Detection of qacEΔ1, qacG, qacE, qacF resistance genes in Escherichia coli producing broad-spectrum beta-lactamases to benzalkonium chloride

BACKGROUND AND OBJECTIVE: The resistance genes of quaternary ammonium compounds(qac) play an important role in the resistance of gram-negative bacteria producing broad-spectrum beta-lactamases to disinfectants. The aim of this study was detection of qacEΔ1, qacG, qacE, qacF resistance genes in Escherichia coli producing broad-spectrum beta-lactamases to benzalkonium chloride. METHODS: This study cross sectional-descriptive was conducted on 150 clinical samples of selected hospitals in Arak. ESBL strains were identified by using phenotypic methods of disc diffusion and combinatory disc method and evaluating the SHV, TEM, CTXM1 genes by genotyping method. The PCR was performed to determine the resistance genes qacEΔ1, qacG, qacE and qacF.The electrophoresis of PCR products and the MIC of benzalkonium chloride were relative to E. coli producing ESBL. Antibiotic pattern of Escherichia coli (ESBL), quadruple ammonium resistance genes and benzalkonium chloride MIC were also investigated. FINDINGS: This study showed that 60% of Escherichia coli were ESBL producer. The qacEΔ1 genes were observed in all of them and qacE, qacF, qacG genes were not found in any of the strains. The strains had MIC range from 32 to 64 mg/l for benzalkonium chloride. Resistance to carbapenems (33.33%) was observed. CONCLUSION: This study showed that qacEΔ1 resistance gene and resistance to disinfectant benzalkonium chloride increased. Also increased resistance to the antibiotics studied were observed in E. coli ESBL strains

Immuno-Transcriptomic Profiling of Blood and Tumor Tissue Identifies Gene Signatures Associated with Immunotherapy Response in Metastatic Bladder Cancer.

Blood-based biomarkers represent ideal candidates for the development of non-invasive immuno-oncology-based assays. However, to date, no blood biomarker has been validated to predict clinical responses to immunotherapy. In this study, we used next-generation sequencing (RNAseq) on bulk RNA extracted from whole blood and tumor samples in a pre-clinical MIBC mouse model. We aimed to identify biomarkers associated with immunotherapy response and assess the potential application of simple non-invasive blood biomarkers as a therapeutic decision-making assay compared to tissue-based biomarkers. We established that circulating immune cells and the tumor microenvironment (TME) display highly organ-specific transcriptional responses to ICIs. Interestingly, in both, a common lymphocytic activation signature can be identified associated with the efficient response to immunotherapy, including a blood-specific CD8+ T cell activation/proliferation signature which predicts the immunotherapy response

Cleidocranial dysplasia presenting with retained deciduous teeth in a 15-year-old girl: a case report

<p>Abstract</p> <p>Introduction</p> <p>Cleidocranial dysplasia is a rare congenital defect of autosomal dominant inheritance caused by mutations in the <it>Cbfa1 </it>gene, also called <it>Runx2</it>, located on the short arm of chromosome 6. It primarily affects bones which undergo intramembranous ossification. This condition is of clinical significance to dentistry due to the involvement of the facial bones, altered eruption patterns and multiple supernumerary teeth.</p> <p>Case presentation</p> <p>Our patient, a 15-year-old Indian girl, presented with the typical features of prolonged retention of deciduous dentition and delayed eruption of permanent teeth, that is, mandibular prognathism along with other skeletal abnormalities like shrugged shoulder and the absence of clavicles. A multidisciplinary approach was followed, comprising orthodontic, surgical and pedodontic teams for management.</p> <p>Conclusion</p> <p>Successful treatment of such a case lies in a holistic approach that takes care of all aspects, including the primary pathology, the deformity itself and even the psychological angle.</p

Effects of different lower-limb sensory stimulation strategies on postural regulation – A systematic review and meta-analysis

Systematic reviews of balance control have tended to only focus on the effects of single lower-limb stimulation strategies, and a current limitation is the lack of comparison between different relevant stimulation strategies. The aim of this systematic review and meta-analysis was to examine evidence of effects of different lower-limb sensory stimulation strategies on postural regulation and stability. Moderate- to high- pooled effect sizes (Unbiased (Hedges’ g) standardized mean differences (SMD) = 0.31 – 0.66) were observed with the addition of noise in a Stochastic Resonance Stimulation Strategy (SRSS), in three populations (i.e., healthy young adults, older adults, and individuals with lower-limb injuries), and under different task constraints (i.e., unipedal, bipedal, and eyes open). A Textured Material Stimulation Strategy (TMSS) enhanced postural control in the most challenging condition – eyes-closed on a stable surface (SMD = 0.61), and in older adults (SMD = 0.30). The Wearable Garments Stimulation Strategy (WGSS) showed no or adverse effects (SMD = -0.68 – 0.05) under all task constraints and in all populations, except in individuals with lower-limb injuries (SMD = 0.20). Results of our systematic review and meta-analysis revealed that future research could consider combining two or more stimulation strategies in intervention treatments for postural regulation and balance problems, depending on individual need

Novel genes in Human Asthma Based on a Mouse Model of Allergic Airway Inflammation and Human Investigations

PURPOSE: Based on a previous gene expression study in a mouse model of asthma, we selected 60 candidate genes and investigated their possible roles in human asthma. METHODS: In these candidate genes, 90 SNPs were genotyped using MassARRAY technology from 311 asthmatic children and 360 healthy controls of the Hungarian (Caucasian) population. Moreover, gene expression levels were measured by RT PCR in the induced sputum of 13 asthmatics and 10 control individuals. t-tests, chi-square tests, and logistic regression were carried out in order to assess associations of SNP frequency and expression level with asthma. Permutation tests were performed to account for multiple hypothesis testing. RESULTS: The frequency of 4 SNPs in 2 genes differed significantly between asthmatic and control subjects: SNPs rs2240572, rs2240571, rs3735222 in gene SCIN, and rs32588 in gene PPARGC1B. Carriers of the minor alleles had reduced risk of asthma with an odds ratio of 0.64 (0.51-0.80; P=7×10(-5)) in SCIN and 0.56 (0.42-0.76; P=1.2×10(-4)) in PPARGC1B. The expression levels of SCIN, PPARGC1B and ITLN1 genes were significantly lower in the sputum of asthmatics. CONCLUSIONS: Three potentially novel asthma-associated genes were identified based on mouse experiments and human studies

Tumour brain: pre‐treatment cognitive and affective disorders caused by peripheral cancers

People that develop extracranial cancers often display co-morbid neurological disorders, such as anxiety, depression and cognitive impairment, even before commencement of chemotherapy. This suggests bidirectional crosstalk between non-CNS tumours and the brain, which can regulate peripheral tumour growth. However, the reciprocal neurological effects of tumour progression on brain homeostasis are not well understood. Here, we review brain regions involved in regulating peripheral tumour development and how they, in turn, are adversely affected by advancing tumour burden. Tumour-induced activation of the immune system, blood–brain barrier breakdown and chronic neuroinflammation can lead to circadian rhythm dysfunction, sleep disturbances, aberrant glucocorticoid production, decreased hippocampal neurogenesis and dysregulation of neural network activity, resulting in depression and memory impairments. Given that cancer-related cognitive impairment diminishes patient quality of life, reduces adherence to chemotherapy and worsens cancer prognosis, it is essential that more research is focused at understanding how peripheral tumours affect brain homeostasis

Kaposi’s sarcoma in renal transplantation : report of three cases

Kaposi's sarcoma (KS) is one of the most common post transplant malignancies. A variety of factors appears to contribute to the development of KS including genetic factors, sex hormones, immunosuppression and oncogene viruses. We present 3 cases with concurrent KS and cytomegalovirus (CMV) infection in the first year after kidney transplantation. The suspicion on KS due to the skin lesions was confirmed by biopsy. The diagnosis of CMV infection was made by detecting pp65 antigen in blood. The KS lesions were limited to the skin in 2 patients, while skin and gastrointestinal tract were involved in 1 patient. Many factors are reported to be involved in KS development, but the simultaneous occurrence of KS and CMV infection in our three cases suggested CMV as an inducing factor for KS

Clinical manifestation, laboratory findings, and the response of treatment in kidney transplant recipients with CMV infection

Objectives. To report clinical manifestations, laboratory findings, and treatment outcomes of in kidney transplant recipients who had cytornegalovirus (CMV) infections. Methods. This retrospective study evaluated the records of kidney transplant recipients followed regularly from 2001 to 2006. In some patients information was also gathered through a telephone call or physical examination. The CMV infection diagnosis was also made by detecting PP.65 antigen per 50,000 peripheral blood leukocytes. Results. Of the 200 kidney transplant recipients, 66 were infected with CMV including 42 men and 24 women. The mean patient age was 40 13 years (range, 14 to 67 years). Seventy-nine percent of the infected patients were diagnosed during the first 6-months after transplantation. All except 22 patients (33%) had constitutional complaints. Fever was present in 65% of patients, abdominal pain in 21%, diarrhea in 20%, and vomiting in 15%. Likewise, pulmonary complaints including cough and dyspnea were reported by 32% and 23%, respectively. However, 20% of patients were completely asymptomatic. Hematologic laboratory data showed anemia (64%), thrombocytopenia (47%), and leukopenia (21%). Seventy eight percent of patients had a serum creatinine <= 2 mg/dL before infection, but it was <= 2 in just 26% at the time CMV was diagnosed and 60% after treatment. Antiviral therapy included intravenous gancyclovir in 80% of patients and gancyclovir plus oral acyclovir in 20%. Corticosteroid pulse therapy was also administered in 78% of patients. No statistically significant correlation was observed between CMV antigen load and the severity of clinical manifestations or the time of response to treatment or the recurrence prognosis. In our series, 1 patient died, 28 treated patients (42%) experienced CMV recurrence, and 37 (56%) showed no recurrence. Conclusions. CMV infection should be considered in any renal transplant recipient who has a rise in creatinine even if symptom-free. Despite the results of other studies, we found no prognostic value for the viral antigen load

Exploring Biosynthetic Pathways for the Production of Five Methyl Ethyl Ketone Precursors

Limited reserves of oil and natural gas and the establishment of new environmental policies sparked off intensive research towards sustainable production of the 2nd generation of biofuels, with Methyl Ethyl Ketone (MEK) being one promising fuel candidate. MEK is a commercially valuable petrochemical with an extensive application as a solvent. However, as of today, a sustainable and economically viable production of MEK has not yet been achieved despite several attempts of introducing biosynthetic pathways in industrial microorganisms. We used BNICE.ch as a retrobiosynthesis tool to discover all novel pathways around MEK. Out of 1’325 identified compounds connecting to MEK with one reaction step, we selected 3-oxopentanoate, but-3-en-2-one, but-1-en-2-olate, butylamine, and 2-hydroxy-2-methyl-butanenitrile for further study. We reconstructed 3’679’610 novel biosynthetic pathways towards these 5 compounds. We then embedded these pathways into the genome-scale model of E. coli, and a set of 18’622 were found to be most biologically feasible ones based on thermodynamics and their yields. For each novel reaction in the viable pathways, we proposed the most similar KEGG reactions, with their gene and protein sequences, as candidates for either a direct experimental implementation or as a basis for enzyme engineering. Through pathway similarity analysis we classified the pathways and identified the enzymes and precursors that were vital for the production of the target molecules. These retrobiosynthesis studies demonstrate the potential of BNICE.ch for discovery, systematic evaluation, and analysis of novel pathways in synthetic biology and metabolic engineering studies