A novel mutation in CDKN1C in sibs with Beckwith–Wiedemann syndrome and cleft palate,sensorineural hearing loss,and supernumerary flexion creases

We report on two daughters and a son of a Thai family who were affected with BWS. Their clinical findings consist of cleft palate, omphalocele, anterior ear creases, indented lesions on the posterior rim of the helix, macroglossia, posterior crossbite, and anterior open bite. The younger daughter and son had newly recognized findings of the BWS including sensorineural hearing loss and supernumerary flexion creases of the fingers. A novel mutation in CDKN1C (c.579delT; p.A193AfsX46) was found in all affected individuals and their mother. This mutation is located in the central highly polymorphic hexanucleotide repeat encoding a proline‐alanine series of repeats (PAPA‐domain). This domain is involved in MAP kinase phosphorylation. This is for the first time that sensorineural hearing loss and supernumerary flexion creases of the fingers are associated with mutation in CDKN1C. © 2012 Wiley Periodicals, Inc.     

A 24-month evaluation of amalgam and resin-based composite restorations: Findings from The National Dental Practice-Based Research Network

BackgroundKnowing which factors influence restoration longevity can help clinicians make sound treatment decisions. The authors analyzed data from The National Dental Practice-Based Research Network to identify predictors of early failures of amalgam and resin-based composite (RBC) restorations.MethodsIn this prospective cohort study, the authors gathered information from clinicians and offices participating in the network. Clinicians completed a baseline data collection form at the time of restoration placement and annually thereafter. Data collected included patient factors, practice factors and dentist factors, and the authors analyzed them by using mixed-model logistic regression.ResultsA total of 226 practitioners followed up 6,218 direct restorations in 3,855 patients; 386 restorations failed (6.2 percent) during the mean (standard deviation) follow-up of 23.7 (8.8) months. The number of tooth surfaces restored at baseline helped predict subsequent restoration failure; restorations with four or more restored surfaces were more than four times more likely to fail. Restorative material was not associated significantly with longevity; neither was tooth type. Older patient age was associated highly with failure (P N/A .001). The failure rate for children was 4 percent, compared with 10 percent for people 65 years or older. Dentist’s sex and practice workload were associated significantly with restoration longevity.ConclusionsIn this prospective cohort study, these factors were significantly predictive of failure for amalgam and RBC restorations: patient’s age, a higher number of surfaces restored at baseline, the dentist’s sex and the practice workload. Material choice was not significantly predictive in these early results.Practical ImplicationsIf clinicians can recognize and identify the risk factors associated with early restoration failure, more effective treatment plans may be offered to the patient.     

Transmission of resistant HIV type 1 variants and epidemiological chains in Italian newly diagnosed individuals

Transmission of HIV-1 and drug resistance continue to occur at a considerable level in Italy, influenced mainly by changes in modality of infection. However, the long period of infectivity makes difficult the interpretation of epidemiological networks, based on epidemiological data only. We studied 510 naive HIV-1-infected individuals, of whom 400 (78.4%) were newly diagnosed patients with an unknown duration of infection (NDs), with the aim of identifying sexual epidemiological networks and transmitted drug resistance (TDR) over a 7-year period. Clusters were identified by Bayesian methods for 412 patients with B subtype; 145 individuals (35.2%) clustered in 34 distinct clades. Within epidemiological networks males were 93.1% (n=135); the same proportion of patients has been infected by the sexual route; 62.1% (n=90) were men having sex with men (MSM) of whom 67.8% (n=61) were NDs. Among heterosexuals (n=44), males were predominant (79.5%, n=35) and 77.3% (n=34) were NDs. TDR in clusters was 11.7 % (n=17), of whom 76.5% (n=13) was found in MSM. TDR was predominantly associated with NRTI resistance in individuals with chronic infection (n=11). A high prevalence of epidemiological networks has been found in the metropolitan area of Milan, indicating a high frequency of transmission events. The cluster analysis of networks suggested that the source of new infections was mainly represented by males and MSM who have long lasting HIV-1 infection. Notably, the prevalence of resistance-conferring mutations was higher in chronically infected patients, carrying mainly resistance to thymidine analogs, the backbone of first antiretroviral (ARV) generation. Intervention strategies of public health are needed to limit HIV-1 transmission and the associated TDR.     

Negative correlation between D-dimer and plasminogen activator inhibitor-1 levels is absent in obese women

Obesity is characterized by alterations in haemostatic processes that lead to a prothrombotic state. D-dimer (D-Di) is the last product of the fibrinolysis and may reflect the haemostatic balance. As the plasminogen activator inhibitor (PAI)-1 is the main inhibitor of fibrinolysis and it is elevated in obese, we hypothesize that negative correlation exists between PAI-1 and D-Di. In addition, we evaluated if plasma levels of PAI-1 and D-Di may be correlated with clinical parameters of adiposity [waist circumference and waist-to-hip ratio (WHR)]. We measured plasma PAI-1 and D-Di concentrations using ELISA in 60 women: 21 lean women without comorbidities and 39 obese women. We found higher levels of D-Di and PAI-1 in obese groups compared to control group (P < 0.05). No differences were observed between obese and obese untreated hypertensives. PAI-1 levels, but not of D-Di, are positively correlated with BMI (control, r = 0.44) and WHR (all obese, r = 0.40). Negative correlation was found between PAI-1 and D-Di in control (r = -0.56), no association was observed in obese, signalizing to a particular attention regarding the clinical use of D-Di. Our results indicate the magnitude of central obesity as a risk factor for development of disorders related to prothrombotic states.     

"PancPro" as a tool for selecting families eligible for pancreatic cancer screening: an Italian study of incident cases

BackgroundPancPRO is a computer program that estimates the risk of pancreatic cancer for asymptomatic individuals based on a genetic model of susceptibility and the familial incidence of cancer.AimTo evaluate the distribution of the familial risk in a series of incident cases of pancreatic adenocarcinoma.Materials and methodsThe lifetime risk of pancreatic cancer was calculated by PancPro for a hypothetical 40-year-old son of 570 consecutive probands with pancreatic cancer.ResultsThe 570 risk values were included between 1% and 13%. The distribution was bimodal, with the antimode located at risk = 7.5%. Considering a 10-fold risk over the general population as a threshold for including a subject in a surveillance program, 19 families (3.3%) would be selected, totalling 92 first-degree relatives with age >40 years.ConclusionsPancPro is a valid instrument to rank families based on risk of pancreatic cancer.