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Abstract Background Pre-diagnostic disturbances in the microbiome-derived metabolome have been associated with an increased risk of diabetes in non-pregnant populations. However, the roles of microbiome-derived metabolites, the end-products of microbial metabolism, in gestational diabetes (GDM) remain understudied. We examined the prospective association of microbiome-derived metabolites in early to mid-pregnancy with GDM risk in a diverse population. Methods We conducted a prospective discovery and validation study, including a case–control sample of 91 GDM and 180 non-GDM individuals within the multi-racial/ethnic The Pregnancy Environment and Lifestyle Study (PETALS) as the discovery set, a random sample from the PETALS (42 GDM, 372 non-GDM) as validation set 1, and a case–control sample (35 GDM, 70 non-GDM) from the Gestational Weight Gain and Optimal Wellness randomized controlled trial as validation set 2. We measured untargeted fasting serum metabolomics at gestational weeks (GW) 10–13 and 16–19 by gas chromatography/time-of-flight mass spectrometry (TOF–MS), liquid chromatography (LC)/quadrupole TOF–MS, and hydrophilic interaction LC/quadrupole TOF–MS. GDM was diagnosed using the 3-h, 100-g oral glucose tolerance test according to the Carpenter-Coustan criteria around GW 24–28. Results Among 1362 annotated compounds, we identified 140 of gut microbiome metabolism origin. Multivariate enrichment analysis illustrated that carbocyclic acids and branched-chain amino acid clusters at GW 10–13 and the unsaturated fatty acids cluster at GW 16–19 were positively associated with GDM risk (FDR

Summary: Interleukin (IL)-22 promotes host-microbiota homeostasis. We sought to identify microbiota metabolite(s) that drive intestinal IL-22 production. We observed that exposing Peyer’s patch cells (PPCs), ex vivo, to fecal supernatants (FSs) recapitulates fermentable fiber- and microbiota-dependent IL-22 production, and cellular sources thereof, thus supporting the use of this model. An interrogation of FSs generated from mice fed the fermentable fiber inulin (FS-Inu) revealed that its IL-22-inducing activity is mediated by heat-labile protein. Fractionation of FS-Inu by ion-exchange chromatography, and subsequent proteomic analysis of IL-22-inducing fractions, indicates that outer membrane protein A (OmpA) might be a microbial driver of IL-22 expression. Concomitantly, recombinant OmpA from Parabacteroides goldsteinii, which is enriched by an inulin diet, induces IL-22 production and expression of the IL-22-dependent genes REG3γ and -β, in PPCs and mice. Thus, OmpA is one bacterial inducer of IL-22 expression, potentially linking diet, mucosal immune homeostasis, and gut health.

The emergence of Japanese encephalitis virus (JEV) in eastern Australia in 2022 caused extensive reproductive disease in pigs and is a threat to public health. Groups of weaned piglets were experimentally infected with the Australian outbreak strain of JEV (genotype 4). All pigs challenged at 5 weeks of age were infected after an intradermal injection of 1 × 105.5 (n = 4) or 1 × 104.5 TCID50/pig (n = 5). Intranasal instillation was less effective at this age, infecting 3/4 pigs with the same higher dose and 1/5 with the lower dose. Intradermal injection using 1 × 105.0 TCID50/pig also infected 9/9 pigs at 11 weeks of age. Infection in all cases was confirmed by qRT-PCR of blood samples, which identified a viremia peak at 3–4 days and detected JEV-specific antibodies as early as 5 days after the challenge. The detection of JEV in oral and nasal swabs and in saliva from chew ropes was less consistent. JEV was detected in the tonsils of 21/22 infected pigs and was isolated from the tonsils of 9/9 pigs sampled 19 days after the challenge at 11 weeks of age. The infected pigs showed no clinical signs other than pyrexia on Days 4–6. Histopathology consistent with JEV infection was evident in the nervous tissues of all but two pigs sampled 28 days after the challenge and was characterized by meningitis, encephalitis and gliosis throughout the brain. Serological studies showed extensive cross-reactivity between JEV and Murray Valley encephalitis virus using blocking ELISAs. However, the determination of limiting-dilution titres allowed for the identification of the infecting virus. This in vivo infection model will be useful in evaluating JEV vaccines and for comparative pathogenesis studies with other JEV genotypes.

Background & Aims: The protection provided by rotavirus (RV) vaccines is highly heterogeneous among individuals. We hypothesized that microbiota composition might influence RV vaccine efficacy. Methods: First, we examined the potential of segmented filamentous bacteria (SFB) colonization to influence RV vaccine efficacy in mice. Next, we probed the influence of human microbiomes on RV vaccination via administering mice fecal microbial transplants (FMTs) from children with robust or minimal RV vaccine responsiveness. Post-FMT, mice were subjected to RV vaccination followed by RV challenge. Results: SFB colonization induced a phenotype that was reminiscent of RV vaccine failure (ie, failure to generate RV antigens and, consequently, anti-RV antibodies following RV vaccination resulting in proneness to RV challenge after SFB levels diminished). FMTs from children to mice recapitulated donor vaccination phenotype. Specifically, mice receiving FMTs from high-responsive vaccinees copiously shed RV antigens and robustly generated anti-RV antibodies following RV vaccination. Concomitantly, such mice were impervious to RV challenge. In contrast, mice receiving FMTs from children who had not responded to RV vaccination exhibited only modest responses to RV vaccination and, concomitantly, remained prone to RV challenge. Microbiome analysis ruled out a role for SFB but suggested involvement of Clostridium perfringens. Oral administration of cultured C. perfringens to gnotobiotic mice partially recapitulated the RV vaccine non-responder phenotype. Analysis of published microbiome data found C. perfringens abundance in children modestly associated with RV vaccine failure. Conclusion: Microbiota composition influences RV vaccine efficacy with C. perfringens being one, perhaps of many, potential contributing taxa.

ABSTRACTImpacts of dietary fiber on intestinal inflammation are complex, but some specific semi-purified fibers, particularly psyllium, can protect humans and rodents against colitis. Mechanisms underlying such protection are not fully understood but may involve activation of the FXR bile acid receptor. Obesity and its associated consequences, referred to as metabolic syndrome, are associated with, and promoted by, low-grade inflammation in a variety of tissues including the intestine. Hence, we examined whether psyllium might ameliorate the low-grade intestinal inflammation that occurs in diet-induced obesity and, moreover, the extent to which it might ameliorate adiposity and/or dysglycemia in this disease model. We observed that enriching a high-fat diet with psyllium provided strong protection against the low-grade gut inflammation and metabolic consequences that were otherwise induced by the obesogenic diet. Such protection was fully maintained in FXR-deficient mice, indicating that distinct mechanisms mediate psyllium’s protection against colitis and metabolic syndrome. Nor did psyllium’s protection associate with, or require, fermentation or IL−22 production, both of which are key mediators of beneficial impacts of some other dietary fibers. Psyllium’s beneficial impacts were not evident in germfree mice but were observed in Altered Schaedler Flora mice, in which psyllium modestly altered relative and absolute abundance of the small number of taxa present in these gnotobiotic mice. Thus, psyllium protects mice against diet-induced obesity/metabolic syndrome by a mechanism independent of FXR and fermentation but nonetheless requires the presence of at least a minimal microbiota.

ABSTRACTPrevention of rotavirus (RV) infection by gut-resident segmented filamentous bacteria (SFB) is an example of the influence of gut microbiota composition on enteric viral infection. Yet, the mechanism by which SFB prevents RV infection is poorly understood. A recent report that SFB colonization of germfree mice generates retinoic acid (RA) thus activating RA receptor (RAR) signaling, which protected against Citrobacter rodentium infection, prompted us to investigate whether this pathway might contribute to SFB’s protection against RV infection. Colonization of conventional mice by SFB indeed increased intestinal RA levels and direct administration of RA partially mimicked the protection against RV infection conferred by SFB. Moreover, blockade of RAR signaling eliminated SFB’s protection against RV infection. Blockade of RAR signaling did not impact RV infection in the absence of SFB, nor did it alter the protection against RV infection conferred by bacterial flagellin, which in contrast to SFB, is dependent upon IL-22 signaling. SFB/RA-mediated prevention of RV infection was associated with an RA-dependent increase in enterocyte migration, consistent with the notion that enhanced anoikis is the ultimate means by which SFB, IL-22, and RA impede RV infection.

Background & Aims: Fiber-rich foods promote health, but mechanisms by which they do so remain poorly defined. Screening fiber types, in mice, revealed psyllium had unique ability to ameliorate 2 chronic inflammatory states, namely, metabolic syndrome and colitis. We sought to determine the mechanism of action of the latter. Methods: Mice were fed grain-based chow, which is naturally rich in fiber or compositionally defined diets enriched with semi-purified fibers. Mice were studied basally and in models of chemical-induced and T-cell transfer colitis. Results: Relative to all diets tested, mice consuming psyllium-enriched compositionally defined diets were markedly protected against both dextran sulfate sodium- and T-cell transfer-induced colitis, as revealed by clinical-type, histopathologic, morphologic, and immunologic parameters. Such protection associated with stark basal changes in the gut microbiome but was independent of fermentation and, moreover, maintained in mice harboring a minimal microbiota (ie, Altered Schaedler Flora). Transcriptomic analysis revealed psyllium induced expression of genes mediating bile acids (BA) secretion, suggesting that psyllium’s known ability to bind BA might contribute to its ability to prevent colitis. As expected, psyllium resulted in elevated level of fecal BA, reflecting their removal from enterohepatic circulation but, in stark contrast to the BA sequestrant cholestyramine, increased serum BA levels. Moreover, the use of BA mimetics that activate the farnesoid X receptor (FXR), as well as the use of FXR-knockout mice, suggested that activation of FXR plays a central role in psyllium’s protection against colitis. Conclusions: Psyllium protects against colitis via altering BA metabolism resulting in activation of FXR, which suppresses pro-inflammatory signaling.

Abstract 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.

Abstract 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.

Introduction Type 2 diabetes mellitus (T2DM) is a powerful risk factor for cardiovascular disease (CVD), conferring a greater relative risk in women than men. We sought to examine sex differences in cardiometabolic risk factors and management in the contemporary cohort represented by the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE).Research design and methods GRADE enrolled 5047 participants (1837 women, 3210 men) with T2DM on metformin monotherapy at baseline. The current report is a cross-sectional analysis of baseline data collected July 2013 to August 2017.Results Compared with men, women had a higher mean body mass index (BMI), greater prevalence of severe obesity (BMI≥40 kg/m2), higher mean LDL cholesterol, greater prevalence of low HDL cholesterol, and were less likely to receive statin treatment and achieve target LDL, with a generally greater prevalence of these risk factors in younger women. Women with hypertension were equally likely to achieve blood pressure targets as men; however, women were less likely to receive ACE inhibitors or angiotensin receptor blockers. Women were more likely to be divorced, separated or widowed, and had fewer years of education and lower incomes.Conclusions This contemporary cohort demonstrates that women with T2DM continue to have a greater burden of cardiometabolic and socioeconomic risk factors than men, particularly younger women. Attention to these persisting disparities is needed to reduce the burden of CVD in women.Trial registration number ClinicalTrials.gov (NCT01794143)

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.

Abstract 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.

Abstract 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.

Abstract Introduction This compilation presents a comprehensive review of the literature on common chronic pain conditions of the hand. It briefly presents these common conditions with their biological background, diagnosis, and common management options. It then presents and compares the latest literature available for injection techniques to treat these diagnoses and compares the available evidence. Methods A comprehensive literature review was performed in MEDLINE, PubMed, and Cochrane databases from 1996 to 2019 using the terms “hand pain”, “injection techniques”, “steroid injection”, “chronic pain”, “osteoarthritis”, “rheumatoid arthritis”, “carpal tunnel syndrome”, “De Quervain’s tenosynovitis”, “ganglion cyst”, “gout”, “Raynaud’s”, and “stenosing tenosynovitis”. Results Hand pain is a common condition with 9.7% prevalence in men and 21.6% in women and can cause significant morbidity and disability. It also carries a significant cost to the individuals and the healthcare system, totaling in $4 billion dollars in 2003. Injection therapy is an alternative when conservative treatment fails. Osteoarthritis is the most common chronic hand pain syndrome and affects about 16% of the population. Its mechanism is largely mechanic, and as such, there is controversy if steroid injections are of benefit. Hyaluronic acid (HA) appears to provide substantial relief of pain and may increase functionality. More studies of HA are required to make a definite judgment on its efficacy. Similarly, steroid ganglion cyst injection may confer little benefit. Carpal tunnel syndrome is a compressive neuropathy, and only temporarily relieved with injection therapy. US-guidance provides significant improvement and, while severe cases may still require surgery, can provide a valuable bridge therapy to surgery when conservative treatment fails. Similar bridging treatments and increased efficacy under US-guidance are effective for stenosing tenosynovitis (“trigger finger”), though, interestingly, inflammatory background is associated with decreased effect in this case. When the etiology of the pain is inflammatory, such as in RA, corticosteroid (CS) injections provide significant pain relief and increased functionality. They do not, however, change the course of disease (unlike DMARDs). Another such example is De-Quervain tenosynovitis that sees good benefit from CS injections, and an increased efficacy with US-guidance, and similarly are CS injections for gout. For Raynaud’s phenomenon, Botox injections have encouraging results, but more studies are needed to determine safety and efficacy, as well as the possible difference in effect between primary and secondary Raynaud’s. Conclusions Chronic hand pain is a prevalent and serious condition and can cause significant morbidity and disability and interferes with independence and activities of daily living. Conservative treatment remains the first line of treatment; however, when first-line treatments fail, steroid injections can usually provide benefit. In some cases, HA or Botox may also be beneficial. US-guidance is increasing in hand injection and almost ubiquitously provides safer, more effective injections. Hand surgery remains the alternative for refractory pain.

Objective Household food insufficiency (HFIS) is a major public health threat to children. Children may be particularly vulnerable to HFIS as a psychological stressor due to their rapid growth and accelerated behavioural and cognitive states, whereas data focusing on HFIS and childhood mental disorders are as-yet sparse. We aimed to examine the associations of HFIS with depression and anxiety in US children.Design Cross-sectional study.Setting The 2016–2018 National Survey of Children’s Health, a nationally-representative study.Participants Primary caregivers of 102 341 children in the USA.Primary and secondary outcome measures Physician diagnosed depression and anxiety were assessed by questionnaires administered to primary caregivers of 102 341 children. Multivariable logistic regression models estimated adjusted OR (aOR) for current depression or anxiety associated with HFIS measured through a validated single-item instrument.Results Among children aged 3–17 years, 3.2% and 7.4% had parent-reported physician-diagnosed current depression and anxiety, respectively. Compared with children without HFIS, children with HFIS had approximately twofold higher weighted prevalence of anxiety or depression. After adjusting for covariates, children with versus without HFIS had a 1.53-fold (95% CI 1.15 to 2.03) and 1.48-fold (95% CI 1.20 to 1.82) increased odds of current depression and anxiety, respectively. Associations were slightly more pronounced among girls (aOR (95% CI): depression 1.69 (1.16 to 2.48); anxiety 1.78 (1.33 to 2.38)) than boys (1.42 (0.98 to 2.08); 1.32 (1.00 to 1.73); both P-for-interaction

Gut microbiota and their metabolites regulate homeostasis of the intestine, but their effects on intestine development are unclear. Here the authors use RNAseq and germ free mice to show that intestinal microbiota promote the expression of Erdr1, which increases Lgr5+ intestinal stem cell number and activity.

Abstract Introduction Cosmetic breast surgery is commonly performed in the United States; 520,000 procedures of the total 1.8 million cosmetic surgical procedures performed in 2018 were breast related. Postoperative chronic pain, defined as lasting 3 or more months, has been reported in a wide variety of breast surgical procedures including breast augmentation, reduction mammaplasty, mastectomy, and mastectomy with reconstruction. Patient characteristics associated with the development of postoperative chronic pain following cosmetic breast surgery include a younger age, larger BMI, smaller height, postoperative hyperesthesia, and elevated baseline depression, anxiety, and catastrophizing scores. The anatomical distribution of chronic pain following breast augmentation procedures is dependent upon incision site placement; pectoral and intercostal nerves have been implicated. The purpose of this review is to provide an update on the current literature addressing the pathophysiology, clinical presentation, and treatment of patients presenting with chronic postoperative pain following cosmetic breast surgery. Methods A comprehensive literature review was performed in MEDLINE, PubMed, and Cochrane databases from 1996 to 2019 using the terms “cosmetic surgery”, “breast surgery”, “postoperative pain”, and “chronic pain”. Results Cosmetic breast surgery can have a similar presentation as post-mastectomy pain syndrome and thus have overlapping diagnostic criteria. Seven domains are identified for a diagnosis of PBSPS: Pain after breast surgery, neuropathic in nature, at least a moderate intensity of pain, as defined as within the middle one-third of the selected pain scale, pain for at least 6 months, symptoms occurring for 12 or more hours a day for a minimum of 4 days each week, pain in at least one of the following sites: breast, chest wall, axilla, or arm on the affected side, pain exacerbated by movement. Patient risk factors and surgical risk factors may influence the development of chronic post-cosmetic surgery breast pain. Improved perioperative analgesia including preoperative regional nerve anesthesia and postoperative catheter infusion have been shown to improve chronic postoperative pain outcomes. Conclusions The present review provides a discussion of clinical presentation, pathophysiology, and treatment and preventative strategies for chronic breast pain following cosmetic surgery. This review provides evidence from multiple randomized controlled trials (RCTs) and systematic reviews of efficacy and effectiveness. While chronic postoperative breast pain remains challenging to treat, various preventative strategies have been described to improve postoperative pain outcomes.

Objective Multiple clinical trials fail to identify clinically measurable health benefits of daily multivitamin and multimineral (MVM) consumption in the general adult population. Understanding the determinants of widespread use of MVMs may guide efforts to better educate the public about effective nutritional practices. The objective of this study was to compare self-reported and clinically measurable health outcomes among MVM users and non-users in a large, nationally representative adult civilian non-institutionalised population in the USA surveyed on the use of complementary health practices.Design Cross-sectional analysis of the effect of MVM consumption on self-reported overall health and clinically measurable health outcomes.Participants Adult MVM users and non-users from the 2012 National Health Interview Survey (n=21 603).Primary and secondary outcome measures Five psychological, physical, and functional health outcomes: (1) self-rated health status, (2) needing help with routine needs, (3) history of 10 chronic diseases, (4) presence of 19 health conditions in the past 12 months, and (5) Kessler 6-Item (K6) Psychological Distress Scale to measure non-specific psychological distress in the past month.Results Among 4933 adult MVM users and 16 670 adult non-users, MVM users self-reported 30% better overall health than non-users (adjusted OR 1.31; 95% CI 1.17 to 1.46; false discovery rate adjusted p

In this review, we evaluate recent literature on use of ER granisetron in clinical practice as compared with current antiemetics and describe its potential uses for perioperative PONV prophylaxis and treatment. Recent literature was evaluated on ER granisetron use compared with currently used antiemetic agents ondansetron, droperidol, metoclopramide, promethazine, and dexamethasone with a focus on procedural anti-emesis. Though promising great effect, application of extended release granisetron to clinical use may be limited by it's increased relative cost.

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During our 2019 ConVerge2Xcelerate (ConV2X) conference in Boston, we focused on the theme "Proving Market Value with Pragmatic Innovation in Healthcare" (see https://conv2x-2019.eventcreate.com/). This year, along with BHTY editorial board members, conference speakers were invited to join with Tory Cenaj, Publisher of BHTY, to contribute their expertise and share insights for the near-term landscape of blockchain in healthcare.

Interleukin (IL)-2 is expressed during T cell activation and induces the proliferation and differentiation of T cells. CD4+Foxp3+ regulatory T cells (Tregs) constitutively express the high affinity IL-2 receptor (CD25/IL-2Rα) and rapidly respond to IL-2 to elaborate numerous suppressive mechanisms that limit immune-mediated pathologies. Accumulating evidence supports the concept that an aberrant balance between Tregs and Teff contribute to the pathology of intestinal inflammation and that the IL-2/Treg axis is a potential pathway to exploit for the treatment of inflammatory bowel disease (IBD). Here, we show that treatment of mice with IL-2/IL-2 antibody (JES6-1) immunocomplex during DSS-induced colitis induced Foxp3+ Treg expansion, but also potently stimulated GATA3+ type 2 innate lymphoid cell (ILC2) proliferation and high-level expression of IL-5. Furthermore, IL-2/JES6-1 treatment resulted in massive eosinophil accumulation and activation in the inflamed colon, and afforded only modest protection from colitis. In light of these findings, we observed that combined IL-2/JES6-1 and anti-IL-5 mAb treatment was most effective at ameliorating DSS-induced colitis compared to either treatment alone and that this regimen allowed for Foxp3+ Treg expansion without concomitant eosinophilia. Collectively, our findings provide insight into how blockade of IL-5 may aid in optimizing IL-2 immunotherapy for the treatment of intestinal inflammation.

Medical school learning communities have many benefits for students. In this perspective, the authors briefly describe how learning communities have benefited them as faculty. These include finding other like-minded faculty, improving communication and clinical skills, career advancement through scholarly work associated with the learning community, and above all, developing mutually beneficial relationships with students. Here, they offer viewpoints from junior and senior faculty members on how the learning community has positively affected them.

To review blockchain lessons learned in 2018 and near-future predictions for blockchain in healthcare, Blockchain in Healthcare Today (BHTY) asked the world's blockchain in healthcare experts to share their insights. Here, our internationally-renowned BHTY peer-review board discusses their major predictions. Based on their responses, presented in detail below, ten major themes (Table ) for the future of blockchain in healthcare will emerge over the 12 months. CORRIGENDUM: This following paragraph has been corrected (page 3, first paragraph) from: "Fourth, with over 1000 insurance companies in the country, filling out paperwork to document provider training and licensure is a nightmare. The Synaptic Health Alliance aims to simplify this process by putting all credentialing information on a distributed public ledger for all stakeholders to access.1" To: "Fourth, keeping health care provider directories maintained by health plans up-to-date is a critical, complex issue facing organizations across the health care system. The first project of the Synaptic Health Alliance aims to simplify this process by putting provider demographic information on a permissioned blockchain for Alliance members to access and maintain.1"