Comparative in-vitro activity of new quinolones against clinical isolates and resistant mutants

The in-vitro activity of five new fluoroquinolones, WIN 57273, sparfloxacin, flerox-acin, temafloxacin and tiprofloxacin was determined against 543 recent clinical isolates and eight quinolone resistant strains derived by mutation and their five parent strains. WIN 57273 was the most active compound against Gram-positive bacteria, sparfloxacin had a broad spectrum which was similar to that of cipro-floxacin. Ciprofloxacin showed the greatest activity against Gram-negative bacteria. Temafloxacin showing some activity against Gram-positive organisms and Acinetobacter spp. Fleroxacin was the least active compound studied. Compared to wild type parent strains, the mutated strains produced the following results. In Enterobacter cloacae OmpF deficiency increased the MICs of all quinolones by 8-32-fold. In Pseudomonas aeruginosa OmpF deficiency had a limited effect, Omp D2 deficiency combined with an increased lipopolysaccharide content produced greater resistance, i.e. 4-16-fold; mutations in gyrase were associated with variously increased MICs, depending on the strain and compound teste

A Systematic Review and Metaanalysis on the Effects of Garlic Preparations on Blood Pressure in Individuals With Hypertension

BACKGROUND Many patients prefer herbal medications to conventional drugs. Limited trial evidence suggests that garlic preparations reduce high blood pressure (BP). METHODS We searched electronic databases through March 2014 to identify all randomized controlled trials that compared a garlic preparation to placebo in hypertensive patients. Trials were required to report BP values at baseline and after a follow-up of at least 4 weeks. RESULTS Nine double-blind trials with 482 individuals fulfilled our inclusion criteria. Included trials were rather small, and the quality of the majority of included trials was moderate. Follow-up ranged from 8 to 26 weeks. All trials reported office BP measurements. Systolic BP and diastolic BP (SBP and DBP) were more effectively reduced in individuals treated with garlic preparations than in individuals treated with placebo. However, heterogeneity was high (weighted mean difference (WMD) for SBP was −9.1mm Hg; 95% confidence interval (CI), −12.7 to −5.4; P for heterogeneity = 0.0006; and I 2 = 71%; WMD for BP was −3.8mm Hg; 95% CI, −6.7 to −1.0; P for heterogeneity = 0.00001; I 2 = 80%). When analyses were restricted to higher-quality trials using intention-to-treat analysis or to trials with concealed treatment allocation and standardized and blinded BP measurement, effect sizes for SBP but not for DBP were lower and heterogeneity disappeared. CONCLUSIONS Although evidence from this review suggests that garlic preparations may lower BP in hypertensive individuals, the evidence is not strong. A well-conducted and powered trial of longer duration is needed to confirm these finding

Cryptic Variation in Morphological Evolution: HSP90 as a Capacitor for Loss of Eyes in Cavefish

In the process of morphological evolution, the extent to which cryptic, preexisting variation provides a substrate for natural selection has been controversial. We provide evidence that heat shock protein 90 (HSP90) phenotypically masks standing eye-size variation in surface populations of the cavefish Astyanax mexicanus. This variation is exposed by HSP90 inhibition and can be selected for, ultimately yielding a reduced-eye phenotype even in the presence of full HSP90 activity. Raising surface fish under conditions found in caves taxes the HSP90 system, unmasking the same phenotypic variation as does direct inhibition of HSP90. These results suggest that cryptic variation played a role in the evolution of eye loss in cavefish and provide the first evidence for HSP90 as a capacitor for morphological evolution in a natural setting

Fetal cardiac cine magnetic resonance imaging in utero.

Fast magnetic resonance imaging (MRI) led to the emergence of 'cine MRI' techniques, which enable the visualization of the beating heart and the assessment of cardiac morphology and dynamics. However, established cine MRI methods are not suitable for fetal heart imaging in utero, where anatomical structures are considerably smaller and recording an electrocardiogram signal for synchronizing MRI data acquisition is difficult. Here we present a framework to overcome these challenges. We use methods for image acquisition and reconstruction that robustly produce images with sufficient spatial and temporal resolution to detect the heart contractions of the fetus, enabling a retrospective gating of the images and thus the generation of images of the beating heart. To underline the potential of our approach, we acquired in utero images in six pregnant patients and compared these with their echocardiograms. We found good agreement in terms of diameter and area measurements, and low inter- and intra- observer variability. These results establish MRI as a reliable modality for fetal cardiac imaging, with a substantial potential for prenatal evaluation of congenital heart defects

Interleukin-1 receptor antagonist is upregulated during diet-induced obesity and regulates insulin sensitivity in rodents

Aims/hypothesis: The IL-1 receptor antagonist (IL-1Ra) is an anti-inflammatory cytokine known to antagonise the actions of IL-1. We have previously shown that IL-1Ra is markedly upregulated in the serum of obese patients, is correlated with BMI and insulin resistance, and is overexpressed in the white adipose tissue (WAT) of obese humans. The aim of this study was to examine the role of IL-1Ra in the regulation of glucose homeostasis in rodents. Methods: We assessed the expression of genes related to IL-1 signalling in the WAT of mice fed a high-fat diet, as well as the effect of Il1rn (the gene for IL-1Ra) deletion and treatment with IL-1Ra on glucose homeostasis in rodents. Results: We show that the expression of Il1rn and the gene encoding the inhibitory type II IL-1 receptor was upregulated in diet-induced obesity. The blood insulin:glucose ratio was significantly lower in Il1rn −/− animals, which is compatible with an increased sensitivity to insulin, reinforced by the fact that the insulin content and pancreatic islet morphology of Il1rn −/− animals were normal. In contrast, the administration of IL-1Ra to normal rats for 5days led to a decrease in the whole-body glucose disposal due to a selective decrease in muscle-specific glucose uptake. Conclusions/interpretation: The expression of genes encoding inhibitors of IL-1 signalling is upregulated in the WAT of mice with diet-induced obesity, and IL-1Ra reduces insulin sensitivity in rats through a muscle-specific decrease in glucose uptake. These results suggest that the markedly increased levels of IL-1Ra in human obesity might contribute to the development of insulin resistanc

The potential of food fortification to add micronutrients in young children and women of reproductive age - findings from a cross-sectional survey in Abidjan, Côte d'Ivoire

Poor micronutrient intakes are a major contributing factor to the high burden of micronutrient deficiencies in Côte d'Ivoire. Large-scale food fortification is considered a cost-effective approach to deliver micronutrients, and fortification of salt (iodine), wheat flour (iron and folic acid), and vegetable oil (vitamin A) is mandatory in Côte d'Ivoire. A cross-sectional survey on households with at least one child 6-23 months was conducted to update coverage figures with adequately fortified food vehicles in Abidjan, the capital of and largest urban community in Côte d'Ivoire, and to evaluate whether additional iron and vitamin A intake is sufficient to bear the potential to reduce micronutrient malnutrition. Information on demographics and food consumption was collected, along with samples of salt and oil. Wheat flour was sampled from bakeries and retailers residing in the selected clusters. In Abidjan, 86% and 97% of salt and vegetable oil samples, respectively, were adequately fortified, while only 32% of wheat flour samples were adequately fortified, but all samples contained some added iron. There were no major differences in additional vitamin A and iron intake between poor and non-poor households. For vitamin A in oil, the additional percentage of the recommended nutrient intake was 27% and 40% for children 6-23 months and women of reproductive age, respectively, while for iron from wheat flour, only 13% and 19% could be covered. Compared to previous estimates, coverage has remained stable for salt and wheat flour, but improved for vegetable oil. Fortification of vegetable oil clearly provides a meaningful additional amount of vitamin A. This is not currently the case for iron, due to the low fortification levels. Iron levels in wheat flour should be increased and monitored, and additional vehicles should be explored to add iron to the Ivorian diet

High awareness butlow coverage of a locally produced fortified complementary food in Abidjan, Côte d'Ivoire : findings from a cross-sectional survey

Poor complementary feeding practices among infants and young children in Côte d'Ivoire are major contributing factors to the country's high burden of malnutrition. As part of a broad effort to address this issue, an affordable, nutritious, and locally produced fortified complementary food product was launched in the Côte d'Ivoire in 2011. The objective of the current research was to assess various levels of coverage of the program and to identify coverage barriers. A cross-sectional household survey was conducted among caregivers of children less than 2-years of age living in Abidjan, Côte d'Ivoire. Four measures of coverage were assessed: "message coverage" (i.e., has the caregiver ever heard of the product?), "contact coverage" (i.e., has the caregiver ever fed the child the product?), "partial coverage" (i.e., has the caregiver fed the child the product in the previous month?), and "effective coverage" (i.e., has the caregiver fed the child the product in the previous 7 days?). A total of 1,113 caregivers with children between 0 and 23 months of age were interviewed. Results showed high message coverage (85.0%), moderate contact coverage (37.8%), and poor partial and effective coverages (8.8% and 4.6%, respectively). Product awareness was lower among caregivers from poorer households, but partial and effective coverages were comparable in both poor and non-poor groups. Infant and young child feeding (IYCF) practices were generally poor and did not appear to have improved since previous assessments. In conclusion, the results from the present study indicate that availability on the market and high awareness among the target population is not sufficient to achieve high and effective coverage. With market-based delivery models, significant efforts are needed to improve demand. Moreover, given the high prevalence of malnutrition and poor IYCF practices, additional modes of delivering IYCF interventions and improving IYCF practices should be considered

Cervical cancer screening cascade for women living with HIV: a cohort study from Zimbabwe

Countries with high HIV prevalence, predominantly in sub-Sahahran Africa, have the highest cervical cancer rates globally. HIV care cascades successfully facilitated the scale-up of antiretroviral therapy. A cascade approach could similarly succeed to scale-up cervical cancer screening, supporting WHO's goal to eliminate cervical cancer. We defined a Cervical Cancer Screening Cascade for women living with HIV (WLHIV), evaluating the continuum of cervical cancer screening integrated into an HIV clinic in Zimbabwe. We included WLHIV aged ≥18 years enrolled at Newlands Clinic in Harare from June 2012-2017 and followed them until June 2018. We used a cascade approach to evaluate the full continuum of secondary prevention from screening to treatment of pre-cancer and follow-up. We report percentages, median time to reach cascade stages, and cumulative incidence at two years with 95% confidence intervals (CI). We used univariable Cox proportional hazard regressions to calculate cause-specific hazard ratios with 95% CIs for factors associated with completing the cascade stages. We included 1624 WLHIV in the study. The cumulative incidence of cervical screening was 85.4% (95% CI 83.5-87.1) at two years. Among the 396 WLHIV who received screen-positive tests in the study, the cumulative incidence of treatment after a positive screening test was 79.5% (95% CI 75.1-83.2) at two years. The cumulative incidence of testing negative at re-screening after treatment was 36.1% (95% CI 31.2-40.7) at two years. Using a cascade approach to evaluate the full continuum of cervical cancer screening, we found less-than 80% of WLHIV received treatment after screen-positive tests and less-than 40% were screen-negative at follow-up. Interventions to improve linkage to treatment for screen-positive WLHIV and studies to understand the clinical significance of screen-positive tests at follow-up among WLHIV are needed. These gaps in the continuum of care must be addressed in order to prevent cervical cancer

Overfeeding, Autonomic Regulation and Metabolic Consequences

The autonomic nervous system plays an important role in the regulation of body processes in health and disease. Overfeeding and obesity (a disproportional increase of the fat mass of the body) are often accompanied by alterations in both sympathetic and parasympathetic autonomic functions. The overfeeding-induced changes in autonomic outflow occur with typical symptoms such as adiposity and hyperinsulinemia. There might be a causal relationship between autonomic disturbances and the consequences of overfeeding and obesity. Therefore studies were designed to investigate autonomic functioning in experimentally and genetically hyperphagic rats. Special emphasis was given to the processes that are involved in the regulation of peripheral energy substrate homeostasis. The data revealed that overfeeding is accompanied by increased parasympathetic outflow. Typical indices of vagal activity (such as the cephalic insulin release during food ingestion) were increased in all our rat models for hyperphagia. Overfeeding was also accompanied by increased sympathetic tone, reflected by enhanced baseline plasma norepinephrine (NE) levels in both VMH-lesioned animals and rats rendered obese by hyperalimentation. Plasma levels of NE during exercise were, however, reduced in these two groups of animals. This diminished increase in the exercise-induced NE outflow could be normalized by prior food deprivation. It was concluded from these experiments that overfeeding is associated with increased parasympathetic and sympathetic tone. In models for hyperphagia that display a continuously elevated nutrient intake such as the VMH-lesioned and the overfed rat, this increased sympathetic tone was accompanied by a diminished NE response to exercise. This attenuated outflow of NE was directly related to the size of the fat reserves, indicating that the feedback mechanism from the periphery to the central nervous system is altered in the overfed state.