Background: Klebsiella pneumoniae as an opportunistic pathogen can be the cause of a range of nosocomial and community - acquired infections. Many virulence factors help these bacteria overcome an ...immune system and cause various diseases. K1 and K2 capsular antigens, also magA, wcaG, and rmpA are well - known K. pneumoniae virulence factors. Klebsiella pneumoniae has been revealed to have the ability to acquire resistance to many antibiotics, which cause treatment failure.Objectives: This study aimed at determining the prevalence of magA, wcaG, rmpA, Capsular type K1, Capsular type K2, TEM, and SHV in K. pneumoniae isolates.Methods: A total of 173 non - duplicate K. pneumoniae isolates were collected from two different hospitals in Semnan, Iran, from urine specimens. Klebsiella pneumoniae was identified by conventional bacteriological tests. Disk diffusion test was performed according to the guidelines of the Clinical and Laboratory Standards Institute (CLSI). Detection of virulence factors, TEM, and SHV gene was performed by specific primers.Results: Frequency of virulence factors was as follow: capsular type K2: 32.9%, rmpA: 20.2%, capsular type K1: 6.9%, and wcaG: 16.2%. Also, the SHV and TEM were observed in 46.8% and 33.5%, respectively. Antibiotics resistance rates were as follow, imipenem: 7.5%, ciprofloxacin: 16.1%, levofloxacin: 17.3%, amoxicillin - clavulanic acid: 30%, trimethoprim - sulfamethoxazole: 32.9%, cefepime: 34.1%, nitrofurantoin: 35.8%, amikacin: 36.4%, aztreonam: 39.3%, ceftazidime: 42.7%.Conclusions: Frequency of some virulence factors including capsular type K2, rmpA, wcaG, and also resistant rate to imipenem, amikacin, and ceftazidime were significantly higher than similar studies. Presence of virulence factors accompanied by drug resistance should make bacteria an infectious agent and lead to treatment failure.
We report the structure activity relationships of short 14-mer phosphorothioate gapmer antisense oligonucleotides (ASOs) modified with α-L-locked nucleic acid (LNA) and related modifications ...targeting phosphatase and tensin homologue (PTEN) messenger RNA in mice. α-L-LNA represents the α-anomer of enantio-LNA and modified oligonucleotides show LNA like binding affinity for complementary RNA. In contrast to sequence matched LNA gapmer ASOs which showed elevations in plasma alanine aminotransferase (ALT) levels indicative of hepatotoxicity, gapmer ASOs modified with α-L-LNA and related analogs in the flanks showed potent downregulation of PTEN messenger RNA in liver tissue without producing elevations in plasma ALT levels. However, the α-L-LNA ASO showed a moderate dose-dependent increase in liver and spleen weights suggesting a higher propensity for immune stimulation. Interestingly, replacing α-L-LNA nucleotides in the 3′- and 5′-flanks with R-5′-Me-α-L-LNA but not R-6′-Me- or 3′-Me-α-L-LNA nucleotides, reversed the drug induced increase in organ weights. Examination of structural models of dinucleotide units suggested that the 5′-Me group increases steric bulk in close proximity to the phosphorothioate backbone or produces subtle changes in the backbone conformation which could interfere with recognition of the ASO by putative immune receptors. Our data suggests that introducing steric bulk at the 5′-position of the sugar-phosphate backbone could be a general strategy to mitigate the immunostimulatory profile of oligonucleotide drugs. In a clinical setting, proinflammatory effects manifest themselves as injection site reactions and flu-like symptoms. Thus, a mitigation of these effects could increase patient comfort and compliance when treated with ASOs.
Networks are used as highly expressive tools in different disciplines. In recent years, the analysis and mining of temporal networks have attracted substantial attention. Frequent pattern mining is ...considered an essential task in the network science literature. In addition to the numerous applications, the investigation of frequent pattern mining in networks directly impacts other analytical approaches, such as clustering, quasi-clique and clique mining, and link prediction. In nearly all the algorithms proposed for frequent pattern mining in temporal networks, the networks are represented as sequences of static networks. Then, the inter- or intra-network patterns are mined. This type of representation imposes a computation-expressiveness trade-off to the mining problem. In this paper, we propose a novel representation that can preserve the temporal aspects of the network losslessly. Then, we introduce the concept of constrained interval graphs (<inline-formula><tex-math notation="LaTeX">CIG</tex-math> <mml:math><mml:mrow><mml:mi>C</mml:mi><mml:mi>I</mml:mi><mml:mi>G</mml:mi></mml:mrow></mml:math><inline-graphic xlink:href="jazayeri-ieq1-3324799.gif"/> </inline-formula>s). Next, we develop a series of algorithms for mining the complete set of frequent temporal patterns in a temporal network data set. We also consider four different definitions of isomorphism for accommodating minor variations in temporal data of networks. Implementing the algorithm for three real-world data sets proves the practicality of the proposed approach and its capability to discover unknown patterns in various settings.
Non-alcoholic fatty liver disease (NAFLD) is one of the main causes of chronic liver disease worldwide. Flavonoids, a group of natural compounds, have garnered a great deal of attention in the ...management of NAFLD because of their profitable effects on glucose and lipid metabolism, inflammation, and oxidative stress which are the pivotal pathophysiological pathways in NAFLD. Naringenin is a citrus-derived flavonoid with a broad spectrum of potential biological effects including anti-inflammatory and antioxidant properties, which may exert protective effects against NAFLD. The present clinical trial aims to examine the efficacy of naringenin supplementation on plasma adiponectin and neurogulin-4 (NRG-4) concentrations, metabolic parameters, and liver function indices in overweight/obese patients with NAFLD.
This is a double-blind, randomized, placebo-controlled clinical study that will investigate the impacts of naringenin supplementation in overweight/obese patients with NAFLD. Liver ultrasonography will be applied to diagnose NAFLD. Forty-four eligible overweight/obese subjects with NAFLD will be selected and randomly assigned to receive naringenin capsules or identical placebo (each capsule contains 100 mg of naringenin or cellulose), twice daily for 4 weeks. Participants will be asked to remain on their usual diet and physical activity. Safety of naringenin supplementation was confirmed by the study pharmacist. The primary outcome of this study is changes in adiponectin circulating levels. The secondary outcomes include changes in NRG-4 levels, liver function indices, metabolic parameters, body weight, body mass index (BMI), waist circumference (WC), blood pressure, and hematological parameters. Statistical analysis will be conducted using the SPSS software (version 25), and P value less than 0.05 will be regarded as statistically significant.
We hypothesize that naringenin administration may be useful for treating NAFLD by modulating energy balance, glucose and lipid metabolism, oxidative stress, and inflammation through different mechanisms. The current trial will exhibit the effects of naringenin, whether negative or positive, on NAFLD status.
The current trial received approval from the Medical Ethics Committee of Tehran University of Medical Sciences, Tehran, Iran (IR.TUMS.MEDICNE.REC.1399.439).
Iranian Registry of Clinical Trials IRCT201311250155336N12 . Registered on 6 June 2020.
Homozygosity mapping (HM), also known as autozygosity mapping, was originally used to map genes underlying homozygous autosomal recessive Mendelian diseases in patients from closely genetically ...related populations, followed by Sanger sequencing. With the increase in use of next-generation sequencing approaches, such as whole-exome sequencing and whole-genome sequencing, together with advanced bioinformatics filtering approaches, HM is again emerging as a powerful method for the identification of genes involved in disease etiology. In addition to its usefulness for research, HM is effective in clinical genetic services, increasing the efficiency of molecular diagnostics. For autosomal recessive Mendelian disorders with extensive genetic heterogeneity, HM can reduce both cost and turnaround time of mutation detection in the context of next-generation sequencing and can obviate expensive screening, such as biochemical testing in the setting of metabolic genodermatoses or antigen mapping for epidermolysis bullosa. It is therefore important for dermatology clinicians and researchers to understand the processes, principal uses, and advantages and limitations of HM when ordering or performing genetic tests for patients affected by heritable skin disorders.
ObjectivesDifferent studies have been conducted on the role of curcumin in health since having multiple properties, including antioxidant and anti-inflammatory effects. Due to the lack of studies ...regarding curcumin effects on obese patients with non-alcoholic fatty liver disease (NAFLD), our protocol was designed to assess nanocurcumin impacts on blood sugar, lipids, inflammatory indices, insulin resistance and liver function, especially by nesfatin.SettingThis trial will be conducted in the Oil Company central hospital of Tehran, Iran with a primary level of care.Participants84 obese patients with NAFLD diagnosed using ultrasonography will be employed according to the eligibility criteria.InterventionsThe patients will be randomly divided into two equal groups (nanocurcumin and placebo, two 40 mg capsules per day with meals for 3 months, follow-up monthly). Also, lifestyle changes (low-calorie diet and physical activity) will be advised.Measures of the primary and secondary outcomesA general questionnaire, 24 hours food recall (at the beginning, middle and end) and short-form International Physical Activity Questionnaire will be completed. Blood pressure, anthropometrics, serum sugar indices (fasting blood sugar and insulin, insulin resistance and sensitivity and glycosylated haemoglobin), lipids (triglyceride, total cholesterol and low-density and high-density lipoprotein-cholesterol, inflammatory profiles (interleukin-6, high-sensitivity C-reactive protein, and tumour necrosis factor-alpha), liver function (alanine and aspartate transaminase) and nesfatin will be measured at the beginning and end of the study.ConclusionThis trial would be the first experiment to determine nanocurcumin efficacy on certain blood factors among obese patients with NAFLD. Nevertheless, studying the potential consequences of curcumin in various diseases, especially NAFLD, is required for clinical use.Trial registration numberIRCT2016071915536N3; pre-results.
Persistent left superior vena cava (PLSVC) represents the most common thoracic venous anomaly and is an important clinical entity for cardiologists and electrophysiologists, among others. In ...approximately 30% of cases, a bridging innominate vein connects the left superior vena cava to the right. The present report highlights the value of defining the venous anatomy with a case of dual-chamber pacemaker implantation in the PLSVC with the right ventricular lead placed via the innominate vein. Pertinent considerations for device implantation in the setting of this anomaly are discussed and relevant venography reviewed.
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