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Suicide rates and frequency of pediatric emergency department (ED) visits for suicidal thoughts and behaviors have increased among Black preadolescents in the United States in recent years. This study examined whether characteristics of ED visits and treatment management of preadolescents with suicidal thoughts and behaviors differed by race.An electronic medical record query identified patients ages 8-12 (N=504) who visited a pediatric ED with a psychiatric-related chief complaint in 2019. The authors examined suicidal thoughts and behaviors that were reported with the Ask Suicide-Screening Questions tool, ED clinical impression, and ED disposition overall and by race.Compared with other racial groups, Black preadolescents were less likely to report suicidal thoughts, despite equivalent lifetime histories of suicide attempts, and were more likely to be brought to the ED by police and discharged (instead of being admitted to inpatient psychiatric care).Research to better understand racial disparities in suicide risk among preadolescents can inform prevention efforts.

The optimal management of small bowel obstruction (SBO) remains a matter of debate and treatment varies internationally. In Denmark, a more surgically aggressive strategy has traditionally been used, but to what extent patient outcomes differ from international reports is unknown. This study aimed to describe the current management and outcomes of patients admitted with SBO in Denmark.This was a prospective cohort study conducted at six acute hospitals in Denmark over a 4-month period. Patients aged ≥ 18 years with a clinical or radiological diagnosis of SBO were eligible. Primary outcomes were 30 day morbidity and mortality rates.316 patients were included during the study period. The median age was 72 years and 56% were female. Diagnosis was made by computed tomography (CT) in 313 patients (99.1%), with the remaining three diagnosed clinically. Non-operative management was the initial strategy in 152 patients (48.1%) and successful in 119 (78.3%). Urgent surgery was performed in the remaining 164 (51.9%), with a laparoscopic approach used in 84 patients (51.2%). The entire cohort had a 30 day mortality rate of 7.3% and a 30 day morbidity rate of 17.1%.The management of SBO in Denmark differs markedly to previous international reports, with an almost ubiquitous use of CT for diagnosis and a high proportion of patients undergoing urgent surgery. Despite higher rates of surgery, patient outcomes are broadly similar to reports of more conservative strategies, perhaps due to a reduction in delayed operations.Trial registration number: NCT04750811. Trial registration date: 11/02/2021.

Background The COVID-19 pandemic led to training programs abruptly stopping in-person learning and redesigning curricula. Trainees had decreased patient contact time and use of telehealth visits became more prominent. Trainee well-being became even more vital with social isolation and fears of infecting loved ones increased. Our study evaluated impacts of COVID-19 on pediatric emergency medicine (PEM) fellowship programs, including effects on fellows’ clinical, didactic, and research experiences, and effects on fellows’ well-being. Methods Two surveys were developed using an iterative process, 1 for program leadership and 1 for fellows. Survey questions reflected the objectives of this study. Surveys were distributed a total of 3 times in 2-week intervals. Program directors (PDs) were asked to forward the fellow survey to their fellows. Survey responses were anonymous. Surveys were completed online using Qualtrics software between March 17, 2021 and April 19, 2021. Results PDs had a 56.8% (50/88) response rate, fellows 34.6% (144/416). All PDs reported a decrease in pediatric patient volumes during the height of the pandemic. Most common responses included change in rotations and block schedules, didactics moving to a virtual platform, increased frequency of speakers from outside the institution, fellows being able to participate in COVID-related research, and additional mental health services for providers. PDs and trainees report being required to provide service to COVID patients outside of a pediatric ED, commonly the adult ED and medical intensive care units. Conclusion The impact of COVID-19 on fellowship training remains unclear. Decreases in pediatric patient volumes, canceled electives, taking care of adults, and altering didactics/conferences in accordance to CDC guidelines may have adversely affected training. Future research might assess pandemic-related differences on in-training exam scores or how prepared fellows feel for unsupervised practice.

The glycemic index (GI) is the ability of a food to vary postprandial blood sugar. Frequent consumption of high GI foods is believed to cause chronic hyperglycemia which worsens the complications due to diabetes. The search for low GI foods would be of great interest in the prevention of postprandial hyperglycemia. Our work therefore has focused on determining the GI of a dish based on Pleurotus pulmonarius and the influence of its consumption. The dish studied was sautéed Pleurotus mushrooms (P. pulmonarius) with unripe plantains. We included for this study after obtaining ethical clearance, thirty (30) male volunteers (15 diabetic subjects and 15 non-diabetic subjects) aged between 20 and 70 years old. We determined the influence of consumption on some biochemical parameters of the participants. To do this, we took blood samples at the beginning of the experiment (preprandial) and at the end of the experiment (postprandial). After obtaining the serum, we performed for each participant the lipid profile (total cholesterol, HDL cholesterol, LDL cholesterol and triglyceride) we determined cretinemia, transaminase and total protein increased in concentration at the end of the test experimentation. This work brings added value concerning the use of edible mushrooms in the management of type 2 diabetes. From this study, we can highlight the ability of the test dish to minimize excessively marked variations in postprandial glycemia in diabetics.

The interplay between mesenchymal stem/stromal cells (MSCs) and preservation conditions is critical to maintain the viability and functionality of these cells before administration. We observed that Ringer lactate (RL) maintained high viability of bone marrow–derived MSCs for up to 72 h at room temperature (18°C–22°C), whereas adipose‐derived and umbilical cord‐derived MSCs showed the highest viability for 72 h at a cold temperature (4°C–8°C). These cells maintained their adherence ability with an improved recovery rate and metabolic profiles (glycolysis and mitochondrial respiration) similar to those of freshly harvested cells. Growth factor and cytokine analyses revealed that the preserved cells released substantial amounts of leukaemia inhibitory factors (LIFs), hepatocyte growth factor (HGF) and vascular endothelial growth factor‐A (VEGF‐A), as well as multiple cytokines (eg IL‐4, IL‐6, IL‐8, MPC‐1 and TNF‐α). Our data provide the simplest clinically relevant preservation conditions that maintain the viability, stemness and functionality of MSCs from perinatal and adult tissue sources.

OBJECTIVE This study aimed to evaluate both applicant and interviewer satisfaction with the virtual interviewing process for pediatric emergency medicine (PEM) fellowship in hopes to improve the fellowship interviewing process. It was proposed that fellowship programs and applicants would prefer virtual interviews over traditional interviews. METHODS A survey developed in collaboration with UT Southwestern PEM fellowship leaders and national PEM leaders was sent to all PEM fellowship applicants and programs at the conclusion of the 2020 interview season and rank list submission. The applicant survey obtained information on ease of virtual interviews and whether applicants felt that they obtained adequate information from virtual interviews to make informed program selections. Program director surveys collected data on thoughts and feelings about virtual interviews and obstacles encountered during the recruitment season. Both surveys asked about costs for interviews and interview type preference. RESULTS A response rate of 49% from applicants and 47% from programs was obtained. Virtual interview days were similar in the amount of time and staff hours used compared with traditional days. Applicants spent less on virtual interviews compared with those who underwent traditional interviews (average $725 vs $4312). Programs received more applications than the prior year and spent less money during the virtual cycle. The majority of the applicants (90%) were comfortable with the virtual interview platform, and most (66%) agreed that virtual interviews provided adequate information to determine program rank. Geography was the number 1 rank determining factor. Programs and applicants preferred a form of in-person interviews. CONCLUSIONS Virtual interviews provide cost savings for both applicants and programs. Despite this, both parties prefer a form of in-person interviews.

Background The efficacy of catheter ablation of atrial fibrillation (AF) is reported to stabilise at 5-year, but most studies report up to 3-year-outcomes only. Objective To perform a systematic review and meta-analysis of outcomes at 5-years following AF ablation. Methods We searched PubMed and Embase for studies reporting on ≥5-year outcomes following AF ablation, including freedom from atrial arrhythmia, all-cause death, stroke, and major bleeding. All meta-analyses were performed using the “meta” package in R with pooled incidence calculated using log transformation. Results Among 5,764 studies screened, 58 (n=41,344 patients) were included for analysis. The pooled mean age was 60.3y, 68.7% male, 78.4% paroxysmal AF, and radiofrequency was the most common ablation energy (72.4%). Most (51.5%) patients had hypertension, but the pooled rates of other comorbidities were low (heart failure: 9.0%, coronary artery disease: 12.8%, diabetes: 11.0%, and previous stroke: 8.5%). Pooled incidence of freedom from atrial arrhythmia at 5-years was 47.6% (95% CI 43.8%-51.6%, I2=98.4%) after a single procedure and increased to 64.3% (95% CI 59.6%-69.3%, I2=98.3%) after multiple procedures (Figure 1). The incidence was higher among patients with paroxysmal compared with non paroxysmal AF (55.9% vs. 28.7% and 82.2% vs. 47.6% after single and multiple procedures respectively). Retrospective studies reported slightly higher incidence of arrhythmia freedom (single procedure: 51.2% vs. 46.7%; multiple procedures: 66.9% vs. 61.9%) than did prospective studies. Few studies reported outcomes other than atrial arrhythmia free survival at 5-years (n=14) and incidences of these outcomes could only be pooled for multiple procedures. Pooled incidences of death, stroke, and major bleeding at 5-years were 8.0% (95% CI 4.2%-15.2%, I2=95.8%), 2.3% (95% CI 1.4%-3.6%, I2=72.9%), and 1.1% (95% CI 0.6%-1.8%, I2=32.5%), respectively (Figure 2). Conclusion At five-years, only up to 65% of patients undergoing AF ablations remained free from atrial arrhythmia although there was significant heterogeneity among individual studies. Encouragingly, these patients had low risk of dying, experiencing a stroke or major bleeding (all incidences Funding Acknowledgement Type of funding sources: None.

Background Gestational diabetes (GDM) is prevalent and benefits from timely and effective treatment, given the short window to impact glycemic control. Clinicians face major barriers to choosing effectively among treatment modalities [medical nutrition therapy (MNT) with or without pharmacologic treatment (antidiabetic oral agents and/or insulin)]. We investigated whether clinical data at varied stages of pregnancy can predict GDM treatment modality. Methods Among a population-based cohort of 30,474 pregnancies with GDM delivered at Kaiser Permanente Northern California in 2007–2017, we selected those in 2007–2016 as the discovery set and 2017 as the temporal/future validation set. Potential predictors were extracted from electronic health records at different timepoints (levels 1–4): (1) 1-year preconception to the last menstrual period, (2) the last menstrual period to GDM diagnosis, (3) at GDM diagnosis, and (4) 1 week after GDM diagnosis. We compared transparent and ensemble machine learning prediction methods, including least absolute shrinkage and selection operator (LASSO) regression and super learner, containing classification and regression tree, LASSO regression, random forest, and extreme gradient boosting algorithms, to predict risks for pharmacologic treatment beyond MNT. Results The super learner using levels 1–4 predictors had higher predictability [tenfold cross-validated C-statistic in discovery/validation set: 0.934 (95% CI: 0.931–0.936)/0.815 (0.800–0.829)], compared to levels 1, 1–2, and 1–3 (discovery/validation set C-statistic: 0.683–0.869/0.634–0.754). A simpler, more interpretable model, including timing of GDM diagnosis, diagnostic fasting glucose value, and the status and frequency of glycemic control at fasting during one-week post diagnosis, was developed using tenfold cross-validated logistic regression based on super learner-selected predictors. This model compared to the super learner had only a modest reduction in predictability [discovery/validation set C-statistic: 0.825 (0.820–0.830)/0.798 (95% CI: 0.783–0.813)]. Conclusions Clinical data demonstrated reasonably high predictability for GDM treatment modality at the time of GDM diagnosis and high predictability at 1-week post GDM diagnosis. These population-based, clinically oriented models may support algorithm-based risk-stratification for treatment modality, inform timely treatment, and catalyze more effective management of GDM.

Recent advancements in stem cell technology open a new door for patients suffering from diseases and disorders that have yet to be treated. Stem cell-based therapy, including human pluripotent stem cells (hPSCs) and multipotent mesenchymal stem cells (MSCs), has recently emerged as a key player in regenerative medicine. hPSCs are defined as self-renewable cell types conferring the ability to differentiate into various cellular phenotypes of the human body, including three germ layers. MSCs are multipotent progenitor cells possessing self-renewal ability (limited in vitro) and differentiation potential into mesenchymal lineages, according to the International Society for Cell and Gene Therapy (ISCT). This review provides an update on recent clinical applications using either hPSCs or MSCs derived from bone marrow (BM), adipose tissue (AT), or the umbilical cord (UC) for the treatment of human diseases, including neurological disorders, pulmonary dysfunctions, metabolic/endocrine-related diseases, reproductive disorders, skin burns, and cardiovascular conditions. Moreover, we discuss our own clinical trial experiences on targeted therapies using MSCs in a clinical setting, and we propose and discuss the MSC tissue origin concept and how MSC origin may contribute to the role of MSCs in downstream applications, with the ultimate objective of facilitating translational research in regenerative medicine into clinical applications. The mechanisms discussed here support the proposed hypothesis that BM-MSCs are potentially good candidates for brain and spinal cord injury treatment, AT-MSCs are potentially good candidates for reproductive disorder treatment and skin regeneration, and UC-MSCs are potentially good candidates for pulmonary disease and acute respiratory distress syndrome treatment.

AIM Paediatric emergency departments (ED) nationwide experience a shared burden of boarding mental health patients. Whilst boarding, some patients have a change in disposition from hospitalization to discharge home. This phenomenon raises concern because EDs often have scarce resources for mental health patients. We sought to understand which patient and clinical factors are associated with a change in disposition outcome. METHODS A nested age-sex-race frequency-matched case-control study was conducted including paediatric patients who presented to an urban PED for mental healthcare over a 36-month period. Control patients included patients admitted to an inpatient psychiatric facility, whilst case patients were those discharged home. Descriptive statistics and multivariable logistic regression analyses were performed to compare groups. RESULTS Case patients were more likely to receive intramuscular Haloperidol (OR 2.2 [CI 1.1-4.4]) for agitation and a psychiatric consult (OR 2.3 [1.4-3.9]) whilst boarding. Case patients were also more likely to present with behavioural concerns (OR 1.8 [CI 1.1-3.1]) and have additional complexities such as medical comorbidities (OR 1.8 [CI 1.1-2.9]) or suicidal ideation/attempt (OR 2.6 [CI 1.1-6.1]). Amongst the most common themes for disposition change was improved patient status (58.8%). CONCLUSION These findings suggest that boarding mental health patients have different disposition outcomes and thus may benefit from patient-specific treatment interventions. Given that patients' statuses may change during the boarding period prompting discharge to home, more focus should be directed to developing brief evidence-based practises that may be implemented in the ED and effectively bridge the gap to outpatient mental health services.

The physiological role of T cell anergy induction as a key mechanism supporting self-tolerance remains undefined, and natural antigens that induce anergy are largely unknown. In this report, we used TCR sequencing to show that the recruitment of CD4+CD44+Foxp3-CD73+FR4+ anergic (Tan) cells expands the CD4+Foxp3+ (Tregs) repertoire. Next, we report that blockade in peripherally-induced Tregs (pTregs) formation due to mutation in CNS1 region of Foxp3 or chronic exposure to a selecting self-peptide result in an accumulation of Tan cells. Finally, we show that microbial antigens from Akkermansia muciniphila commensal bacteria can induce anergy and drive conversion of naive CD4+CD44-Foxp3- T (Tn) cells to the Treg lineage. Overall, data presented here suggest that Tan induction helps the Treg repertoire to become optimally balanced to provide tolerance toward ubiquitous and microbiome-derived epitopes, improving host ability to avert systemic autoimmunity and intestinal inflammation.

Interleukin 36 (IL‐36) constitutes a group of cytokines that belong to the IL‐1 superfamily. Emerging evidence has suggested a role of IL‐36 in the pathogenesis of many inflammatory disorders. Intriguingly, in the gastrointestinal tract, IL‐36 has a rather complex function. IL‐36 receptor ligands are overexpressed in both animal colitis models and human IBD patients and may play both pathogenic and protective roles, depending on the context. IL‐36 cytokines comprise three receptor agonists: IL‐36α, IL‐36β and IL‐36γ, and two receptor antagonists: IL‐36Ra and IL‐38. All IL‐36 receptor agonists bind to the IL‐36R complex and exert pleiotropic effects during inflammatory settings. Here, we first briefly review the processing and secretion of IL‐36 cytokines. We then focus on the current understanding of the immunology effects of IL‐36 in gut immunity. In addition, we also discuss the ongoing trials that aim to blockage IL‐36R signalling for treating chronic intestinal inflammation and present some unexplored questions regarding IL‐36 research.

Although unnecessary blood component transfusions are costly and pose substantial patient risks, the extent of unnecessary blood use in a community hospital setting has not been systematically measured.A 15-hospital observational analysis was performed using comprehensive retrospective review. Approximately 100 encounters (x¯ = 103.9, standard deviation [SD] ± 7.6) per hospital (6,696 total component transfusion events) were reviewed between 2012 and 2018. Review was performed by two medical directors. Findings were supported by blind intra- and inter-reviewer double review and blind external review by 10 independent reviewers.Patients received an average of 4.3 (± 1.3) units. Only 8.2% (± 6.7) of patient encounters did not receive unnecessary units. Fifty-five percent (54.6% ± 13.5) could have been managed without at least one component type, while 44.6% (± 14.9) could have been managed completely without transfusion. Forty-five percent (45.4% ± 17.0) of red blood cell, 54.9% (± 19.3) of plasma-cryoprecipitate, and 38.0% (± 15.6) of plateletpheresis encounters could likely have been managed without transfusion. Between 2,713 units (40.5%) and 3,306 units (49.4%) were likely unnecessary. In patients who could have been managed without transfusion of at least one component type, unnecessary blood use was associated with a 0.38 (± 0.11)-day increase in length of hospital stay for each additional unnecessary unit received (p0.001).Substantial unnecessary blood use was identified, all of which was unrecognized by hospitals prior to review. Unnecessary blood use was attributed to overreliance on laboratory transfusion criteria and failure to follow common blood management principles, which resulted in potential harm to patients and avoidable cost.

Gestational diabetes (GDM) predisposes pregnant individuals to perinatal complications and long-term diabetes and cardiovascular diseases. We developed and validated metabolomic markers for GDM in a prospective test-validation study. In a case-control sample within the PETALS cohort (91 GDM, 180 non-GDM; discovery set), a random PETALS subsample (42 GDM, 372 non-GDM; validation set 1), and a case-control sample within the GLOW trial (35 GDM, 70 non-GDM; validation set 2), fasting serum untargeted metabolomics were measured by gas chromatography/time-of-flight mass spectrometry. Multivariate enrichment analysis examined metabolites-GDM associations. Ten-fold cross-validated LASSO regression identified predictive metabolomic markers at gestational weeks (GW) 10-13 and 16-19 for GDM. The purinone metabolites at GW 10-13 and 16-19, and the amino acids, amino alcohols, hexoses, indoles, and pyrimidines metabolites at GW 16-19 were positively associated with GDM risk (FDR P

Enteropathogenic bacterial infections are a global health issue associated with high mortality, particularly in developing countries. Efficient host protection against enteropathogenic bacterial infection is characterized by coordinated responses between immune and nonimmune cells. In response to infection in mice, innate immune cells are activated to produce interleukin (IL)-23 and IL-22, which promote antimicrobial peptide (AMP) production and bacterial clearance. IL-36 cytokines are proinflammatory IL-1 superfamily members, yet their role in enteropathogenic bacterial infection remains poorly defined. Using the enteric mouse pathogen, C. rodentium, we demonstrate that signaling via IL-36 receptor (IL-36R) orchestrates a crucial innate-adaptive immune link to control bacterial infection. IL-36R-deficient mice (Il1rl2(−/−)) exhibited significant impairment in expression of IL-22 and AMPs, increased intestinal damage, and failed to contain C. rodentium compared to controls. These defects were associated with failure to induce IL-23 and IL-6, two key IL-22 inducers in the early and late phases of infection, respectively. Treatment of Il1rl2(−/−) mice with IL-23 during the early phase of C. rodentium infection rescued IL-22 production from group 3 innate lymphoid cells (ILCs), whereas IL-6 administration during the late phase rescued IL-22-mediated production from CD4(+) T cell, and both treatments protected Il1rl2(−/−) mice from uncontained infection. Furthermore, IL-36R-mediated IL-22 production by CD4(+) T cells was dependent upon NFκB-p65 and IL-6 expression in dendritic cells (DCs), as well as aryl hydrocarbon receptor (AhR) expression by CD4(+) T cells. Collectively, these data demonstrate that the IL-36 signaling pathway integrates innate and adaptive immunity leading to host defense against enteropathogenic bacterial infection.

Purpose of Review This is a comprehensive review of the current literature on the usage of galcanezumab for migraine treatment. It reviews the biology, pathophysiology, epidemiology, diagnosis, and conventional treatment of migraines, then compares the literature available for galcanezumab with historical treatment options. Recent Findings Migraine is a common headache disorder and constitutes a significant source of distress from both a personal and societal perspective. Conventional treatment includes abortive and preventive treatment. Treatment options are limited and may be only partially or minimally effective in some of the population. Recent evidence points to metabolic changes in the brain as possible causes of migraine, via reduced available energy or a spiking need for it, resulting in a relative insufficiency. This leads to trigeminocervical complex (TCC) activation and a headache episode, modulated by calcitonin gene-related peptide (CGRP). Galcanezumab (Emgality) is a monoclonal antibody targeting CGRP that is given in a monthly injection for the prevention of migraines. Its safety was previously shown in phase 1 and 2 trials, and recent phase 3 trials showed efficacy, with up to 50% reduction in monthly migraine days and improved functional capacity in migraineurs. Studies show that the drug is well tolerated and safe. Summary Migraine headache is a common neurological syndrome that causes great pain and suffering. Treatment options today are limited. Galcanezumab does not prevent migraines, but it is effective in decreasing their frequency and length. It is also much better tolerated than the currently existing therapies. While it is unlikely to provide monotherapy for migraines, it is a novel therapy that may be added for cases of severe or frequent migraines.

OBJECTIVES Spinal cord stimulation (SCS) therapies are used in the management of patients with complex regional pain syndrome I (CRPS I) and failed back surgery syndrome (FBSS). The purpose of this study was to investigate the racial and health insurance inequalities with SCS therapy in patients with chronic pain who had CRPS I and FBSS. METHODS Patients with chronic pain who had a discharge diagnosis of FBSS and CRPS I were identified using the National Inpatient Sample database. Our primary outcome was defined as the history of SCS utilization by race/ethnicity, income quartile, and insurance status. Multivariable logistic regression was used to determine the variables associated with utilization of SCS therapy. RESULTS Between 2011 and 2015, 40,858 patients who were hospitalized with a primary diagnosis of FBSS and/or CRPS I were identified. Of these patients, 1,082 (2.7%) had a history of SCS therapy. Multivariable regression analysis revealed that compared to White patients, Black and Hispanic patients had higher odds of having SCS therapy (Black patients: odds ratio [OR] = 1.41; 95% confidence interval [CI], 1.12 to 1.77; P = 0.003; Hispanic patients: OR = 1.41; 95% CI, 1.10 to 1.81; P = 0.007). Patients with private insurance had significantly higher odds of having SCS therapy compared with those with Medicare (OR = 1.24; 95% CI, 1.08 to 1.43; P = 0.003). Compared to patients with Medicare, Medicaid patients had lower odds of having SCS therapy (OR = 0.50; 95% CI, 0.36 to 0.70; P

Purpose of Review This is a comprehensive review of the literature about the use of bupivacaine hydrochloride for the treatment of post-herpetic neuralgia (PHN). It briefly reviews the background, biology, diagnosis and conventional treatment for PHN, and then introduces and compares the recent evidence for the use of topical bupivacaine. Recent Findings PHN is defined by pain lasting 90 days or more after the initial presentation of herpes zoster (“Shingles”, HZ) rash and is the most common complication of this disease. A product of re-activation of the Varicella-Zoster virus (VZV), HZ is diagnosed more than 1 million times annually in the United States. Approximately 20% of patients with HZ will experience PHN and will continue to suffer intermittent neuropathic symptoms, including itching and pain, that is sharp, stabbing, throbbing or burning, with the pain localized to the site of their original rash. This long-lasting pain compares with the severity of long-standing rheumatics and osteo-arthritis and is accompanied by severe allodynia causing significant suffering, and a financial burden that is manifested in both healthcare costs and loss of quality-adjusted life years. Prevention of PHN may be achieved with the Zoster vaccine, although there is still a large segment of unvaccinated population. Moreover, the Zoster vaccine is not always effective for prevention. Current treatment includes medical (systemic tricyclic antidepressants, anticonvulsants and opioids, topical lidocaine and capsaicin) and interventional (subcutaneous Botox injections, nerve blocks and nerve stimulation) therapies. These therapies are not always effective, and each carries their own profile of side effects and risks. Moreover, up to 50% of patients with PHN are refractory to management. Recent evidence is emerging to support the use of topical local anesthetics for the treatment of PHN. Two small studies recently found topical lidocaine spray to be effective in treating paroxysmal pain attacks associated with PHN. Bupivacaine is a longer-lasting local anesthetic, and a film-forming formulation allows easy and durable application to the affected skin. Recent studies show that topical film-forming bupivacaine is safe and as effective as lidocaine for the treatment of PHN. Summary PHN is an important though common complication of HZ and can cause long-lasting pain and disability. Current treatment for PNH is limited by efficacy and safety profiles of individual therapies. Recent evidence points to topical local anesthetics as an effective and safe alternative to conventional therapy. Film-forming bupivacaine may offer a durable and safe option for this otherwise difficult to treat syndrome.

Migraine headache is a common, chronic, debilitating disease with a complex etiology. Current therapy for migraine headache comprises either treatments targeting acute migraine pain or prophylactic therapy aimed at increasing the length of time between migraine episodes. Recent evidence suggests that calcium gene-related peptide (CGRP) is a critical component in the pathogenesis of migraines. Fremanezumab, a monoclonal antibody against CGRP, was recently approved by the Food and Drug Administration (FDA) after multiple studies showed that it was well-tolerated, safe, and effective in the treatment of migraines. Further research is needed to elucidate the long-term effects of fremanezumab and CGRP-antagonists in general, and additional data is required in less healthy patients to estimate its effects in these populations and potentially increase the eligible group of recipients. This is a comprehensive review of the current literature on the efficacy and safety of fremanezumab for the treatment of chronic migraine. In this review we provide an update on the epidemiology, pathogenesis, diagnosis, and current treatment of migraine, and summarize the evidence for fremanezumab as a treatment for migraine.

Recent advancements in stem cell technology open a new door for patients suffering from diseases and disorders that have yet to be treated. Stem cell-based therapy, including human pluripotent stem cells (hPSCs) and multipotent mesenchymal stem cells (MSCs), has recently emerged as a key player in regenerative medicine. hPSCs are defined as self-renewable cell types conferring the ability to differentiate into various cellular phenotypes of the human body, including three germ layers. MSCs are multipotent progenitor cells possessing self-renewal ability (limited in vitro) and differentiation potential into mesenchymal lineages, according to the International Society for Cell and Gene Therapy (ISCT). This review provides an update on recent clinical applications using either hPSCs or MSCs derived from bone marrow (BM), adipose tissue (AT), or the umbilical cord (UC) for the treatment of human diseases, including neurological disorders, pulmonary dysfunctions, metabolic/endocrine-related diseases, reproductive disorders, skin burns, and cardiovascular conditions. Moreover, we discuss our own clinical trial experiences on targeted therapies using MSCs in a clinical setting, and we propose and discuss the MSC tissue origin concept and how MSC origin may contribute to the role of MSCs in downstream applications, with the ultimate objective of facilitating translational research in regenerative medicine into clinical applications. The mechanisms discussed here support the proposed hypothesis that BM-MSCs are potentially good candidates for brain and spinal cord injury treatment, AT-MSCs are potentially good candidates for reproductive disorder treatment and skin regeneration, and UC-MSCs are potentially good candidates for pulmonary disease and acute respiratory distress syndrome treatment.

Evaluate if same-day cervical preparation is associated with a clinically acceptable complication rate compared with overnight osmotic dilators for dilation and evacuation (DE).This retrospective, noninferiority, cohort study compared complication rates for same-day versus overnight cervical preparation with DE between 14 and 16 weeks gestation. Cervical preparation was achieved with misoprostol, osmotic dilators, or both. Our primary outcome was the acute complication rate, defined as: hemorrhage (≥500 mL); hospitalization or hospital transfer; transfusion; or unplanned procedure occurring within 24 hours of the index procedure. Secondarily we evaluated nonmajor (re-aspiration, suture repair of cervical laceration, uterine tamponade, or emergency department only transfer) and major (transfusion, uterine artery embolization, abdominal surgery, or hospital admission) complications separately. Inverse probability of treatment weighting using the propensity score was used to perform an adjusted analysis, taking into account age, ethnicity, clinic location, insurance, gestational age, gravidity, and prior pregnancy outcomes.We analyzed 1,319 subjects (n = 864 same-day, n = 455 overnight). Same-day cervical preparation patients were more likely to have Medicaid and a prior vaginal delivery. In both unadjusted and adjusted analyses, acute complication rates for same-day were noninferior to overnight preparation (unadjusted 0.93% vs 1.98%, difference of -1.05%, CI: -2.48% to 0.38%; adjusted difference -0.50%, CI: -1.45 to 0.44%). Only one major complication in the same-day group, a cervical laceration resulting in hemorrhage requiring transfusion, occurred in the entire sample.In this retrospective review, same-day cervical preparation was noninferior to overnight preparation for DE between 14 and 16 weeks gestation, both with low complication rates.For early second trimester dilation and evacuation, same-day cervical preparation should be considered a safe alternative to overnight cervical preparation.

Gestational diabetes mellitus (GDM) predisposes pregnant individuals to perinatal complications and long-term diabetes and cardiovascular diseases. We developed and validated metabolomic markers for GDM in a prospective test-validation study. In a case-control sample within the PETALS cohort (GDM n = 91 and non-GDM n = 180; discovery set), a random PETALS subsample (GDM n = 42 and non-GDM n = 372; validation set 1), and a case-control sample within the GLOW trial (GDM n = 35 and non-GDM n = 70; validation set 2), fasting serum untargeted metabolomics were measured by gas chromatography/time-of-flight mass spectrometry. Multivariate enrichment analysis examined associations between metabolites and GDM. Ten-fold cross-validated LASSO regression identified predictive metabolomic markers at gestational weeks (GW) 10–13 and 16–19 for GDM. Purinone metabolites at GW 10–13 and 16–19 and amino acids, amino alcohols, hexoses, indoles, and pyrimidine metabolites at GW 16–19 were positively associated with GDM risk (false discovery rate

Deposition of high molecular weight paraffins and subsequent plugging is one of the most prevalent flow assurance risks in both onshore and offshore oil and gas production. Several thermal (e.g., insulation, heat treatment), mechanical (e.g., pigging, cutting), and chemical (e.g., paraffin crystal modifiers, dispersants, and solvents) techniques are used for wax deposition prevention and remediation. Various chemistries such as long-chain poly alkyl acrylates, olefin vinyl acetate copolymers, alkyl phenol resins and esterified olefin maleic anhydride polymers are used as wax crystal modifiers. This study investigates the impact of the alpha olefin maleic anhydride co-polymers structure on the composition and deposition of paraffin. Eight different crude samples from condensates to black oils with API gravity in the range of 30 to 50° were studied. The focus of this research is on paraffin inhibitors’ effectiveness in reducing paraffin deposition that is driven by thermal driving force between the bulk oil and the pipe wall. Inhibitor performance was measured by cold finger testing. Three different alpha olefin (short, medium and long) maleic anhydrides esterified with different fatty alcohols with varying chain lengths were tested for performance. The impact of selected chemicals on amount and composition of paraffin deposit under different test conditions was studied. Wax deposit composition was characterized using high temperature gas chromatography (HTGC) and differential scanning calorimetry (DSC) techniques. Effect of pendant side chain length as well as the composition and molecular weight of the alpha-olefin backbone on paraffin inhibition is presented. Additionally, the impact of test conditions on the composition and hence the performance of the selected chemicals is investigated. We present our findings on selective inhibition of lower molecular weight paraffin depending on the composition of the oil, leaving a much harder deposit rich in high molecular weight paraffin. This is an important observation since a hard deposit would be extremely difficult to remediate in the field and should be avoided. In summary this work provides guidelines for tailoring paraffin inhibitor molecules based on crude oil composition and field conditions, through a systematic structure-performance study.

Diet, especially fiber content, plays an important role in sustaining a healthy gut microbiota, which promotes intestinal and metabolic health. Another major determinant of microbiota composition is the specific microbes that are acquired early in life, especially maternally. Consequently, we hypothesized that alterations in maternal diet during lactation might lastingly impact the microbiota composition and health status of offspring. Accordingly, we observed that feeding lactating dams low-fiber diets resulted in offspring with lasting microbiota dysbiosis, including reduced taxonomic diversity and increased abundance of Proteobacteria species, despite the offspring consuming a fiber-rich diet. Such microbiota dysbiosis was associated with increased encroachment of bacteria into inner mucus layers, low-grade gut inflammation, and a dramatically exacerbated microbiota-dependent increase in adiposity following exposure to an obesogenic diet. Thus, maternal diet is a critical long-lasting determinant of offspring microbiota composition, impacting gut health and proneness to obesity and its associated disorders.

Real-time Polymerase Chain Reaction (realtime PCR) is an important medical diagnostic technique in which target DNA is amplified and the amplification process is monitored in realtime. However, most realtime PCR systems are expensive, especially for laboratories in developing countries. To increase accessibility to the realtime PCR technique, we developed a low-cost and portable real-time PCR system. The system was composed of two main parts: a thermocycler and an optical system. The thermocycler's core was a Peltier and a heatsink fan, in tandem with an electronic circuit to control the heating process’s temperature. A custom-made fluorescence optical setup was built using a blue LED chip (450 nm), an excitation filter, a dichroic mirror, an emission filter, and a CMOS camera. The results were displayed on a screen connected to a Raspberry Pi module. The thermocycler worked stably and accurately under the control of a PID controller. The system’s performance was tested using samples of rice phospholipase D (PLD) gene and maize Bt11 gene. The results showed that, at the end of the amplification process, fluorescence signals from positive samples were significantly higher than from negative samples. Nucleic acid amplification products were verified using gel electrophoresis. With the cost of ~$320 USD, the system could be a suitable candidate for realtime PCR tests in laboratories in rural and remote areas of developing countries.

Like many specialty chemicals used in pharmaceutical, personal care, and cosmetic products, few life cycle inventory data are available to describe the synthesis of isostearic acids (IAs). We inves...

Resident and attending concern about the potential for decreased teaching has been cited as one of the drawbacks to the adoption of family-centered rounds (FCR). Despite these concerns, FCR can enhance clinical education through direct exposure to multiple patients by all team members, as well as by allowing faculty to teach, model, observe, and assess learners' clinical skills more effectively than in nonbedside settings. This article provides many strategies and approaches to bedside teaching designed to enhance education and communication among care team members as well as patients and their families.

Chromatographic techniques were used to prepare rosmarinic acid rich extract from Orthosiphon aristatus. Such extract is highly required for herbal product development because of its remarkable bio...

Incorporation of membrane-anchored flagellin molecules into the surfaces of influenza virus-like particles (VLP) was previously reported to promote T helper (Th) 1-biased IgG antibody production and protective efficacy of co-presented vaccine antigens. Herein, we investigated the potential adjuvant effects and mechanisms of flagellin-expressing VLP (FliC-VLP) as an independent component on influenza vaccination in wild-type and mutant mouse models. FliC-VLP adjuvanted influenza vaccination was highly effective in promoting the induction of Th1-biased IgG isotype switched antibodies, enhanced protection, and long-lasting IgG antibody responses in both wild-type and CD4-knockout mice. In contrast, the adjuvant effects of soluble flagellin were Th2-biased and required CD4 T helper cells. The adjuvant effects of FliC-VLP were less dependent on CD4 T cells and flagellin-mediated innate immune signaling pathways. The results suggest that FliC-VLP might play an effective adjuvant role in an immune competent condition as well as in a defect of CD4 T cells.

ImportanceGlycemic control is the cornerstone of gestational diabetes management. Glycemic control trajectories account for differences in longitudinal patterns throughout pregnancy; however, studies on glycemic control trajectories are scarce.ObjectiveTo examine whether glycemic control trajectories from gestational diabetes diagnosis to delivery were associated with differential risk of perinatal complications.Design, Setting, and ParticipantsThis population-based cohort study included individuals with gestational diabetes with longitudinal electronic health record data from preconception to delivery who received prenatal care at Kaiser Permanente Northern California (KPNC) and were enrolled in KPNC’s telemedicine-based gestational diabetes care program between January 2007 and December 2017. Data analysis was conducted from September 2021 to January 2022.ExposuresGlycemic control trajectories were derived using latent class modeling based on the American Diabetes Association’s recommended self-monitoring of blood glucose measurements. Optimal glycemic control was defined as at least 80% of all measurements meeting the targets at KPNC clinical settings.Main Outcomes and MeasuresMultivariable Poisson regression models were used to estimate the associations of glycemic control trajectories with cesarean delivery, preterm birth, shoulder dystocia, large- and small-for-gestational-age, and neonatal intensive care unit admission and stay of 7 days or longer.ResultsAmong a total of 26 774 individuals (mean [SD] age, 32.9 [5.0] years; 11 196 Asian or Pacific Islander individuals [41.8%], 1083 Black individuals [4.0%], 7500 Hispanic individuals [28.0%], and 6049 White individuals [22.6%]), 4 glycemic control trajectories were identified: stably optimal (10 528 individuals [39.3%]), rapidly improving to optimal (9151 individuals [34.2%]), slowly improving to near-optimal (4161 individuals [15.5%]), and slowly improving to suboptimal (2934 individuals [11.0%]). In multivariable models with the rapidly improving to optimal trajectory group as the reference group, glycemic control trajectories were associated with perinatal complications with a gradient across stably optimal to slowly improving to suboptimal. For individuals in the stably optimal trajectory group, there were lower risks of cesarean delivery (adjusted relative risk [aRR], 0.93 [95% CI, 0.89-0.96]), shoulder dystocia (aRR, 0.75 [95% CI, 0.61-0.92]), large-for-gestational age (aRR, 0.74 [95% CI, 0.69-0.80]), and neonatal intensive care unit admission (aRR, 0.90 [95% CI, 0.83-0.97]), while for patients in the slowly improving to suboptimal glycemic control trajectory group, risks were higher for cesarean delivery (aRR, 1.18 [95% CI, 1.12-1.24]; (P for trend P for trend P for trend P for trend Conclusions and RelevanceThese findings suggest that slowly improving to near-optimal and slowly improving to suboptimal glycemic control trajectories were associated with increased risk of perinatal complications. Future interventions should help individuals achieve glycemic control early after gestational diabetes diagnosis and throughout pregnancy to decrease the risk of perinatal complications.

Background & Aims Nourishment of gut microbiota via consumption of fermentable fiber promotes gut health and guards against metabolic syndrome. In contrast, how dietary fiber impacts type 1 diabetes is less clear. Methods To examine impact of dietary fibers on development of type 1 diabetes in the streptozotocin (STZ)-induced and spontaneous non-obese diabetes (NOD) models, mice were fed grain-based chow (GBC) or compositionally defined diets enriched with a fermentable fiber (inulin) or an insoluble fiber (cellulose). Spontaneous (NOD mice) or STZ-induced (wild-type mice) diabetes was monitored. Results Relative to GBC, low-fiber diets exacerbated STZ-induced diabetes, whereas diets enriched with inulin, but not cellulose, strongly protected against or treated it. Inulin’s restoration of glycemic control prevented loss of adipose depots, while reducing food and water consumption. Inulin normalized pancreatic function and markedly enhanced insulin sensitivity. Such amelioration of diabetes was associated with alterations in gut microbiota composition and was eliminated by antibiotic administration. Pharmacologic blockade of fermentation reduced inulin’s beneficial impact on glycemic control, indicating a role for short-chain fatty acids (SCFA). Furthermore, inulin’s microbiota-dependent anti-diabetic effect associated with SCFA-independent restoration of interleukin 22, which was necessary and sufficient to ameliorate STZ-induced diabetes. Inulin-enriched diets significantly delayed diabetes in NOD mice. Conclusions Fermentable fiber confers microbiota-dependent increases in SCFA and interleukin 22 that, together, may have potential to prevent and/or treat type 1 diabetes., Graphical abstract

Frailty, a specific condition of increased vulnerability and reduced general health associated with aging in older people, is an emerging problem worldwide with major implications for clinical practice and public health. Recent preclinical and clinical studies have supported the safety of mesenchymal stem/stromal cells (MSCs) in the treatment of frailty. Comprehensive study is needed to assess the interrelationship between the condition of frailty and the effects of MSC-based therapy. This randomized controlled phase I/II trial aims to investigate the safety and potential therapeutic efficacy of the allogeneic administration of umbilical cord-derived MSCs (UC-MSCs) in combination with the standard treatment for frailty in Vietnam. Moreover, this study describes the rationales, study designs, methodologies, and analytical strategies currently employed in stem cell research and clinical studies. The primary outcome measures will include the incidences of prespecified administration-associated adverse events and serious adverse events. The potential efficacy will be evaluated based on improvements in frailty conditions (including those determined through a physical examination, patient-reported outcomes, quality of life, immune markers of frailty, metabolism analysis, and cytokine markers from patient plasma). This clinical trial and stem cell analysis associated with patient sampling at different time points aim to identify and characterize the potential effects of UC-MSCs on improving frailty based on the stem cell quality, cytokine/growth factor secretion profiles of UC-MSCs, cellular senescence, and metabolic analysis of patient CD3+ cells providing fundamental knowledge for designing and implementing research strategies in future studies. Clinical Trials Registration Number: NCT04919135

PURPOSE OF REVIEW: This comprehensive review discusses the adverse effects known today about marijuana, for either medical or recreational use. It reviews the role of cannabis in the treatment of chronic pain, cognitive and neurological adverse effects, special cases and addiction. RECENT FINDINGS: Cannabinoids work through the endocannabinoids system and inhibit the release of GABA and glutamate in the brain, impact neuromodulation, as well as dopamine, acetylcholine and norepinephrine release. They affect reward, learning and pain. The use of cannabis is increasing nationally and world-wide for both recreational and medicinal purposes, however, there is relatively only low quality evidence to the efficacy and adverse effects of this. Cannabis and its derivatives may be used for treatment of chronic pain. They are via CB1 receptors that are thought to modulate nociceptive signals in the brain. CB2 receptors in the DRG likely affect pain integration in the afferent pathways, and peripherally CB2 also affects noradrenergic pathways influencing pain. A large proportion of users may see more than 50% of chronic pain alleviation compared with placebo. Cannabis affects cognition, most notably executive function, memory and attention, and may deteriorate the boundary between emotional and executive processing. Cannabis impairs memory in the short run, which become more significant with chronic use, and may also be accompanied by poorer effort, slower processing and impacted attention. It is generally believed that long-term use and earlier age are risk factor for neurocognitive deficits; neuroimaging studies have shown reduced hippocampal volume and density. Executive functions and memory are worse in adolescent users versus adults. Cannabis addiction is different and likely less common than other addictive substances, but up to 10% of users meet criteria for lifetime cannabis dependence. Addiction patterns may be linked to genetic and epigenetic differences. It is still unclear whether abstinence reverses patterns of addiction, and more research is required into this topic. SUMMARY: Cannabis use has become more abundant for both medical and recreational use. It carries likely benefits in the form of analgesia, anti-emesis and improved appetite in chronic patients. The evidence reviewing adverse effects of this use are still limited, however, exiting data points to a clear link with neurocognitive deterioration, backed by loss of brain volume and density. Addiction is likely complex and variable, and no good data exists to support treatment at this point. It is becoming clear that use in earlier ages carries a higher risk for long-term deficits. As with any other drug, these risks should be considered alongside benefits prior to a decision on cannabis use.

Human bone marrow‐derived mesenchymal stem/stromal cells (BM‐MSCs) represent promising stem cell therapy for the treatment of type 2 diabetes mellitus (T2DM), but the results of autologous BM‐MSC administration in T2DM patients are contradictory. The purpose of this study was to test the hypothesis that autologous BM‐MSC administration in T2DM patient is safe and that the efficacy of the treatment is dependant on the quality of the autologous BM‐MSC population and administration routes. T2DM patients were enrolled, randomly assigned (1:1) by a computer‐based system into the intravenous and dorsal pancreatic arterial groups. The safety was assessed in all the treated patients, and the efficacy was evaluated based on the absolute changes in the hemoglobin A1c, fasting blood glucose, and C‐peptide levels throughout the 12‐month follow‐up. Our data indicated that autologous BM‐MSC administration was well tolerated in 30 T2DM patients. Short‐term therapeutic effects were observed in patients with T2DM duration of, Human bone marrow‐derived mesenchymal stem/stromal cells (BM‐MSCs) represent promising stem cell therapy for the treatment of type 2 diabetes, but the results of autologous BM‐MSC admniistration in T2DM patients are contradicted. Our data indicated that autologous BM‐MSC administration was well tolerated in 30 T2DM patients. The potential therapeutic effects of the treatments were observed in patients with less than 10 years of T2DM and a BMI

BACKGROUND: Adhesive capsulitis of the shoulder (AC) is characterized by fibrosis and contracture of the glenohumeral joint capsule, resulting in progressive stiffness, pain, and restriction of motion of the shoulder. The prevalence of AC is estimated to be 2–5% of the general population. Patients with AC typically have an insidious onset of pain and can progress to severe limitation of the shoulder leading to significant disability and decreased quality of life. OBJECTIVES: The objective of this manuscript is to provide a comprehensive review of AC with a focus on clinical presentation, natural history, pathophysiology, and various treatment modalities. STUDY DESIGN: A review article. SETTING: A review of literature. METHODS: A search was made on the Pubmed database using the keywords of adhesive capsulitis, frozen shoulder, shoulder capsulitis, arthrofibrosis, shoulder pain, shoulder stiffness. RESULTS: Our search identified numerous studies in order to provide a comprehensive review of the current understanding of the treatment and management of AC. LIMITATIONS: There remains limited evidence in literature about the understanding of AC and optimal treatment. CONCLUSION: AC is an important cause of chronic pain and disability. There is currently no consensus on treatment. Initial treatment modalities revolve around conservative measures as well as aggressive physical therapy. Further treatment options include intraarticular injections, hydro-dilation, nerve blocks, and for more refractory cases, surgical interventions such as arthroscopic capsulotomy.

Impacts of respiratory tract viruses have long been appreciated to highly heterogeneous both between and within various populations. The SARS-CoV-2 pandemic, which is the first time that a pathogen's spread across the globe has been extensively monitored by direct detection of the pathogen itself rather just than the morbidity left in its wake, indicates such heterogeneity is not limited to outcomes of infections but whether infection of a particular host occurs at all. This suggests an important role for yet to be discovered environmental (i.e. non-genetic) factors that influence whether an exposure to the virus initiates a productive infection and, moreover, the severity of disease that results. This article discusses the emerging hypothesis that the composition of a host's commensal microbial communities, that is, its 'microbiome', may be one such determinant that influences outcomes following encounters with respiratory viral pathogens in general and SARS-CoV-2 in particular. Specifically, we will review the rationales and evidence that supports this hypothesis and, moreover, speculate as to possible approaches to manipulate microbiota to ameliorate disease induced by respiratory viral pathogens.