helsinki.fi© 2021 The Authors

Hospitalized, malnourished older adults with chronic obstructive pulmonary disease (COPD) have an elevated risk of readmission and mortality.Post-hoc, sub-group analysis from the NOURISH study cohort examined the effect of a high-protein oral nutritional supplement (ONS) containing HMB (HP-HMB) in malnourished, hospitalized older adults with COPD and to identify predictors of outcomes.The NOURISH study (n = 652) was a multicenter, randomized, placebo-controlled, double-blind trial. The COPD subgroup (n = 214) included hospitalized, malnourished (based on Subjective Global Assessment), older adults (≥65 y), with admission diagnosis of COPD who received either standard-of-care plus HP-HMB (n = 109) or standard-of-care and a placebo supplement (n = 105) prescribed 2 servings/day from within 3 days of hospital admission (baseline) and up to 90 days after discharge. The primary study outcome was a composite endpoint of incidence of death or non-elective readmission up to 90-day post-discharge, while secondary endpoints included changes in hand-grip strength, body weight, and nutritional biomarkers over time. Categorical outcomes were analyzed using Cochran-Mantel-Haenszel tests, longitudinal data by repeated measures analysis of covariance; and changes from baseline by analysis of covariance. p-values ≤ 0.05 were considered statistically significant. Multivariate logistic regression was used to model predictors of the primary outcome and components.In patients with COPD, 30, 60, and 90-day hospital readmission rate did not differ, but in contrast, 30, 60, and 90-day mortality risk was approximately 71% lower with HP-HMB supplementation relative to placebo (1.83%, 2.75%, 2.75% vs. 6.67%, 9.52% and 10.48%, p = 0.0395, 0.0193, 0.0113, resp.). In patients with COPD, compared to placebo, intake of HP-HMB resulted in a significant increase in handgrip strength (+1.56 kg vs. -0.34 kg, p = 0.0413) from discharge to day 30; increased body weight from baseline to hospital discharge (0.66 kg vs. -0.01 kg, p 0.05) and, improvements in blood nutritional biomarker concentrations. The multivariate logistic regression predictors of the death, readmission or composite endpoints in these COPD patients showed that participants who were severely malnourished (p = 0.0191) and had a Glasgow prognostic score (GPS) Score of 1 or 2 had statistically significant odds of readmission or death (p = 0.0227).Among malnourished, hospitalized patients with COPD, supplementation with HP-HMB was associated with a markedly decreased mortality risk, and improved handgrip strength, body weight, and nutritional biomarkers within a 90-day period after hospital discharge. This post-hoc, subgroup analysis highlights the importance of early identification of nutritional risk and administration of high-protein ONS in older, malnourished patients with COPD after hospital admission and continuing after hospital discharge.

Background Large volumes of non-resuscitation fluids are often administered to critically ill children. We hypothesize that excess maintenance fluid is a significant contributor to non-resuscitation fluid and that non-resuscitation fluid administered beyond hydration requirements is associated with worse clinical outcomes in critically ill children. Methods We evaluated all patients admitted to two large urban pediatric intensive care units (PICU) between January 2010-August 2016 and January 2010-August 2018, respectively, who survived and remained in the hospital for at least 3 days following PICU admission. The primary outcome was in-hospital mortality. Association of excess fluid with outcomes was adjusted for confounders (age, Pediatric Risk of Mortality III score, study site, day 3 acute kidney injury, PICU era, resuscitation volume, and volume output) using multivariable regression. Results We evaluated 14,483 patients; 52% received non-resuscitation fluid in excess of hydration requirements. Non-resuscitation fluid in excess of hydration requirements was associated with higher in-hospital mortality after adjustment for confounders (adjusted odds ratio 1.01 per 10 mL/kg in excess fluid, 95% confidence interval: 1.002-1.02). Conclusions Non-resuscitation fluid in excess of hydration requirements is associated with increased mortality in critically ill children. Excess maintenance fluid is a modifiable contributor to this fluid volume. Strategies to reduce excess maintenance fluids warrant further study. Impact Critically ill children frequently receive non-resuscitation fluid in excess of their estimated hydration requirements. Non-resuscitation fluid volume in excess of estimated hydration requirements is associated with higher morbidity and mortality in critically ill children. Critically ill children receive a large volume burden from maintenance fluid. Maintenance fluid represents a modifiable contributor of non-resuscitation fluid in excess of hydration requirements. Strategies focused on limitation of maintenance fluid warrant further study.

Postmeiotic spermatids use a unique strategy to coordinate gene expression with morphological transformation, in which transcription and translation take place at separate developmental stages, but how mRNAs stored as translationally inert messenger ribonucleoproteins in developing spermatids become activated remains largely unknown. Here, we report that the RNA binding protein FXR1, a member of the fragile X–related (FXR) family, is highly expressed in late spermatids and undergoes liquid-liquid phase separation (LLPS) to merge messenger ribonucleoprotein granules with the translation machinery to convert stored mRNAs into a translationally activated state. Germline-specific Fxr1 ablation in mice impaired the translation of target mRNAs and caused defective spermatid development and male infertility, and a phase separation–deficient FXR1 L351P mutation in Fxr1 knock-in mice produced the same developmental defect. These findings uncover a mechanism for translational reprogramming with LLPS as a key driver in spermiogenesis.

Background Regular physical activity (PA) promotes health and can prevent and treat diseases among both humans and dogs. Unfortunately, most U.S. adults do not meet PA recommendations, and many dogs are also insufficiently active. Veterinary-prescribed PA programs have shown some success in increasing activity among overweight dogs, but the impacts of such programs have not yet been tested for efficacy among otherwise-healthy dogs and owners. In addition, although wearable devices that monitor PA and provide individuals with feedback (e.g., progress toward a daily step goal) can effectively increase human PA, it is unclear what impact similar wearable devices have on human and dog PA when the PA-monitoring devices are worn by dogs. The present study assessed the impact of an 8-week veterinary-prescribed PA program on activity and health among dogs and their owners, and randomized participants (n = 59) to two groups: one in which PA was measured but not visible to participants (n = 30), and one in which PA was measured and real time feedback was visible through a wearable device (n = 29). Results Participants in both groups showed significant PA increases over the course of the 8-week program. Biomedical testing performed at the veterinary clinic facilitated early diagnosis of systemic illness in one human participant. The frequency of hypertension in human participants decreased significantly from baseline to the end of the program (week 8). Other health indices (e.g., BMI in humans, body weight and BCS in dogs) improved, albeit not to a statistically significant extent, over the course of the program. There were no significant differences on the outcomes of interest between the two experimental conditions. Conclusions Veterinary-prescribed PA programs appear promising for increasing PA among insufficiently active but otherwise healthy dogs as well as their owners. Additional testing of veterinary-prescribed PA is warranted, particularly at other types of veterinary clinics (e.g., private practices). Incorporating wearable devices permitting owners to track canine PA did not appear necessary for obtaining these benefits; however, additional studies investigating alternative devices or different time periods may be warranted.

Purpose: We examined the differences in physical health outcomes over a 20-year period between lesbian, gay, and bisexual (LGB) adults and heterosexual adults. We also examined whether the associat...

Objectives Methamphetamine (MA) is a widely used illicit drug and a nationwide public health concern. Although dental complications are consistently reported among MA users, yet limited nationally representative studies on the associations between MA use and oral health currently exist. Methods Using the National Health and Nutrition Examination Survey 2009-2014, we analyzed 8,762 respondents aged 30-64 years who had completed a periodontal examination. MA use was self-reported; periodontitis, untreated caries, and missing teeth were assessed by calibrated dentists. Descriptive statistics as well as multivariable regression analyses were performed. Data were weighted to yield representative estimates of the US adult population. Results Overall 7.8 percent of US adults aged ≥30 years had ever used MA. Ever-use prevalence was higher among males, whites, and individuals below the federal poverty level. Established MA users had a higher prevalence of untreated dental caries (36.6 percent), any periodontitis (54.8 percent), and severe periodontitis (12.2 percent) than those who had never used MA. The prevalence of any periodontitis was higher among current MA users (PR: 1.31; 95% CI: 1.05-1.62) than those who never used MA. Prevalence of untreated dental caries was higher among current MA users (PR: 1.53; 95% CI: 1.10-2.13) and established users (PR: 1.21; 95% CI: 1.02-1.48) than never users. Taking MA orally and/or through injection was associated with higher odds of severe periodontitis than orally only (AOR: 3.72; CI: 1.79-7.75). Conclusions MA users had a higher prevalence of periodontitis and dental caries. Continued research assessing the relationship between MA use and oral health can inform clinical interventions and management of dental diseases in MA users.

The COVID-19 pandemic has disrupted every aspect of society in a way never previously experienced by our nation's orthopaedic surgeons. In response to the challenges the American Board of Orthopaedic Surgery has taken steps to adapt our Board Certification and Continuous Certification processes. These changes were made to provide flexibility for as many Candidates and Diplomates as possible to participate while maintaining our high standards. The American Board of Orthopaedic Surgery is first and foremost committed to the safety and well-being of our patients, physicians, and families while striving to remain responsive to the changing circumstances affecting our Candidates and Diplomates.

African Americans (AA), the second largest racial/ethnic minority group in the United States (US), carry the largest mortality burden of cancer compared with other racial/ethnic groups (Cancer Facts & Figures for African Americans, 2019-2021, American Cancer Society).One solution to address this disparity is through cancer-related genetic counseling and testing (CGT). Although CGT is utilized among the general population, it remains underutilized among AA populations. Community-engaged and community-driven health promotion programs within faith-based organizations (FBOs) have been successfully implemented and delivered among AA populations (Israel et al., American Journal of Public Health, 100, 2010, 2094). FBOs are well positioned for cancer-related health promotion and equipped as conduits of health education and information distribution for cancer prevention. In the present pilot study, a community-based participatory approach (CBPR) was used to collect exploratory data on attitudes, perceptions, and beliefs toward CGT and uptake among an AA sample in the Midwest. Focus groups were conducted in two churches where respondents (N=34) answered a pre-focus group survey prior to a discussion. Respondents were largely unaware of CGT and thought of testing as primarily for ancestral discovery and not for an inheritable disease. Themes identified through qualitative analysis included emotional experiences with cancer; perception of cancer risk; different pictures of genetic testing; other things to worry about; trust in the healthcare system/faith in God and the healthcare system; and ideas and insights regarding promotion of CGT. These primary themes showed participants' perceptions of CGT were shaped by their experiences with cancer, faith, faith communities/FBOs, and cost and access to CGT. Overall, participants within these organizations had positive perceptions about the church as a conduit of genetic testing information but had mixed opinions about the rationale for completing CGT. These findings have implications for genetic counselors, medical providers, and health promotion personnel as to how AA faith populations view CGT and the utility of FBOs as promoters of CGT information.

Objective The Accreditation Council for Graduate Medical Education and the Council on Resident Education in Obstetrics and Gynecology have milestones and/or competencies relating to colposcopy; however, the optimal way to reach these objectives is not proscribed and left to individual programs. Here, we aim to assess resident skill, confidence levels, perceived level of knowledge, and satisfaction with colposcopic training before and after implementation of a new interactive learning module with visual feedback. Materials and methods A new online educational intervention was developed by the author (E.L.N.) based on adult learning theory and introduced into our obstetrics and gynecology resident colposcopy curriculum in July 2014. We assessed performance on an objective competency examination administered at baseline and repeated after 6 months of our 24 residents.In addition, we assessed resident confidence levels, perceived level of knowledge, and satisfaction with training before and 6 months after intervention. Results Scores on a national online examination improved after the intervention (p = .014). Significant improvements on the examination were seen in the sections of medical knowledge (p = .031) and management (p = .011). Residents' perceived knowledge increased significantly after the intervention (p = .030). Conclusions Learning outcomes improved after introduction of a novel teaching intervention.

Prior work has found links between consistency in toddler handedness for the fine motor skill role-differentiated bimanual manipulation (RDBM), and language development at 2 and 3 years of age. The current study investigated whether consistency in handedness from 18 to 24 months (N = 90) for RDBM predicts receptive and expressive language abilities assessed using the Preschool Language Scales 5th edition (PLS-5) at 5 years old. Latent class growth analyses identified 3 stable RDBM hand preference trajectories: a left hand preference with moderate right hand use (left-moderate right), a right hand preference with moderate left hand use (right-moderate left), and a right hand preference with only mild left hand use (right-mild left). At 5 years of age, children with a right-mild left handedness trajectory as toddlers scored significantly higher on receptive and expressive language abilities compared to children with a left-moderate right hand preference. Children with a right-mild left hand preference for RDBM also scored significantly higher on receptive language abilities compared to children with a right-moderate left RDBM hand preference. Children with left-moderate right and children with a right-moderate left hand preference for RDBM as toddlers did not differ in receptive or expressive language abilities at 5 years. Results indicate that individual differences in hand preference consistency for fine motor skill in toddlerhood have cascading effects on language outcomes into the preschool years. (PsycINFO Database Record (c) 2020 APA, all rights reserved).

Fragile X–associated tremor/ataxia syndrome (FXTAS) is a debilitating late-onset neurodegenerative disease in premutation carriers of the expanded CGG repeat in FMR1 that presents with a spectrum of neurological manifestations, such as gait ataxia, intention tremor, and parkinsonism [P. J. Hagerman, R. J. Hagerman, Ann. N. Y. Acad. Sci. 1338, 58–70 (2015); S. Jacquemont et al., JAMA 291, 460–469 (2004)]. Here, we performed whole-genome sequencing (WGS) on male premutation carriers (CGG55–200) and prioritized candidate variants to screen for candidate genetic modifiers using a Drosophila model of FXTAS. We found 18 genes that genetically modulate CGG-associated neurotoxicity in Drosophila, such as Prosbeta5 (PSMB5), pAbp (PABPC1L), e(y)1 (TAF9), and CG14231 (OSGEPL1). Among them, knockdown of Prosbeta5 (PSMB5) suppressed CGG-associated neurodegeneration in the fly as well as in N2A cells. Interestingly, an expression quantitative trait locus variant in PSMB5, PSMB5rs11543947-A, was found to be associated with decreased expression of PSMB5 and delayed onset of FXTAS in human FMR1 premutation carriers. Finally, we demonstrate evidence that PSMB5 knockdown results in suppression of CGG neurotoxicity via both the RAN translation and RNA-mediated toxicity mechanisms, thereby presenting a therapeutic strategy for FXTAS.

Cancer testis antigens are ideal for tumor immunotherapy due to their testis-restricted expression. We previously showed that an immunotherapeutic vaccine targeting the germ cell-specific transcription factor BORIS (CTCFL) was highly effective in treating aggressive breast cancer in the 4T1 mouse model. Here, we further tested the therapeutic efficacy of BORIS in a rat 13762 breast cancer model. We generated a recombinant VEE-VRP (Venezuelan Equine Encephalitis-derived replicon particle) vector-expressing modified rat BORIS lacking a DNA-binding domain (VRP-mBORIS). Rats were inoculated with the 13762 cells, immunized with VRP-mBORIS 48 h later, and then, subsequently, boosted at 10-day intervals. The Kaplan–Meier method was used for survival analysis. Cured rats were re-challenged with the same 13762 cells. We demonstrated that BORIS was expressed in a small population of the 13762 cells, called cancer stem cells. Treatment of rats with VRP-BORIS suppressed tumor growth leading to its complete disappearance in up to 50% of the rats and significantly improved their survival. This improvement was associated with the induction of BORIS-specific cellular immune responses measured by T-helper cell proliferation and INFγ secretion. The re-challenging of cured rats with the same 13762 cells indicated that the immune response prevented tumor growth. Thus, a therapeutic vaccine against rat BORIS showed high efficacy in treating the rat 13762 carcinoma. These data suggest that targeting BORIS can lead to the elimination of mammary tumors and cure animals even though BORIS expression is detected only in cancer stem cells.

ObjectivesTo evaluate the capacity of general practice (GP) electronic medical record (EMR) data to assess risk factor detection, disease diagnostic testing, diagnosis, monitoring and pharmacotherapy for the interrelated chronic vascular diseases—chronic kidney disease (CKD), type 2 diabetes (T2D) and cardiovascular disease.DesignCross-sectional analysis of data extracted on a single date for each practice between 12 April 2017 and 18 April 2017 incorporating data from any time on or before data extraction, using baseline data from the Chronic Disease early detection and Improved Management in PrimAry Care ProjecT. Deidentified data were extracted from GP EMRs using the Pen Computer Systems Clinical Audit Tool and descriptive statistics used to describe the study population.SettingEight GPs in Victoria, Australia.ParticipantsPatients were ≥18 years and attended GP ≥3 times within 24 months. 37 946 patients were included.ResultsRisk factor and disease testing/monitoring/treatment were assessed as per Australian guidelines (or US guidelines if none available), with guidelines simplified due to limitations in data availability where required. Risk factor assessment in those requiring it: 30% of patients had body mass index and 46% blood pressure within guideline recommended timeframes. Diagnostic testing in at-risk population: 17% had diagnostic testing as per recommendations for CKD and 37% for T2D. Possible undiagnosed disease: Pathology tests indicating possible disease with no diagnosis already coded were present in 6.7% for CKD, 1.6% for T2D and 0.33% familial hypercholesterolaemia. Overall prevalence: Coded diagnoses were recorded in 3.8% for CKD, 6.6% for T2D, 4.2% for ischaemic heart disease, 1% for heart failure, 1.7% for ischaemic stroke, 0.46% for peripheral vascular disease, 0.06% for familial hypercholesterolaemia and 2% for atrial fibrillation. Pharmaceutical prescriptions: the proportion of patients prescribed guideline-recommended medications ranged from 44% (beta blockers for patients with ischaemic heart disease) to 78% (antiplatelets or anticoagulants for patients with ischaemic stroke).ConclusionsUsing GP EMR data, this study identified recorded diagnoses of chronic vascular diseases generally similar to, or higher than, reported national prevalence. It suggested low levels of extractable documented risk factor assessments, diagnostic testing in those at risk and prescription of guideline-recommended pharmacotherapy for some conditions. These baseline data highlight the utility of GP EMR data for potential use in epidemiological studies and by individual practices to guide targeted quality improvement. It also highlighted some of the challenges of using GP EMR data.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected more than 180 million people since the onset of the global pandemic. Despite similar viral load and infectivity rates between children and adults, children rarely develop severe illness. Differences in the host response to the virus at the primary infection site are among the mechanisms proposed to account for this disparity. Our objective was to investigate the host response to SARS-CoV-2 in the nasal mucosa in children and adults and compare it to the host response to respiratory syncytial virus (RSV) and influenza virus (IV). We analyzed clinical outcomes and gene expression in the nasal mucosa of 36 children with SARS-CoV-2, 24 children with RSV, 9 children with IV, 16 adults with SARS-CoV-2, and 7 healthy pediatric and 13 healthy adult controls. In both children and adults, infection with SARS-CoV-2 led to an interferon response in the nasal mucosa. The magnitude of the interferon response correlated with the abundance of viral reads, not the severity of illness, and was comparable between children and adults infected with SARS-CoV-2 and children with severe RSV infection. Expression of ACE2 and TMPRSS2 did not correlate with age or presence of viral infection. SARS-CoV-2-infected adults had increased expression of genes involved in neutrophil activation and T cell receptor signaling pathways compared to SARS-CoV-2-infected children, despite similar severity of illness and viral reads. Age-related differences in the immune response to SARS-CoV-2 may place adults at increased risk of developing severe illness. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Background Prescription opioids play a large role in the opioid epidemic. Even short-term prescriptions provided postoperatively can lead to dependence. Objective To provide opioid prescription recommendations after Mohs micrographic surgery (MMS) and reconstruction. Methods This was a multi-institutional Delphi consensus study consisting of a panel of members of the American College of Mohs Surgery from various practice settings. Participants were first asked to describe scenarios in which they prescribe opioids at various frequencies. These scenarios then underwent 2 Delphi ratings rounds that aimed to identify situations in which opioid prescriptions should, or should not, be routinely prescribed. Consensus was set at ≥80% agreement. Prescription recommendations were then distributed to the panelists for feedback and approval. Results Twenty-three Mohs surgeons participated in the study. There was no scenario in which consensus was met to routinely provide an opioid prescription. However, there were several scenarios in which consensus were met to not routinely prescribe an opioid. Conclusion Opioids should not be routinely prescribed to every patient undergoing MMS. Prescription recommendations for opioids after MMS and reconstruction may decrease the exposure to these drugs and help combat the opioid epidemic.

Objective To investigate whether rates of self-reported Woman's Condom (WC) clinical failure and semen exposure from a functionality study are comparable to results from a contraceptive efficacy substudy. Study design We structured our comparative analysis to assess whether functionality studies might credibly supplant contraceptive efficacy studies when evaluating new female condom products. Couples not at risk of pregnancy in the functionality (breakage/slippage/invagination/penile misdirection) study and women in the contraceptive efficacy study completed condom self-reports and collected precoital and postcoital vaginal samples for up to four uses of the WC. Both studies used nearly identical self-report questions and the same self-sampling procedures and laboratory for prostatic specific antigen (PSA), a well-studied semen biomarker. We compared condom failure and semen exposure proportions using generalized estimating equations methods accounting for within-couple correlation. Results Ninety-five (95) efficacy substudy participants used 334 WC and 408 functionality participants used 1572 WC. Based on self-report, 19.2% WC (64 condoms) clinically failed in the efficacy substudy compared to 12.3% WC (194 condoms) in the functionality study (p=.03). Of the 207 WC efficacy uses with evaluable postcoital PSA levels, 14.5% (30 uses) resulted in semen exposure compared to 14.2% (184 uses) of the 1293 evaluable WC functionality study uses. Conclusions When evaluating the ability of an experimental condom to prevent semen exposure, the rate of clinical condom failure reported by participants risking pregnancy in an efficacy substudy was significantly higher than the rate reported by participants not risking pregnancy in a functionality study. The rate of semen exposure, assessed by an objective biomarker was nearly identical for the two studies. Implications Our results suggest that an objective marker of semen exposure in functionality studies could provide a reasonable alternative to contraceptive efficacy studies in evaluating risk of unintended pregnancy and inferring protection from sexually transmitted infection than condom failure rates based on self-report.

Mating strategy theories assert that women's preferences for androgen dependent traits in men are stronger when the costs of reduced paternal investment are lowest. Past research has shown that preferences for facial masculinity are stronger among nulliparous and non-pregnant women than pregnant or parous women. In two studies, we examine patterns in women's preferences for men's facial hair - likely the most visually conspicuous and sexually dimorphic of men's secondary sexual traits - when evaluating men's masculinity, dominance, age, fathering, and attractiveness. Two studies were conducted among heterosexual pregnant women, mothers, non-contractive and contraceptive users. Study 1 used a between-subjects sample (N = 2103) and found that mothers had significantly higher preferences for beards when judging fathering than all other women. Pregnant women and mothers also judged beards as more masculine and older, but less attractive, than non-contractive and contraceptive users. Parous women judged beards higher for age, masculinity and fathering, but lower for attractiveness, than nulliparous women. Irrespective of reproductive status, beards were judged as looking more dominant than clean-shaven faces. Study 2 used a within-subjects design (N = 53) among women surveyed during pregnancy and three months post-partum. Judgments of parenting skills were higher for bearded stimuli during pregnancy among women having their first baby, whereas among parous women parenting skills judgments for bearded stimuli were higher post-partum. Our results suggest that mothers are sensitive to beardedness as a masculine secondary sexual characteristic that may denote parental investment, providing evidence that women's mate preferences could reflect sexual selection for direct benefits.

Adults' first impressions of others are influenced by subtle facial expressions; happy faces are perceived as high in trustworthiness, whereas angry faces are rated as low in trustworthiness and high in threat and dominance. Little is known about the influence of emotional expressions on children's first impressions. Here we examined the influence of subtle expressions of happiness, anger, and fear on children's implicit judgments of trustworthiness and dominance with the aim of providing novel insights about both the development of first impressions and whether children are able to utilize emotional expressions when making implicit, rather than explicit, judgments of traits. In the context of a computerized storybook, children (4- to 11-year-olds) and adults selected one of two twins (two images of the same identity displaying different emotional expressions) to help them face a challenge; some challenges required a trustworthy partner, and others required a dominant partner. One twin posed a neutral expression, and the other posed a subtle emotional expression of happiness, fear, or anger. Whereas adults were more likely to select a happy partner on trust trials than on dominance trials and were more likely to select an angry partner on dominance trials than on trust trials, we found no evidence that children's choices reflected a combined influence of desirable trait and emotion. Follow-up experiments involving explicit trait judgments, explicit emotion recognition, and implicit first impression judgments in the context of intense emotional expressions provide valuable insights into the slow development of implicit trait judgments based on first impressions.

Improved sanitation has been hypothesized to reduce soil-transmitted helminth (STH) infections by reducing the prevalence and concentration of STH eggs/larvae in soil. We evaluated the effect of a randomized sanitation program (providing households with an improved dual-pit latrine, tools for child/animal feces management, and behavioral messaging) on reducing the prevalence and concentration of STH eggs in soil from household courtyards. We collected soil samples from 1405 households enrolled in the sanitation intervention (n = 419) and control (n = 914) groups of a cluster-randomized controlled trial (WASH Benefits) in rural Bangladesh approximately 2 years after the initiation of the interventions. We analyzed samples for Ascaris lumbricoides, Trichuris trichiura, and hookworm eggs by microscopy. We estimated prevalence ratios (PR) and egg count ratio (ECR) to compare the prevalence of STH eggs and arithmetic and geometric mean egg counts for STH eggs per gram of soil in the sanitation and control arms. Among intervention households, latrines achieved high and sustained user uptake by adults while child open defecation remained common and most households did not dispose of child feces hygienically. In courtyard soil from control households, the prevalence of any STH eggs was 75.7% and the prevalence of any larvated STH eggs was 67.3%. A. lumbricoides was detected in 63.0% of control samples and T. trichiura in 55.7% of control samples; hookworm was not detected in any sample. In the control arm, the arithmetic mean egg count for any STH was 3.96 eggs/dry gram, while the geometric mean was 1.58 eggs/dry gram. There was no difference between the intervention and control groups in the prevalence of any STH eggs (PR = 0.98 (95% CI: 0.91, 1.05)) or mean egg counts (ECR = 0.08 (95% CI: -0.10, 0.26) for geometric mean and 0.07 (95% CI: -0.22, 0.37) for arithmetic mean). Adjusted models gave similar results. A compound-level sanitation intervention that provided improved latrines and tools for disposal of child and animal feces did not have an impact on STH eggs in soil. In order to effectively reduce the prevalence and concentration of STH eggs in the environment, sustained, widespread use of sanitation strategies to isolate and hygienically dispose of child and animal feces may need to complement traditional strategies for containment of adult human feces. Trial Registration:NCT01590095., Author summary Improved sanitation has been hypothesized to reduce soil-transmitted helminth (STH) infections by reducing the prevalence and concentration of STH eggs/larvae in soil. We evaluated the effect of a randomized sanitation program (providing households with an improved dual-pit latrine, tools for child/animal feces management, and behavioral messaging) on reducing the prevalence and concentration of STH eggs in soil from household courtyards. We collected soil samples from 1405 households enrolled in the control and sanitation intervention arms of a cluster-randomized controlled trial (WASH Benefits) in rural Bangladesh approximately 2 years after the initiation of the interventions. We analyzed samples for Ascaris lumbricoides, Trichuris trichiura and hookworm eggs by microscopy. We found no effect of the sanitation intervention on STH eggs in soil. In order to effectively reduce the prevalence and concentration of STH eggs in the environment, sustained, widespread use of sanitation strategies to isolate and hygienically dispose of child and animal feces may need to complement traditional strategies for containment of adult human feces.

Aims It has been shown that the preoperative modification of risk factors associated with obesity may reduce complications after total knee arthroplasty (TKA). However, the optimal method of doing so remains unclear. The aim of this study was to investigate whether a preoperative Risk Stratification Tool (RST) devised in our institution could reduce unexpected intensive care unit (ICU) transfers and 90-day emergency department (ED) visits, readmissions, and reoperations after TKA in obese patients. Methods We retrospectively reviewed 1,614 consecutive patients undergoing primary unilateral TKA. Their mean age was 65.1 years (17.9 to 87.7) and the mean BMI was 34.2 kg/m2 (SD 7.7). All patients underwent perioperative optimization and monitoring using the RST, which is a validated calculation tool that provides a recommendation for postoperative ICU care or increased nursing support. Patients were divided into three groups: non-obese (BMI < 30 kg/m2, n = 512); obese (BMI 30 kg/m2 to 39.9 kg/m2, n = 748); and morbidly obese (BMI > 40 kg/m2, n = 354). Logistic regression analysis was used to evaluate the outcomes among the groups adjusted for age, sex, smoking, and diabetes. Results Obese patients had a significantly increased rate of discharge to a rehabilitation facility compared with non-obese patients (38.7% (426/1,102) vs 26.0% (133/512), respectively; p < 0.001). When stratified by BMI, discharge to a rehabilitation facility remained significantly higher compared with non-obese (26.0% (133)) in both obese (34.2% (256), odds ratio (OR) 1.6) and morbidly obese (48.0% (170), OR 3.1) patients (p < 0.001). However, there was no significant difference in unexpected ICU transfer (0.4% (two) non-obese vs 0.9% (seven) obese (OR 2.5) vs 1.7% (six) morbidly obese (OR 5.4); p = 0.054), visits to the ED (8.6% (44) vs 10.3% (77) (OR 1.3) vs 10.5% (37) (OR 1.2); p = 0.379), readmissions (4.5% (23) vs 4.0% (30) (OR 1.0) vs 5.1% (18) (OR 1.4); p = 0.322), or reoperations (2.5% (13) vs 3.3% (25) (OR 1.2) vs 3.1% (11) (OR 0.9); p = 0.939). Conclusion With the use of a preoperative RST, morbidly obese patients had similar rates of short-term postoperative adverse outcomes after primary TKA as non-obese patients. This supports the assertion that morbidly obese patients can safely undergo TKA with appropriate perioperative optimization and monitoring. Cite this article: Bone Joint J 2021;103-B(6 Supple A):45–50.

Multiple organ dysfunction syndrome (MODS) is one of the major causes of death and long-term impairment in critically ill patients. MODS is a complex, heterogeneous syndrome consisting of different phenotypes, which has limited the development of MODS-specific therapies and prognostic models. We used an unsupervised learning approach to derive novel phenotypes of MODS based on the type and severity of six individual organ dysfunctions. In a large, multi-center cohort of pediatric, young and middle-aged adults admitted to three different intensive care units, we uncovered and characterized three distinct data-driven phenotypes of MODS which were reproducible across age groups, where independently associated with outcomes and had unique predictors of in-hospital mortality.

BackgroundHyperchloremia and chloride load have been associated with worse clinical outcomes in critically ill patients. We sought to evaluate the electrolyte profile and clinical outcomes associated with a unit-wide transition from saline to balanced fluids for resuscitation and maintenance fluids in a pediatric intensive care unit (PICU).MethodsA before and after analysis of all patients admitted to the PICU in a large, urban, academic hospital between August 2018 and March 2020. The transition from the use of saline to the use of balanced fluids for both resuscitation and maintenance fluid as standard care occurred in June 2019. The primary outcome was day 3 acute kidney injury (AKI). The secondary outcomes included mortality, ventilator-free days (VFDs), need for renal replacement therapy (RRT), hospital length of stay (LOS), and electrolyte abnormalities.ResultsOverall, 2863 patients (47% female) with a day 3 AKI rate of 12.9% (n = 130) and a mortality rate of 2.8% (n = 79) were included. After adjusting for confounders (age, PRISM III, mechanical ventilation, and immunocompromised state, septic shock), there were no significant differences in the odds of day 3 AKI (pre 13%, post 12.5%; adjusted odds ratio [aOR] 0.96, 95%CI 0.65–1.42). There were no differences in the secondary outcomes. The post-intervention period had fewer patients with hyperchloremia (pre 15.5% vs. post 10.4%,p = p = 0.02) and more patients with hypochloremia (pre 9.5% vs. post 14.4%,p = p = ConclusionsFollowing a unit-wide implementation of balanced fluids as standard care, there were no differences in rates of day 3 AKI or other clinical outcomes. However, there were lower rates of hyperkalemia and hyperchloremia and higher rates of hypokalemia and hypochloremia. Further evaluation of the effect of balanced fluids and the clinical significance of electrolyte abnormalities in critically ill children is needed.

Assess the impact of surgical technique used to address level IV on the rate of postoperative chyle leak.Retrospective chart review.Academic tertiary care center.An analysis of 436 consecutive neck dissections (NDs) in 368 patients was performed by 3 head and neck surgeons between 2014 and 2017. Variation in technique reflects individual approaches to the management of level IV and included suture ligation (SL), monopolar electrocautery (MC), and harmonic scalpel transection (HS). Data points included patient demographics, surgical technique, intraoperative findings, postoperative chyle leaks, and leak management. Correlation between variables was analyzed through χOverall, 12 patients (3.2%) developed chyle leaks postoperatively. Nine of 12 and 3 of 12 presented with left- and right-sided leaks, respectively. Five of 12 leaks occurred following bilateral ND, 5 of 12 following left ND, and 2 of 12 following right ND. Univariate analysis showed a statistically significant difference (SL and MC techniques demonstrated superiority over the HS technique in preventative management of chyle leak in level IV, with a significantly higher rate of chyle leak observed in endocrine-related pathology.

Dentigerous cysts, also known as follicular cysts, are among the most common developmental cysts of the gnathic bones. The majority of cases are clinically asymptomatic and discovered incidentally on panographic radiographs during routine dental care. The cyst appears as a radiolucency, classically unilocular, associated with the crown of an unerupted or impacted tooth. Usually diagnosed in the 2nd-3rd decade, third molars of the mandible are the most commonly affected teeth. Histologically, dentigerous cysts demonstrate a fibrous or fibromyxoid connective tissue wall lined by squamous epithelium, classically lacking rete ridges. Inflammation may introduce histologic changes, however. The differential diagnosis includes hyperplastic dental follicle, periapical or radicular cyst, unicystic ameloblastoma, odontogenic keratocyst, and other odontogenic cysts and tumors. While the findings are generally classic and pose no diagnostic dilemma, the diagnosis is best made in the context of the appropriate clinical and radiographic setting. Submitted tissue with a lack of history, to include a detailed relationship with the affected tooth, may result in misdiagnosis and subsequent confusion for the clinician. So, despite its simple features, dentigerous cysts are not uncommonly mischaracterized. Therefore a review of a classic case of dentigerous cyst is presented.

Narrativity has been proposed as an indicator of episodic memory strength when people discuss their past (Nelson and Horowitz in Discourse Processes 31:307–324, 2001. https://doi.org/10.1207/S15326950dp31-3_5 ). Referential Activity, the extent to which words convey a speaker's experience of being present in the event being described, has been independently hypothesized to indicate episodic memory strength (Maskit in J Psycholinguist Res, 2021. https://doi.org/10.1007/s10936-021-09761-8 ). These hypotheses are tested using a linguistic measure of narrativity and a computerized measure of referential activity to predict previous independent ratings of episodic memory strength that used the Levine et al. (Psychol Aging 17(4):677–689, 2002. https://doi.org/10.1037//0882-7974.17.4.677 ) measure of internal details in retold personal memories provided by Schacter (Addis et al. in Psychol Sci 19(1):33–41, 2008. https://doi.org/10.1111/j.1467-9280.2008.02043.x ). Raters scored narrativity on four brief near and far past memories elicited from 32 subjects, using Nelson's narrative temporal sequence method based on Labov’s (J Narrat Life Hist 7(1–4):395–415, 1997. https://doi.org/10.1075/jnlh.7.49som ) analysis of spoken narratives of personal experience; computerized weighted scores of referential activity (WRAD) were obtained on these same 128 memories. Data analysis showed that narrative temporal sequences predict internal details and WRAD predict internal details. Adding WRAD to narrative temporal sequences improved the prediction of internal details.

Objectives When healthcare systems are overwhelmed, accurate assessments of patients' predicted mortality risks are needed to ensure effective allocation of scarce resources. Organ dysfunction scores can serve this essential role, but their evaluation in this context has been limited so far. In this study, we sought to assess the performance of three organ dysfunction scores in both critically ill adults and children at clinically relevant mortality thresholds and timeframes for resource allocation and compare it with two published prioritization schemas. Design Retrospective observational cohort study. Setting Three large academic medical centers in the United States. Patients Critically ill adults and children. Interventions None. Measurements and main results We calculated the daily Sequential Organ Failure Assessment score in adults and the Pediatric Logistic Organ Dysfunction 2 score and the Pediatric Sequential Organ Failure Assessment score in children. There were 49,290 (11.6% mortality) and 19,983 children (2.5% mortality) included in the analysis. Both the Sequential Organ Failure Assessment and Pediatric Sequential Organ Failure Assessment scores had adequate discrimination across relevant timeframes and adequate distribution across relevant mortality thresholds. Additionally, we found that the only published state prioritization schema that includes pediatric and adult patients had poor alignment of mortality risks, giving adults a systematic advantage over children. Conclusions In the largest analysis of organ dysfunction scores in a general population of critically ill adults and children to date, we found that both the Sequential Organ Failure Assessment and Pediatric Sequential Organ Failure Assessment scores had adequate performance across relevant mortality thresholds and timeframes for resource allocation. Published prioritization schemas that include both pediatric and adult patients may put children at a disadvantage. Furthermore, the distribution of patient and mortality risk in the published schemas may not adequately stratify patients for some high-stakes allocation decisions. This information may be useful to bioethicists, healthcare leaders, and policy makers who are developing resource allocation policies for critically ill patients.

Acute kidney injury (AKI) that improves in the pediatric intensive care unit (PICU) is associated with better outcomes compared to AKI that persists, but no study has investigated whether this also occurs in children undergoing cardiopulmonary bypass (CPB).A retrospective study of children ≤18 years who underwent CPB in three children's hospitals was conducted. Patients were classified into groups by kidney recovery after AKI according to Acute Disease Quality Initiative (ADQI) guidelines. Adjusted regression models evaluated associations between kidney recovery group and hospital outcomes.Among 3620 children, AKI developed in 701 (19.4%): 610 transient AKI, 47 persistent AKI, and 44 acute kidney disease (AKD). Mortality increased with severity of kidney recovery group: 4.5% in the never developed AKI group, 8.9% in the transient AKI group, 25.5% in the persistent AKI group, and 31.8% in the AKD group (p0.0001). In adjusted analysis, transient AKI (HR 1.4, CI 1.02, 2), persistent AKI (HR 22.4, CI 10.2, 49.2), and AKD (HR 3.7, CI 1.7, 7.9) had a greater hazard of mortality when compared to the never developed AKI group. Patients with transient AKI had a longer length of PICU stay than those with never developed AKI (HR 5.1, CI 2.9, 7.3).Patterns of kidney recovery after AKI were associated with worse PICU outcomes in children after CPB compared to those who did not develop AKI, even after rapid AKI recovery. Identification of factors that increase risk for these AKI patterns is necessary for prevention of AKI during CPB in children. A higher resolution version of the Graphical abstract is available as Supplementary information.

Reduced protein levels of SMARCB1 (also known as BAF47, INI1, SNF5) have long been observed in synovial sarcoma. Here, we show that combined Smarcb1 genetic loss with SS18–SSX expression in mice synergized to produce aggressive tumors with histomorphology, transcriptomes, and genome-wide BAF-family complex distributions distinct from SS18–SSX alone, indicating a defining role for SMARCB1 in synovial sarcoma. Smarcb1 silencing alone in mesenchyme modeled epithelioid sarcomagenesis. In mouse and human synovial sarcoma cells, SMARCB1 was identified within PBAF and canonical BAF (CBAF) complexes, coincorporated with SS18–SSX in the latter. Recombinant expression of CBAF components in human cells reconstituted CBAF subcomplexes that contained equal levels of SMARCB1 regardless of SS18 or SS18–SSX inclusion. In vivo, SS18–SSX expression led to whole-complex CBAF degradation, rendering increases in the relative prevalence of other BAF-family subtypes, PBAF and GBAF complexes, over time. Thus, SS18–SSX alters BAF subtypes levels/balance and genome distribution, driving synovial sarcomagenesis. Significance: The protein level of BAF component SMARCB1 is reduced in synovial sarcoma but plays a defining role, incorporating into PBAF and SS18–SSX-containing canonical BAF complexes. Reduced levels of SMARCB1 derive from whole-complex degradation of canonical BAF driven by SS18–SSX, with relative increases in the abundance of other BAF-family subtypes. See related commentary by Maxwell and Hargreaves, p. 2375 This article is highlighted in the In This Issue feature, p. 2355

We investigated the heritability of educational attainment and how it differed between birth cohorts and cultural-geographic regions. A classical twin design was applied to pooled data from 28 cohorts representing 16 countries and including 193,518 twins with information on educational attainment at 25 years of age or older. Genetic factors explained the major part of individual differences in educational attainment (heritability: a(2)=0.43; 0.41-0.44), but also environmental variation shared by co-twins was substantial (c(2)=0.31; 0.30-0.33). The proportions of educational variation explained by genetic and shared environmental factors did not differ between Europe, North America and Australia, and East Asia. When restricted to twins 30 years or older to confirm finalized education, the heritability was higher in the older cohorts born in 1900-1949 (a(2)=0.44; 0.41-0.46) than in the later cohorts born in 1950-1989 (a(2)=0.38; 0.36-0.40), with a corresponding lower influence of common environmental factors (c(2)=0.31; 0.29-0.33 and c(2)=0.34; 0.32-0.36, respectively). In conclusion, both genetic and environmental factors shared by co-twins have an important influence on individual differences in educational attainment. The effect of genetic factors on educational attainment has decreased from the cohorts born before to those born after the 1950s. This study was conducted within the CODATwins project. We thank Wendy Cozen, University of Southern California, for sharing data with us. Funding for collaborators: Netherlands Twin Register acknowledges the Netherlands Organization for Scientific Research (NWO) and MagW/ZonMW grants 904-61-090, 985-10-002, 912-10-020, 904-61-193,480-04-004, 463-06-001, 451-04-034, 400-05-717, Addiction-31160008, Middelgroot-911-09-032, Spinozapremie 56-464-14192; VU University's Institute for Health and Care Research (EMGO+); the European Research Council (ERC - 230374), the Avera Institute, Sioux Falls, South Dakota (USA). Data collection and analyses in Finnish twin cohorts have been supported by ENGAGE - European Network for Genetic and Genomic Epidemiology, FP7-HEALTH-F4-2007, Grant Agreement Number 201413, National Institute of Alcohol Abuse and Alcoholism (Grants AA-12502, AA-00145, and AA-09203 to R J Rose, the Academy of Finland Center of Excellence in Complex Disease Genetics (Grant Numbers: 213506, 129680), and the Academy of Finland (Grants 100499, 205585, 118555, 141054, 265240, 263278 and 264146 to J Kaprio). Since its origin the East Flanders Prospective Survey has been partly supported by grants from the Fund of Scientific Research, Flanders and Twins, a non-profit Association for Scientific Research in Multiple Births (Belgium). Anthropometric measurements of the Hungarian twins were supported by Medexpert Ltd., Budapest, Hungary. The Murcia Twin Registry is supported by Fundacion Seneca, Regional Agency for Science and Technology, Murcia, Spain (08633/PHCS/08, 15302/PHCS/10 & 19479/PI/14) and Ministry of Science and Innovation, Spain (PSI2009-11560 & PSI2014-56680-R). K Silventoinen is supported by Osaka University's International Joint Research Promotion Program. We acknowledge The Swedish Twin Registry for access to data. The Swedish Twin Registry is managed by Karolinska Institutet and receives funding through the Swedish Research Council under the grant no 2017-00641. This research was facilitated through access to Twins Research Australia, a national resource supported by a Centre of Research Excellence Grant (ID: 1079102), from the National Health and Medical Research Council. California Twin Program was supported by The California Tobacco-Related Disease Research Program (7RT-0134H, 8RT-0107H, 6RT-0354H) and the National Institutes of Health (1R01ESO15150-01). The Carolina African American Twin Study of Aging (CAATSA) was funded by a grant from the National Institute on Aging (grant 1RO1-AG13662-01A2) to K. E. Whitfield. Colorado Twin Registry is funded by NIDA funded center grant DA011015, & Longititudinal Twin Study HD10333; Author Huibregtse is supported by 5T32DA017637 and 5T32AG052371. Washington State Twin Registry (formerly the University of Washington Twin Registry) was supported in part by grant NIH RC2 HL103416 (D. Buchwald, PI). Vietnam Era Twin Study of Aging was supported by National Institute of Health grants NIA R01 AG018384, R01 AG018386, R01 AG022381, and R01 AG022982, and, in part, with resources of the VA San Diego Center of Excellence for Stress and Mental Health. The Cooperative Studies Program of the Office of Research & Development of the United States Department of Veterans Affairs has provided financial support for the development and maintenance of the Vietnam Era Twin (VET) Registry. The content of this manuscript is solely the responsibility of the authors and does not necessarily represent the official views of the NIA/NIH, or the VA. The NAS-NRC Twin Registry acknowledges financial support from the National Institutes of Health grant number R21 AG039572. Korean Twin-Family Register was supported by the Global Research Network Program of the National Research Foundation (NRF 2011-220-E00006). Osaka University Aged Twin Registry is supported by grants from JSPS KAKENHI JP (23593419, 24792601, 26671010, 24590695, 26293128, 16K15385, 16K15978, 16K15989, 16H03261).

BACKGROUND Standardized pathways decrease variability and improve outcomes and safety. PURPOSE The article aims to evaluate outcomes of a standardized postoperative care pathway compared with individual surgeon preference. METHODS A review of patients prestandardization and poststandardization was performed. Patients between the ages of 10-21 years with adolescent idiopathic scoliosis (ICD-9 code 737.30) admitted to the hospital for posterior spinal fusion (CPT code 22630) were included in the study. The prestandardization group (25 patients) was enrolled from April 1, 2010, through March 30, 2011, and the poststandardization group (25 patients) from April 1, 2014, to March 30, 2015. Exclusion criteria were renal disease, epilepsy, neurological disorder, or postoperative complications that led to change in routine care including ileus or fever greater than 102 °F. Data were analyzed using the Wilcoxon signed rank test, with significance set at p < .001. RESULTS The length of stay (p = .0166), time to ambulation (p < .0001), patient-controlled analgesia use (p < .0001), and postoperative time to resumption of regular diet (p < .0001) were all significantly decreased in the poststandardization group. There were no complications or readmissions in either group. CONCLUSION The standardized pathway resulted in shorter length of stay, decreased narcotic use, decreased time to regular diet, and decreased time to ambulation with no increase in complication rates.

To what extent do children believe in real, unreal, natural and supernatural figures relative to each other, and to what extent are features of culture responsible for belief? Are some figures, like Santa Claus or an alien, perceived as more real than figures like Princess Elsa or a unicorn? We categorized 13 figures into five a priori categories based on 1) whether children receive direct evidence of the figure’s existence, 2) whether children receive indirect evidence of the figure’s existence, 3) whether the figure was associated with culture-specific rituals or norms, and 4) whether the figure was explicitly presented as fictional. We anticipated that the categories would be endorsed in the following order: ‘Real People’ (a person known to the child, The Wiggles), ‘Cultural Figures’ (Santa Claus, The Easter Bunny, The Tooth Fairy), ‘Ambiguous Figures’ (Dinosaurs, Aliens), ‘Mythical Figures’ (unicorns, ghosts, dragons), and ‘Fictional Figures’ (Spongebob Squarepants, Princess Elsa, Peter Pan). In total, we analysed responses from 176 children (aged 2–11 years) and 56 adults for ‘how real’ they believed 13 individual figures were (95 children were examined online by their parents, and 81 children were examined by trained research assistants). A cluster analysis, based exclusively on children’s ‘realness’ scores, revealed a structure supporting our hypotheses, and multilevel regressions revealed a sensible hierarchy of endorsement with differing developmental trajectories for each category of figures. We advance the argument that cultural rituals are a special form of testimony that influences children’s reality/fantasy distinctions, and that rituals and norms for ‘Cultural Figures’ are a powerful and under-researched factor in generating and sustaining a child’s endorsement for a figure’s reality status. All our data and materials are publically available at https://osf.io/wurxy/.

Aims Rates of readmission and reoperation following primary total knee arthroplasty (TKA) are under scrutiny due to new payment models, which penalize these negative outcomes. Some risk factors are more modifiable than others, and some conditions considered modifiable such as obesity may not be as modifiable in the setting of advanced arthritis as many propose. We sought to determine whether controlling for hypoalbuminaemia would mitigate the effect that prior authors had identified in patients with obesity. Methods We reviewed the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database for the period of January 2008 to December 2016 to evaluate the rates of reoperation and readmission within 30 days following primary TKA. Multivariate logistic regression modelling controlled for preoperative albumin, age, sex, and comorbidity status. Results Readmission rates only differed significantly between patients with Normal Weight and Obesity Class II, with a decreased rate of readmission in this group (odds ratio (OR) 0.82; 95% confidence interval (CI) 0.71 to 0.96; p = 0.010). The only group demonstrating association with increased risk of reoperation within 30 days was the Obesity Class III group (OR 1.38; 95% CI 1.05 to 1.82; p = 0.022). Hypoalbuminaemia (preoperative albumin < 35 g/L) was significantly associated with readmission (OR 1.62; 95% CI 1.41 to 1.86; p < 0.001) and reoperation (OR 1.52; 95% CI 1.18 to 1.96; p = 0.001) within 30 days. Conclusion In this study, hypoalbuminaemia appears to be a more significant risk factor for readmission and reoperation than even the highest obesity categories. Future studies may assess whether preoperative albumin restoration or weight loss may improve outcomes for patients with hypoalbuminaemia. The implications of this study may allow surgeons to discuss risk of surgery with obese patients planning to undergo primary TKA procedures if other comorbidities are adequately controlled. Cite this article: Bone Joint J 2020;102-B(6 Supple A):31–35.

A 47-year-old man presented to the otolaryngology service with complaint of 6 months of intermittent globus sensation. He reported constant throat clearing and subjective lowering of his voice. Flexible nasolaryngoscopy revealed a large pedunculated mass originating from the left vocal process of the arytenoid, lying superior to the vocal fold. The patient was treated conservatively with an anti-reflux regiment and speech language therapy for 2 months, however he noted marginal worsening in voice over the proceeding interval with an increasing raspy quality. He underwent suspension microlaryngoscopy with biopsy. Microscopic examination demonstrated mucosal epithelium with surface ulceration and considerable fibrinoid necrosis, a mixed inflammatory infiltrate, and abundant granulation tissue with reactive endothelial cells. The diagnosis of laryngeal contact ulcer was rendered. The patient was treated with KTP (potassium titanyl phosphate) laser ablation and corticosteroid microinjection; he tolerated the procedures well and on follow-up noted reduced cough, improving voice quality and no residual dysphagia.

Secretion of the acrosome, a single vesicle located rostrally in the head of a mammalian sperm, through a process known as "acrosome exocytosis" (AE), is essential for fertilization. However, the mechanisms leading to and regulating this complex process are controversial. In particular, poor understanding of Ca2+ dynamics between sperm subcellular compartments and regulation of membrane fusion mechanisms have led to competing models of AE. Here, we developed a transgenic mouse expressing an Acrosome-targeted Sensor for Exocytosis (AcroSensE) to investigate the spatial and temporal Ca2+ dynamics in AE in live sperm. AcroSensE combines a genetically encoded Ca2+ indicator (GCaMP) fused with an mCherry indicator to spatiotemporally resolve acrosomal Ca2+ rise (ACR) and membrane fusion events, enabling real-time study of AE. We found that ACR is dependent on extracellular Ca2+ and that ACR precedes AE. In addition, we show that there are intermediate steps in ACR and that AE correlates better with the ACR rate rather than absolute Ca2+ amount. Finally, we demonstrate that ACR and membrane fusion progression kinetics and spatial patterns differ with different stimuli and that sites of initiation of ACR and sites of membrane fusion do not always correspond. These findings support a model involving functionally redundant pathways that enable a highly regulated, multistep AE in heterogeneous sperm populations, unlike the previously proposed "acrosome reaction" model.

We examined the utility of a gaze cueing paradigm to examine sensitivity to differences among negatively valenced expressions. Participants judged target stimuli (dangerous or safe), the location of which was cued by the gaze direction of a central face. Dawel et al. reported that gaze cueing effects (faster response times on valid vs. invalid trials) were larger when the central face displayed fear than when it displayed happiness. Our aim was to determine whether this effect was specific to fear, to all threat-related expressions (fear, anger), or to all negatively valenced expressions (fear, anger, sadness, disgust) with the aim of using this protocol to study the development of implicit discrimination of negatively valenced expressions. Across five experiments in which we varied the number of models (1 vs. 4), the number of expressions (2 vs. 5), and the country of residence of participants (Canada vs. Australia) we found no evidence that the magnitude of gaze cueing effects is modulated by expression. We discuss our failure to replicate in the context of the broader literature.

Introduction:Low serum albumin is associated with higher perioperative complications following total hip arthroplasty (THA). The distinct threshold for a significant rise in perioperative complications has not been defined for THA. The purpose of this study was to define the threshold at which perioperative complications rise after THA.Methods:We analysed the American College of Surgeons NSQIP database from 2006 to 2013. Our study cohort included unilateral primary THA with reported preoperative albumin levels. Patients were stratified by albumin level. We analysed mortality and 6 composite complication variables (any complication, any complication without transfusion, wound infection, systemic infection, cardiac/pulmonary complications, and any major complication). All data analysis was executed in STATA statistical software. Multivariable logistic regression analysis was used to adjust for odds ratios.Results:The final cohort included 24,586 patients who were stratified based upon serum albumin levels. Odds ratios after multivariable regression adjustment for age, gender, race, body mass index, ASA classification, and Charlson Comorbidity Index indicated a trend to elevated odds of complication for all composite complications (3 of which were statistically significant) when serum albumin level was Conclusion:Low serum albumin is associated with increased perioperative complications following THA. The threshold associated with an increase in major perioperative complications appears to be an albumin level of

While handedness questionnaires are widely used in adults, there is no comparable measure designed specifically for children. The current study developed the Home Handedness Questionnaire (HHQ), a new measure for preschoolers administered by parents using common household items. The HHQ has two scales that distinguish action types typically combined on other measures: actions performed with only the right or left hand (i.e., unimanual, such as holding a toothbrush), and actions performed with one hand holding the object for the other hand's action (i.e., role-differentiated bimanual manipulation or RDBM, such as unscrewing a lid from a jar). The HHQ was able to detect right preference, left preference, and no preference for unimanual and RDBM actions in a proof of concept study in 3-year-olds (N = 64). The HHQ identified a majority of children as right-handed, but was also sensitive to variability in direction across skill types. Approximately one-quarter of children in the sample had mixed preferences for the two types of manual skills, suggesting that for a subgroup of children, hand use patterns may still be undergoing change. Suggestions for refining the HHQ are discussed. Overall, the HHQ is a promising multidimensional parent-led tool for assessing preschool handedness.

Background The Pipeline Flex (PED Flex; Medtronic, Dublin, Ireland) was designed to facilitate deployment and navigation compared to its previous iteration to reduce the rate of technical events and complications. Objective To assess the neurological morbidity and mortality rates of the PED Flex at 30 d. Methods Information from 9 neurovascular centers was retrospectively obtained between July 2014 and March 2016. Data included patient/aneurysm characteristics, periprocedural events, clinical, and angiographic outcomes. Multivariate logistic regression was performed to determine predictors of unfavorable clinical outcome (modified Rankin Scale [mRS] > 2). Results A total of 205 patients harboring 223 aneurysms were analyzed. The 30-d neurological morbidity and mortality rates were 1.9% (4/205) and 0.5% (1/205), respectively. The rate of intraprocedural events without neurological morbidity was 6.8% (14/205), consisting of intraprocedural ischemic events in 9 patients (4.5%) and hemorrhage in 5 (2.4%). Other technical events included difficulty capturing the delivery wire in 1 case (0.5%) and device migration after deployment in another case (0.5%). Favorable clinical outcome (mRS 0-2) was achieved in 186 patients (94.4%) at discharge and in 140 patients (94.5%) at 30 d. We did not find predictors of clinical outcomes on multivariate analysis. Conclusion The 30-d rates of neurological morbidity and mortality in this multicenter cohort using the PED Flex for the treatment of intracranial aneurysms were low, 1.9% (4/205) and 0.5% (1/205), respectively. In addition, technical events related to device deployment were also low, most likely due to the latest modifications in the delivery system.

Background: Despite lower cancer screening rates and survival rates in the Medicaid population compared with those with private insurance, there is a dearth of population-based, evidence-based interventions targeting Medicaid clients to address this problem. Methods: This study reports results of a population-based randomized controlled trial (RCT) among all individuals enrolled in Minnesota's Medicaid program who were overdue for breast cancer (n = 22,113) and/or colorectal cancer (n = 94,294) screening. Individuals were randomized to intervention or control groups. The intervention group received persuasive and innovative direct mail materials coupled with a $20 incentive for using their Medicaid benefit to get screened. Direct mail materials provided a phone number to a call center staffed by patient navigators who addressed barriers and scheduled appointments via three-way calls. The control group received the intervention 15 months later. Primary outcomes were completion of mammography or colonoscopy within 12 weeks of the intervention. Billing claims served as evidence of screening. Results: Multivariate logistic regression showed significant differences for both breast cancer (P < 0.001) and colorectal cancer (P < 0.01). The odds of receiving a mammogram for the treatment group were significantly higher than the control group [OR = 1.30; 95% confidence interval (95% CI) = 1.16–1.46], and the treatment group was more likely to receive a colonoscopy than the control group (OR = 1.12; 95% CI = 1.04–1.21). Conclusions: This population-based intervention increased breast cancer and colorectal cancer screening in a Medicaid population overdue for screening. Impact: These findings may have broad application for reaching individuals who generally remain outside the health care system despite having public health insurance. Cancer Epidemiol Biomarkers Prev; 27(9); 1047–56. ©2018 AACR.

AIMS: DNA release by dying β cells leads to increased circulating levels of unmethylated preproinsulin (INS) DNA. Consistent with large-scale β cell destruction, this biomarker is elevated before and at the time of type 1 diabetes (T1D) onset. We measured serum INS DNA to evaluate whether β cells continue to undergo death in later stages of T1D. MATERIALS AND METHODS: We analyzed fasting banked sera from a cross-section of 90 participants in the T1D Exchange Registry with long standing T1D (median duration of 9 years). Subjects were determined to be C-peptide (−) or (+) based on mixed-meal tolerance testing. Results were compared to 54 adult nondiabetic controls. Stimulated samples were assayed in a subset of subjects. Levels of unmethylated and methylated INS DNA were analyzed using digital droplet PCR. RESULTS: Fasting and stimulated circulating unmethylated INS DNA levels were increased among both C-peptide (−) and C-peptide (+) subjects with longstanding T1D compared to non-diabetic controls (p

In recent years, evidence has emerged about the importance of healthy fluid intake in children for physical and mental performance and health, and in the prevention of obesity. Accurate data on water intake are needed to inform researchers and policymakers and for setting dietary reference values. However, to date, there are few published data on fluid or water intakes in children. This is due partly to the fact that drinking water is not always reported in dietary surveys. The aim of this paper is to review the current status of the literature and highlight the challenges of assessing total fluid intake in children and adolescents. From the dietary assessment literature it is apparent that children present unique challenges to assessing intake due to ongoing cognitive capacity development, limited literacy skills, difficulties in estimating portion sizes and multiple caregivers during any 1 day making it difficult to track intakes. As such, many issues should be considered when assessing total fluid intakes in children or adolescents. Various methods to assess fluid intakes exist, each with its own strengths and weaknesses; the ultimate choice of method depends on the research question and resources available. Based on the literature review, it is apparent that if the research focus is to assess only fluid intake, a fluid-specific method, such as a diary or record, appears to be a feasible approach to provide an accurate estimate of intakes.

Although tibial component loosening has been considered a concern after total knee arthroplasty without cement, such implants have been used in younger patients because of the potential for ingrowth and preservation of bone stock. However, mid-term and long-term studies of modern uncemented implants are lacking. We previously reported promising prospective 5-year outcomes after using an uncemented porous tantalum tibial component in patients who underwent surgery before the age of 60 years. The purpose of this study was to determine clinical and radiographic implant survivorship at 10 years in this large series of young patients.The original cohort included 79 patients (96 knees) who were60 years old at the time of surgery. All procedures were performed with an uncemented, posterior-stabilized femoral component and a porous tantalum monoblock tibial component by 1 high-volume arthroplasty surgeon at a single institution. Patients were followed prospectively. The Knee Society Score (KSS), radiographic findings, and any complications or revisions were recorded.At the latest follow-up, 76% (60) of the 79 patients (74% [71] of the 96 knees) were available for evaluation or had undergone revision (n = 6); 7 patients had died with the implants in place, and 12 patients were lost to follow-up. The average follow-up for the available implants was 10 years (range, 8 to 12 years). There were no progressive radiolucencies on radiographic review. The mean functional KSS was 68 points (range, 0 to 100 points). All revisions were for reasons unrelated to tibial fixation: femoral component loosening (1), stiffness (1), pain and swelling (2), and instability (2). The all-cause revision rate was 6% (6 of 96 knees).Uncemented porous tantalum monoblock tibial components provided reliable fixation, excellent radiographic findings, and satisfactory functional outcomes at a mean of 10 years postoperatively. We identified no cases of tibial component loosening. These promising clinical and radiographic results support the use of uncemented tibial components. Such implants may produce well-integrated, durable long-term constructs in young patients.Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Sperm entering the epididymis are immotile and cannot respond to stimuli that will enable them to fertilize. The epididymis is a highly complex organ, with multiple histological zones and cell types that together change the composition and functional abilities of sperm through poorly understood mechanisms. Sperm take up taurine during epididymal transit, which may play antioxidant or osmoregulatory roles. Cysteine dioxygenase (CDO) is a critical enzyme for taurine synthesis. A previous study reported that male CDO(−/−) mice exhibit idiopathic infertility, prompting us to investigate the functions of CDO in male fertility. Immunoblotting and quantitative reverse transcription-polymerase chain reaction analysis of epididymal segments showed that androgen-dependent CDO expression was highest in the caput epididymidis. CDO(−/−) mouse sperm demonstrated a severe lack of in vitro fertilization ability. Acrosome exocytosis and tyrosine phosphorylation profiles in response to stimuli were normal, suggesting normal functioning of pathways associated with capacitation. CDO(−/−) sperm had a slight increase in head abnormalities. Taurine and hypotaurine concentrations in CDO(−/−) sperm decreased in the epididymal intraluminal fluid and sperm cytosol. We found no evidence of antioxidant protection against lipid peroxidation. However, CDO(−/−) sperm exhibited severe defects in volume regulation, swelling in response to the relatively hypo-osmotic conditions found in the female reproductive tract. Our findings suggest that epididymal CDO plays a key role in post-testicular sperm maturation, enabling sperm to osmoregulate as they transition from the male to the female reproductive tract, and provide new understanding of the compartmentalized functions of the epididymis.

A 23 year old male presented to the Otolaryngology clinic with 6 months of hoarseness and poor voice projection without improvement from speech therapy or medical anti-reflux medication. Upon examination he was found to have multiple polypoid lesions emanating from bilateral false vocal folds, left true vocal fold, and the anterior commissure. Biopsy and potassium titanyl phosphate (KTP) laser ablation with bevacizumab injection provided treatment and confirmed the clinical suspicion of squamous cell papilloma. Despite 3 years of treatment, the papillomatosis proved difficult to control, requiring a procedure approximately every 3 months. In an attempt to control the course of the disease the patient received a series of three bevacizumab and three cidofovir injections. Serial biopsies showed mild atypia within the squamous cell papillomas. Two separate biopsies confirmed presence of human papillomavirus (HPV) 6/11 via in situ hybridization with appropriate controls. There is promising research that the quadrivalent HPV (types 6, 11, 16, and 18) vaccine both reduces the disease burden in patients with active disease and reduces the incidence of recurrent respiratory papillomatosis (RRP). Other studies have shown that local immunologic dysregulation may play a role in RRP pathogenesis. Therefore new treatment options, to include PDL-1 blockade, offer hope in treating this benign condition with high morbidity and rare mortality.

Objective To assess beliefs about the safety of oral contraceptives compared to pregnancy to determine if men and women possess accurate information to make informed choices. Study design In each of six surveys conducted in Southern California from 2008 to 2017, participants were asked “Which do you think is more hazardous to a woman's health — birth control pills or pregnancy?” Results A total of 28.4% of all 1839 male and female respondents and 29.1% of the 1712 female respondents answered correctly that the health risks posed by pregnancy were greater. In subgroup analyses, 64.4%–81.9% rated oral contraceptives at least as hazardous to a woman's health as pregnancy. Conclusion The vast majority of respondents incorrectly believed that oral contraceptives are more hazardous than pregnancy. Implications Health decision making relies upon patients' understanding of the relative risks and benefits of each available option. Most sexually active women do not understand that there is no contraceptive method current guidelines would offer them that is as hazardous to their health as pregnancy. Such misconceptions can lead to risky decisions. Clinicians need to explicitly provide their sexually active patients more accurate and balanced information, putting contraception in the context of its probable alternative — pregnancy.