Knock-out of BnHva22c reduces the susceptibility of Brassica napus to infection with the fungal pathogen Verticillium longisporum

Verticillium longisporum(Vl43)is a soilborne hemibiotrophic fungal pathogen causing stem striping on oilseed rape(OSR)and severe yield losses.Breeding for resistant varieties is the most promising approach to control this disease.Here,we report the identification of Hva22c as a novel susceptibility factor and its potential for improving OSR resistance.Hva22c is a member of the Hva22 gene family,originally described for barley(Hordeum vulgare).Several Hva22 members have been located at the endoplasmic reticulum.Hva22c is up-regulated in response to Vl43 in both Arabidopsis and OSR.We demonstrate that knock-out of Hva22c in OSR by CRISPR/Cas9 and its homolog in Arabidopsis by T-DNA insertion reduced plants’susceptibility to Vl43 infection and impaired the development of disease symptoms.To understand the underlying mechanism,we analysed transcriptomic data from infected and non-infected roots of hva22c knock-out and wild type plants.We identified a homozygous mutant with frame-shifts in all four BnHva22c loci displaying a vastly altered transcriptional landscape at 6 dpi.Significantly,a large set of genes was suppressed under mock conditions including genes related to the endomembrane systems.Among the up-regulated genes we found several defense-related and phytohormone-responsive genes when comparing mutant to the wild type.These results demonstrate that Hva22c is functionally required for a fully compatible plant-fungus interaction.Its loss of function reduces plant susceptibility,most likely due to endoplasmatic reticulum and Golgi dysfunction accompanied by additionally activated defense responses.These findings can help improve OSR resistance to V.longisporum infection.

Impact of microplastics and nanoplastics on liver health:Current understanding and future research directions

With continuous population and economic growth in the 21st century,plastic pollution is a major global issue.However,the health concern of microplastics/nanoplastics(MPs/NPs)decomposed from plastic wastes has drawn public attention only in the recent decade.This article summarizes recent works dedicated to understanding the impact of MPs/NPs on the liver-the largest digestive organ,which is one of the primary routes that MPs/NPs enter human bodies.The interrelated mechanisms including oxidative stress,hepatocyte energy re-distribution,cell death and autophagy,as well as immune responses and inflammation,were also featured.In addition,the disturbance of microbiome and gut-liver axis,and the association with clinical diseases such as metabolic dysfunction-associated fatty liver disease,steatohepatitis,liver fibrosis,and cirrhosis were briefly discussed.Finally,we discussed potential directions in regard to this trending topic,highlighted current challenges in research,and proposed possible solutions.

Colon Adenocarcinoma in a Retrograde Intussusception: A Case Report and Literature Review

Background: Intussusception is defined as a telescoping of a proximal gastrointestinal segment with its mesentery to a distal one, only 5% occur in adults and in colon the probability that it is caused by a malignant disease is up to 65%. Only 1% occurs in a retrograde manner, the rest occur in an anterograde manner. Aim: Describe the clinical presentation of an intussusception in the adult patient as well as its most frequent causes and possible complications that influence decision making for a definitive treatment. Case Presentation: A 66-year-old woman diagnosed with colon adenocarcinoma who underwent elective transverse colectomy and colonic anastomosis with an incidental finding of a transverse colon tumor in a retrograde intussusception was studied. Conclusion: In any adult patient with an intussusception especially in colon a neoplasia should be suspected and the affected segment should be resected without being reduced due to the risk of perforation and tumor dissemination.

Intraductal Prostatic Carcinoma: Epidemiological and Anatomopathological Aspects in Dakar

Introduction: Intraductal carcinoma is often associated with high-grade, high-stage adenocarcinoma. Its frequency is variable and it is considered a poor prognostic factor. In our context, when prostatic carcinoma is diagnosed, pathologists do not always report the presence of this anatomopathological entity. We therefore conducted a study to determine the epidemiological and anatomopathological profile of patients with this lesion in Dakar. Materials and Methods: This is a retrospective descriptive study covering a 1-year period from January to December 2022. It focused on cases of intraductal carcinoma diagnosed among prostatic carcinomas collected in the anatomopathology laboratories of Hôpital Général Idrissa Pouye (HOGIP) and Hôpital Militaire de Ouakam (HMO). It was based on archives of anatomopathological reports, blocks and slides. A total of 200 cases of prostatic carcinoma were collated and reviewed to identify those presenting with intraductal carcinoma according to the diagnostic criteria of Guo and Epstein. Results: 87 cases of intraductal carcinoma were found, representing 43.5% of prostatic carcinomas. The mean age was 71 years. Patients in their seventh decade were the most represented, i.e. 42.5%. The majority of samples examined were biopsies (72.4%). The mean PSA level was 965.91 ng/ml, with extremes ranging from 0.03 to 10,000 ng/ml. Histologically, 96.5% of cases (N = 84) were invasive prostatic carcinoma. Gleason score 8 (4 + 4) was the most common, accounting for 42.53% (N = 37). On average, the study found four (04) foci of intraductal carcinoma per specimen, with extremes ranging from 1 to 30. Dense cribriform architecture accounted for 78.16%, loose cribriform for 11.5%, solid for 8.04% and micropapillary for 2.3%. Six cases (6.9%) showed foci of comedonecrosis. The vast majority of radical prostatectomies (87.5%) were classified as pT3. Node invasion and perineural sheathing were observed in 12.5% and 52.32% of cases respectively. Conclusion: Intraductal carcinoma is a poor prognostic factor that must be systematically reported in the anatomopathological report. In Senegal, it is often associated with advanced stage, high-grade carcinoma and high PSA levels.

Contribution of Anti-p63 Antibodies in the Interpretation of Benign Label Prostatic Biopsies

Introduction: Prostate cancer is the second most common cancer in men. The diagnosis is most often based on the prostate biopsies’ analysis and on histological criteria recognizable on standard coloring. In some cases, the use of immunohistochemistry is important. Objectives: This paper aims to specify the p63 phenotypic profile of lesions diagnosed benign, with minimal suspect foci, difficult to interpret, HGPIN (high grade intraepithelial neoplasia) and LGPIN (low-grade prostatic intraepithelial neoplasia) and evaluate the manual technique of p63 immunohistochemistry. Patients and Method: This was a retrospective, descriptive study of prostate biopsies recorded in the PAC service of the HALD from January 1st, 2018 to December 31st, 2018. It was completed by a manual immunohistochemical study of the blocks enrolled from November 19th to December 4th, 2020 in the PAC department of the HPD. The studied parameters were: registry number, age, clinical stage, prostate volume, PSA level, microscopic appearance and p63 immunohistochemical profile. Results: Our study included 60 prostate biopsies. The ages of our patients varied from 45 to 77 years, with an average of 64.2 years and a standard deviation of 6.2. The majority of patients were at clinical stage cT2b (33%) with a prostate volume varying between 33.15 and 169.4 cc. The minimum value of PSA in our series is 5 ng/ml, the maximum being 100 ng/ml with an average level of 24.1 ng/ml and a standard deviation of 21.2. Our series included 50 adenomyomatous hyperplasias, 7 adenomyomatous hyperplasias associated with chronic prostatitis, 2 HGPIN and 1 LGPIN. After re-reading we found 5 discordant cases, which corresponded to minimal suspect foci (kappa = 0.5098). The p63 marking was informative in 53 cases, i.e. 88%, and non-informative in 7 cases, i.e. 12%. Among the uninformative markings, 2 were due to lack of tissue adhesion to the slides. Among the informative markings, 11 were negative. p63 immunohistochemistry was useful in all suspected foci and detected 6 other minimal foci of adenocarcinoma. Conclusion: The immunostaining with the anti-p63 antibody in the prostate cancer diagnosis is of considerable benefit. It made it possible to correct 11.3% of benign diagnosis in minimal malignant focus in our context. Despite the difficulties associated with the manual technique, it is possible to have an informative rate, similar to the automatic technique.

Bullous Pemphigoid Induced by Doxycycline: Case Report and Literature Review

Bullous pemphigoid (BP) is the most prevalent autoimmune sub-epidermal blistering disease that affects mainly the elderly and could lead to serious morbidity. It has numerous risk factors and triggers, including an aging population with several comorbidities and drug exposure. In the published paper, we reported a case about a 32 years old male patient with unknown medical conditions who presented with erythematous patches and plaques on the scalp, face, and trunk with scattered blisters two weeks after initiating doxycycline treatment for folliculitis. The exact pathogenesis of the drug-reaction in drug- associated bullous pemphigoid (DABP) remains controversial. In conclusion, it is crucial for clinicians to be aware of DABP when prescribing doxycycline. The purpose of this case report is to raise awareness of the possible association between bullous pemphigoid and doxycycline.

Enteric neuropathology of congenital intestinal obstruction:A case report

试验性的证据显示肠的长期的机械亚吸藏可以损坏伤寒神经系统(ENS ) ，尽管在人的数据正在缺乏。我们这里描述伤寒的第一诉讼与内脏的先天的阻塞有关的退化神经病。3 年的 A 和老女孩开始抱怨了呕吐的 9 瞬间，腹的扩张，有空气液体的便秘在飞机铺平腹的辐射学。她的随后的病历被 3 操作描绘：首先显示出的扩大 duodeno-jejunal 当闭塞的损害不在时循环；第二(2 年以后) 被执行获得扩大的肠的环的完整厚度的活体检视并且在组织病理学说揭示了 hyperganglionosis；第三(在 hyperganglionosis 以后的 9 年被识别) 揭示了 Ladd 被移开的乐队，联系内脏旋转不良被改正。完整厚度的活体检视显示出的重复 intraoperative 与 Cajal 的减少的空隙的房间一起的退化神经病在 Ladd 的乐队下面在阻塞和正常的神经与肌的层上面在扩大的环联网的伤寒。病人容忍了的在最近的外科以后的一年口头的喂并且很好，建议那先天(部分) 在人的小肠的机械阻塞能唤起类似于在肠的机械吸藏的动物模型发现的那些的 ENS 的进步适应变化。如此的 ENS 变化模仿在肠的伪阻塞观察的神经元畸形。

A matched-pair analysis of laparoscopic versus open pancreaticoduodenectomy: oncological outcomes using Leeds Pathology Protocol

BACKGROUND： Laparoscopic pancreaticoduodenectomy（LPD）is a safe procedure. Oncological safety of LPD is still a matter for debate. This study aimed to compare the oncological outcomes,in terms of adequacy of resection and recurrence rate following LPD and open pancreaticoduodenectomy（OPD）.METHODS： Between November 2005 and April 2009, 12LPDs（9 ampullary and 3 distal common bile duct tumors）were performed. A cohort of 12 OPDs were matched for age,gender, body mass index（BMI） and American Society of Anesthesiologists（ASA） score and tumor site.RESULTS： Mean tumor size LPD vs OPD（19.8 vs 19.2 mm,P=0.870）. R0 resection was achieved in 9 LPD vs 8 OPD（P=1.000）. The mean number of metastatic lymph nodes and total number resected for LPD vs OPD were 1.1 vs 2.1（P=0.140）and 20.7 vs 18.5（P=0.534） respectively. Clavien complications grade I/II（5 vs 8）, III/IV（2 vs 6） and pancreatic leak（2 vs 1）were statistically not significant（LPD vs OPD）. The mean high dependency unit（HDU） stay was longer in OPD（3.7 vs 1.4 days,P〈0.001）. There were 2 recurrences each in LPD and OPD（logrank,P=0.983）. Overall mortality for LPD vs OPD was 3 vs 6（log-rank, P=0.283） and recurrence-related mortality was 2 vs 1.There was one death within 30 days in the OPD group secondary to severe sepsis and none in the LPD group.CONCLUSIONS： Compared to open procedure, LPD achieved a similar rate of R0 resection, lymph node harvest and longterm recurrence for tumors less than 2 cm. Though technically challenging, LPD is safe and does not compromise oncological outcome.

Identification and Localization of Prostate Cancer with Combined Use of T2-Weighted,Diffusion Weighted MRI and Proton MR Spectroscopy,Correlation with Histopathology

Purpose: To predict the diagnostic performance of combined use of T2-weighted imaging (T2W)-diffusion weighted MRI (DWI) and apparent diffusion coefficient (ADC)-proton MR spectroscopy (H-MRS) for the detection of prostate cancer, correlated to histopathology as the reference standard. Method: After institutional review board approval, 40 patients with prostate cancer were included in this retrospective research. Two readers evaluated the results of T2W, DWI-ADC mapping and H-MRS independently for the depiction of prostate cancer. Reference standard was the TRUS-guided biopsy and the surgical histopathological results. Statistical analysis was assessed by Fisher’s exact t-test, Wilcoxon signed rank test, variance analysis test with Kappa (k) values and receiver operating characteristics (ROC) curve for ADC values, Cho/Cit and Cho + Cre/Cit ratios for each observer. Results: Both readers declined 46% sensitivity and 68% specificity for T2W sequence, 29% sensitivity and 82% specificity for DWI-ADC mapping and 49% specificity for Cho/Cit and Cho + Cre/Cit ratios, 69% sensitivity for Cho/Cit 70% sensitivity for Cho + Cre/Cit ratios of H-MRS. T2W + DWI-ADC mapping + H-MRS (Cho/Cit and Cho + Cre/Cit ratios) regarded 81% sensitivity and 66% specificity, with significant statistical differences to the reference histopathology (p 0.05). Conclusion: Combination of T2W, DWI and H-MRS were more sensitive and more accurate than either sequences alone, for prostate cancer localization and detection.

New era for pancreatic endoscopic ultrasound: From imaging to molecular pathology of pancreatic cancer

With recent advances in molecular pathology and the development of new chemotherapy regimens,the knowledge of the molecular alterations of pancreatic ductal adenocarcinoma(PDAC)is becoming appealing for stratifying patients for prognosis and response to a defined treatment.Archival formalin-fixed,paraffinembedded samples are a useful source of genomic deoxyribonucleic acid;nevertheless,most studies employed formalin-fixed,paraffin-embedded samples deriving from surgical specimens,which are therefore representative of<20%of PDAC patients.Indeed,the development of a reliable methodology for endoscopic ultrasound-guided tissue acquisition,stabilization,and analysis is crucial for the development of molecular markers for clinical use in order to achieve“personalized medicine”.With the development of new needles,this technique is able to retrieve a high quantity and quality of PDAC tissue that can be used not only for diagnosis but also for mutational and transcriptome evaluations and for the development of primary cell or tissue cultures.In the present editorial,we discuss the current knowledge regarding the use of endoscopic ultrasound as a tool to obtain samples for molecular analyses,its possible pitfalls,and its use for the development of disease models such as xenografts or organoids.

Predictors of Malignant Pathology and the Role of Trans-Thoracic Needle Biopsy in Management of Solitary Fibrous Tumors of the Pleura: A 30-Year Review of a Tertiary Care Center Patient Cohort

Background: Solitary fibrous tumors of the pleura (SFTP) are rare neoplasms with unpredictable behavior. Lack of unifying criteria for benign or malignant SFTP has resulted in reports of SFTP exhibiting malignant behavior years after complete surgical resection (despite benign initial diagnosis). Additionally, the role of trans-thoracic needle biopsy in initial management of SFTP is unclear. Understanding predictors of malignancy identifies patients at unacceptably high risk for non-surgical primary therapy, and for recurrence despite complete surgical resection. Objectives: The primary objectives were to identify clinicopathological predictors of malignancy & recurrence in SFTP. The secondary aim was to determine the role of trans-thoracic needle biopsy in the management decision algorithm of SFTP. Methods: Retrospective chart review was conducted (Jan. 1983-Dec. 2013) at the Ottawa Hospital for pathologically confirmed SFTP. Data were collected on biopsy-related, clinical, histopathological & immunohistochemistry (IHC) variables. Appropriate tests of statistical inference were conducted for all variables. Results: Pathologically confirmed SFTP was identified in 26 cases. Transthoracic needle biopsy was conducted in 22 (84.6%);with 16 (72.7%) biopsies diagnostic of SFTP with IHC;3 (13.6%) being malignant. Primary management was surveillance in 3 and complete surgical resection in 23. Surgical pathology reported 15 (65.2%) benign and 8 (34.8%) malignant cases. Local recurrence occurred in 3 and distant recurrence in 1. Initial pathology was benign in 3 (75%) with recurrence. Clinicopathologic variables analyzed did not predict recurrent disease. IHC features did not differ between malignant & benign pathology significantly. Predictors of malignant pathology included: infiltrative cellular pattern (p = 0.042), nuclear crowding (p = 0.006), tumour necrosis (p 4 mitoses/ 10 high power field (p Conclusion: Because numerous variables analyzed did not predict recurrent disease, long-term follow-up is warranted regardless of benign or malignant initial histology. Histologic not IHC features predicted malignant pathology. Trans-thoracic needle biopsy did identify malignant SFTP;however its main use should be to differentiate SFTP from other pleural neoplasms using IHC.

Play therapy in children with autism:Its role,implications,and limitations

Play is a pleasurable physical or mental activity that enhances the child’s skills involving negotiation abilities,problem-solving,manual dexterity,sharing,decision-making,and working in a group.Play affects all the brain's areas,structures,and functions.Children with autism have adaptive behavior,adaptive response,and social interaction limitations.This review explores the different applications of play therapy in helping children with autism disorder.Play is usually significantly impaired in children with autism.Play therapy is mainly intended to help children to honor their unique mental abilities and developmental levels.The main aim of play therapy is to prevent or solve psychosocial difficulties and achieve optimal child-healthy growth and development.Play therapy helps children with autism to engage in play activities of their interest and choice to express themselves in the most comfortable ways.It changes their way of self-expression from unwanted behaviors to more non-injurious expressive behavior using toys or activities of their choice as their words.Play therapy also helps those children to experience feeling out various interaction styles.Every child with autism is unique and responds differently.Therefore,different types of intervention,like play therapy,could fit the differences in children with autism.Proper evaluation of the child is mandatory to evaluate which type fits the child more than the others.This narrative review revised the different types of play therapy that could fit children with autism in an evidence-based way.Despite weak evidence,play therapy still has potential benefits for patients and their families.

Pleural effusion in critically ill patients and intensive care setting

Pleural effusion usually causes a diagnostic dilemma with a long list of differential diagnoses.Many studies found a high prevalence of pleural effusions in critically ill and mechanically ventilated patients,with a wide range of variable prevalence rates of up to 50%-60%in some studies.This review emphasizes the importance of pleural effusion diagnosis and management in patients admitted to the intensive care unit(ICU).The original disease that caused pleural effusion can be the exact cause of ICU admission.There is an impairment in the pleural fluid turnover and cycling in critically ill and mechanically ventilated patients.There are also many difficulties in diagnosing pleural effusion in the ICU,including clinical,radiological,and even laboratory difficulties.These difficulties are due to unusual presentation,inability to undergo some diagnostic procedures,and heterogenous results of some of the performed tests.Pleural effusion can affect the patient’s outcome and prognosis due to the hemodynamics and lung mechanics changes in these patients,who usually have frequent comorbidities.Similarly,pleural effusion drainage can modify the ICUadmitted patient’s outcome.Finally,pleural effusion analysis can change the original diagnosis in some cases and redirect the management toward a different way.

Role of Vascular Endothelial Growth Factor-C during Stem Cell Therapy Using Autologous Bone Marrow Mononuclear Cells in Patients with Lower Limb Lymphedema

Introduction: Vascular endothelial growth factor-C (VEGF-C) is the primary lymphangiogenic factor that stimulates lymphangiogenesis by signaling via specific receptor, vascular endothelial growth factor receptor 3 (VEGFR3). This study was conducted to evaluate the change in the level of VEGF-C before and after autologous bone marrow mononuclear cell transplantation for treatment of Lower limb lymphedema. Patient and methods: Forty patients with lower limb lymphedema were divided into two groups. Group I included 20 patients with chronic lower limb lymphedema who underwent autologous bone marrow mononuclear cell transplantation. Group II included 20 patients with chronic lower limb lymphedema who were exposed only to compression therapy as a control group. VEGF-C level in the diseased limbs was measured in both groups at the beginning of the study then 3 and 6 months respectively. Results: Group I included 20 patients, 8 patients were male (40%) and 12 patients were females (60%) with mean age 29.5 ± 12.15 while group II included 20, 10 patients were male (50%) and 10 patients were females (50%) with mean age 39.5 ± 11.5. In group I, the specimens were taken at 3 and 6 months after transplantation showed a marked decrease in the VEGF-C level with statistically significant p value, 0.02 and 0.001 respectively. In group II the level of VEGF-C after compression therapy alone at 3 and 6 months interval showed fluctuation with statistically non-significant p value, 0.64 and 0.55 respectively. Conclusion: VEGF-C is essential for regulation of lymphangiogenesis. The level of VEGF-C was found elevated in patients with lymphedema and decrease after autologous mononuclear bone marrow cells, however these results were statically non-significant.

Expression and prognosis of inducible T-cell co-stimulator and its ligand in Chinese stage I–III lung adenocarcinoma patients

Background:Immunotherapy has become the fastest-adopting treatment paradigm for lung cancer with improved survival.By binding with its ligand(inducible T-cell costimulator and its ligand[ICOSL]),an inducible T-cell co-stimulator(ICOS)could contribute to reversing immunosuppression and improving immune response and thus be a potential target for cancer immunotherapy.Methods:We selected 54 formalin-fixed,paraffin-embedded tumor tissues from cases with stage I–III lung adenocarcinoma cancer.Immunohistochemical expression of ICOS and ICOSL was evaluated.The correlation with clinical parameters in Chinese patients was also compared with TCGA results.Results:The positive rates of ICOS and ICOSL were 68%and 81.5%,respectively,in lung tumor tissues.Of these,9 cases had a low expression of ICOS,and 22 cases had a high expression of ICOS;ICOSL expression was low in 20 cases and high in 24 cases.According to the International Association for the Study of Lung Cancer(8th edition),phase I lesions were detected in 21 cases,phase II lesions in 15 cases,and phase III lesions in 18 cases.The median survival time of all patients was 44.5 months,and the median disease-free survival was 32 months.Univariate analysis showed that the factors significantly associated with overall survival were tumor size,regional lymph node involvement,stage,and expression level of ICOS/ICOSL.Survival analysis using log-rank test indicated that the lower ICOS+cell infiltration may predict poor prognosis,whereas lower ICOSL protein expression may be associated with better prognosis,but ICOSL data need further validation in larger samples due to inconsistency in TCGA mRNA prediction.Conclusion:ICOS/ICOSL might be associated with prognosis of lung cancer,and ICOS and its ligand may be potential therapeutic targets in non-small cell lung cancer.

Hydroxysafflor yellow A protects against thioacetamide-induced liver fibrosis in rats via suppressing proinflammatory/fibrogenic mediators and promoting hepatic stellate cell senescence and apoptosis

Objective:To evaluate the effect of hydroxysafflor yellow A(HSYA)on thioacetamide-induced liver fibrosis.Methods:Thioacetamide was administered to rats intraperitoneally in doses of 200 mg/kg twice a week for 12 weeks.Thioacetamide-intoxicated rats were given silymarin(50 mg/kg)or HSYA(5 mg/kg)orally every day for 8 weeks.Liver enzymes,fibrosis markers,histological changes as well as immunohistochemistry of TNF-α,IL-6,p21,α-SMA,and caspase-3 were examined.The effect of HSYA on HSC-T6 activation/proliferation and apoptosis was also determined in vitro.Results:HSYA decreased liver enzymes,TNF-α,IL-6,and p21 expressions,hepatic PDGF-B,TIMP-1,TGF-β1,and hydroxyproline levels,as well as fibrosis score(S2 vs.S4)compared to the thioacetamide group.HSYA also downregulatedα-SMA while increasing caspase-3 expression.Surprisingly,at 500μg/mL,HSYA had only a slightly suppressive effect on HSC proliferation,with a 9.5%reduction.However,it significantly reduced TGF-β1,inhibitedα-SMA expression,induced caspase-3 expression,and promoted cell senescence.Conclusions:HSYA may be a potential therapeutic agent for delaying and reversing the progression of liver fibrosis.More research on HSYA at higher doses and for a longer period is warranted.

A Th2-score in the tumor microenvironment as a predictive biomarker of response to Bacillus Calmette Guérin in patients with non-muscle invasive bladder carcinoma:A retrospective study

Intravesical Bacillus Calmette Guerin(BCG)is the gold standard therapy for intermediate/high-risk nonmuscle invasive bladder cancer(NMIBC).However,the response rate is~60%,and 50%of non-responders will progress to muscle-invasive disease.BCG induces massive local infiltration of inflammatory cells(Th1)and ultimately cytotoxic tumor elimination.We searched for predictive biomarker of BCG response by analyzing tumor-infiltrating lymphocyte(TIL)polarization in the tumor microenvironment(TME)in pre-treatment biopsies.Pre-treatment biopsies from patients with NMIBC who received adequate intravesical instillation of BCG(n=32)were evaluated retrospectively by immunohistochemistry.TME polarization was assessed by quantifying the T-Bet+(Th1)and GATA-3+(Th2)lymphocyte ratio(G/T),and the density and degranulation of EPX+eosinophils.In addition,PD-1/PD-L1 staining was quantified.The results correlated with BCG response.In most non-responders,Th1/Th2 markers were compared in pre-and post-BCG biopsies.ORR was 65.6%in the study population.BCG responders had a higher G/T ratio and a greater number of degranulated EPX+cells.Variables combined into a Th2-score showed a significant association with higher scores in responders(p=0.027).A Th2-score cut-off value>48.1 allowed discrimination of responders with 91%sensitivity but lower specificity.Relapse-free survival was significantly associated with the Th2-score(p=0.007).In post-BCG biopsies from recurring patients,TILs increased Th2-polarization,probably reflecting BCG failure to induce a pro-inflammatory status and,thus,a lack of response.PD-L1/PD-1 expression was not associated with the response to BCG.Our results support the hypothesis that a preexisting Th2-polarized TME predicts a better response to BCG,assuming a reversion to Th1 polarization and antitumor activity.

COVID-19-induced gastrointestinal autonomic dysfunction:A systematic review

BACKGROUND It is common for severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection to occur in the gastrointestinal tract,which can present itself as an initial symptom.The severity of coronavirus disease 2019(COVID-19)is often reflected in the prevalence of gastrointestinal symptoms.COVID-19 can damage the nerve supply to the digestive system,leading to gastrointestinal autonomic dysfunction.There is still much to learn about how COVID-19 affects the autonomic nervous system and the gastrointestinal tract.AIM To thoroughly explore the epidemiology and clinical aspects of COVID-19-induced gastrointestinal autonomic dysfunction,including its manifestations,potential mechanisms,diagnosis,differential diagnosis,impact on quality of life,prognosis,and management and prevention strategies.METHODS We conducted a thorough systematic search across various databases and performed an extensive literature review.Our review encompassed 113 studies published in English from January 2000 to April 18,2023.RESULTS According to most of the literature,gastrointestinal autonomic dysfunction can seriously affect a patient's quality of life and ultimate prognosis.Numerous factors can influence gastrointestinal autonomic nervous functions.Studies have shown that SARS-CoV-2 has a well-documented affinity for both neural and gastrointestinal tissues,and the virus can produce various gastrointestinal symptoms by reaching neural tissues through different pathways.These symptoms include anorexia,dysgeusia,heartburn,belching,chest pain,regurgitation,vomiting,epigastric burn,diarrhea,abdominal pain,bloating,irregular bowel movements,and constipation.Diarrhea is the most prevalent symptom,followed by anorexia,nausea,vomiting,and abdominal pain.Although COVID-19 vaccination may rarely induce autonomic dysfunction and gastrointestinal symptoms,COVID-19-induced autonomic effects significantly impact the patient's condition,general health,prognosis,and quality of life.Early diagnosis and proper recognition are crucial for improving outcomes.It is important to consider the differential diagnosis,as these symptoms may be induced by diseases other than COVID-19-induced autonomic dysfunction.Treating this dysfunction can be a challenging task.CONCLUSION To ensure the best possible outcomes for COVID-19 patients,it is essential to take a multidisciplinary approach involving providing supportive care,treating the underlying infection,managing dysfunction,monitoring for complications,and offering nutritional support.Close monitoring of the patient's condition is crucial,and prompt intervention should be taken if necessary.Furthermore,conducting thorough research on the gastrointestinal autonomic dysfunction caused by COVID-19 is vital to manage it effectively.

Antibiotic resistance and molecular typing of clinical Staphylococcus aureus isolates from Malaysian military hospital

Objective:To determine the antibiotic resistance profile(ARP)of Staphylococcus(S.)aureus isolates and molecular typing of the methicillin-resistant S.aureus(MRSA)isolates from Tuanku Mizan Armed Forces Hospital(TMAFH),Kuala Lumpur.Methods:The ARP and presence of the pvl gene were determined for 209 S.aureus isolates from clinical specimens.Of these,123 were methicillin-susceptible S.aureus(MSSA)isolates and 86 were MRSA isolates.All MRSA isolates were characterized using SCCmec typing and spa typing.Descriptive analysis was performed to compare the demographic data with the phenotypic and genotypic variables of the S.aureus isolates.Results:No vancomycin-intermediate and-resistant S.aureus(VISA and VRSA,respectively)were detected among the study isolates.The MSSA isolates showed low resistance rates to all tested antibiotics,were commonly invasive(28/42,66.7%),and mostly harboured pvl(35/42,83.3%).Meanwhile,MRSA isolates showed high resistance to penicillin(86/86,100%),ampicillin(86/86,100%),sulbactam/ampicillin(86/86,100%),cefuroxime(81/86,94.19%),cefoperazone(76/86,88.37%),azithromycin(56/86,65.12%),and erythromycin(54/86,62.79%).The majority of MRSA isolates were of SCCmec type IVh(65/86,75.58%),spa type t032(55/85,63.95%),and grouped into spaCC-t022(66/85,77.65%).The t032 type was found to be associated with resistance traits to azithromycin and erythromycin(P<0.05).We also found several spa types that are typically associated with hospital-,community-,and livestock-associated MRSA co-existing in our MRSA population.Conclusions:This study reflected the consistent absence of VISA and VRSA and corroborated the clonal shifting of MRSA isolates in the Malaysian MRSA isolates.