Stereocontrolled synthesis and functionalization of cyclobutanes and cyclobutanones

In the last decade a certain number of new cyclobutane and cyclobutanone synthesis and functionalization protocols have been published. Organo- and biocatalyzed eco-friendly approaches to cyclobutane-containing molecules have been developed with interesting results. Also, successful new total synthesis of bioactive compounds and drugs have been recently reported where a four membered ring represented the key intermediate. Therefore, the rising interest in this field represents a great point of discussion for the scientific community, disclosing the synthetic potential of strained four membered ring carbocyclic compounds. Herein we report a critical survey on the literature concerning the enantiocontrolled synthesis and functionalization of cyclobutane derivatives, with particular attention to metal-free, low impact methodologies, published during the period 2000–2013

Tandem Baeyer–Villiger/Wittig/oxa-Michael addition: One-step to 5-substituted γ-lactones

The results reported in this study provide a practical protocol for the construction, in one single step of synthetically important γ-lactones in good yields starting from α-hydroxy cyclobutanone, H2O2 and several stabilized phosphonium ylides. Our synthetic strategy relies on a tandem Baeyer–Villiger oxidation/Wittig reaction/oxa-Michael addition

Reverse cycle chewing before and after orthodontic-surgical correction in class III patients.

Objective: The aim of this study was to investigate the prevalence of reverse-sequence chewing cycles in skeletal class III patients before and after orthodontic-surgical therapy to evaluate whether the occlusal and skeletal correction is followed by a functional improvement. Study Design: Twenty skeletal class III patients (11 males and 9 females, 22.7 ± 3.0 years old) were recruited for this study. All patients received orthodontic and surgical treatment. Chewing cycles were recorded with a kinesiograph before (T0) and after (T1) therapy. Results: A significant decrease in the number of reverse chewing cycles after surgical correction was exhibited in all recordings, when chewing either soft or hard boluses, on both the right and the left side. Conclusions: Evaluation of the prevalence of reverse chewing cycles could be considered an indicator of functional adaptation after therapy and a method for the early detection of nonresponding patients who may require further consideration using a different approach

Internal characterization of embankment dams using ground penetrating radar (GPR) and thermographic analysis: A case study of the Medau Zirimilis Dam (Sardinia, Italy)

The stability of embankment dams without an impermeable core depends on the characteristics of the face slab that prevents internal erosion, piping and eventual collapse of the structure. Under a Mediterranean climate, the impermeable asphaltic face slab is subjected to high solar radiation and consequent temperature changes, which can generate the creation of cracks and joints. The Medau Zirimilis Dam, located in the Casteddu River (Sardinia), is an embankment dam that has undergone seepage and continuous repairs in its asphalt face slab. These reparations have been conducted because of the occurrence of cracks and relative movement of different segments of the slab. To evaluate if seepage endangers the integrity of the dam, GPR was used, with different antennas (100, 250 and 500 MHz), along its crest and upstream and downstream faces, and the data were integrated with infrared thermographic images. Although geophysical data do not show structural changes affecting the main dam structure, deformation structures at shallow levels and in particular in the upstream face and along the crest of the dam have been identified. Such deformation affects the road atop the crest, the face slab and underlying levels, resulting in landslides that include material from several meters below the surface. The analysis permitted the identification of the origin of surficial cracks and their effects on the face slab. These sectors, independent of current movement, define the most unstable areas against water level changes that can affect the dam integrity. GPR analysis at the embankments usually has the handicap of high clay content that precludes electromagnetic wave penetration; however, in this case, the obtained resolution and extent of penetration using the different antennas was sufficient, due to the absence of an inner waterproof unit, and permitted the evaluation of the inner structure of the dam and the application of GPR for construction quality surveillance, internal structural characterization and dam monitoring

Axiography and MRI in the diagnosis of temporomandibular joint pathology

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Solvent-Free Synthesis of Quaternary Oxazolidine-2-thione β3-Amino Ester Analogs

A solvent-free organocatalyzed intermolecular cyclization reaction starting from β-substituted γ-hydroxy-α,β-unsaturated esters and aryl isothiocyanates proceeds via an aza-Michael addition to provide previously unknown quaternary oxazolidine-2-thione β3 amino ester analogs. A panel of diversely-substituted esters was investigated, including β,γ-disubstituted examples which provided the target molecules with very high cis diastereoselectivity

Age- and sex-related variations in platelet count in Italy: a proposal of reference ranges based on 40987 subjects' data

BACKGROUND AND OBJECTIVES: Although several studies demonstrated that platelet count is higher in women, decreases with age, and is influenced by genetic background, most clinical laboratories still use the reference interval 150-400×10(9) platelets/L for all subjects. The present study was to identify age- and sex-specific reference intervals for platelet count. METHODS: We analysed electronic records of subjects enrolled in three population-based studies that investigated inhabitants of seven Italian areas including six geographic isolates. After exclusion of patients with malignancies, liver diseases, or inherited thrombocytopenias, which could affect platelet count, reference intervals were estimated from 40,987 subjects with the non parametric method computing the 2.5° and 97.5° percentiles. RESULTS: Platelet count was similar in men and women until the age of 14, but subsequently women had steadily more platelets than men. The number of platelets decreases quickly in childhood, stabilizes in adulthood, and further decreases in oldness. The final result of this phenomenon is that platelet count in old age was reduced by 35% in men and by 25% in women compared with early infancy. Based on these findings, we estimated reference intervals for platelet count ×10(9)/L in children (176-452), adult men (141-362), adult women (156-405), old men (122-350) and, old women (140-379). Moreover, we calculated an extended reference interval that takes into account the differences in platelet count observed in different geographic areas. CONCLUSIONS: The age-, sex-, and origin-related variability of platelet count is very wide, and the patient-adapted reference intervals we propose change the thresholds for diagnosing both thrombocytopenia and thrombocytosis in Italy

Maturity-Onset Diabetes of the Young in Children With Incidental Hyperglycemia:: A multicenter Italian study of 172 families

OBJECTIVE - To investigate the prevalence of maturity-onset diabetes of the young (MODY) in Italian children With incidental hyperglycemia. RESEARCH DESIGN AND METHODS - Among 748 subjects age 1-18 years with incidental hyperglycemia, minimal diagnostic criteria for MODY were met by 172 families. Mutational analyses of the glucokinase (GCK) and hepatocyte nuclear factor lot (HNF1A) genes were performed. RESULTS - We identified 85 GCK gene mutations in 109 probands and 10 HNF1A mutations in 12 probands. In GCK patients, the median neonatal weight and age at the first evaluation were lower than those found in patients with HNF1A mutations. Median fasting plasma glucose and impaired fasting glucose/impaired glucose tolerance frequency after oral glucose tolerance testing were higher in GCK patients, who also showed a lower frequency of diabetes than HNF1A patients. CONCLUSIONS - GCK mutations are the prevailing cause of MODY (63.4%) when the index case is recruited in Italian children with incidental hyperglycemia

Insulin pump failures in Italian children with Type 1 diabetes: retrospective 1-year cohort study

AimsInsulin pump failure and/or malfunction requiring replacement have not been thoroughly investigated. This study evaluated pump replacement in children and adolescents with Type 1 diabetes using insulin pump therapy.MethodsData were collected for all participants younger than 19 years, starting insulin pump therapy before 31 December 2013. For each child, age, disease duration, date of insulin pump therapy initiation, insulin pump model, failure/malfunction/replacement yes/no and reason were considered for the year 2013.ResultsData were returned by 40 of 43 paediatric centres belonging to the Diabetes Study Group of the Italian Society of Paediatric Endocrinology and Diabetology. In total, 1574 of 11 311 (13.9%) children and adolescents with Type 1 diabetes were using an insulin pump: 29.2% Animas VIBE, 9.4% Medtronic MiniMed 715/515, 34.3% Medtronic MiniMed VEO, 24.3% Accu-Check Spirit Combo and 2.8% other models. In 2013, 0.165 insulin pump replacements per patient-year (11.8% due to pump failure/malfunction and 4.7% due to accidental damage) were recorded. Animas VIBE (22.1%) and Medtronic MiniMed VEO (17.7%) were the most replaced.ConclusionsIn a large cohort of Italian children and adolescents with Type 1 diabetes, insulin pump failure/malfunction and consequent replacement are aligned with rates previously reported and higher in more sophisticated pump models

Development and psychometric properties of the Suicidality:Treatment Occurring in Paediatrics (STOP) Suicidality Assessment Scale (STOP-SAS) in children and adolescents

Background: To create a self-reported, internet-based questionnaire for the assessment of suicide risk in children and adolescents.Methods: As part of the EU project `Suicidality: Treatment Occurring in Paediatrics' (STOP project), we developed web-based Patient Reported Outcome Measures (PROMs) for children and adolescents and for proxy reports by parents and clinicians in order to assess suicidality. Based on a literature review, expert panels and focus groups of patients, we developed the items of the STOP Suicidality Assessment Scale (STOP-SAS) in Spanish and English, translated it into four more languages, and optimized it for web-based presentation using the HealthTracker (TM) platform. Of the total 19 questions developed for the STOP-SAS, four questions that assess low-level suicidality were identified as screening questions (three of them for use with children, and all four for use with adolescents, parents and clinicians). A total of 395 adolescents, 110 children, 637 parents and 716 clinicians completed the questionnaire using the HealthTracker (TM), allowing us to evaluate the internal consistency and convergent validity of the STOP-SAS with the clinician-rated Columbia Suicide Severity Rating Scale (C-SSRS). Validity was also assessed with the receiver operating characteristic (ROC) area of the STOP-SAS with the C-SSRS.Results: The STOP-SAS comprises 19 items in its adolescent, parent, and clinician versions, and 14 items in its children's version. Good internal consistency was found for adolescents (Cronbach's alpha: 0.965), children (Cronbach's alpha: 0.922), parents (Cronbach's alpha: 0.951) and clinicians (Cronbach's alpha: 0.955) versions. A strong correlation was found between the STOP-SAS and the C-SSRS for adolescents (r:0.670), parents (r:0.548), clinicians (r:0.863) and children (r:0.654). The ROC area was good for clinicians' (0.917), adolescents' (0.834) and parents' (0.756) versions but only fair (0.683) for children's version.Conclusions: The STOP-SAS is a comprehensive, web-based PROM developed on the HealthTracker (TM) platform, and co-designed for use by adolescents, children, parents and clinicians. It allows the evaluation of aspects of suicidality and shows good reliability and validity.</p