Biomarkers in neuroendocrine tumors.

Here, we review the role of clinical biomarkers (tissue and circulating markers) in the management of neuroendocrine tumors. These tumors may originate in different organs, from cells embriologically different but expressing common phenotypic characteristics, such as the immuno-reactivity for markers of neuro endocrine differentiation (defined as "pan-neuroendocrine"), the capacity to sec rete specific or aspecific peptide and hormones, and the expression of some receptors, that are at the basis of the current diagnostic and therapeutic approach

Nutrition in oncologic patients during antiblastic treatment.

Cancer may induce weight loss and cachexia, and cancer treatment may contribute to nutritional impairment. Here, we review the literature on the mechanisms of cancer cachexia and the pharmacological interventions both in use in clinical practice and currently under development. Based on this analysis, several nutritional proposals for cancer patients are suggested and the importance of good nutritional status in candidates for hematopoietic stem cell transplantation is highlighted

A Genetic and Metabolic Staging System for Predicting the Outcome of Nonalcoholic Fatty Liver Disease

Nonalcoholic fatty liver disease (NAFLD) is an emerging cause of liver-related events (LREs). Here, we have assessed the ability of a composite score based on clinical features, metabolic comorbidities, and genetic variants to predict LREs. A total of 546 consecutive patients with NAFLD were recruited and stratified according to the fibrosis-4 (FIB-4) index. LREs were defined as occurrence of hepatocellular carcinoma or hepatic decompensation. Cox regression multivariate analysis was used to identify baseline variables associated with LREs. The UK Biobank was used as the validation cohort, and severe liver disease (incidence of cirrhosis, decompensated liver disease, hepatocellular carcinoma, and/or liver transplantation) was used as the outcome. LREs were experienced by 58 patients, only one of whom was in the cohort of patients with a FIB-4 score < 1.3. Multivariate Cox regression analysis of 229 patients with a FIB-4 score ≥ 1.3 highlighted clinical variables independently associated with the development of LREs, including older age, low platelet count, low albumin, low high-density lipoprotein cholesterol, certain genetic factors, and interactions between genetic factors and sex or diabetes. The area under the curve (AUC) for the model was 0.87 at 1, 3, and 5 years. Our novel Genetic and Metabolic Staging (GEMS) scoring system was derived from the Cox model linear predictor, ranked from 0 to 10, and categorized into five classes (0-5, 5-6, 6-7, 7-8, and 8-10). The risk of LREs increased from 4% in patients in the best class (GEMS score 0-5) to 91% in the worst (GEMS score 8-10). GEMS score was associated with incident severe liver disease in the study population (hazard ratio, 1.56; 95% confidence interval, 1.48-1.65; P < 0.001) as well as in the UK Biobank cohort where AUCs for prediction of severe liver disease at 1, 3, and 5 years were 0.70, 0.69, and 0.67, respectively. Conclusion: The novel GEMS scoring system has an adequate ability to predict the outcome of patients with NAFLD

Hypertonic Saline in Conjunction with High-Dose Furosemide Improves Dose–Response Curves in Worsening Refractory Congestive Heart Failure

Introduction: Diuretic responsiveness in patients with chronic heart failure (CHF) is better assessed by urine production per unit diuretic dose than by the absolute urine output or diuretic dose. Diuretic resistance arises over time when the plateau rate of sodium and water excretion is reached prior to optimal fluid elimination and may be overcome when hypertonic saline solution (HSS) is added to high doses of furosemide. Methods: Forty-two consecutively hospitalized patients with refractory CHF were randomized in a 1:1:1 ratio to furosemide doses (125 mg, 250 mg, 500 mg) so that all patients received intravenous furosemide diluted in 150 ml of normal saline (0.9%) in the first step (0–24 h) and the same furosemide dose diluted in 150 ml of HSS (1.4%) in the next step (24–48 h) as to obtain 3 groups as follows: Fourteen patients receiving 125 mg (group 1), fourteen patients receiving 250 mg (group 2), and fourteen patients receiving 500 mg (group 3) of furosemide. Urine samples of all patients were collected at 30, 60, and 90 min, and 3, 4, 5, 6, 8, and 24 h after infusion. Diuresis, sodium excretion, osmolality, and furosemide concentration were evaluated for each urine sample. Results: After randomization, 40 patients completed the study. Two patients, one in group 2 and one in group 3 dropped out. Patients in group 1 (125 mg furosemide) had a mean age of 77 ± 17 years, 43% were male, 6 (43%) had heart failure with a preserved ejection fraction (HFpEF), and 64% were in New York Heart Association (NYHA) class IV; the mean age of patients in group 2 (250 mg furosemide) was 80 ± 8.1 years, 15% were male, 5 (38%) had HFpEF, and 84% were in NYHA class IV; and the mean age of patients in group 3 (500 mg furosemide) was 73 ± 12 years, 54% were male, 6 (46%) had HFpEF, and 69% were in NYHA class IV. HSS added to furosemide increased total urine output, sodium excretion, urinary osmolality, and furosemide urine delivery in all patients and at all time points. The percentage increase was 18,14, and 14% for urine output; 29, 24, and 16% for total sodium excretion; 45, 34, and 20% for urinary osmolarity; and 27, 36, and 32% for total furosemide excretion in groups 1, 2, and 3, respectively. These findings were translated in an improvement in the furosemide dose–response curves in these patients. Conclusion: These results may serve as new pathophysiological basis for HSS use in the treatment of refractory CHF

Lmx1a-Dependent Activation of miR-204/211 Controls the Timing of Nurr1-Mediated Dopaminergic Differentiation

The development of midbrain dopaminergic (DA) neurons requires a fine temporal and spatial regulation of a very specific gene expression program. Here, we report that during mouse brain development, the microRNA (miR-) 204/211 is present at a high level in a subset of DA precursors expressing the transcription factor Lmx1a, an early determinant for DA-commitment, but not in more mature neurons expressing Th or Pitx3. By combining different in vitro model systems of DA differentiation, we show that the levels of Lmx1a influence the expression of miR-204/211. Using published transcriptomic data, we found a significant enrichment of miR-204/211 target genes in midbrain dopaminergic neurons where Lmx1a was selectively deleted at embryonic stages. We further demonstrated that miR-204/211 controls the timing of the DA differentiation by directly downregulating the expression of Nurr1, a late DA differentiation master gene. Thus, our data indicate the Lmx1a-miR-204/211-Nurr1 axis as a key component in the cascade of events that ultimately lead to mature midbrain dopaminergic neurons differentiation and point to miR-204/211 as the molecular switch regulating the timing of Nurr1 expression

Self-formed LaAlO3/SrTiO3LaAlO_3/SrTiO_3 Micro-Membranes

Oxide heterostructures represent a unique playground for triggering the emergence of novel electronic states and for implementing new device concepts. The discovery of 2D conductivity at the $LaAlO_3/SrTiO_3$ interface has been linking for over a decade two of the major current research fields in Materials Science: correlated transition-metal-oxide systems and low-dimensional systems. A full merging of these two fields requires nevertheless the realization of $LaAlO_3/SrTiO_3$ heterostructures in the form of freestanding membranes. Here we show a completely new method for obtaining oxide hetero-membranes with micrometer lateral dimensions. Unlike traditional thin-film-based techniques developed for semiconductors and recently extended to oxides, the concept we demonstrate does not rely on any sacrificial layer and is based instead on pure strain engineering. We monitor through both real-time and post-deposition analyses, performed at different stages of growth, the strain relaxation mechanism leading to the spontaneous formation of curved hetero-membranes. Detailed transmission electron microscopy investigations show that the membranes are fully epitaxial and that their curvature results in a huge strain gradient, each of the layers showing a mixed compressive/tensile strain state. Electronic devices are fabricated by realizing ad hoc circuits for individual micro-membranes transferred on silicon chips. Our samples exhibit metallic conductivity and electrostatic field effect similar to 2D-electron systems in bulk heterostructures. Our results open a new path for adding oxide functionality into semiconductor electronics, potentially allowing for ultra-low voltage gating of a superconducting transistors, micromechanical control of the 2D electron gas mediated by ferroelectricity and flexoelectricity, and on-chip straintronics.Comment: 8 pages, 4 figure

Xerostomia, gustatory and olfactory dysfunctions in patients with COVID-19

Background The novel Coronavirus Disease-19 (COVID-19) continues to have profound effect on global health. Our aim was to evaluate the prevalence and characterize specific symptoms associated with COVID-19. Methods This retrospective study included 326 patients with confirmed SARS-CoV-2 infection evaluated at the Emergency Department of the Umberto I Polyclinic Hospital, Rome, Italy between March 6th and April 30th, 2020. In order to assess xerostomia, olfactory and gustatory dysfunctions secondary to COVID-19, a telephone-based a modified survey obtained from the National Health and Nutrition Examination Survey (NHANES) 2013–2014 for taste and smell disorders and the Fox Questionnaire for dry mouth were administered to 111 patients (34%) after discharge between June 4th and June 12th. Results Taste dysfunction was the most common reported symptom (59.5%; n = 66), followed by xerostomia (45.9%; n = 51) and olfactory dysfunctions (41.4%; n = 46). The most severe symptom was olfactory dysfunction with a median severity score of 8.5 (range: 5–10). Overall 74.5% (n = 38) of patients with xerostomia, 78.8% (n = 52) of patients with gustatory dysfunctions and 71.1% (n = 33) of patients with olfactory dysfunctions reported that all symptoms appeared before COVID-19 diagnosis. Overall, the majority of patients reported one symptom only (45.9%, n = 51), 37 (33.3%) reported the association of two symptoms, and 23 (20.7%) patients reported the association of three symptoms at the same time. Conclusion Xerostomia, gustatory and olfactory dysfunctions may present as a prodromal or as the sole manifestation of COVID-19. Awareness is fundamental to identify COVID-19 patients at an early stage of the disease and limit the spread of the virus

LIFE Monza: comparison between ante and post-operam noise and air quality monitoring activities in a Noise Low Emission Zone

AbstractLIFE MONZA project (Methodologies fOr Noise low emission Zones introduction And management) aims at defining an easy-replicable method for the identification and management of theNoise Low Emission Zones(Noise LEZ), urban areas subject to traffic restrictions, usually introduced in order to ensure compliance with the air pollutants limit values, prescribed by the European Directive on ambient air quality 2008/50/EC, whose impacts and potential benefits regarding noise issues have been taken into account, tested and analysed in a pilot area of the city of Monza, located in North Italy. Noise LEZ has been established in Libertà district, introducing infrastructural interventions carried out by the municipality (top-down actions) and encouraging an active involvement of the citizens, in the definition of a more sustainable lifestyle (bottom-up actions). The analysis of potential effects on noise reduction due to the Noise LEZ can contribute to the implementation of the EU Directive 2002/49/EC, related to the assessment and management of environmental noise (Environmental Noise Directive – END), which introduces noise action plans, designed to manage noise issues and their effects, suggesting the adoption of urban and mobility planning. Noise and air quality monitoring activities have been carried out in pilot area inanteandpost-operamconditions. The monitoring methods, the measurement techniques, the analysis procedures, able to describe the effects due to Noise LEZ establishment, for both the main environmental issues are reported in this paper, as proposals to be applied in other different contexts. Results of monitoring activities highlight a reduction of noise, in term of sound pressure levels, betweenanteandpost-operam, during the day and particularly during the night period, and it is essentially due to the interventions realised. The effect of the Noise LEZ on air pollution seems to be negligible for combustion related pollutant and carbon fractions of PM, due both to the moderate spatial effects of the measures undertaken and confounding factors due to concomitant emission sources and meteorology

Erratum to: Constraining theories of gravity by GINGER experiment

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Cyclic Vomiting Syndrome in Children

Cyclic Vomiting Syndrome (CVS) is an underdiagnosed episodic syndrome characterized by frequent hospitalizations, multiple comorbidities, and poor quality of life. It is often misdiagnosed due to the unappreciated pattern of recurrence and lack of confirmatory testing. CVS mainly occurs in pre-school or early school-age, but infants and elderly onset have been also described. The etiopathogenesis is largely unknown, but it is likely to be multifactorial. Recent evidence suggests that aberrant brain-gut pathways, mitochondrial enzymopathies, gastrointestinal motility disorders, calcium channel abnormalities, and hyperactivity of the hypothalamic-pituitary-adrenal axis in response to a triggering environmental stimulus are involved. CVS is characterized by acute, stereotyped and recurrent episodes of intense nausea and incoercible vomiting with predictable periodicity and return to baseline health between episodes. A distinction with other differential diagnoses is a challenge for clinicians. Although extensive and invasive investigations should be avoided, baseline testing toward identifying organic causes is recommended in all children with CVS. The management of CVS requires an individually tailored therapy Management of acute phase is mainly based on supportive and symptomatic care. Early intervention with abortive agents during the brief prodromal phase can be used to attempt to terminate the attack. During the interictal period, non-pharmacologic measures as lifestyle changes and the use of reassurance and anticipatory guidance seem to be effective as a preventive treatment. The indication for prophylactic pharmacotherapy depends on attack intensity and severity, the impairment of the QoL and if attack treatments are ineffective or cause side effects. When children remain refractory to acute or prophylactic treatment, or the episode differs from previous ones, the clinician should consider the possibility of an underlying disease and further mono- or combination therapy and psychotherapy can be guided by accompanying comorbidities and specific sub-phenotype. This review was developed by a joint task force of the Italian Society of Pediatric Gastroenterology Hepatology and Nutrition (SIGENP) and Italian Society of Pediatric Neurology (SINP) to identify relevant current issues and to propose future research directions on pediatric CV