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Sha-sha LI

and 1 more

Brendan Furneaux

and 4 more

Rainer Glauben

and 6 more

Background: The present study aims to detect, quantify and analyze circulating nutritional antigen-specific T-cells in patients with celiac disease (CeD) as well as inflammatory bowel disease (IBD), thus comparing the specific T-cell response following barrier disruption and antigen translocation. Methods: The antigen-reactive T-cell enrichment (ARTE) technique was applied allowing for a phenotypical and functional flow cytometric analysis of rare nutritional antigen-specific T-cells, including the CeD-causing gliadin (gluten), in the peripheral blood. Results: Our study indicates that by applying the ARTE technique, differences of gluten-specific T-cells as well as the differential cytokine expression between the patient groups can be detected, even without the burdening gluten re-exposure of the patients. CeD patients, independent from the presence or absence of gluten exposure in their current diet, featured an increase of the frequency of gliadin-specific T-cells, which were characterized by a pro-inflammatory phenotype. However, only for active CeD and a consecutive small intestinal barrier breach, an increase of distinct nutritional T-cells could be detected. Accordingly, frequency as well as pro-inflammatory phenotype of nutritional antigen-specific T cells were highest in Crohn’s disease patients with small intestinal inflammation whereas no significant increase was observed in ulcerative colitis. Conclusion: In summary, the ARTE method allows not only for detection but also for functional analysis of these rare cells even in healthy subjects. Applying this method, we were able to demonstrate that for non-CeD-related nutritional antigens, small intestinal barrier breach is mandatory for a peripheral antigen-specific T-cell.

Huixin Yang

and 9 more

Cynthia Mapendere

and 3 more

In Southern Africa, the African Swine Fever (ASF) sylvatic cycle presents a permanent threat for the development of the pig farming industry. Warthogs (Phacochoerus africanus) and bushpigs (Potamochoerus larvatus), wild reservoirs of ASF are present in Ndumo Game Reserve (NGR), located in Northern KwaZulu Natal Province in South Africa and within 30 km of the locations of endemic ASF outbreaks in Mozambique where sylvatic disease transmission has been implicated. To assess if wild suids represent a risk of ASF virus spillover to domestic pigs in the neighbouring community, transect counts and fence patrols were conducted and camera traps were deployed in NGR to estimate wild suid abundance and incursions outside NGR boundaries. We searched for Ornithodoros ticks in 35 warthog burrows distributed across different NGR areas. Pig farmers (n=254) surrounding Mathenjwa Community were interviewed to gather information on interactions between domestic and wild suids and the occurrence of ASF. We conclude that NGR has established populations of bushpigs and warthogs, estimated at 5 and 3-5 individuals/km2 respectively. Both species move out of the reserve regularly (15.4 warthogs/day and 6.35 bushpigs/day), with a significant increase of movements during the dry season. Some farmers observed warthogs and bushpigs as far as 8 and 19 km from the reserve respectively, but no direct wild-domestic suids interactions nor any ASF outbreaks were reported. In addition, no soft ticks were found among the 35 warthog burrows. The absence of ticks in warthog burrows from NGR and the absence of reported outbreaks and familiarity with ASF in the surrounding farming area, suggest that a sylvatic cycle of ASF is at present unlikely in NGR. However, further research should be undertaken to confirm this by surveying a larger number of warthog burrows and monitoring potential antibodies in warthogs from NGR and domestic pigs in the neighbouring community.

Xiaoqin Liu

and 5 more

Background: Rivaroxaban is an oral anticoagulant used widely for stroke prevention in patients with non-valvular atrial fibrillation (NVAF). During long-term anticoagulant therapy, delayed or missed doses are common. However, a lack of practical instructions on remedial methods has created a barrier to maximise the benefit of the medications. This study aimed to explore appropriate remedial dosing regimens for non-adherent rivaroxaban-treated patients. Methods: Monte Carlo simulation based on a previously established rivaroxaban population pharmacokinetic/pharmacodynamic (PK/PD) model for patients with NVAF was employed to design remedial dosing regimens. The proposed regimens were compared with remedial strategies in the European Heart Rhythm Association (EHRA) guide by assessing deviation time in terms of drug concentration, factor Xa activity, and prothrombin time under various scenarios of non-adherence. Results: The proposed remedial dosing regimens were dependent on delay duration. The missed dose should be taken immediately when the delay does not exceed 6 h; a half dose is advisable when the delay is between 6-20 h. A missed dose should be skipped if less than 4 h remains before the next dose. Age or renal function does not significantly influence remedial dosing regimens. The proposed regimens resulted in shorter deviation time than that of the EHRA guide in most non-adherence scenarios. Conclusion: EHRA guide may not provide optimal remedial strategies for rivaroxaban-treated non-adherent patients based on simulation. PK/PD and simulation provide valid evidence on the remedial dosing regimen of rivaroxaban for patients with NVAF, which could help to minimise the risk of bleeding and thromboembolism.

Ruoyan Gai Tobe

and 5 more

Objective: This study aimed to evaluate the effectiveness of maternal and child health handbook (MCH) enhanced by mobile tools and to generate evidence informing the adoption of the program in Bangladesh Design: Cluster randomized controlled trial Setting: Two Upazilas in Bangladesh Population or Sample: Pregnant women Methods: Unions of the study settings were randomly allocated in either one of three groups: (1) Intervention 1 using both mobile platform and MCH, (2) Intervention 2 using MCH alone, or (3) the Control. A total of 3,002 participants were recruited. The interventions were designed to promote two-way communications between pregnant women/their families and community health workers by an empowering approach. Main outcome measures: continuum of care (CoC), neonatal mortality and morbidities Results: The interventions both significantly improved the utilization of CoC, although the overall proportion of CoC was relevantly low: 2.79% in the Control (95% CI: 1.37-3.54%), 6.16% in Intervention 2 (95% CI: 4.67-7.86%), and 7.89% in Intervention 1 (95% CI: 6.29-9.90%). Neonatal mortality rate with and without CoC was 5.43 per 1,000 (95% CI: 3.63 - 9.57 per 1,000) and 34.8 per 1,000 (95% CI: 24.3 - 45.4 per 1,000), respectively. Conclusion: our study indicated the effectiveness of the interventions by leveraging MCH and a mobile platform to promote uptake of CoC throughout prepartum, intrapartum and postpartum/neonatal periods, potentially bringing long-lasting benefits to mothers and their offspring. The explicit approach is expected to guide policy makers to adopt MCH interventions in primary healthcare strengthening at the community level.

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Yue Liang

and 5 more

Internal erosion is one of the most common causes of failure in hydraulic engineering structures, such as embankments and levees. It also plays a vital role in the geohazards (such as landslides and sinkhole developments) and more importantly, the earth landscape evolution, which has a broad environmental and ecosystem impacts. The groundwater seepage is multi-directional, and its multi-dimensional nature could affect the initiation and the progression of internal erosion. With a newly developed apparatus, we carry out nine internal erosion experiments under five different seepage directions. The results reveal that the critical hydraulic gradient increases as the seepage direction varies from the horizontal to the vertical. After a global erosion is triggered, preferential erosion paths distribute randomly from the bottom to the top of the specimen. If the seepage direction is not vertical, small preferential erosion paths merge into a large erosion corridor, in which the loss of fine particles is significant but negligible outside. Results of experiments manifest that the erosion is heterogeneous and three-dimensional, even in the unidirectional seepage flow. The particles are rapidly eroded at the early stage of the erosion, indicating a high erosion rate. With the erosion time increasing, the particle loss slows down and even ceases if the time is long enough. The erosion rate increases if the seepage direction approaches a vertical direction. Overall, the erosion rate approximately decreases with erosion time exponentially. We proposed exponential equations to illustrate the variation of the erosion rate in the erosion process.

Gary Ghahremani

and 2 more

Summary Background: Torus is a protuberant and lobulated exostosis that develops on the lingual aspect of the jaws or hard palate in 10-30% of adults. They can interfere with mastication, speech, oral hygiene, and denture placement. Their enlargement with advancing age may also lead to superficial ulceration, inflammation, osteonecrosis and various other complications. Methods: A retrospective analysis of the authors’ experience with 17 adults who had large symptomatic tori was performed. The patients were examined by intraoral imaging and radiographic or computed tomography of their maxillofacial bones. Their dental and medical records were reviewed along with the pertinent literature concerning the prevalence and reported complications of this entity. Results: This series included 6 men and 11 women, ranging in age from 36 to 85 years (Mean age: 56.5 years).There were 6 patients with torus mandibularis, 8 with torus palatinus, and 3 with torus maxillaris. Four of our 17 patients required surgical excision of their tori because of large size, recurrent superficial erosions and associated symptoms. Conclusion: The majority of tori are asymptomatic and incidental finding, but the more prominent tori are prone to mucosal inflammation and ulceration that may require surgical removal of the lesion. Large tori can also interfere with mastication, speech, dental hygiene, placement and function of prosthetic dentures, and may cause snoring, sleep apnea or other complications. Therefore, the practicing physicians should be familiar with the appearance, radiological features, clinical implications and management of tori.

Wahaj Munir

and 3 more

Background: Acute type A aortic dissection (ATAAD), is a surgical emergency often requiring intervention on the aortic root. There is much controversy regarding root management; aggressively pursuing a root replacement, versus more conservative approaches to preserve native structures. Methods: Electronic database search we performed through PubMed, Embase, SCOPUS, google scholar and Cochrane identifying studies that reported on outcomes of surgical repair of ATAAD through either root preservation or replacement. The identified articles focused on short- and long-term mortalities, and rates of re-operation on the aortic root. Results: There remains controversy on replacing or preserving aortic root in ATAAD. Current evidence supports practice of both trends following an extensive decision-making framework, with conflicting series suggesting favourable results with both procedures as the approach that best defines higher survival rates and lower perioperative complications. Yet, the decision to perform either approach remains surgeon decision and bound to the extent of the dissection and tear entries in strong correlation with status of the aortic valve and involvement of coronaries in the dissection. Conclusions: There exists much controversy regarding fate of the aortic root in ATAAD. There are conflicting studies for impact of root replacement on mortality, whilst some study’s report no significant results at all. There is strong evidence regarding risk of re-operation being greater when root is not replaced. Majority of these studies are limited by the single centred, retrospective nature of these small sample sized cohorts, further hindered by potential of treatment bias.

Nicholas Hess

and 3 more

Background: This study compared outcomes of patients bridged with extracorporeal membrane oxygenation (ECMO) to orthotopic heart transplantation (OHT) following the recent heart allocation policy change. Methods: The United Network of Organ Sharing Registry (UNOS) database was queried to examine OHT patients between 2010-2020 that were bridged with ECMO. Waitlist outcomes and one-year posttransplant survival were compared between patients waitlisted and/or transplanted before and after the heart allocation policy change. Secondary outcomes included posttransplant stroke, renal failure, and one-year rejection. Results: 285 waitlisted patients were included, 173 (60.7%) waitlisted under the old policy and 112 (39.3%) under the new policy. New policy patients were more likely to receive OHT (82.2% vs 40.6%), and less likely to be removed from the waitlist due to death or clinical deterioration (15.0% vs 41.3%) (both P<0.001). 165 patients bridged from ECMO to OHT were analyzed, 72 (43.6%) transplanted during the old policy and 93 (56.3%) under the new. Median waitlist time was reduced under the new policy (4 days [IQR 2-6] vs 47 days [IQR 10-228]). Postoperative renal failure was higher in the new policy group (23% vs 6%; P=0.002), but rates of stroke and one-year acute rejection were equivalent. One-year survival was lower the new policy but was not significant (79.8% vs 90.3%; P=0.3917). Conclusions: The UNOS heart allocation policy change has resulted in decreased waitlist times and higher likelihood of transplant in patients supported with ECMO. Posttransplant one-year survival has remained comparable although absolute rates are lower.

Matthew Sussman

and 9 more

The recognition of fibrinolysis phenotypes in trauma patients has led to a reevaluation of antifibrinolytic therapy (AF). Many cardiac patients also receive AF, however the distribution of fibrinolytic phenotypes in that population is unknown. The purpose of this study was to fill that gap. Methods: Data were retrospectively reviewed from 78 cardiac surgery patients. Phenotypes were defined as hypofibrinolytic (LY30 <0.8%), physiologic (LY30 0.8-3.0%) and hyperfibrinolytic (LY30 >3%). Continuous variables were expressed as M ± SD or median (interquartile range). Results: The study population was 65±10 yrs old, 74% male, average body mass index of 29±5 kg/m2. Fibrinolytic phenotypes were distributed as physiologic=45%, hypo=32% and hyper = 23%. There was no obvious effect of age, gender, race, or ethnicity on the distribution of fibrinolysis phenotypes; 47% received AF. The time with chest tube during post-operative recovery was longer in those who received AF (4[3,5] days) vs no AF (3[2,4] days), P=0.037). All cause morbidity occurred in 51% of patients who received AF vs 25% with no AF (p=0.017). However, with AF vs no AF, apparent differences in median chest tube output (1379 vs 820ml, p=0.075), hospital LOS (13 vs 10 days, P=0.873), estimated blood loss (1100 vs 775 ml, P=0.127), units of transfused RBCs (4 vs 2], P=0.152) or all-cause mortality (5.4% [2/37] vs 10% [4/41], P=0.518) were not statistically significant. Conclusion: This is the first description of three distinctly different fibrinolytic phenotypes in cardiac surgery patients. In this population, the use of AF was associated with increased morbidity.

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