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Hepatitis C is a liver illness caused by the hepatitis C virus (HCV). Acute and chronic hepatitis can be caused by the virus. Hepatitis C infection affects an estimated 71 million people worldwide. Two hundred blood samples were collected (128 males and 72 females), ranged in age from 4 to 80 years and diagnosed through a rapid test and the real time-PCR from the teaching medical city hospital in Baghdad from October 2018 until April 2019. The results showed that 89 samples were positive for HCV by serological tests, and other samples are not. Also, the most frequent age of infection of HCV was between 51 and 80 years. In all samples, the partial region of the NS5A gene was successfully amplified and sequenced. PCR-sequencing revealed three subtyping were; subtype 1a, 1b, and 4a. Phylogenetic analysis revealed subtype concordance of 99 % with a bootstrap hepatitis C virus subtype 1b isolate AASN1 Iraq (ID:MT554101.1). The clusters including HCV subtype 1a isolate AASN20 Iraq (ID:MT554100.1) the identical 96 %, and the clusters including HCV subtype 4a isolate AASN35 Iraq (ID:MT554099.1) the identical 99%.

Introduction Advances in the development of drugs with novel mechanisms of action have not been sufficient to significantly reduce the percentage of patients presenting drug-resistant epilepsy. This lack of satisfactory clinical results has led to the search for more effective treatment alternatives with new mechanisms of action. Development The aim of this study is to examine epidemiological aspects of the use of cannabis-based products for the treatment of epilepsy, with particular emphasis on the main mechanisms of action, indications for use, clinical efficacy, and safety. We conducted a narrative review of articles gathered from the PubMed, EMBASE, and Google Scholar databases and from the reference sections of relevant publications. Conclusions In recent years there has been growing interest in the use of cannabis-based products for the treatment of a wide range of diseases, including epilepsy. The cannabis plant is currently known to contain more than 100 terpenophenolic compounds, known as cannabinoids. The 2 most abundant are delta-9-tetrahydrocannabinol and cannabidiol. Studies of preclinical models of epilepsy have shown that these cannabinoids have anticonvulsant properties, and 100% purified cannabidiol and cannabidiol-enriched cannabis extracts are now being used to treat epilepsy in humans. Several open-label studies and randomised controlled clinical trials have demonstrated the efficacy and safety of these products.

Klebsiella pneumoniae has been identified as one of the important pathogens involved in the pathogenesis of urinary tract infections (UTIs) in humans. This study sought to determine the prevalence of K. pneumoniae and its ability to produce extended-spectrum-β-lactamases (ESBLs) in patients with UTIs. Besides, the predictive significance of interleukin (IL)-15 in UTIs caused by ESBLs-producing K. pneumoniae (K-ESBLs) was also assessed.: During October 2020 – January 2021, a cross-sectional and case-control study was performed on 587 patients with UTIs. Serum level of IL-15 was assessed using an enzyme-linked immunosorbent assay kit. The prevalence of K. pneumonia was 15.8%. It was also found that 68.8% of the K. pneumonia isolates were K-ESBLs (64patients). IL-15 levels were significantly elevated in serum of UTI patients with K-ESBLs compared to 24 control subjects (29.4 ± 9.2 vs. 22.1 ± 5.1; p-value

Introduction During pregnancy, women are at an increased risk of developing iron-deficiency anemia. Objective The objective of this study was to assess the diagnostic performance of the reticulocyte hemoglobin equivalent (RET-He) in the early detection of iron-deficiency anemia in a group of pregnant women and to establish a reference range for this parameter in a group of control individuals. Method: A total of 60 patients and 130 control subjects were included in the study. Blood samples collected from the subjects were submitted to a complete blood count and a serum ferritin test and the data were analyzed by comparing the groups and ROC curves. Results The reference range found for the RET-He was between 29.75pg and 38.24pg, with a median of 35pg. The receiver operating characteristic (ROC) curve analysis for the ferritin parameter showed an area under the curve of 0.732 for the RET-He, 0.586 for hemoglobin, 0.551 for the mean corpuscular hemoglobin concentration and 0.482 for the mean corpuscular volume. Conclusion Early diagnosis of iron deficiency anemia in pregnancy is essential to prevent damage to both maternal and fetal health. The RET-He presents an excellent potential as an auxiliary tool for the diagnosis of iron deficiency in pregnant women.

Introduction: Cognitive deficit is one of the common comorbidity accompanying epilepsy. The present study evaluated the effect of Celastrus paniculatus seed extract on seizure severity and cognitive deficit following the pentylenetetrazole (PTZ)-induced chemical kindling model. Methods: PTZ kindling model was developed by daily administration of the sub-convulsive dose of PTZ 30 mg/kg for four weeks. After four weeks of induction, the following treatment, namely sodium valproic acid (SVA) 200 mg/kg, C. paniculatus 500 mgkg, pergolide 2 mg/kg, C. paniculatus (250 mgkg)+ Pergolide (1 mg/kg), and C. paniculatus (250 mgkg)+ SVA (100 mg/kg) were administered 30 minutes prior to PTZ (30 mg/kg) injection for a period of next 14 days. Neurobehavioral parameters, including superoxide dismutase (SOD), Catalase (CAT), glutathione (GSH), and dopamine levels were assessed and the Morris water maze test (MWM) and Grip strength test (GPS) were performed. Hematoxylin & Eosin (H&E) staining of hippocampal cornu ammonis (CA1), CA2, CA3, dentate gyrus (DG), and frontal cortex was performed. Results: C. paniculatus (500 mg/kg) alone and in combination ( C. paniculatus (250 mgkg)+ pergolide (1 mg/kg) and C. paniculatus (250 mgkg)+ SVA (100 mg/kg)) significantly (p

Cryptococcus neoformans is a capsule containing yeast pathogen, commonly found in urban environments that causes Cryptococcosis which is a worldwide fungal disease. The current study. This study was aimed to compare the ability of some culture media to detect melanin production by C. neoformans isolates. A total of 202 clinical samples obtained from patients suffering from meningitis, during the period from September 2020 through April 2021. The isolation and identification results revealed that 179 (88.61%) samples were positive for yeast growth. 29 (14.35%). Twenty-nine from 202 of samples were C. neoformans according to the morphological characteristics and the biochemical tests, and 150 (74.25%) samples for Candida spp. All C. neoformans isolates produced blue dry colonies on cryptococcus differential agar. Several differential media were used for the purpose of testing the ability of C. neoformans to produce melanin pigment, these includes: Niger seed agar medium (Staib’s Agar), and the colonies of C. neoformans appeared on this medium in a brown color after 2–5 days of incubation, Tobacco agar where those colonies gave a dark brown color after 48–72 h, and Methyldopa agar which was the best medium for the detection of melanin production because the results were faster from the other media, interestingly the colonies can produce the pigment and can growth very fast within 24hr.

Neurological paraneoplastic syndrome is a relatively rare condition in patients with malignant tumors. Recently, it has been reported that anti-Aquaporin 4 (AQP4) antibody is highly specific for neuromyelitis optica. The patient was a 76-year-old man. He underwent right upper lobectomy for squamous cell carcinoma of the lung. Although the immediate postoperative course was uneventful, neurological symptoms became apparent from postoperative day (POD) 4. Magnetic resonance imaging showed longitudinally extended edematous lesions in the spinal cord, and a cerebrospinal fluid examination was positive for anti-AQP4 antibody, leading to the diagnosis of paraneoplastic neuromyelitis optica. Despite multiple rounds of steroid pulse therapy and plasma exchange, the neurological symptoms worsened and the patient died on POD 46. The development of neuromyelitis optica in the early postoperative period could be related to the influence of surgical stress or epidural anesthesia.

Background: KIAA1456 is effective in the inhibition of tumorigenesis. We previously confirmed that KIAA1456 inhibits cell proliferation and metastasis in epithelial ovarian tumours. In the current study, the specific molecular mechanisms and clinical significance of KIAA1456 underlying the repression of epithelial ovarian cancer were investigated.Methods: Immunohistochemistry was used to evaluate the protein expression of KIAA1456 and SSX1 in epithelial ovarian tumours and normal ovarian tissues. The relationship of KIAA1456 and SSX1 with overall survival of patients with epithelial ovarian cancer was analysed with Kaplan–Meier survival curve and log-rank tests. KIAA1456 was overexpressed and silenced in HO8910PM cells with a lentivirus. The anticancer activity of KIAA1456 was tested by CCK8, plate clone formation assay, flow cytometry, wound healing assay and Transwell invasion assay. Xenograft tumour models were used to investigate the effects of KIAA1456 on tumour growth in vivo. Bioinformatics analyses of microarray profiling indicated that SSX1 and the PI3K/AKT signalling pathway were differentially expressed in KIAA1456-overexpressing and control cells. Therefore, the biological function of HO8910PM cotransfected with KIAA1456- and SSX1-overexpressing cells was detected to validate the rescue effect of SSX1. The downstream factors of PI3K/AKT that are related to cell growth and apoptosis, including p-AKT, PCNA, MMP9, CyclinD1 and Bcl-2, were detected by Western blot analysis.Results: KIAA1456 expression was lower in epithelial ovarian tumours than in normal ovarian tissues. Its expression level negatively correlated with pathological grade. Pearson’s correlation analysis showed that KIAA1456 negatively correlated with SSX1 expression. The overexpression of KIAA1456 in HO8910PM cells inhibited proliferation, migration and invasion and promoted apoptosis. By contrast, the silencing of KIAA1456 resulted in the opposite behaviour. A xenograft tumour experiment showed that KIAA1456 overexpression inhibited tumour growth in vivo. Mechanistically, the overexpression of KIAA1456 inhibited SSX1 expression and AKT phosphorylation in HO8910PM cells, causing the inactivation of the AKT signalling pathway and eventually reducing the expression of PCNA, CyclinD1, MMP9 and Bcl2. Similarly, the silencing of KIAA1456 resulted in the opposite behaviour. Finally, SSX1 overexpression could partially reverse the KIAA1456-induced biological effect.Conclusion: KIAA1456 may serve as a tumour suppressor via the inactivation of SSX1 and the AKT pathway, providing a promising therapeutic target for epithelial ovarian cancers.

Helicobacter pylori (H. pylori) is a spiral microorganism considered as a gram-negative, this organism colonize the microenvironment of gastric for more than 50% of world population. The present study involved 78 patients, 39 of them had a clinical diagnosis of gastric ulcer and the remaining 39 had a clinical diagnosis of gastric cancer. Biopsies were taken from December 2018” until the end of July 2019 and the patients were between 25 and 60 years old. The initial diagnosis of H. pylori was performed by the rapid urease test (RUT). The samples also have been tested for IL-17 gene expression by immunihistochemical techniques. All the samples have been investigated for UreA gene, and the results showed the H.pylori positive in 32 (82%) samples and it was negative in 7 (18%) samples in gastric cancer, whereas the gastric ulcer group showed 29 (75%) negative samples and 10 (25%) positive for H.pylori. Furthermore, the sequencing result of gastric cancer group showed 95% compatibility, while gastric ulcer patients showed 98% compatibility with NCBI. The phylogenetic analysis exhibited the genetic dimension among the samples and the world was 96% and 99% compatibility values.

The advent of immunotherapy has revolutionised the treatment of metastatic lung cancer and it has recently been established as the standard of care in the radical treatment of lung cancer. However, immune-related adverse events (IrAEs) frequently occur in patients treated with immunotherapy, and rare IrAEs continue to be identified. We report a case of immunotherapy-induced coeliac disease due to adjuvant durvalumab post-chemoradiotherapy in a patient receiving curative treatment for lung cancer. The patient had raised anti-tissue transglutaminase IgA and histological findings consistent with coeliac disease. This is the first published case report of probable immunotherapy-induced coeliac disease both with the immunotherapy drug durvalumab and in the curative lung cancer setting.

Essential thrombocythaemia (ET) is a myeloproliferative neoplasm where there is a clonal proliferation of thrombocytes. Whilst most often diagnosed incidentally, it can uncommonly present with arterial thrombosis. This is a case presentation of a 36-year-old male who was diagnosed with ET following myocardial infarction caused by multiple thrombotic emboli. The patient was initially misdiagnosed with viral myopericarditis based on an atypical history of chest pain with a viral prodrome. Reattendance a month later with further chest pain, dynamically raised troponin and ECG changes raised suspicions of ACS. Analysis of blood markers from both admissions showed consistently elevated platelet counts. A CMR scan revealed focal ischaemic scars in multiple cardiac segments consistent with an acute coronary event or coronary embolisation. A subsequent coronary angiography demonstrated minimal coronary artery disease. JAK2 gene V617F mutation was detected, confirming ET. The patient was commenced on pegylated interferon-alpha and dual antiplatelet therapy, and discharged with follow-up.

Eight-and-a-half syndrome is a rare entity characterised by conjugate horizontal gaze palsy, ipsilateral internuclear ophthalmoplegia and ipsilateral lower motor neuron type facial palsy. It is due to a lesion affecting median longitudinal fasciculus, paramedian pontine reticular formation and facial nerve fascicle on the same side at the level of pons. The diagnosis is easily missed as it needs detailed ocular movement examination. It is mainly caused due to infarction or demyelinating conditions. We are reporting an interesting case of a 54-year-old man with right-side eight-and-a-half syndrome due to acute ischaemic stroke and ST-elevation myocardial infarction of the inferior wall.

Primary pneumomediastinum is the presence of air in the interstitium of the mediastinum. The exact aetiology is unclear; nevertheless, it has been reported more frequently in patients with asthma and in individuals who use recreational drugs. It is commonly preceded by a sharp rise in intrathoracic pressure as in a Valsalva-like manoeuvre. We describe a rare case of severe pneumomediastinum with a small pneumothorax related to cannabis smoking and aggravated by vigorous sexual intercourse. The patient was successfully treated conservatively due to clinical and radiological stability and the absence of secondary cause.

Background Allergic bronchopulmonary aspergillosis (ABPA) is an allergic reaction to colonisation of the lungs with the fungus Aspergillus fumigatus and affects around 10% of people with cystic fibrosis. ABPA is associated with an accelerated decline in lung function. High doses of corticosteroids are the main treatment for ABPA; although the long-term benefits are not clear, their many side effects are well-documented. A group of compounds, the azoles, have activity against Aspergillus fumigatus and have been proposed as an alternative treatment for ABPA. Of this group, itraconazole is the most active. A separate antifungal compound, amphotericin B, has been employed in aerosolised form to treat invasive infection with Aspergillus fumigatus, and may have potential for the treatment of ABPA. Antifungal therapy for ABPA in cystic fibrosis needs to be evaluated. This is an update of a previously published review. Objectives The review aimed to test the hypotheses that antifungal interventions for the treatment of ABPA in cystic fibrosis: 1. improve clinical status compared to placebo or standard therapy (no placebo); 2. do not have unacceptable adverse effects. If benefit was demonstrated, we aimed to assess the optimal type, duration and dose of antifungal therapy. Search methods We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register which comprises references identified from comprehensive electronic database searches, handsearches of relevant journals and abstract books of conference proceedings. In addition, pharmaceutical companies were approached. Date of the most recent search of the Group's Trials Register: 29 September 2016. Selection criteria Published or unpublished randomised controlled trials, where antifungal treatments have been compared to either placebo or no treatment, or where different doses of the same treatment have been used in the treatment of ABPA in people with cystic fibrosis. Data collection and analysis Four trials were identified by the searches; none of which was judged eligible for inclusion in the review. Main results No completed randomised controlled trials were included. Authors' conclusions At present, there are no randomised controlled trials to evaluate the use of antifungal therapies for the treatment of ABPA in people with cystic fibrosis, although trials in people who do not have cystic fibrosis have shown clinical and serological evidence of improvement and a reduction in the use of corticosteroids with no increase in adverse effects. Trials with clear outcome measures are needed to properly evaluate this potentially useful treatment for cystic fibrosis.

Background Gastric cancer is worldwide the fourth more common cancer type by incidence, and the third by mortality. We analyzed three missense variants of TAS2R38 gene: rs713598 (A49P), rs1726866 (V262A), and rs10246939 (I296V). These variants and their combination in haplotypes (proline, alanine and valine/tasters or alanine, valine and isoleucine/nontasters) and diplotypes are responsible for individual differences in bitter perception. The single-nucleotide polymorphisms and the related phenotypes are known to be associated with susceptibility to Gram-negative bacterial infections, such as Helicobacter pylori, and with risk of various cancer types. An association between intermediate tasters (as defined by TAS2R38 diplotypes) and increased risk of gastric cancer was reported in a Korean population. Methods We analyzed 2616 individuals of Latin American origin, representing the whole spectrum of lesions from gastritis to gastric cancer. Results Comparing cancer cases vs. noncancers we observed a decrease in risk associated with heterozygous carriers of rs10246939 (P = 0.006) and rs1726866 (P = 0.003) when compared with homozygotes of the more common allele. Also, the analysis of diplotypes/phenotypes reflected the same association, with super-tasters showing a borderline increased risk of developing gastric cancer compared to medium-tasters [odds ratio (OR) = 1.63; 95% confidence interval (CI), 1.04-2.56; P = 0.033]. Also, nontasters showed an increased risk when compared to medium-tasters although not reaching statistical significance (OR = 1.58; 95% CI, 0.80-2.87; P = 0.203). We also tested the interactions between the TAS2R38 genotypes and H. pylori cagA status in a subset of samples and found no interaction. Conclusion In conclusion, our results suggest only a modest contribution of TAS2R38 gene genetic variability in gastric cancer etiology.

SIGNIFICANCE Reactive oxygen species (ROS) contribute to multiple aspects of peripheral nervous system (PNS) biology ranging from physiological processes (e.g. axonal outgrowth and regeneration), to pathophysiology (e.g. nerve degeneration). Although ROS are derived from multiple sources, NADPH oxidase (Nox) family members are dedicated to ROS generation. Noxs are expressed in the PNS and their overexpression is associated with detrimental effects on nerve function and contribute, at least in part, to peripheral neuropathies. Recent Advances: Of the 7 members, studies mostly focused on Nox1, Nox2, and Nox4, which are expressed in the PNS in a cell-specific manner. We have also recently identified human Nox5 in sural nerve biopsies. When maintained at homeostatic levels, Noxs regulate several aspects of peripheral nerve health, most notably neurite outgrowth and axonal regeneration following nerve lesion. While Nox2 and Nox4 dysregulation is a major source of oxidative stress in PNS disorders, including neuropathic pain and diabetic peripheral neuropathy, recent evidence also implicates Nox1 and Nox5. CRITICAL ISSUES Although there is compelling evidence for a direct role of Noxs on nerve function, little is known about their subcellular localization, intercellular regulation, and interaction. These, together with redox signaling, are considered crucial components of nerve redox status. Additionally, the lack of isoform-specific inhibitors limits conclusions about the physiological role of Noxs in the PNS and their therapeutic potential in peripheral neuropathies. FUTURE DIRECTIONS Future research using isoform-specific genetic and pharmacological approaches are therefore needed to better understand the significance of Nox enzymes in PNS (patho) physiology.

We present a case of a 7-year-old Afro-Caribbean girl presenting with rapidly progressive bilateral sensorineural hearing loss. She was found to have an elevated Angiotensin converting enzyme (ACE) and mediastinal lymphadenopathy containing non-caseating granulomas with multinucleate giant cells, in keeping with sarcoidosis. Cranial imaging demonstrated labyrinthitis. She underwent urgent bilateral cochlear implantation with rehabilitation of hearing sufficient to restart education within 1 month.

Vancomycin is a widely used antibiotic and rarely can cause drug-induced thrombocytopenia. A patient with hospital-acquired meningitis after neurosurgery was treated with systemic and intrathecal vancomycin. On 9th day of antibiotic treatment, the patient’s platelets dropped to 0.68×109/L. Multiple platelet transfusions had minimal influence on platelet count. After cessation of vancomycin therapy, platelets returned to normal values without any additional interventions. Diagnosis of vancomycin-induced thrombocytopenia was confirmed by detection of drug-dependent antiplatelet IgG antibodies.

Introduction: Cannabis use is common in the setting of inflammatory bowel disease (IBD). Patients frequently use cannabis to treat IBD-associated symptoms, and there is evidence that cannabis and its derivatives are helpful for this purpose. However, it is unclear how the symptom profiles of active IBD cannabis users and nonusers compare and how these symptoms may relate to their underlying disease state and/or complications. Materials and Methods: We performed a retrospective cohort study using a consented IBD natural history registry from a single tertiary care referral center between January 1, 2015 and August 31, 2020. We asked patients about current cannabis use and frequency. We also abstracted demographic and clinical characteristic information, including endoscopic severity, and totals and subscores of surveys assessing IBD characteristics, presence of anxiety/depression, and IBD-associated symptoms. We compared clinical and demographic factors of cannabis users and nonusers and developed a logistic regression model to evaluate for independent associations with cannabis use. Results: Three hundred eighty-three IBD patients met the inclusion criteria (206 females, 177 males; 258 Crohn's disease [CD], 118 ulcerative colitis, and 7 indeterminate colitis). Thirty patients (7.8%) were active cannabis users, consuming it for an average of 2.7 times per week. Cannabis users were more likely to report abdominal pain (83.3% vs. 61.7%), gas (66.7% vs. 45.6%), tenesmus (70.0% vs. 47.6%), and arthralgias (53.3% vs. 20.3%) compared to those that did not use cannabis (p

Objective: The objective of this study was to evaluate the safety and efficacy of medications commonly used in autism spectrum disorder (ASD) and compare this to what current research has shown regarding medical cannabis use in this population. Methods: Searches were performed to collect information surrounding currently used medications and their safety and efficacy profiles, biologic plausibility of cannabis use for symptoms of ASD, and studies detailing cannabis' safety and efficacy profile for use in the ASD population. Results were used to compare medications to cannabis as a proposed treatment. Results: The heterogeneity of ASD produces great difficulties in finding appropriate treatment, leading to many medication changes or treatment trials throughout a patient's life. Commonly prescribed medications display varying levels of efficacy, safety, and tolerability between patients and symptoms targeted. Some of the most common side effects cited are also considered the most troubling symptoms associated with ASD; aggression, anxiety, irritability, and a negative effect on cognition, leading many patients to discontinue use as the side effects outweigh benefits. Recent case reports and retrospective studies have displayed the potential efficacy, safety, and tolerability of cannabidiol (CBD)-rich medical cannabis use for treating both core symptoms of ASD and many comorbid symptoms such as irritability and sleep problems. Studies have also identified circulating endocannabinoids as a possible biomarker for ASD, providing another possible method of diagnosis. Conclusions: Currently, there are no approved medications for the core symptoms of ASD and only two medications Food and Drug Administration approved for associated irritability. Prescribed medications for symptoms associated with ASD display varying levels of efficacy, safety, and tolerability among the heterogeneous ASD population. At the time of this study there are no published placebo-controlled trials of medical cannabis for ASD and the observational studies have limitations. CBD-rich medical cannabis seems to be an effective, tolerable, and relatively safe option for many symptoms associated with ASD, however, the long-term safety is unknown at this time.

Introduction: The hematopoietic cytokine granulocyte-colony stimulating factor (G-CSF) is well known to stimulate proliferation of blood stem/progenitor cells of the leukocyte lineage, but is also ...

Chronic cavitary pulmonary aspergillosis (CCPA) is a slow destructive type of chronic pulmonary aspergillosis, characterised by multiple pulmonary cavities that develop and expand over several months or years. Pleural involvement in the form of pneumothorax has been rarely reported in CCPA. We report such an unusual case of an immunocompromised male, with a history of chronic cough and fever, presenting with acute onset of shortness of breath. Chest imaging showed bilateral multiple cavitating nodules, ground glass opacities and dense right middle lobe consolidations and right-sided pneumothorax. Bronchoalveolar lavage (BAL) showed septate hyaline hyphae on KOH (potassium hydroxide) staining and fungal culture grew Aspergillus fumigatus. BAL and serum galactomanan were positive and serum IgG for A. fumigatus was 58 MgA/L (0–40MgA/L) confirming the cause of spontaneous secondary pneumothorax in our patient as CCPA.

A 42 year-old Caribbean woman with, known type 2 diabetes, was admitted with worsening fatigue, arthritis and rashes. She was diagnosed with multisystem systemic lupus erythematosus and was initially treated with systemic steroids. During this admission, she had persistently elevated capillary glucose levels with insulin requirements over 8 U/kg/day that still did not control her blood glucose levels. Due to her profound hyperglycaemia, serum samples of fasting insulin, C-peptide, paired with blood glucose were analysed, which confirmed significant hyperinsulinaemia. Further analysis confirmed the presence of insulin receptor antibodies consistent with type B insulin resistance.She was started on intravenous cyclophosphamide (Euro-Lupus regimen) along with continuous glucose monitoring system. After completing her six cycles of cyclophosphamide, she no longer required insulin treatment. The goal of therapy for our patient with confirmed type B insulin resistance was to manage hyperglycaemia with high doses of insulin until autoantibodies were eliminated with immunosuppressive therapy.

Infection is a serious adverse event limiting left ventricular assist device (LVAD) therapy in advanced heart failure patients, but a reliable means to identify patients at increased risk of infection is still lacking. We hypothesized that preoperative elevated levels of plasma Oncostatin M (OSM), a cytokine marker of leukocyte activation and inflammation, would be predictive of subsequent infection. We measured plasma OSM in 41 LVAD patients one day before LVAD implantation and postoperatively over two months. Preoperative plasma OSM levels were normal in 27 patients (group A, 4.9 ± 3.2 pg/ml) but elevated in 14 patients (group B, 1649.0 ± 458.9 pg/ml) ( p = 0.003). Early postoperative levels rose in both groups and declined rapidly in group A, with group B declining slowly over two months. Significantly more infections developed in group B than group A patients over two months postimplantation ( p = 0.004). No other routine clinical assessment or laboratory testing afforded this differentiation. These findings suggest that preoperative plasma OSM levels may assist in identifying patients at increased risk of infections after LVAD implantation.

We report a case of vancomycin-induced thrombocytopenia (VIT) with rapid onset after re-exposure to vancomycin. A 58-year-old man with cellulitis was initiated on vancomycin. Approximately 1 hour into the vancomycin infusion, the patient developed an infusion-related reaction. Vancomycin infusion was stopped. A complete blood count obtained 4 hours after discontinuation of the vancomycin infusion revealed a platelet count of 31 ×10­9/L. Investigations ruled out likely causes of thrombocytopenia. VIT was diagnosed based on clinical symptoms and confirmed with drug-dependent platelet antibody testing. Without complications, platelet counts recovered within 7 days after discontinuation of vancomycin. No correlation between vancomycin level and VIT was observed.

The fibronectin type III domain containing 5 (FNDC5)/Irisin, a novel energy-regulating hormone, is associated with lipid and carbohydrate metabolism. It is produced in low amounts by normal hepatic tissue, while in human hepatocellular carcinoma (HCC), in which aberrant de novo lipogenesis (DNL) occurs, the hepatic expression of FNDC5/Irisin is still unknown. The gene expression of FNDC5/Irisin, associated to key regulators of DNL, inflammation and cancer progression was evaluated in liver tissue of 18 patients with HCC undergoing liver transplantation and of 18 deceased donors. Hepatic mRNA expression of FNDC5/Irisin and stearoyl-CoA desaturase (SCD-1), main enzymatic regulator of DNL, were significantly higher in HCC patients than in donors (p, This pre-print version may be used for non-commercial purposes in accordance with CC BY-NC-ND license terms and conditions.

A 49-year-old female emergency room nurse presented with painless papular rash that started on both arms and legs and spread to her palms and soles ([figure 1][1]). She also endorsed fatigue, low-grade fever and transient arthralgia. She was sent home on topical steroids, which improved her pruritus

We describe a case of a 42-year-old man who presented with anginal chest pain. He had objective evidence of ongoing cardiac injury. After initial treatment for coronary arterial disease, cardiac catheterisation revealed diffuse coronary arterial thrombosis with embolisation. Follow-up testing implicated new-onset antiphospholipid antibody syndrome as the aetiology.

Posterior reversible encephalopathy syndrome (PRES) is characterised by headache, altered mental status, seizures and visual loss that resolve spontaneously in a short span of time. The typical radiographic findings include symmetrical hyper intensities in Magnetic Resonance Fluid Attenuated

Background Protection against Plasmodium falciparum is observed in a population deficient in glucose-6-phosphate dehydrogenase (G6PD), particularly in African and Mediterranean regions. However, such protection remains unknown among G6PD-deficient individuals in Southeast Asia. Methods In this study, we assessed the invasion and maturation of P falciparum K1 in a culture of erythrocytes isolated from Thai subjects carrying Viangchan (871G > A) and Mahidol (487G > A). Results We found that the parasites lost their ability to invade hemizygous and homozygous G6PD-deficient erythrocytes of Viangchan and Mahidol variants in the second and third cycles of intraerythrocytic development. It is interesting to note that P falciparum parasites selectively grew in erythrocytes from hemi- and homozygous genotypes with normal G6PD activity. Moreover, externalization of phosphatidylserine upon P falciparum infection was significantly increased only in Viangchan hemizygous variant cells. Conclusions This study is the first to show that blockage of invasion in long-term culture and potentially enhanced removal of parasitized erythrocytes were observed for the first time in erythrocytes from Viangchan and Mahidol G6PD-deficient individuals.

We reported a case of gnathostomiasis in a 42-year-old woman with an unclear history of eating high-risk foods and had a non-migratory skin lesion, negative serological testing and normal blood eosinophil counts. A diagnosis of gnathostomiasis was based on a live, third-stage Gnathostoma spinigerum larva that was randomly taken from the patient’s skin lesion by herself. The presenting case report demonstrates challenges in correctly diagnose cutaneous gnathostomiasis even in endemic countries due to atypical skin lesions, negative serology testing and the absence of eosinophilia and thus, the widely used classic triad of suggestive evidence of gnathostomiasis is not fulfilled.

We describe antiglomerular basement membrane (anti-GBM) disease with rapidly progressive glomerulonephritis and concurrent parainfluenza pneumonia. Circulating anti-GBM antibodies were barely detectable and disappeared rapidly following corticosteroids, cyclophosphamide and plasma exchange. Kidney biopsy demonstrated strong linear GBM staining for IgG and IgG4 and unusually prominent endocapillary hypercellularity, suggesting ‘atypical anti-GBM disease’, although glomerular necrosis and crescents were also seen. When kidney function deteriorated further, despite persistently absent circulating anti-GBM antibodies, a repeat kidney biopsy was performed, showing crescents in 100% of glomeruli with ongoing endocapillary hypercellularity and strong IgG and IgG4 GBM staining. This case highlights complexities in the diagnosis of anti-GBM disease, with clinical and histological features bridging the atypical to typical anti-GBM disease spectrum. We hypothesise that these findings might be explained by the presence of IgG4 (rather than traditional IgG1 or IgG3) autoantibodies. To our knowledge, this is also the first report of parainfluenza associated with anti-GBM disease.

Morgagni hernia is the rarest type of congenital diaphragmatic hernia, which can present late in adulthood. Here, we report a case of Morgagni hernia in an elderly woman who presented as an acute coronary syndrome with raised troponin level. X-ray of the chest (CXR) showed air–fluid level in the right lower hemithorax with loss of right diaphragmatic outline and subsequently confirmed strangulated Morgagni hernia with CT. She was treated with emergency laparotomy to reduce the hernia content and surgical repair with mesh done. In conclusion, Troponin can be falsely positive in Morgagni hernia patients, possibly due to strain on the heart by herniated bowel contents. Basic imaging such as a (CXR) is useful in the case of chest pain to rule out the non-cardiac causes. Although ‘time is the myocardium’ in the setting of all cases of chest pain with raised troponin, CXR should be done before treatment that poses bleeding risk and unnecessary delay in laparotomy.

PURPOSE: To describe the incidence, prevalence, and clinical characteristics of presumed ocular histoplasmosis syndrome (POHS) in a Histoplasma endemic region. METHODS: The International Classification of Diseases, 9(th) and 10(th) Revision codes were used to search the Rochester Epidemiology Project, a record-linkage system for medical care provided in Olmsted County, MN. Medical records were reviewed to confirm POHS diagnoses in county residents from January 1, 2006 to December 31, 2015. Age- and sex-adjusted incidence rates were calculated and adjusted to the 2010 U.S. White population. RESULTS: There were 18 incident cases (30 eyes) and 87 prevalent cases (131 eyes). The incidence rate was 1.35 per 100,000 per year. The mid-study prevalence rate was 0.064%. Choroidal neovascularization (CNV) occurred in 17.4% of affected eyes. At last follow-up, 16.8% of affected eyes had POHS-related decreased VA (

The ability to distinguish endometrial serous carcinoma (SC) from high-grade endometrioid adenocarcinoma is of great importance given their differences in prognosis and management. In practice, this distinction typically relies upon the use of a focused immunohistochemical panel including p53, p16, and mismatch repair proteins. The expression of p16 is characteristically strong and diffuse in SCs, and weak and/or patchy in many high-grade endometrioid adenocarcinomas. Here, we report a subset of SCs that are entirely negative for p16 immunostaining, a pattern we refer to as "p16 null." This pattern was identified in 2 of 63 cases of SC diagnosed at our institution-1 with histologically classic features and 1 with ambiguous high-grade histologic features. These tumors otherwise showed a SC signature by immunohistochemical and demonstrated an SC pattern of genetic mutations. No mutation in the gene for p16, cyclin-dependent kinase inhibitor 2A (CDKN2A), was identified in either case. However, molecular correlates for the absent p16 expression were present, including homozygous deletion of CDKN2A in one case and hemizygous deletion of CDKN2A with promotor hypermethylation of the remaining allele in the other case. To our knowledge, this constitutes the first report conclusively demonstrating the existence of a small subset of SCs that are completely negative by p16 immunohistochemistry, and the molecular lesions responsible for this pattern. In the context of an otherwise clinically and histologically classic example of SC, we endorse this "null" p16 staining pattern as an alternative aberrant staining pattern that should not deter one from committing to this diagnosis.

Congenital factor V (FV) deficiency is a rare hemorrhagic disorder that can cause excessive bleeding during and after surgery in the affected patient. This report is the case of a patient who had FV deficiency with recurrent posthemorrhoidectomy bleeding treated with the hemostatic procedure and fresh frozen plasma (FFP) transfusions. A 45-year-old male patient had previously undergone hemorrhoidectomy for multiple hemorrhoids at a local hospital. Hemorrhoidectomy was successful; however, he was transferred to our hospital for evaluation of the origin of the recurrent posthemorrhoidectomy bleeding and underwent a hemostatic procedure. This bleeding was treated with coagulation using electrocautery, multiple sutures, and FFP transfusion (1,600 mL/day) for 7 consecutive days. The patient’s plasma FV activity was 23%. Early detection of clotting factor deficiency in patients with hemorrhagic events after surgical treatments may prevent unnecessary procedures such as reoperations and minimize the cost of replacement therapy such as large-volume FFP transfusion.

The aim of the study is to evaluate the seroprevalence of human herpes virus type 8 (HHV-8) in women with breast cancer. The study has been conduct in Kirkuk city for the period from January 1, 2019 to April 1, 2019 on 50 breast cancer women with age group 21-70 years. The study has also included 40 healthy women as control group. The study included the collection of 3 ml of venous blood for identification and measurement of IgG antibodies towards the HHV-8 by using ELISA technique (KomaBiotech, Co, USA). The study also included taking of full information from cases like living situation, age. The study showed that the maximum frequency of HHV-8 infection (34%) recorded among breast cancer women comparing with the control group (10%), with highly significant relation. The majority of breast cancer women with positive IgG were within the age group 51-60 (41.18%) and the lowest rate was in the age group 21-3 years. The study showed that the maximum frequency of HHV-8 infection in breast cancer women was found in women with 2nd stage of breast cancer (58.83%) and the lowest rate was in the 1st stage. The highest rate of HHV-8 infection in breast cancer women (76.47%) were with metastasis to neighbor lymph nodes while compared with 23.53% without metastasis while all breast\t cancer women with HHV-8 negative were without metastasis. It has concluded that there was significant association between HHV-8 infection and occurrence of breast cancer and high rate of this infection has related to metastasis.

Background: Although exposure to stings has been identified as the leading risk factor for anaphylaxis due to Hymenoptera venom allergy, professional beekeepers receive hundreds of stings yearly without developing systemic reactions. Objective: This study aims to analyze the mechanisms underlying bee venom tolerance in beekeepers. Methods: A cross-sectional study was conducted. Participants were recruited and classified into 3 groups: allergic patients (APs), who experienced systemic reactions after bee stings, with a positive intradermal test and specific IgE (sIgE) to Apis mellifera venom (AmV); tolerant beekeepers (TBKs), who received ≥50 stings/year; and healthy nonexposed controls (HCs). We measured serum levels of sIgE and specific IgG4 (sIgG4) to AmV, rApi m 1, rApi m 2, rApi m 3, Api m 4, rApi m 5, and rApi m10, as well as AmV-induced basophil degranulation, percentage of T-cell subsets, regulatory T cells (Treg), and IL-10 production. Results: Compared with TBKs, APs had high levels of sIgE to AmV and all its allergic components (P

Background: Men over the age of 40 are more likely to develop benign prostatic hyperplasia (BPH). BPH is characterized by proliferation of the prostatic epithelium and stroma. Selenium nanoparticles (SeNPs), is an essential metalloid mineral and antioxidant. In this study, SeNPs were tested for their potential protective and curative impacts on BPH in rats. Materials and methods: 50 male Sprague-Dawley rats were randomly divided into five groups: Group I (Control group); Group II (Orchiectomized group): bilateral orchiectomy was conducted on rats; Group III (BPH group): testosterone (TE) enanthate injection was used to induce BPH; Group IV (Protective group): rats were given SeNP before subjecting rats to BPH; Group V (Curative group): rats were succumbed to BPH, followed by administration of SeNP. Measurement of prostate specific antigen (PSA) and TE in serum was performed and prostates were weighed and prepared for histological, immunohistochemical and ultrastructural examination. Results: In the BPH group, serum TE- and PSA-levels, as well as prostate weight, increased significantly and significant decreases in the protective and curative groups. Reduced acinar lumen, expansion of stroma and epithelial hyperplasia were noticed in the BPH group, which were ameliorated significantly both in protective and curative groups. There was an increase in PCNA immunoreaction in the BPH group and a decrease in both the protective and curative groups. On TEM of BPH group, the nuclei appeared irregular with dilated endoplasmic reticulum, loss of cell boundaries and apical microvilli. The protective group showed more improvement than the curative group. Conclusions: The effects of SeNPs on BPH induced by TE in rats, were both protective and curative, although the protective effects were more pronounced.

KATP channel gain- (GOF) and loss-of-function (LOF) mutations in SUR1 or Kir6.2 underlie human neonatal diabetes mellitus (NDM) and congenital hyperinsulinism (CHI), respectively. Genetically modified mice with transgenic overexpression of GOF mutations recapitulate many features of human NDM and transgenic mice expressing incomplete KATP LOF do reiterate mild hyperinsulinism, although complete KATP knockout mice do not exhibit persistent hyperinsulinism. We have shown that islet excitability and glucose homeostasis in zebrafish are regulated by identical KATP channels to those in mammals, and to explore the possibility of using zebrafish for modeling CHI, we have examined SUR1 truncation mutation (K499X) introduced into the abcc8 gene. Patch-clamp analysis confirmed complete absence of channel activity in β-cells from K499X (SUR1-/-) fish. No difference in random blood glucose was detected in heterozygous SUR1+/- fish, nor in homozygous SUR1-/- fish, mimicking findings in SUR1 knockout mice. Mutant fish also demonstrated impaired glucose tolerance, similar to LOF mouse models. In paralleling features of mammalian hyperinsulinism resulting from loss-of-function mutations, this gene-edited animal provides a valid zebrafish model of KATP LOF driven-dependent pancreatic disease.Key PointsLoss-of function in the Kir6.2 (KCNJ11) and SUR1 (ABCC8)-encoded pancreatic islet β-cell KATP channels underlie congenital hyperinsulinism. Mouse models reiterate key features, but zebrafish models could provide a powerful model for further analysis and therapy testing.An early nonsense mutation in exon 10 of SUR1 was generated by ENU mutagenesis.Patch-clamp analysis revealed an absence of β-cells of SUR1 truncation mutants.Ca imaging demonstrated elevated basal [Ca]i in β-cells with SUR1 truncation.Homozygous SUR1 truncation mutants had normal fasting glucose but impaired glucose tolerance as adults, mimicking findings in mouse SUR1 knockouts.In paralleling features of mammalian diabetes and hyperinsulinism resulting from equivalent loss-of-function mutations, this gene-edited animal provides a valid zebrafish model of KATP -LOF dependent pancreatic diseases.

Background: Cyclooxygenase (COX) and Lipoxygenase (LOX) enzymes catalyze the production of pain mediators like Prostaglandins (PGs) and Leukotrienes (LTs), respectively from arachidonic acid. Introduction: The COX and LOX enzyme modulators are responsible for the major PGs and LTs mediated complications like asthma, osteoarthritis, rheumatoid arthritis, cancer, Alzheimer’s disease, neuropathy and Cardiovascular Syndromes (CVS). Many synthetic Nonsteroidal Anti- Inflammatory Drugs (NSAIDs) used in the treatment have serious side effects like nausea, vomiting, hyperacidity, gastrointestinal ulcers, CVS, etc. Methods: The natural inhibitors of pain mediators have great acceptance worldwide due to fewer side effects on long-term uses. The present review is an extensive study of the advantages of plantbased vs synthetic inhibitors. Results: These natural COX and LOX inhibitors control inflammatory response without causing side-effect-related complicacy. Conclusion: Therefore, the natural COX and LOX inhibitors may be used as alternative medicines for the management of pain and inflammation due to their less toxicity and resistivity.

BACKGROUND Burkholderia cepacia complex (BCC) represents a group of multidrug-resistant gram-negative bacteria that cause infections among immunocompromised hosts. Bacteremia occurs in patients who are chronically ill and is associated with substantial morbidity and mortality. The aim of this study was to investigate the clinical characteristics and outcomes of BCC bacteremic patients without cystic fibrosis. METHODS We conducted a retrospective study at the National Taiwan University Hospital. Adults with BCC bacteremia from January 2015 to May 2019 were enrolled. The primary outcome was 14-day mortality. Multivariable logistic regression was performed for outcome analysis. RESULTS One-hundred and ninety-five patients were analyzed and their mean age was 67 years. Over 95% of the BCC isolates were susceptible to trimethoprim/sulfomethoxazole (TMP/SXT). Levofloxacin resistance rates were high, with only 25.1% of isolates being susceptible. Pairwise comparisons were made between different definitive regimens including meropenem-monotherapy, ceftazidime-monotherapy, levofloxacin-monotherapy, TMP/SXT-monotherapy, tigecycline-monotherapy as well as combination versus monotherapy. No regimen was significantly associated with survival in our study. Multivariable logistic regression showed that the Pitt bacteremia score (adjust odds ratio [aOR],1.46; 95% confidence interval [CI],1.19-1.79; p

Association of SOD2 V16A single-nucleotide polymorphism (rs4880) with drug hepatotoxicity were reported but relationships with amiodarone prescriptions remained unexplored. Research was an exploratory, controlled prospective clinical trial. Patients hospitalized and treated in Clinical Center in Kragujevac, Serbia (in year 2017) were divided into experimental (using amiodarone, having liver injury, n=29, 19 males, the mean age 66.8±10.4 years), control A (neither amiodarone use nor hepatotoxicity, n=29, 19, 66.1±10.3) and control B group (using amiodarone, not having hepatotoxicity, n=29, 19, 66.8±9.8). From blood samples, among other routine biochemistry, genotyping for SOD2 polymorphism Val16Ala was conducted using real-time PCR method with TaqMan® Genotyping Master Mix and TaqMan® DME Genotyping Assay for rs4880. Patients taking amiodarone and having liver injury were mostly carriers of Val/Val (TT) genotype (13 of 24 patients, 54.2%) while Val/Ala (TC) and Ala/Ala (CC) genotypes prevailed in control group A (19 of 40, 47.5%) and control group B (9 of 23, 39.1%), respectively (2=10.409, p=0.034). Frequency of Val (T) and Ala (C) alleles were 0.51 and 0.49, respectively in the whole study sample (Hardy Weinberg equilibrium, 2=0.56, p=0.454). Carriers of TT genotype had significantly higher ALT (437.0±1158.0 vs 81.9131.5 U/L), total bilirubin (28.320.5 vs 15.313.0 mol/L) and total bile acid concentrations (10.910.2 vs 6.45.3 mol/L) compared to carriers of TC genotype (U=2.331, p=0.020, U=3.204, p=0.001 and U=2.172, p=0.030, respectively). Higher incidence of 47T allele of SOD2 was inpatients with amiodarone-associated liver injury as compared to patients on amiodarone not experiencing hepatotoxic effects.

OBJECTIVES Neonatal rodents and piglets naturally regenerate the injured heart after myocardial infarction. We hypothesized that neonatal rabbits also exhibit natural heart regeneration after myocardial infarction. METHODS New Zealand white rabbit kits underwent sham surgery or left coronary ligation on postnatal day 1 (n = 94), postnatal day 4 (n = 11), or postnatal day 7 (n = 52). Hearts were explanted 1 day postsurgery to confirm ischemic injury, at 1 week postsurgery to assess cardiomyocyte proliferation, and at 3 weeks postsurgery to assess left ventricular ejection fraction and scar size. Data are presented as mean ± standard deviation. RESULTS Size of ischemic injury as a percentage of left ventricular area was similar after myocardial infarction on postnatal day 1 versus on postnatal day 7 (42.3% ± 5.4% vs 42.3% ± 4.7%, P = .9984). Echocardiography confirmed severely reduced ejection fraction at 1 day after postnatal day 1 myocardial infarction (33.7% ± 5.3% vs 65.2% ± 5.5% for postnatal day 1 sham, P = .0001), but no difference at 3 weeks after postnatal day 1 myocardial infarction (56.0% ± 4.0% vs 58.0% ± 3.3% for postnatal day 1 sham, P = .2198). Ejection fraction failed to recover after postnatal day 4 myocardial infarction (49.2% ± 1.8% vs 58.5% ± 5.8% for postnatal day 4 sham, P = .0109) and postnatal day 7 myocardial infarction (39.0% ± 7.8% vs 60.2% ± 5.0% for postnatal day 7 sham, P

Pseudohypoparathyroidism type 1A (PHP1A) is a disorder of multiple hormone resistance, mainly parathyroid hormone. It is associated with Albright hereditary osteodystrophy phenotypes. Patients with PHP1A may initially present with hypothyroidism during infancy and later develop typical PHP1A characteristics during their childhood. Central precocious puberty (CPP) is extremely rare among PHP1A patients in whom gonadotropin resistance is more usual. This study reported a 9.5-year-old boy with congenital hypothyroidism who developed hypocalcemia secondary to pseudohypoparathyroidism. He had relatively short stature with height standard deviation score of -0.9. Obesity had been noted since the age of 2 years. At the presentation of pseudohypoparathyroidism, pubertal-sized testes of 10 mL were observed, and CPP was documented with serum testosterone concentration of 298 ng/dL (normal for Tanner stage III, 100-320), luteinizing hormone of 3.9 IU/L (normal, 0.2-5.0), and follicle-stimulating hormone of 4.8 IU/L (normal, 1.2-5.8). Pituitary magnetic resonance imaging was unremarkable. Genetic analysis confirmed the diagnosis of PHP1A with a novel heterozygous missense variant of GNAS gene in the exon 13, c.1103A>G (p.Asp368Gly). Awareness of PHP1A diagnosis in patients with congenital hypothyroidism and early childhood-onset obesity is crucial for early diagnosis. Apart from multiple hormone resistance, CPP could be manifested in patients with PHP1A.

Objective Calcified aortic valvular disease is known as an inflammation-related process related to force. The purpose of this study was to determine whether micromechanical force could induce valve calcification of porcine valvular interstitial cells and to examine the role of integrin αvβ3 in valvular calcification by using a novel method: magnetic twisting cytometry. Methods Porcine valvular interstitial cells were cultured in vitro, and micromechanical force was applied to porcine valvular interstitial cells using magnetic twisting cytometry. Changes in calcification-related factors osteopontin and RUNX2 were detected. By using the calcification medium, the optimal magnetic twisting cytometry parameters for inducing valvular interstitial cell calcification were determined, and a magnetic twisting cytometry calcification promotion model was established. The role of αvβ3 in calcification was studied by using αvβ3 antagonists to block the function of αvβ3. Results Reverse transcription polymerase chain reaction assays showed that the expression of osteopontin was enhanced 30 minutes after 25G-1Hz 5 minutes of stimulation. Western blotting assays showed that the expression of osteopontin and RUNX2 was upregulated 24 hours after 25G-1Hz 5 minutes of stimulation. The optimal magnetic twisting cytometry parameter for inducing porcine valvular interstitial cell calcification was 25G-2Hz for 10 minutes. The expression of osteopontin and RUNX2 decreased significantly after the addition of αvβ3 antagonist. Clinically, patients with bicuspid aortic valves had high expression of RUNX2 and β3 in the aortic valve, and β3 significantly correlated with RUNX2. Conclusions By using magnetic twisting cytometry, we established a porcine valvular interstitial cell calcification model by micromechanical force stimulation and obtained the optimal parameters. Integrin αvβ3 plays a key role in the aortic valve calcification process.