The placebo response in trials of drug treatments for cancer-related fatigue: A systematic review, meta-analysis and meta-regression

Background: Cancer-related fatigue (CRF) is one of the most distressing symptoms experienced by patients. There is no gold standard treatment, although multiple drugs have been tested with little evidence of efficacy. Randomised controlled trials (RCTs) of these drugs have commented on the existence or size of the placebo response (PR). The objective of this systematic review was to establish the magnitude of the PR in RCTs of drugs to relieve CRF and to identify contributing factors. Method: RCTs were included in which the objective was to treat CRF. A meta-analysis was conducted using the standardised mean change (SMC) between baseline and final measurement in the placebo group. To explore factors that may be associated with the PR (eg, population or drug), a meta-regression was undertaken. Risk of bias was assessed using the revised Cochrane tool. Results: From 3916 citations, 30 relevant RCTs were identified. All had limitations that increased their risk of bias. The pooled SMC in reduction in fatigue status in placebo groups was −0.23 (95% confidence intervals −0.42 to −0.04). None of the variables analysed in the meta-regression were statistically significant related to PR. Conclusion: There is some evidence, based on trials with small samples, that the PR in trials testing drugs for CRF is non-trivial in size and statistically significant. We recommend that researchers planning drug studies in CRF should consider implementing alternative trial designs to better account for PR and decrease impact on the study results

Analysis of a spontaneous mutant and selected clones of cv. Italia (Vitis vinifera) by AFLP markers

A spontaneously formed mutant and selected clones (from clonal selection) of the table grape cv. Italia (Vitis vinifera) were evaluated with regard to the the possible use of molecular markers for grapevine clone differentiation. The identified off-type grapevine, which presents a mutated branch and a normal one on the same plant, removes any doubt as to its origin and allows a better evaluation of the suitability of molecular markers for the differentiation of grape clones. AFLPs were used as molecular markers because a large number of loci can be screened in a single assay, which is useful for any study on genotype relationships when a large number of bands (variables) is required. Different primer combinations (49) produced 3880 scorable AFLP bands but none showed any polymorphism among clones. Nevertheless it is suggested to use both AFLP and morphological markers for the differentiation of grapevine clones. The AFLPs would confirm the high level of DNA similarity among the suspected clones while morphological characters would allow to verify, through appropriate field experimental designs, the reliability of the phenotypic differences detected among grape clones.

Are supramodality and cross-modal plasticity the yin and yang of brain development? From blindness to rehabilitation

Research in blind individuals has primarily focused for a long time on the brain plastic reorganization that occurs in early visual areas. Only more recently, scientists have developed innovative strategies to understand to what extent vision is truly a mandatory prerequisite for the brain’s fine morphological architecture to develop and function. As a whole, the studies conducted to date in sighted and congenitally blind individuals have provided ample evidence that several ‘visual’ cortical areas develop independently from visual experience and do process information content regardless of the sensory modality through which a particular stimulus is conveyed: a property named supramodality. At the same time, lack of vision leads to a structural and functional reorganization within 'visual' brain areas, a phenomenon known as cross-modal plasticity. Cross-modal recruitment of the occipital cortex in visually deprived individuals represents an adaptative compensatory mechanism that mediates processing of non-visual inputs. Supramodality and cross-modal plasticity appear to be the 'yin and yang' of brain development: supramodal is what takes place despite the lack of vision, whereas cross-modal is what happens because of lack of vision. Here we provide a critical overview of the research in this field and discuss the implications that these novel findings have for the development of educative/rehabilitation approaches and sensory substitution devices in sensory-impaired individuals

Almond diversity and homozygosity define structure, kinship, inbreeding, and linkage disequilibrium in cultivated germplasm, and reveal genomic associations with nut and seed weight

Almond [Prunus dulcis Miller (D.A. Webb)] is the main tree nut species worldwide. Here, genotyping-by-sequencing (GBS) was applied to 149 almond cultivars from the ex situ collections of the Italian Council for Agricultural Research (CREA) and the Spanish National Research Council (CSIC), leading to the detection of 93,119 single-nucleotide polymorphisms (SNPs). The study of population structure outlined four distinct genetic groups and highlighted diversification between the Mediterranean and Californian gene pools. Data on SNP diversity and runs of homozygosity (ROHs) allowed the definition of kinship, inbreeding, and linkage disequilibrium (LD) decay in almond cultivated germplasm. Four-year phenotypic observations, gathered on 98 cultivars of the CREA collection, were used to perform a genome-wide association study (GWAS) and, for the first time in a crop species, homozygosity mapping (HM), resulting in the identification of genomic associations with nut, shell, and seed weight. Both GWAS and HM suggested that loci controlling nut and seed weight are mostly independent. Overall, this study provides insights on the almond cultivation history and delivers information of major interest for almond genetics and breeding. In a broader perspective, our results encourage the use of ROHs in crop science to estimate inbreeding, choose parental combinations minimizing the risk of inbreeding depression, and identify genomic footprints of selection for specific traits

Metabolic reprogramming promotes myogenesis during aging

Sarcopenia is the age-related progressive loss of skeletal muscle mass and strength finally leading to poor physical performance. Impaired myogenesis contributes to the pathogenesis of sarcopenia, while mitochondrial dysfunctions are thought to play a primary role in skeletal muscle loss during aging. Here we studied the link between myogenesis and metabolism. In particular, we analyzed the effect of the metabolic modulator trimetazidine (TMZ) on myogenesis in aging. We show that reprogramming the metabolism by TMZ treatment for 12 consecutive days stimulates myogenic gene expression in skeletal muscle of 22-month-old mice. Our data also reveal that TMZ increases the levels of mitochondrial proteins and stimulates the oxidative metabolism in aged muscles, this finding being in line with our previous observations in cachectic mice. Moreover, we show that, besides TMZ also other types of metabolic modulators (i.e., 5-Aminoimidazole-4-Carboxamide Ribofuranoside-AICAR) can stimulate differentiation of skeletal muscle progenitors in vitro. Overall, our results reveal that reprogramming the metabolism stimulates myogenesis while triggering mitochondrial proteins synthesis in vivo during aging. Together with the previously reported ability of TMZ to increase muscle strength in aged mice, these new data suggest an interesting non-invasive therapeutic strategy which could contribute to improving muscle quality and neuromuscular communication in the elderly, and counteracting sarcopenia

Brief review on semileptonic B decays

We concisely review semileptonic B decays, focussing on recent progress on both theoretical and experimental sides.Comment: 18 pages, 2 figures; version to be published in Mod. Phys. Lett.

Food Selectivity in Children with Autism: Guidelines for Assessment and Clinical Interventions

Autisms Spectrum Disorders (ASD) are characterized by core symptoms (social communication and restricted and repetitive behaviors) and related comorbidities, including sensory anomalies, feeding issues, and challenging behaviors. Children with ASD experience significantly more feeding problems than their peers. In fact, parents and clinicians have to manage daily the burden of various dysfunctional behaviors of children at mealtimes (food refusal, limited variety of food, single food intake, or liquid diet). These dysfunctional behaviors at mealtime depend on different factors that are either medical/sensorial or behavioral. Consequently, a correct assessment is necessary in order to program an effective clinical intervention. The aim of this study is to provide clinicians with a guideline regarding food selectivity concerning possible explanations of the phenomenon, along with a direct/indirect assessment gathering detailed and useful information about target feeding behaviors. Finally, a description of evidence-based sensorial and behavioral strategies useful also for parent-mediated intervention is reported addressing food selectivity in children with ASD

Sign-changing tower of bubbles for a sinh-Poisson equation with asymmetric exponents

Motivated by the statistical mechanics description of stationary 2D-turbulence, for a sinh-Poisson type equation with asymmetric nonlinearity, we construct a concentrating solution sequence in the form of a tower of singular Liouville bubbles, each of which has a different degeneracy exponent. The asymmetry parameter $\gamma\in(0,1]$ corresponds to the ratio between the intensity of the negatively rotating vortices and the intensity of the positively rotating vortices. Our solutions correspond to a superposition of highly concentrated vortex configurations of alternating orientation; they extend in a nontrivial way some known results for $\gamma=1$. Thus, by analyzing the case $\gamma\neq1$ we emphasize specific properties of the physically relevant parameter $\gamma$ in the vortex concentration phenomena

Optical response of a misaligned and suspended Fabry-Perot cavity

The response to a probe laser beam of a suspended, misaligned and detuned optical cavity is examined. A five degree of freedom model of the fluctuations of the longitudinal and transverse mirror coordinates is presented. Classical and quantum mechanical effects of radiation pressure are studied with the help of the optical stiffness coefficients and the signals provided by an FM sideband technique and a quadrant detector, for generic values of the product $\varpi \tau$ of the fluctuation frequency times the cavity round trip. A simplified version is presented for the case of small misalignments. Mechanical stability, mirror position entanglement and ponderomotive squeezing are accommodated in this model. Numerical plots refer to cavities under test at the so-called Pisa LF facility.Comment: 14 pages (4 figures) submitted to Phys. Rev.