Anxiolytic and Analgesic Effects of Melatonin in Paediatric Dentistry

Aim: Fear and anxiety are the principal obstacles for dental treatment in children and can turn into dental phobia, leading to patients avoiding dental treatment. Melatonin, an endogenous indolamines produced and secreted by the pineal gland, is involved in many physiological functions such as regulation of circadian rhythm as well as possessing antioxidant, oncostatic, anti-inflammatory and anticonvulsant activity; it may be administered orally or sublingually, without any evidence of substantial side effects. After oral administration, melatonin undergoes first-pass effect, reaches the plasma peak after about 60 min and blood levels decrease in about 4 h. Study Design: This is a retrospective case-control age and sex matched study. We collected data about first visit and treatment of 50 patients admitted to the Dental Clinic and to the Private Center of the investigators. Methods: According to literature, 25 children received 0.5 mg/ kg Melatonin 60\u2019 before being subjected to first visit and pedodontic treatment. No preventive treatment was given to 25 children. We compared the success of treatment and the pain experienced by the child assessed by FLACC behavioural pain scale. Results: Both groups included 25 patients (15 male), mean age 7.6 yrs in Group A, 7.1 yrs in Group B. Melatonin treatment was well tolerated by 100% of children. According to FLACC scale categories, 42% of all children presented relaxed and comfortable or mild discomfort (FLACC scale 0-3), 42% moderate pain (FLACC scale 4-6), and 16% severe discomfort or pain or both (FLACC scale 7-10). Statistics: Operators found greater compliance by children receiving melatonin with 96 % successful treatment versus 68% (p 0.012). We found 60% of children receiving melatonin experienced relaxed and comfortable o mild discomfort versus 40% in Group B (p 0.001). Conclusions: Although a larger population study is needed, the anxiolytic and analgesic properties of melatonin seem to offer new therapeutic opportunity in the pedodontic field

Amyand's hernia in a child with permanent neonatal diabetes due to pancreatic agenesis

Acute or perforated appendicitis within inguinal hernia is rarely encountered and it is known as Amyand's hernia. We report on the first case occurring in a 4-year-old boy affected by permanent neonatal diabetes mellitus due to pancreatic agenesis, an extremely rare condition. The initial suspicion of inguinal hernia was confirmed by ultrasound examination of the right inguinal region which revealed omental layers inside a swollen inguinal canal; this finding and the clinical presentation allowed a prompt and appropriate surgical management. The careful evaluation of this patient and early recognition of this unique presentation of appendicitis allowed trans-hernial appendectomy and immediate herniorrhaphy. Ultrasonography played a pivotal role to reach the correct diagnosis and to start a prompt treatment

Testing the steady-state fluctuation relation in the solar photospheric convection

The turbulent thermal convection on the Sun is an example of an irreversible non-equilibrium phenomenon in a quasi-steady state characterized by a continuous entropy production rate. Here, the statistical features of a proxy of the local entropy production rate, in solar quiet regions at different timescales, are investigated and compared with the symmetry conjecture of the steady-state fluctuation theorem by Gallavotti and Cohen. Our results show that solar turbulent convection satisfies the symmetries predicted by the fluctuation relation of the Gallavotti and Cohen theorem at a local level

Long-term safety and efficacy of daclizumab beta in relapsing-remitting multiple sclerosis : 6-year results from the SELECTED open-label extension study

Objective: SELECTED, an open-label extension study, evaluated daclizumab beta treatment for up to 6 years in participants with relapsing multiple sclerosis who completed the randomized SELECT/SELECTION studies. We report final results of SELECTED. Methods: Eligible participants who completed 1-2 years of daclizumab beta treatment in SELECT/SELECTION received daclizumab beta 150 mg subcutaneously every 4 weeks for up to 6 years in SELECTED. Safety assessments were evaluated for the SELECTED treatment period; efficacy data were evaluated from first dose of daclizumab beta in SELECT/SELECTION. Results: Ninety percent (410/455) of participants who completed treatment in SELECTION enrolled in SELECTED. Within SELECTED, 69% of participants received daclizumab beta for > 3 years, 39% for > 4 years, and 9% for > 5 years; 87% of participants experienced an adverse event and 26% a serious adverse event (excluding multiple sclerosis relapse). No deaths occurred. Overall, hepatic events were reported in 25% of participants; serious hepatic events in 2%. There were no confirmed cases of immune-mediated encephalitis. Based on weeks from the first daclizumab beta dose in SELECT/SELECTION, adjusted annualized relapse rate (95% confidence interval) for weeks 0-24 was 0.21 (0.16-0.29) and remained low on continued treatment. Overall incidence of 24-week confirmed disability progression was 17.4%. Mean numbers of new/newly enlarging T2 hyperintense lesions remained low; percentage change in whole brain volume decreased over time. Conclusions: The effects of daclizumab beta on clinical and radiologic outcomes were sustained for up to ~ 8 years of treatment. No new safety concerns were identified in SELECTED. Trial registration: Clinicaltrials.gov NCT01051349; first registered on January 15, 2010

Allergic sensitization to common pets (cats/dogs) according to different possible modalities of exposure: an Italian Multicenter Study

Background: The query "are there animals at home?" is usually administered for collecting information on anamnesis. This modality to consider exposure to pet allergens constitutes a potential bias in epidemiological studies and in clinical practice. The aim of our study was to evaluate/quantify different modalities of exposure to cat/dog in inducing allergic sensitization. Methods: Thirty Italian Allergy units participated in this study. Each centre was required to collect the data of at least 20 consecutive outpatients sensitized to cat/dog allergens. A standardized form reported all demographic data and a particular attention was paid in relieving possible modalities of exposure to cat/dog. Results: A total 723 patients sensitized to cat/dog were recorded, 359 (49.65%) reported direct pet contact, 213 patients (29.46%) were pet owners, and 146 subjects (20.19%) were exposed to pets in other settings. Other patients were sensitized by previous pet ownership (150-20.75%) or indirect contact (103-14.25%), in 111 subjects (15.35%) any contact was reported. Conclusions: Only 213 patients (29.46%) would be classified as "exposed to animals" and 510 (70.54%) as "not exposed" according to usual query. Our classification has shown that many "not-exposed" subjects (399-55.19%) were "really exposed". The magnitude of exposure to pet allergens at home is not related exclusively to pet ownership. These considerations should be taken into account during the planning of epidemiological studies and in clinical practice for the management of pet allergic individuals

Carriers of ADAMTS13 Rare Variants Are at High Risk of Life-Threatening COVID-19

Thrombosis of small and large vessels is reported as a key player in COVID-19 severity. However, host genetic determinants of this susceptibility are still unclear. Congenital Thrombotic Thrombocytopenic Purpura is a severe autosomal recessive disorder characterized by uncleaved ultra-large vWF and thrombotic microangiopathy, frequently triggered by infections. Carriers are reported to be asymptomatic. Exome analysis of about 3000 SARS-CoV-2 infected subjects of different severities, belonging to the GEN-COVID cohort, revealed the specific role of vWF cleaving enzyme ADAMTS13 (A disintegrin-like and metalloprotease with thrombospondin type 1 motif, 13). We report here that ultra-rare variants in a heterozygous state lead to a rare form of COVID-19 characterized by hyper-inflammation signs, which segregates in families as an autosomal dominant disorder conditioned by SARS-CoV-2 infection, sex, and age. This has clinical relevance due to the availability of drugs such as Caplacizumab, which inhibits vWF-platelet interaction, and Crizanlizumab, which, by inhibiting P-selectin binding to its ligands, prevents leukocyte recruitment and platelet aggregation at the site of vascular damage

An explainable model of host genetic interactions linked to COVID-19 severity

We employed a multifaceted computational strategy to identify the genetic factors contributing to increased risk of severe COVID-19 infection from a Whole Exome Sequencing (WES) dataset of a cohort of 2000 Italian patients. We coupled a stratified k-fold screening, to rank variants more associated with severity, with the training of multiple supervised classifiers, to predict severity based on screened features. Feature importance analysis from tree-based models allowed us to identify 16 variants with the highest support which, together with age and gender covariates, were found to be most predictive of COVID-19 severity. When tested on a follow-up cohort, our ensemble of models predicted severity with high accuracy (ACC = 81.88%; AUCROC = 96%; MCC = 61.55%). Our model recapitulated a vast literature of emerging molecular mechanisms and genetic factors linked to COVID-19 response and extends previous landmark Genome-Wide Association Studies (GWAS). It revealed a network of interplaying genetic signatures converging on established immune system and inflammatory processes linked to viral infection response. It also identified additional processes cross-talking with immune pathways, such as GPCR signaling, which might offer additional opportunities for therapeutic intervention and patient stratification. Publicly available PheWAS datasets revealed that several variants were significantly associated with phenotypic traits such as "Respiratory or thoracic disease", supporting their link with COVID-19 severity outcome.A multifaceted computational strategy identifies 16 genetic variants contributing to increased risk of severe COVID-19 infection from a Whole Exome Sequencing dataset of a cohort of Italian patients

Gain- and Loss-of-Function CFTR Alleles Are Associated with COVID-19 Clinical Outcomes

Carriers of single pathogenic variants of the CFTR (cystic fibrosis transmembrane conductance regulator) gene have a higher risk of severe COVID-19 and 14-day death. The machine learning post-Mendelian model pinpointed CFTR as a bidirectional modulator of COVID-19 outcomes. Here, we demonstrate that the rare complex allele [G576V;R668C] is associated with a milder disease via a gain-of-function mechanism. Conversely, CFTR ultra-rare alleles with reduced function are associated with disease severity either alone (dominant disorder) or with another hypomorphic allele in the second chromosome (recessive disorder) with a global residual CFTR activity between 50 to 91%. Furthermore, we characterized novel CFTR complex alleles, including [A238V;F508del], [R74W;D1270N;V201M], [I1027T;F508del], [I506V;D1168G], and simple alleles, including R347C, F1052V, Y625N, I328V, K68E, A309D, A252T, G542*, V562I, R1066H, I506V, I807M, which lead to a reduced CFTR function and thus, to more severe COVID-19. In conclusion, CFTR genetic analysis is an important tool in identifying patients at risk of severe COVID-19

The polymorphism L412F in TLR3 inhibits autophagy and is a marker of severe COVID-19 in males

The polymorphism L412F in TLR3 has been associated with several infectious diseases. However, the mechanism underlying this association is still unexplored. Here, we show that the L412F polymorphism in TLR3 is a marker of severity in COVID-19. This association increases in the sub-cohort of males. Impaired macroautophagy/autophagy and reduced TNF/TNFα production was demonstrated in HEK293 cells transfected with TLR3L412F-encoding plasmid and stimulated with specific agonist poly(I:C). A statistically significant reduced survival at 28 days was shown in L412F COVID-19 patients treated with the autophagy-inhibitor hydroxychloroquine (p = 0.038). An increased frequency of autoimmune disorders such as co-morbidity was found in L412F COVID-19 males with specific class II HLA haplotypes prone to autoantigen presentation. Our analyses indicate that L412F polymorphism makes males at risk of severe COVID-19 and provides a rationale for reinterpreting clinical trials considering autophagy pathways. Abbreviations: AP: autophagosome; AUC: area under the curve; BafA1: bafilomycin A1; COVID-19: coronavirus disease-2019; HCQ: hydroxychloroquine; RAP: rapamycin; ROC: receiver operating characteristic; SARS-CoV-2: severe acute respiratory syndrome coronavirus 2; TLR: toll like receptor; TNF/TNF-α: tumor necrosis factor

Bollettino Sismico Italiano settembre – dicembre 2018

Gli analisti del BSI hanno revisionato tutti gli eventi di magnitudo M≥1.5, localizzati dal 1 settembre al 31 dicembre 2018. I parametri dei terremoti di magnitudo inferiore a tale soglia di revisione, sono quelli calcolati in tempo reale, nella sala di sorveglianza sismica di Roma.Istituto Nazionale di Geofisica e Vulcanologia - Dipartimento di Protezione CivilePublished4IT. Banche dat