15N-DNA stable isotope probing reveals niche differentiation of ammonia oxidizers in paddy soils.

Chemoautotrophic canonical ammonia oxidizers (ammonia-oxidizing archaea (AOA) and ammonia-oxidizing bacteria (AOB)) and complete ammonia oxidizers (comammox Nitrospira) are accountable for ammonia oxidation, which is a fundamental process of nitrification in terrestrial ecosystems. However, the relationship between autotrophic nitrification and the active nitrifying populations during 15N-urea incubation has not been totally clarified. The 15N-labeled DNA stable isotope probing (DNA-SIP) technique was utilized in order to study the response from the soil nitrification process and the active nitrifying populations, in both acidic and neutral paddy soils, to the application of urea. The presence of C2H2 almost completely inhibited NO3--N production, indicating that autotrophic ammonia oxidation was dominant in both paddy soils. 15N-DNA-SIP technology could effectively distinguish active nitrifying populations in both soils. The active ammonia oxidation groups in both soils were significantly different, AOA (NS (Nitrososphaerales)-Alpha, NS-Gamma, NS-Beta, NS-Delta, NS-Zeta and NT (Ca. Nitrosotaleales)-Alpha), and AOB (Nitrosospira) were functionally active in the acidic paddy soil, whereas comammox Nitrospira clade A and Nitrosospira AOB were functionally active in the neutral paddy soil. This study highlights the effective discriminative effect of 15N-DNA-SIP and niche differentiation of nitrifying populations in these paddy soils. KEY POINTS: • 15N-DNA-SIP technology could effectively distinguish active ammonia oxidizers. • Comammox Nitrospira clade A plays a lesser role than canonical ammonia oxidizers. • The active groups in the acidic and neutral paddy soils were significantly different.

Formation of a conceptual framework during the development of a patient-reported outcome measure for early gastrointestinal recovery: phase I of the PRO-diGi study.

AIM: Patients admitted to hospital for abdominal surgery often experience gastrointestinal dysfunction. Many studies have reported outcomes following gastrointestinal dysfunction, yet there is no unified definition of recovery or a validated patient-reported outcome measure (PROM). The first stage of PROM development requires formation of a conceptual framework to identify key themes to patients. The aim of this study was to utilize semistructured interviews to identify core themes and concepts relevant to patients to facilitate development of a conceptual framework. METHOD: Adult patients admitted to hospital for major gastrointestinal, urological or gynaecological surgery, in an emergency or elective setting, were eligible to participate. Patients treated nonoperatively for small bowel obstruction were also eligible. Interviews were conducted by telephone, audio-recorded, transcribed, coded and analysed using NVivo software by two researchers and reviewed by lay members of the steering group. Interviews continued until data saturation was reached. Ethical approval was gained prior to interviews (21/WA/0231). RESULTS: Twenty nine interviews were completed (17 men, median age 64 years) across three specialties (20 gastrointestinal, six gynaecological, three urological). Two overarching themes of 'general recovery' and 'gastrointestinal symptoms' were identified. General recovery included three themes: 'life impact', 'mental impact', including anxiety, and 'physical impact', including fatigue. Gastrointestinal symptoms included three themes: 'abdominal symptoms' such as pain, 'diet and appetite' and 'expulsory function', such as stool frequency. A total of 18 gastrointestinal symptoms were identified during patient recovery-many of which lasted several weeks following discharge. CONCLUSION: This study reports a range of gastrointestinal and nongastrointestinal symptoms experienced by patients during early gastrointestinal recovery. Identified symptoms have been synthesized into a conceptual framework to enable development of a definitive PROM for early gastrointestinal recovery.

Dietary tryptophan-rich protein hydrolysate can acutely impact physiological and psychological measures of mood and stress in healthy adults.

BACKGROUND: Tryptophan is the precursor to the mood regulating neurotransmitter serotonin. Its brain bioavailability from food can be dependent on the dietary source. Egg protein hydrolysate (EPH), a dietary supplement rich in tryptophan, has previously shown to acutely impact cognition, mood and stress benefits at 2 g dose. No data exist on the acute effects of lower doses in a food matrix. METHODS: This exploratory study tested the acute effects of low-doses EPH (0.5, 1 g) in a food matrix on cognition, mood and stress. The study employed a double-blinded randomized controlled parallel design in 45 participants with three arms. The effects of the interventions were measured after a multi-task cognitive stressor on blood biomarkers, self-reported mood states, performances of attention, autonomic parameters and, emotional reactivity responses from electroencephalographic recording. RESULTS: As compared to the reference, the 1 g EPH dose increased tryptophan bioavailability from baseline, and, both doses improved heart rate variability parameters related to parasympathetic activation while showing differences in the late neural response to negative versus neutral emotions. Post-hoc analyses indicated a gender difference in the baseline tryptophan bioavailability and further examination suggested the change in mood rating depends on the interaction between gender and change from baseline of tryptophan bioavailability. CONCLUSIONS: Overall, this study suggests that low levels of tryptophan rich EPH in a food matrix positively impact mood or stress in acute settings and adds to the body of evidence linking tryptophan and dietary sources thereof with these benefits. Confirmatory randomized controlled trials are needed to confirm these findings.Trial registration number: CER-VD N°2019-00218.

Postoperative nonsteroidal anti-inflammatory drugs in relation to recurrence, survival and anastomotic leakage after surgery for colorectal cancer.

AIM: The aim of this work was to investigate whether nonsteroidal anti-inflammatory drugs (NSAIDs) could be beneficial or harmful when used perioperatively for colorectal cancer patients, as inflammation may affect occult disease and anastomotic healing. METHOD: This is a protocol-based retrospective cohort study on colorectal cancer patients operated on between 2007 and 2012 at 21 hospitals in Sweden. NSAID exposure was retrieved from postoperative analgesia protocols, while outcomes and patient data were retrieved from the Swedish Colorectal Cancer Registry. Older or severely comorbid patients, as well as those with disseminated or nonradically operated tumours were excluded. Multivariable regression with adjustment for confounders was performed, estimating hazard ratios (HRs) for long-term outcomes and odds ratios (ORs) for short-term outcomes, including 95% confidence intervals (CIs). RESULTS: Some 6945 patients remained after exclusion, of whom 3996 were treated at hospitals where a NSAID protocol was in place. No association was seen between NSAIDs and recurrence-free survival (HR 0.97, 95% CI 0.87-1.09). However, a reduction in cancer recurrence was detected (HR 0.83, 95% CI 0.72-0.95), which remained significant when stratifying into locoregional (HR 0.68, 95% CI 0.48-0.97) and distant recurrences (HR 0.85, 95% CI 0.74-0.98). Anastomotic leakage was less frequent (HR 0.69%, 95% CI 0.51-0.94) in the NSAID-exposed, mainly due to a risk reduction in colo-rectal and ileo-rectal anastomoses (HR 0.47, 95% CI 0.33-0.68). CONCLUSION: There was no association between NSAID exposure and recurrence-free survival, but an association with reduced cancer recurrence and the rate of anastomotic leakage was detected, which may depend on tumour site and anastomotic location.

Diagnosis of cystic fibrosis in adulthood and eligibility for novel CFTR modulator therapy.

BACKGROUND: Cystic fibrosis (CF) is an autosomal recessive condition that primarily manifests as a chronic respiratory disease. CF is usually diagnosed in early childhood or through newborn screening although in a small but important group, diagnosis is not made until adulthood. Highly effective cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapies are now available for most genetic causes of CF highlighting the importance of identifying people with late presentations of CF. AIM: We aimed to identify the clinical characteristics of people diagnosed with CF in adulthood and their resulting eligibility for novel CFTR modulator therapies. DESIGN: Retrospective single-centre cohort study. METHODS: Patients diagnosed with CF at age 18 years or older were identified from a patient database. Paper and electronic medical records were reviewed and clinical, microbiological and radiological data at diagnosis were recorded. RESULTS: Nineteen patients were identified. Median age at diagnosis was 38 years (range: 19-71) and 9 (47%) were female. All patients had a history of chronic respiratory symptoms and 18/19 (94%) had radiological evidence of bronchiectasis. All patients had two pathogenic CFTR mutations identified with 16/19 (84%) compound heterozygotes for the F508del mutation. The majority of patients had a CFTR genotype considered eligible for CFTR modulator therapy (84% and 89% according to European and US licences, respectively). CONCLUSIONS: Adult patients with unexplained chronic bronchiectasis should be thoroughly investigated for CF. A low index of suspicion will help to identify adults with undiagnosed CF who are likely to benefit from CFTR modulator therapy.

The Incidence of Low Anterior Resection Syndrome as Assessed in an International Randomized Controlled Trial (MRC/NIHR ROLARR).

OBJECTIVE: To investigate the incidence of LARS in patients undergoing elective anterior resection within the MRC/NIHR ROLARR trial and to explore perioperative variables that might be associated with major LARS. SUMMARY BACKGROUND DATA: Sphincter-preserving rectal cancer surgery is frequently accompanied by defaecatory dysfunction known as Low anterior resection syndrome (LARS). This is distressing for patients and is an unmet clinical challenge. METHODS: An international, retrospective cohort study of patients undergoing anterior resection within the ROLARR trial was undertaken. Trial participants with restoration of gastrointestinal continuity and free from disease recurrence completed the validated LARS questionnaire between August 2015 and April 2017. The primary outcome was the incidence of LARS and secondary outcome was severity (minor versus major). RESULTS: LARS questionnaires were received from 132/155 (85%) eligible patients. The median time from surgery to LARS assessment was 1065 days (range 174-1655 d). The incidence of LARS was 82.6% (n = 109/132), which was minor in 26/132 (19.7%) and major in 83/132 (62.9%). The most common symptoms were incontinence to flatus (n = 86/132; 65.2%) and defaecatory clustering (88/132; 66.7%). In a multivariate model, predictors of major LARS were: 1 cm decrease in tumor height above the anal verge (OR = 1.290, 95% CI: 1.101,1.511); and an ASA grade greater than 1 (OR = 2.920, 95% CI: 1.239, 6.883). Treatment allocation (laparoscopic vs robotic) did not predict major LARS. CONCLUSIONS: LARS is a common after rectal cancer surgery and patients should be appropriately counselled preoperatively, particularly before surgery for low tumors or in comorbid populations.

Noninvasive vagus nerve stimulation to reduce ileus after major colorectal surgery: early development study.

AIM: Vagus nerve stimulation has emerged as a plausible intervention to reduce ileus after surgery. An early development study was undertaken with the aim of exploring the feasibility of self-administered, noninvasive vagus nerve stimulation (nVNS) after major colorectal surgery. METHOD: A parallel-group, randomized controlled trial was undertaken between 1 January 2018 and 31 August 2019. Forty patients undergoing colorectal surgery for malignancy were allocated equally to Sham and Active stimulation groups. Electrical vagus nerve stimulation was self-administered bilaterally over the cervical surface landmarks for 5 days before and after surgery. Outcomes of interest were postoperative complications and adverse events measured using the Clavien-Dindo scale, treatment compliance, device usability according to the Systems Usability Scale (SUS) and clinical measures of bowel recovery. RESULTS: Forty patients were randomized and one withdrew, leaving 39 for analysis. Postoperative complications occurred in 9/19 (47.4%) participants receiving Sham and 11/20 (55.0%) receiving Active stimulation and were mostly minor. Compliance with treatment before surgery was 4.7 ± 0.9 days out of 5 days in the Sham group and 4.7 ± 1.1 in the Active group. Compliance with treatment after surgery was 4.1 ± 1.1 and 4.4 ± 1.5, respectively. Participants considered the intervention to be 'acceptable' according to the SUS. The most prominent differences in bowel recovery were days to first flatus (2.35 ± 1.32 vs 1.65 ± 0.88) and tolerance of solid diet (2.18 ± 2.21 vs 1.75 ± 0.91) for Sham and Active groups, respectively. CONCLUSION: This study supports the safety, treatment compliance and usability of self-administered nVNS in patients undergoing major colorectal surgery.

Information needs for recovery after colorectal surgery: a patient focus group study.

AIM: The provision of information to patients is an important part of recovery after colorectal surgery. This study aimed to define patient information needs, barriers to effective understanding and insights into how information provision may be improved. METHOD: A patient focus group was convened. This comprised a broad, convenience sample of 11 participants from across the United Kingdom with experience of major colorectal surgery. A semistructured topic guide was used to facilitate discussion about previous experiences of information provision and how this may be improved. Data were analysed thematically and are presented as major themes. RESULTS: Overall, participants felt that their information needs are poorly prioritized by healthcare professionals. Barriers to understanding and retaining information include highly emotional situations (such as receiving bad news) and inappropriate information design (such as the use of inaccessible language). Participants expressed how information resources should: (a) address patients' individual information needs; (b) empower patients to take an active role in their recovery; (c) support patients with meaningful education and sign-posted resources; and (d) recognize patients' heightened need for information during recovery at home. CONCLUSION: This study provides key insights into the information needs of patients undergoing colorectal surgery. These should inform the development of future information resources, whose format, timing and design are currently supported by low-quality evidence.

Elevated risk of invasive group A streptococcal disease and host genetic variation in the human leucocyte antigen locus.

Invasive group A streptococcal (GAS) disease is uncommon but carries a high case-fatality rate relative to other infectious diseases. Given the ubiquity of mild GAS infections, it remains unclear why healthy individuals will occasionally develop life-threatening infections, raising the possibility of host genetic predisposition. Here, we present the results of a case-control study including 43 invasive GAS cases and 1540 controls. Using HLA imputation and linear mixed models, we find each copy of the HLA-DQA1*01:03 allele associates with a twofold increased risk of disease (odds ratio 2.3, 95% confidence interval 1.3-4.4, P = 0.009), an association which persists with classical HLA typing of a subset of cases and analysis with an alternative large control dataset with validated HLA data. Moreover, we propose the association is driven by the allele itself rather than the background haplotype. Overall this finding provides impetus for further investigation of the immunogenetic basis of this devastating bacterial disease.

Gastrointestinal malignancy in cystic fibrosis.

Cystic fibrosis (CF) is a multisystem disease affecting the gastrointestinal (GI) tract as well as the lungs. As survival has increased significantly over the past few decades, complications not seen previously have become apparent. There is an overall increased rate of malignancy in CF, particularly from the GI tract and in the post-transplant population. The most common sites of malignancy are the pancreatico-biliary and digestive tract, as well as an increased rate of testicular cancer. Using an illustrative case of metastatic oesophageal malignancy which initially appeared to be hepatic in origin, we have reviewed the literature surrounding malignancy in CF with a particular focus on the GI tract.

Interactive Clinical Avatar Use in Pharmacist Preregistration Training: Design and Review.

BACKGROUND: Virtual patients are interactive computer-based simulations that are being increasingly used in modern health care education. They have been identified as tools that can provide experiential learning and assessment in a standardized and safe environment. However, the study of high-fidelity virtual patients such as interactive clinical avatars within pharmacy is limited. OBJECTIVE: The aim of this paper is to describe the design and review of three interactive clinical avatar simulations as part of pharmacist preregistration training. METHODS: A multistep design approach was taken to create interactive clinical avatar simulations on the topics of emergency hormonal contraception (EHC), calculation of renal function, and childhood illnesses. All case studies were reviewed by registered pharmacists to establish content and face validity. The EHC case study and data collection questionnaire were also reviewed by a purposive sample of preregistration trainees and newly qualified pharmacists. The questionnaire used Likert ranking statements and open-ended questions to obtain users' feedback on the design, usability, and usefulness of the interactive clinical avatars as learning tools. Descriptive statistics and content analysis were undertaken on the data. RESULTS: Ten preregistration trainees and newly qualified pharmacists reviewed the EHC interactive clinical avatars and data collection questionnaire. The data collection questionnaire was associated with a Cronbach alpha=.95, demonstrating good reliability. All three interactive clinical avatar simulations were reported as usable and appropriately designed for preregistration training. Users perceived they were developing skills and knowledge from the simulations. The high-fidelity nature of the avatars and relevance of the simulations to real-life practice were reported as aspects that encouraged the application of theory to practice. Improvements were suggested to ensure the simulations were more user-friendly. CONCLUSIONS: The design and creation of the interactive clinical avatar simulations was successful. The multistep review process ensured validity and reliability of the simulations and data collection questionnaire. The in-depth explanation of the design process and provision of a questionnaire may help widen the use and evaluation of interactive clinical avatars or other simulation tools in pharmacy education. The interactive clinical avatars were reported as novel learning tools that promoted experiential learning and allowed users to feel like they were engaging in real-life scenarios, thus developing transferable knowledge and skills. This may be potentially beneficial for many health care training courses as a way to provide standardized experiences promoting active learning and reflection.

Global academic response to COVID-19: Cross-sectional study.

This study explores the response to COVID-19 from investigators, editors, and publishers and seeks to define challenges during the early stages of the pandemic. A cross-sectional bibliometric review of COVID-19 literature was undertaken between 1 November 2019 and 24 March 2020, along with a comparative review of Middle East respiratory syndrome (MERS) literature. Investigator responsiveness was assessed by measuring the volume and type of research published. Editorial responsiveness was assessed by measuring the submission-to-acceptance time and availability of original data. Publisher-responsiveness was assessed by measuring the acceptance-to-publication time and the provision of open access. Three hundred and ninety-eight of 2,835 COVID-19 and 55 of 1,513 MERS search results were eligible. Most COVID-19 studies were clinical reports (n = 242; 60.8%). The submission-to-acceptance [median: 5 days (IQR: 3-11) versus 71.5 days (38-106); P < .001] and acceptance-to-publication [median: 5 days (IQR: 2-8) versus 22.5 days (4-48·5-; P < .001] times were strikingly shorter for COVID-19. Almost all COVID-19 (n = 396; 99.5%) and MERS (n = 55; 100%) studies were open-access. Data sharing was infrequent, with original data available for 104 (26.1%) COVID-19 and 10 (18.2%) MERS studies (P = .203). The early academic response was characterized by investigators aiming to define the disease. Studies were made rapidly and openly available. Only one-in-four were published alongside original data, which is a key target for improvement. Key points: COVID-19 publications show rapid response from investigators, specifically aiming to define the disease.Median time between submission and acceptance of COVID-19 articles is 5 days demonstrating rapid decision-making compared with the median of 71.5 days for MERS articles.Median time from acceptance to publication of COVID-19 articles is 5 days, confirming the ability to introduce rapid increases at times of crisis, such as during the SARS outbreak.The majority of both COVID-19 and MERS articles are available open-access.

Systematic Review and Meta-analysis of Nonsteroidal Anti-inflammatory Drugs to Improve GI Recovery After Colorectal Surgery.

BACKGROUND: The management of delayed GI recovery after surgery is an unmet challenge. Uncertainty over its pathophysiology has limited previous research, but recent evidence identifies intestinal inflammation and activation of µ-opioid receptors as key mechanisms. Nonsteroidal anti-inflammatory drugs are recommended by enhanced recovery protocols for their opioid-sparing and anti-inflammatory properties. OBJECTIVES: The purpose of this study was to explore the safety and efficacy of nonsteroidal anti-inflammatory drugs to improve GI recovery and to identify opportunities for future research. DATA SOURCES: MEDLINE, Embase, and the Cochrane Library were systematically searched from inception up to January 2018. STUDY SELECTION: Randomized controlled trials assessing the effect of nonsteroidal anti-inflammatory drugs on GI recovery after elective colorectal surgery were eligible. MAIN OUTCOME MEASURES: Postoperative GI recovery, including first passage of flatus, stool, and oral tolerance, were measured. RESULTS: Six randomized controlled trials involving 563 participants were identified. All of the participants received patient-controlled morphine and either nonsteroidal anti-inflammatory drug (nonselective: n = 4; cyclooxygenase-2 selective: n = 1; either: n = 1) or placebo. Patients receiving the active drug had faster return of flatus (mean difference: -17.73 h (95% CI, -21.26 to -14.19 h); p < 0.001), stool (-9.52 h (95% CI, -14.74 to -4.79 h); p < 0.001), and oral tolerance (-12.00 h (95% CI, -18.01 to -5.99 h); p < 0.001). Morphine consumption was reduced in the active groups of 4 studies (average reduction, 12.9-30.0 mg), and 1 study demonstrated significantly reduced measures of systemic inflammation. Nonsteroidal anti-inflammatory drugs were not associated with adverse events, but 1 study was temporarily suspended for safety. LIMITATIONS: The data presented are relatively outdated but represent the best available evidence. CONCLUSIONS: Nonsteroidal anti-inflammatory drugs may represent an effective and accessible intervention to improve GI recovery, but hesitancy over their use after colorectal surgery persists. Additional preclinical research to characterize their mechanisms of action, followed by well-designed clinical studies to test safety and patient-reported efficacy, should be considered.

Limited effect of planting transgenic rice on the soil microbiome studied by continuous 13CO2 labeling combined with high-throughput sequencing.

The planting of transgenic rice has aroused ongoing controversy, due to the public anxiety surrounding the potential risk of transgenic rice to health and the environment. The soil microbial community plays an important environmental role in the plant-soil-microbe system; however, few studies have focused on the effect of transgenic rice on the soil rhizospheric microbiome. We labeled transgenic gene rice (TT51, transformed with Cry1Ab/1Ac gene), able to produce the Bt (Bacillus thuringiensis) toxin, its parental variety (Minghui 63), and a non-parental variety (9931) with 13CO2. The DNA of the associated soil rhizospheric microbes was extracted, subjected to density gradient centrifugation, followed by high-throughput sequencing of bacterial 16S rRNA gene. Unweighted unifrac analysis of the sequencing showed that transgenic rice did not significantly change the soil bacterial community structure compared with its parental variety. The order Opitutales, affiliated to phylum Verrucomicrobia and order Sphingobacteriales, was the main group of labeled bacteria in soil planted with the transgenic and parental varieties, while the orders Pedosphaerales, Chthoniobacteraceae, also affiliated to Verrucomicrobia, and the genus Geobacter, affiliated to class Deltaproteobacteria, dominated in the soil of the non-parental rice variety. The non-significant difference in soil bacterial community structure of labeled microbes between the transgenic and parental varieties, but the comparatively large difference with the non-parental variety, suggests a limited effect of planting transgenic Bt rice on the soil microbiome.

Fate of tetracycline and sulfonamide resistance genes in a grassland soil amended with different organic fertilizers.

This study provided an assessment of the environmental fate of antibiotic resistance genes (ARGs) in a Scottish grassland field repeatedly treated with different organic fertilizers. The impacts of manure, biosolids and municipal food-derived compost on the relative abundances of tetracycline ARGs (tetA, tetB, tetC, tetG and tetW), sulfonamide ARGs (sul1 and sul2) and class 1 integron-integrase gene (IntI1) in soils were investigated, with inorganic fertilizer (NPK) as a comparison. The background soil with a history of low intensity farming showed a higher total relative abundance of tet ARGs over sul ARGs, with tetracycline efflux genes occurring in a higher frequency. In all treatments, the relative abundances of most ARGs detected in soils decreased over time, especially IntI1 and tet ARGs. This general attenuation of soil ARGs is a reflection of changes in the soil microbial community, which is supported by the result that almost all the soils at the end of the experiment had different bacterial communities from the untreated soil at the beginning of the experiment. Multiple applications of organic fertilizers to some extent counteracted the decreasing trend of soil ARGs relative abundances, which resulted in higher ARGs relative abundances in comparison to NPK, either by a lesser decrease of IntI1 and tet ARGs or an increase of sul ARGs. The enhancement of existing soil ARG prevalence by organic fertilizers was strongly dependent on the organic fertilizer type and the particular ARG. Compost contained the lowest relative abundance of inherent ARGs and had the least effect on the soil ARG decrease after application. The relative increase of tet ARGs caused by biosolids was larger than that of sul ARGs, while manure caused the opposite effect. Fertilization practices did not exert effective impacts on the soil bacterial community, although it caused significant changes in the profile of the ARG pool. Organic fertilization may thus accelerate the dissemination of ARGs in soil mainly through horizontal gene transfer (HGT), consistent with the enrichment of IntI1 in organic fertilized soils.

Role of Grain Boundaries under Long-Time Radiation.

Materials containing a high proportion of grain boundaries offer significant potential for the development of radiation-resistant structural materials. However, a proper understanding of the connection between the radiation-induced microstructural behavior of a grain boundary and its impact at long natural time scales is still missing. In this Letter, point defect absorption at interfaces is summarized by a jump Robin-type condition at a coarse-grained level, wherein the role of interface microstructure is effectively taken into account. Then a concise formula linking the sink strength of a polycrystalline aggregate with its grain size is introduced and is well compared with experimental observation. Based on the derived model, a coarse-grained formulation incorporating the coupled evolution of grain boundaries and point defects is proposed, so as to underpin the study of long-time morphological evolution of grains induced by irradiation. Our simulation results suggest that the presence of point defect sources within a grain further accelerates its shrinking process, and radiation tends to trigger the extension of twin boundary sections.

Human genetic susceptibility to infectious disease.

Recent genome-wide studies have reported novel associations between common polymorphisms and susceptibility to many major infectious diseases in humans. In parallel, an increasing number of rare mutations underlying susceptibility to specific phenotypes of infectious disease have been described. Together, these developments have highlighted a key role for host genetic variation in determining the susceptibility to infectious disease. They have also provided insights into the genetic architecture of infectious disease susceptibility and identified immune molecules and pathways that are directly relevant to the human host defence.

A Cross-Sectional Review of Reporting Variation in Postoperative Bowel Dysfunction After Rectal Cancer Surgery.

BACKGROUND: Postoperative bowel dysfunction affects quality of life after sphincter-preserving rectal cancer surgery, but the extent of the problem is not clearly defined because of inconsistent outcome measures used to characterize the condition. OBJECTIVE: The purpose of this study was to assess variation in the reporting of postoperative bowel dysfunction and to make recommendations for standardization in future studies. If possible, a quantitative synthesis of bowel dysfunction symptoms was planned. DATA SOURCES: MEDLINE and EMBASE databases, as well as the Cochrane Library, were queried systematically between 2004 and 2015. STUDY SELECTION: The studies selected reported at least 1 component of bowel dysfunction after resection of rectal cancer. MAIN OUTCOME MEASURES: The main outcome measures were reporting, measurement, and definition of postoperative bowel dysfunction. RESULTS: Of 5428 studies identified, 234 met inclusion criteria. Widely reported components of bowel dysfunction were incontinence to stool (227/234 (97.0%)), frequency (168/234 (71.8%)), and incontinence to flatus (158/234 (67.5%)). Urgency and stool clustering were reported less commonly, with rates of 106 (45.3%) of 234 and 61 (26.1%) of 234. Bowel dysfunction measured as a primary outcome was associated with better reporting (OR = 3.49 (95% CI, 1.99-6.23); p < 0.001). Less than half of the outcomes were assessed using a dedicated research tool (337/720 (46.8%)), and the remaining descriptive measures were infrequently defined (56/383 (14.6%)). LIMITATIONS: Heterogeneity in the reporting, measurement, and definition of postoperative bowel dysfunction precluded pooling of results and limited interpretation. CONCLUSIONS: Considerable variation exists in the reporting, measurement, and definition of postoperative bowel dysfunction. These inconsistencies preclude reliable estimates of incidence and meta-analysis. A broadly accepted outcome measure may address this deficit in future studies.

Systematic Review and Meta-analysis of Prophylactic Mesh During Primary Stoma Formation to Prevent Parastomal Hernia.

BACKGROUND: Implantation of mesh at the time of stoma formation may reduce the rate of parastomal hernia. Until recently, the evidence has been limited to only a few small randomized controlled trials. OBJECTIVE: We present an updated systematic review and meta-analysis to assess the effect of mesh prophylaxis on rates of parastomal hernia. We examine ongoing and unpublished trials via online registries and propose recommendations for future research. DATA SOURCES: MEDLINE, EMBASE, and the Cochrane Library were searched up to March 2016 for published randomized controlled trials. Sixteen international trial registries were inspected for ongoing and unpublished trials. STUDY SELECTION: Randomized controlled trials comparing mesh versus no mesh on the incidence of parastomal hernia after colostomy or ileostomy formation were selected. MAIN OUTCOME MEASURES: The primary outcome measure was rate of parastomal hernia at least 12 months after stoma formation. Secondary outcomes included rates of stoma-related complications. RESULTS: Of 3005 studies identified, 7 randomized controlled trials (432 patients) were eligible for inclusion in the final analysis. All were at high risk of bias. Mesh reduced the incidence of clinically detected parastomal hernia (10.8% vs 32.4%; p = 0.001) (risk ratio, 0.34; 95% CI, 0.18-0.65; I = 39%) and the rate of radiologically detected parastomal hernia (34.6% vs 55.3%; p = 0.01) (risk ratio, 0.61; 95% CI, 0.42-0.89; I = 44%). No increase in the incidence of stoma-related complications was observed with the use of prophylactic mesh. Results from ongoing and unpublished randomized controlled trials are expected, but few will report on alternative mesh types or surgical techniques. LIMITATIONS: Heterogeneity of interventions, small patient populations, and a high risk of bias seen in all studies implicate cautious interpretation of the results. CONCLUSION: Mesh prophylaxis at the time of stoma formation appears safe and effective in preventing parastomal hernia; however, limitations of the primary evidence justify larger, more rigorous randomized controlled trials.