A systematic review and meta-analysis on the antibiotic resistance of Neisseria meningitidis in the last 20 years in the world

BackgroundNeisseria meningitidis is one of the most important causes of meningitis and pathogens-associated deaths in developing and developed countries. Effective anti-microbial agents are pivotal to treat and control N. meningitidis infections. The aim of the present study was to systematically review published studies on the antibiotic resistance of N. meningitidis in the last 20 years (2000–2020) in the world.MethodsPublished researches were identified through a literature search using reputable databases including PubMed, Scopus, and Web of Science. Finally, 24 studies were included for a random-effects model meta-analysis.ResultsThe overall resistance to most commonly used antibiotics such as ceftriaxone, cefotaxime, ciprofloxacin and rifampin was low, ranging from 1 to 3.4%. However, non-sensitivity to penicillin, as the first-line antibiotic against N. meningitidis, was higher (27.2%). Altogether, the resistance to the first-line antibiotics (except penicillin) is still low indicating these drugs are effective against meningococcal meningitis. We also found a significant gap between MIC and disk diffusion for evaluating resistance to antibiotics in which disk diffusion overestimate the resistance rate.ConclusionsTo properly management and prevent the spread of N. miningitidis isolates resistant antibiotics, it is necessary to monitor the pattern of antibiotic susceptibility regionally and globally using the MIC methods.     

In vitro cytotoxic effect of garlic extract on malignant and nonmalignant cell lines

Cancer is one of the major causes of death in the world and despite many years of research, the treatment of cancer is still a problem. Epidemiological observations and laboratory studies have indicated anticarcinogenic potential of garlic, which has been traditionally used for various human diseases around the world. In this study the cytotoxicity of garlic extract against three malignant cancer cell lines including gastric (AGS), breast (MCF-7) and colon (HT-29) and a nonmalignant cell line (L929) were evaluated by the MTT assay. The results of this study reveal MCF-7 and AGS cells were sensitive to garlic extract. Despite a many reports on inhibitory effects of garlic on cancer cell line, our data showed these effects are tumor specific and dose dependent. Further studies on animal models and humans are needed to clarify the important molecules and their mechanisms.     

Determination of Conversion Coefficient to Evaluate Couple-year of Protection （CYP） for Tubectomy and Vasectomy in Urban and Rural Regions of Iran： IMES Study

Objective To calculate couple-year of protection （CYP） by conversion coefficient （F） of tubectomy and vasectomy in urban and rural regions of Iran. Methods A total of 103 450 married women aged 10-49 years in 2005 across urban and rural regions of lran were sampled by multi stage cluster sampling. The data were collected by household survey and direct interview and analyzed by STATA8.0 software and survey analysis commands. Results Mean age of the women at the time of tubectomy estimated 31.9 years and conversion coefficient of tubectomy was 17.1 ±0.1. Mean age of women at the time of her husband vasectomy estimated 31.48 years and its conversion coefficient was 17. 5 ± 0. 1. Cluster analysis defined different regions of Iran on the basis of evaluated conversion coefficients of tubectomy and vasectomy which both of them presented seven clusters. Literacy of women and total coverage of family planning in a region had a direct relationship with this conversion coefficient （P〈0.05）. Conclusion The variations observed in the conversion coefficients and their dissimilarity among different regions of Iran may be due to a variety of fundamental factors of which literacy and culture are of important factors.     

Integrin alpha 11 regulates IGF2 expression in fibroblasts to enhance tumorigenicity of human non-small-cell lung cancer cells

Integrin alpha11 (ITGA11/alpha11) is localized to stromal fibroblasts and commonly overexpressed in non-small-cell lung carcinoma (NSCLC). We hypothesized that stromal alpha11 could be important for the tumorigenicity of NSCLC cells. SV40 immortalized mouse embryonic fibroblasts established from wild-type (WT) and Itga11-deficient [knockout (KO)] mice were tested for their tumorigenicity in immune-deficient mice when implanted alone or coimplanted with the A549 human lung adenocarcinoma cells. A549 coimplanted with the fibroblasts showed a markedly enhanced tumor growth rate compared with A549, WT, or KO, which alone formed only small tumors. Importantly, the growth was significantly greater for A549+WT compared with A549+KO tumors. Reexpression of human alpha11 cDNA in KO cells rescued a tumor growth rate to that comparable with the A549+WT tumors. These findings were validated in two other NSCLC cell lines, NCI-H460 and NCI-H520. Gene expression profiling indicated that IGF2 mRNA expression level was >200 times lower in A549+KO compared with A549+WT tumors. Stable short-hairpin RNA (shRNA) down-regulation of IGF2 in WT (WT(shIGF2)) fibroblasts resulted in a decreased growth rate of A549+WT(shIGF2), compared with A549+WT tumors. The results indicate that alpha11 is an important stromal factor in NSCLC and propose a paradigm for carcinoma-stromal interaction indirectly through interaction between the matrix collagen and stromal fibroblasts to stimulate cancer cell growth.     

The Ross operation: clinical results and echocardiographic findings

Between November 2001 and September 2004, 80 patients aged 11 to 56 years (mean, 27.6 years) underwent the Ross operation. The mean preoperative New York Heart Association functional class was 2.37 +/- 0.72, and the mean ejection fraction was 52.8% +/- 16%. Aortic involvement included stenosis in 19 (24%) patients, regurgitation in 22 (28%), and both in 39 (49%). Root replacement was the technique used in all cases. The mean hospital stay was 5 days, and 74 patients (93%) were followed up for 4-48 months. Four-year actuarial survival rate was 96.25%. Postoperative echocardiography revealed no pulmonary autograft insufficiency in 50 patients (63%), trivial to mild insufficiency in 22 (28%), moderate insufficiency in 2 (3%), and severe insufficiency in one (1%). Two patients required autograft re-intervention. Postoperative echocardiography of the pulmonary homograft valve showed severe stenosis (peak gradient > 50 mm Hg) in 2 patients, and moderate stenosis (peak gradient 25-50 mm Hg) in one. The mean postoperative left ventricular ejection fraction was 51.4%. The Ross operation can be considered an elegant alternative to prosthetic valves in the treatment of aortic valve diseases in developing countries.     

Oral ascorbic acid in combination with beta-blockers is more effective than beta-blockers alone in the prevention of atrial fibrillation after coronary artery bypass grafting

Because adrenergic beta antagonists are not sufficient to prevent atrial fibrillation after coronary artery bypass grafting, this prospective, randomized trial was designed to evaluate the effects of ascorbic acid as an adjunct to beta-blockers. Fifty patients formed our ascorbic acid group, and another 50 patients formed our control group. All patients were older than 50 years, were scheduled to undergo coronary artery bypass grafting, and had been treated with beta-blockers for at least 1 week before surgery. The mean age of the population was 60.19+/-7.14 years; 67% of the patients were men. Patients in the ascorbic acid group received 2 g of ascorbic acid on the night before the surgery and 1 g twice daily for 5 days after surgery. Patients in the control group received no ascorbic acid. Patients in both groups continued to receive beta-blockers after surgery. Telemetry monitoring was performed in the intensive care unit, and Holter monitoring was performed for 4 days thereafter. The incidence of postoperative atrial fibrillation was 4% in the ascorbic acid group and 26% in the control group (odds ratio, 0.119; 95% confidence interval, 0.025-0.558, P = 0.002). We conclude that ascorbic acid is effective, in addition to being well-tolerated and relatively safe. Therefore, it can be prescribed as an adjunct to beta-blockers for the prophylaxis of post-bypass atrial fibrillation.     

Anatomical distribution of 3He apparent diffusion coefficients in severe chronic obstructive pulmonary disease

PURPOSE: To evaluate the anatomical distribution of apparent diffusion coefficients (ADC) using hyperpolarized helium-3 (3He) MRI in chronic obstructive pulmonary disease (COPD). MATERIALS AND METHODS: Hyperpolarized 3He MRI was performed in eight healthy and seven COPD subjects under breathhold conditions in the supine position to determine ADC values from diffusion-weighted images and evaluate anterior-posterior (AP) and superior-inferior (SI) differences. RESULTS: ADC differences between anterior and posterior slices, DeltaAP, was 0.06 +/-0.01 cm2/second for healthy volunteers and 0.04 +/-0.02 cm2/second for COPD subjects and was significant for each subject (P < 0.01). The AP ADC gradient was -3.98 x 10(-3) +/-0.59 cm2/second/cm for healthy volunteers and -2.04 x 10(-3) +/-0.89 cm2/second/cm for COPD subjects. The difference in ADC between superior and inferior regions of interest (ROIs), DeltaSI, was 0.02 +/-0.02 cm2/second for healthy volunteers and 0.10 +/-0.09 cm2/second for COPD subjects, which was significant for each subject (P < 0.05). The SI ADC gradient was -0.63 x 10(-3) +/-2.23 cm2/second/cm for healthy volunteers and -6.61 x 10(-3) +/-6.68 cm2/second/cm for COPD subjects. DeltaAP, AP-gradient, and SI-gradient were significantly different between healthy volunteers and COPD subjects (P < 0.05). CONCLUSION: In all subjects, ADC anatomical differences were significant and mean ADC was dependent on anatomic location and disease status.     

Bortezomib treatment causes remission in a Ph+ALL patient and reveals FoxO as a theranostic marker

BCR-ABL is a key mediator in the pathogenesis of all cases of chronic myelogenous leukemia (CML) and a subset of precursor B-acute lymphoblastic leukemia (Ph+ALL). Previous animal and cell-based studies have shown that the expression of members of the Forkhead family of tumor suppressors, including FoxO3, is suppressed in BCR-ABL-expressing cells. Furthermore, it has been reported that the proteasomal degradation pathway plays an important role in suppression of FoxO expression in BCR-ABL-transformed cells. In this study, a patient diagnosed with Ph+ALL and refractory to standard therapies was treated with a proteasome inhibitor (bortezomib)-based chemotherapy regimen. This treatment resulted in complete hematologic, cytogenetic and molecular remission with excellent performance status for > 4 years since her initial diagnosis. FoxO3 was not detectable within the blasts of this patient at diagnosis and was 'rescued' following treatment with bortezomib therapy, leading to her recovery. As a next step, in the attempt to propose FoXO3 as a therapeutic target and a theranostic marker, we further validated FoxO3 expression in human bone marrow biopsy samples. Human core biopsy samples of Ph+ALL and Ph-negative-negative ALL, along with uninvolved controls, revealed that FoxO3 down-regulation was specific to Ph+ALL. This study provides support that FoxO3 is a good biomarker for BCR-ABL-mediated leukemogenesis. Additionally, proteasomal inhibition by bortezomib may be a promising therapeutic option in Philadelphia-positive ALL, where FoxO3 is downregulated.     

Association of changes in oxidative and proinflammatory states with changes in vascular function after a lifestyle modification trial among obese children

BACKGROUND: The association of changes in oxidative and proinflammatory states with vascular function after diet and exercise intervention among obese children has not been previously explored. METHODS: In this 6-week diet and exercise intervention study in 35 obese children, age 12 to 18 years, we evaluated the relationship between changes in anthropometric indices, measures of insulin resistance, C-reactive protein (CRP), oxidized LDL (ox-LDL), and oxidative stress markers with changes in carotid intima-media thickness (C-IMT) and flow mediated dilation (FMD) of the brachial artery. RESULTS: At the end of the study, body mass index (BMI), waist circumference, and percentage body fat were decreased (P <0.05), but participants remained overweight (BMI > or = 95th percentile). Although FMD improved (P <0.05), the improvement in C-IMT did not reach statistical significance. The changes in BMI, waist circumference, fat mass, ox-LDL, malondialdehyde (MDA), CRP, insulin, and homeostasis model assessment for insulin resistance (HOMA-IR) had an inverse correlation with the changes in mean FMD after adjustment for age and sex, with the highest correlations documented for ox-LDL, CRP, and WC. The age- and sex-adjusted changes in ox-LDL, waist circumference, CRP, MDA, and body fat mass had the highest correlations with changes in C-IMT. CONCLUSIONS: Our findings suggest that a common inflammatory stress condition associated with childhood obesity, notably with abdominal fat deposition, may play a role in the development of the earliest stages of proatherosclerotic inflammatory processes and subsequent vascular dysfunction. These changes might be partially reversible by short-term diet and exercise intervention, even if patients do not reach ideal body weight.