Ricerca ed innovazione migliorano la qualità della vita (occorre coraggio impegno e talvolta ribellione).

Coraggio, impegno e talvolta ribellione, non disgiunti dal necessario rispetto, sono le doti adatte a praticare ricerca ed innovazione. Meno importante è il campo di elezione, dalla scienza alla tecnica, come dalle lettere alle arti, con interessanti contaminazioni e fruttuose ibridazioni. La filosofia scientifica e la storia della scienza e della tecnica servono a mostrare, quanto fruttifera sia la via e quanto ben distinta dai retaggi spiritualisti, idealisti e storicisti. Infatti queste dottrine pretendono di fornire spiegazioni a priori e certezze assolute, quando la conoscenza della realtà è possibile solo con approssimazioni probabilistiche. In questo contesto, si colloca anche una concezione moderna delle discipline del rilevamento che devono sempre tener conto della grande complessità ed estrema variabilità della realtà fisica ed antropica

Ambulatory Care Pharmacy Resident

Objectives: 1. Review the background, epidemiology, and diagnostic criteria for the antiphospholipid syndrome 2. List clinical manifestations associated with antiphospholipid syndrome 3. Describe the pathophysiology of thrombosis in the antiphospholipid syndrome 4. Evaluate the evidence for the different intensities of oral anticoagulation in the 1. Background 1-3 i. Antiphospholipid syndrome (APS) is an autoimmune disease characterized by the presence of antiphospholipid antibodies (aPL)

A Novel Muco-Gingival Approach for Immediate Implant Placement to Obtain Soft- and Hard-Tissue Augmentation

The aim of this article is to describe a novel approach combining muco-gingival, regenerative and prosthetics concepts for immediate implant insertion that overcomes the limits traditionally considered as contraindications for Type 1 flapless implant positioning, simultaneously obtaining soft- and hard-tissue augmentation. After pre-surgical CBCT evaluation, the surgical technique consisted in the execution of a lateral-approach coronally advanced envelope flap, with oblique submarginal interproximal incisions directed towards the flap’s center of rotation (the tooth to be extracted); after buccal-flap elevation, the atraumatic extraction of the tooth was performed. Following guided implant insertion, a mixture of biomaterial and autologous bone was placed, stabilized by a pericardium membrane and a connective-tissue graft sutured in the inner aspect of the buccal flap. The peri-implant soft tissues were conditioned with a provisional crown until the shape and position for the mucosal scallop to resemble the gingival margin of the adjacent corresponding tooth were obtained; then, the definitive screw-retained restoration was placed. Within the limitations of this case report, the proposed immediate implant placement approach combining CTG application and buccal bone regeneration showed the possibility of obtaining 1-year-follow-up implant success, stable bone level, good esthetic results and high patient satisfaction

Effects of Growth Hormone (GH) Therapy Withdrawal on Glucose Metabolism in Not Confirmed GH Deficient Adolescents at Final Height.

CONTEXT OBJECTIVE: Growth hormone deficiency (GHD) is associated with insulin resistance and diabetes, in particular after treatment in children and adults with pre-existing metabolic risk factors. Our aims were. i) to evaluate the effect on glucose metabolism of rhGH treatment and withdrawal in not confirmed GHD adolescents at the achievement of adult height; ii) to investigate the impact of GH receptor gene genomic deletion of exon 3 (d3GHR). DESIGN SETTING: We performed a longitudinal study (1 year) in a tertiary care center. METHODS: 23 GHD adolescent were followed in the last year of rhGH treatment (T0), 6 (T6) and 12 (T12) months after rhGH withdrawal with fasting and post-OGTT evaluations. 40 healthy adolescents were used as controls. HOMA-IR, HOMA%\u3b2, insulinogenic (INS) and disposition (DI) indexes were calculated. GHR genotypes were determined by multiplex PCR. RESULTS: In the group as a whole, fasting insulin (p<0.05), HOMA-IR (p<0.05), insulin and glucose levels during OGTT (p<0.01) progressively decreased from T0 to T12 becoming similar to controls. During rhGH, a compensatory insulin secretion with a stable DI was recorded, and, then, HOMA\u3b2 and INS decreased at T6 and T12 (p<0.05). By evaluating the GHR genotype, nDel GHD showed a decrease from T0 to T12 in HOMA-IR, HOMA\u3b2, INS (p<0.05) and DI. Del GHD showed a gradual increase in DI (p<0.05) and INS with a stable HOMA-IR and higher HDL-cholesterol (p<0.01). CONCLUSIONS: In not confirmed GHD adolescents the fasting deterioration in glucose homeostasis during rhGH is efficaciously coupled with a compensatory insulin secretion and activity at OGTT. The presence of at least one d3GHR allele is associated with lower glucose levels and higher HOMA-\u3b2 and DI after rhGH withdrawal. Screening for the d3GHR in the pediatric age may help physicians to follow and phenotype GHD patients also by a metabolic point of view

Adherence to the Mediterranean Diet Is Associated with Better Metabolic Features in Youths with Type 1 Diabetes

Our aim was to evaluate adherence to the Mediterranean diet (MedDiet) among children and adolescents with type 1 diabetes (T1D) in relation to metabolic control. Adherence to the MedDiet was assessed with the Mediterranean Diet Quality Index (KIDMED)questionnaire and physical activity by the International Physical Activity Questionnaire for Adolescent (IPAQ-A) on 65 subjects (32 males, 9–18 years) with T1D. Clinical and metabolic evaluation was performed (standardized body mass index(BMI-SDS), hemoglobin A1C (HbA1c), continuous glucose monitoring metrics when present, blood pressure, lipid profile). Parental characteristics (age, body mass index (BMI), socio-economic status) were reported. The adherence to the MedDiet was poor in 12.3%, average in 58.6%, and high in 29.1% of the subjects. Furthermore, 23.4% of patients were overweight/obese. The most impacting factors on BMI-SDS were skipping breakfast and their father’s BMI. HbA1c and time in range % were positively associated with sweets and fish intake, respectively. Additionally, the father’s socio-economic status (SES) and mother’s age were associated with glucose control. Blood pressure was associated with travelling to school in vehicles, extra-virgin olive oil intake and milk/dairy consumption at breakfast. The promotion of the MedDiet, mainly having a healthy breakfast, is a good strategy to include in the management of T1D to improve glucose and metabolic control. This research is valuable for parents to obtain the best results for their children with T1D

Prevalence, risk factors and outcomes of patients coming from the community with sepsis due to multidrug resistant bacteria

Background: Although previous studies showed an increasing prevalence of infections due to multi-drug resistant (MDR) bacteria in the community, specific data on sepsis are lacking. We aimed to assess prevalence, risk factors and outcomes of patients with sepsis due to MDR bacteria. Methods: An observational, retrospective study was conducted on consecutive adult patients coming from the community and admitted to the Policlinico Hospital, Milan, Italy, with a diagnosis of sepsis between January 2011 and December 2015. Primary study outcome was in-hospital mortality. Results: Among 518 patients, at least one MDR bacteria was isolated in 88 (17%). ESBL+ Enterobacteriaceae were the most prevalent MDR bacteria (9.7%) followed by MRSA (3.9%). Independent risk factors for sepsis due to MDR bacteria were septic shock (OR: 2.2; p = 0.002) and hospitalization in the previous 90 days (OR: 2.3; p = 0.003). Independent risk factors for sepsis due to ESBL+ bacteria were hospitalization in the previous 90 days (OR: 2.1; p = 0.02) and stroke (OR: 2.1; p = 0.04). A significantly higher mortality was detected among patients with vs. without MDR bacteria (40.2% vs. 23.1% respectively, p = 0.001). Independent risk factors for mortality among patients with sepsis were coagulation dysfunction (OR: 3.2; p = 0.03), septic shock (OR: 3.2; p = 0.003), and isolation of a MDR bacteria (OR: 4.6; p &lt; 0.001). Conclusion: In light of the prevalence and impact of MDR bacteria causing sepsis in patients coming from the community, physicians should consider ESBL coverage when starting an empiric antibiotic therapy in patients with specific risk factors, especially in the presence of septic shock

SHANK3 controls maturation of social reward circuits in the VTA.

Haploinsufficiency of SHANK3, encoding the synapse scaffolding protein SHANK3, leads to a highly penetrant form of autism spectrum disorder. How SHANK3 insufficiency affects specific neural circuits and how this is related to specific symptoms remains elusive. Here we used shRNA to model Shank3 insufficiency in the ventral tegmental area of mice. We identified dopamine (DA) and GABA cell-type-specific changes in excitatory synapse transmission that converge to reduce DA neuron activity and generate behavioral deficits, including impaired social preference. Administration of a positive allosteric modulator of the type 1 metabotropic glutamate receptors mGluR1 during the first postnatal week restored DA neuron excitatory synapse transmission and partially rescued the social preference defects, while optogenetic DA neuron stimulation was sufficient to enhance social preference. Collectively, these data reveal the contribution of impaired ventral tegmental area function to social behaviors and identify mGluR1 modulation during postnatal development as a potential treatment strategy

Exhaled nitric oxide and nitric oxide synthase expression in Hodgkin's disease

Hodgkin's disease (HD) is a malignant lymphoma with frequent mediastinal involvement, characterized by a significant inflammatory infiltration. Exhaled Nitric Oxide (FENO), is present in healthy humans, and has been proven to be increased in eosinophilic diseases such as allergic asthma. We investigated whether FENO is increased in mediastinal HD and whether NO is produced by lymphoma tissue. To this aim FENO was measured in 56 HD patients, 17 with and 39 without bulky mediastinal involvement, in the period from January 2007 to December 2008. Thirty-seven patients were reassessed after remission. Lymph node biopsies of 10 patients were evaluated for inducible (iNOS) and constitutive (eNOS) nitric oxide synthase expression by immunohistochemistry. FENO resulted significantly related to the mediastinal mass maximum diameter (p=0.009) and was significantly higher in patients with as compared to those without bulky mediastinal disease (38.7 ppb, CI95% 19.3–58.0, versus 20.7 ppb, CI95% 16.6–24.7; p=0.009). iNOS and eNOS immunoreactivity was observed in tumour and inflammatory cells (eosinophils and histiocytes). Only in patients with bulky mediastinal HD there was a significant decrease in FENO (from 50.4 ppb CI95% 18.0–82.8 to 11.1 ppb CI95% 4.4–17.8, p=0.011). In conclusion, high FENO and NOS expression in lymph-nodes indicate that NO is a component of the inflammatory network of HD. FENO may be proposed for the assessment and follow up of bulky mediastinal HD patients

Copy number variations residing outside the SHOX enhancer region are involved in Short Stature and Léri-Weill dyschondrosteosis

Background: SHOX enhancer CNVs, affecting one or more of the seven recognized evolutionary conserved non-coding elements (CNEs) represent one of the most frequent cause of SHOX-haploinsufficiency. During the diagnostic workflow deletions/duplications have been identified downstream SHOX not including any of the these CNEs. Methods: Fine tiling aCGH and breakpoint PCR were used to characterize the critical interval and to search for novel alterations in a cohort of selected patients. Results: Screening of 252 controls provided evidence that duplications in this area represent likely benign variants whereas none of the deletions were detected. These findings suggested that other alterations relevant for SHOX-haploinsufficiency might be missed by the standard diagnostic methods. To identify such undisclosed elements, the aCGH was used to reanalyze 52 unresolved cases with clinical features strongly suggestive of SHOX-haploinsufficiency. This analysis followed by the screening of 210 patients detected two partially overlapping small deletions of ~12 and ~8 kb in four unrelated individuals, approximately 15 kb downstream SHOX, that were absent in 720 normal stature individuals. Conclusion: Our results strengthen the hypothesis that alterations of yet unidentified cis-regulatory elements residing outside those investigated through conventional methods, might explain the phenotype in ISS/LWD patients thus enlarging the spectrum of variants contributing to SHOX-haploinsufficiency