Enhancing Wheat Growth, Physiology, Yield, and Water Use Efficiency under Deficit Irrigation by Integrating Foliar Application of Salicylic Acid and Nutrients at Critical Growth Stages.

Transitioning from full to deficit irrigation (DI) has become a key strategy in arid regions to combat water scarcity and enhance irrigation water use efficiency (IWUE). However, implementing DI requires additional approaches to counter its negative effects on wheat production. One effective approach is the foliar application of salicylic acid (SA), micronutrients (Mic; zinc and manganese), and macronutrients (Mac; nitrogen, phosphorus, and potassium). However, there is a lack of knowledge on the optimal combinations and timing of foliar application for these components to maximize their benefits under arid conditions, which is the primary focus of this study. A two-year field study was conducted to assess the impact of the foliar application of SA alone and in combination with Mic (SA + Mic) or Mic and Mac (SA + Mic + Mac) at various critical growth stages on wheat growth, physiology, productivity, and IWUE under DI conditions. Our result demonstrated that the foliar application of different components, the timing of application, and their interaction had significant effects on all investigated wheat parameters with few exceptions. Applying different components through foliar application at multiple growth stages, such as tillering and heading or tillering, heading, and grain filling, led to significant enhancements in various wheat parameters. The improvements ranged from 7.7% to 23.2% for growth parameters, 8.7% to 24.0% for physiological traits, 1.4% to 21.0% for yield and yield components, and 14.8% to 19.0% for IWUE compared to applying the components only at the tillering stage. Plants treated with different components (SA, Mic, Mac) exhibited enhanced growth, production, and IWUE in wheat compared to untreated plants. The most effective treatment was SA + Mic, followed by SA alone and SA + Mic + Mac. The foliar application of SA, SA + Mic, and SA + Mic + Mac improved growth parameters by 1.2-50.8%, 2.7-54.6%, and 2.5-43.9%, respectively. Yield parameters were also enhanced by 1.3-33.0%, 2.4-37.2%, and 3.0-26.6% while IWUE increased by 28.6%, 33.0%, and 18.5% compared to untreated plants. A heatmap analysis revealed that the foliar application of SA + Mic at multiple growth stages resulted in the highest values for all parameters, followed by SA alone and SA + Mic + Mac applications at multiple growth stages. The lowest values were observed in untreated plants and with the foliar application of different components only at the tillering stage. Thus, this study suggested that the foliar application of SA + Mic at various growth stages can help sustain wheat production in arid regions with limited water resources.

Fecal microbiota and volatile metabolome pattern alterations precede late-onset meningitis in preterm neonates.

OBJECTIVE: The fecal microbiota and metabolome are hypothesized to be altered before late-onset neonatal meningitis (LOM), in analogy to late-onset sepsis (LOS). The present study aimed to identify fecal microbiota composition and volatile metabolomics preceding LOM. METHODS: Cases and gestational age-matched controls were selected from a prospective, longitudinal preterm cohort study (born <30 weeks' gestation) at nine neonatal intensive care units. The microbial composition (16S rRNA sequencing) and volatile metabolome (gas chromatography-ion mobility spectrometry (GC-IMS) and GC-time-of-flight-mass spectrometry (GC-TOF-MS)), were analyzed in fecal samples 1-10 days pre-LOM. RESULTS: Of 1397 included infants, 21 were diagnosed with LOM (1.5%), and 19 with concomitant LOS (90%). Random Forest classification and MaAsLin2 analysis found similar microbiota features contribute to the discrimination of fecal pre-LOM samples versus controls. A Random Forest model based on six microbiota features accurately predicts LOM 1-3 days before diagnosis with an area under the curve (AUC) of 0.88 (n=147). Pattern recognition analysis by GC-IMS revealed an AUC of 0.70-0.76 (P<0.05) in the three days pre-LOM (n=92). No single discriminative metabolites were identified by GC-TOF-MS (n=66). CONCLUSION: Infants with LOM could be accurately discriminated from controls based on preclinical microbiota composition, while alterations in the volatile metabolome were moderately associated with preclinical LOM.

The use of faecal microbiota transplant as treatment for recurrent or refractory Clostridioides difficile infection and other potential indications: second edition of joint British Society of Gastroenterology (BSG) and Healthcare Infection Society (HIS) guidelines.

The first British Society of Gastroenterology (BSG) and Healthcare Infection Society (HIS)-endorsed faecal microbiota transplant (FMT) guidelines were published in 2018. Over the past 5 years, there has been considerable growth in the evidence base (including publication of outcomes from large national FMT registries), necessitating an updated critical review of the literature and a second edition of the BSG/HIS FMT guidelines. These have been produced in accordance with National Institute for Health and Care Excellence-accredited methodology, thus have particular relevance for UK-based clinicians, but are intended to be of pertinence internationally. This second edition of the guidelines have been divided into recommendations, good practice points and recommendations against certain practices. With respect to FMT for Clostridioides difficile infection (CDI), key focus areas centred around timing of administration, increasing clinical experience of encapsulated FMT preparations and optimising donor screening. The latter topic is of particular relevance given the COVID-19 pandemic, and cases of patient morbidity and mortality resulting from FMT-related pathogen transmission. The guidelines also considered emergent literature on the use of FMT in non-CDI settings (including both gastrointestinal and non-gastrointestinal indications), reviewing relevant randomised controlled trials. Recommendations are provided regarding special areas (including compassionate FMT use), and considerations regarding the evolving landscape of FMT and microbiome therapeutics.

Faecal Microbiota Transplantation [FMT] in the Treatment of Chronic Refractory Pouchitis: A Systematic Review and Meta-analysis.

BACKGROUND: The aim of this systematic review and meta-analysis is to assess the efficacy and safety of faecal microbiota transplantation [FMT] in the treatment of chronic pouchitis. METHODS: A PRISMA-compliant systematic review and meta-analysis was conducted using the following databases and clinical trial registers: Medline, Embase, Scopus, Cochrane Database of Systematic Reviews [CENTRAL], clinical trials.gov, ScienceDirect, and VHL [virtual health library]. The primary outcome was clinical response/remission in patients treated with FMT. Secondary outcomes included safety profile, quality of life, and changes in the gut microbiome. RESULTS: Seven observational cohort studies/case series and two randomised, controlled trials with a total of 103 patients were included. The route, preparation, and quantity of FMT administered varied among the included studies. Clinical response rate of 42.6% with a remission rate of 29.8% was estimated in our cohort following FMT therapy. Minor, self-limiting, adverse events were reported, and the treatment was well tolerated with good short- and long-term safety profiles. Successful FMT engraftment in recipients varied and, on average, microbial richness and diversity was lower in patients with pouchitis. In some instances, shifts with specific changes towards abundance of species, suggestive of a 'healthier' pouch microbiota, were observed following treatment with FMT. CONCLUSION: The evidence for FMT in the treatment of chronic pouchitis is sparse, which limits any recommendations being made for its use in clinical practice. Current evidence from low-quality studies suggests a variable clinical response and remission rate, but the treatment is well tolerated, with a good safety profile. This review emphasises the need for rationally designed, well-powered, randomised, placebo-controlled trials to understand the efficacy of FMT for the treatment of pouchitis.

Prevalence of Extraintestinal Manifestations in Inflammatory Bowel Disease: A Systematic Review and Meta-analysis.

BACKGROUND: Inflammatory bowel disease (IBD) is a multisystem disease impacting various body systems including musculoskeletal, ocular, skin, hepatobiliary, pulmonary, cardiac, and haematological systems. The extraintestinal manifestations of IBD are frequent, common in both ulcerative colitis (UC) and Crohn's disease (CD), and impact the morbidity and mortality of patients. METHODS: The Embase, Embase classic, and PubMed databases were searched between January 1979 and December 2021. A random effects model was performed to find the pooled prevalence of joint, ocular, and skin extraintestinal manifestations of UC and CD. RESULTS: Fifty-two studies were included that reported on 352 454 patients. The prevalence of at least 1 joint, ocular, or skin extraintestinal manifestation in all IBD, UC, and CD was 24%, 27%, and 35% respectively. The prevalence between UC and CD were similar for pyoderma gangrenosum and axial joint manifestations. Ocular manifestations were found to be more common in CD than in UC. Peripheral joint manifestations and erythema nodosum were found to be more common in CD than UC. DISCUSSION: To our knowledge, this is the first meta-analysis that reports on the prevalence of at least 1 joint, ocular, or skin extraintestinal manifestation in IBD. Our results are largely consistent with figures and statements quoted in the literature. However, our findings are based on significantly larger cohort sizes. Thus, our results have the potential to better power studies and more accurately counsel patients.

The prevalence of joint, ocular, or skin extraintestinal manifestations in IBD, UC, and CD was 24%, 27%, and 35% respectively. Ocular manifestations were more common in CD. Peripheral joint manifestations and erythema nodosum were more common in CD.

Biochemical responses in mice induced by saxitoxins extracted from the cockles Acanthocardia tuberculatum.

Harmful algae blooms have increased in frequency and geographic range in recent decades, and they produce toxins strains such as saxitoxins (STXs). they block voltage-gated sodium channels and can lead to several poisonings and the death of organisms that pose a significant risk to public and environmental health. The study of STXs toxicity has been carried out but little is known about the response of antioxidant enzymes activities to STXs in mice. The purpose of this study was to evaluate biochemical responses and oxidative stress induced by STXs extracted from Acanthocardia tuberculatum. To this end, daily, mice were treated orally for 7 days with sublethal concentrations (10 mg/100 g mouse). The animal's liver was assessed using biomarkers such as activities of catalase (CAT), thiobarbituric acid reactive substances (TBARS), glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and succinate dehydrogenase (SDH). In the blood, plasmatic markers were analysed as glutamic oxalic transaminase (GOT), glutamic pyruvic transaminase (GPT), creatinine phosphokinase (CPK), lactate dehydrogenase (LDH), urea and creatinine. Globally, test toxicity test showed a significant decrease in the weight at 10 mg /100 g mouse, and the results showed an increase of GPT, GOT, CPK, LDH, CAT and TBARS activities and the inhibitory effect of GAPDH activities but creatinine, urea and SDH activities showed no significative difference from the control. We concluded that STXs induce oxidative stress breaking in mice the balance of the defence system and causing oxidations reactions. Moreover, STXs affect energy metabolism in mice, however, renal function in mice is not affected by exposure to STXs.

Establishing key performance indicators for inflammatory bowel disease in the UK.

Background and aims: Healthcare quality improvement (QI) is the systematic process to continuously improve the quality of care and outcomes for patients. The landmark Inflammatory Bowel Disease (IBD) UK National Audits provided a means to measure the variation in care, highlighting the need to define the standards of excellence in IBD care. Through a consensus approach, we aimed to establish key performance indicators (KPIs), providing reliable benchmarks for IBD care delivery in UK. Methods: KPIs that measure critical aspects of a patient journey within an IBD service were identified though stakeholder meetings. A two-stage Delphi consensus was then conducted. The first involved a multidisciplinary team of IBD clinicians and patients to refine definitions and methodology. The second stage assessed feasibility and utility of the proposed QI process by surveying gastroenterology services across UK. Results: First, the four proposed KPIs were refined and included time from primary care referral to diagnosis in secondary care, time to treatment recommendation following a diagnosis, appropriate use of steroids and advanced therapies prescreening and assessment. Second, the Delphi consensus reported >85% agreement on the feasibility of local adoption of the QI process and >75% agreement on the utility of benchmarking of the KPIs. Conclusions: Through a structured approach, we propose quantifiable KPIs for benchmarking to improve and reduce the individual variation in IBD care across the UK.

Noise reduction strategies in metagenomic chromosome confirmation capture to link antibiotic resistance genes to microbial hosts.

The gut microbiota is a reservoir for antimicrobial resistance genes (ARGs). With current sequencing methods, it is difficult to assign ARGs to their microbial hosts, particularly if these ARGs are located on plasmids. Metagenomic chromosome conformation capture approaches (meta3C and Hi-C) have recently been developed to link bacterial genes to phylogenetic markers, thus potentially allowing the assignment of ARGs to their hosts on a microbiome-wide scale. Here, we generated a meta3C dataset of a human stool sample and used previously published meta3C and Hi-C datasets to investigate bacterial hosts of ARGs in the human gut microbiome. Sequence reads mapping to repetitive elements were found to cause problematic noise in, and may importantly skew interpretation of, meta3C and Hi-C data. We provide a strategy to improve the signal-to-noise ratio by discarding reads that map to insertion sequence elements and to the end of contigs. We also show the importance of using spike-in controls to quantify whether the cross-linking step in meta3C and Hi-C protocols has been successful. After filtering to remove artefactual links, 87 ARGs were assigned to their bacterial hosts across all datasets, including 27 ARGs in the meta3C dataset we generated. We show that commensal gut bacteria are an important reservoir for ARGs, with genes coding for aminoglycoside and tetracycline resistance being widespread in anaerobic commensals of the human gut.

Effects of Salicylic Acid and Macro- and Micronutrients through Foliar and Soil Applications on the Agronomic Performance, Physiological Attributes, and Water Productivity of Wheat under Normal and Limited Irrigation in Dry Climatic Conditions.

Ensuring food security with severe shortages of freshwater and drastic changes in climatic conditions in arid countries requires the urgent development of feasible and user-friendly strategies. Relatively little is known regarding the impacts of the co-application (Co-A) of salicylic acid (SA), macronutrients (Mac), and micronutrients (Mic) through foliar (F) and soil (S) application strategies on field crops under arid and semiarid climatic conditions. A two-year field experiment was designed to compare the impacts of seven (Co-A) treatments of this strategy, including a control, FSA + Mic, FSA + Mac, SSA + FMic, SSA + FSA + Mic, SSA + Mic + FSA, and SSA + Mic + FMac + Mic on the agronomic performance, physiological attributes, and water productivity (WP) of wheat under normal (NI) and limited (LMI) irrigation conditions. The results reveal that the LMI treatment caused a significant reduction in various traits related to the growth (plant height, tiller and green leaf numbers, leaf area index, and shoot dry weight), physiology (relative water content and chlorophyll pigments), and yield components (spike length, grain weight and grain numbers per spike, thousand-grain weight, and harvest index) of wheat by 11.4-47.8%, 21.8-39.8%, and 16.4-42.3%, respectively, while WP increased by 13.3% compared to the NI treatment. The different Co-A treatments have shown a 0.2-23.7%, 3.6-26.7%, 2.3-21.6%, and 12.2-25.0% increase in various traits related to growth, physiology, yield, and WP, respectively, in comparison to the control treatment. The SSA+ FSA + Mic was determined as the best treatment that achieved the best results for all studied traits under both irrigation conditions, followed by FSA + Mic and SSA + Mic + FSA under LMI in addition to FSA + Mac under NI conditions. It can be concluded that the Co-A of essential plant nutrients along with SA accomplished a feasible, profitable, and easy-to-use strategy to attenuate the negative impacts of deficit irrigation stress, along with the further improvement in the growth and production of wheat under NI conditions.

Germline mutations of B-Raf proto-oncogene and pathological implications in prostate cancer: observational study.

B-Raf proto-oncogene has been found in a variety of neoplasms. BRAF stimulation can promote tumour proliferation through the activation of the MAP/ERK kinase pathway. This study aimed to determine the germline spectra of BRAF and the association with pathological criteria of prostate tumours. Methods: Fifty blood samples from men treated with prostate cancer were analyzed for BRAF germline mutations and confirmed by Sanger sequencing, in addition, to establishing the frequencies and clinical correlations of frequent mutations in the BRAF gene for both exon 11 and exon 15. The frequency and distribution of high-frequency mutations were analyzed according to the pathological criteria of the patients. Results: Frameshift mutations: c.1628_1629insA and c.1624_1625insT with a frequency of (46%) and (18%), respectively, Nonsense mutations: c.1181C>A (p.Ser394Ter) was detected in one patient, missense mutations: c.1226A>G (p.Gln409Arg), c.1270T>C (p.Trp424Arg), c.1270_1271delins2 (p.Trp424Leu), with a frequency of (4%) were detected. There was no significant difference between mutation carriers and non-carriers regarding medical and surgical history, but prostate-specific antigen concentration was significantly different between the two groups. Conclusion: The results of this study elucidate the presence and involvement of germline mutations in prostate cancer, which could serve as a potential indicator for the diagnosis and therapeutic management of prostate cancer in the population studied.

The analysis of gut microbiota in patients with bile acid diarrhoea treated with colesevelam.

Introduction: Bile acid diarrhoea (BAD) is a common disorder that results from an increased loss of primary bile acids and can result in a change in microbiome. The aims of this study were to characterise the microbiome in different cohorts of patients with BAD and to determine if treatment with a bile acid sequestrant, colesevelam, can alter the microbiome and improve microbial diversity. Materials and methods: Patients with symptoms of diarrhoea underwent 75-selenium homocholic acid (75SeHCAT) testing and were categorised into four cohorts: idiopathic BAD, post-cholecystectomy BAD, post-operative Crohn's disease BAD and 75SeHCAT negative control group. Patients with a positive 75SeHCAT (<15%) were given a trial of treatment with colesevelam. Stool samples were collected pre-treatment, 4-weeks, 8-weeks and 6-12 months post-treatment. Faecal 16S ribosomal RNA gene analysis was undertaken. Results: A total of 257 samples were analysed from 134 patients. α-diversity was significantly reduced in patients with BAD and more specifically, in the idiopathic BAD cohort and in patients with severe disease (SeHCAT <5%); p < 0.05. Colesevelam did not alter bacterial α/ß-diversity but patients who clinically responded to treatment had a significantly greater abundance of Fusobacteria and Ruminococcus, both of which aid in the conversion of primary to secondary bile acids. Conclusion: This is the first study to examine treatment effects on the microbiome in BAD, which demonstrated a possible association with colesevelam on the microbiome through bile acid modulation in clinical responders. Larger studies are now needed to establish a causal relationship with colesevelam and the inter-crosstalk between bile acids and the microbiome.

Appropriate Application Methods for Salicylic Acid and Plant Nutrients Combinations to Promote Morpho-Physiological Traits, Production, and Water Use Efficiency of Wheat under Normal and Deficit Irrigation in an Arid Climate.

Freshwater shortage and inadequate nutrient management are the two major challenges for sustainable wheat production in arid agro-ecosystems. Relatively little is known about the positive roles of the application methods for the combination of salicylic acid (SA) and plant nutrients in sustaining wheat production under arid climatic conditions. A two-year field study was undertaken to assess the impact of seven treatments for the integrated application of SA, macronutrients, and micronutrients on the morpho-physiological traits, yield, and irrigation water use efficiency (IWUE) of wheat subjected to full (FL) and limited (LM) irrigation regimes. The results showed that the LM regime caused a significant reduction in different plant growth traits, relative water content, chlorophyll pigments, yield components, and yield, while a significant increase was observed in IWUE. The sole application of SA or co-application with micronutrients through soil did not significantly affect the studied traits under the FL regime, while they achieved some improvement over untreated plants under the LM regime. Based on the different multivariate analyses, the soil and foliar applications for the combinations of SA and micronutrients, as well as a foliar application for the combinations of SA, macronutrients, and micronutrients were identified as an efficient option for mitigating the negative impacts of water deficit stress and enhancing the growth and production of wheat under normal conditions. In conclusion, the results obtained herein indicated that the co-application of SA and macro- and micronutrients is an effective option to greatly enhance and improve the growth and production of wheat crops in water-scarce countries of arid regions, such as Saudi Arabia, while an appropriate application method for this combination was required for positive effects.

Integrating Application Methods and Concentrations of Salicylic Acid as an Avenue to Enhance Growth, Production, and Water Use Efficiency of Wheat under Full and Deficit Irrigation in Arid Countries.

As water deficit in arid countries has already become the norm rather than the exception, water conservation in crop production processes has become very critical. Therefore, it is urgent to develop feasible strategies to achieve this goal. Exogenous application of salicylic acid (SA) has been proposed as one of the effective and economical strategies for mitigating water deficit in plants. However, the recommendations concerning the proper application methods (AMs) and the optimal concentrations (Cons) of SA under field conditions seem contradictory. Here, a two-year field study was conducted to compare the effects of twelve combinations of AMs and Cons on the vegetative growth, physiological parameters, yield, and irrigation water use efficiency (IWUE) of wheat under full (FL) and limited (LM) irrigation regimes. These combinations included seed soaking in purified water (S0), 0.5 mM SA (S1), and 1.0 mM SA (S2); foliar spray of SA at concentrations of 1.0 mM (F1), 2.0 mM (F2), and 3.0 mM (F3); and combinations of S1 and S2 with F1 (S1F1 and S2F1), F2 (S1F2 and S2F2), and F3 (S1F3 and S2F3). The results showed that the LM regime caused a significant reduction in all vegetative growth, physiological, and yield parameters, while it led to an increase in IWUE. The application of SA through seed soaking, foliar application, and a combination of both methods increased all of the studied parameters in all the evaluated times, resulting in higher values for all parameters than the treatment without SA (S0). The multivariate analyses, including principal component analysis and heatmapping, identified the foliar application method with 1-3 mM SA alone or in combination with seed soaking with 0.5 mM SA as the best treatments for the optimal performance of wheat under both irrigation regimes. Overall, our results indicated that exogenous application of SA has the potential to greatly improve growth, yield, and IWUE under limited water application, while optimal coupling combinations of AMs and Cons were required for positive effects in field conditions.

Cupressus sempervirens L. flavonoids as potent inhibitors to xanthine oxidase: in vitro, molecular docking, ADMET and PASS studies.

Excessive intake of purine-rich foods such as seafood and red meat leads to excess xanthine oxidase activity and provokes gout attacks. The aim of this paper is to evaluate in vitro and in silico, the inhibition effect of Cupressus sempervirens plant extracts (flavonoids (Cae) and alkaloids (CaK)) and its six derivative compounds on bovine xanthine oxidase (BXO). The in silico study consists of molecular docking with GOLD v4.0 based on the best PLPchem score (PLP) and prediction of biological activity with the PASS server tool. The inhibitors used were lignan (cp1), Amentoflavone (cp2), Cupressuflavone (cp3), Isocryptomerin (cp4), Hinokiflavone (cp5), and Neolignan (cp6). The in vitro results showed that CaK gives an IC50 of 3.52 ± 0.04 µg/ml. Similarly, Cae saved an IC50 of 8.46 ± 1.98 µg/ml compared with the control (2.82 ± 0.10 µg/ml). The in silico results show that cp1 was the best inhibitor model (PLP of 88.09) with approved pharmacokinetics. These findings suggest that cp1 and cp2 may offer good alternatives for the treatment of hyperuricemia; cp3 was moderate, while the others (cp4 to cp6) were considered weak inhibitors according to their PLP.Communicated by Ramaswamy H. Sarma.

Integration of stool microbiota, proteome and amino acid profiles to discriminate patients with adenomas and colorectal cancer.

BACKGROUND: Screening for colorectal cancer (CRC) reduces its mortality but has limited sensitivity and specificity. Aims We aimed to explore potential biomarker panels for CRC and adenoma detection and to gain insight into the interaction between gut microbiota and human metabolism in the presence of these lesions. METHODS: This multicenter case-control cohort was performed between February 2016 and November 2019. Consecutive patients ≥18 years with a scheduled colonoscopy were asked to participate and divided into three age, gender, body-mass index and smoking status-matched subgroups: CRC (n = 12), adenomas (n = 21) and controls (n = 20). Participants collected fecal samples prior to bowel preparation on which proteome (LC-MS/MS), microbiota (16S rRNA profiling) and amino acid (HPLC) composition were assessed. Best predictive markers were combined to create diagnostic biomarker panels. Pearson correlation-based analysis on selected markers was performed to create networks of all platforms. RESULTS: Combining omics platforms provided new panels which outperformed hemoglobin in this cohort, currently used for screening (AUC 0.98, 0.95 and 0.87 for CRC vs controls, adenoma vs controls and CRC vs adenoma, respectively). Integration of data sets revealed markers associated with increased blood excretion, stress- and inflammatory responses and pointed toward downregulation of epithelial integrity. CONCLUSIONS: Integrating fecal microbiota, proteome and amino acids platforms provides for new biomarker panels that may improve noninvasive screening for adenomas and CRC, and may subsequently lead to lower incidence and mortality of colon cancer.

Proposed pathway for therapeutic drug monitoring and dose escalation of vedolizumab.

Vedolizumab is a gut-selective monoclonal antibody approved for the management of Crohn's disease and ulcerative colitis. The available data demonstrate a favourable response to dose escalation in patients with primary non-response or secondary loss of response to vedolizumab. While therapeutic drug monitoring has a proven clinical utility for tumour necrosis factor antagonists, the available guidance for therapeutic drug monitoring and dose escalation of vedolizumab is rather limited. The present review proposes a practical algorithm to use vedolizumab trough levels in the management of treatment failure. Therapeutic drug monitoring can differentiate underexposed patients from those with mechanistic failure. Underdosed patients can respond to dose escalation instead of unnecessarily switching to other treatment modalities. We also review the safety and potential cost-effectiveness of vedolizumab dose escalation, the role of antidrug antibodies and the possible applicability of this strategy to subcutaneous vedolizumab.

Efficacy of Intraoperative Low Dose Intravenous Amiodarone in Pharmacologic Cardioversion in Patients with Preoperative Atrial Fibrillation Presenting for Mitral Valve Replacement Surgery Randomized Control Trial.

BACKGROUND: Atrial fibrillation (AF) is the most common form of dysrhythmia observed in the clinical field, causing multiple morbidities, such as thromboembolic complications. Hence, the maintenance of sinus rhythm is superior to rate control. This study tests the efficacy of single- and low-dose amiodarone on the persistence of AF after surgery before transfer to the intensive care unit. METHODS: A double-blinded, randomized controlled trial assessed 113 patients who underwent mitral valve surgery with preoperative chronic AF. Patients were divided into two groups: the control group (N = 55) who received 50 mL of 5% dextrose over 10 min after general anesthesia induction, and the amiodarone group (N = 58) who received 1 mg/kg of amiodarone diluted in 50 mL of 5% dextrose over 10 min shortly after anesthesia induction. RESULTS: The amiodarone group had a statistically significant successful conversion of preoperative AF to normal sinus rhythm in 40 patients (72.73%). The control group demonstrated spontaneous conversion from AF to a normal sinus rhythm in seven patients (12.73%). The sinus rhythm was maintained in 60% of patients (36), as four patients reverted to AF during the hospital stay despite the initial normal sinus rhythm after the operation. In contrast, 53 (96.36%) patients in the control group were discharged from the hospital with a controlled rate of AF. In addition, low-dose amiodarone caused a statistically significant reduction in heart rates at 10, 30, and 60 min after declamping, extended throughout the first 24 h with mean heart rates of 97.233±7.311, 99.509±8.482, and 97.940±7.715 bpm, respectively. In comparison, the control group had heart rates of 115.382±7.547, 115.055±13.919, and 113.618±8.765 bpm at these times. The mean postoperative heart rate at the end of the first 24 h was 97.793±7.189 bpm in the amiodarone group and 113.036±9.737 bpm in the control group. No mortality or need for mechanical support was recorded in either group. CONCLUSIONS: Single and low-dose intraoperative intravenous amiodarone during mitral valve surgery may be practical to aid in pharmacological cardioversion of patients with preoperative chronic AF presenting for mitral valve surgery.

Relation of post-stroke headachto cerebrovascular pathology and hemodynamics.

Despite high prevalence of cerebrovascular stroke, headache attributed to ischemic strokes is often undertreated and overlooked. The aim is to detect the relation of a post-stroke headache to cerebrovascular pathology and changes in hemodynamics through a high-resolution duplex ultrasound examination. The present study was a case-control study conducted among 239 patients, who presented with an acute ischemic stroke. Patients were sub-divided into two groups: group I included patients with headache attributed to ischemic stroke (cases) and group II included headache-free stroke patients (controls). History consisted of headache characteristics and risk factors. Clinical and radiological examination were preformed to detect the type of stroke. Ultrasound duplex examination of extra-cranial and intra-cranial cerebrovascular system was carried for both groups. Group I included 112 patients (mean age, 57.66 ±6.59 years), and group II included 127 patients (mean age 57.73 ±7.89 years). Post-stroke headache was more frequent in patients with posterior circulation infarction (58%). Post-stroke headache was reported within 7 days post-stroke in 61.6% of patients. Pre-stroke headache was an independent predictor for post-stroke headache occurrence (OR = 28.187, 95% CI: 6.612-120.158%, p < 0.001). Collateral opening and various degrees of intra-cranial vascular stenosis were strong predictors of headache occurrence (OR = 25.071, 95% CI: 6.498-96.722%, p < 0.001). In conclusion, post-stroke headache is a common phenomenon, especially in patients with pre-stroke headache, history of old stroke, posterior circulation infarction, and large artery disease. This headache was of moderate-intensity with clinical characteristics of tension-type. Intra-cranial cerebrovascular pathological changes including opening of collateral channels and variable degrees of stenosis of cerebrovascular systems were implicated in the production of that headache.

Gut microbiome and autoimmune disorders.

Autoimmune diseases have long been known to share a common pathogenesis involving a dysregulated immune system with a failure to recognize self from non-self-antigens. This immune dysregulation is now increasingly understood to be induced by environmental triggers in genetically predisposed individuals. Although several external environmental triggers have been defined in different autoimmune diseases, much attention is being paid to the role of the internal micro-environment occupied by the microbiome, which was once termed "the forgotten organ." In this regard, the gut microbiome, serving as an intermediary between some of those external environmental effectors and the immune system, helps programming of the immune system to be tolerant to innocent external and self-antigens. However, in the presence of perturbed gut microbiota (dysbiosis), the immune system could be erroneously directed in favor of pro-inflammatory pathways to instigate different autoimmune processes. An accumulating body of evidence, including both experimental and human studies (observational and interventional), points to the role of the gut microbiome in different autoimmune diseases. Such evidence could provide a rationale for gut microbiome manipulation with therapeutic and even preventative intent in patients with established or predisposed to autoimmune diseases, respectively. Perturbations of the gut microbiome have been delineated in some immune mediated diseases, IBD in particular. However, such patterns of disturbance (microbiome signatures) and related pathogenetic roles of the gut microbiome are context dependent and cannot be generalized in the same exact way to other autoimmune disorders, and the contribution of the gut microbiome to different disease phenotypes has to be precisely defined. In this review, we revise the evidence for a role of the gut microbiome in various autoimmune diseases and possible mechanisms mediating such a role.