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The majority of the so-called heavy metals are suspected to be involved in a number of pathologies and play a role in human carcinogenesis. Some of them (i.e. arsenic (As), cadmium (Cd), chromium (Cr), lead (Pb), mercury (Hg) and nickel (Ni)) have been defined as carcinogens, increasing the susceptibility of tumor development and progression in humans. Moreover, Ni, Cr, Cd, Hg, and Pb together with zinc (Zn) and iron (Fe), may be capable of stimulating the progression of breast cancer and reducing a patient's sensitivity to treatment through alterations to DNA methylation. In patients with gastric cancers, levels of various heavy metals are augmented and hypothesized to amplify the expression of the human epidermal growth factor receptor type 2 gene. Cd may increase the risk of lung cancer development and have a negative impact on the overall survival of lung cancer patients. To investigate the relation between heavy metals in biological samples and risk, occurrence and survival cancer individuals, a comprehensive review work was performed, with a focus on breast, lung, prostate and gastric cancers. An extensive search strategy was devised to ensure relevant literature could be identified, with the PECO framework being adopted to facilitate this and identify key search terms. As evidenced in this review, there is substantial data to support the hypothesis that heavy metals influence tumor development and progression. Unluckily the number of papers dealing with the determination of metals directly in samples from cancer tissues is still rather limited, so we decided to expand the scope of this review also to analyses carried out on other biological samples, as urine, plasma, hair, nail, etc. The studies reviewed showed that several limitations and current knowledge gaps are present in the literature that require further investigation to improve our comprehension of the impact of different heavy metals on tumorigenesis. [ABSTRACT FROM AUTHOR]

The aims of this study is to evaluate the association between angiotensin-converting enzyme inhibitor (ACE-I), angiotensin II receptor blocker (ARBs) and/or statin use with the risk of pneumonia, as well as and with in-hospital and short-term outpatient mortality in hospitalized older patients with pneumonia. Patients aged 65 years or older hospitalized in internal medicine and/or geriatric wards throughout Italy and enrolled in the REPOSI (REgistro Politerapuie SIMI–Società Italiana di Medicina Interna) register from 2010 to 2019 were screened to assess the diagnosis of pneumonia and classified on whether or not they were prescribed with at least one drug among ACE-I, ARBs, and/or statins. Further study outcomes were mortality during hospital stay and at 3 months after hospital discharge. Among 5717 cases included (of whom 18.0% with pneumonia), 2915 (51.0%) were prescribed at least one drug among ACE-I, ARBs, and statins. An inverse association was found between treatment with ACE-I or ARBs and pneumonia (OR = 0.79, 95% CI 0.65–0.95). A higher effect was found among patients treated with ACE-I or ARBs in combination with statins (OR = 0.67, 95% CI 0.52–0.85). This study confirmed in the real-world setting that these largely used medications may reduce the risk of pneumonia in older people, who chronically take them for cardiovascular conditions. [ABSTRACT FROM AUTHOR]

With his bicentennial breeding history based on athletic performance, the Thoroughbred horse can be considered the equine sport breed. Although genomic and transcriptomic tools and knowledge are at the state of the art in equine species, the epigenome and its modifications in response to environmental stimuli, such as training, are less studied. One of the major epigenetic modifications is cytosine methylation at 5′ of DNA molecules. This crucial biochemical modification directly mediates biological processes and, to some extent, determines the organisms' phenotypic plasticity. Exercise indeed affects the epigenomic state, both in humans and in horses. In this study, we highlight, with a genome-wide analysis of methylation, how the adaptation to training in the Thoroughbred can modify the methylation pattern throughout the genome. Twenty untrained horses, kept under the same environmental conditions and sprint training regimen, were recruited, collecting peripheral blood at the start of the training and after 30 and 90 days. Extracted leukocyte DNA was analyzed with the methylation content sensitive enzyme ddRAD (MCSeEd) technique for the first time applied to animal cells. Approximately one thousand differently methylated genomic regions (DMRs) and nearby genes were called, revealing that methylation changes can be found in a large part of the genome and, therefore, referable to the physiological adaptation to training. Functional analysis via GO enrichment was also performed. We observed significant differences in methylation patterns throughout the training stages: we hypothesize that the methylation profile of some genes can be affected early by training, while others require a more persistent stimulus. [ABSTRACT FROM AUTHOR]

HER2+ breast cancer (BC) is an aggressive subtype genetically and biologically heterogeneous. We evaluate the predictive and prognostic role of HER2 protein/gene expression levels combined with clinico-pathologic features in 154 HER2+ BCs patients who received trastuzumab-based neoadjuvant chemotherapy (NACT). The tumoral pathological complete response (pCR) rate was 40.9%. High tumoral pCR show a scarce mortality rate vs subjects with a lower response. 93.7% of ypT0 were HER2 IHC3+ BC, 6.3% were HER2 IHC 2+/SISH+ and 86.7% of ypN0 were HER2 IHC3+, the remaining were HER2 IHC2+/SISH+. Better pCR rate correlate with a high percentage of infiltrating immune cells and right-sided tumors, that reduce distant metastasis and improve survival, but no incidence difference. HER2 IHC score and laterality emerge as strong predictors of tumoral pCR after NACT from machine learning analysis. HER2 IHC3+ and G3 are poor prognostic factors for HER2+ BC patients, and could be considered in the application of neoadjuvant therapy. Increasing TILs concentrations, lower lymph node ratio and lower residual tumor cellularity are associated with a better outcome. The immune microenvironment and scarce lymph node involvement have crucial role in clinical outcomes. The combination of all predictors might offer new options for NACT effectiveness prediction and stratification of HER2+ BC during clinical decision-making. [ABSTRACT FROM AUTHOR]

Purpose: Triple negative breast cancer (TNBC) is an aggressive clinical tumor, accounting for about 25% of breast cancer (BC) related deaths. Chemotherapy is the only therapeutic option to treat TNBC, hence a detailed understanding of the biology and its categorization is required. To investigate the clinical relevance of BCL11A in TNBC subtype, we focused on gene and protein expression and its mutational status in a large cohort of this molecular subtype. Methods: Gene expression profiling of BCL11A and its isoforms (BCL11A-XL, BCL11A-L and BCL11A-S) has been determined in Luminal A, Luminal B, HER2-enriched and TNBC subtypes. BCL11A protein expression has been analyzed by immunohistochemistry (IHC) and its mutational status by Sanger sequencing. Results: In our study, BCL11A was significantly overexpressed in TNBC both at transcriptional and translational levels compared to other BC molecular subtypes. A total of 404 TNBCs were selected and examined showing a high prevalence of BCL11A-XL (37.3%) and BCL11A-L (31.4%) isoform expression in TNBC, associated with a 26% of BCL11A protein expression levels. BCL11A protein expression predicts scarce LIV (HR = 0.52; 95% CI, 0.29–0.92, P = 0.03) and AR downregulation (HR = 0.37; 95% CI, 0.16–0.88; P = 0.02), as well as a higher proliferative index in TNBC cells. BCL11A-L expression is associated with more aggressive TNBC histological types, such as medullary and metaplastic carcinoma. Conclusion: Our finding showed that BCL11A protein expression acts as an unfavorable prognostic factor in TNBC patients, especially in non luminal TNBCs subgroups. These results may yield a better treatment strategy by providing a new parameter for TNBC classification. [ABSTRACT FROM AUTHOR]

Diabetes is an increasing global health burden with the highest prevalence (24.0%) observed in elderly people. Older diabetic adults have a greater risk of hospitalization and several geriatric syndromes than older nondiabetic adults. For these conditions, special care is required in prescribing therapies including anti- diabetes drugs. Aim of this study was to evaluate the appropriateness and the adherence to safety recommendations in the prescriptions of glucose-lowering drugs in hospitalized elderly patients with diabetes. Data for this cross-sectional study were obtained from the REgistro POliterapie–Società Italiana Medicina Interna (REPOSI) that collected clinical information on patients aged ≥ 65 years acutely admitted to Italian internal medicine and geriatric non-intensive care units (ICU) from 2010 up to 2019. Prescription appropriateness was assessed according to the 2019 AGS Beers Criteria and anti-diabetes drug data sheets.Among 5349 patients, 1624 (30.3%) had diagnosis of type 2 diabetes. At admission, 37.7% of diabetic patients received treatment with metformin, 37.3% insulin therapy, 16.4% sulfonylureas, and 11.4% glinides. Surprisingly, only 3.1% of diabetic patients were treated with new classes of anti- diabetes drugs. According to prescription criteria, at admission 15.4% of patients treated with metformin and 2.6% with sulfonylureas received inappropriately these treatments. At discharge, the inappropriateness of metformin therapy decreased (10.2%, P < 0.0001). According to Beers criteria, the inappropriate prescriptions of sulfonylureas raised to 29% both at admission and at discharge. This study shows a poor adherence to current guidelines on diabetes management in hospitalized elderly people with a high prevalence of inappropriate use of sulfonylureas according to the Beers criteria. [ABSTRACT FROM AUTHOR]

Background and objective: Chronic obstructive pulmonary disease (COPD) and heart failure (HF) mutually increase the risk of being present in the same patient, especially if older. Whether or not this coexistence may be associated with a worse prognosis is debated. Therefore, employing data derived from the REPOSI register, we evaluated the clinical features and outcomes in a population of elderly patients admitted to internal medicine wards and having COPD, HF or COPD + HF. Methods: We measured socio-demographic and anthropometric characteristics, severity and prevalence of comorbidities, clinical and laboratory features during hospitalization, mood disorders, functional independence, drug prescriptions and discharge destination. The primary study outcome was the risk of death. Results: We considered 2,343 elderly hospitalized patients (median age 81 years), of whom 1,154 (49%) had COPD, 813 (35%) HF, and 376 (16%) COPD + HF. Patients with COPD + HF had different characteristics than those with COPD or HF, such as a higher prevalence of previous hospitalizations, comorbidities (especially chronic kidney disease), higher respiratory rate at admission and number of prescribed drugs. Patients with COPD + HF (hazard ratio HR 1.74, 95% confidence intervals CI 1.16–2.61) and patients with dementia (HR 1.75, 95% CI 1.06–2.90) had a higher risk of death at one year. The Kaplan–Meier curves showed a higher mortality risk in the group of patients with COPD + HF for all causes (p = 0.010), respiratory causes (p = 0.006), cardiovascular causes (p = 0.046) and respiratory plus cardiovascular causes (p = 0.009). Conclusion: In this real-life cohort of hospitalized elderly patients, the coexistence of COPD and HF significantly worsened prognosis at one year. This finding may help to better define the care needs of this population. [ABSTRACT FROM AUTHOR]

The aim of the present study is to investigate a possible delay in diagnosis and therapy administration for Head and Neck oncological patients, during the Sars-Cov2 pandemic and to compare the median tumor stage (MTS) at presentation. This is a retrospective review on patients who presented at the University Hospital of Modena with a newly diagnosis of Head and Neck cancer (HNC), comparing the first pandemic period (from March 1st, to October 15th 2020) to the same period of 2019. The time in days from the diagnostic suspicion to the beginning of the treatment, hereafter referred to as delay in treatment initiation (DTI), and the tumor stage were calculated for all the enrolled patients. Mean percentage of reduction of the clinical and surgical activities was − 25.8% (range: − 66–1.5%), with higher percentages in phase 1 for all the analyzed activities. 125 HNC patients were enrolled in the analysis as the study group, compared with a cohort of 140 patients from the previous year. The MTS was III for both groups, however a significant statistical difference was determined in the stage comparison, p = 0.023. When DTI was analyzed no statistically significant differences were appreciated. A more advanced stage at presentation was demonstrated at our institution for HNC patients during the first phase of the Covid-19 pandemic in 2020. However, a statistically significant delay in time between diagnosis and therapy administration was not assessed, thus confirming the maintenance of a high level of care even in the COVID-19 era. [ABSTRACT FROM AUTHOR]

Aims: The association between hyperglycemia at hospital admission and relevant short- and long-term outcomes in elderly population is known. We assessed the effects on mortality of hyperglycemia, disability, and multimorbidity at admission in internal medicine ward in patients aged ≥ 65 years. Methods: Data were collected from an active register of 102 internal medicine and geriatric wards in Italy (RePoSi project). Patients were recruited during four index weeks of a year. Socio-demographic data, reason for hospitalization, diagnoses, treatment, severity and comorbidity indexes (Cumulative Illness rating Scale CIRS-SI and CIRS-CI), renal function, functional (Barthel Index), and cognitive status (Short Blessed Test) and mood disorders (Geriatric Depression Scale) were recorded. Mortality rates were assessed in hospital 3 and 12 months after discharge. Results: Of the 4714 elderly patients hospitalized, 361 had a glycemia level ≥ 250 mg/dL at admission. Compared to subjects with lower glycemia level, patients with glycemia ≥ 250 mg/dL showed higher rates of male sex, smoke and class III obesity. These patients had a significantly lower Barthel Index (p = 0.0249), higher CIRS-SI and CIRS-CI scores (p = 0.0025 and p = 0.0013, respectively), and took more drugs. In-hospital mortality rate was 9.2% and 5.1% in subjects with glycemia ≥ 250 and < 250 mg/dL, respectively (p = 0.0010). Regression analysis showed a strong association between in-hospital death and glycemia ≥ 250 mg/dL (OR 2.07; [95% CI 1.34–3.19]), Barthel Index ≤ 40 (3.28[2.44–4.42]), CIRS-SI (1.87[1.27–2.77]), and male sex (1.54[1.16–2.03]). Conclusions: The stronger predictors of in-hospital mortality for older patients admitted in general wards were glycemia level ≥ 250 mg/dL, Barthel Index ≤ 40, CIRS-SI, and male sex. [ABSTRACT FROM AUTHOR]

Diabetic kidney disease is the leading cause of end-stage kidney disease in high-income countries. The strict control of glycemic oscillations is the principal therapeutic target, but this could be hard to achieve in uremic patients due to their unpredictable insulin sensitivity. Currently, the evaluation of the glycemic profile relies on serum markers (glycated hemoglobin HbA1c, glycated albumin, and fructosamine), capillary glucose blood control (self-monitoring of blood glucose), and interstitial glucose control (continue glucose monitoring). We conducted a systematic review of published articles on continue glucose monitoring in hemodialysis patients with type 2 diabetes, which included 12 major articles. Four studies found significant fluctuations in glucose levels during hemodialysis sessions. All studies reported a higher mean amplitude of glucose variations on the hemodialysis day. Three studies agreed that continue glucose monitoring is better than glycated hemoglobin in detecting these abnormalities. Moreover, continue glucose monitoring was more accurate and perceived as easier to use by patients and their caregivers. In patients with type 2 diabetes on hemodialysis, glucose levels show different variation patterns than the patients on hemodialysis without diabetes. Considering manageability, accuracy, and cost-effectiveness, continue glucose monitoring could be the ideal diagnostic tool for the patient with diabetes on hemodialysis. [ABSTRACT FROM AUTHOR]

Introduction: Cancer immunotherapy represents one of the most important innovations in modern medicine. Durvalumab is an anti-programmed cell death ligand 1 (PDL-1) agent which is currently under investigation in several studies in combination with the anti-cytotoxic T lymphocyte-associated protein 4 (CTLA-4) drug tremelimumab. The aim of this review was to systematically identify and revise the current scientific literature investigating the combination of these two drugs in solid tumors. Methods: A digital search on the Medline (PubMed interface) and Scopus databases for articles published from inception to 26 February 2021 was performed. The terms used for the search were durvalumab AND tremelimumab. Trials reported in English involving adult patients with solid cancers treated with the combination durvalumab plus tremelimumab were retrieved; the references of the articles were cross-checked to identify missing papers. Results: The electronic search produced 267 results; after exclusion of duplicates, irrelevant articles, reviews, and papers not in English or missing data, 19 articles were included for revision. The total number of patients treated with the combination of durvalumab and tremelimumab in the studies retrieved was 2052. Conclusion: The combination of durvalumab plus tremelimumab showed some oncological advantages in comparison with traditional chemotherapies in some subsets of tumors, but generally has not shown consistent advantages in comparison with the employment of durvalumab monotherapy. A number of the studies examined had intrinsic methodological limitations; therefore, future well-designed studies involving larger cohorts are warranted. [ABSTRACT FROM AUTHOR]

In the last decade, the Kepler and CoRoT space-photometry missions have demonstrated the potential of asteroseismology as a novel, versatile and powerful tool to perform exquisite tests of stellar physics, and to enable precise and accurate characterisations of stellar properties, with impact on both exoplanetary and Galactic astrophysics. Based on our improved understanding of the strengths and limitations of such a tool, we argue for a new small/medium space mission dedicated to gathering high-precision, high-cadence, long photometric series in dense stellar fields. Such a mission will lead to breakthroughs in stellar astrophysics, especially in the metal poor regime, will elucidate the evolution and formation of open and globular clusters, and aid our understanding of the assembly history and chemodynamics of the Milky Way's bulge and a few nearby dwarf galaxies. [ABSTRACT FROM AUTHOR]

Understanding our Galaxy's structure, formation, and evolution will, over the next decades, continue to benefit from the wonderful large survey by Gaia, for astrometric, kinematic, and spectroscopic characterization, and by large spectroscopic surveys for chemical characterization. The weak link for full exploitation of these data is age characterization, and stellar age estimation relies predominantly on mass estimates. The ideas presented in this White Paper shows that a seismology survey is the way out of this situation and a natural complement to existing and planned surveys. These ideas are strongly rooted in the past decade's experience of the so-called Seismology revolution, initiated with CoRoT and Kepler. The case of red giant stars is used here as the best current illustration of what we can expect from seismology for large samples, but premises for similar developments exist in various other classes of stars covering other ranges of age or mass. Whatever the star considered, the first information provided by stellar pulsations is always related to the mean density and thus to the mass (and age). In order to satisfy the need for long-duration and all-sky coverage, we rely on a new instrumental concept which decouples integration time and sampling time. We thus propose a long (~1 year) all-sky survey which would perfectly fit between TESS, PLATO, and the Rubin Observatory (previously known as LSST) surveys to offer a time domain complement to the current and planned astrometric and spectroscopic surveys. The fine characterization of host stars is also a key aspect for the interpretation and exploitation of the various projects -- anticipated in the framework of the Voyage 2050 programme -- searching for atmospheric characterization of terrestrial planets or, more specifically, looking for a signature of life, in distant planets. [ABSTRACT FROM AUTHOR]

Currently, chronic obstructive pulmonary disease (COPD) represents the fourth cause of death worldwide with significant economic burden. Comorbidities increase in number and severity with age and are identified as important determinants that influence the prognosis. In this observational study, we retrospectively analyzed data collected from the RePoSI register. We aimed to investigate comorbidities and outcomes in a cohort of hospitalized elderly patients with the clinical diagnosis of COPD. Socio-demographic, clinical characteristics and laboratory findings were considered. The association between variables and in-hospital, 3-month and 1-year follow-up were analyzed. Among 4696 in-patients, 932 (19.8%) had a diagnosis of COPD. Patients with COPD had more hospitalization, a significant overt cognitive impairment, a clinically significant disability and more depression in comparison with non-COPD subjects. COPD patients took more drugs, both at admission, in-hospital stay, discharge and 3-month and 1-year follow-up. 14 comorbidities were more frequent in COPD patients. Cerebrovascular disease was an independent predictor of in-hospital mortality. At 3-month follow-up, male sex and hepatic cirrhosis were independently associated with mortality. ICS-LABA therapy was predictor of mortality at in-hospital, 3-month and 1-year follow-up. This analysis showed the severity of impact of COPD and its comorbidities in the real life of internal medicine and geriatric wards. [ABSTRACT FROM AUTHOR]

Strong spin–orbit semiconductor nanowires coupled to a superconductor are predicted to host Majorana zero modes. Exchange (braiding) operations of Majorana modes form the logical gates of a topological quantum computer and require a network of nanowires. Here, we utilize an in-plane selective area growth technique for InSb–Al semiconductor–superconductor nanowire networks. Transport channels, free from extended defects, in InSb nanowire networks are realized on insulating, but heavily mismatched InP (111)B substrates by full relaxation of the lattice mismatch at the nanowire/substrate interface and nucleation of a complete network from a single nucleation site by optimizing the surface diffusion length of the adatoms. Essential quantum transport phenomena for topological quantum computing are demonstrated in these structures including phase-coherence lengths exceeding several micrometers with Aharonov–Bohm oscillations up to five harmonics and a hard superconducting gap accompanied by 2e-periodic Coulomb oscillations with an Al-based Cooper pair island integrated in the nanowire network. Indium-Antimonide (InSb) possesses specific properties that makes it a suitable candidate for realizing Majorana-based topological quantum computers. The authors describe a method to fabricate single crystalline InSb nanowire networks from single nuclei enabling them to realize high-quality quantum transport in their devices. [ABSTRACT FROM AUTHOR]

Established breed-specific reference intervals are important for monitoring the health status of horses. Serum biochemical breed-specific reference intervals have been evaluated in horses and other animal breeds, but there are no studies for the Italian Heavy Draft horse. The aim of this study was to determine biochemical reference intervals for the Italian Heavy Draft horse living in central Italy. Moreover, the comparison between different physiological status (pregnancy and no pregnancy) and age (foals and adults) has been executed. Inclusion criteria were established before blood collection. Blood samples were collected from 309 apparently healthy horses (mares, stallions and foals). Serum parameters were evaluated in the Clinical Pathology Laboratory at the Teaching Veterinary Hospital of the University of Perugia. Reference intervals were determined by using well-described, modern analytical and statistical methods (Anderson-Darling test, Mann-Withney U test). Serum biochemical RIs for the IHDH are reported. Differences between the IHDH and both sport and other working horses are evident. Significant differences are indicated between pregnant and non-pregnant mares and between foals and adults. This is the first study reporting the serum biochemical RIs in the IHDH. The results suggest that breed-specific RIs should be used for the IHDH. Moreover, significant variations of biochemical analytes have been found between subjects with different physiological status and age. [ABSTRACT FROM AUTHOR]

Established breed-specific reference intervals (RIs) are important for monitoring the health status of horses. Breed-specific RIs have been evaluated in horses and other animal breeds, but there are no studies on breed-specific RIs for Italian Heavy Draft horse (IHDH). The aim of this study was to determine hematologic RIs for the IHDH living in central Italy. The comparison between different physiological status (pregnancy) and age (foals and adults) have been executed. Inclusion criteria were established for selection of subjects and for blood collection and handling. Blood samples were collected from 309 apparently healthy horses (mares, stallions and foals). Complete blood count (CBC) was performed on Sysmex-XT1800iV hematology at the Teaching Veterinary Hospital of the University of Perugia. RIs for IHDH were determined by using well-described, modern analytical and statistical methods as recommended by the CLSI and QALS guidelines. Hematologic RIs for the IHDH are reported. Differences between hot-blooded, cold-blooded, and warm-blooded horses are evident. Significant differences have been found for five analytes (WBC, MCHC, PLT, monocytes, basophils) between pregnant and non-pregnant mares and 12 analytes (RBC, Hgb, MCV, MCH, MCHC, RDW, PLT, WBC, lymphocytes, monocytes, eosinophils, basophils) between foals and adults. This is the first study reporting the hematologic RIs in the IHDH. The results suggest that breed-specific RIs should be used for IHDH due to the difference with published data regarding cold-blooded, hot-blooded, and warm-blooded breeds. Moreover, significant variations of hematological analytes have been found between subjects with different physiological status and age. [ABSTRACT FROM AUTHOR]

Fumarate adduction to cysteines has been implicated in the pathogenesis of several disorders. Its role, however, still remains elusive, and the need of predictive methods has not yet been met. The reactivity of cysteines found in fumarate-sensitive proteins was predicted when the collected data for eight network-type features were analyzed using classification models. Therefore, methods for evaluating the likelihood of a cysteine site to be modified by fumarate could be developed by combining concepts of network theory and machine learning. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Real-world evidence on glucagon-like peptide-1 receptor agonist (GLP-1 RAs) usage is emerging in different European countries but is lacking in Italy. This retrospective cohort study aimed to describe the real-world drug utilization patterns in patients initiating GLP-1 RAs for treating T2DM in Italy. METHODS: Adults aged ≥ 20 years and with ≥ 1 oral antidiabetic drug (alone or in combination with insulin) other than GLP-1 RAs in the 6 months prior to initiating exenatide twice daily (exBID), exenatide once weekly (exQW), dulaglutide once weekly (DULA), liraglutide once daily (LIRA) or lixisenatide once daily (LIXI) between March and July 2016 were retrospectively identified in the Italian IMS LifeLink™ longitudinal prescriptions database (retail pharmacy data). Patients with ≥ 6-month follow-up (defined as evidence of any prescription activity) were included. Proportions of patients who remained persistent (continued treatment until discontinuation/switch) in the first 6 months and of those who discontinued or switched to a different GLP-1 RA over the entire follow-up were recorded. For each treatment, the average daily/weekly dosage (ADD/AWD) while persistent during the available follow-up was calculated. RESULTS: We identified 7319 patients: 92 exBID, 970 exQW, 3368 DULA, 2573 LIRA and 316 LIXI. Across treatments, 89% patients were ≥ 50 years old, 54% were males, and the median follow-up duration ranged between 8.1 and 8.7 months. At 6 months, 35% exBID, 47% exQW, 62% DULA, 50% LIRA and 40% LIXI patients remained persistent. Over the entire follow-up, median persistence days varied from 73 (exBID) to > 300 days (DULA). The mean ± SD ADD/AWD was exBID: 17.7 ± 2.1 μg/day; exQW: 2.1 ± 0.1 mg/week; DULA: 1.5 ± 0.2 mg/week; LIRA: 1.5 ± 0.2 mg/day; LIXI: 21.0 ± 5.5 μg/day. CONCLUSIONS: This real-world analysis suggests differences exist in persistence between patients treated with various GLP-1 RAs. Among the investigated treatments, patients prescribed exBID recorded the lowest and those prescribed DULA the highest persistence with therapy. [ABSTRACT FROM AUTHOR]

Objective: To analyze the characteristics of patients scheduled for discharge from acute psychiatric inpatient facilities in Italy, and their pattern of care.Methods: Socio-demographic and clinical characteristics, and patterns of care of 1,330 patients discharged from public and private inpatient facilities in Italy were assessed with a standardized methodology during an index period in the year 2004.Results: About one half of the sample had schizophrenia or bipolar disorder. However, the case-mix differed between public and private facilities, where in-patients had more frequently mood and anxiety disorders. The use of two or more drugs was very common, involving more than 90% of patients and including typically benzodiazepines and antipsychotics. Structured psychosocial treatments were rarely initiated during the hospital stay. Increasing age, male gender, long stay in the facility (>60 days), personality disorder and type of facility were associated with a higher likelihood of being discharged to a community residential facility. Predictors of discharge to another psychiatric facility were increasing age, being single, schizophrenia, personality disorder and organic mental disorder. Families were not involved in decisions about patients' discharge in a significant proportion of cases. University psychiatric clinics and private facilities were less coordinated with the community system of care than General Hospital Psychiatric Units. Referral of patients with substance use disorder to drug addiction services occurred in just 30% of subjects.Conclusions: This study provides information on the characteristics and the pattern of care of patients discharged from inpatient facilities in a country that has closed down all its mental hospitals. This information may be relevant for those countries that are affording now the downsizing of MHs, and the expansion of community-based models of care. [ABSTRACT FROM AUTHOR]

Canine mammary tumors (CMTs) share many features with human breast cancer (HBC), specifically concerning cancer-related pathways. Although the human epidermal growth factor receptor 2 (HER2) plays a significant role as a therapeutic and prognostic biomarker in HBC, its relevance in the pathogenesis and prognosis of CMT is still controversial. The aim of this study was to investigate HER2 expression in canine mammary hyperplasic and neoplastic tissues as well as to evaluate the specificity of the most commonly used polyclonal anti HER2 antibody by multiple molecular approaches. HER2 protein and RNA expression were determined by immunohistochemistry (IHC) and by quantitative real-time (qRT) PCR. A strong cell membrane associated with non-specific cytoplasmic staining was observed in 22 % of carcinomas by IHC. Adenomas and carcinomas exhibited a significantly higher HER2 mRNA expression when compared to normal mammary glands, although no significant difference between benign and malignant tumors was noticed by qRT-PCR. The IHC results suggest a lack of specificity of the FDA-approved antibody in CMT samples as further demonstrated by Western immunoblotting (WB) and reverse phase protein arrays (RPPA). Furthemore, HER2 was not detected by mass spectrometry (MS) in a protein-expressing carcinoma at the IHC investigation. This study highlights that caution needs to be used when trying to translate from human to veterinary medicine information concerning cancer-related biomarkers and pathways. Further investigations are necessary to carefully assess the diagnostic and biological role specifically exerted by HER2 in CMTs and the use of canine mammary tumors as a model of HER2 over-expressing breast cancer. [ABSTRACT FROM AUTHOR]

This study investigated the clinical relevance of acute pancreatitis in allogeneic hemopoietic stem cell (bone marrow or peripheral blood) transplants (BMT). We studied 26 patients undergoing BMT. The preparative regimen was busulfan and cyclophosphamide in 17 patients and total body irradiation and cyclophosphamide in 9 patients. Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporin A and short-term methotrexate in all 26 patients. The pancreas was studied using amylase and lipase serum levels, abdominal contrast-enhanced tomography, and/or ultrasound. Clinical and laboratory signs of acute pancreatitis were found in two patients with acute hepatointestinal GVHD, and in one patient with acute hepatic GVHD and cytomegalovirus infection. This patient died of multiorgan failure, with interstitial acute pancreatitis at autopsy; the other two patients recovered with general supportive care and GVHD therapy. We suggest that in the patients with complications after BMT, particularly acute hepatic/hepatointestinal GVHD, and cytomegalovirus infection, the possibility of acute pancreatitis should be considered. [ABSTRACT FROM AUTHOR]

The present study aims to develop a methodology via Fourier transform infrared (FT-IR) spectroscopy for the semiquantitative determination of triacylglycerols (TAGs) in microalgal consortia, consistent with the use of the technique as process control. FT-IR spectroscopy has proved to be a powerful analytical tool for the identification of macromolecular pools (e.g., proteins, lipids, and carbohydrates) and in monitoring biochemical changes (including lipids) in response to nutrient stress or environmental modifications. In the Oocystis-based consortium under examination, the synthesis of neutral lipid in the form of TAGs can be induced, applying stress condition, and these lipids are suitable as biodiesel precursors. In the exponential growing phase, the consortium shows a low TAGs content, in the order of 5 %w, that can be increased till around 22 %w on ash free dry matter, after nitrogen starvation. [ABSTRACT FROM AUTHOR]

Various authors hold that some emotions (i.e., moral emotions) have the function of orienting people toward ethical actions. In addition to embarrassment, shame and pride, the moral emotion of guilt is believed to affect humans' behavior when they carry out transgressions that violate social and cultural standards. Over the past century, many studies (including controversial ones) have been conducted on guilt. In this study, we analyzed and summarized mainly the most recent literature on this emotion. On one side, the destructiveness of guilt is emphasized. It inflicts punishment and pain on individuals for their errors and can lead to psychopathology (e.g., depression). On the other side, it is described as a 'friendly' emotion that motivates behavior adapted to social and cultural rules. How can this asymmetry be explained? Different existing views on guilt are presented and discussed, together with recent proposals, supported by research data. Finally, we discussed some systematic models that try to incorporate these different views in a single framework that could facilitate future researches. [ABSTRACT FROM AUTHOR]

The fabrication of advanced devices increasingly requires materials with different properties to be combined in the form ofmonolithic heterostructures. In practice thismeans growing epitaxial semiconductor layers on substrates often greatly differing in lattice parameters and thermal expansion coefficients. With increasing layer thickness the relaxation ofmisfit and thermal strainsmay cause dislocations, substrate bowing and even layer cracking. Minimizing these drawbacks is therefore essential for heterostructures based on thick layers to be of any use for device fabrication. Here we prove by scanning X-ray nanodiffraction that mismatched Ge crystals epitaxially grown on deeply patterned Si substrates evolve into perfect structures away from the heavily dislocated interface. We show that relaxing thermal and misfit strains result just in lattice bending and tiny crystal tilts. We may thus expect a new concept in which continuous layers are replaced by quasi-continuous crystal arrays to lead to dramatically improved physical properties [ABSTRACT FROM AUTHOR]

Background:As epidermal growth factor receptor (EGFR) is involved in the pathogenesis of malignant pleural mesotheliomas (MPMs), the anti-EGFR drugs may be effective in treating MPM patients. Mutations of the EGFR gene or its downstream effectors may cause constitutive activation leading to cell proliferation, and the inhibition of apoptosis and metastases. Consequently, molecular profiling is essential for select patients with MPM who may respond to anti-EGFR therapies.Methods:After manual macrodissection, genomic DNA was extracted from 77 histological samples of MPM: 59 epithelioid, 10 biphasic, and 8 sarcomatoid. Epidermal growth factor receptor gene mutations were sought by means of real-time polymerase chain reaction (PCR) and direct sequencing, KRAS gene mutations by mutant-enriched PCR, and PIK3CA and BRAF gene mutations by direct sequencing.Results:Gene mutations were identified in nine cases (12%): five KRAS, three BRAF, and one PI3KCA mutation; no EGFR gene mutations were detected. There was no difference in disease-specific survival between the patients with or without gene mutations (P=0.552).Conclusions:Mutations in EGFR downstream pathways are not rare in MPM. Although none of those found in this study seemed to be prognostically significant, they may support a more specific selection of patients for future trials. [ABSTRACT FROM AUTHOR]

Purpose: Postprandial metabolic stress as a consequence of ingestion of high-energy meals is recognized as an important risk factor for cardiovascular disease. The objective of this study was to evaluate the inflammatory and antioxidant response of the body to the acute ingestion of a high-fat meal (HFM). Methods: Fifteen healthy overweight subjects were recruited for the study. After HFM consumption, plasma glucose, insulin, uric acid (UA), triglycerides (TG), total cholesterol (TC), thiols (SH), inflammatory cytokines (IL-6 and TNF-α) and dietary antioxidants were measured at 0, 0, 5, 1, 2, 4, 6 and 8 h points from ingestion. Results: The ingestion of HFM induced significant increases in both TG and TC, with peaks at 4 h ( p < 0.001) and 8 h ( p < 0.01), respectively. IL-6 and TNF-α significantly increased postprandially, reaching maximum concentrations 8 h after meal consumption ( p < 0.001). Whereas plasma concentrations of vitamins and carotenoids were not changed by HFM, SH and UA increased, peaking 2-4 h postingestion ( p < 0.001 and 0.01, respectively). Increments of SH and UA were positively correlated with AUC for TG (Pearson coefficient 0.888, p < 0.001 and 0.923, p < 0.001, respectively). Conclusions: Present results indicate that as a consequence of an excess of dietary fat, the body responds through an inflammatory reaction, which is accompanied by an increment of endogenous antioxidant defenses, mediated by UA and SH, but not by vitamins C and E and carotenoids. Although further studies are needed, results of the current investigation represent novel findings on endogenous strategies of redox defense from fat overloads. [ABSTRACT FROM AUTHOR]

Objective and design: The renal expression of H and H receptors has previously been demonstrated, while that of the H receptor has been poorly investigated, and thus the aim of this research was to investigate the expression of the H receptor in the kidney of diabetic rats. Material or subjects: 24 8-week-old male Wistar rats. Treatment: Diabetes was induced in 12 rats by a single intravenous injection of streptozotocin, and animals were killed 6 weeks later. Methods: Kidneys were collected and processed for quantitative PCR or immunohistochemical analyses. To ascertain the renal topology of the H receptor, colocalization experiments were performed with a series of markers. Results: H receptor is expressed in healthy rats, although at a very low level, and is strongly upregulated in diabetic animals. Immunohistochemical analysis revealed the highest immune-positivity in the medulla. Colocalization experiments revealed a close overlap in expression topology of the H receptor and both Tamm-Horsfall glycoprotein and aquaporin 1 was observed. Conclusions: The results demonstrate, for the first time, that the H receptor is expressed in the kidney mainly by resident renal cells of the loop of Henlé and that this receptor is significantly overexpressed in diabetic animals, thus suggesting a possible role in the pathogenesis of diabetes-associated renal disease. [ABSTRACT FROM AUTHOR]

Objective: High levels of both angiotensin (Ang) II and tumor necrosis factor (TNF)-α have been implicated in the pathogenesis of glomerular injury by affecting podocytes. The aim of this study was to investigate the Ang II-TNF-α relationship in human podocytes. Methods: Immortalized podocytes were exposed to Ang II for 6 days in the absence or presence of either losartan or PD123,319 (both at 100 nM), AT and AT receptor antagonists, respectively. Results: Ang II, after at least 72 h of repeated treatment, increased basal TNFA gene expression and cytokine release with a biphasic pattern and maximum response at 10 nM. Losartan dampened the effects of Ang II on TNF-α production throughout the experimental period, demonstrating an AT receptor contribution. PD123,319 affected the second TNF-α production peak, showing also an AT receptor contribution. Moreover, Ang II causes tumor necrosis factor receptor (TNFR) 1 and TNFR2 over-expression in a time-dependent manner. The functional interaction between Ang II and TNF-α was demonstrated when the pro-proliferative effect of Ang II was antagonized by a neutralizing TNF-α antibody. Conclusions: Our results show a functional interaction between Ang II and TNF-α and implicate this cytokine as a mediator in Ang II long-term pathoadaptive podocytes changes. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Ultrasound is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of La Radiologia Medica is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

case of disseminated angiostrongylosis caused by Angiostrongylus vasorum in a dog living in Italy is here described. The dog was referred for severe respiratory distress and epileptic seizures; clinicopathological findings were consistent with severe pneumonia associated with right-sided heart failure and multifocal involvement of the brain. Bronchoalveolar fluid analysis identified a multitude of nematode larvae, identified as A. vasorum by conventional and biomolecular (PCR) methods. The major anatomo-histopathological lesions were chronic granulomatous pneumonia, a severe multifocal granulomatous myocarditis and multifocal mild vascular and inflammatory disease in the brain. A. vasorum should be included among the differentials of dogs with cardiovascular and neurologic disease. [ABSTRACT FROM AUTHOR]

Red giants are evolved stars that have exhausted the supply of hydrogen in their cores and instead burn hydrogen in a surrounding shell. Once a red giant is sufficiently evolved, the helium in the core also undergoes fusion. Outstanding issues in our understanding of red giants include uncertainties in the amount of mass lost at the surface before helium ignition and the amount of internal mixing from rotation and other processes. Progress is hampered by our inability to distinguish between red giants burning helium in the core and those still only burning hydrogen in a shell. Asteroseismology offers a way forward, being a powerful tool for probing the internal structures of stars using their natural oscillation frequencies. Here we report observations of gravity-mode period spacings in red giants that permit a distinction between evolutionary stages to be made. We use high-precision photometry obtained by the Kepler spacecraft over more than a year to measure oscillations in several hundred red giants. We find many stars whose dipole modes show sequences with approximately regular period spacings. These stars fall into two clear groups, allowing us to distinguish unambiguously between hydrogen-shell-burning stars (period spacing mostly ∼50 seconds) and those that are also burning helium (period spacing ∼100 to 300 seconds). [ABSTRACT FROM AUTHOR]