PDB is genetically heterogeneous. Mutations of the sequestosome1 gene have been reported in sporadic and familial forms of Paget's in patients of French Canadian and British descent. Mutational ...analyses in different ethnic groups are needed to accurately investigate hereditary diseases. We describe two novel mutations of sequestosome1 in 62 Italian sporadic patients, confirming the role of the encoded protein in this disorder.
Introduction: Paget's disease of bone (PDB) is a relatively common disease of bone metabolism reported to affect up to 3% of whites over 55 years of age. The disorder is genetically heterogeneous, and at present, there is scientific evidence that at least eight different human chromosomal loci are correlated with its pathogenesis. Mutations of the sequestosome1 (SQSTM1) gene were identified as responsible for most of the sporadic and familial forms of Paget in patients of French Canadian and British descent. Such mutations were located at exon 7 and 8 levels, encoding for the ubiquitin protein‐binding domain (UBA) and representing a mutational hot spot area.
Materials and Methods: To verify the involvement of this gene in Italian subjects affected by PDB, we performed mutational analysis in 62 sporadic PDB cases.
Results: We described three different mutations at exon 8 level: P392L, already described in the French Canadian population and families predominantly of British descendent, and two novel mutations consisting of the amino acid substitutions M404V and G425R. No significant differences in the clinical history of PDB have been observed in patients with SQSTM1 mutations in respect to those without.
Conclusions: Even though our findings suggest a minor involvement of the SQSTM1 gene in the pathogenesis of sporadic Italian Paget's cases, the identification of different significant mutations within the SQSTM1 gene in unrelated, but clinically similar individuals, offers extremely convincing evidence for a causal relationship between this gene and PDB. Longitudinal studies are needed to assess the penetrance of genotype/phenotype correlations. Our findings confirm the evidence of a clustered mutation area at this level in this disorder.
The presence of pyrethroid compounds in hepatic tissue of Guiana dolphins (Sotalia guianensis) is reported for the first time. Twelve pyrethroids were determined in 50 animals from eight locations of ...the Brazilian coast. The highest average concentration of total pyrethroids (∑PYR) was 1166 ng.g−1 lw, with values ranging from 148 to 5918 ng.g−1 lw, in Ilha Grande Bay, Rio de Janeiro State, while the Espírito Santo State had the highest median, 568 ng.g−1 lw. Permethrin was the predominant compound in most areas, contributing for 42% to 81% of the ∑PYR, whereas cypermethrin was the most abundant compound in Guanabara and Sepetiba bays (79% and 81%, respectively), both located in Rio de Janeiro State. Biological factors were not correlated with pyrethroids concentration. Tetramethrin and es/fenvalerate compounds were negatively correlated to the age, suggesting degradation/metabolization capacity in these animals that increases throughout life. Despite being metabolized and excreted, the wide use of these pollutants is reflected in relevant concentrations found in Guiana dolphins. This is the first study evaluating pyrethroids in a representative number of hepatic samples and covering >2600 km of coast. The overall lack of information on pyrethroids in cetaceans highlights the importance of understanding the profile and distribution of these pollutants in dolphins which exclusively inhabit the Southwestern Atlantic coast.
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•Pyrethroids (PYR) in the liver of Guiana dolphins were reported for the first time.•Fifty animals along the Southwestern Atlantic coast were analyzed.•The highest average concentration for total pyrethroids was 1166 ng.g−1, lw.•Permethrin and cypermethrin were the most abundant compounds.•The wide use of PYR is reflected in the concentrations found in Guiana dolphins.
Objective
To evaluate the basal/total ratio of daily insulin dose (b/T) in outpatients with diabetes type 1 (DM1) and type 2 (DM2) on basal-bolus regimen, by investigating whether there is a ...relationship with HbA1c and episodes of hypoglycemia.
Methods
Multicentric, observational, cross-sectional study in Italy. Adult DM1 (
n
= 476) and DM2 (
n
= 541) outpatients, with eGFR >30 mL/min/1.73 m
2
, on a basal-bolus regimen for at least six months, were recruited from 31 Italian Diabetes services between March and September 2016.
Clinicaltrials.gov
ID: NCT03489031.
Results
Total daily insulin dose was significantly higher in DM2 patients (52.3 ± 22.5 vs. 46 ± 20.9 U/day), but this difference disappeared when insulin doses were normalized for body weight. The b/T ratio was lower than 0.50 in both groups: 0.46 ± 0.14 in DM1 and 0.43 ± 0.15 in DM2 patients (
p
= 0.0011). The b/T was significantly higher in the patients taking metformin in both groups, and significantly different according to the type of basal insulin (Degludec, 0.48 in DM1 and 0.44 in DM2; Glargine, 0.44 in DM1 and 0.43 in DM2; Detemir, 0.45 in DM1 and 0.39 in DM2). The b/T ratio was not correlated in either group to HbA1c or incidence of hypoglycemia (<40 mg/dL, or requiring caregiver intervention, in the last three months). In the multivariate analysis, metformin use and age were independent predictors of the b/T ratio in both DM1 and DM2 patients, while the type of basal insulin was an independent predictor only in DM1.
Conclusion
The b/T ratio was independent of glycemic control and incidence of hypoglycemia.
Purpose
Evaluation of the phenotype of primary hyperparathyroidism (PHPT), adherence to International Guidelines for parathyroidectomy (PTx), and rate of surgical cure.
Method
From January ...2014–January 2016, we performed a prospective, multicenter study in patients with newly diagnosed PHPT. Biochemical and instrumental data were collected at baseline and during 1-year follow-up.
Results
Over the first year we enrolled 604 patients (age 61 ± 14 years), mostly women (83%), referred for further evaluation and treatment advice. Five hundred sixty-six patients had sporadic PHPT (93.7%, age 63 ± 13 years), the remaining 38 (6.3%, age 41 ± 17 years) had familial PHPT. The majority of patients (59%) were asymptomatic. Surgery was advised in 281 (46.5%). Follow-up data were available in 345 patients. Eighty-seven of 158 (55.1%) symptomatic patients underwent PTx. Sixty-five (53.7%) of 121 asymptomatic patients with at least one criterion for surgery underwent PTx and 56 (46.3%) were followed without surgery. Negative parathyroid imaging studies predicted a conservative approach symptomatic PHPT: OR 18.0 (95% CI 4.2–81.0)
P
< 0.001; asymptomatic PHPT: OR 10.8, (95% CI 3.1–37.15)
P
< 0.001). PTx was also performed in 16 of 66 (25.7%) asymptomatic patients without surgical criteria. Young age, serum calcium concentration, 24 h urinary calcium, positive parathyroid imaging (either ultrasound or MIBI scan positive in 75% vs. 16.7%,
P
= 0.001) were predictors of parathyroid surgery. Almost all (94%) of patients were cured by PTx.
Conclusions
Italian endocrinologists do not follow guidelines for the management of PHPT. Negative parathyroid imaging studies are strong predictors of a non-surgical approach. PTx is successful in almost all patients.
The article The basal to total insulin ratio in outpatients with diabetes on basal-bolus regimen, written by Elena Castellano, R. Attanasio, V. A. Giagulli, A. Boriano, M. Terzolo, E. Papini, E. ...Guastamacchia, S. Monti, A. Aglialoro, D. Agrimi, E. Ansaldi, A. C. Babini, A. Blatto, D. Brancato.
Las virosis son la principal limitante del rendimiento de batata, quinto cultivo alimenticio del mundo. En Argentina, el “encrespamiento amarillo” (EA), complejo viral con siete agentes ...involucra-dos, causa notables pérdidas en los genotipos de toda región productiva. Se analizó la influencia del EA en componentes de rendimiento de los cvs Arapey INIA y Beauregard. mediante ensayos comparativos que combinaron dos condiciones sanitarias (sana vs enferma) y dos genotipos. Las plantas sanas se obtuvieron por termoterapia y cultivo in vitro de meristemas, y las enfermas, injertando púas con EA. Hubo diferencias significativas entre condiciones sanitarias, para contenido de clorofilas y mermas de caracteres de rendimiento cercanas al 90%, donde peso y número de raíces comerciales fueron los más afectados por EA en ambas variedades. Se corrobora la relevancia del EA como limitante del cultivo y del empleo de materiales saneados junto a buenas prácticas de manejo para alcanzar rendimientos potenciales.
The time-depending stress transfer in existing structures strengthened with externally bonded fiber reinforced polymer (FRP) systems, due to viscous effects of reinforcement, is analysed in this ...paper. A new modelling strategy for assessing the long-term response of these composite beams was developed, by assembling two one-dimensional components (existing structural element and external strengthening) and accounting for thin-walled sectional geometry of FRPs. Several numerical experiments dealing with FRP laminates-reinforced concrete (RC) composite beams were performed and the corresponding results were compared with the predictions of the Effective Modulus Method (EM). A relevant stress redistribution between the components of the examined strengthened structures was observed.
The aim of the study was to evaluate: 1) the cardiovascular function and the autonomic drive to the heart in patients affected by primary hyperparathyroidism (pHPT) with no evidence of renal and ...cardiovascular complications; 2) the cardiovascular effects of acute administration of PTH in normal subjects. In 14 patients affected by mild asymptomatic pHPT echocardiographic assessment of cardiovascular function and of the mechanic properties of the brachial and carotid artery, heart rate variability and the dispersion of QT interval were performed before and 6 months after successful surgery. Twenty age- and sex-matched healthy subjects were included in the study. Five healthy volunteers underwent a single blind, placebo-controlled, random order, cross-over study with infusion of PTH (hPTH 1-34, 200 U in saline over 5 min) or placebo. Echocardiographic assessment of cardiovascular function, heart rate variability, and QT interval were performed between 20 and 25 min after the start of the infusion and repeated after 15 min of tilting at 60 degrees. In pHPT patients the echocardiographic parameters were normal; left ventricular isovolumetric relaxation time was always in the normal range, but significantly shorter than in control subjects, suggesting an increased sympathetic stimulation. Arterial diameters and thickness, blood pressure, and QT interval were not significantly different with respect to normal subjects and were unchanged 6 months after surgery. pHPT patients lacked the circadian rhythm of the low frequency to high frequency ratio, suggesting an increased sympathetic drive to the heart at nighttime. In normal subjects there were no significant differences in basal echocardiographic measurements during PTH infusion with respect to placebo and in the hemodynamic response to tilt. These results suggest that cardiovascular function is substantially normal in normotensive pHPT patients with mild hypercalcemia. A modulation of the adrenergic control of circulation seems to be associated with hypercalcemia and/or chronic PTH excess, but its biological relevance needs further investigations.
Context:
Cell-free nucleic acids circulating in plasma are considered a promising noninvasive tool for cancer monitoring. BRAFV600E mutation in cell-free DNA (cfDNA) could represent an appropriate ...marker for papillary thyroid carcinoma (PTC).
Objective:
Our aim is to investigate the role of BRAFV600E-mutated allele in cfDNA as a marker for the diagnosis and follow-up of PTC.
Study Design:
BRAFV600E allele was detected and quantified by an allele-specific real-time quantitative PCR assay in plasma from 103 patients affected by nodular goiter. As control populations, we enrolled 49 healthy subjects and 16 patients with non-nodular thyroid diseases.
Results:
The percentage of circulating BRAFV600E was significantly different between patients and controls and throughout different cytological categories of ultrasound-assisted fine-needle aspiration. Patients with a histopathological diagnosis of PTC showed a higher percentage of circulating BRAFV600E (P = .035) compared to those with benign histology. In 19 patients, a second blood draw, taken 3–6 months after surgery, showed a lower percentage of BRAFV600E in cfDNA than the presurgical sample (P < .001). The diagnostic performance of circulating BRAFV600E was assessed by receiver operating characteristic curve analysis resulting in an area under the curve of 0.797. A cutoff value was chosen corresponding to maximum specificity (65%) and sensitivity (80%). On this basis, we evaluated the predictive value of BRAFV600E in Thy 3 patients with a resulting positive predictive value of 33% and a negative predictive value of 80%.
Conclusions:
The results of the present study provide encouraging data supporting the possibility to take advantage of circulating BRAFV600E in the management of PTC.
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