Fatty liver index as an indicator of metabolic syndrome

ObjectiveThe aim of this study was to find an early indicator of metabolic syndrome (MetS).Design and methodsWe measured several anthropometric, biochemical, haematological, and oxidative damage parameters in 128 middle-aged Caucasian men divided into two groups: patients with MetS (n = 69) and healthy controls (n = 59), and used Weka REPTree and SimpleCART algorithms to identify the most reliable predictor of MetS.ResultsOxidative damage parameters did not differ between the groups, suggesting that oxidative damage is less prominent at the early stage of MetS. The algorithms singled out fatty liver index (FLI) as the best variable for discriminating between healthy and MetS subjects. This finding was confirmed by the receiver–operating characteristic (ROC) curve analysis, which set FLI 68.53 as the threshold value for MetS diagnosis.ConclusionsFLI is the most reliable tool for diagnosing MetS. The absence of oxidative damage does not rule out oxidative stress but may indicate that MetS is at an early stage.     

Measles and rubella eradication in the Americas

The challenge for regions embarking on measles elimination will be to maintain high population immunity with excellent vaccination coverage and high-quality surveillance. Meeting this challenge will be especially critical for dealing with importations of measles virus that will occur as long as the virus is circulating anywhere in the world. Implementation of measles elimination strategies will uncover the "hidden" disease burden of rubella and congenital rubella syndrome. As was the experience in countries of Latin America and the Caribbean (LAC), integrating the elimination of measles with the elimination of rubella will greatly enhance the capacity of countries to sustain progress in the reduction of measles mortality. Countries of LAC prioritized the routine national immunization program over short-term successes. While doing so, they have also encountered new opportunities to expand the benefits of disease control and elimination activities to other aspects of public health, most importantly towards improving health care for women and newborns and reducing inequities in health in the region's poorest communities. Implementation of similar strategies could lead to the global eradication of measles, rubella, and congenital rubella syndrome early this century, while strengthening routine immunization programs, and developing the capacity to introduce new and underutilized vaccines.     

Von Willebrand disease in children: diagnosis and management of a pediatric cohort in one single center in Argentina

Clinical and laboratory data of children with von Willebrand disease (VWD) types have been derived from retrospective studies and small case series. This article reports on the clinical and laboratory data of a large pediatric cohort in one single Argentinian center. The biological and clinical responses to desmopressin and replacement therapies are also described. Over a 15-year period, 194 of 1150 children (16.9%) were diagnosed as having type 1 VWD (80%), type 2 VWD (19%), and type 3 VWD (1%). The distribution of the different type 2 VWD subtypes was type 2A VWD, 43%; type 2B VWD, 32%; type 2M VWD, 19%; and type 2N VWD, 6%. Eighty patients with type 1 VWD and 12 patients with type 2 VWD were prospectively evaluated to desmopressin (DDAVP) response. A complete response was observed in all children with type 1 VWD, whereas 40% of the children with severe type 1 VWD and with type 2 VWD achieved a complete response. All the children who received DDAVP as prophylaxis or treatment for bleeding had good clinical evolution. Considering the restricted availability of specialized hemostasis centers, we believe our clinical and laboratory approach appropriate for the detection of patients with different types of VWD. Further studies are necessary to determine epidemiological aspects of VWD in Argentina to estimate the necessary facilities and trained personnel for the diagnosis and management of patients with VWD.     

Growth hormone secretagogue receptor signalling affects high‐fat intake independently of plasma levels of ghrelin and LEAP2, in a 4‐day binge eating model

The growth hormone secretagogue receptor (GHSR) is a G protein‐coupled receptor that is highly expressed in the central nervous system. GHSR acts as a receptor for ghrelin and for liver‐expressed antimicrobial peptide 2 (LEAP2), which blocks ghrelin‐evoked activity. GHSR also displays ligand‐independent activity, including a high constitutive activity that signals in the absence of ghrelin and is reduced by LEAP2. GHSR activity modulates a variety of food intake‐related behaviours, including binge eating. Previously, we reported that GHSR‐deficient mice daily and time‐limited exposed to a high‐fat (HF) diet display an attenuated binge‐like HF intake compared to wild‐type mice. In the present study, we aimed to determine whether ligand‐independent GHSR activity affects binge‐like HF intake in a 4‐day binge‐like eating protocol. We found that plasma levels of ghrelin and LEAP2 were not modified in mice exposed to this binge‐like eating protocol. Moreover, systemic administration of ghrelin or LEAP2 did not alter HF intake in our experimental conditions. Interestingly, we found that central administration of LEAP2 or K‐(D‐1‐Nal)‐FwLL‐NH₂, which are both blockers of constitutive GHSR activity, reduced binge‐like HF intake, whereas central administration of ghrelin or the ghrelin‐evoked GHSR activity blockers [D‐Lys3]‐GHRP‐6 and JMV2959 did not modify binge‐like HF intake. Taken together, current data indicate that GHSR activity in the brain affects binge‐like HF intake in mice independently of plasma levels of ghrelin and LEAP2.     

Effects of a 3-Week Hospital-Controlled Very-Low-Calorie Diet in Severely Obese Patients

Although a very-low-calorie diet (VLCD) is considered safe and has demonstrated benefits among other types of diets, data are scarce concerning its effects on improving health and weight loss in severely obese patients. As part of the personalized weight loss program developed at the Duga Resa Special Hospital for Extended Treatment, Croatia, we evaluated anthropometric, biochemical, and permanent DNA damage parameters (assessed with the cytochalasin B-blocked micronucleus cytome assay—CBMN) in severely obese patients (BMI ≥ 35 kg m⁻²) after 3-weeks on a 567 kcal, hospital-controlled VLCD. This is the first study on the permanent genomic (in)stability in such VLCD patients. VLCDs caused significant decreases in weight (loss), parameters of the lipid profile, urea, insulin resistance, and reduced glutathione (GSH). Genomic instability parameters were lowered by half, reaching reference values usually found in the healthy population. A correlation was found between GSH decrease and reduced DNA damage. VLCDs revealed susceptible individuals with remaining higher DNA damage for further monitoring. In a highly heterogeneous group (class II and III in obesity, differences in weight, BMI, and other categories) consisting of 26 obese patients, the approach demonstrated its usefulness and benefits in health improvement, enabling an individual approach to further monitoring, diagnosis, treatment, and risk assessment based on changing anthropometric/biochemical VLCD parameters, and CBMN results.     

Mapping the brain network of the phonological loop

The cortical and subcortical neural correlates underlying item and order information in verbal short‐term memory (STM) were investigated by means of digit span in 29 patients with direct electrical stimulation during awake surgery for removal of a neoplastic lesion. Stimulation of left Broca's area interfered with span, producing significantly more item than order errors, as compared to the stimulation of the supramarginal/angular gyrus, which also interfered with span but, conversely, produced more order than item errors. Similarly, stimulation of the third segment of the left superior longitudinal fasciculus (SLF ‐ III), also known as anterior segment of the arcuate fascicle (AF), produced more order than item errors. Therefore, we obtained two crucial results: first, we were able to distinguish between content and order information storage. Second, we demonstrated that the SLF‐III is involved in transferring order information from Geschwind's area to Broca's area. In a few patients, we demonstrated that also order information of nonverbal material was disrupted by left supramarginal gyrus stimulation. Order information is thus likely stored in the supramarginal gyrus, possibly independently from the nature of the material. Hum Brain Mapp 38:3011–3024, 2017. © 2017 Wiley Periodicals, Inc.     

Daily Vegetables Intake and Response to COPD Rehabilitation. The Role of Oxidative Stress,Inflammation and DNA Damage

Chronic obstructive pulmonary disease (COPD) is a respiratory disease associated with airways inflammation and lung parenchyma fibrosis. The primary goals of COPD treatment are to reduce symptoms and risk of exacerbations, therefore pulmonary rehabilitation is considered the key component of managing COPD patients. Oxidative airway damage, inflammation and reduction of endogenous antioxidant enzymes are known to play a crucial role in the pathogenesis of COPD. Recently, also natural antioxidants have been considered as they play an important role in metabolism, DNA repair and fighting the effects of oxidative stress. In this paper we evaluated the response of 105 elderly COPD patients to pulmonary rehabilitation (PR), based on high or low vegetable consumption, by analyzing clinical parameters and biological measurements at baseline and after completion of the three weeks PR. We found that daily vegetable intake in normal diet, without any specific intervention, can increase the probability to successfully respond to rehabilitation (65.4% of responders ate vegetables daily vs. 40.0% of non-responders, p = 0.033). The association was especially evident in subjects ≥ 80 year of age (OR = 17.0; p < 0.019). Three weeks of pulmonary rehabilitation are probably too short to reveal a reduction of the oxidative stress and DNA damage, but are enough to show an improvement in the patient’s inflammatory state.     

Inhibition of Junin virus RNA synthesis by an antiviral acridone derivative

There are no specific approved drugs for the treatment of agents of viral hemorrhagic fevers (HF) and antiviral therapies against these viruses are urgently needed. The present study characterizes the potent and selective antiviral activity against the HF causing arenavirus Junin virus (JUNV) of the compound 10-allyl-6-chloro-4-methoxy-9(10H)-acridone, designated 3f. The effectiveness of 3f to inhibit JUNV multiplication was not importantly affected by the initial multiplicity of infection, with similar effective concentration 50% (EC₅₀) values in virus yield inhibition assays performed in Vero cells in the range of 0.2-40 plaque forming units (PFU)/cell. Mechanistic studies demonstrated that 3f did not affect the initial steps of adsorption and internalization. The subsequent process of viral RNA synthesis was strongly inhibited, as quantified by real time RT-PCR in compound-treated cells relative to non-treated cells. The addition of exogenous guanosine rescued the infectivity and RNA synthesis of JUNV in 3f-treated cells in a dose-dependent manner, but the reversal was partial, suggesting that the reduction of the GTP pool contributed to the antiviral activity of 3f, but it was not the main operative mechanism. The comparison of 3f with two other viral RNA inhibitors, ribavirin and mycophenolic acid, showed that ribavirin did not act against JUNV through the cellular enzyme inosine monophosphate dehydrogenase (IMPDH) inhibition whereas the anti-JUNV activity of mycophenolic acid was mainly targeted at this enzyme.