A telemedicine-based approach with real-time transmission of blood glucose data improves metabolic control in insulin-treated diabetes: the DIAMONDS randomized clinical trial.

PURPOSE: To evaluate if a web-based telemedicine system (the Glucoonline® system) is effective to improve glucose control in insulin-treated patients with type 1 and type 2 diabetes, as compared to standard of care. METHODS: This was a prospective, randomized, controlled trial, carried out at three tertiary referral centers for diabetes in Italy. Adults with insulin-treated type 1 and type 2 diabetes, inadequate glycemic control, and no severe diabetes-related complications and/or comorbidities were eligible for this study. Patients were randomized to either perform telemedicine-assisted (Group A) or standard (Group B) self-monitoring blood glucose (SMBG) for 6 months. In Group A, patients received prompt feedback about their blood glucose levels and therapy suggestions from the study staff via phone/SMS, when appropriate. In Group B, patients had no remote assistance from the study staff between planned visits. RESULTS: 123 patients were included in the final analysis. After 6 months, patients achieved a significant reduction in HbA1c in Group A (-0.38%, p < 0.05) but not in Group B (+ 0.08%, p = 0.53). A significant difference in the percentage of patients with HbA1c < 7% between Group A and Group B was found after 3 months (28.6% vs 11.1%, p = 0.02). Also, fewer patients (p < 0.05) with HbA1c > 8.5% were found in Group A vs Group B, respectively, after both 3 months (14.3% vs 35.2%) and 6 months (21.8% vs 42.9%). CONCLUSIONS: The use of the Glucoonline™ system resulted in improved metabolic control. Telemedicine services have potential to support diabetes self-management and provide the patients with remote, prompt assistance using affordable technological equipment. Trial registration This study was registered at clinicaltrials.gov (NCT01804803) on March 5, 2013.

Association between MBOAT7 rs641738 polymorphism and non-alcoholic fatty liver in overweight or obese children.

BACKGROUND AND AIM: The association between non-alcoholic fatty liver (NAFL) and the variant rs641738 within the membrane bound O-acyltransferase domain-containing 7 (MBOAT7) gene is currently uncertain, especially in the paediatric population. We examined whether there is an association between this genetic variant and NAFL in a large multicentre, hospital-based cohort of Italian overweight/obese children. METHODS AND RESULTS: We studied 1760 overweight or obese children [mean age (SD): 11.1(2.9) years, z-body mass index (zBMI) 3.2(0.9)], who underwent ultrasonography for the diagnosis of NAFL. A subgroup of these children (n = 182) also underwent liver biopsy. Genotyping of the MBOAT7 rs641738 polymorphism was performed by TaqMan-Based RT-PCR system in each subject. Overall, 1131 (64.3%) children had ultrasound-detected NAFL; 528 (30%) had rs641738 CC genotype, 849 (48.2%) had rs641738 CT genotype, and 383 (21.8%) had rs641738 TT genotype, respectively. In the whole cohort, the interaction of MBOAT7 genotypes with zBMI was not associated with NAFL after adjustment for age, sex, serum triglycerides, serum alanine aminotransferase levels and patatin-like phospholipase domain-containing protein-3 (PNPLA3) genotype (adjusted-odds ratio 1.02 [95% CI 0.98-1.06]). Similarly, no association was found between MBOAT7 genotypes and NAFL after stratification by obesity status. MBOAT7 genotypes were not associated with the presence of non-alcoholic steatohepatitis or the stage of liver fibrosis in a subgroup of 182 children with biopsy-proven NAFLD. CONCLUSIONS: The results of this study did not show any significant contribution of MBOAT7 rs641738 polymorphism to the risk of having either NAFL on ultrasonography or NASH on histology in a large hospital-based cohort of Italian overweight/obese children.

Preliminary considerations about the presence of Aedes albopictus (Skuse 1897) (Diptera: Culicidae) during winter in the Northwestern Italy.

Aedes albopictus, the Asian tiger mosquito, was unintentionally introduced in Italy at the beginning of the 1990s. In few decades it spread almost in the whole Country. In Piedmont, the first report dates back to 1994. Usually, temperate populations are affected by seasonal temperature and photoperiodicity and can overwinter by producing eggs that undergo a winter diapause. In Rome females of the species extended their trophic activity to the coldest months of the year, but there is no notice about a similar behaviour for northern areas of the Country. In our routine work, we often inspect residential and public buildings according to people requests due to the presence of annoying mosquitoes. During these inspections, we try to identify and solve the problem looking for adults and breeding sites of annoying species. Samples are conveniently collected and identified in the field or returning in the labs. We report seven cases of Ae. albopictus female trophic activity in both residential and public buildings, from November to March, in urban and rural areas in Piedmont, ranging between 44°33'11" N and 45°05'09" N. In one case, some larval breeding sites with a large number of larvae and pupae of this species were identified. Ae. albopictus can show trophic and reproductive activity during the winter in the northwestern Italy under favourable conditions. This evidence is of particular concern because of seasonality of Aedes mosquito-borne disease in returned travellers. Dengue, for example, has its higher morbidity in returned travellers from Caribbean and Central America typically during the winter period.

Nonalcoholic fatty pancreas disease and Nonalcoholic fatty liver disease: more than ectopic fat.

OBJECTIVE: The aim of this study was to evaluate the metabolic effects of fatty pancreas (nonalcoholic fatty pancreas disease - NAFPD) in a group of obese paediatric patients with nonalcoholic fatty liver disease (NAFLD). METHODS: We included 121 consecutive children with echographic evidence of hepatic steatosis. All patients underwent to abdominal ultrasound to evaluate pancreatic echogenic pattern. We divided the patients into two groups on the basis of the presence of fatty pancreas. In all patients liver function tests, lipid and gluco-insulinemic profile were evaluated. A selected subset of patients (67) underwent to liver biopsy. RESULTS: Of these 121 patients, 58 showed NAFPD and 63 patients exhibited a normal pancreatic echogenic pattern. No differences were found in age, transaminases serum levels, lipid profile and pancreatic enzymes between the two groups. The patients with NAFPD had a significantly higher z-BMI, fasting insulin, insulin resistance (HOMA-IR) and lower ISI respect to the group without fatty pancreas. The patients with fatty pancreas showed a more advanced form of liver disease, with higher values of fibrosis, ballooning and NAS score with respect to the group without NAFPD. CONCLUSIONS: Our study demonstrated that NAFPD is a frequent condition in obese paediatric patients affected by NAFLD. Our data suggest that pancreatic fat should not be considered an inert accumulation of fat, but as an additional factor able to affect glucose metabolism and severity of liver disease, increasing the risk of develop metabolic syndrome.

Molecular characterization of 39 de novo sSMC: contribution to prognosis and genetic counselling, a prospective study.

Small supernumerary marker chromosomes (sSMCs) are structurally abnormal chromosomes that cannot be characterized by karyotype. In many prenatal cases of de novo sSMC, the outcome of pregnancy is difficult to predict because the euchromatin content is unclear. This study aimed to determine the presence or absence of euchromatin material of 39 de novo prenatally ascertained sSMC by array-comparative genomic hybridization (array-CGH) or single nucleotide polymorphism (SNP) array. Cases were prospectively ascertained from the study of 65,000 prenatal samples [0.060%; 95% confidence interval (CI), 0.042-0.082]. Array-CGH showed that 22 markers were derived from non-acrocentric markers (56.4%) and 7 from acrocentic markers (18%). The 10 additional cases remained unidentified (25.6%), but 7 of 10 could be further identified using fluorescence in situ hybridization; 69% of de novo sSMC contained euchromatin material, 95.4% of which for non-acrocentric markers. Some sSMC containing euchromatin had a normal phenotype (31% for non-acrocentric and 75% for acrocentric markers). Statistical differences between normal and abnormal phenotypes were shown for the size of the euchromatin material (more or less than 1 Mb, p = 0.0006) and number of genes (more or less than 10, p = 0.0009). This study is the largest to date and shows the utility of array-CGH or SNP array in the detection and characterization of de novo sSMC in a prenatal context.

Use of potentially harmful skin-lightening products among immigrant women in Rome, Italy: a pilot study.

BACKGROUND: Skin-lightening products are increasingly common in European cities. These products may contain substances that are banned under EU regulations as they can induce adverse effects, including cutaneous and systemic reactions (e.g., mercury, hydroquinone and topical corticosteroids). OBJECTIVES: To assess the knowledge, attitudes and practices of women regarding skin-lightening products and to quantify the potentially harmful substances in the products used. METHODS: We performed a cross-sectional study among 82 non-Italian women visiting an outpatient facility in Rome, Italy. The women completed a questionnaire on product use, side effects and risk awareness. We performed patch tests among a subgroup of 48 women who presented with contact dermatitis. We also quantified the allergenic and toxic substances in the 14 products reported, using dynamic reaction cell inductively coupled plasma mass spectrometry for metals and high-performance liquid chromatography for hydroquinone and topical corticosteroids. RESULTS: Out of the 82 women, 33 used skin-lightening products; about one fourth of these women were aware of potential risks. Three cosmetic creams and two soaps contained high concentrations of metals (Cr, Ni and Pb); hydroquinone was found in three creams and one oil. The only topical corticosteroid detected was dexamethasone, in one product. More than half of the women in the clinical evaluation had irritant contact dermatitis (i.e., negative response to patch test). CONCLUSIONS: Among immigrant women in Rome, the use of skin-lightening products seems to be fairly common, and some of these products contain potentially hazardous substances. Consumers must be informed of the potential risks, and EU regulations must be more strictly enforced.

To bridge or not to bridge: Moral Judgement in Cocaine Use Disorders, a case-control study on human morality.

BACKGROUND: In the "Dual-Process theory", morality is characterized by the interaction between an automatic-emotional process, mediated by the Anterior Cingulate Cortex (ACC) and linked to personal-deontological decisions, and a rational-conscious one, mediated by the Dorso-Lateral Prefrontal Cortex (DLPFC) and linked to impersonal-utilitarian decisions. These areas are altered by chronic use of cocaine, with a possible impact on moral decision-making. OBJECTIVE: To evaluate the difference between a group of Cocaine Use Disorder (CUD) patients and a control group in moral decision-making. METHODS: Subjects with CUD were compared to an equal-sized healthy group regarding their moral decision-making. Trolley and Footbridge Moral Dilemmas were administered to each group. The quality of the answer (yes or no) and the time needed to answer were recorded. RESULTS: The recruited group includes 72 subjects, 36 with CUD and 36 healthy subjects (average age of 39.51 ± 9.89). In the Trolley dilemma, almost all the subjects (97.3%) answered "yes", while in the Footbridge dilemma CUD subjects answered "yes" more often (52.7%) than the healthy group (19.4%). CONCLUSION: For strong emotional dilemmas (Footbridge), cocaine users answered "yes" with a higher frequency compared to healthy subjects, highlighting a wider utilitarian tendency in decision-making and a poor emotional participation.

Nasal cytology: the "infectious spot", an expression of a morphological-chromatic biofilm.

The purpose of this study was to describe some "morphological-chromatic" patterns (i.e. spots of cyan colour) identified during the study of nasal cytology in patients with both bacterial and fungal infectious rhinological disorders. These peculiar aspects strongly suggest the presence of a microscopic biofilm. We retrospectively examined 1,410 nasal cytology specimens from subjects who underwent clinical-instrumental investigations (history, ENT visit, nasal endoscopy and nasal cytology) from January to August 2010. The control samples were represented by 30 subjects not suffering from infectious rhinological diseases. The presence of particular spots of "cyan" was found in colour in 107/1,410 rhinocytograms (7.6%), within which bacterial colonies and/or fungal spores were found. We called these coloured spot formations "infectious spots" (IS). The positivity to periodic acid Schiff (PAS) staining confirmed the polysaccharide nature of the coloured spots and allowed us to relate them to biofilms. This study demonstrates, for the first time, that nasal cytology performed by optical microscope can play an important role in detecting biofilms.

The general use of glycated haemoglobin for the diagnosis of diabetes and other categories of glucose intolerance: still a long way to go.

Glycated haemoglobin (HbA(1c)) is considered the 'gold standard' for monitoring metabolic control in diabetes. An International Expert Committee recently recommended HbA(1c) as a better method than measurement of glucose to use in the diagnosis of diabetes, based on its strong association with microvascular complications, a lower day-to-day variability and ease of use, not necessarily in the fasting state. These recommendations have been embraced by the American Diabetes Association (ADA), which stated in its Standards of Medical Care in Diabetes 2010 that "A(1c), fasting plasma glucose or the 2 h 75 g oral glucose tolerance test (OGTT) are appropriate for testing diabetes and assessing the risk of future diabetes," and that "a confirmed A(1c) ≥ 6.5% is diagnostic for diabetes." Measuring HbA(1c) has several advantages over glucose measurements, but its exclusive use should only be considered if the test is conducted under standardised conditions and its limitations are taken into due account. The impact of its use on the epidemiology of diabetes and other categories of glucose intolerance, as seen from recent reports, is also discussed.

Genetic characterization of an almond germplasm collection and volatilome profiling of raw and roasted kernels.

Almond is appreciated for its nutraceutical value and for the aromatic profile of the kernels. In this work, an almond collection composed of 96 Sicilian accessions complemented with 10 widely cultivated cultivars was phenotyped for the production of volatile organic compounds using a proton-transfer time-of-flight mass spectrometer and genotyped using the Illumina Infinium®18 K Peach SNP array. The profiling of the aroma was carried out on fresh and roasted kernels enabling the detection of 150 mass peaks. Sixty eight, for the most related with sulfur compounds, furan containing compounds, and aldehydes formed by Strecker degradation, significantly increased during roasting, while the concentration of fifty-four mass peaks, for the most belonging to alcohols and terpenes, significantly decreased. Four hundred and seventy-one robust SNPs were selected and employed for population genetic studies. Structure analysis detected three subpopulations with the Sicilian accessions characterized by a different genetic stratification compared to those collected in Apulia (South Italy) and the International cultivars. The linkage-disequilibrium (LD) decay across the genome was equal to r2 = 0.083. Furthermore, a high level of collinearity (r2 = 0.96) between almond and peach was registered confirming the high synteny between the two genomes. A preliminary application of a genome-wide association analysis allowed the detection of significant marker-trait associations for 31 fresh and 33 roasted almond mass peaks respectively. An accurate genetic and phenotypic characterization of novel germplasm can represent a valuable tool for the set-up of marker-assisted selection of novel cultivars with an enhanced aromatic profile.

Cannabis use disorder and dissociation: A report from a prospective first-episode psychosis study.

BACKGROUND: Cannabis is the most used recreational drug worldwide. Its use can increase the risk of developing psychotic disorders and exacerbate their course. However, the relationship between cannabis use and dissociative symptoms has been scarcely investigated. AIMS: To examine differences in psychotic and dissociative symptoms, and in functioning in first-episode psychotic patients (FEPp) using cannabis compared with those not using cannabis. METHODS: Between January 2014 and December 2019, seventy FEPp with cannabis use disorder (N = 35) and without it (N = 35) were recruited in psychiatric inpatient facilities in the Italian regions of Lazio and Piemonte. All subjects were assessed at FEP, after 4 and 8 months, using the Positive and Negative Syndrome Scale (PANSS), the Global Assessment of Functioning (GAF) scale and the Dissociative Experiences Scale - II (DES-II). Detailed information on the pattern of cannabis and other substance use were collected. RESULTS: FEP using cannabis showed higher levels of positive symptomatology, dissociative experiences and worse functioning than their non-user counterpart, despite a comparable antipsychotic treatment. At an eight-month prospective evaluation, FEP using cannabis still showed higher levels of positive symptomatology and dissociation. Moreover, global functioning worsened over time in FEPp using cannabis, whereas it improved those not using it. DISCUSSION: Our findings suggest that a greater degree of dissociation and positive symptoms at FEPp and their persistence over time may characterise cannabis-associated psychosis. Both these factors might explain the overall functioning worsening over time that we observed in the cannabis-user group compared to the functioning improvement in the non-user group.

Radical metastasectomy followed by sorafenib versus observation in patients withclear cell renal cell carcinoma: extended follow -up of efficacy results from the randomized phase II RESORT trial.

Background: The RESORT trial showed no longer relapse free survival (RFS) with sorafenib following radical metastasectomy in metastatic renal cell carcinoma. We present the updated 42-month follow-up data.Methods: The phase II RESORT trial randomized patients to sorafenib or observation within 12 weeks from surgery. RFS was the primary endpoint.Results: We analyzed 68 patients (32 in sorafenib and 36 in the observation arm), randomized between November 2012 and November 2017. Eighty-one percent in the sorafenib arm and 80% in the observation arm had one metastasis . At a median follow-up of 42 months (interquartile range 31-58), in the observation arm the median RFS was 35 months, RFS probability was 57% (95% CI 42-76%) at 24 and 44% (95% CI 30-65%) at 48 months. In the sorafenib arm, median RFS was 21 months, RFS probability was 50% (95% CI 34-71%) at 24 and 32% (95% CI 18-57%) at 48 months (p = 0.342;HR 1.35;95% CI 0.72-2.54). Forty-seven percent and 37.5% of the patients in the two arms, respectively, are disease free. The site of relapses was independent of the previous metastasectomy site.Expert commentary: Sorafenib after metastasectomy did not improve RFS, but surgery in selected patients should be considered in order to potentially improve survival.Clinical trial registration: www.clinicaltrials.gov identifier is NCT0144480.

Identification of two new HLA-DRB1 alleles, DRB1*040405 and DRB1*1190.

We describe here two novel DRB1 alleles, officially named *040405 and *1190. DRB1*040405 differs from DRB1*0404 for one point mutation at codon 72 with no coding changes. DRB1*1190 is identical to DRB1*110101 except for a nucleotide substitution at codon 24 which causes an aminoacidic mutation from valine to methionine. Over time we have been witnessing the identification of a great number of new HLA alleles. DRB1 allelic variability is mostly present in the second exon and more that 760 alleles have been so far identified. Here, we report the description of two novel DRB1 alleles, named *040405 and *1190, and identified in two Caucasoid subjects.

Prospective multicentre study on azole resistance in Aspergillus isolates from surveillance cultures in haematological patients in Italy.

OBJECTIVES: This study was conducted to assess the prevalence of azole resistance in Aspergillus isolates from patients with haematological malignancies or who were undergoing haematopoietic stem cell transplantation and to identify the molecular mechanism of resistance. METHODS: In this 28-month prospective study involving 18 Italian centres, Aspergillus isolates from surveillance cultures were collected and screened for azole resistance, and mutations in the cyp51A gene were identified. Resistant isolates were genotyped by microsatellite analysis, and the allelic profiles were compared with those of resistant environmental and clinical isolates from the same geographical area that had been previously genotyped. RESULTS: There were 292 Aspergillus isolates collected from 228 patients. The isolates belonged mainly to the section Fumigati (45.9%), Nigri (20.9%), Flavi (16.8%) and Terrei (4.8%). Three isolates showed itraconazole resistance: Aspergillus fumigatus sensu stricto, Aspergillus lentulus (section Fumigati) and Aspergillus awamori (section Nigri). The itraconazole resistance rates were 1% and 1.48% considering all Aspergillus spp. isolates and the Aspergillus section Fumigati, respectively. The prevalence of azole resistance among all the patients was 1.3%. Among patients harbouring A. fumigatus sensu stricto isolates, the resistance rate was 0.79%. The A. fumigatus isolate, with the TR34/L98H mutation, was genotypically distant from the environmental and clinical strains previously genotyped. CONCLUSIONS: In this study, the Aspergillus azole resistance rate was 1% (3/292). In addition to A. fumigatus sensu stricto, A. lentulus and A. awamori azole-resistant isolates were identified. Therefore, it is important have a correct identification at the species level to address a rapid therapy better, quickly understand the shift towards cryptic species and have an updated knowledge of the local epidemiology.