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Donald E Bailey Jr,1,2 Sharron L Docherty,1 Judith A Adams,1 Dana L Carthron,3 Kirsten Corazzini,1,2 Jennifer R Day,1 Elizabeth Neglia,1 Marcus Thygeson,4 Ruth A Anderson1,21School of Nursing, Duke University, 2Center for the Study of Aging and Human Development, Duke University, Durham, NC, 3School of Health Science, Division of Nursing, Winston Salem State University, Winston Salem, NC, 4Medical Services, Blue Shield of California, San Francisco, CA, USAAbstract: In this paper we discuss the concept of leadership as a personal capability, not contingent on one's position in a hierarchy. This type of leadership allows us to reframe both the care-giving and organizational roles of nurses and other front-line clinical staff. Little research has been done to explore what leadership means at the point of care, particularly in reference to the relationship between health care practitioners and patients and their family caregivers. The Adaptive Leadership framework, based on complexity science theory, provides a useful lens to explore practitioners' leadership behaviors at the point of care. This framework proposes that there are two broad categories of challenges that patients face: technical and adaptive. Whereas technical challenges are addressed with technical solutions that are delivered by practitioners, adaptive challenges require the patient (or family member) to adjust to a new situation and to do the work of adapting, learning, and behavior change. Adaptive leadership is the work that practitioners do to mobilize and support patients to do the adaptive work. The purpose of this paper is to describe this framework and demonstrate its application to nursing research. We demonstrate the framework's utility with five exemplars of nursing research problems that range from the individual to the system levels. The framework has the potential to guide researchers to ask new questions and to gain new insights into how practitioners interact with patients at the point of care to increase the patient's ability to tackle challenging problems and improve their own health care outcomes. It is a potentially powerful framework for developing and testing a new generation of interventions to address complex issues by harnessing and learning about the adaptive capabilities of patients within their life contexts.Keywords: nursing, patient care, providers, health care practitioners, patient centered care, nursing providers, complex adaptive systems

Earth- and space-based observations provide synergistic information for space mission encounters by providing data over longer timescales, at different wavelengths and using techniques that are impossible with an in situ flyby. We report here such observations in support of the EPOXI spacecraft flyby of comet 103P/Hartley 2. The nucleus is small and dark, and exhibited a very rapidly changing rotation period. Prior to the onset of activity, the period was 16.4hr. Starting in 2010 August the period changed from 16.6hr to near 19hr in December. With respect to dust composition, most volatiles and carbon and nitrogen isotope ratios, the comet is similar to other Jupiter-family comets. What is unusual is the dominance of CO 2 -driven activity near perihelion, which likely persists out to aphelion. Near perihelion the comet nucleus was surrounded by a large halo of water-ice grains that contributed significantly to the total water production. © 2011. The American Astronomical Society. All rights reserved..

Background: Asphyxia is one of the most common causes of pediatric cardiac arrest, and becoming a more frequently recognized cause in adults. Periodic acceleration (pGz) is a novel method of cardiopulmonary resuscitation (CPR). pGz is achieved by rapid motion of the supine body headward-footward that generates adequate perfusion and ventilation during cardiac arrest. In a swine ventricular fibrillation cardiac arrest model, pGz produced a higher return of spontaneous circulation (ROSC), superior neurological outcome, less echocardiography evidence of post resuscitation myocardial stunning, and decreased indices of tissue injury. In contrast to standard chest compression CPR, pGz does not produce rib fractures. We investigated the feasibility of pGz in severe asphyxia cardiac arrest and assessed whether beneficial effects seen in the VF model of cardiac arrest could be realized. Methods and Results: Sixteen swine weight 4+/-1 kg were anesthetized, tracheally intubated, and instrumented to measure, hemodynamics and echocardiography. Asphyxia was induced by occlusion of the tracheal tube. After loss of aortic pulsations (median time 10 min) animals were observed for three additional minutes following which all were in cardiac arrest. The animals were then randomized to receive 10 min of pGz or standard chest compression ventilation performed with a commercial device (Thumper). A single dose of epinephrine (adrenaline) and sodium bicarbonate were given and defibrillation attempted if appropriate for a maximum of 10 min. Both groups received fractional inspired O2 concentration of 100% during CPR and after resuscitation. Four animals in each group (50%) had an initial ROSC, however only two of the four initial survivors remained alive 3h after ROSC. There were no significant differences in blood pressure, coronary perfusion pressure during CPR and after early ROSC between groups. pGz treated animals had significantly lower pulmonary artery pressure; 20+/-4 mmHg compared to Thumper 46+/-5 mmHg, 30 min after ROSC (p<0.01). Surviving animals in both groups had severe myocardial dysfunction at 30 min after ROSC. At necropsy, 25% of the Thumper treated animals had rib fractures, while none occurred in the pGz group. Conclusions: In a lethal model of asphyxia cardiac arrest, pGz is equivalent to standard CPR, with respect to acute outcomes and resuscitation survival rates but is associated with significantly lower pulmonary artery pressures and does not produce traumatic rib fractures. [ABSTRACT FROM AUTHOR]

Rationale: Nitric oxide is released from vascular endothelium in response to increased pulsatile shear stress. Nitric oxide inhibits mast cell activation and is antiinflammatory and therefore might be protective in asthma. Objectives: We determined if a noninvasive motion platform that imparts periodic sinusoidal inertial forces to the whole body along the spinal axis (pGz) causing release of endothelial nitric oxide modulates experimental asthma in sheep. Methods: Allergic sheep were untreated (control) or were treated with pGz alone or after receiving intravenously the nitric oxide synthase inhibitor N(w)-nitro-L-arginine methyl ester (L-NAME) before aerosol challenge with Ascaris suum, and the effect on antigen-induced airway responses was determined. Bronchoalveolar lavage cells obtained 6 h after antigen challenge were analyzed for nuclear factor-kappaB (NF-kappaB) activity in the respective groups. Results: pGz treatment for 1 h before antigen challenge reduced the early airway response and blocked the late airway response but did not prevent the antigen-induced airway hyperresponsiveness 24 h after challenge. Administration of L-NAME before pGz completely reversed this protection, whereas L-NAME alone did not affect the antigen-induced responses. NF-kappaB activity was 1.9- and 1.8-fold higher in the control and L-NAME + pGz groups, respectively, compared with pGz-treated animals. Extending the pGz treatment to twice daily for 3 d and then 1 h before antigen challenge blocked the early and late airway responses, the 24-h airway hyperresponsiveness, and the airway inflammatory cell response. Conclusion: Whole-body pGz modulates allergen-induced airway responses in allergic sheep. [ABSTRACT FROM AUTHOR]

The Rutherford Appleton Laboratory (RAL) runs the UK Tier-1 which supports all the LHC experiments, as well as a growing number of others in HEP, Astronomy and Space Science. In September 2020, RAL was provided with funds to upgrade its network. The Tier-1 not only wants to meet the demands of LHC Run 3, it also wants to ensure that it can take an active role in data lake development and the network data challenges in the preparation for HL-LHC. It was therefore decided to completely rebuild the Tier-1 network with a Spine / Leaf architecture. This paper describes the network requirements and design decision that went into building the new Tier-1 network. It also includes a cost analysis, to understand if the ever increasing network requirements are deliverable in a continued flat cash environment and what limitations or opportunities this may place on future data lakes.

BACKGROUND. Studies of alleged victims of child sexual abuse vary greatly in the reported frequency of physical findings based on differences in definition of abuse and of 'findings.' This study was designed to determine the frequency of abnormal findings in a population of children with legal confirmation of sexual abuse, using a standardized classification system for colposcopic photographic findings. METHODS. Case files and colposcopic photographs of 236 children with perpetrator conviction for sexual abuse, were reviewed. The photos were reviewed blindly by a team member other than the examiner, and specific anatomical findings were noted and classified as normal to abnormal on a scale of 1 to 5. Historical and behavioral information, as well as legal outcome was recorded, and all data entered into a dBase III program. Correlations were sought between abnormal findings and other variables. RESULTS. The mean age of the patients was 9.0 years (range 8 months to 17 years, 11 months), with 63% reporting penile-genital contact. Genital examination findings in girls were normal in 28%, nonspecific in 49%, suspicious in 9%, and abnormal in 14% of cases. Abnormal anal findings were found in only 1% of patients. Using discriminant analysis, the two factors which significantly correlated with the presence of abnormal genital findings in girls were the time since the last incident, and a history of blood being reported at the time of the molest. CONCLUSIONS. Abnormal genital findings are not common in sexually abused girls, based on a standardized classification system. More emphasis should be placed on documenting the child's description of the molestation, and educating prosecutors that, for children alleging abuse: 'It's normal to be normal.' [ABSTRACT FROM AUTHOR]

A new database of proton episode-integrated fluences is described. This database contains data from two different instruments on multiple satellites. The data are from instruments on the Interplanetary Monitoring Platform-8 (IMP8) and the Geostationary Operational Environmental Satellites (GOES) series. A method to normalize one set of data to one another is presented to create a seamless database spanning 1973 to 2016. A discussion of some of the characteristics that episodes exhibit is presented, including episode duration and number of peaks. As an example of what can be understood about episodes, the July 4, 2012 episode is examined in detail. The coronal mass ejections and solar flares that caused many of the fluctuations of the proton flux seen at Earth are associated with peaks in the proton flux during this episode. The reasoning for each choice is laid out to provide a reference for how CME and solar flares associations are made.

Abstract Background Vitamin/mineral supplements are among the most commonly used treatments for autism, but the research on their use for treating autism has been limited. Method This study is a randomized, double-blind, placebo-controlled three month vitamin/mineral treatment study. The study involved 141 children and adults with autism, and pre and post symptoms of autism were assessed. None of the participants had taken a vitamin/mineral supplement in the two months prior to the start of the study. For a subset of the participants (53 children ages 5-16) pre and post measurements of nutritional and metabolic status were also conducted. Results The vitamin/mineral supplement was generally well-tolerated, and individually titrated to optimum benefit. Levels of many vitamins, minerals, and biomarkers improved/increased showing good compliance and absorption. Statistically significant improvements in metabolic status were many including: total sulfate (+17%, p = 0.001), S-adenosylmethionine (SAM; +6%, p = 0.003), reduced glutathione (+17%, p = 0.0008), ratio of oxidized glutathione to reduced glutathione (GSSG:GSH; -27%, p = 0.002), nitrotyrosine (-29%, p = 0.004), ATP (+25%, p = 0.000001), NADH (+28%, p = 0.0002), and NADPH (+30%, p = 0.001). Most of these metabolic biomarkers improved to normal or near-normal levels. The supplement group had significantly greater improvements than the placebo group on the Parental Global Impressions-Revised (PGI-R, Average Change, p = 0.008), and on the subscores for Hyperactivity (p = 0.003), Tantrumming (p = 0.009), Overall (p = 0.02), and Receptive Language (p = 0.03). For the other three assessment tools the difference between treatment group and placebo group was not statistically significant. Regression analysis revealed that the degree of improvement on the Average Change of the PGI-R was strongly associated with several biomarkers (adj. R2 = 0.61, p < 0.0005) with the initial levels of biotin and vitamin K being the most significant (p < 0.05); both biotin and vitamin K are made by beneficial intestinal flora. Conclusions Oral vitamin/mineral supplementation is beneficial in improving the nutritional and metabolic status of children with autism, including improvements in methylation, glutathione, oxidative stress, sulfation, ATP, NADH, and NADPH. The supplement group had significantly greater improvements than did the placebo group on the PGI-R Average Change. This suggests that a vitamin/mineral supplement is a reasonable adjunct therapy to consider for most children and adults with autism. Trial Registration Clinical Trial Registration Number: NCT01225198

Abstract We present the first case of a head and neck oncological procedure accomplished in a Jehovah's Witness using the Ultracision Harmonic Scalpel (Ethicon, Cincinnati, OH). Jehovah's Witnesses present a serious challenge to the head and neck cancer surgeon due to their refusal to accept transfusion of any blood products. However, our experience reinforces the view that surgical management of head and neck cancer is possible in these patients. We show the Harmonic Scalpel, an ultrasonic tissue dissector, to be a useful surgical tool in obviating the need for blood transfusion. Preoperative optimisation, intra-operative surgical and anaesthetic techniques are also fully discussed.

Abstract Background The relationship between relative metabolic disturbances and developmental disorders is an emerging research focus. This study compares the nutritional and metabolic status of children with autism with that of neurotypical children and investigates the possible association of autism severity with biomarkers. Method Participants were children ages 5-16 years in Arizona with Autistic Spectrum Disorder (n = 55) compared with non-sibling, neurotypical controls (n = 44) of similar age, gender and geographical distribution. Neither group had taken any vitamin/mineral supplements in the two months prior to sample collection. Autism severity was assessed using the Pervasive Development Disorder Behavior Inventory (PDD-BI), Autism Treatment Evaluation Checklist (ATEC), and Severity of Autism Scale (SAS). Study measurements included: vitamins, biomarkers of vitamin status, minerals, plasma amino acids, plasma glutathione, and biomarkers of oxidative stress, methylation, sulfation and energy production. Results Biomarkers of children with autism compared to those of controls using a t-test or Wilcoxon test found the following statistically significant differences (p < 0.001): Low levels of biotin, plasma glutathione, RBC SAM, plasma uridine, plasma ATP, RBC NADH, RBC NADPH, plasma sulfate (free and total), and plasma tryptophan; also high levels of oxidative stress markers and plasma glutamate. Levels of biomarkers for the neurotypical controls were in good agreement with accessed published reference ranges. In the Autism group, mean levels of vitamins, minerals, and most amino acids commonly measured in clinical care were within published reference ranges. A stepwise, multiple linear regression analysis demonstrated significant associations between several groups of biomarkers with all three autism severity scales, including vitamins (adjusted R2 of 0.25-0.57), minerals (adj. R2 of 0.22-0.38), and plasma amino acids (adj. R2 of 0.22-0.39). Conclusion The autism group had many statistically significant differences in their nutritional and metabolic status, including biomarkers indicative of vitamin insufficiency, increased oxidative stress, reduced capacity for energy transport, sulfation and detoxification. Several of the biomarker groups were significantly associated with variations in the severity of autism. These nutritional and metabolic differences are generally in agreement with other published results and are likely amenable to nutritional supplementation. Research investigating treatment and its relationship to the co-morbidities and etiology of autism is warranted.

Abstract Background Despite the high prevalence of seizure, epilepsy and abnormal electroencephalograms in individuals with autism spectrum disorder (ASD), there is little information regarding the relative effectiveness of treatments for seizures in the ASD population. In order to determine the effectiveness of traditional and non-traditional treatments for improving seizures and influencing other clinical factor relevant to ASD, we developed a comprehensive on-line seizure survey. Methods Announcements (by email and websites) by ASD support groups asked parents of children with ASD to complete the on-line surveys. Survey responders choose one of two surveys to complete: a survey about treatments for individuals with ASD and clinical or subclinical seizures or abnormal electroencephalograms, or a control survey for individuals with ASD without clinical or subclinical seizures or abnormal electroencephalograms. Survey responders rated the perceived effect of traditional antiepileptic drug (AED), non-AED seizure treatments and non-traditional ASD treatments on seizures and other clinical factors (sleep, communication, behavior, attention and mood), and listed up to three treatment side effects. Results Responses were obtained concerning 733 children with seizures and 290 controls. In general, AEDs were perceived to improve seizures but worsened other clinical factors for children with clinical seizure. Valproic acid, lamotrigine, levetiracetam and ethosuximide were perceived to improve seizures the most and worsen other clinical factors the least out of all AEDs in children with clinical seizures. Traditional non-AED seizure and non-traditional treatments, as a group, were perceived to improve other clinical factors and seizures but the perceived improvement in seizures was significantly less than that reported for AEDs. Certain traditional non-AED treatments, particularly the ketogenic diet, were perceived to improve both seizures and other clinical factors. For ASD individuals with reported subclinical seizures, other clinical factors were reported to be worsened by AEDs and improved by non-AED traditional seizure and non-traditional treatments. The rate of side effects was reportedly higher for AEDs compared to traditional non-AED treatments. Conclusion Although this survey-based method only provides information regarding parental perceptions of effectiveness, this information may be helpful for selecting seizure treatments in individuals with ASD.

Abstract Background Children with autism have often been reported to have gastrointestinal problems that are more frequent and more severe than in children from the general population. Methods Gastrointestinal flora and gastrointestinal status were assessed from stool samples of 58 children with Autism Spectrum Disorders (ASD) and 39 healthy typical children of similar ages. Stool testing included bacterial and yeast culture tests, lysozyme, lactoferrin, secretory IgA, elastase, digestion markers, short chain fatty acids (SCFA's), pH, and blood presence. Gastrointestinal symptoms were assessed with a modified six-item GI Severity Index (6-GSI) questionnaire, and autistic symptoms were assessed with the Autism Treatment Evaluation Checklist (ATEC). Results Gastrointestinal symptoms (assessed by the 6-GSI) were strongly correlated with the severity of autism (assessed by the ATEC), (r = 0.59, p < 0.001). Children with 6-GSI scores above 3 had much higher ATEC Total scores than those with 6-GSI-scores of 3 or lower (81.5 +/- 28 vs. 49.0 +/- 21, p = 0.00002). Children with autism had much lower levels of total short chain fatty acids (-27%, p = 0.00002), including lower levels of acetate, proprionate, and valerate; this difference was greater in the children with autism taking probiotics, but also significant in those not taking probiotics. Children with autism had lower levels of species of Bifidobacter (-43%, p = 0.002) and higher levels of species of Lactobacillus (+100%, p = 0.00002), but similar levels of other bacteria and yeast using standard culture growth-based techniques. Lysozyme was somewhat lower in children with autism (-27%, p = 0.04), possibly associated with probiotic usage. Other markers of digestive function were similar in both groups. Conclusions The strong correlation of gastrointestinal symptoms with autism severity indicates that children with more severe autism are likely to have more severe gastrointestinal symptoms and vice versa. It is possible that autism symptoms are exacerbated or even partially due to the underlying gastrointestinal problems. The low level of SCFA's was partly associated with increased probiotic use, and probably partly due to either lower production (less sacchrolytic fermentation by beneficial bacteria and/or lower intake of soluble fiber) and/or greater absorption into the body (due to longer transit time and/or increased gut permeability).

Abstract Introduction Autism is complex neuro-developmental disorder which has a symptomatic diagnosis in patients characterized by disorders in language/communication, behavior, and social interactions. The exact causes for autism are largely unknown, but is has been speculated that immune and inflammatory responses, particularly those of Th2 type, may be involved. Thiazolidinediones (TZDs) are agonists of the peroxisome proliferator activated receptor gamma (PPARγ), a nuclear hormone receptor which modulates insulin sensitivity, and have been shown to induce apoptosis in activated T-lymphocytes and exert anti-inflammatory effects in glial cells. The TZD pioglitazone (Actos) is an FDA-approved PPARγ agonist used to treat type 2 diabetes, with a good safety profile, currently being tested in clinical trials of other neurological diseases including AD and MS. We therefore tested the safety and therapeutic potential of oral pioglitazone in a small cohort of children with diagnosed autism. Case description The rationale and risks of taking pioglitazone were explained to the parents, consent was obtained, and treatment was initiated at either 30 or 60 mg per day p.o. A total of 25 children (average age 7.9 ± 0.7 year old) were enrolled. Safety was assessed by measurements of metabolic profiles and blood pressure; effects on behavioral symptoms were assessed by the Aberrant Behavior Checklist (ABC), which measures hyperactivity, inappropriate speech, irritability, lethargy, and stereotypy, done at baseline and after 3–4 months of treatment. Discussion and evaluation In a small cohort of autistic children, daily treatment with 30 or 60 mg p.o. pioglitazone for 3–4 months induced apparent clinical improvement without adverse events. There were no adverse effects noted and behavioral measurements revealed a significant decrease in 4 out of 5 subcategories (irritability, lethargy, stereotypy, and hyperactivity). Improved behaviors were inversely correlated with patient age, indicating stronger effects on the younger patients. Conclusion Pioglitazone should be considered for further testing of therapeutic potential in autistic patients.

Abstract Salvia miltiorrhiza (Labiatae, Laminaceae), danshen, is an annual sage mainly found in China and neighboring countries. The crude drug (dried root) and its preparations are currently used in China to treat patients suffering from heart attack, angina pectoris, stroke and some other conditions. The use of S. miltiorrhiza has been increasing in the management of stroke. Pharmacological examinations showed that the plant and its active ingredients, tanshinones and salvianolic acids, have anticoagulant, vasodilatory, increased blood flow, anti-inflammatory, free radical scavenging, mitochondrial protective and other activities. This review discusses the pharmacology, medicinal chemistry and clinical studies published, especially in China, for danshen and tanshinone preparations. Clinical examinations are evaluated in terms of S. miltiorrhiza preparation, dose, double blinding, control, clinical assessments of outcomes and other parameters. Meta-analyses of S. miltiorrhiza are also discussed.

Abstract Background This study was designed to evaluate if erythropoietin (EPO) is effective in the treatment of cancer related anemia, and if its effect remains unchanged when data are analyzed according to various clinical and methodological characteristics of the studies. We also wanted to demonstrate that cumulative meta-analysis (CMA) can be used to resolve uncertainty regarding clinical questions. Methods Systematic Review (SR) of the published literature on the role of EPO in cancer-related anemia. A cumulative meta-analysis (CMA) using a conservative approach was performed to determine the point in time when uncertainty about the effect of EPO on transfusion-related outcomes could be considered resolved. Participants: Patients included in randomized studies that compared EPO versus no therapy or placebo. Main outcome measures: Number of patients requiring transfusions. Results Nineteen trials were included. The pooled results indicated a significant effect of EPO in reducing the number of patients requiring transfusions [odds ratio (OR) = 0.41; 95%CI: 0.33 to 0.5; p < 0.00001;relative risk (RR) = 0.61; 95% CI: 0.54 to 0.68]. The results remain unchanged after the sensitivity analyses were performed according to the various clinical and methodological characteristics of the studies. The heterogeneity was less pronounced when OR was used instead of RR as the measure of the summary point estimate. Analysis according to OR was not heterogeneous, but the pooled RR was highly heterogeneous. A stepwise metaregression analysis did point to the possibility that treatment effect could have been exaggerated by inadequacy in allocation concealment and that larger treatment effects are seen at hb level > 11.5 g/dl. We identified 1995 as the point in time when a statistically significant effect of EPO was demonstrated and after which we considered that uncertainty about EPO efficacy was resolved. Conclusion EPO is effective in the treatment of anemia in cancer patients. This could have already been known in 1995 if a CMA had been performed at that time.

The endothelium is a viable target for injury, repair and cellular modulation. Because of its vast extension and active metabolic status of producing mediators for vasomotor tone, coagulation, and inflammation, it is a key target for therapy during ischemia/reperfusion injury. Cardiopulmonary resuscitation is a model of whole-body ischemia/reperfusion injury. It has become apparent that the endothelium participates in a host of responses elicited by ischemia/reperfusion. This review examines the role of the endothelium during and after ischemia/reperfusion and the participation by its mediators and evidence for endothelial involvement during and after cardiopulmonary resuscitation. The strategic location of the endothelium makes it an excellent signal transduction mechanism for a host of disease processes. In addition to biochemical stimuli, mechanical stimulation of the endothelium elicits production of several mediators, including endothelium-derived nitric oxide, prostaglandins, and antithrombotics and anticoagulants. Whole-body, periodic acceleration is a novel method of stimulating the endothelium via pulsatile shear stress. Periodic acceleration has been shown to be an effective experimental method of cardiopulmonary resuscitation, with evidence of postresuscitation cardioprotective effects. This review indicates that understanding endothelial modulation during and after ischemia/reperfusion will significantly improve therapeutic choices. [ABSTRACT FROM AUTHOR]

Background: Hepatitis A is a disease of public health significance that typically causes acute, self-limiting infection. Understanding the risk factors and demographics associated with individual infections and outbreaks can guide public health communication and interventions., Objective: To assess the number of hepatitis A cases and outbreaks in Ontario from January 1, 2015, to November 22, 2022, and to identify common risk factors associated with sporadic and outbreak-associated infections in Ontario., Methods: Confirmed and probable hepatitis A cases reported between January 1, 2015, and November 22, 2022, were extracted from the Ontario electronic reporting system. Descriptive analyses were used to summarize and compare risk factors reported by sporadic and outbreak-associated hepatitis A cases. Annual rates of infection for individual public health units were calculated using annual population estimates for Ontario health regions., Results: During the study period, 938 cases of hepatitis A were reported in Ontario (an average annual rate of 0.9 cases per 100,000 population), with 31.3% (n=294) of cases linked to one of 18 unique outbreaks of hepatitis A. Four of 13 local outbreaks were associated with elementary school settings. Reported risk factors differed between sporadic cases (predominantly travel-related) and cases linked to known outbreaks (anal-oral contact, illicit drug use, diapering/assisting in toileting, close contact with a case). Rates of sporadic infection differed across public health units in Ontario over the study period., Conclusion: Public health interventions that aim to increase awareness of hepatitis A risk factors and increase vaccine uptake among those at increased risk of exposure could help to reduce the incidence of both locally acquired and travel-related sporadic infections and outbreaks., Competing Interests: Competing interests The authors declare that they have no competing interests.

Urea cycle impairment and its relationship to obesity and inflammation remained elusive, partly due to the dramatic clinical presentation of classical urea cycle defects. We generated mice with hepatocyte-specific arginase 2 deletion (Arg2 LKO ) and revealed a mild compensated urea cycle defect. Stable isotope tracing and respirometry revealed hepatocyte urea and TCA cycle flux defects, impaired mitochondrial oxidative metabolism, and glutamine anaplerosis despite normal energy and glucose homeostasis during early adulthood. Yet during middle adulthood, chow- and diet-induced obese Arg2 LKO mice develop exaggerated glucose and lipid derangements, which are reversible by replacing the TCA cycle oxidative substrate nicotinamide adenine dinucleotide. Moreover, serum-based hallmarks of urea, TCA cycle, and mitochondrial derangements predict incident fibroinflammatory liver disease in 106,606 patients nearly a decade in advance. The data reveal hierarchical urea-TCA cycle control via ARG2 to drive oxidative metabolism. Moreover, perturbations in this circuit may causally link urea cycle compromise to fibroinflammatory liver disease., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Undergraduate introductory human anatomy and human physiology courses are either taught as discipline-specific or integrated anatomy and physiology (A&P) sequences. An institution underwent a curricular revision to change the course approach from discipline-specific Human Anatomy and Human Physiology to an integrated A&P I and II sequence, allowing the unique opportunity to explore the potential role of contextual learning in academic achievement and content retention. Mediation and moderation analysis was used to evaluate lecture examinations, laboratory practical examinations, and anatomical content retention between the different course approaches. Undergraduate students in the integrated A&P I course approach performed significantly better on lecture assessments and had a higher anatomy content retention rate at the end of the year than students enrolled in the standalone Human Anatomy course. The lecture examination averages between Human Physiology and A&P II (the second course in the sequence), as well as the anatomy laboratory practical examinations, were not significantly different between discipline-specific and integrated course approaches. The results suggest contextual learning-providing physiological context to anatomical structures-increases the anatomical content retention and academic achievement overall., (© 2024 American Association for Anatomy.)

Background: The rates and risk factors for wound complications following staged reconstruction after facial lentigo maligna (LM) resection have not been well described. Objectives: (1) To identify the rate and types of wound complications, including infection, graft necrosis, distal flap necrosis, hematoma, superficial epidermolysis, and seroma among patients undergoing staged reconstruction after resection of LM as documented in the surgeon's clinical notes within 30 days of the procedure. (2) To determine a threshold defect size that may predict the development of wound complications. Design and Outcomes: Retrospective review at an academic medical center of patients who underwent staged reconstruction after facial LM resection over a 5-year period. Results: Ninety-eight patients were identified with a mean age of 69.2 ± 13.6 years; 37% of patients were female. The most common defect sites were the cheek ( n = 41; 42%) and nose ( n = 22; 22%). Twenty-five of 98 patients (26%) demonstrated complications, with the most common being wound infection (36%) and graft necrosis (24%). Those receiving perioperative antibiotics had lower rates of complication (odds ratio [OR]: 0.36; 95% confidence interval [CI]: 0.13,0.96; p = 0.041). Defects greater than 2.7 cm in maximal diameter had the highest sensitivity for predicting complications. Conclusions: Patients undergoing staged reconstruction after facial LM resection have a high rate of wound complication (26%) and defect size > 2.7 cm may be an important risk factor.

Objective: To identify the impact of race, ethnicity, and socioeconomic status (SES) on the rate of tympanostomy tube placement., Study Design: Retrospective medical review and population-level analyses., Setting: Tertiary referral center., Methods: Demographic and population-level characteristics (age, gender, race, insurance status, and ZIP code) compared to the regional, health system, and otolaryngology clinic demographics., Results: Among 38,461 children diagnosed with otitis media (OM) 61.4% were white, 27.4% were black, 32.7% had private insurance, and 18.2% were Hispanic. Among patients seen in the pediatric ear, nose, and throat (ENT) clinics, 70.0% were white, 20.0% were black, 46.6% had private insurance, and 14.9% were Hispanic. Further disparity was noted among those receiving tympanostomy tubes: 75.6% white, 15.6% black, 61.9% private insurance, and 11.7% Hispanic. Higher rates of tube placement were noted for those of white race [odds ratio, OR: 1.96, (95% confidence interval, CI: 1.85-2.04), <.001] and non-Hispanic ethnicity [OR: 1.67, (95% CI: 1.56-1.75), <.001]. Geographically, rates of tube placement were significantly lower in areas with higher deprivation indices, areas with lower proportions of white residents, and areas with the lowest median incomes. These markers correlate strongly with black race and Hispanic ethnicity. Lower rates of tube placement were also seen in majority white locales with higher deprivation indices and lower median incomes., Conclusion: Rates of access to pediatric ENT clinics, and of tube placement, are significantly lower for those of Hispanic ethnicity and black race than for non-Hispanic white children. Higher rates of tube placement were noted among white children and those with private insurance. Lower rates of tube placement were seen in areas of lower SES regardless of racial demographics., Competing Interests: The authors note no competing interests relevant to this study., (© 2024 The Author(s). OTO Open published by Wiley Periodicals LLC on behalf of American Academy of Otolaryngology–Head and Neck Surgery Foundation.)

Dinoflagellates are diverse and ecologically important protists characterized by many morphological and molecular traits that set them apart from other eukaryotes. These features include, but are not limited to, massive genomes organized using bacterially-derived histone-like proteins (HLPs) and dinoflagellate viral nucleoproteins (DVNP) rather than histones, and a complex history of photobiology with many independent losses of photosynthesis, numerous cases of serial secondary and tertiary plastid gains, and the presence of horizontally acquired bacterial rhodopsins and type II RuBisCo. Elucidating how this all evolved depends on knowing the phylogenetic relationships between dinoflagellate lineages. Half of these species are heterotrophic, but existing molecular data is strongly biased toward the photosynthetic dinoflagellates due to their amenability to cultivation and prevalence in culture collections. These biases make it impossible to interpret the evolution of photosynthesis, but may also affect phylogenetic inferences that impact our understanding of character evolution. Here, we address this problem by isolating individual cells from the Salish Sea and using single cell, culture-free transcriptomics to expand molecular data for dinoflagellates to include 27 more heterotrophic taxa, resulting in a roughly balanced representation. Using these data, we performed a comprehensive search for proteins involved in chromatin packaging, plastid function, and photoactivity across all dinoflagellates. These searches reveal that 1) photosynthesis was lost at least 21 times, 2) two known types of HLP were horizontally acquired around the same time rather than sequentially as previously thought; 3) multiple rhodopsins are present across the dinoflagellates, acquired multiple times from different donors; 4) kleptoplastic species have nucleus-encoded genes for proteins targeted to their temporary plastids and they are derived from multiple lineages, and 5) warnowiids are the only heterotrophs that retain a whole photosystem, although some photosynthesis-related electron transport genes are widely retained in heterotrophs, likely as part of the iron-sulfur cluster pathway that persists in non-photosynthetic plastids., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Nursing faculty have been called to incorporate social determinants of health (SDOH) in nursing courses to equip nurses in better addressing disparities in care and health outcomes., Method: Prior to clinical experiences, students were introduced to concepts of health promotion and the SDOH framework. In the maternal child nursing course, core concepts of reproduction and sexuality were introduced through an SDOH framework lens. Outpatient clinical sites were chosen to provide a comprehensive, health promotion-focused clinical experience., Results: As students immersed themselves in providing care outside of the acute care setting, they assessed specific populations' needs and resources and participated in delivering care that addressed financial and access issues., Conclusion: Incorporating outpatient maternal child clinical experiences broadens students' perspective on health outcomes impacted by SDOH. By implementing health promotion interventions in community settings, students can grasp a more vivid picture of nursing's role and impact outside of hospital walls. [ J Nurs Educ . 2024;63(7):482-484.] .

Purpose: To describe the experiences of registered nurses and certified nurse midwives who provided labor support and care in the early months of the COVID-19 pandemic., Study Design and Methods: A descriptive, qualitative approach was used to explore nurses' and midwives' perceptions via in-depth interviews. Data were analyzed via thematic analysis., Results: Thirteen nurses, four of whom were also midwives, participated in semi-structured interviews. All provided care during the first 9 months of the pandemic and represented seven states across the United States. The analysis revealed an overarching theme, A New World but still a Celebration. This overarching theme encompasses participants' accounts of trying to provide the same support, presence, and celebration while dealing with constant policy changes, the impact of limited family presence in labor, and their own fears and risks. Four sub-themes were identified: The Impact of Nursing during COVID-19; Challenges, Changes, and Consequences; Unexpected Benefits; and The Cost., Clinical Implications: The first year of the COVID-19 pandemic saw unprecedented challenges for nurses. Practice changes due to these changing policies had negative and positive effects. Negative practices affected family support, decreased interprofessional collaboration, and caused shorter hospital stays for new mothers. Some positive aspects of practice changes included additional time for mother-newborn bonding due to restrictive visitation policies, increased initiation of breastfeeding, and focused patient education. Nurses across the United States are still coping with practice changes from the pandemic. Our study highlights the need to support nurses in adapting care in the midst of practice changes., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: Obstructive sleep apnea (OSA) is associated with metabolic, cardiovascular, and cerebrovascular comorbidities. Appropriate diagnosis and treatment of OSA might mitigate these comorbidities. This retrospective review sought to assess the impact of sex, age, race, ethnicity, and insurance status on polysomnography (PSG) referral rates., Methods: An institutional STOP-Bang database of 299,320 patients was filtered for patients admitted to the hospital with an acute cardiac diagnosis between 2015-2020. A cohort of 4,735 patients were risk stratified by STOP-Bang (SB) score and correlations were made between PSG referrals and demographic and clinical variables (sex, age, race, ethnicity, and insurance status)., Results: Of the 25.3% of the cohort with high SB scores (5-8) only 21.3% were referred for PSG. Age and female sex were negatively associated with sleep study referrals (p < 0.001). No correlation was found between sleep study referral rates and race or ethnicity. No correlation was found between sleep study referrals and insurance provider. Admitting cardiac diagnosis significantly influenced sleep study referrals with diagnoses of arrhythmias and myocardial infarction being associated with an increased rate of PSG referrals compared to heart failure patients (p < 0.002)., Conclusions: Our study found no significant correlation between PSG referral rates and race, ethnicity, or insurance provider. However, we found low overall rates of PSG referral, with negative correlations between older age and female sex and a high-risk cardiac population. This represents a substantial missed opportunity to identify patients at risk for OSA, obtain a diagnosis, and provider adequate treatment., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

The alternative splicing of PML precursor mRNA gives rise to various PML isoforms, yet their expression profile in breast cancer cells remains uncharted. We discovered that PML1 is the most abundant isoform in all breast cancer subtypes, and its expression is associated with unfavorable prognosis in estrogen receptor-positive (ER+) breast cancers. PML depletion reduces cell proliferation, invasion, and stemness, while heterologous PML1 expression augments these processes and fuels tumor growth and resistance to fulvestrant, an FDA-approved drug for ER+ breast cancer, in a mouse model. Moreover, PML1, rather than the well-known tumor suppressor isoform PML4, rescues the proliferation of PML knockdown cells. ChIP-seq analysis reveals significant overlap between PML-, ER-, and Myc-bound promoters, suggesting their coordinated regulation of target gene expression, including genes involved in breast cancer stem cells (BCSCs), such as JAG1, KLF4, YAP1, SNAI1, and MYC. Loss of PML reduces BCSC-related gene expression, and exogenous PML1 expression elevates their expression. Consistently, PML1 restores the association of PML with these promoters in PML-depleted cells. We identified a novel association between PML1 and WDR5, a key component of H3K4 methyltransferase (HMTs) complexes that catalyze H3K4me1 and H3K4me3. ChIP-seq analyses showed that the loss of PML1 reduces H3K4me3 in numerous loci, including BCSC-associated gene promoters. Additionally, PML1, not PML4, re-establishes the H3K4me3 mark on these promoters in PML-depleted cells. Significantly, PML1 is essential for recruiting WDR5, MLL1, and MLL2 to these gene promoters. Inactivating WDR5 by knockdown or inhibitors phenocopies the effects of PML1 loss, reducing BCSC-related gene expression and tumorsphere formation and enhancing fulvestrant's anticancer activity. Our findings challenge the conventional understanding of PML as a tumor suppressor, redefine its role as a promoter of tumor growth in breast cancer, and offer new insights into the unique roles of PML isoforms in breast cancer., (© 2024. The Author(s).)

National pharmacy associations have increasingly explored regulation according to a "standard of care." In such a model, pharmacists can provide a wide range of clinical services aligned with their education and training. Based on Idaho's experience implementing this model, there are five critical steps states must take to enact a standard of care: 1) Adopt a broad definition of "practice of pharmacy;" 2) Allow elasticity for practice innovation over time; 3) Decide which limited instances still necessitate prescriptive regulation; 4) Eliminate all unnecessary regulations; and 5) Strengthen accountability for deviations from the standard of care. States wishing to adopt a standard of care approach can follow this five-step process to enhance patient care and mitigate the lag that is otherwise constant between laws and practice., Competing Interests: Disclosure The authors declare no relevant conflicts of interest or financial relationships., (Copyright © 2024 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.)

Objectives: Limited research exists evaluating the impact of social determinants of health in influencing care pathways for patients with dysphagia. A better understanding of whether these determinants correlate to altered care and resource utilization is essential as it relates to patient outcomes., Study Design: Retrospective chart review., Methods: All adult patients seen at a tertiary midwestern hospital were screened for ICD codes of dysphagia diagnoses from 2009 to 2019. Demographic information was collected from these patients with dysphagia including sex, race, ethnicity, and insurance status. Subgroup analysis was performed to assess referral pattern rates and types of diagnostic interventions ordered (none, videofluoroscopic swallow study, esophagram, and esophagogastroduodenoscopy)., Results: A total of 31,858 patients with dysphagia were seen at our institution during the study period, with a majority being female (56.36%), Caucasian (79.83%), and publicly insured (63.16%), at a median age of 60.35 years. There were no significant care delivery pattern differences based on geography/zip code analyses. African American patients were significantly more likely to have imaging or interventions performed (odds ratio [OR] 1.463, p = 0.005). Patients with public insurance also had higher rates of diagnostic study utilization (OR 1.53, p = 0.01). Only 3% of all patients with dysphagia were seen by laryngologists., Conclusion: No significant differences were seen in dysphagia evaluation modalities based on zip code analyses surrounding this tertiary care facility. African American patients and those with public insurance had significantly higher utilization of subsequent testing and intervention for dysphagia care. Further studies are necessary to delineate causes and outcome differences for these measurable differences in dysphagia care pathways., Level of Evidence: 4 Laryngoscope, 134:1139-1146, 2024., (© 2023 The American Laryngological, Rhinological and Otological Society, Inc.)

Src-homology-2-domain-containing PTP-2 (SHP2) is a widely expressed signaling enzyme whose misregulation is associated with multiple human pathologies. SHP2's enzymatic activity is controlled by a conformational equilibrium between its autoinhibited ("closed") state and its activated ("open") state. Although SHP2's closed state has been extensively characterized, the putative structure of its open form has only been revealed in the context of a highly activated mutant (E76K), and no systematic studies of the biochemical determinants of SHP2's open-state stabilization have been reported. To identify amino-acid interactions that are critical for stabilizing SHP2's active state, we carried out a mutagenic study of residues that lie at potentially important interdomain interfaces of the open conformation. The open/closed equilibria of the mutants were evaluated, and we identified several interactions that contribute to the stabilization of SHP2's open state. In particular, our findings establish that an ion pair between glutamate 249 on SHP2's PTP domain and arginine 111 on an interdomain loop is the key determinant of SHP2's open-state stabilization. Mutations that disrupt the R111/E249 ion pair substantially shift SHP2's open/closed equilibrium to the closed state, even compared to wild-type SHP2's basal-state equilibrium, which strongly favors the closed state. To the best of our knowledge, the ion-pair variants uncovered in this study are the first known SHP2 mutants in which autoinhibition is augmented with respect to the wild-type protein. Such "hyperinhibited" mutants may provide useful tools for signaling studies that investigate the connections between SHP2 inhibition and the suppression of human disease progression.

Background: Postoperative cognitive dysfunction (POCD) is a common disorder after general anesthesia in elderly patients, the precise mechanisms of which remain unclear. Methods: We investigated the effect of isoflurane with or without dantrolene pretreatment on intracellular calcium concentration ([Ca 2+ ] i ), reactive oxygen species (ROS) production, cellular lactate dehydrogenase (LDH) leak, calpain activity, and cognitive function using the Morris water maze test of young (3 months), middle-aged (12-13 months), and aged (24-25 months) C57BL6/J mice. Results: Aged cortical and hippocampal neurons showed chronically elevated [Ca 2+ ] i compared to young neurons. Furthermore, aged hippocampal neurons exhibited higher ROS production, increased LDH leak, and elevated calpain activity. Exposure to isoflurane exacerbated these markers in aged neurons, contributing to increased cognitive deficits in aged mice. Dantrolene pretreatment reduced [Ca 2+ ] i for all age groups and prevented or significantly mitigated the effects of isoflurane on [Ca 2+ ] i , ROS production, LDH leak, and calpain activity in aged neurons. Dantrolene also normalized or improved age-associated cognitive deficits and mitigated the cognitive deficits caused by isoflurane. Conclusions: These findings suggest that isoflurane-induced cytotoxicity and cognitive decline in aging are linked to disruptions in neuronal intracellular processes, highlighting the reduction of [Ca 2+ ] i as a potential therapeutic intervention.

Alzheimer's disease (AD) affects more than 40 million people worldwide and is the leading cause of dementia. This disease is a challenge for both patients and caregivers and puts a significant strain on the global healthcare system. To address this issue, the Lancet Commission recommends focusing on reducing modifiable lifestyle risk factors such as hypertension, diabetes, and physical inactivity. Passive pulsatile shear stress (PPSS) interventions, which use devices like whole-body periodic acceleration, periodic acceleration along the Z-axis (pGz), and the Jogging Device, have shown significant systemic and cellular effects in preclinical and clinical models which address these modifiable risks factors. Based on this, we propose that PPSS could be a potential non-pharmacological and non-invasive preventive or therapeutic strategy for AD. We perform a comprehensive review of the biological basis based on all publications of PPSS using these devices and demonstrate their effects on the various aspects of AD. We draw from this comprehensive analysis to support our hypothesis. We then delve into the possible application of PPSS as an innovative intervention. We discuss how PPSS holds promise in ameliorating hypertension and diabetes while mitigating physical inactivity, potentially offering a holistic approach to AD prevention and management.

Background & Aims: Restoring hepatic and peripheral insulin sensitivity is critical to prevent or reverse metabolic syndrome and type 2 diabetes. Glucose homeostasis comprises in part the complex regulation of hepatic glucose production and insulin-mediated glucose uptake and oxidation in peripheral tissues. We previously identified hepatocyte arginase 2 (Arg2) as an inducible ureahydrolase that improves glucose homeostasis and enhances glucose oxidation in multiple obese, insulin-resistant models. We therefore examined structure-function determinants through which hepatocyte Arg2 governs systemic insulin action and glucose oxidation., Methods: To do this, we generated mice expressing wild-type murine Arg2, enzymatically inactive Arg2 (Arg2 H160F ) and Arg2 lacking its putative mitochondrial targeting sequence (Arg2 Δ1-22 ). We expressed these hepatocyte-specific constructs in obese, diabetic (db/db) mice and performed genetic complementation analyses in hepatocyte-specific Arg2-deficent (Arg2 LKO ) mice., Results: We show that Arg2 attenuates hepatic steatosis, independent of mitochondrial localization or ureahydrolase activity, and that enzymatic arginase activity is dispensable for Arg2 to augment total body energy expenditure. In contrast, mitochondrial localization and ureahydrolase activity were required for Arg2-mediated reductions in fasting glucose and insulin resistance indices. Mechanistically, Arg2 Δ1-22 and Arg2 H160F failed to suppress glucose appearance during hyperinsulinemic-euglycemic clamping. Quantification of heavy-isotope-labeled glucose oxidation further revealed that mistargeting or ablating Arg2 enzymatic function abrogates Arg2-induced peripheral glucose oxidation., Conclusion: We conclude that the metabolic effects of Arg2 extend beyond its enzymatic activity, yet hepatocyte mitochondrial ureahydrolysis drives hepatic and peripheral oxidative metabolism. The data define a structure-based mechanism mediating hepatocyte Arg2 function and nominate hepatocyte mitochondrial ureahydrolysis as a key determinant of glucose oxidative capacity in mammals., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: To identify the impact of social determinants of health and clinical status on referral and intervention for congenital sensorineural hearing loss., Study Design: Retrospective chart review of children with confirmed sensorineural or mixed hearing loss between 2013 and 2021 at a single academic medical institution., Methods: Referral rates and timing for hearing rehabilitation, rates and timing of completed evaluation, and rate and timing of amplification were recorded. Patient demographics included gestational age, race, ethnicity, sex, hearing loss severity, and CMV status., Results: There were 216 children with confirmed sensorineural or mixed hearing loss, of which 77 had a unilateral hearing loss and 89 a severe or profound hearing loss. Delayed referral for hearing aid evaluation was noted in premature patients (median 375 days premature, median 147 term; p < 0.01) and publicly insured patients (median 215 days, median 123 private; p = 0.04). Delayed time to hearing aid fitting was noted for non-white patients (median 325 days, median 203 white patients; p < 0.01), publicly insured patients (median 309 days, median 212 private insurance; p < 0.02), and premature patients (median 462 days, median 224 term; p = 0.03). White patients were more likely to be referred for cochlear implant (p = 0.03).Privately insured patients and patients with a positive CMV test were more likely to be referred for cochlear implant evaluation, be seen in the cochlear implant clinic, and undergo implantation (p < 0.05). Non-white patients had a delay in cochlear implantation referral (median 928 days, median 398 days white patients; p = 0.05). Prolonged interval between evaluation in cochlear implant clinic to implantation was noted for privately insured patients (median 125 days; median 78 days publicly insured; p = 0.05)., Conclusions: Sociodemographic factors were significantly associated with hearing amplification referral rates and time until amplification for children with identified congenital sensorineural hearing loss. For cochlear implantation, insurance type, CMV status were significantly associated with rate and timing of cochlear implant pathway., Competing Interests: Declaration of competing interest None., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The amount of nitrogen stored in terrestrial soils, its "nitrogen pool", moderates biogeochemical cycling affecting primary productivity, nitrogen pollution and even carbon budgets. The soil nitrogen pools and the transformation of nitrogen forms within them are heavily influenced by environmental factors including anthropogenic activities. However, our understanding of the global distribution of soil nitrogen with respect to anthropogenic activity and human land use remains unclear. We constructed a meta-analysis from a global sampling, in which we compare soil total nitrogen pools and the driving mechanisms affecting each pool across three major classifications of human land use: natural, agricultural, and urban. Although the size of the nitrogen pool can be similar across natural, agricultural and urban soils, the ecological and human associated drivers vary. Specifically, the drivers within agricultural and urban soils as opposed to natural soils are more complex and often decoupled from climatic and soil factors. This suggests that the nitrogen pools of those soils may be co-moderated by other factors not included in our analyses, like human activities. Our analysis supports the notion that agricultural soils act as a nitrogen source while urban soils as a nitrogen sink and informs a modern understanding of the fates and distributions of anthropogenic nitrogen in natural, agricultural, and urban soils., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)