Remote regulation of type 2 immunity by intestinal parasites.

The intestinal tract is the target organ of most parasitic infections, including those by helminths and protozoa. These parasites elicit prototypical type 2 immune activation in the host's immune system with striking impact on the local tissue microenvironment. Despite local containment of these parasites within the intestinal tract, parasitic infections also mediate immune adaptation in peripheral organs. In this review, we summarize the current knowledge on how such gut-tissue axes influence important immune-mediated resistance and disease tolerance in the context of coinfections, and elaborate on the implications of parasite-regulated gut-lung and gut-brain axes on the development and severity of airway inflammation and central nervous system diseases.

Impact of patient motivation on compliance and outcomes for incontinence.

OBJECTIVES: Physiotherapeutic treatment of pelvic floor dysfunction in women has variable outcomes, and identification of the predictors of outcomes is important in developing service provision and treatment planning. This study explored whether patient motivation affects treatment compliance and outcomes of physiotherapeutic treatment in a cohort of patients with pelvic floor dysfunction. DESIGN, SETTING AND PARTICIPANTS: A prospective observational study of 141 adult female patients referred consecutively to the physiotherapy clinic of an urogynaecological outpatients unit at a UK hospital. INTERVENTION: A 6-month (one group session per month) pelvic floor muscle training programme, which included a home exercise programme. MAIN OUTCOME MEASURES: Modified Oxford Grading System and Queensland Pelvic Floor Questionnaire ratings of pelvic floor function were taken pre- and post-intervention, and the University of Rhode Island Change Assessment Scale assessed patient motivation to change pre-intervention. RESULTS: Motivation to change predicted attendance at the intervention sessions and patient-rated improvements in function. Patients with higher baseline motivation to change also reported greater improvements in pelvic symptoms, given the same pelvic floor muscle strength improvement. CONCLUSIONS: Patient motivation affects physiotherapeutic treatment adherence and outcomes, and should be considered as part of future assessment/screening procedures. CLINICAL TRIAL REGISTRATION: NCT02549157.

Non-steroidal anti-inflammatory agents and anastomotic leak rates across colorectal cancer operations and anastomotic sites: A systematic review and meta-analysis of anastomosis specific leak rate and confounding factors.

BACKGROUND: Surgical intervention presents a fundamental therapeutic choice in the management of colorectal malignancies. Complications, the most serious one being anastomotic leak (AL), still have detrimental effects upon patients' morbidity and mortality. We aimed to assess whether NSAIDs, and their sub-categories, increase AL in colonic anastomoses and to identify whether this affects specific anastomotic sites. MATERIALS AND METHODS: A systematic search of MEDLINE, Cochrane Library, ClinicalTrials.gov, Web of Science, Science Direct, Google Scholar was conducted between January 1, 1999 till the October 30, 2020. Cohort studies and randomized control trials examining AL events in NSAID-exposed, colorectal cancer patients were included. NSAIDs were grouped according to the 2019 NICE guidelines in non-specific (NS-NSAIDs) and specific COX-2 inhibitors. The primary outcome was AL events in NSAID-exposed patients undergoing operations with either ileocolic, colocolic or colorectal anastomoses. Secondary outcomes included NSAID category-specific AL events and demographic confounding factors increasing AL risk in this patient population. RESULTS: Fifteen studies involving 25,395 patients were included in the systematic review and meta-analysis. Of all anastomoses, colocolic anastomoses were found to be statistically more prone to AL events in the NS-NSAID-exposed population [OR 3.24 (95% CI 0.98-10.72), p = 0.054]. Male gender was an independent confounder increasing AL rate regardless of NSAID exposure. CONCLUSION: The association between NSAID exposure and AL in oncology patients remains undetermined. Whilst in present work, colocolic anastomoses appear to be more sensitive to AL events, the observed association may be anastomotic site and NSAID-category dependent.

20 Armoured Infantry Brigade downgrade study: epidemiology of principal conditions and plugging leaks in the rehabilitation pipeline.

INTRODUCTION: In April 2017, 22% of Army Full-time Trade Trained Strength was downgraded, reducing fully deployable strength to 60 546, against a target of 82 000. In June 2017, Commander 20 Armoured Infantry Brigade (20 AI Bde) initiated a study to look at the principal conditions causing medical downgrading, as a stepping stone to finding ways of reducing injury, enhancing rehabilitation and improving deployability. METHOD: The Defence Medical Information Capability Programme medical records for every downgraded soldier in 20 AI Bde and supporting units were scrutinised to identify their Medical Deployment Standard and the primary condition causing downgrading. RESULTS: A total of 842 downgraded soldiers were identified from a held strength of 3827 personnel. Sixty-five per cent of these downgrades were due to musculoskeletal injury (MSKI). Of this 65%, the majority were due to knee (31%), spine (28%) and foot/ankle (23%). Of the remaining 35%, the majority were due to noise-induced hearing loss (NIHL) (22%), adjustment disorders (19%) and non-freezing cold injury (NFCI) (13%).Several factors that slowed an individual's recovery pathway were identified. They mainly relate to soldiers being lost to follow-up through lack of active case management. CONCLUSIONS: MSKI is responsible for most downgraded personnel at Brigade level. The distribution of principal conditions is similar to previous studies looking at recruits and individual units.The creation of a rehabilitation troop, delivering active case management, can reduce the number of soldiers leaking out of the rehabilitation pipeline.

Individual and family-based approaches to increase physical activity in adolescents with intellectual and developmental disabilities: Rationale and design for an 18 month randomized trial.

Adolescents with intellectual and developmental disabilities (IDD) are less physically active and have lower cardiovascular fitness compared with their typically developing peers. This population faces additional barriers to participation in moderate-to-vigorous physical activity (MVPA) such as reliance on parents, lack of peer-support, and lack of inclusive physical activity opportunities. Previous interventions to increase MVPA in adolescents with IDD have met with limited success, at least in part due to requiring parents to transport their adolescent to an exercise facility. We recently developed a remote system to deliver MVPA to groups of adolescents with IDD in their homes via video conferencing on a tablet computer. This approach eliminates the need for transportation and provides social interaction and support from both a health coach and other participants. We will conduct a 18-mo. trial (6 mos. active, 6 mos. maintenance, 6 mos. no-contact follow-up) to compare changes in objectively assessed MVPA in 114 adolescents with IDD randomized to a single level intervention delivered only to the adolescent (AO) or a multi-level intervention delivered to both the adolescent and a parent (A + P). Our primary aim is to compare increases in MVPA (min/d) between the AO and A + P groups from 0 to 6 mos. Secondarily we will compare changes in MVPA, sedentary time, cardiovascular fitness, muscular strength, motor ability, quality of life, and the percentage of adolescents achieving the US recommendation of 60 min. MVPA/d across 18 mos. We will also explore the influence of process variables/participant characteristics on changes in MVPA across 18 mos. NCT registration: NCT03684512.

Updated Diploma in Immediate Medical Care: applicability to military and civilian clinicians.

The Diploma in Immediate Medical Care (DipIMC) is the entry-level interprofessional civilian qualification for prehospital emergency care (PHEC) in the UK. It is designed to test the knowledge, skills and behaviours of PHEC practitioners. Military personnel are eligible to enter, dependent on the level of PHEC experience they have. The DipIMC examination has changed in recent years; this paper aims to update aspiring candidates on the application process, recommended preparation and skill-set required to pass.

Thrombocytosis as a Marker for Postoperative Complications in Colorectal Surgery.

BACKGROUND: Blood platelet measurement is a widely available and inexpensive test that is performed routinely. Platelets are thought to act by inducing inflammation and play a role in clotting and antimicrobial defence. A postoperative rise in the platelet count (thrombocytosis) is often dismissed as an incidental finding, but there is growing evidence to suggest that it may act as an indicator to underlying pathology. It correlates with significant pyogenic infections as well as multiple malignancies. In addition to this, recent research indicates that thrombocytosis may be a useful prognostic indicator for postoperative outcomes in patients with malignancies. In patients undergoing surgery for gastric cancer, a combination of platelet count and neutrophil-to-lymphocyte (NLR) ratio collected preoperatively was shown to correlate with postoperative survival. OBJECTIVE: To evaluate whether there is a positive correlation between pre- and postoperative thrombocytosis and the risk of complications following colorectal surgery. METHODS: This was a retrospective observational study based in Morriston Hospital, Swansea. Patients undergoing elective colorectal surgery for an 18-month period between 2014 and 2016 were included. Data on patient demographics, pre- and postoperative platelet count, the first date at which the highest platelet count was recorded, length of stay, type of operation, and postoperative complications using the Clavien-Dindo classification was obtained from the theatre booking software (TOMS) and Welsh Clinical Portal. Pearson's chi-square test was used for the analysis of the categorical variables. RESULTS: Of the 201 patients studied, 75 (37%) had postoperative thrombocytosis (platelets ≥ 500 × 109/L, range 501-1136), 120 (59%) had postoperative normocytosis (platelets < 500 × 109/L, range 107-499), and 6 (2.9%) patients were excluded due to insufficient data. Peak platelet level was seen at a median of 8 days postoperatively but ranged from days 1 to 49. In patients with thrombocytosis, the mean time to peak platelet count was 9.5 days and ranged 1 to 49 days. 101/195 (52%) patients had a Clavien-Dindo III/V postoperative complication: 63% patients with postoperative normocytosis and 24% with postoperative thrombocytosis. In the thrombocytosis group, 16/75 (21%) were found to have postoperative pelvic collections compared to 1/120 (0.8%) of the normocytic patients. The total percentage of medical complications (44% versus 20%, p = 0.006) and surgical complications (64% versus 15.8%, p = 0.0001) was higher in the thrombocytosis group compared to the normocytosis group. CONCLUSION: In this retrospective study, thrombocytosis was shown to have a positive correlation with postoperative medical and surgical complications. An elevated platelet count in the postoperative period should alert the clinician to a developing complication. We recommend that further studies with a larger sample size would test the specific associations with individual complications.

The prevalence and potential determinants of dysmenorrhoea and other pelvic pain in women: a prospective study.

OBJECTIVE: To estimate the prevalence of pelvic pain and model associations with potential demographic, obstetric, gynaecological and psychosocial determinants. DESIGN, SETTING AND SAMPLE: A cohort study of women born between 1972 and 1973 in Dunedin, New Zealand, most recently assessed when aged 38 years (95% of survivors retained); 429 women were eligible for analysis. METHODS: Women self-completed reproductive health questionnaires at ages 21, 26, 32 and 38 years, with questions on dysmenorrhoea at ages 13 and 15, and on all pelvic pain at age 38. Prevalence and 95% confidence intervals (CI) were calculated and Poisson regression used to model associations. MAIN OUTCOME MEASURES: The prevalence of pain and adjusted relative risks (ARR) for potential explanatory factors. RESULTS: Over half (54.5%, 95% CI 49.7-59.3%) of women experienced pelvic pain in the past 12 months at age 38. Dysmenorrhoea was reported by 46.2% (41.3-51.3%), dyspareunia by 11.6% (8.7-15.2%) and other pelvic pain (OPP) by 17.3% (13.8-21.2%). After adjusting for multiple factors, pregnancy (ARR 0.60, 95% CI 0.32-1.13) and childbirth (ARR 0.52, 95% CI 0.25-1.09) were borderline protective for dyspareunia and OPP, respectively. However, childbirth was not associated with dysmenorrhoea (ARR 0.97, 95% CI 0.74-1.28). Dysmenorrhoea and dyspareunia were strongly associated, and both were associated with endometriosis. CONCLUSIONS: Our data confirm that female pelvic pain is common, and suggest common gynaecological and obstetric causal pathways, but there was no strong evidence supporting a benefit of childbirth for dysmenorrhoea. Further research on obstetric events and pelvic pain is needed, with both being common experiences. TWEETABLE ABSTRACT: Pelvic pain was common at age 38, especially dysmenorrhoea (46.2%), and no improvement was detected following childbirth.

Distraction during Deployment: Marital Relationship Associations with Spillover for Deployed Army Soldiers.

Military spouses often have concerns regarding the impact of their communication on soldiers during deployment. However, literature is mixed regarding how communication between soldiers and spouses may impact soldiers' self-reported work functioning during deployment, suggesting the need to evaluate moderating factors. In the current study, three relationship factors (marital satisfaction, conflictual communication, and proportion of conversation focused on problems) were tested as moderators of communication frequency and negative marriage-to-work spillover for soldiers. Whereas the three relationship factors were independently related to negative spillover, none significantly moderated the relationship between communication frequency and spillover. The overall pattern of results suggests that (a) lower marital satisfaction, a focus on problems during communication, and conflictual communication are each strongly linked to spillover for deployed soldiers, and (b) military couples may be self-restricting deployment communication frequency when experiencing less marital satisfaction and higher rates of negative communication. Implications for communication during deployment are discussed.

The prostaglandin D2 receptor CRTH2 regulates accumulation of group 2 innate lymphoid cells in the inflamed lung.

Group 2 innate lymphoid cells (ILC2s) promote type 2 cytokine-dependent immunity, inflammation, and tissue repair. Although epithelial cell-derived cytokines regulate ILC2 effector functions, the pathways that control the in vivo migration of ILC2s into inflamed tissues remain poorly understood. Here, we provide the first demonstration that expression of the prostaglandin D2 (PGD2) receptor CRTH2 (chemoattractant receptor-homologous molecule expressed on Th2 cells) regulates the in vivo accumulation of ILC2s in the lung. Although a significant proportion of ILC2s isolated from healthy human peripheral blood expressed CRTH2, a smaller proportion of ILC2s isolated from nondiseased human lung expressed CRTH2, suggesting that dynamic regulation of CRTH2 expression might be associated with the migration of ILC2s into tissues. Consistent with this, murine ILC2s expressed CRTH2, migrated toward PGD2 in vitro, and accumulated in the lung in response to PGD2 in vivo. Furthermore, mice deficient in CRTH2 exhibited reduced ILC2 responses and inflammation in a murine model of helminth-induced pulmonary type 2 inflammation. Critically, adoptive transfer of CRTH2-sufficient ILC2s restored pulmonary inflammation in CRTH2-deficient mice. Together, these data identify a role for the PGD2-CRTH2 pathway in regulating the in vivo accumulation of ILC2s and the development of type 2 inflammation in the lung.

Clustering autism: using neuroanatomical differences in 26 mouse models to gain insight into the heterogeneity.

Autism is a heritable disorder, with over 250 associated genes identified to date, yet no single gene accounts for >1-2% of cases. The clinical presentation, behavioural symptoms, imaging and histopathology findings are strikingly heterogeneous. A more complete understanding of autism can be obtained by examining multiple genetic or behavioural mouse models of autism using magnetic resonance imaging (MRI)-based neuroanatomical phenotyping. Twenty-six different mouse models were examined and the consistently found abnormal brain regions across models were parieto-temporal lobe, cerebellar cortex, frontal lobe, hypothalamus and striatum. These models separated into three distinct clusters, two of which can be linked to the under and over-connectivity found in autism. These clusters also identified previously unknown connections between Nrxn1α, En2 and Fmr1; Nlgn3, BTBR and Slc6A4; and also between X monosomy and Mecp2. With no single treatment for autism found, clustering autism using neuroanatomy and identifying these strong connections may prove to be a crucial step in predicting treatment response.

A Coordinated Effort to Manage Soybean Rust in North America: A Success Story in Soybean Disease Monitoring.

Existing crop monitoring programs determine the incidence and distribution of plant diseases and pathogens and assess the damage caused within a crop production region. These programs have traditionally used observed or predicted disease and pathogen data and environmental information to prescribe management practices that minimize crop loss. Monitoring programs are especially important for crops with broad geographic distribution or for diseases that can cause rapid and great economic losses. Successful monitoring programs have been developed for several plant diseases, including downy mildew of cucurbits, Fusarium head blight of wheat, potato late blight, and rusts of cereal crops. A recent example of a successful disease-monitoring program for an economically important crop is the soybean rust (SBR) monitoring effort within North America. SBR, caused by the fungus Phakopsora pachyrhizi, was first identified in the continental United States in November 2004. SBR causes moderate to severe yield losses globally. The fungus produces foliar lesions on soybean (Glycine max) and other legume hosts. P. pachyrhizi diverts nutrients from the host to its own growth and reproduction. The lesions also reduce photosynthetic area. Uredinia rupture the host epidermis and diminish stomatal regulation of transpiration to cause tissue desiccation and premature defoliation. Severe soybean yield losses can occur if plants defoliate during the mid-reproductive growth stages. The rapid response to the threat of SBR in North America resulted in an unprecedented amount of information dissemination and the development of a real-time, publicly available monitoring and prediction system known as the Soybean Rust-Pest Information Platform for Extension and Education (SBR-PIPE). The objectives of this article are (i) to highlight the successful response effort to SBR in North America, and (ii) to introduce researchers to the quantity and type of data generated by SBR-PIPE. Data from this system may now be used to answer questions about the biology, ecology, and epidemiology of an important pathogen and disease of soybean.

Occurrence and Distribution of Triticum mosaic virus in the Central Great Plains.

Wheat curl mite (WCM)-transmitted viruses-namely, Wheat streak mosaic virus (WSMV), Triticum mosaic virus (TriMV), and the High Plains virus (HPV)-are three of the wheat-infecting viruses in the central Great Plains of the United States. TriMV is newly discovered and its prevalence and incidence are largely unknown. Field surveys were carried out in Colorado, Kansas, Nebraska, and South Dakota in spring and fall 2010 and 2011 to determine TriMV prevalence and incidence and the frequency of TriMV co-infection with WSMV or HPV in winter wheat. WSMV was the most prevalent and was detected in 83% of 185 season-counties (= s-counties), 73% of 420 season-fields (= s-fields), and 35% of 12,973 samples. TriMV was detected in 32, 6, and 6% of s-counties, s-fields, and samples, respectively. HPV was detected in 34, 15, and 4% of s-counties, s-fields, and samples, respectively. TriMV was detected in all four states. In all, 91% of TriMV-positive samples were co-infected with WSMV, whereas WSMV and HPV were mainly detected as single infections. The results from this study indicate that TriMV occurs in winter wheat predominantly as a double infection with WSMV, which will complicate breeding for resistance to WCM-transmitted viruses.

Extension plant pathology: strengthening resources to continue serving the public interest.

Extension plant pathologists deliver science-based information that protects the economic value of agricultural and horticultural crops in the United States by educating growers and the general public about plant diseases. Extension plant pathologists diagnose plant diseases and disorders, provide advice, and conduct applied research on local and regional plant disease problems. During the last century, extension plant pathology programs have adjusted to demographic shifts in the U.S. population and to changes in program funding. Extension programs are now more collaborative and more specialized in response to a highly educated clientele. Changes in federal and state budgets and policies have also reduced funding and shifted the source of funding of extension plant pathologists from formula funds towards specialized competitive grants. These competitive grants often favor national over local and regional plant disease issues and typically require a long lead time to secure funding. These changes coupled with a reduction in personnel pose a threat to extension plant pathology programs. Increasing demand for high-quality, unbiased information and the continued reduction in local, state, and federal funds is unsustainable and, if not abated, will lead to a delay in response to emerging diseases, reduce crop yields, increase economic losses, and place U.S. agriculture at a global competitive disadvantage. In this letter, we outline four recommendations to strengthen the role and resources of extension plant pathologists as they guide our nation's food, feed, fuel, fiber, and ornamental producers into an era of increasing technological complexity and global competitiveness.

Efficacy and Stability of Integrating Fungicide and Cultivar Resistance to Manage Fusarium Head Blight and Deoxynivalenol in Wheat.

Integration of host resistance and prothioconazole + tebuconazole fungicide application at anthesis to manage Fusarium head blight (FHB) and deoxynivalenol (DON) in wheat was evaluated using data from over 40 trials in 12 U.S. states. Means of FHB index (index) and DON from up to six resistance class-fungicide management combinations per trial (susceptible treated [S_TR] and untreated [S_UT]; moderately susceptible treated [MS_TR] and untreated [MS_UT]; moderately resistant treated [MR_TR] and untreated [MR_UT]) were used in multivariate meta-analyses, and mean log response ratios across trials were estimated and transformed to estimate mean percent control ( ) due to the management combinations relative to S_UT. All combinations led to a significant reduction in index and DON (P < 0.001). MR_TR was the most effective combination, with a of 76% for index and 71% for DON, followed by MS_TR (71 and 58%, respectively), MR_UT (54 and 51%, respectively), S_TR (53 and 39%, respectively), and MS_UT (43 and 30%, respectively). Calculations based on the principle of treatment independence showed that the combination of fungicide application and resistance was additive in terms of percent control for index and DON. Management combinations were ranked based on percent control relative to S_UT within each trial, and nonparametric analyses were performed to determine management combination stability across environments (trials) using the Kendall coefficient of concordance (W). There was a significant concordance of management combinations for both index and DON (P < 0.001), indicating a nonrandom ranking across environments and relatively low variability in the within-environment ranking of management combinations. MR_TR had the highest mean rank (best control relative to S_UT) and was one of the most stable management combinations across environments, with low rank stability variance (0.99 for index and 0.67 for DON). MS_UT had the lowest mean rank (poorest control) but was also one of the most stable management combinations. Based on Piepho's nonparametric rank-based variance homogeneity U test, there was an interaction of management combination and environment for index (P = 0.011) but not for DON (P = 0.147), indicating that the rank ordering for index depended somewhat on environment. In conclusion, although the magnitude of percent control will likely vary among environments, integrating a single tebuconazole + prothioconazole application at anthesis with cultivar resistance will be a more effective and stable management practice for both index and DON than either approach used alone.

Development of Weather-Based Predictive Models for Fusarium Head Blight and Deoxynivalenol Accumulation for Spring Malting Barley.

The associations between Fusarium head blight (FHB), caused by Gibberella zeae, and deoxynivalenol (DON) accumulation in spring malting barley (Hordeum vulgare) and hourly weather conditions predictive of DON accumulation were examined using data from six growing seasons in the U.S. Northern Great Plains. Three commonly grown cultivars were planted throughout the region, and FHB disease and DON concentration were recorded. Nine predictor variables were calculated using hourly temperature and relative humidity during the 10 days preceding full head spike emergence. Simple logistic regression models were developed using these predictor variables based on a binary threshold for DON of 0.5 mg/kg. Four of the nine models had sensitivity greater than 80%, and specificity of these models ranged from 67 to 84% (n = 150). The most useful predictor was the joint effect of average hourly temperature and a weighted duration of uninterrupted hours (h) with relative humidity greater than or equal to 90%. The results of this study confirm that FHB incidence is significantly associated with DON accumulation in the grain and that weather conditions prior to full head emergence could be used to accurately predict the risk of economically significant DON accumulation for spring malting barley.

Selective ablation of the YxxM motif of IL-7Ralpha suppresses lymphomagenesis but maintains lymphocyte development.

Tumor progression is a multiple step process in which, in addition to oncogenic mutation, other supporting factors can contribute to transformation. The role these factors have in cancer is an open question. Using the Emicro-myc model of B-cell transformation, we evaluated the contribution of the cytokine interleukin-7 (IL-7) in supporting lymphomagenesis. We have previously shown that disruption of the Y449xxM motif of the IL-7 receptor alpha (IL-7Ralpha) in a knock-in mouse model (IL-7Ralpha(449F)) has minor effects on lymphocyte production, but interferes with the activation of survival effectors. To address the hypothesis that targeted signal ablation would selectively affect lymphocyte transformation, IL-7Ralpha(449F) mice were crossed with two lymphomagenesis models, transgenic (Tg) IL-7 and Emicro-myc mice. We found that the loss of IL-7Ralpha Y449 signaling prevented Tg IL-7-mediated T- and B-lymphocyte transformation and decreased the development of Emicro-myc-induced B-cell tumors. We showed that the IL-7Ralpha(449F) mutation prevented increased survival of Tg IL-7 CD8 T cells, and decreased viability of bone marrow progenitor B cells, as well as Emicro-myc-induced proliferation. This study shows that IL-7Ralpha Y449 is important for lymphocyte transformation, and that unlike deficiencies in pre-B cell receptor signaling, Myc overexpression cannot compensate for the loss of IL-7Ralpha signals in early B-cell development.