Unusual skin metastasis due to adenocarcinoma of the stomach: a case report

Clinical Findings A 68- year-old man presented with a skin thickening of the anterior neck started few months earlier. Upper respiratory and digestive tract had already been examined which proved normal. On clinical examination a hyper pigmented massively indurated leathery plaque was seen on the anterior and lateral aspect of the neck from the submandibular region down to the jugular fossae. The plaque was firm, well demarcated and measured 15 by 12 cm in diameter. It had a cobblestone like appearance with exaggerated folds, and was non painful. Patient complained of a mild discomfort while swallowing saliva of recent onset, but was otherwise asymptomatic. All his routine blood test was normal. The full skin examination was otherwise unremarkable. Our main differential diagnosis at that stage included a reactive process such as a sclerodermatous process, a neoplastic reaction or a lymph proliferative disease.</br

Genetic variants involved in Blood Pressure response to hydrochlorothiazide identified by GWAS methodology

Aim: To identify new loci regulating blood pressure response to thiazide diuretics (HCTZ) with a genome wide association analysis, thus optimizing therapeutic advantages and minimizing side effects. Methods: Treatment started after a 8 week run-in period under standardized dietary regimen to qualify patients as “essential hypertensives”. Never treated mild-to-moderate hypertensive patients were studied in two Italian cohorts: n=343 patients in Sardinia and 142 in Milano. A genome-wide association study and imputation were performed: variants associated with blood pressure response to HCTZ over an 8-weeks follow up period were analysed. The specificity of our findings was confirmed in an independent cohort of never treated essential hypertensives treated with Losartan. Results: We identified 141 SNPs and 130 SNPs showing a significant association with for deltaSBP8 for deltaDBP8 (P≤10-5). Six SNPs showed the best association with deltaSBP8 and five SNPs with deltaDBP8, respectively. TET2 and CSMD1 gene variants showed the best effect on deltaSBP after 8 weeks of HCTZ treatment. No association was found in Losartan sample. We looked for replication in other studies (GENRES, GERA1, NORDIL, PEAR and CSN-StayOnDiur). Conclusions: TET2 and CSMD1 affect SBP response to HCTZ. TET2, may affect the transcription of αENaC gene thus acting as an aldosterone-responsive mediator. CSMD1 gene was associated with increased risk of hypertension: its putative role in BP regulation remains to be clarified

Genetic variation of goat Y chromosome in the Sardinian population

Sardinian goat population is commonly considered a crossbred of autochthonous animals with improved Mediterranean breeds, mainly the Maltese. It has been demonstrated by using autosomal microsatellites that the Sardinian goats can be divided into three subpopulations: Sardinian, crossbred with Maltese, and Maltese. The aim of this study was to evaluate sequence variation at Y chromosome in Sardinian bucks and to integrate autosomal microsatellites data. Blood from 190 bucks from 68 farms spread in the main Sardinian goat farming areas was sampled. Three ECONOGENE project primer pairs plus an additional one corresponding to a total of 7 SNPs were used. For all common SNPs, the most frequent allele corresponded to the ECONOGENE one. The additional analysed SNP showed allelic frequencies similar to the other markers. The comparison with haplotypes based on the 6 common SNPs showed that the Sardinian most frequent haplotype corresponded to the predominant one in Central Europe. Results of this study showed that the Sardinian goat population has 8 haplotypes resulting in a large diversity of paternal lineages. The next step will be linking autosomal information to Y chromosome data. In fact, up to date, it seems unfeasible to detect recent upgrading breeds by using Y chromosome variation only

Haplotype affinities resolve a major component of goat (<i>Capra hircus</i>) MtDNA D-loop diversity and reveal specific features of the Sardinian stock

Goat mtDNA haplogroup A is a poorly resolved lineage absorbing most of the overall diversity and is found in locations as distant as Eastern Asia and Southern Africa. Its phylogenetic dissection would cast light on an important portion of the spread of goat breeding. The aims of this work were 1) to provide an operational definition of meaningful mtDNA units within haplogroup A, 2) to investigate the mechanisms underlying the maintenance of diversity by considering the modes of selection operated by breeders and 3) to identify the peculiarities of Sardinian mtDNA types. We sequenced the mtDNA D-loop in a large sample of animals (1,591) which represents a non-trivial quota of the entire goat population of Sardinia. We found that Sardinia mirrors a large quota of mtDNA diversity of Western Eurasia in the number of variable sites, their mutational pattern and allele frequency. By using Bayesian analysis, a distance-based tree and a network analysis, we recognized demographically coherent groups of sequences identified by particular subsets of the variable positions. The results showed that this assignment system could be reproduced in other studies, capturing the greatest part of haplotype diversity. We identified haplotype groups overrepresented in Sardinian goats as a result of founder effects. We found that breeders maintain diversity of matrilines most likely through equalization of the reproductive potential. Moreover, the relevant amount of inter-farm mtDNA diversity found does not increase proportionally with distance. Our results illustrate the effects of breeding practices on the composition of maternal gene pool and identify mtDNA types that may be considered in projects aimed at retrieving the maternal component of the oldest breeds of Sardinia.</br

Photoexcitations and Emission Processes in Organometal Trihalide Perovskites

Organometal halide perovskites have recently attracted widespread attention among scientists, as they combine the advantages of low-cost processability with strong light absorption, band-gap tunability from the near-infrared to the visible region of the electromagnetic spectrum, efficient light emission and charge transport. Such combination of features is unique among solution-processed materials and makes perovskites appealing for several optoelectronic applications, in particular those related to energy sustainability, which could help the advent of a new generation of low-cost but efficient solar cells and large-area light-emitting devices.This chapter reports a critical review of the efforts that scientists have made until now to understand the photophysics of organometal halide perovskites. We address the ongoing debate on the nature of the photoexcited species, namely the role played by free carriers and excitons, the determination of the exciton binding energy as a measure of the Coulomb interaction strength in these materials, the competition between radiative and non-radiative processes, the role and density of charge carrier traps, and last but not least a critical analysis of those phenomena at the base of laser action, highlighting the most relevant results and possible solutions to issues that still remain open

Systems medicine in colorectal cancer: from a mathematical model toward a new type of clinical trial

Current colorectal cancer (CRC) treatment guidelines are primarily based on clinical features, such as cancer stage and grade. However, outcomes may be improved using molecular treatment guidelines. Potentially useful biomarkers include driver mutations and somatically inherited alterations, signaling proteins (their expression levels and (post) translational modifications), mRNAs, micro-RNAs and long noncoding RNAs. Moving to an integrated system is potentially very relevant. To implement such an integrated system: we focus on an important region of the signaling network, immediately above the G1-S restriction point, and discuss the reconstruction of a Molecular Interaction Map and interrogating it with a dynamic mathematical model. Extensive model pretraining achieved satisfactory, validated, performance. The model helps to propose future target combination priorities, and restricts drastically the number of drugs to be finally tested at a cellular, in vivo, and clinical-trial level. Our model allows for the inclusion of the unique molecular profiles of each individual patient's tumor. While existing clinical guidelines are well established, dynamic modeling may be used for future targeted combination therapies, which may progressively become part of clinical practice within the near future. WIREs Syst Biol Med 2016, 8:314\u2013336. doi: 10.1002/wsbm.1342. For further resources related to this article, please visit the WIREs website

A water-soluble, mucoadhesive quaternary ammonium chitosan-methyl-β-cyclodextrin conjugate forming inclusion complexes with dexamethasone

The ocular bioavailability of lipophilic drugs, such as dexamethasone, depends on both drug water solubility and mucoadhesion/permeation. Cyclodextrins and chitosan are frequently employed to either improve drug solubility or prolong drug contact onto mucosae, respectively. Although the covalent conjugation of cyclodextrin and chitosan brings to mucoadhesive drug complexes, their water solubility is restricted to acidic pHs. This paper describes a straightforward grafting of methyl-β-cyclodextrin (MCD) on quaternary ammonium chitosan (QA-Ch60), mediated by hexamethylene diisocyanate. The resulting product is a water-soluble chitosan derivative, having a 10-atom long spacer between the quaternized chitosan and the cyclodextrin. The derivative is capable of complexing the model drug dexamethasone and stable complexes were also observed for the lyophilized products. Furthermore, the conjugate preserves the mucoadhesive properties typical of quaternized chitosan and its safety as solubilizing excipient for ophthalmic applications was preliminary assessed by in vitro cytotoxicity evaluations. Taken as a whole, the observed features appear promising for future processing of the developed product into 3D solid forms, such as controlled drug delivery systems, films or drug eluting medical devices

Participants with Normal Weight or with Obesity Show Different Relationships of 6-n-Propylthiouracil (PROP) Taster Status with BMI and Plasma Endocannabinoids

Reduced taste sensitivity to 6-n-propylthiouracil (PROP), a genetic trait regarded as a general index for oral chemosensory perception, has been associated with a calorie-rich food preference and lower circulating endocannabinoid levels in participants with normal weight (NW), which suggests an adaptive mechanism to maintain a lean phenotype. In this study, we assessed whether participants with obesity (OB) show different patterns of plasma endocannabinoids and lipid metabolism biomarkers from those of NW, with further categorization based on their PROP sensitivity. NW and OB were classified by their PROP taster status as non-tasters (NT), medium-tasters (MT) and supertasters (ST). The blood samples were analysed for plasma endocannabinoids, nonesterified fatty acids (NEFA) and retinol, which have been associated to metabolic syndrome. In OB, we found a higher BMI and lower circulating endocannabinoids in ST vs. OB NT. However, OB ST showed lower circulating NEFA and retinol levels, which suggested a more favourable lipid metabolism and body fat distribution than those of OB NT. We confirmed lower plasma endocannabinoid levels in NW NT than in NW ST. These data suggest that PROP taste sensitivity determines metabolic changes and ultimately body mass composition differently in OB and NW

Only Words Count; the Rest Is Mere Chattering: A Cross-Disciplinary Approach to the Verbal Expression of Emotional Experience

The analysis of sequences of words and prosody, meter, and rhythm provided in an interview addressing the capacity to identify and describe emotions represents a powerful tool to reveal emotional processing. The ability to express and identify emotions was analyzed by means of the Toronto Structured Interview for Alexithymia (TSIA), and TSIA transcripts were analyzed by Natural Language Processing to shed light on verbal features. The brain correlates of the capacity to translate emotional experience into words were determined through cortical thickness measures. A machine learning methodology proved that individuals with deficits in identifying and describing emotions (n = 7) produced language distortions, frequently used the present tense of auxiliary verbs, and few possessive determiners, as well as scarcely connected the speech, in comparison to individuals without deficits (n = 7). Interestingly, they showed high cortical thickness at left temporal pole and low at isthmus of the right cingulate cortex. Overall, we identified the neuro-linguistic pattern of the expression of emotional experience

Only Words Count; the Rest Is Mere Chattering: A Cross-Disciplinary Approach to the Verbal Expression of Emotional Experience

The analysis of sequences of words and prosody, meter, and rhythm provided in an interview addressing the capacity to identify and describe emotions represents a powerful tool to reveal emotional processing. The ability to express and identify emotions was analyzed by means of the Toronto Structured Interview for Alexithymia (TSIA), and TSIA transcripts were analyzed by Natural Language Processing to shed light on verbal features. The brain correlates of the capacity to translate emotional experience into words were determined through cortical thickness measures. A machine learning methodology proved that individuals with deficits in identifying and describing emotions (n = 7) produced language distortions, frequently used the present tense of auxiliary verbs, and few possessive determiners, as well as scarcely connected the speech, in comparison to individuals without deficits (n = 7). Interestingly, they showed high cortical thickness at left temporal pole and low at isthmus of the right cingulate cortex. Overall, we identified the neuro-linguistic pattern of the expression of emotional experience