The constitutive expression of Speckled-100 (Sp100) is known to restrict the replication of many clinically important DNA viruses. This pre-existing (intrinsic) immune defense to virus infection can be further upregulated upon interferon (IFN) stimulation as a component of the innate immune response. In humans, Sp100 is encoded by a single gene locus, which can produce alternatively spliced isoforms. The widely studied Sp100A, Sp100B, Sp100C and Sp100HMG have functions associated with the transcriptional regulation of viral and cellular chromatin, either directly through their characteristic DNA-binding domains, or indirectly through post-translational modification (PTM) and associated protein interaction networks. Sp100 isoforms are resident component proteins of promyelocytic leukemia-nuclear bodies (PML-NBs), dynamic nuclear sub-structures which regulate host immune defenses against many pathogens. In the case of human herpesviruses, multiple protein antagonists are expressed to relieve viral DNA genome transcriptional silencing imposed by PML-NB and Sp100-derived proteinaceous structures, thereby stimulating viral propagation, pathogenesis, and transmission to new hosts. This review details how different Sp100 isoforms are manipulated during herpesviruses HSV1, VZV, HCMV, EBV, and KSHV infection, identifying gaps in our current knowledge, and highlighting future areas of research.Poison inhibitors of DNA topoisomerase II (TOP2) are clinically used drugs that cause cancer cell death by inducing DNA damage, which mechanism of action is also associated with serious side effects such as secondary malignancy and cardiotoxicity. In contrast, TOP2 catalytic inhibitors induce limited DNA damage, have low cytotoxicity, and are effective in suppressing cancer cell proliferation. They have been sought after to be prospective anticancer therapies. Herein the discovery of new TOP2 catalytic inhibitors is described. A new druggable pocket of TOP2 protein at its DNA binding domain was used as a docking site to virtually screen ~6 million molecules from the ZINC15 library. The lead compound, T60, was characterized to be a catalytic TOP2 inhibitor that binds TOP2 protein and disrupts TOP2 from interacting with DNA, resulting in no DNA cleavage. It has low cytotoxicity, but strongly inhibits cancer cell proliferation and xenograft growth. T60 also inhibits androgen receptor activity and prostate cancer cell growth. These results indicate that T60 is a promising candidate compound that can be further developed into new anticancer drugs.

Cabozantinib (XL-184) is a small molecule inhibitor of the tyrosine kinases c-Met, AXL, and VEGFR2 that has been shown to reduce tumor growth, metastasis, and angiogenesis. After the promising results from the METEOR and CABOSUN trials, cabozantinib was approved for use in the first- and second-line setting in patients with advanced RCC. Previously, targeted therapies have been used in the neoadjuvant setting for tumor size reduction and facilitating nephrectomies. The increased response rates with cabozantinib in metastatic renal cell carcinoma (mRCC), along with the other neoadjuvant TKI data, strongly support an expanded role for cabozantinib in the neoadjuvant setting.

We report on a 59-year-old gentleman presenting with an unresectable 21.7cm left renal cell carcinoma (RCC) with extension to soft tissue and muscles of the thoracic cage, psoas muscle, posterior abdominal wall, tail of pancreas, splenic flexure of colon, and inferior margin of spleen. Presurgical, neoadjuvant systemic therapy with caboction in this patient with locally advanced RCC. Our findings demonstrate that neoadjuvant cabozantinib to facilitate subsequent surgical resection may be a feasible option for patients presenting with unresectable RCC.

Triple-negative breast cancer (TNBC) is characterized by high malignancy and a poor prognosis. Patients with TNBC who survive longer than 5 years represent a unique portion of the population. This study aimed to analyze the clinicopathological features, explore prognostic factors, and evaluate treatment options for these patients.

A total of 24,943 TNBC patients were enrolled from the national Surveillance, Epidemiology, and End Results (SEER) database between January 2010 and December 2016. The patients were divided into three groups group 1, survival time <3 years; group 2, 3-5 years; and group 3, survival time ≥5 years. The overall survival (OS) and breast cancer cause-specific survival (BCSS) were primarily assessed in this study. A propensity score analysis was used to avoid bias caused by the data selection criteria. We used a Cox hazard ratio analysis to determine prognostic factors, which were selected as nomogram parameters to develop a model for predicting patient survival.

Patients who surognostic factors. A prognostic nomogram directly quantified patient risk and was better able to predict long-term survival in TNBC patients.

A localized surgical approach may represent a superior choice for TNBC patients with a survival time longer than 5 years. Our study indicated that age, race, tumor size, LN status, and chemotherapy were independent prognostic factors. A prognostic nomogram directly quantified patient risk and was better able to predict long-term survival in TNBC patients.

Survival after post-transplant recurrence of HCC is dismal, and almost all treatments for recurrent HCC are off-labeled, without an extensive large-scale analysis. We aimed to delineate their post-recurrence courses and define benchmarks for comparing future treatment effectiveness.

Three national databases, including health insurance, catastrophic illness, and the cause of death, were linked for cohort establishment and data collection during the period from 2005 to 2016. Patients with HCC recurrence ≥6 months after transplant surgery and under treatment were recruited for survival analysis. Selection of treatment strategies for HCC recurrence after liver transplant was based on the same criteria for those without liver transplant.

Of 2,123 liver transplant recipients, 349 developed HCC recurrence ≥6 months after liver transplant, and the median recurrence time was 17.8 months post-transplant. Within 2 years of treatment, 61% patients showed recurrence (early recurrence group), and survival in these patients was poorer than in the late recurrence group. According to a multivariable analysis, the transplant era before 2008 and radiofrequency ablation were associated with good prognosis, whereas receiving sorafenib and radiotherapy was associated with poor prognosis. The effect of transplant era became insignificant after stratification by recently receiving pretransplant transarterial chemoembolization.

Timing of recurrence and interventions used were associated with the outcomes of patients with post-transplant HCC recurrence. These data provide the benchmark and indicate the critical period and high-risk factors for further therapeutic trial consideration.

Timing of recurrence and interventions used were associated with the outcomes of patients with post-transplant HCC recurrence. These data provide the benchmark and indicate the critical period and high-risk factors for further therapeutic trial consideration.Angiosarcoma is a rare cancer of blood vessel-forming cells with a high patient mortality and few treatment options. Although chemotherapy often produces initial clinical responses, outcomes remain poor, largely due to the development of drug resistance. We previously identified a subset of doxorubicin-resistant cells in human angiosarcoma and canine hemangiosarcoma cell lines that exhibit high lysosomal accumulation of doxorubicin. Hydrophobic, weak base chemotherapeutics, like doxorubicin, are known to sequester within lysosomes, promoting resistance by limiting drug accessibility to cellular targets. Drug synergy between the beta adrenergic receptor (β-AR) antagonist, propranolol, and multiple chemotherapeutics has been documented in vitro, and clinical data have corroborated the increased therapeutic potential of propranolol with chemotherapy in angiosarcoma patients. Because propranolol is also a weak base and accumulates in lysosomes, we sought to determine whether propranolol enhanced doxorubicin cytotport the repurposing of the R-(+) enantiomer of propranolol with weak base chemotherapeutics to increase cytotoxicity and reduce the development of drug-resistant cell populations without the cardiovascular and other side effects associated with antagonism of β-ARs.

The extent of bowel resection is widely debated in colon cancer surgery. Right hemicolectomy (RHC) and partial colectomy (PC) are the most common operation options for right-sided colon cancer (RCC). However, there are still no treatment guidelines or published studies to guide surgical options for mucinous adenocarcinoma (MAC) of RCC.

Patients with MAC and non-specific adenocarcinoma (AC) of RCC who underwent RHC and PC from 2010 to 2015 in the Surveillance, Epidemiology, and End Results (SEER) database were retrieved. The general characteristics and survival were compared and analyzed.

A total of 27,910 RCC patients were enrolled in this study, among them 3,413 were MAC. The results showed that race, carcinoembryonic antigen (CEA) level, perineural invasion (PNI), tumor size, tumor location, TNM stage, liver metastasis, chemotherapy were significantly different between MAC and AC groups. The MAC group had similar dissected lymph nodes, but more positive lymph nodes than the AC group. The overall surviprovide some evidence for surgery treatment selection for MAC of RCC, which has important clinical value in individual management of colon cancer patients.

Radiation-induced lung fibrosis (RILF) is an important late toxicity in patients with non-small-cell lung cancer (NSCLC) after radiotherapy (RT). Clinically significant RILF can impact quality of life and/or cause non-cancer related death. This study aimed to determine whether pre-treatment plasma cytokine levels have a significant effect on the risk of RILF and investigate the abilities of machine learning algorithms for risk prediction.

This is a secondary analysis of prospective studies from two academic cancer centers. The primary endpoint was grade≥2 (RILF2), classified according to a system consistent with the consensus recommendation of an expert panel of the AAPM task for normal tissue toxicity. Eligible patients must have at least 6 months’ follow-up after radiotherapy commencement. Baseline levels of 30 cytokines, dosimetric, and clinical characteristics were analyzed. Support vector machine (SVM) algorithm was applied for model development. Data from one center was used for model training and dhine learning, this study constructed and validated a weighted-SVM classifier incorporating circulating CCL4 levels with significant dosimetric and clinical parameters which predicts RILF2 risk with a reasonable accuracy. Further study with larger sample size is needed to validate the role of CCL4, and this SVM classifier in RILF2.Esophageal cancer is one of the most common cancers with a low overall 5-year relative survival rate of approximately 20%. Trastuzumab (Herceptin®) targets HER2 and is an effective therapeutic strategy in HER2-positive breast cancer. However, few reports have described targeted therapy for treating esophageal squamous cell carcinoma (ESCC). A patient with advanced ESCC who had received chemotherapy, radiotherapy, and had undergone a clinical study is described here. The tumor had not been controlled. Herceptin and chemotherapy were used as salvage therapy in this patient because of high HER2 expression. Good therapeutic results were observed in this patient. Therefore, Herceptin is a potential target therapy for patients with HER2-positive advanced ESCC. A study with a large population and a prospective random study are necessary to validate these results.

The most common disadvantage of

C-choline positron emission tomography and computed tomography (PET/CT) in diagnosing early-stage prostate cancer (PCa) is its poor sensitivity. In spite of many efforts, this imaging modality lacks the ideal parameter of choline metabolism for the diagnosis of PCa, and the single metabolic parameter, that is, maximal standardized uptake value (SUVmax), based on this imaging modality is insufficient.

C-choline PET/CT-based multi-metabolic parameter combination can help break this limitation.

Before surgery, SUVmax of choline, which is the most common metabolic parameter of

C-choline PET/CT, mean standardized uptake value (SUVmean), prostate-to-muscle (P/M) ratio, metabolic tumor volume (MTV) and total lesion glycolysis (TLG) from 74 patients with histologically proven PCa were quantified. A total of 13 patients with focal chronic prostatitis without severe features and 30 patients with benign prostate hyperplasia were used for comparison. Univariable and multivariableeter in early-stage PCa diagnosis. According to our data, the combination of SUVmax, SUVmean, and P/M ratio as a composite parameter for diagnosis of early stage PCa improves the diagnostic accuracy of

C-choline PET/CT.

P/M ratio is a more ideal parameter than SUVmax as a single parameter in early-stage PCa diagnosis. According to our data, the combination of SUVmax, SUVmean, and P/M ratio as a composite parameter for diagnosis of early stage PCa improves the diagnostic accuracy of 11C-choline PET/CT.Radiation-induced oral mucositis (RIOM) is a common side effect after radiotherapy (RT) in head and neck cancer (HNC) patients. RIOM patients with severe pain have difficulty in eating, which increases the incidence of malnutrition and affects patients’ quality of life and the process of RT. The mechanism of RIOM is not fully understood, and inflammatory response and oxidative stress appear to be important for RIOM occurrence and development. The nutritional status of patients is very important for their RT tolerance and recovery. Malnutrition, which can lead to anemia, low protein, decreased immunity and other problems, is an important clinical factor affecting tumor progression and treatment. Recent studies have shown that early nutritional intervention can ameliorate oral mucositis and nutritional status of patients with HNC. However, in clinical practice, early nutritional intervention for patients with HNC is not a conventional intervention strategy. Therefore, this review summarized the possible pathogenesis of RIOM, commonly used assessment tools for malnutrition in patients, and recent studies on the effects of early nutritional interventions on RIOM and nutritional status of patients with HNC. We hope to provide the basis and reference for the clinical application of early nutritional intervention models.CISD2, a NEET protein that coordinates 2Fe-2S clusters through its CDGSH domain, is critical for normal development and iron homeostasis. CISD2 plays an important role in Fe-S cluster transfer and promotes cancer proliferation. However, its specific role in the development of non-small cell lung cancer (NSCLC) remains unclear. Bioinformatics of pan-cancer analysis from The Cancer Genome Atlas show that CISD2 has an aberrant expression in most types of human cancers. Moreover, CISD2 expression is associated with a higher hazard ratio and exhibits significantly poorer overall survival in lung adenocarcinoma (LUAD), uveal melanoma, head and neck squamous cell carcinoma, brain lower grade glioma, kidney chromophobe, and liver hepatocellular carcinoma. Further investigation revealed that CISD2 is highly expressed in LUAD and LUSC, which is associated with clinical pathological stages. In addition, survival data collected from GSE31210 and GSE13213, two datasets from the NCBI Gene Expression Omnibus, also confirmed that high CISD2 expression is associated with unfavorable survival in patients with LUAD. A cell-based assay indicated that the knockdown of CISD2 inhibited proliferation, invasion, and migration in A549 cells. Additionally, CISD2 knockdown accelerated the accumulation of cellular and mitochondrial reactive oxygen species, destroying the mitochondrial morphology and function. Moreover, CISD2 inhibition activated the iron starvation response, thus, accelerating iron accumulation in A549 cells. Pretreatment with DFO, the iron chelator, blocked mitochondrial dysfunction in CISD2-knockdown cells. Collectively, the present study provides novel insights into the regulatory role of CISD2 in NSCLC and presents a potential target to improve antitumor activity based on oxidative stress.Surgical resection remains primary curative treatment for patients with hepatocellular carcinoma (HCC) while over 50% of patients experience recurrence, which calls for individualized recurrence prediction and early surveillance. This study aimed to develop a machine learning prognostic model to identify high-risk patients after surgical resection and to review importance of variables in different time intervals. The patients in this study were from two centers including Eastern Hepatobiliary Surgery Hospital (EHSH) and Mengchao Hepatobiliary Hospital (MHH). The best-performed model was determined, validated, and applied to each time interval (0-1 year, 1-2 years, 2-3 years, and 3-5 years). Importance scores were used to illustrate feature importance in different time intervals. In addition, a risk heat map was constructed which visually depicted the risk of recurrence in different years. A total of 7,919 patients from two centers were included, of which 3,359 and 230 patients experienced recurrence, metastasis or died during the follow-up time in the EHSH and MHH datasets, respectively. The XGBoost model achieved the best discrimination with a c-index of 0.713 in internal validation cohort. Kaplan-Meier curves succeed to stratify external validation cohort into different risk groups (p less then 0.05 in all comparisons). Tumor characteristics contribute more to HCC relapse in 0 to 1 year while HBV infection and smoking affect patients’ outcome largely in 3 to 5 years. Based on machine learning prediction model, the peak of recurrence can be predicted for individual HCC patients. Therefore, clinicians can apply it to personalize the management of postoperative survival.Recent studies have reported a close association between circRNAs and cancer development. CircRNAs have been recognized to be involved in various biological processes. Up to now, the function of circRNAs in hepatocellular carcinoma (HCC) is still poorly known. qRT-PCR was used to test circ_0014717 expression in HCC tissue samples and cells was determined. It was shown that circ_0014717 was significantly decreased in HCC. Then, we observed overexpression of circ_0014717 obviously repressed HCC cell growth, migration and invasion. Next, we predicted circ_0014717 acted as a sponge of miR-668-3p. miR-668-3p has been reported to participate in several diseases. In our work, it was shown miR-668-3p was greatly increased in HCC and the direct binding sites between circ_0014717 and miR-668-3p were validated. In addition, B-cell translocation gene 2 (BTG2) is closely involved in cellular carcinogenic processes. BTG2 was predicted as a target for miR-668-3p. By performing rescue assays, we demonstrated that circ_0014717 repressed HCC progression via inhibiting BTG2 expression and sponging miR-668-3p. It was manifested loss of circ_0014717 induced HCC progression, which was reversed by BTG2 in Hep3B cells. In conclusion, our findings illustrated a novel circ_0014717/miR-668-3p/BTG2 regulatory signaling pathway in HCC.Cellular ribonucleic acids (RNAs), including messenger RNAs (mRNAs) and non-coding RNAs (ncRNAs), harbor more than 150 forms of chemical modifications, among which methylation modifications are dynamically regulated and play significant roles in RNA metabolism. Recently, dysregulation of RNA methylation modifications is found to be linked to various physiological bioprocesses and many human diseases. Gastric cancer (GC) and colorectal cancer (CRC) are two main gastrointestinal-related cancers (GIC) and the most leading causes of cancer-related death worldwide. In-depth understanding of molecular mechanisms on GIC can provide important insights in developing novel treatment strategies for GICs. In this review, we focus on the multitude of epigenetic changes of RNA methlyadenosine modifications in gene expression, and their roles in GIC tumorigenesis, progression, and drug resistance, and aim to provide the potential therapeutic regimens for GICs.

PD-L1 and HER-2 are routine biomarkers for gastric cancer (GC). However, little research has been done to investigate the correlation among PD-L1, HER-2, immune microenvironment, and clinical features in GC.

Between January 2013 and May 2020, a total of 120 GC patients treated with chemotherapy were admitted to Henan Tumor Hospital. We retrospectively identified PD-L1, HER-2 level before chemotherapy and abstracted clinicopathologic features and treatment outcomes. Univariate and multivariate survival analyses were performed to assess the relationship between PD-L1/HER-2 levels and progression-free survival (PFS). The mRNA and tumor microenvironment of 343 patients with GC from The Cancer Genome Atlas (TCGA) were used to explore the underlying mechanism.

We retrospectively analyzed 120 patients with gastric cancer, including 17 patients with HER-2 positive and 103 patients with HER-2 negative GC. The results showed that the expression of PD-L1 was closely correlated with HER-2 (P = 0.015). Patients withgnosis of GC patients.

HER-2 status could predict the efficacy of immune checkpoint inhibitors, and HER-2 status combined with PD-L1 level could predict the prognosis of GC patients.

Aspirin use has been suggested to reduce the incidence of ovarian cancer (OC) in women. However, previous studies regarding the association between aspirin use and mortality in women with OC showed inconsistent results. We aimed to evaluate the association between aspirin use and mortality in women with OC in a meta-analysis.

Relevant cohort studies were obtained

search of PubMed, Cochrane’s Library, and Embase databases from inception to May 3, 2020.A random-effect model, which incorporates the potential heterogeneity among the included studies, was used to pool the results. Predefined stratified analyses were applied to evaluate the potential study characteristics on the outcome, including the timing of aspirin use, dose of aspirin, age of the women, and the clinical stages of the cancer. Sensitivity analysis by omitting one study at a time was used to assess the stability of the results.

Six cohort studies including 17,981 women with OC were included. Pooled results showed that aspirin use had no nal studies indicated that aspirin use had no statistically significant association with mortality in women with OC.

This study aimed to evaluate the pathological characteristics, immunophenotype, and prognosis of treatment-emergent neuroendocrine prostate cancer (T-NEPC).

We collected 231 repeated biopsy specimens of castration-resistant prostate cancer (CRPC) cases between 2008 and 2019. We used histopathological and immunohistochemical evaluations of Synaptophysin (SYN), ChromograninA (CgA), CD56, androgen receptor (AR), and prostate

specific antigen (PSA) to screen out T-NEPC cases. Multivariate analyses were performed to identify factors in the prognosis of T-NEPC. Further, the results were verified in the Surveillance, Epidemiology, and End Results (SEER) program.

Among the 231 CRPC cases, 94 (40.7%) cases were T-NEPC. T-NEPC were morelikelyto present with negativeimmunohistochemistryfor AR (30.9%) and PSA (47.9%) than that of CRPC (8.8% and 17.5%, respectively). Kaplan-Meier analysis revealed that patients with T-NEPC (median overall survival [OS] 17.6 months, 95% CI 15.3-19.9 months) had significantly worse sV tumor (HR = 2.13, 95%CI = 1.47-3.08) and other races (HR = 1.85, 95%CI = 1.17-2.94) in total NEPC, adjusting for confounders. Similar hazard ratios were observed in pure NEPC, while there was no significant results among prostate adenocarcinoma with NE differentiation tumors.

T-NEPC was associated with an unfavorable prognosis, negative immunohistochemistry for PSA in T-NEPC and serum PSA level ≤ 4 ng/ml had a worse prognosis. Urologists and pathologists should recognize the importance of the second biopsy in CRPC to avoid unnecessary diagnosis and treatment delays.

T-NEPC was associated with an unfavorable prognosis, negative immunohistochemistry for PSA in T-NEPC and serum PSA level ≤ 4 ng/ml had a worse prognosis. Urologists and pathologists should recognize the importance of the second biopsy in CRPC to avoid unnecessary diagnosis and treatment delays.ST3Gal IV is one of the principal sialyltransferases responsible for the biosynthesis of α2, 3-sialic acid to the termini N-glycans or O-glycans of glycoproteins and glycolipids. It has been reported that ST3Gal IV expression is associated with gastric carcinoma, pancreatic adenocarcinoma and breast cancer. While the expression and functions of ST3Gal IV in cervical cancer are still poorly understood. In this study, we found that ST3Gal IV was downregulated in human cervical cancer tissues compared to normal cervix tissues, and ST3Gal IV expression was negatively associated with the pathological grade of cervical cancer. ST3Gal IV upregulation inhibited the growth and proliferation of cervical cancer HeLa and SiHa cells in vitro and in vivo. Furthermore, ST3Gal IV overexpression enhanced the expression of several Notch pathway components such as Jagged1, Notch1, Hes1 and Hey1, while cell cycle protein expression like Cyclin D1, Cyclin E1, CDK2 and CDK4 were decreased. These results indicate that expression of ST3Gal IV is reduced in cervical cancer and plays a negative role in cell proliferation via Notch/p21/CDKs signaling pathway. Thus, sialyltransferase ST3Gal IV might be a target for the diagnosis and therapy of cervical cancer.Imminent upper airway obstruction due to life-threatening tracheal stenosis of any cause is a challenging situation. We present a challenging case of total thyroidectomy for a malignant, invasive, and highly vascularized thyroid carcinoma that has invaded the surrounding tissues, including the sternum and mediastinum, resulting in compression of the trachea with indentation. The patient presented with a significant symptomatic tracheal stenosis, the narrowest area of that was 4 mm. Airway management in such cases presents a particular challenge to the anesthesiologists, especially considering that the option of tracheostomy is very difficult most of the time due to the highly swollen thyroid and distorted anatomy. A meticulous history of the patient’s illness had been taken, and a comprehensive preoperative evaluation was conducted, including construction of a 3D model airway, virtual endoscopy, and transnasal tracheoscopy. On the day of the surgery, the airway was managed through spontaneous respiration using intravenous anesthesia and the high-flow nasal oxygen (STRIVE-Hi) technique. It was then secured with intubation using a straw endotracheal tube (Tritube®) with an internal diameter (ID) of 2.4 mm and an outer diameter of 4.4 mm with the help of a fiberscope and D-MAC blade of a video laryngoscope. At the end of the procedure, the airway was checked with a fiber optic scope, which showed an improvement in the narrowed area. This enabled us to replace the Tritube with an adult cuffed ETT of size 6.5 mm ID, and the patient was transferred intubated to the surgical ICU. Two days later, the patient’s tracheal diameter was evaluated with the help of a fiberoptic scope and extubated successfully in the operating theater.

There has been a growing global interest in the role of gut microbiota in the pathogenesis of diseases and the potentials of targeting the microbiome in clinical interventions. Very few clinical studies in Qatar focused on gut microbiome. This study aimed to assess the awareness of healthcare professionals, scientists, and the general public on the role of gut microbiota in health and diseases and, more specifically, in disorders of the gut-brain axis such as neurodevelopmental disorders (NDDs) or gastrointestinal (GI) disorders. It also aimed to evaluate the readiness of the population to engage in clinical trials involving dietary interventions or fecal transplants.

A total of 156 participants were recruited to answer questionnaires-from healthcare professionals and scientists (HSs; n=44) and the general public (n=112). Participants from the general public self-reported their diagnosis of NDDs-autism or attention deficit hyperactivity disorder (n=36)-or GI diseases or disorders (n=18) or as having none dulation of gut microbiome, thus engaging the general public in lifestyle changes and facilitating clinical research in human microbiome investigations in Qatar.

Enterococcal meningitis/ventriculitis (EMV) is a relatively rare condition that usually affects patients with underlying diseases. This study was designed to describe the clinical profile, laboratory parameters, treatment, and outcomes of EMV in patients admitted to Hamad General Hospital, Qatar.

This retrospective hospital-based study described the patients with EMV from 2009 to 2013.

Eight patients were recruited for the study. Their median age was 42 years (21.50-53.75 years). Six patients (75%) were males, and two (25%) were females. Fever was the most common presenting symptom being present in seven (87.5%) cases. Six patients (75%) had nosocomial EMV, and all acquired the infection after placement of an external ventricular drain (EVD). The isolated species include seven (87.5%)

and one (12.5%)

, and all of them were sensitive to ampicillin and vancomycin. In all patients with nosocomial EMV, the infected EVDs were removed, and the eight patients received empirical antibiotics that were modified upon receipt of culture results. All patients were cured, and no mortality was reported.

EMV is a recognized complication related to the introduction of EVD, whereas community-acquired enterococcal meningitis was reported among children who had no established risk factors or immunosuppression. Because of its nonspecific clinical presentation, treating physicians should have a high suspicion index.

EMV is a recognized complication related to the introduction of EVD, whereas community-acquired enterococcal meningitis was reported among children who had no established risk factors or immunosuppression. Because of its nonspecific clinical presentation, treating physicians should have a high suspicion index.This study aims to collate all metabolic syndrome-related studies among adults in Qatar, shedding light on gaps in knowledge related to this topic to be addressed in future research studies. PubMed was used in searching for metabolic syndrome-related articles in Qatar, which was executed using relevant terms and was conducted with no restrictions. A second search was executed at a later stage to include any recent publications. A total of 20 articles were found to be relevant and related to the topic in hand. Three definitions of metabolic syndrome were used across the reviewed studies, which were classified based on medical specialties. The main findings and key components of each study were summarized. Studies were unevenly distributed across various medical specialties. This article serves to direct future research activities by identifying what aspects of the disease have been covered under current or past research projects and what more needs to be addressed comprehensively in view of clinical and public health significance.Lung cancer is the leading cause of cancer deaths globally. The objective of this study was to investigate the effect of 1,2-diazole (pyrazole) as an anti-cancer drug on human non-small cell lung carcinoma A549 cells. We attempt to examine the expression level of pro-inflammatory proteins such as TNF-α, NF-κB-p65, MMP-2 and E-Cadherin which are commonly associated with an inflammatory response in epithelial cells and apoptosis in A549 cells. The LPS-induced cytokines and inflammatory mediators include TNF-α, IL-6, iNOS and COX-2 levels in A549 cells and the effect of pyrazole was studied. The present study reveals that, pyrazole inhibits A549 cells by suppressing TNF-α induced MMP-2 expression, thereby inhibiting the nuclear translocation of NF-κB-p65. Pyrazole significantly up-regulate the E-cadherin level and down-regulated MMP-2 expression that could probably preventing A549 cancer cells to invade. The study further substantiated the anti-cancer property of pyrazole by regulating the above mentioned level of LPS-induced cytokines and inflammatory mediators. The observations of the present study open a possibility for the development of an effective therapeutic agent that targets inflammatory and signaling pathway mediators to challenge human non-small cell lung carcinoma.Herein, 18 lactic acid bacteria isolated from 30 samples of traditional dairy products were identified, and their probiotic potential was evaluated. According to the results, almost all strains showed the probiotic properties sufficiently, though M1 had better characterise. 16S rRNA gene sequencing revealed that this strain belongs to the Pediococcus sp. ( less then 95 % similarity). This strain had substantial antipathogenic activity and did not show any worrying antibiotic resistance. Also, the strain was resistant to high concentrations of bile salt (1 %), NaCl (6.5 %), and low pH (2). Furthermore, it was revealed that cell-free supernatant (CFS), heat-killed cells and live cells derived from M1 significantly decreased the viability of MCF-7 cells so that the CFS resulted in 85 % cell death. Flow cytometry and western blot analysis determined that this compound induced apoptosis in the cancerous cells through increasing the BAX protein expression and decreasing the Bcl-2 protein expression.Achilea fragmentisma plant is widely distributed along northern regions of Saudi Arabia with various traditional medical uses. The plant was collected from Tabuk and Arar regions to study the effect of the variation in habitat on the chemical compositions, antimicrobial and antioxidant activities of the plant. The results showed significant differences between the two studied region regarding the parameters of the weather in years from 2010-2016.The antioxidant and antimicrobial of the plant showed significant variation in two habitats. Plant collected from Arar showed high antioxidant activity with IC50 (0.21 ± 0.01 g/L) by DPPH radical scavenging methods, and good antibacterial activity with gram-positive bacteria (Staphylococcus epidermidis, Bacillus cereus and Staphylococccus aureus clinical isolate), antibacterial activity ranging between high to no activity (between 14.5 ± 0.5-6.0 ± 0.0 mm zone of inhibition), On the other side the tested plant extracts showed no effect on, all gram-negative bacteria. GC/MS data showed marked variation in chemical compositions of both phenolic and alkaloid compounds in plants collected from both regions. Phenolic compounds were accumulated with higher amounts(Ferulic acid, Eugenol and Salicylic acid ester) in Arar region, while the alkaloid fractions (Ethyl isoallocholate, Pterin 6-carboxylic-acid and kadain) showed higher concentrations in plants collected from Tabuk region. The results reflect the variation in of weather parameter, affect on chemical compositions and biological activities of the plant in two studied regions.

To improve the delivery and reach of primary health care, a robust scientific foundation driven by research is needed. However, few family physicians conduct research, especially in sub-Saharan Africa. Early-career and trainee family physicians are a key part of the primary care research pipeline and have an expressed need for research training and mentorship.

AfriWon Research Collaborative (ARC) was an online research training and mentorship pilot program whose objective was to increase research activity among participants from AfriWon Renaissance, the family physician young doctors’ movement of sub-Saharan Africa.

ARC utilized a 10-module online curriculum, supported by peer and faculty e-mentorship, to guide participants through writing a research protocol. The feasibility, acceptability, and scalability of this program was evaluated via a mixed-methods RE-AIM-guided process evaluation using descriptive statistics and inductive/deductive thematic analysis.

The pilot reached participants from Botswaementation strategies and ability to scale.

Online research training and mentorship for trainee and early-career family physicians in sub-Saharan Africa is feasible and acceptable to participants and mentors. Similar programs must pay careful attention to mentorship training and provide a flexible yet clearly organized structure for mentee-mentor engagement. Additional work is needed to determine optimal implementation strategies and ability to scale.This viewpoint examines the impact of COVID-19 travel bans and remote education on the global health education of students from high-income countries (HIC) and low- and middle-income countries (LMIC) and explores potential opportunities for strengthening global health education based upon more dispersed and equitable practices. Global health is unique in the opportunities it can offer to students during the pandemic if programs can manage and learn from the pandemic’s many challenges. Global health educators can shift to sustainable remote engagement and mobilize resources globally to facilitate this; collaborate with partners to support the efforts to deal with the current pandemic and to prepare for its next phases; partner in new ways with health care professional students and faculty from other countries; collaborate in research with partners in studies of pandemic related health disparities in any country; and document and examine the impact of the pandemic on health care workers and students in different global contexts. These strategies can help work around pandemic travel restrictions, overcome the limitations of existing inequitable models of engagement, and better position global health education and face future challenges while providing the needed support to LMIC partners to participate more equally.The NBOMe (N-2-methoxybenzyl-phenethylamines) family of compounds are synthetic hallucinogens derived from the 2C series. Although this family of compounds has been responsible for multiple cases of acute toxicity and several deaths around the world, to date there are few studies. These compounds act as potent 5-HT2A receptor agonists, including the hallucinogen 25C-NBOMe (2-(4-chloro-2,5-dimethoxyphenyl)-N-[(2-methoxyphenyl)methyl]ethanamine). In this study, we first evaluated the toxicity of 25C-NBOMe in two animal models Artemia salina and zebrafish using the lethality test of Meyer et al. (1982) modified for Artemia salina and the Fish Embryo Toxicity test (FET) for zebrafish (Danio rerio). Subsequently, we determined the behavioral and morphological effects using different concentrations of the 25C-NBOMe. As a result, we found that this substance is highly toxic according to lethality tests in both animal models. We also observe that this hallucinogen induces alterations in swimming and motility patterns in Artemia salina. Similarly, there were alterations in the motor response to a stimulus, as well as abnormal development in the zebrafish. The developmental effects of zebrafish suggest a teratogenic potential for 25C-NBOMe. Therefore, these findings are correlated with side effects, such as motor response abnormalities and muscle deterioration, clinically reported for consumers of this recreational drug. Finally, although recent studies are addressing the neurotoxicity and cardiotoxicity of 25C-NBOMe in cell cultures, to the best of our knowledge, this is the first in vivo report for 25C-NBOMe related to toxicological parameters and their global effects on development. Therefore, it could represent an advance in the study of the substance that contributes to the understanding of the effects on behavior and development in humans.The use of intravesical BCG has improved the survival and outcomes in the treatment of bladder cancer. However, the worldwide shortage of OncoTice BCG has caused disruption and changes in treatment regimes, leading to use of alternative strains. We describe a severe complication as the result of using intravesical SII Onco BCG for the treatment bladder cancer, in an 82 year old man presenting with granulomatous epididymo-orchitis.Giant hydronephrosis is rare to be seen in adults and is often the cause of misdiagnosis, It is usually caused by ureteropelvic junction syndrome. We here report the unusual case of a patient hospitalized with giant hydronephrosis secondary to ureteral calculi, associated with impaired general condition. Diagnosis was based on CT scan. The patient underwent deferred nephrectomy after percutaneous drainage.This case presents a patient with a remote history of complex posterior urethral repair related to a prior motorcycle accident who presented to the urology clinic in urinary retention with associated lower urinary tract symptoms. Due to his altered anatomy, traditional outlet procedures were deferred due to significant reported risks of post treatment urinary incontinence. Decision was made to proceed with prostatic artery embolization, and at follow up he reported resolution of his urinary retention and significant symptomatic improvement in his voiding without development of urinary incontinence.

Niemann-Pick disease type C (NP-C) is a neurodegenerative disease for which only palliative treatment exists, and only miglustat is effective in stabilizing neurological manifestations of NP-C. Ketogenic dietary therapies (KDT) are successfully used in patients with seizure disorders, including those associated with various inherited metabolic diseases (IMD), to reduce seizure frequency and medication requirement as well as to confer neuroprotection. Since patients with NP-C suffer pharmacorefractory seizures associated with ongoing neurodegeneration, KDT might be beneficial. The concomitant use of miglustat and KDT in patients with NP-C has not been reported.

We describe our experience in a now 17-year-old female with NP-C manifest early in childhood who has been successfully and continuously treated with miglustat and KDT in a palliative care setting for 3y. Although the neurodegeneration of NP-C progressed, she benefited from a reduction in seizure activity, fewer hospital stays related to seizure exacerbation, and increased alertness.

KDT could be safely deployed in our patient with NP-C, in whom its effects have been beneficial. Generally KDT is demonstratedly efficacious in patients with epilepsy and IMD. It reduces seizure activity and medication requirements and confers neuroprotection. Intracellular cholesterol trafficking and regulation of cholesterol biosynthesis are impaired in NP-C, which may prompt caution with respect to dietary lipid intake.

KDT could be safely deployed in our patient with NP-C, in whom its effects have been beneficial. Generally KDT is demonstratedly efficacious in patients with epilepsy and IMD. It reduces seizure activity and medication requirements and confers neuroprotection. Intracellular cholesterol trafficking and regulation of cholesterol biosynthesis are impaired in NP-C, which may prompt caution with respect to dietary lipid intake.The smudge cells are well studied as a prognostic factor for chronic lymphocytic leukemia, but it is also found in viral infections. We experienced a case of abnormal hyperleukocytosis (WBC 41,600/mm3) associated with infectious mononucleosis (IM). The smudge cells were observed in peripheral blood smears, and were counted by mistake for the normal lymphocytes by the automatic blood count meter.Talaromyces marneffei (T. marneffei), is an opportunistic pathogenic fungus commonly reported in southeast Asia. T. marneffei infection predominantly occurs in patients with immunodeficiency and can be fatal if diagnosis and treatment were delayed. Conventional diagnosis of T. marneffei infection relies heavily on tissue culture and histologic analysis, which is time consuming and has limited positive rate. Rapid and accurate diagnosis of T. marneffei remains urgent for effective therapy and prevention. This case is the first reported T. marneffei infection in non-HIV patients in north China diagnosed by mNGS. The successful diagnosis of T. marneffei infection assistant by mNGS underlies the potential of this technique in rapid etiological diagnosis.Chickenpox is considered as a mild disease, but sometimes it is associated with complications. Among them sialadenitis is mentioned sporadically. We describe a case of the 6-year-old girl suffering from complicated chickenpox. On the basis of clinical data and ultrasound image we diagnosed in her inflammation of both submandibular glands. Moreover, the ultrasound image suggested possibility of an inflammation developing in the left parotid gland.The Asian native Ashworthius sidemi is now in Europe, and several dozen years after its introduction, it is a widespread parasite of all wild cervids. For bovids, the nematode is a significant threat to the European bison (Bison bonasus) population and has also been found in mouflon (Ovis aries musimon). Our study aimed to assess the risk of infection for the endemic subspecies of northern (Alpine) chamois (Rupicapra rupicapra) – the Tatra chamois (R. r. tatrica), which has a critically endangered status. We conducted the investigation in the mountainous areas of Slovakia and Poland occupied by Tatra chamois (R. r. tatrica), Alpine chamois (R. r. rupicapra), red deer (Cervus elaphus) and roe deer (Capreolus capreolus). Animals (n = 93) shot during licensed hunting and killed in road accidents (roe deer, red deer), or which had died of natural causes (chamois) were post-mortem examined for the presence of Haemonchinae. The investigation confirmed the expansion of Ashworthius sidemi to high mountain regions via Cervidae. A. sidemi affected all of the examined roe deer and 90.0% of the red deer. As for the chamois, A. sidemi was found in one R. rupicapra originating from the Low Tatras, but not in any pure R. r. tatrica individuals living in the High and Western Tatras. Our work is the first confirmation of northern chamois infection with this alien and highly pathogenic blood-sucking nematode. Due to the important health hazard of A. sidemi infection for the Tatra chamois (R. r. tatrica), appropriate measures should be taken to reduce the possibility of parasite transmission between various cervid species living in the Tatra region, as well as the affected population of chamois and the pure Tatra chamois population inhabiting the higher parts of the mountains, constituting their natural habitat.Due to habitat destruction and illegal hunting and trade, the number of pangolins has been sharply reduced. To protect pangolins from extinction, relevant departments are combined and active action have been taken. A total of 21 confiscated Malayan pangolins were rescued in 2019, but died continuously for unknown reasons. This study aimed to investigate the reasons for the death of these pangolin and rescue them. 19 of the 21 confiscated pangolins had ticks on their body integument. A total of 303 ticks were collected and identified as Amblyomma javanense (A. javanense) according to their morphology and the sequences of 16S rRNA and internal transcribed spacer 2 (ITS2). There were multi-organ damages in the dead pangolins, especially congestion and hemorrhage in lung, heart and kidney and inflammation of which were observed using HE staining. Pathogens’ nucleic acid detection showed ticks were only positive for Ehrlichia spp, with 56.7% positive rate of collected ticks (127/224), which was further confirmed in tissues from dead pangolins. Our findings confirm that ehrlichiosis caused by Ehrlichia spp. from A. javanense might accelerate the confiscated pangolin’s death. More attention should be payed to tick-elimination work and the diagnoses and treatment of tick-borne diseases in the follow-up rescue operation.Coronavirus disease 2019 (COVID-19) has been reported to induce persistent symptoms even after an acute phase. However, the pathophysiology and treatment of this condition have been unclear. We report two patients who recovered from COVID-19, but presented persistent respiratory symptoms. Their respiratory conditions deteriorated, and computed tomography showed remaining ground glass opacities and consolidations. The pathological findings of transbronchial lung biopsy corresponded to organizing pneumonia. We diagnosed them with secondary organizing pneumonia after COVID-19. Subsequently, we administered systemic corticosteroids. Their symptoms, oxygenations, radiologic findings, and pulmonary functions rapidly improved after the treatment of corticosteroids. The two cases showed that secondary organizing pneumonia may be a cause of persistent respiratory failure after COVID-19. In this condition, corticosteroids may be effective.Organizing pneumonia is characterized by a distinct histologic pattern in the lung interstitium and presents clinically as hypoxemia, fever, cough, and dyspnea that is not attributable to concurrent infection. Typical etiologies of this condition include inflammatory disease, malignancy, toxic inhalation, and an array of medications including the mTOR inhibitor everolimus. In this report, we describe the case of a female with tuberous sclerosis complex on everolimus therapy for renal angiomyolipomas who presented to the hospital with persistent cough, dyspnea, and fevers and bilateral lower lobe opacities on chest X-ray despite multiple courses of antibiotic therapy. Bronchoscopy was performed with transbronchial biopsies, and results demonstrated a lymphocytic predominance and pathologic findings of intraluminal plugs composed of fibroblasts and myofibroblasts consistent with organizing pneumonia. Everolimus therapy was discontinued and patient completed a steroid course with resolution of symptoms. To our knowledge, this is the first published case of organizing pneumonia secondary to everolimus in a patient with tuberous sclerosis complex.

Micro-osteoperforations is one of the non-invasive surgical techniques used in attempt to accelerate OTM. Conflicting reports on its effectiveness has been reported in the literature.

The objectives of this trial were to investigate the effect of micro-osteoperforations on the rate of space closure and on molar anchorage loss during mini-implant supported maxillary anterior en-masse retraction.

A single center, parallel arm, randomized controlled trial was conducted.

Sixty, male and female subjects (age range 16-25 years) having Class I bimaxillary protrusion or Class II div 1 malocclusion, who required fixed mechanotherapy with either upper 1st premolar or all four 1st premolar extractions were allocated into two groups using 11 allocation ratio. The allocation was done by block randomization method with a block size of 6. In the experimental group, 5 MOPs per side were performed only once just before the en-masse anterior retraction. Mini-screws were placed in order to obtain maximum anchorage. Impressions were taken every month till 4 months and rate of space closure was measured on 3D study models.