Azithromycin resistance and its molecular characteristics in Neisseria gonorrhoeae isolates from a tertiary care centre in North India

Treatment guidelines for management of uncomplicated gonorrhoeae have been recently modified owing to alarming upsurge in azithromycin resistance. This study investigated the prevalence and genetic determinants of gonococcal azithromycin resistance in India. Four (5.7%) of 70 gonococcal isolates were resistant to azithromycin. Of 16 isolates investigated for molecular mechanisms of resistance, 13 (81.3%) and 6 (37.5%) isolates exhibited mutations in coding and promoter regions of mtrR gene, respectively. However, ermA, ermB and ermC genes or mutations in rrl gene were absent in all isolates. Azithromycin resistance is low in India posing no immediate threat to use of dual-therapy for syndromic management.     

Left Ventricular Systolic Dysfunction and Cardiovascular Outcomes in Tetralogy of Fallot: Systematic Review and Meta-analysis

BackgroundAlthough there are robust data about the pathophysiology and prognostic implications of left ventricular (LV) systolic dysfunction in patients with acquired heart disease, similar prognostic data about LV systolic dysfunction are sparse in the tetralogy of Fallot (TOF) population. The purpose of this study was to perform a meta-analysis of all studies that assessed the relationship between LV ejection fraction (LVEF) and cardiovascular adverse events (CAEs) defined as death, aborted sudden death, or sustained ventricular tachycardia.MethodsWe used random-effects models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs).ResultsOf the 1,809 citations, 7 studies with 2,854 patients (age 28 ± 4 years) were included. During 5.6 ± 3.4 years' follow-up, there were 82 deaths, 17 aborted sudden cardiac deaths, and 56 sustained ventricular tachycardia events. Overall, CAEs occurred in 5.1% (144 patients). As a continuous variable, LVEF was a predictor of CAE (HR 1.29, 95% CI, 1.09-1.53, P = 0.001) per 5% decrease in LVEF. Similarly, LVEF < 40% was also a predictor of CAE (HR 3.22, 95% CI, 2.16-4.80, P < 0.001).ConclusionsLV systolic dysfunction was an independent predictor of CAE, and we observed a 30% increase in the risk of CAE for every 5% decrease in LVEF, and a 3-fold increase in the risk of CAE in patients with LVEF <40% compared with other patients. These findings underscore the importance of incorporating LV systolic function in clinical risk stratification of patients with TOF and the need to explore new treatment options to address this problem.     

Effects of Pistacia atlantica on Oxidative Stress Markers and Antioxidant Enzymes Expression in Diabetic Rats

Introduction: Diabetes mellitus (DM) affects many patients all over the world. It involves different parts of the body, such as brain, eyes, kidneys, vessels, and so on. The lack of balance between free radicals and antioxidants is a possible mechanism involved in the pathogenesis of diabetes. Antioxidant treatment, especially natural forms, can be a beneficial solution. Therefore, we evaluated the effects of Pistacia atlantica oleoresin (PAO) on oxidative stress markers and antioxidant enzymes expression in diabetic rats.

Method: Fifty adult male Wistar rats were allotted randomly into five groups as follow: control group, diabetic control group, glibenclamide control group, diabetic glibenclamide group, diabetic treated group with 200?mg/kg PAO. Then PAO was prepared and analyzed by gas chromatography/mass spectroscopy (GC/MS). LD50 was also estimated for essential oil. Oxidative stress markers and antioxidant enzyme including malondialdehyde (MDA), glutathione (GSH), glutathione peroxidase (GPx), catalase (CAT), and superoxide dismutase (SOD) were also measured. The expression of GPx, CAT, and SOD genes was investigated using real-time polymerase chain reaction (PCR).

Results: The main constituents of essential oil gum were beta-pinene (29.38%), followed by alpha-pinene (18.15%), myrcene (7.36%), trans-pinocarveol (7.15%), and camphene (4.12%). Diabetes induced an increased level of MDA (69.92?±?3.92 vs. 43.76?±?3.73) and decreased levels of GSH (2.57?±?0.40 vs. 7.05?±?1.59), GPx (11.66?±?2.2 vs. 16.38?±?2.1), CAT (12.17?±?3.38 vs. 18.7?±?2.66), and SOD (0.78?±?0.67 vs. 2.41?±?0.46). In contrast, PAO treatment significantly decreased MDA (54.59?±?12.54 vs. 69.92?±?3.92) and increased GSH (4.5?±?0.89 vs. 2.57?±?0.40), GPx (25.86?±?5.37 vs. 11.66?±?2.2), CAT (22.69?±?0.36 vs. 12.17?±?3.38), and SOD (3.65?±?1.08 vs. 0.78?±?0.67) (p?<?0.05). Moreover, our results indicated that both GPx and CAT mRNA levels significantly increased approximately 4.46 and 6.23 times in rats fed with 200?mg/kg of PAO, more than that of the healthy control group, respectively (p?<?0.01 and p?<?0.001, respectively). Also, the average expression level of SOD was also significantly 1.57 higher in rats fed with 200?mg/kg of PAO in comparison to the diabetic control group (p?<?0.05).

Conclusion: The results indicated that PAO could be propose as an agent that protects the body against diseases that are associated with oxidative stress.     

Genome‐wide single nucleotide polymorphism‐based autozygosity mapping facilitates identification of mutations in consanguineous families with epidermolysis bullosa

Autozygosity mapping (AM) is a technique utilised for mapping homozygous autosomal recessive (AR) traits and facilitation of genetic diagnosis. We investigated the utility of AM for the molecular diagnosis of heterogeneous AR disorders, using epidermolysis bullosa (EB) as a paradigm. We applied this technique to a cohort of 46 distinct EB families using both short tandem repeat (STR) and genome‐wide single nucleotide polymorphism (SNP) array‐based AM to guide targeted Sanger sequencing of EB candidate genes. Initially, 39 of the 46 cases were diagnosed with homozygous mutations using this method. Independently, 26 cases, including the seven initially unresolved cases, were analysed with an EB‐targeted next‐generation sequencing (NGS) panel. NGS identified mutations in five additional cases, initially undiagnosed due to the presence of compound heterozygosity, deep intronic mutations or runs of homozygosity below the set threshold of 2 Mb, for a total yield of 44 of 46 cases (95.7%) diagnosed genetically.     

Synthesis and docking studies of N-(5-(alkylthio)-1,3,4-oxadiazol-2-yl)methyl)benzamide analogues as potential alkaline phosphatase inhibitors

A series of N-(5-(alkylthio)-1,3,4-oxadiazol-2-yl)methyl)benzamides 6a–i were synthesized as alkaline phosphatase inhibitors. The intermediate 5-substituted 1,3,4-oxadiazole-2-thione 4 was synthesized starting with hippuric acid. Hippuric acid in the first step was converted into corresponding methyl ester 2 which upon reaction with hydrazine hydrate furnished the formation of hydrazide 3 . The hippuric acid hydrazide was then cyclized into 5-substituted 1,3,4-oxadiazole-2-thione 4 . The intermediate 4 was then reacted with alkyl or aryl halides 5a–5i to afford the title compounds N-(5-(methylthio)-1,3,4-oxadiazol-2-yl)methyl)benzamides 6a–i . The bioassay results showed that compounds 6a–i exhibited good to excellent alkaline phosphatase inhibitory activity. The most potent activity was exhibited by the compound 6i having IC₅₀ value 0.420 μM, whereas IC₅₀ value of standard (KH₂PO₄) was 2.80 μM. Molecular docking studies was performed against alkaline phosphatase enzyme (PDBID 1EW2) to check binding affinity of the synthesized compounds 6a–i against target protein. The docking results showed that three compounds 6c , 6e , and 6i have maximum binding interactions with binding energy values of −8 kcal/mol. The compound 6i displayed the interactions of oxadiazole ring nitrogen with amino acid His265 having a binding distance 2.13 Ǻ. It was concluded from our results that synthesized compounds, especially compound 6i may serve as lead structure to design more potent inhibitors of human alkaline phosphatase.     

Oxyhemoglobin changes in the prefrontal cortex in response to cognitive tasks: a systematic review

Purpose of the study: the aim of this study was to synthesize PFC fNIRS outcomes on the effects of cognitive tasks compared to resting/baseline tasks in healthy adults from studies utilizing a pre/post design.

Material and methods: original research studies were searched from seven databases (MEDLINE, EMBASE, CENTRAL, CINAHL, SCOPUS, PEDro and PubMed). Subsequently, two independent reviewers screened the titles and abstracts followed by full-text reviews to assess the studies' eligibility.

Results: eleven studies met the inclusion criteria and had data abstracted and quality assessed. Methodology varied considerably and yet cognitive tasks resulted in the ΔO₂Hb increasing in 8 of the 11 and ΔHHb decreasing in 8 of 8 studies that reported this outcome. The cognitive tasks from 10 of the 11 studies were classified as “Working Memory” and “Verbal Fluency Tasks”.

Conclusions: although, the data comparison was challenging provided the heterogeneity in methodology, the results across studies were similar.     

Evaluation of Nestin and EGFR in Patients with Glioblastoma Multiforme in a Public Hospital in Iran

Introduction: Glioblastoma multiforme (GBM) is a grade IV glioma and accounts for 15% of all primary brain tumors. This GBM has a median survival range of less than 2 years after diagnosis and it is highly vascularized by neoformed vessels. Neoangiogenesis is a crucial factor in the malignant tumoral behavior and prognosis of patients and Nestin protein belongs to class VI which is expressed in endothelial cells of neoformed vessels in GBM. Our study shows the correlation between EGFR mutation and Nestin expression in endothelial of neoformed vessels in GBM. Methods: We analyzed 40 GBM samples by immunohistochemistry staining. The immunohistochemical expression of EGFR in tumoral cells and Nestin in endothelial cells in paraffin sections were analyzed. EGFR scoring was the based on staining intensity. Score 0 shows No staining, Score1, mild to moderate staining and score2 sever staining. Microvascular density (MVD) was evaluated with Nestin-immunoreactive. Results: The mean of MVD was 14.6 ±8.25. Nestin-MVD was significantly higher in GBM with sever vascular prolifration (p-value=0.01). EGFR was expressed in 92.5% of samples. The EGFR scoring for tumoral tissue was 7.5%(score:0), 22.5% (score:1) and 70% (score:2). There was a significant relationship between EGFR expression and MVD (p-value=0.017). Conclusion: We suggest that some important mutations as like as EGFR in GBM is responsible for inducing angiogenesis and vascular proliferation. Nestin overexpression as a novel marker might reflect the extent of neoangiogenesis, thus target therapy against EGFR pathway and anti angiogenic may be useful for GBM treatment.