Very-low-calorie ketogenic diet (VLCKD) in the management of metabolic diseases: systematic review and consensus statement from the Italian Society of Endocrinology (SIE).

BACKGROUND: Weight loss is a milestone in the prevention of chronic diseases associated with high morbility and mortality in industrialized countries. Very-low calorie ketogenic diets (VLCKDs) are increasingly used in clinical practice for weight loss and management of obesity-related comorbidities. Despite evidence on the clinical benefits of VLCKDs is rapidly emerging, some concern still exists about their potential risks and their use in the long-term, due to paucity of clinical studies. Notably, there is an important lack of guidelines on this topic, and the use and implementation of VLCKDs occurs vastly in the absence of clear evidence-based indications. PURPOSE: We describe here the biochemistry, benefits and risks of VLCKDs, and provide recommendations on the correct use of this therapeutic approach for weight loss and management of metabolic diseases at different stages of life.

Psychological predictors of the combined adoption of physical exercise and dietary change among adults with hypercholesterolemia.

BACKGROUND: Although combined changes in eating habits and physical activity are pivotal to hypercholesterolemia management and the prevention of cardiovascular disease, little is known about the factors influencing the adoption of both behaviors by adults with hypercholesterolemia. The goal of this study was to identify psychological factors that predict a combined adoption of dietary modification and physical activity among adults with hypercholesterolemia. METHODS: We recruited a sample of 1100 adults with hypercholesterolemia (56.9% male, mean age=56.5 years) through a nationally representative online panel. Participants reported their physical activity using the International Physical Activity Questionnaire (IPAQ) and their eating habits using a Food-Frequency Questionnaire (FFQ). We assessed a comprehensive set of psychological variables, including hypercholesterolemia knowledge and perception, patient's cardiovascular history, doctor-patient relationship, social-cognitive beliefs, and personality traits. Based on IPAQ and FFQ scores, we classified participants into four groups (dietary modification plus physical exercise, dietary modification, physical exercise, passive). RESULTS: Our analysis showed that subjective hypercholesterolemia knowledge, beliefs about the effects of hypercholesterolemia, external locus of control (other people and chance), nutrition and physical exercise self-efficacy, and trait self-control significantly influenced the simultaneous adoption of physical exercise and dietary modification. CONCLUSIONS: This study highlights the importance of psychological factors in predicting the combined adoption of physical exercise and dietary modification among adults with hypercholesterolemia. Addressing these factors could help improve hypercholesterolemia prevention strategies.

Valuing and understanding fish populations in the Anthropocene: key questions to address.

Research on the values of fish populations and fisheries has primarily focused on bio-economic aspects; a more nuanced and multidimensional perspective is mostly neglected. Although a range of social aspects is increasingly being considered in fisheries research, there is still no clear understanding as to how to include these additional values within management policies nor is there a cogent appreciation of the major knowledge gaps that should be tackled by future research. This paper results from a workshop held during the 50th anniversary symposium of the Fisheries Society of the British Isles at the University of Exeter, UK, in July 2017. Here, we aim to highlight the current knowledge gaps on the values of fish populations and fisheries thus directing future research. To this end, we present eight questions that are deeply relevant to understanding the values of fish populations and fisheries. These can be applied to all habitats and fisheries, including freshwater, estuarine and marine.

Real-time kinetic binding studies at attomolar concentrations in solution phase using a single-stage opto-biosensing platform based upon infrared surface plasmons.

Here we present a new generic opto-bio-sensing platform combining immobilised aptamers on an infrared plasmonic sensing device generated by nano-structured thin film that demonstrates amongst the highest index spectral sensitivities of any optical fibre sensor yielding on average 3.4 × 104 nm/RIU in the aqueous index regime (with a figure of merit of 330) This offers a single stage, solution phase, atto-molar detection capability, whilst delivering real-time data for kinetic studies in water-based chemistry. The sensing platform is based upon optical fibre and has the potential to be multiplexed and used in remote sensing applications. As an example of the highly versatile capabilities of aptamer based detection using our platform, purified thrombin is detected down to 50 attomolar concentration using a volume of 1mm3 of solution without the use of any form of enhancement technique. Moreover, the device can detect nanomolar levels of thrombin in a flow cell, in the presence of 4.5% w/v albumin solution. These results are important, covering all concentrations in the human thrombin generation curve, including the problematic initial phase. Finally, selectivity is confirmed using complementary and non-complementary DNA sequences that yield performances similar to those obtained with thrombin.

Sex change and effective population size: implications for population genetic studies in marine fish.

Large variance in reproductive success is the primary factor that reduces effective population size (Ne) in natural populations. In sequentially hermaphroditic (sex-changing) fish, the sex ratio is typically skewed and biased towards the 'first' sex, while reproductive success increases considerably after sex change. Therefore, sex-changing fish populations are theoretically expected to have lower Ne than gonochorists (separate sexes), assuming all other parameters are essentially equal. In this study, we estimate Ne from genetic data collected from two ecologically similar species living along the eastern coast of South Africa: one gonochoristic, the 'santer' sea bream Cheimerius nufar, and one protogynous (female-first) sex changer, the 'slinger' sea bream Chrysoblephus puniceus. For both species, no evidence of genetic structuring, nor significant variation in genetic diversity, was found in the study area. Estimates of contemporary Ne were significantly lower in the protogynous species, but the same pattern was not apparent over historical timescales. Overall, our results show that sequential hermaphroditism may affect Ne differently over varying time frames, and that demographic signatures inferred from genetic markers with different inheritance modes also need to be interpreted cautiously, in relation to sex-changing life histories.

Circulating SIRT1 inversely correlates with epicardial fat thickness in patients with obesity.

BACKGROUND AND AIM: Obesity is increasing worldwide and is related to undesirable cardiovascular outcomes. Epicardial fat (EF), the heart visceral fat depot, increases with obesity and correlates with cardiovascular risk. SIRT1, an enzyme regulating metabolic circuits linked with obesity, has a cardioprotective effect and is a predictor of cardiovascular events. We aimed to assess the relationship of EF thickness (EFT) with circulating SIRT1 in patients with obesity. METHODS AND RESULTS: Sixty-two patients affected by obesity and 23 lean controls were studied. Plasma SIRT1 concentration was determined by enzyme-linked immunosorbent assay (ELISA). EFT was measured by echocardiography. Body mass index (BMI), waist circumference, heart rate (HR), blood pressure, and laboratory findings (fasting glucose, insulin, HbA1c, cholesterol, and triglycerides) were assessed. SIRT1 was significantly lower (P = 0.002) and EFT was higher (P < 0.0001) in patients with obesity compared with lean controls. SIRT1 showed a negative correlation with EFT and HR in the obesity group (ρ = -0.350, P = 0.005; ρ = -0.303, P = 0.008, respectively). After adjustment for obesity-correlated variables, multiple linear regression analysis showed that EFT remained the best correlate of SIRT1 (ß = -0.352, P = 0.016). CONCLUSIONS: Circulating SIRT1 correlates with the visceral fat content of the heart. Serum SIRT1 levels might provide additional information for risk assessment of coronary artery disease in patients with obesity.

Association between sex, systemic iron variation and probability of Parkinson's disease.

OBJECTIVE: Iron homeostasis appears altered in Parkinson's disease (PD). Recent genetic studies and meta-analyses have produced heterogeneous and inconclusive results. In order to verify the possible role of iron status in PD, we have screened some of the main metal gene variants, evaluated their effects on iron systemic status, and checked for possible interactions with PD. MATERIALS AND METHODS: In 92 PD patients and 112 healthy controls, we screened the D544E and R793H variants of the ceruloplasmin gene (CP), the P589S variant of the transferrin gene (TF), and the H63D and C282Y variants of the HFE gene, encoding for homologous proteins, respectively. Furthermore, we analyzed serum concentrations of iron, copper and their related proteins. RESULTS: The genetic investigation revealed no significant differences in allelic and genotype distributions between patients and controls. Two different multivariable forward stepwise logistic models showed that, when the effect of sex is considered, an increase of the probability of having PD is associated with low iron concentration and Tf-saturation. CONCLUSIONS: This study provides new evidence of the involvement of iron metabolism in PD pathogenesis and reveals a biological effect of sex.

The ART of mating: alternative reproductive tactics and mating success in a nest-guarding fish.

Behavioural observations in the field of male Mediterranean damselfish Chromis chromis were combined with molecular analyses, using bi-parentally and maternally inherited markers, to investigate reproductive success patterns of alternative reproductive tactics (ARTs) in terms of number of eggs sired and number of females contributing to each nest. Cuckoldry was observed in every nest sampled, with at least two and up to seven sneaker males per nest. The nesting male, however, always significantly fertilized the greater number of eggs (on average 49%) in each clutch, whereas each sneaker fertilized around 7% of the clutch. The average number of females whose eggs were fertilized by nesting males was 6·76 (range 2-13), while each sneaker on average fertilized the eggs of 1·74 (range 1-8) females. Using this sibship reconstruction, some of the factors involved in the regulation of the dynamic equilibrium of reproductive success were investigated between the two ARTs shown by C. chromis males. Results show that the sneakers' reproductive success was positively linked to egg clutch size; the density of individuals in the nesting area negatively affected the size of egg clutches; the rate of defence behaviours performed by nesting males negatively influenced the number of females contributing to each nest.

Adenovirus 36 DNA in human adipose tissue.

Recent studies have suggested a possible correlation between obesity and adenovirus 36 (Adv36) infection in humans. As information on adenoviral DNA presence in human adipose tissue are limited, we evaluated the presence of Adv36 DNA in adipose tissue of 21 adult overweight or obese patients. Total DNA was extracted from adipose tissue biopsies. Virus detection was performed using PCR protocols with primers against specific Adv36 fiber protein and the viral oncogenic E4orf1 protein nucleotide sequences. Sequences were aligned with the NCBI database and phylogenetic analyses were carried out with MEGA6 software. Adv36 DNA was found in four samples (19%). This study indicates that some individuals carry Adv36 in the visceral adipose tissue. Further studies are needed to determine the specific effect of Adv36 infection on adipocytes, the prevalence of Adv36 infection and its relationship with obesity in the perspective of developing a vaccine that could potentially prevent or mitigate infection.

Establishment of a coastal fish in the Azores: recent colonisation or sudden expansion of an ancient relict population?

The processes and timescales associated with ocean-wide changes in the distribution of marine species have intrigued biologists since Darwin's earliest insights into biogeography. The Azores, a mid-Atlantic volcanic archipelago located >1000 km off the European continental shelf, offers ideal opportunities to investigate phylogeographic colonisation scenarios. The benthopelagic sparid fish known as the common two-banded seabream (Diplodus vulgaris) is now relatively common along the coastline of the Azores archipelago, but was virtually absent before the 1990 s. We employed a multiple genetic marker approach to test whether the successful establishment of the Azorean population derives from a recent colonisation from western continental/island populations or from the demographic explosion of an ancient relict population. Results from nuclear and mtDNA sequences show that all Atlantic and Mediterranean populations belong to the same phylogroup, though microsatellite data indicate significant genetic divergence between the Azorean sample and all other locations, as well as among Macaronesian, western Iberian and Mediterranean regions. The results from Approximate Bayesian Computation indicate that D. vulgaris has likely inhabited the Azores for ∼ 40 (95% confidence interval (CI): 5.5-83.6) to 52 (95% CI: 6.32-89.0) generations, corresponding to roughly 80-150 years, suggesting near-contemporary colonisation, followed by a more recent demographic expansion that could have been facilitated by changing climate conditions. Moreover, the lack of previous records of this species over the past century, together with the absence of lineage separation and the presence of relatively few private alleles, do not exclude the possibility of an even more recent colonisation event.

Trophic flexibility and opportunism in pike Esox lucius.

The first comprehensive investigation of pike Esox lucius trophic ecology in a region (Ireland) where they have long been thought to be a non-native species is presented. Diet was investigated across habitat types (lake, river and canal) through the combined methods of stable-isotope and stomach content analyses. Variations in niche size, specialization and the timing of the ontogenetic dietary switch were examined, revealing pronounced opportunism and feeding plasticity in E. lucius, along with a high occurrence of invertivory (up to 60 cm fork length, LF ) and a concomitant delayed switch to piscivory. Furthermore, E. lucius were found to primarily prey upon the highly available non-native roach Rutilus rutilus, which may alleviate predation pressure on brown trout Salmo trutta, highlighting the complexity of dynamic systems and the essential role of research in informing effective management.

Second-harmonic generation in AlGaAs microdisks in the telecom range.

We report on second-harmonic generation in whispering-gallery-mode AlGaAs microcavities suspended on a GaAs pedestal. Frequency doubling of a 1.58 µm pump is observed with 7×10(-4) W(-1) conversion efficiency. This device can be integrated in a monolithic photonic chip for classical and quantum applications in the telecom band.

Single nucleotide polymorphism detection by optical DNA-based sensing coupled with whole genomic amplification.

The work presented here deals with the optimization of a strategy for detection of single nucleotide polymorphisms based on surface plasmon resonance imaging. First, a sandwich-like assay was designed, and oligonucleotide sequences were computationally selected in order to study optimized conditions for the detection of the rs1045642 single nucleotide polymorphism in the gene ABCB1. Then the strategy was optimized on a surface plasmon resonance imaging biosensor using synthetic DNA sequences in order to evaluate the best conditions for the detection of a single mismatching base. Finally, the assay was tested on DNA extracted from human blood which was subsequently amplified using a whole genome amplification kit. The direct detection of the polymorphism was successfully achieved. The biochip was highly regenerable and reusable for up to 20 measurements. Furthermore, coupling these promising results with the multiarray assay, we can foresee applying this biosensor in clinical research extended to concurrent analysis of different polymorphisms.

Lesions of the biceps pulley as cause of anterosuperior impingement of the shoulder in the athlete: potentials and limits of MR arthrography compared with arthroscopy.

PURPOSE: This study aimed to evaluate the diagnostic possibilities of MR arthrography in the correct identification of complex tears of the biceps pulley and their possible correlation with anterosuperior impingement (ASI) development. MATERIALS AND METHODS: MR arthrography examinations of 23 athletes with clinical suspicion of ASI were reviewed. All examinations were obtained with a 1.5-T unit (Signa Horizon, GE Healthcare). The shoulders were studied with a dedicated surface coil with the patient's arm in the neutral position and in internal and external rotation. In five patients, images in abduction-external rotation (ABER) were obtained. Within 2 month after MR arthrography, the athletes underwent arthroscopic surgery. RESULTS: MR arthrography images showed a spectrum of tears that, according to the Habermeyer classification, were subdivided into four groups: type 1 in three patients; type 2 in five; type 3 in seven; type 4 in eight. At arthroscopic evaluation, one patient presented type 1 lesion, five type 2, five type 3 and ten type 4. During arthroscopic dynamic manoeuvres, ASI signs were observed in three patients with type 3 lesion and in ten with type 4 lesion. CONCLUSIONS: MR arthrography is the imaging modality of choice for evaluating lesions of the rotator interval structures, and only complex lesions of the biceps pulley are related to the development of ASI.

Tuning of a nonlinear THz emitter.

We numerically study a passive THz source based on difference frequency generation between modes sustained by cylindrical AlGaAs microcavities. We show that ring-like structures are advantageous in that they provide additional degrees of freedom for tuning the nonlinear process and for maximizing the nonlinear overlap integral and conversion efficiency.

Exploring neutral and adaptive processes in expanding populations of gilthead sea bream, Sparus aurata L., in the North-East Atlantic.

Recent studies in empirical population genetics have highlighted the importance of taking into account both neutral and adaptive genetic variation in characterizing microevolutionary dynamics. Here, we explore the genetic population structure and the footprints of selection in four populations of the warm-temperate coastal fish, the gilthead sea bream (Sparus aurata), whose recent northward expansion has been linked to climate change. Samples were collected at four Atlantic locations, including Spain, Portugal, France and the South of Ireland, and genetically assayed using a suite of species-specific markers, including 15 putatively neutral microsatellites and 23 expressed sequence tag-linked markers, as well as a portion of the mitochondrial DNA (mtDNA) control region. Two of the putatively neutral markers, Bld-10 and Ad-10, bore signatures of strong directional selection, particularly in the newly established Irish population, although the potential 'surfing effect' of rare alleles at the edge of the expansion front was also considered. Analyses after the removal of these loci suggest low but significant population structure likely affected by some degree of gene flow counteracting random genetic drift. No signal of historic divergence was detected at mtDNA. BLAST searches conducted with all 38 markers used failed to identify specific genomic regions associated to adaptive functions. However, the availability of genomic resources for this commercially valuable species is rapidly increasing, bringing us closer to the understanding of the interplay between selective and neutral evolutionary forces, shaping population divergence of an expanding species in a heterogeneous milieu.

[Study of hospitalizations for pneumococcal pneumoniae in Centre region, 2004-2008]. / Étude des séjours pour pneumopathie à Streptococcus pneumoniae entre 2004 et 2008 en région Centre.

BACKGROUND: Streptococcus pneumoniae is a significant cause of morbidity-mortality: leading agent of community-acquired pneumonia and the first cause of death due to infectious diseases in France. Vaccines are available for children and adults, avoiding serious complications. We studied hospitalizations for pneumococcal pneumonia in Centre region in 2004-2008, using the 2004-2008 national hospital discharges database and assessed vaccine coverage of a sample population. METHODS: Hospital discharges with diagnosis of pneumococcal pneumonia were selected, using the corresponding code (J13) in the French Diagnosis-Related Group coding system. We analysed hospitalization and patient data using linkage of the inpatient stays with their anonymous identification number. We analysed hospitalization and patient data: number and length of stay/patient, co-morbid factors and pneumococcal immunisation status. RESULTS: One thousand five hundred and forty-one hospitalisations were found for pneumococcal pneumonia in Centre Region, in 2004-2008. The time pattern showed an annual increase in hospital stays: winter hospitalisations were most frequent. The median age was 58 years, range: 2 months-106 years. The sex ratio M/F of the 1417 distinct inpatients was 1.43. The hospital impact was substantial, with prolonged length of stay (mean=9.9 days), frequent stays in intensive care unit (20%) and high death rate (6%). The vaccine coverage of the population with pneumococcal pneumonia was only 23%. CONCLUSION: Using the national hospital discharges database, this study presents a snapshot of pneumococcal pneumonia in one French region and demonstrates the local major clinical impact, as found in France. It shows that the hospital discharge database is a potential tool for epidemiology despite its possible bias. This type of study could be useful for organizing a regional vaccination campaing due to the better knowledge of the disease.

Detecting population structure in a high gene-flow species, Atlantic herring (Clupea harengus): direct, simultaneous evaluation of neutral vs putatively selected loci.

In many marine fish species, genetic population structure is typically weak because populations are large, evolutionarily young and have a high potential for gene flow. We tested whether genetic markers influenced by natural selection are more efficient than the presumed neutral genetic markers to detect population structure in Atlantic herring (Clupea harengus), a migratory pelagic species with large effective population sizes. We compared the spatial and temporal patterns of divergence and statistical power of three traditional genetic marker types, microsatellites, allozymes and mitochondrial DNA, with one microsatellite locus, Cpa112, previously shown to be influenced by divergent selection associated with salinity, and one locus located in the major histocompatibility complex class IIA (MHC-IIA) gene, using the same individuals across analyses. Samples were collected in 2002 and 2003 at two locations in the North Sea, one location in the Skagerrak and one location in the low-saline Baltic Sea. Levels of divergence for putatively neutral markers were generally low, with the exception of single outlier locus/sample combinations; microsatellites were the most statistically powerful markers under neutral expectations. We found no evidence of selection acting on the MHC locus. Cpa112, however, was highly divergent in the Baltic samples. Simulations addressing the statistical power for detecting population divergence showed that when using Cpa112 alone, compared with using eight presumed neutral microsatellite loci, sample sizes could be reduced by up to a tenth while still retaining high statistical power. Our results show that the loci influenced by selection can serve as powerful markers for detecting population structure in high gene-flow marine fish species.

Lymphocyte apoptosis induced by CD95 (APO-1/Fas) ligand-expressing tumor cells--a mechanism of immune evasion?

The CD95 (APO-1/Fas) system is an important mediator of T-cell cytotoxicity. We investigated this system in 22 hepatocellular carcinomas (HCCs) from patients. All HCCs had partially or completely lost the expression of the CD95 receptor constitutively expressed by normal liver cells and might thus evade CD95-mediated killing. We also considered a new mechanism of immune evasion, namely, the active destruction of T-lymphocytes by tumor cells expressing CD95 ligand (CD95L). CD95L messenger RNA and protein could be detected in the HCCs. In coculture experiments, HepG2 hepatoblastoma cells, expressing CD95L mRNA after treatment with cytostatic drugs, killed CD95+ Jurkat lymphocytes. Our data suggest that tumor cells can evade immune attack by down-regulation of the CD95 receptor and killing of lymphocytes through expression of CD95L.

Hepatic failure and liver cell damage in acute Wilson's disease involve CD95 (APO-1/Fas) mediated apoptosis.

Wilson's disease can result in fulminant liver failure due to hepatic copper overload. The CD95 system mediates apoptosis and has been demonstrated to be involved in liver disease. In this study CD95 mediated apoptosis was investigated in patients with fulminant hepatic failure in the course of Wilson's disease and in an in vitro model of copper treated human hepatoma cells. In patients, hepatic expression of CD95 and CD95L mRNA and apoptosis were detected. Copper overload in vitro resulted in hepatocytic apoptosis which could be reduced with a neutralizing anti-CD95L antibody. Copper treatment of hepatocytes results in activation of the CD95 system and induction of apoptosis which is operative during the course of hepatic failure in acute Wilson's disease.