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Abstract Purpose Hepatocellular carcinoma (HCC) is a possible oncogenic progression during persistent hepatitis C-infection +/- type II diabetes mellitus (DM). To investigate the plasma insulin, erythrocytic aldose reductase (AR) and sorbitol dehydrogenase (SDH) as possible predictive tools for HCC in hepatitis C-infected patients (HCV) +/- DM. Erythrocytes (RBCs) were adopted as a possible vehicle for pre-malignant variations being of short life span. Methods The study included 20 healthy control and 100 patients of 48–64 years old, divided into 5 equal groups as; type II DM, HCC, HCC with DM, DM- HCV infected and non-DM HCV infected. Plasma levels of AFP and insulin were measured. Results It showed an elevated AR, significant reduction of SDH in RBCs and plasma of DM patients. These values were greatly elevated among HCV, HCC, diabetic HCV, and diabetic HCC patients. All DM patients showed elevated insulin levels than normoglycemic controls. Conclusion The study substantiated the use of RBCs as a vehicle for early diagnostic markers better than plasma. We recommend the use of insulin/ erythrocytic AR ratio as a new laboratory marker for predicting HCC among type II diabetics or non-treated HCV-infected patients with control insulin/ erythrocytic AR ratio by each laboratory.

Wheat powdery mildew, caused by the obligate biotrophic ascomycete fungal pathogen Blumeria graminis f. sp. tritici (Bgt), is a major threat to wheat production worldwide. It is known that Arabidopsis thaliana glucan synthase-like 5 (AtGSL5) improves the resistance of wheat to powdery mildew by increasing its anti-penetration abilities. However, the function of glucan synthase-like (GSL) orthologs in crop species remains largely unknown. In this study, TaGSL22, a novel functional ortholog of AtGSL5, was isolated as the only Bgt-induced GSL gene in wheat. Phylogenetic analysis indicated that TaGSL22 was conserved within the group of Gramineae and showed a closer relationship to GSL orthologs from monocots than to those from dicots. The TaGSL22 transcript was highest in the wheat leaves, followed by stems then roots. TaGSL22 was localized in the cell membrane and cytoplasm of wheat protoplasts, as predicted by transmembrane structure analysis. In addition, expression of TaGSL22 was induced by the plant hormones ethylene (ETH) and salicylic acid (SA), but down-regulated by jasmonate (JA) and abscisic acid (ABA). The transcript level of TaGSL22 was up-regulated in the incompatible interaction between Bgt and wheat, whereas it remained relatively unchanged in the compatible interaction. Knocking down of TaGSL22 by virus-induced gene silencing (VIGS) induced a higher infection type in the wheat–Bgt interaction. The TaGSL22-silenced plants exhibited reduced resistance to Bgt, accompanied by decreased callose accumulation. Our study shows a conserved function of GSL genes in plant immunity associated with penetration resistance, and it indicates that TaGSL22 can be used to improve papilla composition and enhance resistance to wheat powdery mildew.

The authors describe clinical observations of children with acute mesenteric adenitis with PCRconfirmed COVID-19 infection. Attention during ultrasound diagnostics is drawn to the condition of the lymph nodes – mesenteric adenitis in COVID-19 infection was manifested by a significant increase in the size of the nodes – more than 15 mm, a large number of nodes in the cut with a tendency to form a conglomerate, a more rounded shape, significantly increased blood flow, a reaction of the peritoneum in the form its thickening and the presence of free fluid in the abdominal cavity. Unusual for a «ordinary» respiratory viral or intestinal infection type of lymph nodes was the only sign that distinguishes the manifestations of mesenteric infection in COVID-19 infection.

Background: Musculoskeletal infections ([MSKI]; osteomyelitis, septic arthritis, pyomyositis) are common invasive infections in children. With increasing antibiotic resistance and allergies, treatment options are limited. Trimethoprim-sulfamethoxazole (TMP-SMX) has activity against common MSKI pathogens, yet pediatric MSKI outcomes data are limited. Our aim was to evaluate outcomes of children with MSKI treated with TMP-SMX compared to clindamycin. We hypothesized that outcomes would be similar between groups. Methods: We conducted a retrospective review of children <18 years old, admitted to Riley Hospital for Children from January 2010-June 2021 treated with TMP-SMX or clindamycin for MSKI. Patients were identified by ICD-9/10 codes. Patients were excluded if TMP-SMX or clindamycin was not the main treatment, they had symptoms >30 days, hardware associated infection, or an alternative diagnosis. Treatment success was defined as no evidence of infection at the end therapy. Treatment failure was defined as antibiotic intolerance, or development of recurrent/chronic osteomyelitis. Adverse drug reactions were recorded. Results: One-hundred-sixty-three patients (30 TMP-SMX, 133 clindamycin) met eligibility criteria. The majority were non-Hispanic white males, median age of 1.75 years (IQR, 1-3.75) for the TMP-SMX group, and 7 years (IQR 3-10) for the clindamycin group. Osteomyelitis was the most common infection type in both groups (TMP-SMX 43.3%, clindamycin 54.1%).  S. aureus was the most common pathogen in both groups (TMP-SMX 36.7%, clindamycin 48.1%). Of the patients that completed follow-up, 84% successfully completed treatment with TMP-SMX, compared to 86.4% with clindamycin (odds ratio [OR] 0.82; 95% CI 0.25-2.46, p=0.75). Adverse drug reactions occurred in 6.7% of the TMP-SMX group, compared to 10.5% in the clindamycin group (OR 0.61; 95% CI 0.13-2.57, p=0.52). Conclusions: Preliminary results show that TMP-SMX is well tolerated and not associated with higher risk of treatment failure compared to clindamycin in the treatment of pediatric MSKI. Randomized controlled trials to evaluate optimal treatment are needed.

ObjectivesTo provide a comprehensive assessment of the impact of carbapenem resistance on mortality among patients infected with Enterobacteriaceae and to explore the source of heterogeneity across studies.DesignThis systematic review was conducted following the guidelines of Cochrane Guidance and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses.Data sourcesWe conducted a systematic literature search of the PubMed, Embase, Web of Science and Cochrane Library databases to identify relevant studies published between 1 January 1994 and 30 August 2020.Eligibility criteriaWe included primary observational studies published in English that reported the mortality outcomes for hospitalised patients with confirmed infections due to carbapenem-resistant Enterobacteriaceae (CRE) and carbapenem-susceptible Enterobacteriaceae (CSE). Studies with no comparison group or with a comparison group of patients infected with unconfirmed CSE were excluded.Data extraction and synthesisData extraction and assessment of risk bias were conducted independently by two reviewers. The pooled relative risk and risk difference were calculated as effect measures with 95% CIs using a random effects model. The heterogeneity across studies was assessed by Q-statistic and I2 measures.ResultsOf 10 304 studies initially identified, 50 studies were included in the meta-analyses. The results of the meta-analyses showed that carbapenem resistance has a significant positive effect on the probability of death for patients infected with Enterobacteriaceae for any type of mortality outcome. The results of the stratified analysis and meta-regression suggested that the effect of carbapenem resistance on the risk of death varied by infection type, sample size and year of publication.ConclusionsOur results suggested that patients with CRE infection still face a greater risk of death than patients with CSE infection do, and an urgent need to develop new antibiotics and appropriate treatments to reduce the risk of death.PROSPERO registration numberCRD42020176808.

AbstractPowdery mildew is one of the most destructive diseases in the world, causing substantial grain yield losses and quality reduction in cereal crops. At present 23 powdery mildew resistance genes have been identified in rye, of which the majority are in wheat-rye translocation lines developed for wheat improvement. Here, we investigated the genetics underlying powdery mildew resistance in the Gülzow-type elite hybrid rye (Secale cereale L.) breeding germplasm. In total, 180 inbred breeding lines were genotyped using the state-of-the-art 600 K SNP array and phenotyped for infection type against three distinct field populations of B. graminis f. sp. secalis from Northern Germany (2013 and 2018) and Denmark (2020). We observed a moderate level of powdery mildew resistance in the non-restorer germplasm population, and by performing a genome-wide association study using 261,406 informative SNP markers, we identified a powdery mildew resistance locus, provisionally denoted PmNOS1, on the distal tip of chromosome arm 7RL. Using recent advances in rye genomic resources, we investigated whether nucleotide-binding leucine-rich repeat genes residing in the identified 17 Mbp block associated with PmNOS1 on recent reference genomes resembled known Pm genes.

ObjectiveDirkmeia churashimaensis, belonging to Ustilaginales fungi, has never been reported as clinical pathogenic until very recently. In this study, we report an unusual subcutaneous infection with Dirkmeia churashimaensis and reviewed all human Ustilaginales infections. The aim is to better understand their epidemiology, infection type, risk factors, and the sensitivity to antifungal agents.MethodsAn 80-year-old female farmer developed extensive plaques and nodules on her left arm within 2 years. Pathological and microbiological examinations identified a new pathological agent, Dirkmeia churashimaensis, as the cause of this infection. The patient was successfully cured by oral itraconazole. We reviewed a total of 31 cases of Ustilaginales cases, among of which only three were skin infections.ResultsLocal barrier damage (i.e., surgery, trauma, and basic dermatosis) and systemic immunodeficiency (i.e., preterm and low birthweight, Crohn’s disease, malignant cancer, and chemotherapy) are risk factors for Ustilaginales infection. The D1/D2 and ITS regions are the frequently used loci for identifying the pathogens together with phenotype. Most patients could survive due to antifungal treatment, whereas seven patients died. Amphotericin B, posaconazole, itraconazole, and voriconazole showed good activity against these reported strains, whereas fluconazole, 5-flucytosine, and echinocandins usually showed low susceptibility. Itraconazole had good efficiency for subcutaneous infections.ConclusionsThe present case study and literature review reveal that Ustilaginales can be opportunistic pathogenic normally in immunocompromised and barrier damage people. A proper identification of fungi can be crucial for clinical treatment, and more data of antifungal are needed for choice of medication against this kind of infections.

Abstract Background To investigate the knowledge, attitudes, and practices of the healthcare professionals (HCPs) including physicians and nurses regarding dengue transmission, diagnosis and clinical classification using the warning signs of World Health Organization (WHO) 2009 classification. Results Out of 471 respondents from three countries, 80.9% of physicians and 74% of nurses did not receive previous training regarding the dengue infection. The majority of respondents could identify the primary dengue vector (86%), while only a third of HCPs knew the biting time of dengue mosquitoes. Only half of our respondents knew about immunity induced by serotypes; Moreover, half of our participants could determine the diagnostic tests. On the other hand, about 90% of the respondents took responsibility for talking to the patients about preventive measures. Our respondents also showed wide variations in definition of warning signs listed in the WHO 2009 classification. Multivariate analysis linked the impact of different cofactors including prior training on dengue infection, type of profession, frequency of taking care of dengue patients and country on how HCPs defined these warning signs. Conclusions This study could declare the variation in employing the warning signs listed in the WHO 2009 classification. We have figured that most of the HCPs did not take prior training on the dengue viral infection; Also, we found gaps in the knowledge regarding various topics in dengue fever. This paper recommends the gathering of efforts to establish the proper knowledge of dengue infection and the warning signs listed by the WHO.

Abstract Background Colistin (COL) remains an important therapeutic option for carbapenem-resistant (CR) Gram-negative bacilli (GNB). COL is often utilized in combination with meropenem (MEM), in part due to concerns regarding the development of COL resistance with monotherapy. We recently completed a randomized controlled trial comparing outcomes in patients receiving COL + placebo to those receiving COL + MEM; herein we present data on the emergence of COL resistance in this trial. Methods OVERCOME was an international, multicenter, randomized, double-blind, placebo-controlled study comparing COL and COL + MEM for the treatment of bloodstream infection and/or pneumonia due to CR GNB. Subjects were included in the modified intent to treat population (mITT) if their enrollment pathogen had a COL MIC ≤2 mg/L, as determined by broth microdilution (BMD). Daily blood and/or respiratory samples were obtained in patients per protocol until two consecutive negatives were obtained or the end of study treatment. All subsequent isolates were evaluated for COL resistance via BMD, defined as MIC ≥ 4 mg/L. Results Of the 425 patients in the mITT population, 380 (191 COL; 189 COL + MEM) were evaluable for the endpoint of COL resistance development. The median age of the cohort was 70, 38% were female, 47% were white, and 45% were Asian. 70% had an index infection of pneumonia, 68% were in the intensive care unit at the onset of their infection, and A. baumannii was the most common pathogen (78% of patients). Baseline characteristics, infection type, severity of illness, and index pathogen were similar amongst treatment arms. No significant difference in resistance development was seen between the COL and COL + MEM groups overall (12% vs. 8%; p = 0.31), or in any subgroup (Table). In patients with A. baumannii, there was a trend towards decreased resistance development with COL + MEM (13.3% vs 7.5%; p = 0.13). Conclusion We were unable to identify a significant difference in resistance emergence between treatment arms, but given the low incidence of this outcome, were underpowered to do so. The impact of COL + MEM on preventing emergence of COL resistance in A. baumannii warrants further clinical study. Disclosures Jason M Pogue, PharmD, BCPS, BCIDP, Merck (Consultant)QPex (Consultant)Shionogi (Consultant)Utility Therapeutics (Consultant)VenatoRX (Consultant) Michael J. Rybak, PharmD, MPH, PhD, Paratek Pharmaceuticals (Research Grant or Support) Emmanuel Roilides, MD, PhD, FIDSA, FAAM, FESCMID, Merck Sharp & Dohme Corp. (Consultant, Grant/Research Support) Matthew Sims, MD, PhD, Astra Zeneca (Independent Contractor)Diasorin Molecular (Independent Contractor)Epigenomics Inc (Independent Contractor)Finch (Independent Contractor)Genentech (Independent Contractor)Janssen Pharmaceuticals NV (Independent Contractor)Kinevant Sciences gmBH (Independent Contractor)Leonard-Meron Biosciences (Independent Contractor)Merck and Co (Independent Contractor)OpGen (Independent Contractor)Prenosis (Independent Contractor)Regeneron Pharmaceuticals Inc (Independent Contractor)Seres Therapeutics Inc (Independent Contractor)Shire (Independent Contractor)Summit Therapeutics (Independent Contractor)

Abstract Background: Releasing considerable numbers of radiation-sterilized males is a promising strategy to suppress mosquito vectors. However, releases may also include small percentages of biting females which translate to large numbers when releases are large.Currently, the effects of irradiation on the host-seeking and host-biting behaviors have not been exhaustively investigated. Information is also lacking regarding the effects of sterilizing treatment on the endosymbiotic bacterium Wolbachia, which is known to affect the vector competence of infected mosquitos.Methods: To ascertain the effects of irradiation on females, the pupae of two Aedes albopictus strains, differing in their natural or artificial Wolbachia infection type, and Ae. aegypti—which is not infected by Wolbachia—were treated with various doses of X-rays and monitored for key fitness parameters and biting behavior over a period of two weeks. The effect of radiation on Wolbachia was investigated by qPCR and FISH analysis.Results: Partial Ae. albopictus female sterility was achieved at 28 Gy but the number of weekly bites more than doubled compared to that of the controls. Radiation doses of 35 and 45 Gy completely inhibited progeny production but did not significantly affect the survival or flight ability of Ae. albopictus females and caused a tripling of the number of bites per female per week (compared to untreated controls). These results were also confirmed in Ae. aegypti after treatment at 50 Gy. Wolbachia density decreased significantly in 45-Gray-irradiated females, with the greatest decreases in the early irradiation group (26±2-hour-old pupae). Wolbachia density also decreased as adults aged. This trend was confirmed in ovaries but not in extra-ovarian tissues. FISH analysis showed a strongly reduced Wolbachia-specific fluorescence in the ovaries of 13±1-day-old females.Conclusions: These results suggest that, under SIT programs, the vector capacity of a target population could increase with the frequency of the irradiated females co-released with the sterile males due to an increased biting rate. In the context of a successful suppression, the related safety issues could be generally negligible, but they should be conservatively evaluated when large scale programs relying on imperfect sexing and high overflooding release ratios are run for long time in areas endemic for arboviral diseases. Also, the effects of irradiation on the vector competence deserve further investigation.