Background: Although FoxP3+ regulatory T (Treg) cells constitute a highly heterogeneous population, with different regulatory potential depending on the context, distinct subsets or phenotypes remain poorly defined. This hampers the development of immunotherapy for allergic and autoimmune disorders. This study aimed at characterizing distinct FoxP3+ Treg subpopulations involved in the suppression of Th2-mediated allergic inflammation in the lung. Methods: We used an established mouse model of allergic airway disease based on ovalbumin sensitization and challenge to analyze FoxP3+ Tregs during the induction and resolution of inflammation, and identify markers that distinguish their most suppressive phenotypes. We also developed a new knock-in mouse model (Foxp3creCd103dtr) enabling the specific ablation of CD103+FoxP3+ Tregs for functional studies. Results: We found that during resolution of allergic airway inflammation in mice >50% of FoxP3+ Treg cells expressed the integrin CD103 which marks FoxP3+ Treg cells of high IL-10 production, increased expression of immunoregulatory molecules such as KLRG1, ICOS and CD127, and enhanced suppressive capacity for Th2-mediated inflammatory responses. CD103+FoxP3+ Tregs were essential for keeping allergic inflammation under control as their specific depletion in Foxp3creCd103dtr mice lead to severe alveocapillary damage and eosinophilic pneumonia, markedly reducing the lifespan of the experimental animals. Conversely, adoptive transfer of CD103+FoxP3+ Tregs effectively treated disease, attenuating Th2 responses and allergic inflammation in an IL-10-dependent manner. Conclusion: Our study identifies a novel regulatory T cell population, defined by CD103 expression, programmed to prevent exuberant type 2 inflammation and keep homeostasis in the respiratory tract under control. This has important therapeutic implications.
The presence of pigmented and partially pigmented skin lesions of non-univocal interpretation should always trigger a cautious approach. Albeit the diagnosis of malignant melanoma should remain our main concern, other more common skin conditions, namely basal cells carcinoma, should be taken into consideration in the diagnostic process and management plan. The following case highlights how, sometimes, the diagnosis of partially pigmented basal cells carcinoma may not appear to be immediately evident and the opportunity to deal with non-surgical approach missed. Case report 50-year-old man of Caucasian origin, phototype III in Fitzpatrick scale, initially presenting with a 6-month history of pigmented, inflamed, flat skin lesion at the base of the neck. The lesion had been noticed in the summer months due to the itching and occasional burning it caused (figure 1). Physical examination revealed a 7 mm x 8 mm superficial skin lesion, partially pigmented, not well defined, slightly hyperkeratotic, against a background with several lentigo and nevi. No particular concerns were raised by dermoscopy, or dermatoscopy, and the patient was reassured, even though a small white clod was noted.
Jejunal mucormycosis in a patient with refractory AMLSamuel De l’Etoile-Morel, MD. McGill University Health Centre. Department of Medicine, Division of Infectious Diseases. 1001 Decarie Blvd, Montreal, Quebec H4A 3J1 Room E05.1811.2.Vladimir Sapon-Cousineau, MD. Department of Medicine, Division of Hematology. 1001 Decarie Blvd, Montreal, Quebec H4A 3J1 Room D02.7731.Dan L. Deckelbaum, MD. McGill University Health Centre. Department of Surgery, Divisions of Trauma and General Surgery. 1650 Cedar Ave, Montreal, Quebec H3G 1A4. L9 425.Michael Sebag, MD McGill University Health Centre. Department of Medicine, Division of Hematology. 1001 Decarie Blvd, Montreal, Quebec H4A 3J1 Room D02.7515.Zu-hua Gao, MD McGill University Health Centre. Department of Clinical Laboratory Medicine, Division of Pathology. 1001 Decarie Blvd, Montreal, Quebec H4A 3J1 Room E04.1820.Vivian G. Loo, MD McGill University Health Centre. Department of Medicine, Division of Infectious Diseases. 1001 Decarie Blvd, Montreal, Quebec H4A 3J1 Room E05.1824.Corresponding author : Samuel De l’Etoile-Morel, MD. McGill University Health Centre. Department of Medicine, Division of Infectious Diseases. 1001 Decarie Blvd, Montreal, Quebec H4A 3J1 Room E05.1811.2. Telephone 514-934-1934 extension 53333 [email protected] 47-year-old man received chemotherapy for the treatment of refractory acute myeloid leukemia. Two weeks after re-induction, he developed fever, neutropenia, nausea and severe vomiting with abdominal pain. Computed tomography of the abdomen showed a small bowel obstruction with ischemic changes of the jejunum concerning for mesenteric ischemia (panel A). An urgent open laparotomy was performed revealing two areas of jejunal necrosis (panel B) and the patient underwent a partial small bowel resection with primary anastomosis.Histopathological examination of the jejunum with Grocott staining demonstrated ischemic necrosis associated with angioinvasive zygomycosis (panel C). Rhizopus oryzae was identified as the causative pathogen using polymerase chain reaction followed by DNA sequence analysis on the pathology specimen.The patient was treated intravenously with liposomal amphotericin and subsequently transitioned to oral isavuconazole. He was subsequently discharged from the hospital and died approximately 1 year later of progressive AML.Gastrointestinal mucormycosis remains a rare infection among immunocompromised hosts and a high index of suspicion is imperative (1). Its presentation can mimic ischemic colitis often resulting in a diagnosis made by pathology and not by conventional culture. Successful management includes early surgical resection and initiation of appropriate antifungal therapy.1. Spellberg B. Gastrointestinal mucormycosis: an evolving disease. Gastroenterol Hepatol (N Y). 2012;8(2):140-2.
Brucellosis is an endemic disease in many developing countries and ranked by the World Health Organization among the top seven “neglected zoonoses”. Although a Palestinian brucellosis control program was launched in 1998, the disease reemerged after 2012. Interestingly, a similar reemerging pattern was reported in the neighboring Israeli regions. The aim of this work was to characterize the reemerging strains and delineate their genetic relatedness. During 2015-2017, blood samples from 1324 suspected patients were analyzed using two serological tests. Seropositive samples were cultured, and their DNAs were analyzed by different genetic markers to determine the involved Brucella species and rule out any possible involvement of the Rev.1 vaccine strain. The rpoB gene was sequenced from 9 isolates to screen for rifampicin-resistance mutations. Multi Locus VNTR Analysis (MLVA-16) was used for genotyping the isolates. The molecular analysis showed that all isolates were B. melitensis strains unrelated to the Rev.1 vaccine. The rpoB gene sequences showed four single nucleotide variations (SNVs) not associated with rifampicin resistance. MLVA-16 analysis clustered the isolates into 22 unique genotypes that belong to the East Mediterranean lineage. Altogether, our findings show that the reemergence of brucellosis was due to B. melitensis strains of local origin, the Palestinian and Israeli control programs’ weaknesses could be a major factor behind the reemergence of the disease. However, other socioeconomic and environmental factors must be investigated. Moreover, strengthening brucellosis control programs and enhancing cooperation between all stakeholders is essential to ensure long-term program outcomes to fight brucellosis.
This paper investigates the problem of $H_\infty$ state estimation of delayed recurrent memristive neural networks (DRMNNs) with both continuous-time and discrete-time cases. By utilizing Lyapunov-Krasovskii functional (LKF) and linear matrix inequalities (LMIs), two criterions are provided to guarantee the asymptotically stable of the estimation error systems with a $H_\infty$ performance. The connection weight parameters of DRMNNs are dealed with logical switching signals, which greatly reduces the computational complexity. The given conditions can be easily checked by solving LMIs, the obtained theoretical results are supported demonstrated by two numerical examples.
Background: Takotsubo Syndrome (TTS) is characterized by acute and reversible left ventricular dysfunction with apical ballooning arising during acute stress situations. Acute Ischemic Stroke (AIS) is one of the known triggers to TTS, however, the impact of TTS on in-hospital outcomes of AIS remains unexplored. Methods: We utilized data from the National Inpatient Sample (2007-2014) and using ICD-9-CM diagnosis codes to identify admissions for AIS with TTS and evaluated the temporal trends, baseline characteristics, in-hospital complications, length of stay (LOS) and all-cause mortality. Survey multivariable logistic regression was used to compute adjusted Odds Ratios (OR and 95% confidence intervals (CI). Results: An estimated 2,242 (0.4%) TTS cases were identified among AIS hospitalizations (N=43,92,471). The frequency of TTS was higher in elderly, whites and females (82.2%). After adjustment for confounders, TTS incidence in AIS was associated with higher odds of in-hospital complications including cardiogenic shock (OR8.84, CI:4.07-19.17, p<0.001), cardiac arrest (OR3.17, CI:1.57-6.42, p=0.001), and venous thromboembolism (OR1.68, CI:1.14-2.47, p=0.008). Moreover, AIS hospitalizations with TTS showed higher odds of developing respiratory failure (OR3.13, CI:2.42-4.05, p<0.001) and required mechanical ventilation/intubation (OR4.09, CI:3.14-5.32, p<0.001) more frequently compared to non-TTS cohort. The AIS-TTS cohort had longer LOS (8.59 vs 5.22 days) and the mortality was doubled (10.2% vs 5.1% p<0.001) compared to those without TTS. Conclusion: The prevalence of TTS in AIS remained ~20 times higher than the general inpatient population and it predisposed AIS patients to worse inpatient outcomes. Further studies are needed to evaluate the impact of TTS on long-term outcomes in AIS.
Food-and-mouth disease (FMD) is endemic in Cambodia. The control program for FMD has relied on vaccination, with poor vaccination uptake by smallholder farmers an increasing concern. A study to improve the understanding of farmer knowledge, attitudes and practices of FMD and FMD vaccination was conducted in two Cambodian provinces. The aim was to identify opportunities to improve the disease control programs provided by both the government and private sectors. The survey comprised 300 smallholder farmers using a one-on-one interview technique. Results identified that over two-thirds of the respondent farmers had not vaccinated their cattle over two years. Of those who did, most cattle were vaccinated either once a year or once every three years. A booster had never been administered. FMD outbreaks occurred every year during the study period, with a morbidity rate of over 30%. Isolation of first infected cattle from the household herd was not practiced, with treatment identified as the first preference intervention. Farmers often assisted other farmers to restrain and treat infected cattle both before (57%) and after (43%) their own cattle were infected. This indicated that most farmers did not practice basic biosecurity measures and chose to report FMD outbreaks to the village animal health workers (VAHW), friends, neighbors, and relatives in preference to government officials. It was concluded that poor knowledge of disease transmission and biosecurity, with low FMD vaccination coverage and a focus on treatment, contribute to regular FMD outbreaks in these communities. Improvement of FMD control requires the cooperation of villagers, VAHWs, and village leaders in disease reporting, with either improved funding of government vaccination services or private FMD vaccination service. Training programs for farmers on disease transmission, and the importance of biosecurity and vaccination, including information on the cost-benefits of treatment versus full fee bi-annual FMD vaccination, are required.
Objective: This study aimed to assess the possible role of dermoscopy in the diagnosis of different nail disorders compared with the clinical and histopathological diagnosis. Methods: This study included 104 patients with any nail disorders of both sex and any age. All the patients were subjected to a detailed medical history taken, clinical general examination, clinical and dermoscopic examinations of 20 nails. Potassium hydroxide examination was used to examine all patients with suspicious of onychomycosis. Histopathological evaluation was used to examine of clinically ambiguous nail disorders. Results: The most common nail diseases were onychomycosis (54.81%) followed by nail psoriasis (19.2%), and nail lichen planus (3.8%). Conclusion: Clinical evaluation was an important in diagnosis of different nail diseases. Nail dermoscopy could confirm clinical diagnosis and help in getting an accurate diagnosis of nail diseases and guide in the management of nail diseases by permitting better visualization of nail structure and pathology. Histopathological examination provided the most definitive method in reaching an accurate diagnosis due to it could provide etiologic, diagnostic, and prognostic information. There was good agreement between clinical, dermoscopic, and histopathological examinations for accurate diagnosis of different nail diseases.
The total impact of the worldwide COVID-19 pandemic is still emerging, changing all relationships as a result, including those with pet animals. In the infection process, the use of Angiotensin-converting enzyme 2 (ACE2) as a cellular receptor to the spike protein of the new coronavirus is a fundamental step. In this sense, understanding which residue plays what role in the interaction between SARS-CoV-2 spike glycoprotein and ACE2 from cats, dogs, and ferrets is an important guide for helping to choose which animal model can be used to study the pathology of COVID-19 and if there are differences between these interactions and those occurring in the human system. Hence, trying to help to answer these questions, we performed classical molecular dynamics simulations to evaluate, from an atomistic point of view, the interactions in these systems. Our results show that there are significant differences in the interacting residues between the systems from different animal species, and the role of ACE2 key residues are different in each system and can assist in the search for different inhibitors for each animal.
Toxoplasma gondii was initially classified in three main lineages related to its virulence: Types I, II and III. The recombination of genes during sexual cycle in felids gut led to more than 200 genotypes, found in ToxoDB database, using 11 RFLP markers. Free-range chickens are good bioindicators of soil contamination with T. gondii oocysts. In this sense, there are systematic reviews regarding data of genetic characterization of this parasite in felines and ruminants, but not in chickens heretofore, what makes this work necessary. A systematic review in the literature was performed with papers published prior to September 21st, 2020. The main inclusion criteria was the presence of T. gondii genotypes, isolated strictly from free-range chickens, in experimental works. Initially, a total of 1,343 studies related to the terms were identified on databases and 30 studies were selected to be systematically reviewed. A total of 561 isolates of T. gondii from 6,356 free-range chickens were analyzed for genotyping, revealing 190 genotypes. ToxoDB #59 and #2 were the most frequent in America, #1 was the most frequent in Africa and 3 atypical isolates from genotype ToxoDB #9 were found in Asia. There is not data from Europe and Oceania. The majority of studies were Brazilian (16/30). A total of 68 RFLP genotypes were recognized among the 561 isolates’ DNAs analyzed from the 30 studies. Some studies show new genotypes never described before, which reinforces the idea that some years from now, even more new genotypes will be isolated, due to progressive genetic recombination. The large amount of undefined genotypes makes it necessary to perform Nested PCR technique when genotyping. Moreover, the lack of data in Continents such as Europe, Asia and Oceania makes it necessary to perform new isolating and genotyping studies in these places.
In this paper, with the purpose of improving the mechanical behavior of DeepCwind semi-submersible floating offshore wind turbine (FOWT) platform mooring lines, nonlinear catenary cables of platform are divided into multi-segments and intermediate buoy. The mathematical formulations of the dynamic equation acted on the cable with buoys are described. Present study is employed to the OC4-DeepCwind semi-submersible FOWT platform. It is designed for 200-meter water depth with mooring lines consist of three catenary steel chain cables that have an angle of 120 degrees to each other. The dynamic response of multi-segment catenary mooring line with different buoys radiuses and different positions along the cables were investigated. The full-scale platform was modeled in ANSYS-AQWA software and the simulations are performed in harsh offshore. The tension, strain, anchor uplift, cable uplift for different buoy radiuses and its position along cable are presented and discussed. Moreover, platform motions at three directions (surge, heave and pitch) are also analyzed. It is concluded that by correct selection of the buoy volume and position along cable, the tension of the cable may be reduced up to 45%. By incorrect selection of the buoy, the results will cause adverse effects.
Anthroponotic cutaneous leishmaniasis (ACL) due to Leishmania tropica is spreading to new areas. Exposure to the vector, Phlebotomus sergenti, is the only proven risk factor. Our objective was to compare the densities and genetic characteristics of P. sergenti populations in two nearby localities in Morocco, one within an ACL endemic area (El Borouj) and another undamaged (Sidi Hajjaj). Statistically significant differences were detected between P. sergenti densities with a higher density of P. sergenti in the endemic town (p≤ 0.032). A different main P. sergenti mitochondrial lineage was evidenced in each one of the 2 localities, and for the first time, the lineage of P. sergenti specimens that are acting as a vector of L. tropica has been identified. Bioclimatic differences were detected between both localities. In conclusion, between an ACL endemic locality and another ACL free there are differences in both the density of P. sergenti and the mitochondrial lineage that may explain the different epidemiological situation. Given that the density of P. sergenti in the locality without ACL cases seems sufficient to allow transmission, the main factor that would justify its ACL undamaged character could be the absence of P. sergenti Lineage IV, which seems to prefer warmer and drier climates.
Atrial fibrillation (AF) is the most common heart rhythm disorder in adults and a major cause of stroke. Unfortunately, current treatments for AF are suboptimal as they are not targeting the molecular mechanisms underlying AF. In this regard, gene therapy is emerging as a promising approach for mechanism-based treatment of AF. In this review, we summarize recent advances and challenges in gene therapy for this important cardiovascular disease.
This paper starts with an overview of the application of the three guidelines (GL) of the German Research Association of Mechanical Engineers (FKM). Each of these provides algorithms for calculating fatigue lives of components under constant or variable amplitude loading, however, with underlying different failure criteria, i.e. technical crack initiation life (GL-nonlinear), fatigue crack growth life (GL-fracture mechanics), and total fracture life (GL-linear). This paper introduces the U-Concept which has been evaluated from a large structural durability database. The U-Concept is a small add-on to the Local Strain Approach (LSA) which is the backbone of the GL-nonlinear. It enables 1) to directly calculate the fatigue life to total fracture based on elastic-plastic material behaviour according to the LSA, or 2) to estimate the remaining fatigue life from crack initiation to fracture without a crack growth simulation.
Introduction: Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia, and results in significant morbidity and mortality. The Cox-Maze IV procedure (CMP-IV) has been shown to have excellent efficacy in returning patients to sinus rhythm, but there have been few reports of late follow-up in sizable cohorts of patients with longstanding persistent AF, the most difficult type of AF to treat. Methods & Results: Between May 2003 and March 2020, 174 consecutive patients underwent a stand-alone CMP-IV for longstanding persistent AF. Rhythm outcome was assessed postoperatively for up to 10 years, primarily via prolonged monitoring (Holter monitor, pacemaker interrogation, or implantable loop recorder). Fine-Gray regression was used to investigate factors associated with atrial tachyarrhythmia (ATA) recurrence, with death as a competing risk. Median duration of preoperative AF was 7.8 years (interquartile range [IQR] 4.0-12.0 years), with 71% (124/174) having failed at least one prior catheter-based ablation. There were no 30-day mortalities. Freedom from ATAs was 94% (120/128), 83% (53/64), and 88% (35/40) at 1, 5, and 7 years, respectively. On regression analysis, preoperative AF duration and early postoperative ATAs were associated with late ATAs recurrence. Conclusion: Despite the majority of patients having a long-duration of preoperative AF and having failed at least one catheter-based ablation, the stand-alone CMP-IV had excellent late efficacy in patients with longstanding persistent AF, with low morbidity and no mortality. We recommend consideration of stand-alone CMP-IV for patients with longstanding persistent AF who have failed or are poor candidates for catheter ablation.