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Introduction Fluid resuscitation is the keystone of treatment for acute pancreatitis. Though clinical guidelines and expert opinions agree on large volume resuscitation, debate remains on the optimal fluid type. The most commonly used fluids are Lactated Ringer's (LR) and Normal Saline (NS), but the studies published to date comparing LR vs NS yield conflicting results. We aimed to identify and quantitatively synthesize existing high quality data of the topic of fluid type or acute pancreatitis resuscitation. Methods In collaboration with the study team, an information specialist performed a comprehensive literature review to identify reports addressing type of fluid resuscitation. Studies were screened using the Covidence system by two independent reviewers in order to identify Randomized controlled trials comparing LR versus NS. The main outcome was the development of moderately severe or severe pancreatitis and additional outcomes included local complications, ICU admission, and length of stay. Pooled odds ratios were estimated using the random effects model and standardized mean difference to compare continuous variables. Results We reviewed 7964 abstracts and 57 full text documents. Four randomized controlled trials were identified and included in our meta-analyses. There were a total of 122 patients resuscitated with LR versus 126 with NS. Patients resuscitated with LR were less likely to develop moderately severe/severe pancreatitis (OR 0.49; 95 % CI 0.25–0.97). There was no difference in development of SIRS at 24 or 48 h or development of organ failure between the two groups. Patients resuscitated with LR were less likely to require ICU admission (OR 0.33; 95 % CI 0.13–0.81) and local complications (OR 0.42; 95 % CI 0.2–0.88). While there was a trend towards shorter hospitalizations for LR (SMD -0.18, 99 % CI -0.44-0.07), it was not statistically significant. Conclusion Resuscitation with LR reduces the development of moderately severe-severe pancreatitis relative to NS. Nevertheless, no difference in SIRS development or organ failure underscores the need for further studies to verify this finding and define its mechanism.

Background Historically, a glomerular filtration rate (GFR) of less than 50 mL/min per 1.73 m2 has been considered a contraindication to lung transplantation. Combined or sequential lung–kidney transplantation is an option for those with a GFR less than 30 mL/min per 1.73 m2. Patients with a GFR of 30 to 50 mL/min per 1.73 m2 are provided with no options for transplantation. This study explores factors associated with improved survival in patients who undergo isolated lung transplantation with a GFR of 30 to 50 mL/min per 1.73 m2. Methods The United Network for Organ Sharing database was queried for adult patients undergoing primary isolated lung transplantation between January 2007 and March 2018. Regression models were used to identify factors associated with improved survival in lung recipients with a preoperative GFR of 30 to 50 mL/min per 1.73 m2. The propensity score method was used to match highly performing patients (outpatient recipients aged less than 60 years) with a GFR of 30 to 50 mL/min per 1.73 m2 with patients who had a GFR greater than 50 mL/min per 1.73 m2. Kaplan-Meier, Cox, and logistic regression analyses compared outcomes in matched populations. Results A total of 21,282 lung transplantations were performed during the study period. Compared with patients with a GFR greater than 50 mL/min per 1.73 m2, survival was significantly worse for patients with a GFR of 30 to 50 mL/min per 1.73 m2. Multivariate analysis of patients with a GFR of 30 to 50 mL/min per 1.73 m2 demonstrated outpatient status and age less than 60 years to be predictive of superior survival. After propensity matching, survival of this highly performing subset with a GFR of 30 to 50 mL/min per 1.73 m2 was no different from that of patients with a normal GFR. Conclusions Outpatient recipients aged less than 60 years represent an optimal subset of patients with a GFR of 30 to 50 mL/min per 1.73 m2. Lung transplant listing should not be declined based only on a GFR less than 50 mL/min per 1.73 m2.

BACKGROUND: Synaptic loss is a prominent and early feature of many neurodegenerative diseases. OBJECTIVES: We tested the hypothesis that synaptic density is reduced in the primary tauopathies of progressive supranuclear palsy (PSP) (Richardson's syndrome) and amyloid-negative corticobasal syndrome (CBS). METHODS: Forty-four participants (15 CBS, 14 PSP, and 15 age-/sex-/education-matched controls) underwent PET with the radioligand [11 C]UCB-J, which binds to synaptic vesicle glycoprotein 2A, a marker of synaptic density; participants also had 3 Tesla MRI and clinical and neuropsychological assessment. RESULTS: Nine CBS patients had negative amyloid biomarkers determined by [11 C]PiB PET and hence were deemed likely to have corticobasal degeneration (CBD). Patients with PSP-Richardson's syndrome and amyloid-negative CBS were impaired in executive, memory, and visuospatial tasks. [11 C]UCB-J binding was reduced across frontal, temporal, parietal, and occipital lobes, cingulate, hippocampus, insula, amygdala, and subcortical structures in both PSP and CBD patients compared to controls (P < 0.01), with median reductions up to 50%, consistent with postmortem data. Reductions of 20% to 30% were widespread even in areas of the brain with minimal atrophy. There was a negative correlation between global [11 C]UCB-J binding and the PSP and CBD rating scales (R = -0.61, P < 0.002; R = -0.72, P < 0.001, respectively) and a positive correlation with the revised Addenbrooke's Cognitive Examination (R = 0.52; P = 0.01). CONCLUSIONS: We confirm severe synaptic loss in PSP and CBD in proportion to disease severity, providing critical insight into the pathophysiology of primary degenerative tauopathies. [11 C]UCB-J may facilitate treatment strategies for disease-modification, synaptic maintenance, or restoration. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

The perinatal period constitutes an important window of opportunity for optimizing healthy development of offspring but is heavily influenced by maternal mental health. Maternal pregnancy-related anxiety (PrA), depression, and post-traumatic stress disorder (PTSD) have been implicated in adverse outcomes for both mother and child. The current study examined whether psychopathology during pregnancy and postpartum was associated with greater experienced parenting stress and bonding difficulties in women veterans, who may be predisposed to develop psychopathology due to heightened risk of exposure to traumatic events. Pregnant veterans (N = 28) completed self-report questionnaires regarding their PrA, depression and PTSD symptoms during pregnancy and postpartum, as well as on their experience of parenting stress and bonding with their infant. PrA was a more robust predictor of postpartum depression (PPD) than depression during pregnancy. PPD, in turn, was significantly associated with bonding and parenting stress, such that more depressed mothers were more likely to experience greater general bonding difficulties, increased rejections and pathological anger towards their infants, greater anxiety towards their infants, and more parenting stress. PrA might be a high-yield modifiable risk factor in the prevention of PPD for women veterans and their subsequent experiences with high parenting stress and bonding difficulties.

Background Interactions with healthcare workers can provide effective entrance into treatment, ensuring retention and lifelong recovery for individuals with Substance Use Disorder (SUD). Healthcare providers approach the challenges of patient management with different skills, comfort levels, and viewpoints. Individuals in recovery also provide crucial perspectives relevant to the complex aspects of the drug epidemic. The purpose of this study was to determine if perceptions of SUD diverge among individuals in recovery, physicians, nurses and medical students. Methods A survey consisting of 29 Likert statements was deployed to physicians, nurses, medical students, and persons with SUD in recovery. Respondents were asked to rate their level of agreement on statements about SUD such as treatment, stigma, medications for opioid use disorder (MOUD), naloxone kits, safe injection sites, and methamphetamine usage. Separate Welch's analysis of variances (ANOVAs) were conducted to determine differences between the respondent groups and each statement. For any statistically significant findings, Games-Howell post-hoc analyses were employed. Results A total of 523 individuals provided survey responses: individuals in recovery ( n = 111), physicians ( n = 113), nurses ( n = 206), and medical students ( n = 93). Survey results revealed the majority of items had statistically significant differences in respondent groups. Perceptions diverged on items related to treatment, stigma, MOUD, take-home naloxone kits, safe injection sites, needle exchange programs, and methamphetamine. Conclusion As healthcare providers and policymakers develop treatment strategies to engage those with SUD in quality treatment, they will benefit from understanding how different viewpoints on SUD affect treatment for these individuals. These attitudes impact stigma, willingness to prescribe new treatments, and development of clinical relationships. The insight from this study allows for important discussions on the substance use health crisis and further inquiry on why these differences exist and how the diverging viewpoints may impact the lives of persons with SUD.

Background Acute Type A aortic dissection can be physically and mentally stressful with little known about survivors' postrepair activity levels, exercise habits, and quality of life (QOL). This study was aimed to describe pre- and postdissection changes regarding exercise, understand physician recommendations, quantify use of cardiac rehabilitation, and assess QOL in dissection survivors. Methods A total of 295 acute Type A aortic dissection survivors were surveyed about exercise, cardiac rehabilitation, QOL, sexual activity, and posttraumatic stress disorder (PTSD) with 137 (46%) respondents. Results Respondents were less likely to participate in competitive athletics after than before dissection (1/131 [0.76%] vs. 26/131 [20%], p [McNemar test] Conclusion Physicians should prescribe cardiac rehabilitation, encourage appropriate exercise, promote resumption of sexual activity, and identify and treat PTSD after surgery for acute Type A aortic dissection.

Addressing Latino childhood obesity requires effective health promotion programs and culturally resonant health professionals. The current profiles of public health professionals and registered dietitians point to the need to increase the number of Latino students trained in community-based participatory research and engagement of underserved populations. To address this workforce gap, the Center for Latino Community Health, Evaluation, and Leadership Training developed the Sanos y Fuertes: Healthy & Strong Graduate Research Fellowship to provide Latino graduate students with research training, professional development, and mentorship. Five cohorts of seven graduate students participated in a yearlong experiential learning program. Graduate research fellows received monthly research and professional development training from faculty, staff, and community health workers. Furthermore, fellows engaged in mentored research through the development and implementation of a Latino childhood obesity prevention curriculum and intervention. A mixed-method evaluation approach was used to assess the effectiveness of the program. Fellows completed baseline, posttraining, and follow-up assessments. Assessment surveys measured training experiences (e.g., research methods, community engagement), confidence (e.g., research methods, health education), and knowledge and skills (e.g., community health program skills). The training resulted in significant increases in skills and confidence between pre- and postassessments that were sustained at follow-up. Based on these findings, we recommend that student training programs include research as experiential learning with multidisciplinary, interprofessional teams and that community-based, community-engaged, or translational research teams include community health workers as integral members for research with marginalized, underserved populations.

In chronic infections and in cancer, persistent antigen stimulation under suboptimal conditions can lead to the induction of T-cell exhaustion. Exhausted T cells are characterized by an increased expression of inhibitory markers and a progressive and hierarchical loss of function. Although cancer-induced exhaustion in CD8 T cells has been well-characterized and identified as a therapeutic target (i.e., via checkpoint inhibition), in-depth analyses of exhaustion in other immune cell types, including CD4 T cells, is wanting. While perhaps attributable to the contextual discovery of exhaustion amidst chronic viral infection, the lack of thorough inquiry into CD4 T-cell exhaustion is particularly surprising given their important role in orchestrating immune responses through T-helper and direct cytotoxic functions. Current work suggests that CD4 T-cell exhaustion may indeed be prevalent, and as CD4 T cells have been implicated in various disease pathologies, such exhaustion is likely to be clinically relevant. Defining phenotypic exhaustion in the various CD4 T-cell subsets and how it influences immune responses and disease severity will be crucial to understanding collective immune dysfunction in a variety of pathologies. In this review, we will discuss mechanistic and clinical evidence for CD4 T-cell exhaustion in cancer. Further insight into the derivation and manifestation of exhaustive processes in CD4 T cells could reveal novel therapeutic targets to abrogate CD4 T-cell exhaustion in cancer and induce a robust antitumor immune response.

Introduction Insulin glargine 300 U/mL (Gla-300) is a novel glargine formulation which shows slower and more prolonged absorption following subcutaneous administration in comparison to insulin glargine 100 U/mL. In this prospective, observational, single-arm, multicenter, real-world study conducted in Serbia, we evaluated the effectiveness and safety of Gla-300 in patients with type 2 diabetes mellitus (T2DM) previously inadequately controlled with different basal or premix insulin therapy regimes. Methods A total of 350 patients with T2DM were enrolled by 27 physicians, from date of the first patient in (12 December 2017) to the date of last patient completed/last patient out (30 October 2018), from both medical centers and general hospitals. Patients’ observation and data collection were performed at visit 1 (V1), i.e., the inclusion visit (3–6 months after Gla-300 introduction), including collection of retrospective data from the patients’ medical charts at the time of Gla-300 introduction, and at visit 2 (V2) (3–6 months after V1). The primary objective was to assess the change in glycated hemoglobin (HbA1c) level from day of the Gla-300 initiation to the end of the observational period, while the secondary objectives included other effectiveness, as well as safety and other clinically relevant data. Results The mean age of the 350 patients was 63.4 ± 8.4 years and 56.3% were female. The mean duration of diabetes was 13.4 ± 7.4 years, while the mean duration of insulin therapy prior to Gla-300 initiation was 5.3 ± 3.9 years. There was a significant reduction in HbA1c level at each visit compared to the previous visit (8.63 ± 1.52% at baseline prior to Gla-300 initiation, 7.87 ± 1.13% at V1, 7.45 ± 1.05% at V2; p

While the dire cardiometabolic consequences of the hypercaloric modern ‘Western’ diet are well known, there is not much information on the health impact of a high sucrose diet not inducing weight gain. Here, we tested the hypothesis that rats reared with intermittent binge access to sucrose in addition to normal chow would develop an inflammatory response in brain. To test this hypothesis, we undertook serial PET/MRI scans with the TSPO ligand [18F]DPA714 in a group of (n=9) rats at baseline and again after voluntarily consuming 5% sucrose solution three days a week for three months. Compared to a control group fed with normal chow (n=9), the sucrose rats indeed showed widespread increases in the availability of cerebral binding sites for the microglial marker, despite normal weight gain compared to the control diet group. Subsequent immunofluorescence staining of the brains confirmed the PET findings, showing a widespread 20% increase in the abundance of IBA-1-positive microglia with characteristic ‘semi-activated’ morphology in the binge sucrose rats, which had 23% lower density of microglial endpoints and 25% lower mean process length compared to microglia in the control rats with ordinary feeding. GFAP immunofluorescence showed no difference in astroglial coverage in the sucrose rats, except for a slight reduction in hypothalamus. The binge sucrose diet-induced neuroinflammation was associated with a significant elevation of white blood cell counts. Taking these results together, we find that long-term intake of sucrose in a binge paradigm, similar in sucrose content to the contemporary Western diet, triggered a low-grade systemic and central inflammation in non-obese rats. The molecular mechanism of this phenomenon remains to be established.

Background A study reported low systemic availability of injectable dexamethasone nebulized to healthy horses using the Flexineb mask. When used in horses with severe asthma and a different nebulizer, lack of efficacy and cortisol suppression were observed. Hypothesis Nebulized dexamethasone is as effective as PO administration for the treatment of severe asthma in horses. Animals Twelve horses with severe asthma from a research herd. Methods Randomized clinical trial. Horses were divided into 2 groups and received 5 mg of dexamethasone sodium phosphate by nebulization using a Flexineb mask (NE, n = 6) or PO (OR, n = 6) q24h for 7 days. Lung function and serum cortisol concentrations were evaluated at baseline, after 4 days of treatment (D4) and 1 day after the last treatment (D8). Data were analyzed using linear mixed models with Benjamini‐Hochberg adjustments. Results Lung resistance significantly improved at D4 (mean decrease ± SD, −1.5 ± 0.45 cm H₂O/L/s; 95% confidence interval [CI], −2; −0.6) and D8 (−1.4 ± 0.45 cm H₂O/L/s; 95% CI, −2.4; −0.5) compared to baseline in the OR group only (P = .004 and .01, respectively). Serum cortisol concentration was significantly decreased at D4 and D8 for both groups (maximum decrease, −1.2 ± 0.3 μg/dL; 95% CI, −1.9; −0.6 at D4 for NE group and −2.2 ± 0.3 μg/dL; 95% CI, −2.8; −1.6 at D8 for OR group; P

A chart review study was conducted to determine the prevalence of syphilis and explore the associated risk factors among men who have sex with men (MSM) who attended a large HIV clinic in Trinidad during the period January–December 2019. Patients were routinely screened for syphilis annually, and demographic, clinical, and laboratory data were extracted from the medical records. Descriptive and bivariate analyses were performed, and factors significantly associated with a syphilis diagnosis were assessed using multivariate logistic regression. During the period, 218 MSM were seen, age range 19–67 years, and median age 34.0 years. The prevalence of syphilis was 41.3% (90/218), and 71.1% (64//90) of these infections were asymptomatic. Multivariate analysis using logistic regression showed that MSM living with HIV in the 30–34 years old-age group (OR, 4.32; 95% CI, 1.04–18.02), and those with a previous history of treated syphilis (OR, 10.18; 95% CI, 4.60–22.53) were more likely to be diagnosed with syphilis. The prevalence of syphilis is high among MSM attending the HIV clinic in Trinidad, and most of these infections were asymptomatic; hence, targeted and sustained interventions to reduce syphilis transmission are urgently required. Repeat episodes of syphilis may play a role in the transmission dynamics of syphilis in MSM.

Summary Breast cancer is the most frequent type of cancer affecting female patients. The introduction of breast cancer screening programs led to a substantial reduction of mortality from breast cancer. Nevertheless, doubts are being raised on the real efficacy of breast screening programs. The aim of the present paper is to review the main pathological type of cancers detected in breast cancer screening programs. Specifically, attention will be given to: in situ carcinoma, invasive carcinoma histotypes and interval cancer.

Introduction Several jurisdictions have adopted a more conservative approach to anemia in patients receiving dialysis amid safety concerns from target hemoglobin studies. It is largely unknown if this has contributed to a change in clinical outcomes. Methods A national registry was used to identify 35,945 adult patients who initiated and were maintained on dialysis for ≥90 days in Canada from January 2007 to December 2015. Outcomes were ascertained until March 2017 via linkage with hospital discharge diagnoses. Cox proportional hazards models were used to investigate the association between the era of dialysis initiation and the primary composite outcome (acute myocardial infarction [AMI], stroke, or mortality). Results The mean hemoglobin at dialysis initiation decreased from 102.9 g/l in 2007 to 95.5 g/l in 2015, corresponding with a higher prevalence of hemoglobin, Graphical abstract

On April 10, 2020, the FDA approved selumetinib (KOSELUGO, AstraZeneca) for the treatment of pediatric patients 2 years of age and older with neurofibromatosis type 1 who have symptomatic, inoperable plexiform neurofibromas. Approval was based on demonstration of a durable overall response rate per Response Evaluation in Neurofibromatosis and Schwannomatosis criteria and supported by observed clinical improvements in plexiform neurofibroma–related symptoms and functional impairments in 50 pediatric patients with inoperable plexiform neurofibromas in a single-arm, multicenter trial. The overall reponse rate per NCI investigator assessment was 66% (95% confidence interval, 51–79) with at least 12 months of follow-up. The median duration of response was not reached, and 82% of responding patients experienced duration of response ≥12 months. Clinical outcome assessment endpoints provided supportive efficacy data. Risks of selumetinib are consistent with MAPK (MEK) inhibitor class effects, including ocular, cardiac, musculoskeletal, gastrointestinal, and dermatologic toxicities. Safety was assessed across a pooled database of 74 pediatric patients with plexiform neurofibromas and supported by adult and pediatric selumetinib clinical trial data in cancer indications. The benefit–risk assessment for selumetinib in patients with inoperable plexiform neurofibromas was considered favorable.

Purpose This study aimed to create a trigger tool for our intensive care units (ICUs) to support our departmental quality improvement efforts. Methods We compiled an initial list of triggers used in an ICU setting through literature review. We used a modified Delphi method to develop a unique set of triggers. An expert panel was selected for multidisciplinary and multi-site representation from four adult medical-surgical ICUs of a Canadian city. Respondents ranked triggers on a Likert scale based on its likelihood of being associated with adverse event (sensitivity to harm), and likelihood of being associated with suboptimal ICU processes (specificity for internal recommendations). Outcomes Our literature search yielded 10 articles and 59 triggers. Completion of the rating process resulted in 12 items that achieved consensus. Triggers included specific clinical, hospital-acquired infection, medication related, and procedural occurrences. One additional trigger (cardiopulmonary arrest) which consistently held high scores but did not achieve multidisciplinary consensus, was also included. Conclusions We used the modified Delphi process to derive consensus-selected triggers to identify ICU specific adverse events with opportunity for improvement in local care. This methodology can be adopted by other centers looking to introduce trigger tools in a manner selective to their practice needs.

Background:. Vasovagal syncope (VVS) greatly impairs quality of life. The therapeutic efficacy of oral rehydration saline (ORS) for unselected VVS patients is not satisfactory due to the diverse mechanisms of the disease. Body mass index (BMI) was demonstrated to reflect blood volume to a certain extent. Therefore, the present study explored the capability of BMI to predict the therapeutic response of children with VVS to ORS treatment. Methods:. Seventy-four children with VVS who visited the Syncope Unit of Pediatrics at Peking University First Hospital from November 2010 to June 2019 receiving ORS treatment were enrolled for this retrospective case-control study. A comparison of demographic, clinical, and hemodynamic characteristics was performed between responders and non-responders. The correlation between baseline BMI and response time was analyzed. To determine the value of baseline BMI in predicting the therapeutic efficacy of ORS in children with VVS, a receiver operating characteristic curve analysis was performed. Results:. Fifty-two children were identified as responders, and the remaining 22 children were identified as non-responders. The baseline BMI of the responders was much lower than that of the non-responders (16.4 [15.5, 17.8] kg/m2vs. 20.7 ±e6 kg/m2, P

Data are limited concerning the survival outcomes of locally advanced gastric cancer patients according to the multimodality therapy (MMT) administered. Single institution, retrospective analysis of 235 patients with locally advanced gastric cancer from 2001 to 2015. All patients met criteria for curative-intent surgery and chemotherapy ± radiation therapy. Treatment regimens were: (1) surgery first with adjuvant chemoradiation therapy (S + Adj); (2) perioperative chemotherapy + surgery (Periop); and (3) total neoadjuvant therapy followed by surgery (TNT + S). One hundred twenty-eight (60.0%) patients received S + Adj, 69 (26.8%) Periop, and 38 (13.2%) TNT + S. Of the 235 patients, 222 (94.5%) received surgery. All intended therapy was received by 81.6% of TNT + S, 44.5% of S + Adj, and 42.0% of Periop patients. MMT was significantly more likely to be completed by TNT + S patients (HR 6.67, p

Objective. To test if the direct immunofluorescence can be used for the detection of Borrelia afzelii in brain tissue during the standardization of the animal model of neuroborreliosis in NMRI mice. Methods. The study was performed on 15 mice of NMRI strain. All mice were subcutaneously inoculated with 100 ml of BSK-H medium containing the local isolate of Borrelia afzelii. Animals were sacrificed after inoculation at III (n = 4), IV (n = 6) and V (n = 5) weeks, by cervical dislocation. In the sampled brains of mice, the presence of Borrelia was detected by direct immunofluorescence (DIF) and chain polymerization reaction (PCR). Results. The first brain tested positive for Borrelia three weeks after the inoculation. The bacteria were detected in 1 out of 4 brains (25%). After that, there was a growth in the percentage of positive results. The data showed that 3 out of 6 brains (50%) were found positive on Borrelia presence by the end of the fourth week. Whereas, in 3 out of 5 brains (60%) Borrelia was detected five weeks following the inoculation. Conclusion. According to the preliminary results, direct immunofluorescence appeared to be a practical, low budget method for following the kinetics of neuro-infection. NMRI mice could be considered as an adequate animal model for neuroborreliosis. Thus, more research is needed on the topics of infection kinetics for the period after fifth week post inoculation, as well as sensitivity and specificity of direct immunofluorescence.

Graphical abstract, Background Insulin resistance and impaired insulin secretion lead to disorders of glucose metabolism, which contributes to the development of diabetes. Hydrogen sulfide (H2S), a novel gasotransmitter, is found to play important roles in regulation of glucose metabolism homeostasis. Aim of Review This study aimed to summarize and discuss current data about the function of H2S in insulin secretion and insulin resistance regulation as well as the underlying mechanisms. Key Scientific Concepts of Review H2S could be endogenously produced in islet β cells, liver, adipose, skeletal muscles, and the hypothalamus, and regulates local and systemic glucose metabolism. It is reported that H2S suppresses insulin secretion, promotes or reduces the apoptosis of islet β cells. It plays important roles in the regulation of insulin sensitivity in insulin responsive tissues. H2S inhibits glucose uptake and glycogen storage, and promotes or inhibits gluconeogenesis, mitochondrial biogenesis and mitochondrial bioenergetics in the liver. In adipose tissue, several investigators indicated that H2S promoted glucose uptake in adipocytes, while other studies reported that H2S inhibits this process. H2S has also been shown to promote adipogenesis, inhibit lipolysis, and regulate adiponectin and MCP-1 secretion from adipocytes. In skeletal muscle, H2S increases glucose uptake and improves insulin sensitivity. It is also observed that H2S modulates circadian-clock genes in muscle. Hypothalamic CBS/H2S pathway reduces obesity and improves insulin sensitivity via the brain-adipose interaction. Most studies indicated plasma H2S levels decreased in diabetic patients. However, the mechanisms by which H2S regulates systemic glucose metabolism remain unclear. Whether H2S acts as a new promising target for diabetes mellitus treatment merits further studies.

Alcohol use disorder is a pervasive and detrimental condition that involves changes in neuroplasticity and neurogenesis. Alcohol activates the neuroimmune system and alters the inflammatory status of the brain. Tumour necrosis factor (TNF) is a well characterised neuroimmune signal but its involvement in alcohol use disorder is unknown. In this review, we discuss the variable findings of TNF’s effect on neuroplasticity and neurogenesis. Acute ethanol exposure reduces TNF release while chronic alcohol intake generally increases TNF levels. Evidence suggests TNF potentiates excitatory transmission, promotes anxiety during alcohol withdrawal and is involved in drug use in rodents. An association between craving for alcohol and TNF is apparent during withdrawal in humans. While anti-inflammatory therapies show efficacy in reversing neurogenic deficit after alcohol exposure, there is no evidence for TNF’s essential involvement in alcohol’s effect on neurogenesis. Overall, defining TNF’s role in alcohol use disorder is complicated by poor understanding of its variable effects on synaptic transmission and neurogenesis. While TNF may be of relevance during withdrawal, the neuroimmune system likely acts through a larger group of inflammatory cytokines to alter neuroplasticity and neurogenesis. Understanding the individual relevance of TNF in alcohol use disorder awaits a more comprehensive understanding of TNF’s effects within the brain.

PRECIS In African American patients with glaucoma, iStent/phacoemulsification lowered intraocular pressure and reduced glaucoma medication usage for up to 1 year, even in patients with prior selective laser trabeculoplasty (SLT). PURPOSE Currently, no studies have examined the outcomes of a trabecular microbypass stent and phacoemulsification in African American patients. Here, the authors investigate whether iStent/phacoemulsification decreases intraocular pressure (IOP) and/or medication usage in African American patients with glaucoma. They are also interested in whether prior SLT would affect outcomes of iStent/phacoemulsification. PATIENTS AND METHODS A multicenter, retrospective case series of eyes that underwent iStent/phacoemulsification between 2013 and 2017 with up to 1-year follow-up. Eyes with a confirmed diagnosis of glaucoma in African American patients were included. Eyes with neovascular glaucoma or closed angle glaucoma and eyes that underwent previous incisional glaucoma surgery were excluded. RESULTS Eighty-nine eyes were included in the study and data for 66 eyes were available at postoperative year 1 (POY1). IOP decreased from 18.3±5.7 mm Hg to 15.9±4.6 (P

Osteopathic manipulative treatment (OMT) has been used in the treatment of pediatric patients for decades. The authors performed a systematic review to find evidence showing the safety and efficacy of OMT use in pediatric patients for common pediatric conditions seen in the outpatient setting. The conditions reviewed are otitis media and asthma, as they are the most common acute reason children under age five present to their physician and the most common chronic condition affecting children, respectively. The review found evidence of OMT being beneficial in the reduction of middle ear effusions following otitis media. The use of OMT was also shown to increase the peak expiratory flow of children with asthma. Very few studies have been performed to show the safety of osteopathic manipulative treatment; however one study showed that the incidence of iatrogenesis is minimal. Several easy-to-use techniques are demonstrated in the hopes that this will encourage more osteopathic physicians to incorporate the use of OMT into daily practice. As it stands, more studies are needed to give statistical significance and to prove that OMT is a safe, effective, non-invasive option for the treatment of various pediatric conditions.

The purpose of this study was to evaluate the effects of using video modeling (VM) to teach three young adults with autism spectrum disorder (ASD) and intellectual disability (ID) to independently communicate their physical location via text and phone call. We used a multiple-probe research design across behaviors to evaluate the effects of the intervention. Data indicated most participants required noncontrolling prompts in addition to the VM to acquire and perform the task analysis (TA) steps with accuracy. Yet once participants reached criterion, they independently performed the multistep skills and the newly learned behaviors were generalized and maintained 6 weeks posttreatment. These results extend the potential utility of VM instruction. Implications for research and practical application are discussed.

STUDY OBJECTIVE: The National Heart, Lung, and Blood Institute evidence-based guidelines for timeliness of opioid administration for sickle cell disease (SCD) pain crises recommend an initial opioid within 1 hour of arrival, with subsequent dosing every 30 minutes until pain is controlled. No multisite studies have evaluated guideline adherence, to our knowledge. Our objective was to determine guideline adherence across a multicenter network. METHODS: We conducted a multiyear cross-sectional analysis of children with SCD who presented between January 1, 2016, and December 31, 2018, to 7 emergency departments (EDs) within the Pediatric Emergency Care Applied Research Network. Visits for uncomplicated pain crisis were included, defined with an International Classification of Diseases, Ninth Revision (ICD-9) and ICD-10 code for SCD crisis and receipt of an opioid, excluding visits with other SCD complications or temperature exceeding 38.5°C (101.3°F). Times were extracted from the electronic record. Guideline adherence was assessed across sites and calendar years. RESULTS: A total of 4,578 visits were included. The median time to first opioid receipt was 62 minutes (interquartile range 42 to 93 minutes); between the first and second opioid receipt, 60 minutes (interquartile range 39 to 93 minutes). Overall, 48% of visits (95% confidence interval 47% to 50%) were guideline adherent for first opioid. Of 3,538 visits with a second opioid, 15% (95% confidence interval 14% to 16%) were guideline adherent. Site variation in adherence existed for time to first opioid (range 22% to 70%) and time between first and second opioid (range 2% to 36%; both P.05 for both). CONCLUSION: Guideline adherence for timeliness of SCD treatment is poor, with half of visits adherent for time to first opioid and one seventh adherent for second dose. Dissemination and implementation research/quality improvement efforts are critical to improve care across EDs.

Objective: This review examines the various outcome measures utilized in assessing the safety and efficacy of cochlear implantation (CI) in the elderly population. Findings: Though CI is typically performed under general anesthesia, the surgery is safe for elderly patients. Similar minor and major complications rates have been reported in elderly and young patient populations. One complication specific to elderly patients is flap dehiscence due to age-related reduced vascularization and thinner skin. Speech perception, cognition, and quality of life have all been shown to improve subsequent to CI placement. However, efficacy directly correlates with duration of hearing loss with the best outcomes reported closest to when hearing loss begins. Conclusions: Cochlear Implant surgery has been demonstrated to help patients suffering from sensorineural hearing loss improve measures of speech perception, communication, cognition, and quality of life.

Latinos, especially children, are disproportionately affected by obesity. Sanos y Fuertes is a community-based, participatory research project that created a culturally resonant, bilingual, healthy lifestyle intervention for Latinos in California. Results of the program for families are presented. Methods: The sample consisted of 390 Latino families with at least one 2 to 8-year-old child. Confidential, self-report, paper-and-pencil surveys and objective anthropometrics were assessed. Paired sample t-tests evaluated changes between baseline-to-follow-up assessments. Results: A significant decrease was observed in children’s percent body fat, but not in adults. Improvements were found in adult knowledge, frequency of food label use and serving MyPlate portions. Adult frequency of breakfast, fruit, and vegetable intake increased, while frequency of sugary beverage intake decreased. Concomitant increases in parent-reported frequencies of children’s intake of breakfast, fruits, and vegetables were observed along with a less frequent intake of sugary beverage. Conclusion: Sanos y Fuertes is a promising, short-term healthy lifestyle education program which may lower obesity risk among Latino families. Replication in a randomized controlled trial is needed to establish its effectiveness among diverse Latino populations.

Introduction The overall survival in patients with gliomas has not significantly increased in the modern era, despite advances such as immunotherapy. This is in part due to their notorious ability to suppress local and systemic immune responses, severely restricting treatment efficacy. Methods We have reviewed the preclinical and clinical evidence for immunosuppression seen throughout the disease process in gliomas. This review aims to discuss the various ways that brain tumors, and gliomas in particular, co-opt the body’s immune system to evade detection and ensure tumor survival and proliferation. Results A multitude of mechanisms are discussed by which neoplastic cells evade detection and destruction by the immune system. These include tumor-induced T-cell and NK cell dysfunction, regulatory T-cell and myeloid-derived suppressor cell expansion, M2 phenotypic transformation in glioma-associated macrophages/microglia, upregulation of immunosuppressive glioma cell surface factors and cytokines, tumor microenvironment hypoxia, and iatrogenic sequelae of immunosuppressive treatments. Conclusions Gliomas create a profoundly immunosuppressive environment, both locally within the tumor and systemically. Future research should aim to address these immunosuppressive mechanisms in the effort to generate treatment options with meaningful survival benefits for this patient population.

49,XXXXY is the rarest X and Y chromosomal variation, with an incidence of 1 in 80,000-100,000 live male births and has been associated with numerous musculoskeletal abnormalities. Data was collected from an international cohort of boys with 49,XXXXY over 10 years. Children were evaluated by a multidisciplinary team consisting of a pediatric orthopedist, a neurogeneticist, a neurodevelopmentalist, and two physical therapists. Increased rates of torticollis (32.4%), hamstring tightness (42%), radioulnar synostosis (67.6%), pes planus (65.2%), and other foot abnormalities (86.9%) were observed. Several anomalies increased with age, specifically hamstring tightness, kyphosis, and scoliosis. The elucidation of the orthopedic profile of this population is necessary in order to provide healthcare providers with current medical information. This research further supports the necessity for the comprehensive multidisciplinary treatment of boys with 49,XXXXY.

Treatment options are limited for patients with advanced forms of myeloproliferative neoplasms (MPN) including blast-phase disease (MPN-BP). Decitabine has frequently been deployed but its efficacy and safety profile are not well described in this population. We retrospectively reviewed 42 patients treated with decitabine either alone or in combination with ruxolitinib at our institution: 16 with MPN-BP, 14 with MPN accelerated-phase (MPN-AP), and 12 with myelofibrosis with high-risk features (MF-HR). The median overall survival (OS) for the MPN-BP patients was 2.6 months, and for those who received ≥2 cycles of decitabine therapy, it was 6.7 months (3.8–29.8). MPN-BP patients with a poor performance status and who required hospitalization at the time of the initiation of decitabine had a dismal prognosis. After a median follow-up of 12.4 months for MPN-AP patients, and 38.7 months for MF-HR patients, the median OS was not reached for either cohort, with 1 and 2 patients alive at 60 months, respectively. The probability of spleen length reduction and transfusion independence within 12 months of initiating decitabine was 28.6 and 23.5%, respectively. The combination of decitabine and ruxolitinib appeared to improve overall survival versus single-agent decitabine (21 and 12.9 months, respectively). Decitabine, alone or in combination with ruxolitinib, appears to have clinical benefit for patients with advanced phases of MPN when initiated early in the disease course prior to the development of MPN-BP.

Given the high rate of infection secondary to substance use, infusion nurses have a unique opportunity to compassionately engage individuals with substance use problems. Compassion is an essential ingredient of nursing practice, yet compassionate care of the individual who uses substances may seem difficult to navigate. This article provides the infusion nurse with the essential principles of compassionate care of the patient who uses substances. A fundamental understanding of how to work with patients who use substances may enhance the infusion nurse's practice.

Cannabis has been linked to reduced opioid use, although reasons for cannabis use among adults prescribed opioids are unclear.The purpose of this study was to determine whether motivations for cannabis use differ between adults prescribed opioids for persistent pain versus those receiving opioids as medication-assisted treatment for opioid use disorder.A cross-sectional survey design was used.Adults prescribed opioids for persistent pain (n = 104) or opioid use disorder (n = 139) were recruited from outpatient settings.Data were collected on surveys asking about cannabis use and compared the two populations. A series of regression models examined population characteristics and cannabis use motivations using validated measures of the Marijuana Motives Measure scale.More than half the sample (n = 122) reported current, daily cannabis use and 63% reported pain as a motivation for use. Adults with persistent pain were more likely to be older, female, and have higher levels of education (p.05). Adults with opioid use disorder were more likely to report "enhancement" (p.01) and relief of drug withdrawal symptoms (p.001) as motivations for cannabis use. The most common reasons for cannabis use in both populations were social and recreational use and pain relief.Both studied populations have unmet health needs motivating them to use cannabis and commonly use cannabis for pain. Persistent pain participants were less likely to use cannabis for euphoric effects or withdrawal purposes. Nurses should assess for cannabis use, provide education on known risks and benefits, and offer options for holistic symptom management.

Background: Neonates and infants requiring anaesthesia are at risk of physiological instability and complications, but triggers for peri-anaesthetic interventions and associations with subsequent outcome are unknown. Methods: This prospective, observational study recruited patients up to 60 weeks' postmenstrual age undergoing anaesthesia for surgical or diagnostic procedures from 165 centres in 31 European countries between March 2016 and January 2017. The primary aim was to identify thresholds of pre-determined physiological variables that triggered a medical intervention. The secondary aims were to evaluate morbidities, mortality at 30 and 90 days, or both, and associations with critical events. Results: Infants (n=5609) born at mean (standard deviation [SD]) 36.2 (4.4) weeks postmenstrual age (35.7% preterm) underwent 6542 procedures within 63 (48) days of birth. Critical event(s) requiring intervention occurred in 35.2% of cases, mainly hypotension (>30% decrease in blood pressure) or reduced oxygenation (SpO2

To examine if skin autofluorescence (sAF) differed in early adulthood between individuals with type 1 diabetes and age-matched controls and to ascertain if sAF aligned with risk for kidney disease. Young adults with type 1 diabetes (N = 100; 20.0 ± 2.8 years; M:F 54:46; FBG-11.6 ± 4.9 mmol/mol; diabetes duration 10.7 ± 5.2 years; BMI 24.5(5.3) kg/m2) and healthy controls (N = 299; 20.3 ± 1.8 years; M:F-83:116; FBG 5.2 ± 0.8 mmol/L; BMI 22.5(3.3) kg/m2) were recruited. Skin autofluorescence (sAF) and circulating AGEs were measured. In a subset of both groups, kidney function was estimated by GFRCKD-EPI CysC and uACR, and DKD risk defined by uACR tertiles. Youth with type 1 diabetes had higher sAF and BMI, and were taller than controls. For sAF, 13.6% of variance was explained by diabetes duration, height and BMI (Pmodel = 1.5 × 10–12). In the sub-set examining kidney function, eGFR and sAF were higher in type 1 diabetes versus controls. eGFR and sAF predicted 24.5% of variance in DKD risk (Pmodel = 2.2 × 10–9), which increased with diabetes duration (51%; Pmodel –16) and random blood glucose concentrations (56%; Pmodel –16). HbA1C and circulating fructosamine albumin were higher in individuals with type 1 diabetes at high versus low DKD risk. eGFR was independently associated with DKD risk in all models. Higher eGFR and longer diabetes duration are associated with DKD risk in youth with type 1 diabetes. sAF, circulating AGEs, and urinary AGEs were not independent predictors of DKD risk. Changes in eGFR should be monitored early, in addition to uACR, for determining DKD risk in type 1 diabetes.

Glioblastoma (GBM) is the most common primary brain cancer in adults and remains universally lethal. Despite extensive medical intervention, the median survival remains a bleak 15–17 months from time of diagnosis, calling for new therapeutic strategies. In recent years, immune checkpoint blockade (ICB) has garnered attention for its clinical successes in extending overall survival in many advanced-stage cancers. To date, ICB clinical trials have failed to proffer the same benefit in GBM patients, turning attention in the field toward understanding this shortcoming and employing new strategies. Genomic characteristics such as mutational burden, immunogenicity, and heterogeneity, along with immune infiltrate, CNS location, and immunosuppression (tumor-induced or iatrogenic), have been identified as critical components of ICB responsiveness. Promising results from recent clinical trials have rewarded efforts to understand the features of successful ICB and to restore enthusiasm for ICB as an encouraging therapeutic in the treatment of GBM.

While the Pap test, HPV vaccine, and HPV test are important tools to promote cervical health, the American Cancer Society (ACS) recently updated its cervical cancer prevention recommendations to give primacy to HPV testing for cervical cancer screening. We investigate how women’s health providers view these changes, and the extent to which they have reached American women. To do so, we present results from a novel two-survey study of women’s health providers (N = 558) and White, Black, and Hispanic women (N = 1900). We find that a minority of providers report that the HPV test alone is adequate for cervical cancer screening (18%, CI = 14%, 21%) while 96% (CI = 94%, 97%) indicated that women should regularly have both Pap and HPV screenings. Black (88% CI = 86%, 91%) and Hispanic (87% CI = 84%, 89%) women report lower rates of Pap tests compared to White women (94%, CI = 92%, 96%). Only 35% (CI = 33%, 37%) of women report having had an HPV test, and these levels were similar across groups. White (29%, CI = 25%, 33%) and Hispanic women (26% CI = 23%, 29%) report statistically similar levels of provider recommendation for joint Pap-HPV testing, while Black women report statistically lower rates (22%, CI = 18%, 25%). These patterns hold after controlling for several important socio-demographic variables in logistic regression models. The continued lower rates of Pap tests among Black and Hispanic women, combined with low rates of HPV testing is likely to hinder the ability to reduce cervical cancer incidence and mortality, particularly for Hispanic and Black women.

School librarians work with students across their organizations, including those with disabilities such as autism spectrum disorder (ASD). However, little is known about how prepared school librarians are to serve these students. Using a mixed-methods survey, this study sought to explore training school librarians have taken about ASD and students with disabilities, as well as the effects of training on librarian confidence and library services. Based on results, librarians who received training through their school district or professional development outside of coursework reported being more confident in supporting students with ASD in the school library.

Objective The primary aim was to assess both the type and degree of impact of the COVID-19 pandemic on child and family wellbeing in a cohort with neurodevelopmental disorders. Design This was a single time-point observational study utilizing a combination of surveys and standardized measures, which were administered to parents by researchers by telephone. Setting The Child and Adolescent Neuropsychiatric Clinic of the Department of Clinical and Experimental Medicine, Catania University, Italy. Participants In total, 200 caregivers completed the questionnaires on behalf of themselves and their child. They were predominantly mothers (88.00%) and primary caregivers (93.50%), with a mean age of 42.84 years (sd = 7.13). Primary and Secondary Outcomes Measures A questionnaire featured in a previous study was used to assess the impact of COVID-19 on general wellbeing, types of support, family health, home-based learning, and child behaviors. Children’s diagnoses were recorded. Caregivers provided information about physical, mental, financial, and vocational wellbeing, and completed several standardised measures of mental health and well-being: the Kessler Psychological Distress Scale - K6; the General Anxiety Disorder Scale – GAD-2; and the WHO Well-being Scale – WHO-5. Results Overall, 58.50% of respondents agreed somewhat or strongly that their child’s overall health and wellbeing had been impacted by the pandemic, while 47.74% felt that their own wellbeing as parents had been affected. Whilst home-based learning and disruption to services for children were noted as being significant, child wellbeing appeared to not be correlated with these but rather to restrictions, home isolation, and disruption to routine. Conclusion Children with neurocognitive disorders and their families have been substantially impacted by the COVID-19 pandemic. It is expected that targeted resources and support services will be required in response to this increase in need.

BackgroundForeign body airway obstructions (FBAO, choking) are a significant cause of preventable mortality. Abdominal thrusts, back blows, and chest compressions are traditional interventions; however, suction-based airway clearance devices (anti-choking devices, ACDs) have recently been marketed as an alternative. Of note, there is limited published evidence regarding their efficacy and safety. Our research has two aims: 1) To investigate what situational and patient factors are frequently identified, and which are associated with relief of the FBAO, and survival, in individuals with a FBAO treated with an ACD; and 2) To describe the experience of individuals who have used ACDs in response to a FBAO and identify facilitators and barriers to the use of ACDs compared to traditional interventions.Methods and analysisAll ACD case reports collected a priori by manufacturers will be analyzed up to July 1st, 2021. Following, a prospective database will be developed using an online reporting system to capture future ACD use from July 1st, 2021 to Dec 31st, 2023. Descriptive statistics will be used to summarize cases, 58 outcomes, and adverse events. Where possible, bivariable and multivariable analysis will be employed to assess for predictors of outcomes (relief of FBAO, survival, and survival with good neurological function). Semi-structured interviews will be conducted with a subset of ACD users to describe in detail their experience using the device. Themes from these interviews will be assessed using the Theoretical Domains Framework.Ethics and disseminationThis study has ethics approval from the University of New South Wales Human Research Ethics Committee (HC210242). Findings from this multi-year, multi-method study will be published in peer reviewed literature, presented at conferences and contribute to informing future resuscitation guidelines. Data on ACDs are urgently needed as these devices are already being used by parents, caregivers, lay rescuers, and healthcare professionals to respond to choking emergencies.Strengths and limitations of the study∘Foreign body airway obstruction (FBAO) intervention is an area with limited data, largely based on retrospective case series for traditional techniques (e.g., abdominal thrusts, back blows and chest thrusts)∘A multi-phase, multi-year study will be conducted to evaluate a novel intervention (suction-based airway clearance devices, ACDs) that have the potential to improve pre-hospital response to foreign body airway obstructions and survival∘Utilization of retrospective and prospective data, as well as evaluation of the users’ experience, will help determine the role for airway clearance devices in resuscitation algorithms and future guidelines∘Data will be reliant on self-reporting from users due to the infrequent occurrence of FBAO and few ACDs available to general public∘Previous studies have relied on data collected by manufacturers, which will be improved here by providing users with an independent reporting method

Updated incidence data of acute Delta virus hepatitis (HDV) are lacking worldwide. Our aim was to evaluate incidence of and risk factors for acute HDV in Italy after the introduction of the compulsory vaccination against hepatitis B virus (HBV) in 1991. Data were obtained from the National Surveillance System of acute viral hepatitis (SEIEVA). Independent predictors of HDV were assessed by logistic-regression analysis. The incidence of acute HDV per 1-million population declined from 3.2 cases in 1987 to 0.04 in 2019, parallel to that of acute HBV per 100,000 from 10.0 to 0.39 cases during the same period. The median age of cases increased from 27 years in the decade 1991-1999 to 44 years in the decade 2010-2019 (p

Unraveling the long-term kinetics of antibodies to SARS-CoV-2 and the individual characteristics influencing it, including the impact of pre-existing antibodies to human coronaviruses causing common cold (HCoVs), is essential to understand protective immunity to COVID-19 and devise effective surveillance strategies. IgM, IgA and IgG levels against six SARS-CoV-2 antigens and the nucleocapsid antigen of the four HCoV (229E, NL63, OC43 and HKU1) were quantified by Luminex, and antibody neutralization capacity was assessed by flow cytometry, in a cohort of health care workers followed up to 7 months (N = 578). Seroprevalence increases over time from 13.5% (month 0) and 15.6% (month 1) to 16.4% (month 6). Levels of antibodies, including those with neutralizing capacity, are stable over time, except IgG to nucleocapsid antigen and IgM levels that wane. After the peak response, anti-spike antibody levels increase from ~150 days post-symptom onset in all individuals (73% for IgG), in the absence of any evidence of re-exposure. IgG and IgA to HCoV are significantly higher in asymptomatic than symptomatic seropositive individuals. Thus, pre-existing cross-reactive HCoVs antibodies could have a protective effect against SARS-CoV-2 infection and COVID-19 disease., Long-term characterisation of SARS-CoV-2 antibody kinetics is needed to understand the protective role of the immune response. Here the authors describe antibody levels and neutralisation activity in healthcare workers over seven months and investigate the role of immunity to endemic human coronaviruses.

PurposeCongenital hypopituitarism usually occurs sporadically. In most patients, the etiology remains unknown.MethodsWe studied 13 children with sporadic congenital hypopituitarism. Children with non-endocrine, non-familial idiopathic short stature (NFSS) (n = 19) served as a control group. Exome sequencing was performed in probands and both unaffected parents. A burden testing approach was used to compare the number of candidate variants in the two groups.ResultsFirst, we assessed the frequency of rare, predicted-pathogenic variants in 42 genes previously reported to be associated with pituitary gland development. The average number of variants per individual was greater in probands with congenital hypopituitarism than those with NFSS (1.1 vs. 0.21, mean variants/proband, P = 0.03). The number of probands with at least 1 variant in a pituitary-associated gene was greater in congenital hypopituitarism than in NFSS (62% vs. 21%, P = 0.03). Second, we assessed the frequency of rare, predicted-pathogenic variants in the exome (to capture undiscovered causes) that were inherited in a fashion that could explain the sporadic occurrence of the proband’s condition with a monogenic etiology (de novo mutation, autosomal recessive, or X-linked recessive) with complete penetrance. There were fewer monogenic candidates in the probands with congenital hypopituitarism than those with NFSS (1.3 vs. 2.5 candidate variants/proband, P = 0.024). We did not find any candidate variants (0 of 13 probands) in genes previously reported to explain the phenotype in congenital hypopituitarism, unlike NFSS (8 of 19 probands, P = 0.01).ConclusionOur findings provide evidence that the etiology of sporadic congenital hypopituitarism has a major genetic component but may be infrequently monogenic with full penetrance, suggesting a more complex etiology.

Coronary microvascular dysfunction (CMD) is commonly present in patients with metabolic derangements and is increasingly recognized as an important contributor to myocardial ischaemia, both in the presence and absence of epicardial coronary atherosclerosis. The latter condition is termed ‘ischaemia and no obstructive coronary artery disease’ (INOCA). Notwithstanding the high prevalence of INOCA, effective treatment remains elusive. Although to date there is no animal model for INOCA, animal models of CMD, one of the hallmarks of INOCA, offer excellent test models for enhancing our understanding of the pathophysiology of CMD and for investigating novel therapies. This article presents an overview of currently available experimental models of CMD—with an emphasis on metabolic derangements as risk factors—in dogs, swine, rabbits, rats, and mice. In all available animal models, metabolic derangements are most often induced by a high-fat diet (HFD) and/or diabetes mellitus via injection of alloxan or streptozotocin, but there is also a wide variety of spontaneous as well as transgenic animal models which develop metabolic derangements. Depending on the number, severity, and duration of exposure to risk factors—all these animal models show perturbations in coronary microvascular (endothelial) function and structure, similar to what has been observed in patients with INOCA and comorbid conditions. The use of these animal models will be instrumental in identifying novel therapeutic targets and for the subsequent development and testing of novel therapeutic interventions to combat ischaemic heart disease, the number one cause of death worldwide.

Background Immunoglobulin therapy including intravenous immunoglobulin (IVIg) has been used as an effective treatment for autoimmune/inflammatory conditions with few side effects. However, high-dose IVIg (1-2 g/kg) has been recognized as a cause of hemolytic anemia in non-blood group O patients. Hemolysis when observed has been due to anti-A/anti-B isoagglutinins contained in the IVIg. Recently, an isoagglutinin-reduced IVIg, whereby the anti-A and anti-B titers have been reduced by immunoaffinity chromatography, has been introduced; however, whether this new product is as efficacious as nonreduced immunoglobulin (Ig) or will result in less IVIg-associated hemolysis has not been resolved. Study design and methods We used in vitro phagocytosis by monocytes and proinflammatory/anti-inflammatory macrophages, with isoagglutinin-reduced and -nonreduced Ig opsonized group A1 , B, and A1 B red blood cells, to estimate clinical significance of the IgG isoagglutinins. We also used immune thrombocytopenia (ITP) and rheumatoid arthritis (RA) mouse models to examine the in vivo efficacy of isoagglutinin-reduced versus -nonreduced Ig on the amelioration of the diseases. Results In contrast to nonreduced Ig, phagocytosis was largely absent when isoagglutinin-reduced Ig was used at a concentration equivalent to a patient receiving 2 g/kg. The in vivo efficacy of isoagglutinin-reduced versus nonreduced Ig on the amelioration of experimental ITP and RA was similar, indicating no loss of efficacy due to the chromatographic removal of isoagglutinins. Conclusion Isoagglutinin-reduced Ig should have efficacy similar to nonreduced Ig and result in less IVIg-associated hemolysis.

Background:Methicillin-resistant Staphylococcus aureus (MRSA) nasal polymerase chain reaction (PCR) testing can rapidly detect MRSA colonization via nasopharyngeal swab. With a high negative predictive value for MRSA pneumonia, this test may help minimize the duration of anti-MRSA therapy and associated adverse drug events. Objective: This study aimed to evaluate the impact of a pharmacist-initiated MRSA nasal PCR protocol on pneumonia therapy. Methods: This retrospective, quasi-experimental study evaluated adult patients with pneumonia before and after the implementation of a pharmacist-initiated MRSA nasal PCR protocol. The primary outcome of this study was to compare duration of anti-MRSA therapy between the Pre-PCR group and PCR group. Secondary comparisons included duration of antipseudomonal therapy, time from intravenous (IV) to oral interchange, and clinical outcomes. Results: In total, 210 patients (Pre-PCR: n = 138, PCR: n = 72) were included. The MRSA nasal PCR result was negative for 63 patients (87.5%), and 56 (88.9%) vancomycin orders were discontinued within 24 hours of the negative result. The mean duration of vancomycin therapy was significantly shorter in the PCR group (2.5 vs 1.4 days, P < .001) as well as duration of IV therapy (5 vs 3.9 days, P = .003). There was no difference between groups in duration of antipseudomonal therapy ( P = .425), acute kidney injury (AKI; P = .332), 30-day readmission ( P = .137), or 30-day mortality ( P = .179). Conclusion and Relevance: A pharmacist-driven MRSA nasal PCR protocol significantly decreased the duration of anti-MRSA therapy and IV antibiotics in patients with pneumonia. These findings add to the relatively small body of literature supporting pharmacist-initiated rapid diagnostic testing and follow-up.

Background: Yoga, a complementary health approach known for various therapeutic effects, is used with diverse populations, including students ASD. Limited evidence exists inclusive of the first-hand perspective of students with ASD who participate in yoga. The purpose of this study is to understand the perspective of students 10 and 14 years of age with ASD who participated in a portion of the GRTL yoga program as part of a physical education class. Method: Using a qualitative design, this study examined the student perspective on the GRTL yoga program. A convenience sample of seven male participants between 10 and 14 years of age with ASD, all students at a private school, participated in the study. The participants engaged in the GRTL yoga program for four 45-min sessions and then were interviewed following the final yoga session. Conventional content analysis was used to analyze the participant perspectives as it relates to the GRTL yoga program. Results: Research team analysis of the transcribed interviews revealed two themes: positive behavioral responses and self-efficacy of kinesthetic recall. Conclusion: This study demonstrates the use of the GRTL yoga program as it relates to the student perspective and indicates the need for further investigation with the inclusion of the participant voice.

This cross-sectional, retrospective analysis investigated the possible effect of hormonal replacement therapy (HRT) on working memory (WM) and competency/adaptive functioning (CAF) in boys with 47,XXY; the effect of timing of 47,XXY diagnosis on these variables; and the relationship between WM and CAF, if any. A total of 111 boys with 47,XXY, ranging from 6 to 16 years of age (M = 9 years 4 months; SD = 2 years 1 month), were evaluated using the Wechsler Intelligence Scale for Children, and Child Behavior Checklist. Participants were grouped by HRT status and timing of diagnosis. Analysis of variance testing performed on the prenatally diagnosed boys revealed a statistically significant difference in WM for the HRT groups (F[3,84] = 7.467, p = .000174), where WM of the no-HRT group (M = 92.37, SD = 17.83) was lower than that of the early hormonal therapy group (M = 106.39, SD = 12.01; p = .0092). Additionally, there was a positive correlation between low WM capabilities and poor school performance (r = .5106, p = .0027) in the prenatally diagnosed, untreated boys. Our results highlight the potentially positive effects of HRT on WM and CAF in boys with 47,XXY. Further research is required to better determine the underlying relationship among the biological mechanisms of HRT, WM, and CAF outcomes, and timing of diagnosis in boys with 47,XXY.