Self-Mixing Interferometer for Acoustic Measurements through Vibrometric Calibration.

The Self-Mixing Interformeter (SMI) is a self-aligned optical interferometer which has been used for acoustic wave sensing in air through the acousto-optic effect. This paper presents how to use a SMI for the measurement of Sound Pressure Level (SPL) in acoustic waveguides. To achieve this, the SMI is first calibrated in situ as a vibrometer. The optical feedback parameters C and α in the strong feedback regime (C≥4.6) are estimated from the SMI vibrometric signals and by the solving of non-linear equations governing the SMI behaviour. The calibration method is validated on synthetic SMI signals simulated from SMI governing equations for C ranging from 5 to 20 and α ranging from 4 to 10. Knowing C and α, the SMI is then used as an acoustic pressure sensor. The SPLs obtained using the SMI are compared with a reference microphone, and a maximal deviation of 2.2 dB is obtained for plane waves of amplitudes ranging from 20 to 860 Pa and frequencies from 614 to 17,900 Hz. The SPL measurements are carried out for C values ranging from 7.1 to 21.5.

Sensitivity of an optical feedback interferometer for acoustic waves measurements.

This work presents a sensitivity study on the use of an optical feedback interferometer to measure acoustic pressure from plane waves. The sensitivity is established by linearising the interferometer's governing equations. It is shown to be independent of the acoustic wave frequency but dependent on configuration parameters such as the optical feedback parameter or the length of the laser through which the acoustic wave passes. Experimental validation is carried out using three acoustic waveguides in the 0.5-18 kHz range. The sensitivity obtained enables broadband acoustic pressure measure with a low mean relative error in comparison with a reference condenser microphone.

Liver adenomatosis in patients with hepatocyte nuclear factor-1 alpha maturity onset diabetes of the young (HNF1A-MODY): Clinical, radiological and pathological characteristics in a French series.

BACKGROUND: Liver adenomatosis (LA) is a rare disease resulting from biallelic inactivation of the hepatocyte nuclear factor-1 alpha (HNF1A) gene, which induces the proliferation of adenoma cells in liver parenchyma. Liver adenomatosis has only been documented in case reports from patients carrying a HNF1A germline mutation. We have evaluated the frequency of LA among a large cohort of patients with HNF1A-maturity onset diabetes of the young (MODY), previously termed "MODY3," and herein describe its clinical, radiological, and pathological characteristics. METHODS: In all, 137 HNF1A-MODY subjects from 74 families were screened by liver ultrasonography in 13 centers, and 15 additional cases of LA were later included in the series. Liver adenomatosis was confirmed by liver computed tomography, magnetic resonance imaging (MRI), and/or histopathology. RESULTS: Among 137 carriers of an HNF1A mutation, 9 patients (6.5%) from seven families were diagnosed with LA. Diabetes mellitus was present in 87.5% of patients with LA. In 25% of patients, LA was diagnosed due to intra-abdominal or intratumoral bleeding. Liver biochemistry was near normal in all patients. Liver imaging showed adenomas of various sizes and numbers. On MRI, most nodules had the radiological characteristics of steatotic adenomas. Histopathological confirmation of LA was available in 13 cases, and these adenomas were mostly steatotic. Surgery was initially performed in 37.5% of patients, and liver disease progression was observed in 30%. No disease progression was observed in 14 pregnancies. CONCLUSIONS: The frequency of LA in a cohort of screened HNF1A-MODY patients and the high incidence of LA progression and/or hemorrhage warrants systematic screening for liver adenomatosis in HNF1A-MODY families.

Cancellation of room reflections over an extended area using Ambisonics.

This paper investigates the compensation of room reflections based on Ambisonics. A multichannel room equalization method for Ambisonic playback systems is proposed. The compensation filters are designed to operate in the spherical harmonics domain, prior to the decoding step. Their design requires the inversion of a matrix which can be ill-conditioned at low frequencies and for higher Ambisonic orders. A crossover and cross-order method is proposed to circumvent this problem and to reduce the amount of necessary regularization. Simulation results are presented in frequency, space, and temporal domains over a wide-range of frequencies. It is shown that the proposed method is efficient and can reduce the reproduction error to -14 dB in the reconstruction area defined in free field. Practical considerations such as Ambisonic room response estimation and robustness of the method are investigated. Experimental results are provided and show good agreement with the theory. Finally, a glimpse into the extension of the proposed method to create three-dimensional measurement-based Ambisonic reverberation is discussed.

Long-term results of the surgical management of insulinoma patients with MEN1: a Groupe d'étude des Tumeurs Endocrines (GTE) retrospective study.

OBJECTIVE: Management of insulinomas in the context of MEN1 remains poorly studied. The aim of this study was to evaluate long-term results of various surgical approaches in a large cohort of insulinoma-MEN1 patients. DESIGN AND METHODS: Consecutive insulinoma-MEN1 patients operated on for a nonmetastatic insulinoma between 1957 and 2010 were retrospectively selected from the MEN1 database of the French Endocrine Tumor Group. The type of surgery was categorized as distal pancreatectomy (DP), total pancreatectomy/cephalic duodenopancreatectomy (TP/CDP), or enucleation (E). Primary endpoint was time until recurrence of hypoglycemia after initial surgery. Secondary endpoints were post-operative complications. RESULTS: The study included 73 patients (median age=28 years). Surgical procedures were DP (n=46), TP/CDP (n=9), or E (n=18). After a median post-operative follow-up of 9.0 years (inter-quartile range (IQR): 2.5-16.5 years), 60/73 patients (82.2%) remained hypoglycemia free. E and TP/CDP were associated with a higher risk of recurrent hypoglycemia episodes (unadjusted hazard ratio: 6.18 ((95% CI: 1.54-24.8); P=0.010) for E vs DP and 9.51 ((95% CI: 1.85-48.8); P=0.007) for TP/CDP vs DP. After adjustment for International Union against Cancer pTNM classification, enucleation remained significantly associated with a higher probability of recurrence. Long-term complications had occurred in 20 (43.5%) patients with DP, five (55.6%) with TP/CDP, but in none of the patients who have undergone E (P=0.002). CONCLUSION: In the French Endocrine database, DP is associated with a lower risk for recurrent hypoglycemia episodes. Due to lower morbidity, E alone might be considered as an alternative.

Expression and regulation of INTELECTIN1 in human granulosa-lutein cells: role in IGF-1-induced steroidogenesis through NAMPT.

INTELECTIN (ITLN) is an adipokine involved in the regulation of insulin sensitivity and inflammatory and immunity responses. Serum ITLN levels are lower in obese, diabetic, and polycystic ovary syndrome (PCOS) women than in control subjects. ITLN has never been studied in ovarian cells. Here, we identified ITLN1 in human ovarian follicles and investigated the molecular mechanisms involved in the regulation of its expression in response to the insulin sensitizers metformin and rosiglitazone, in human granulosa-lutein cells (hGLCs) and in a human ovarian granulosa-like tumor cell line (KGN). We also studied the effects of human recombinant ITLN1 (hRom1) on steroid production and on the activation of various signaling pathways. Using RT-PCR, immunoblotting, and immunohistochemistry, we found that INTL1 is present in human follicular cells. Using ELISA, we showed that INTL levels are similar in plasma and follicular fluid (FF) in control patients, whereas they are higher in FF than in plasma in PCOS patients. In KGN cells and hGLCs, insulin (10(-8) M), insulin-like growth factor-1 (IGF-1; 10(-8) M), and metformin (10(-2) M or 10(-3) M) increased INTL1 expression (mRNA and protein) after 12 and 24 h of stimulation. For metformin, this effect was mediated by adenosine monophosphate-activated kinase (PRKA). Furthermore, hRom1 increased nicotinamide phosphoribosyltransferase (NAMPT) expression in KGN and hGLCs. We also showed that hRom1 increased IGF-1-induced progesterone and estradiol secretion and this was associated with an increase in the STAR and CYP19A1 protein levels and an increase in IGF-1R signaling. Furthermore, all these data were abolished when NAMPT was knocked down in KGN cells, suggesting that INTL1 improves IGF-1-induced steroidogenesis through induction of NAMPT in hGLCs.

[Type 2 diabetes in France: epidemiology, trends of medical care, social and economic burden]. / Le diabète de type 2 en France : épidémiologie, évolution de la qualité de la prise en charge, poids social et économique. Entred 2007.

Between 2001 and 2007, treatments for type 2 diabetes have increased and therapeutic choices have improved. However glycemic control remains insufficient. Cardiovascular risk control has widely increased. Statins, hypertensive and antithrombotic treatments are more often prescribed. Blood pressure and LDL cholesterol levels have decreased whatever age. However, progress remains possible, especially regarding blood pressure control. Obesity has increased between 2001 and 2007 to reach 41% whereas the frequency of dietetic visits has decreased. Insulin therapy (more than obesity) determines the frequency of dietetic visits: dietetic care happens too late. Important improvements of the quality of follow-up are observed. However, fundus exams and more specifically albuminuria measurement remain insufficiently performed and their progression is too slow, as well as the podiatric examination. Only 10% of people with type 2 diabetes have an endocrinology visit, which has been stable between 2001 and 2007. Information expectations of people with type 2 diabetes are strong, especially for diet. Education demand is lower but more important for people who have already benefited. This improvement of medical care leads to an increase in the cost of reimbursements. The consequences of diabetes, more than the disease itself, alter the quality of life.

Higher risk of death among MEN1 patients with mutations in the JunD interacting domain: a Groupe d'etude des Tumeurs Endocrines (GTE) cohort study.

Multiple endocrine neoplasia syndrome type 1 (MEN1), which is secondary to mutation of the MEN1 gene, is a rare autosomal-dominant disease that predisposes mutation carriers to endocrine tumors. Although genotype-phenotype studies have so far failed to identify any statistical correlations, some families harbor recurrent tumor patterns. The function of MENIN is unclear, but has been described through the discovery of its interacting partners. Mutations in the interacting domains of MENIN functional partners have been shown to directly alter its regulation abilities. We report on a cohort of MEN1 patients from the Groupe d'étude des Tumeurs Endocrines. Patients with a molecular diagnosis and a clinical follow-up, totaling 262 families and 806 patients, were included. Associations between mutation type, location or interacting factors of the MENIN protein and death as well as the occurrence of MEN1-related tumors were tested using a frailty Cox model to adjust for potential heterogeneity across families. Accounting for the heterogeneity across families, the overall risk of death was significantly higher when mutations affected the JunD interacting domain (adjusted HR = 1.88: 95%-CI = 1.15-3.07). Patients had a higher risk of death from cancers of the MEN1 spectrum (HR = 2.34; 95%-CI = 1.23-4.43). This genotype-phenotype correlation study confirmed the lack of direct genotype-phenotype correlations. However, patients with mutations affecting the JunD interacting domain had a higher risk of death secondary to a MEN1 tumor and should thus be considered for surgical indications, genetic counseling and follow-up.

Adrenal rest tissue in gonads of patients with classical congenital adrenal hyperplasia: multicenter study of 45 French male patients.

OBJECTIVES: Several cases of testicular adrenal rest tumours have been reported in men with congenital adrenal hyperplasia (CAH) due to the classical form of 21-hydroxylase deficiency but the prevalence has not been established. The aims of this report were to evaluate the frequency of testicular adrenal rest tissue in this population in a retrospective multicentre study involving eight endocrinology centres, and to determine whether treatment or genetic background had an impact on the occurrence of adrenal rest tissue. MATERIAL AND METHODS: Testicular adrenal rest tissue (TART) was sought clinically and with ultrasound examination in forty-five males with CAH due to the classical form of 21-hydroxylase deficiency. When the diagnosis of testicular adrenal rest tumours was sought, good observance of treatment was judged on biological concentrations of 17-hydroxyprogesterone (17OHP), delta4-androstenedione, active renin and testosterone. The results of affected and non-affected subjects were compared. RESULTS: TART was detected in none of the 18 subjects aged 1 to 15years but was detected in 14 of the 27 subjects aged more than 15years. Five patients with an abnormal echography result had no clinical signs. Therapeutic control evaluated at diagnosis of TART seemed less effective when diagnosis was made in patients with adrenal rest tissue compared to TART-free subjects. Various genotypes were observed in patients with or without TART. CONCLUSION: Due to the high prevalence of TART in classical CAH and the delayed clinical diagnosis, testicular ultrasonography must be performed before puberty and thereafter regularly during adulthood even if the clinical examination is normal.

PROKR2 variants in multiple hypopituitarism with pituitary stalk interruption.

CONTEXT: Pituitary stalk interruption represents a frequent feature of congenital hypopituitarism, but only rare cases have been assigned to a known genetic cause. OBJECTIVE: Using a candidate gene approach, we tested several genes as potential causes of hypopituitarism with pituitary stalk interruption. We hypothesized that ectopic posterior pituitary may be a consequence of defective neuronal axon projections along the pituitary stalk or defective angiogenesis of hypophyseal portal circulation. Considering the role of the prokineticin 2 pathway in angiogenesis and neuronal migration, we screened PROK2 and PROKR2 genes. DESIGN: PROK2 and PROKR2 and all genes previously known to be involved in hypopituitarism with pituitary stalk interruption (LHX4, HESX1, OTX2, and SOX3) were screened in 72 index cases with pituitary stalk interruption syndrome from the GENHYPOPIT database. In vitro studies were performed to assess the functional consequences of allelic variants. RESULTS: We identified two heterozygous PROKR2 mutations (p.Leu173Arg and p.Arg85His) previously reported in isolated hypogonadotroph hypogonadism and a novel PROKR2 variant (p.Ala51Thr) that, in contrast with both other mutations, did not impair receptor signaling activity. Three allelic variants of HESX1 were identified: the heterozygous p.Phe156Ser and the homozygous p.Arg109X mutations were functionally deleterious, whereas p.Ser67Thr was found as a rare allelic variant in association with p.Arg85His PROKR2 mutation in the same patient. CONCLUSIONS: We report PROKR2 variants in congenital hypopituitarism with pituitary stalk interruption, suggesting a potential role of the prokineticin pathway in pituitary development.

Cyclin-dependent kinase inhibitor 1B (CDKN1B) gene variants in AIP mutation-negative familial isolated pituitary adenoma kindreds.

Familial isolated pituitary adenoma (FIPA) occurs in families and is unrelated to multiple endocrine neoplasia type 1 and Carney complex. Mutations in AIP account only for 15-25% of FIPA families. CDKN1B mutations cause MEN4 in which affected patients can suffer from pituitary adenomas. With this study, we wanted to assess whether mutations in CDKN1B occur among a large cohort of AIP mutation-negative FIPA kindreds. Eighty-eight AIP mutation-negative FIPA families were studied and 124 affected subjects underwent sequencing of CDKN1B. Functional analysis of putative CDKN1B mutations was performed using in silico and in vitro approaches. Germline CDKN1B analysis revealed two nucleotide changes: c.286A>C (p.K96Q) and c.356T>C (p.I119T). In vitro, the K96Q change decreased p27 affinity for Grb2 but did not segregate with pituitary adenoma in the FIPA kindred. The I119T substitution occurred in a female patient with acromegaly. p27(I119T) shows an abnormal migration pattern by SDS-PAGE. Three variants (p.S56T, p.T142T, and c.605+36C>T) are likely nonpathogenic because In vitro effects were not seen. In conclusion, two patients had germline sequence changes in CDKN1B, which led to functional alterations in the encoded p27 proteins in vitro. Such rare CDKN1B variants may contribute to the development of pituitary adenomas, but their low incidence and lack of clear segregation with affected patients make CDKN1B sequencing unlikely to be of use in routine genetic investigation of FIPA kindreds. However, further characterization of the role of CDKN1B in pituitary tumorigenesis in these and other cases could help clarify the clinicopathological profile of MEN4.

Von Hippel-Lindau disease and aggressive GH-PRL pituitary adenoma in a young boy.

Von Hippel-Lindau disease is an autosomal dominant disorder involving the development of specific tumours in multiple organs, both benign and malignant. In the CNS, the syndrome is characterized by haemangioblastomas of the retina, spinal cord and brain. We report the case of a 15-year-old boy with the diagnosis of aggressive GH-PRL pituitary macroadenoma and a family history of VHL disease. Pituitary resection was performed, although complete excision of the lesion could not be confirmed by the neurosurgeon. A control MRI was done 6 months after surgery and the pituitary lesion was similar to the presurgical image. A second operation allowed partial resection of the tumour followed by targeted radiotherapy. Pituitary adenomas are rare benign tumours in children with macroadenomas observed mainly in boys. These tumours in adolescents often occur in a familial setting or in the context of known genetic defects. Angiogenesis is an important feature of pituitary adenomas and a possible inhibitory role of pVHL in pituitary angiogenesis has been suggested. This GH-PRL pituitary macroadenoma with a VHL mutation might be of particular aggressiveness. Pituitary adenomas are not classically described in VHL syndrome and the medical community should be alerted to its rare occurrence in this location.

Normosmic congenital hypogonadotropic hypogonadism due to TAC3/TACR3 mutations: characterization of neuroendocrine phenotypes and novel mutations.

CONTEXT: TAC3/TACR3 mutations have been reported in normosmic congenital hypogonadotropic hypogonadism (nCHH) (OMIM #146110). In the absence of animal models, studies of human neuroendocrine phenotypes associated with neurokinin B and NK3R receptor dysfunction can help to decipher the pathophysiology of this signaling pathway. OBJECTIVE: To evaluate the prevalence of TAC3/TACR3 mutations, characterize novel TACR3 mutations and to analyze neuroendocrine profiles in nCHH caused by deleterious TAC3/TACR3 biallelic mutations. RESULTS: From a cohort of 352 CHH, we selected 173 nCHH patients and identified nine patients carrying TAC3 or TACR3 variants (5.2%). We describe here 7 of these TACR3 variants (1 frameshift and 2 nonsense deleterious mutations and 4 missense variants) found in 5 subjects. Modeling and functional studies of the latter demonstrated the deleterious consequence of one missense mutation (Tyr267Asn) probably caused by the misfolding of the mutated NK3R protein. We found a statistically significant (p<0.0001) higher mean FSH/LH ratio in 11 nCHH patients with TAC3/TACR3 biallelic mutations than in 47 nCHH patients with either biallelic mutations in KISS1R, GNRHR, or with no identified mutations and than in 50 Kallmann patients with mutations in KAL1, FGFR1 or PROK2/PROKR2. Three patients with TAC3/TACR3 biallelic mutations had an apulsatile LH profile but low-frequency alpha-subunit pulses. Pulsatile GnRH administration increased alpha-subunit pulsatile frequency and reduced the FSH/LH ratio. CONCLUSION: The gonadotropin axis dysfunction associated with nCHH due to TAC3/TACR3 mutations is related to a low GnRH pulsatile frequency leading to a low frequency of alpha-subunit pulses and to an elevated FSH/LH ratio. This ratio might be useful for pre-screening nCHH patients for TAC3/TACR3 mutations.

Reproducibility and validity of the French version of the long international physical activity questionnaire in patients with type 2 diabetes.

BACKGROUND: Increasing physical activity and decreasing sedentary time are cornerstones in the management of type 2 diabetes (T2DM). However, there are few instruments available to measure physical activity in this population. We translated the long version of the International Physical Activity Questionnaire (IPAQ-L) into French and studied its reproducibility and validity in patients with T2DM. METHODS: Reproducibility was studied by 2 telephone administrations, 8 days apart. Concurrent validity was tested against pedometry for 7 days during habitual life. RESULTS: One-hundred forty-three patients with T2DM were recruited (59% males; age: 60.9 ± 10.5 years; BMI: 31.2 ± 5.2 kg/m2; HbA1c: 7.4 ± 1.2%). Intraclass correlation coefficients (95% CI) for repeated administration (n = 126) were 0.74 (0.61-0.83) for total physical activity, 0.72 (0.57-0.82) for walking, and 0.65 (0.51-0.78) for sitting time. Total physical activity and walking (MET-min·week-1) correlated with daily steps (Spearman r = .24 and r = .23, respectively, P < .05). Sitting time (min·week-1) correlated negatively with daily steps in women (r = -0.33; P < .05). CONCLUSION: Our French version of the IPAQ-L appears reliable to assess habitual physical activity and sedentary time in patients with T2DM, confirming previous data in nonclinical populations.

Clinical characteristics and diagnostic criteria of maturity-onset diabetes of the young (MODY) due to molecular anomalies of the HNF1A gene.

CONTEXT: The diagnosis of maturity-onset diabetes of the young type 3 (MODY3), associated with HNF1A molecular abnormalities, is often missed. OBJECTIVE: The objective of the study was to describe the phenotypes of a large series of MODY3 patients and to reassess parameters that may improve its diagnosis. DESIGN, SETTING, AND PATIENTS: This retrospective multicenter study included 487 unrelated patients referred because of suspicion of MODY3. Genetic analysis identified 196 MODY3 and 283 non-MODY3 cases. Criteria associated with MODY3 were assessed by multivariate analysis. The capacity of the model to predict MODY3 diagnosis was assessed by the area under the receiver-operating characteristic curve and was further validated in an independent sample of 851 patients (165 MODY3 and 686 non-MODY3). RESULTS: In the MODY3 patients, diabetes was revealed by clinical symptoms in 25% of the cases and was diagnosed by screening in the others. Age at diagnosis of diabetes was more than 25 yr in 40% of the MODY3 patients. There was considerable variability and overlap of all assessed parameters in MODY3 and non-MODY3 patients. The best predictive model was based on criteria available at diagnosis of diabetes, including age, body mass index, number of affected generations, presence of diabetes symptoms, and geographical origin. The area under the curve of the receiver-operating characteristic analysis was 0.81. When sensitivity was set to 90%, specificity was 49%. CONCLUSIONS: Differential diagnosis between MODY3 and early-onset type 2 diabetes remains difficult. Whether the proposed model will improve the pick-up rate of MODY3 diagnosis needs to be confirmed in independent populations.

A novel mutation in the calcium-sensing receptor in a French family with familial hypocalciuric hypercalcaemia.

OBJECTIVE: The calcium-sensing receptor (CASR) has an important role in calcium homoeostasis by controlling PTH secretion and renal calcium handling. Inactivating mutations in the CASR gene (HGNC ID: 1514) cause familial hypocalciuric hypercalcaemia (FHH). We present a case of FHH patient to describe a novel mutation in the CASR. SUBJECTS AND METHODS: A 34-year-old patient was referred because of recurrent hypercalcaemia after resection of two hyperplastic parathyroids. Extensive evaluation found elevated PTH and low calcium/creatinine clearance ratio. One of her three children had high serum calcium concentrations. Genetic studies were performed by PCR amplification of CASR coding exons and direct sequencing of PCR products. Transient transfection of the wild-type (WT) CASR and the mutant CASR into COS-7 was performed to assess functional impact of the mutation and the capacity of either protein to mediate increases in cellular levels of inositol phosphates (IPs). RESULTS: CASR sequencing found a previously undescribed heterozygous base substitution, determining a change of threonine to isoleucine at codon 550 (p.T550I) in the sixth exon. In contrast to those transfected with WT CASR, which showed a five- to eightfold increase in total IPs at high levels of calcium, COS-7 cells transfected with the (p.T550I) mutant showed no increase confirming to the inactivating nature of the mutation. COS-7 cells co-transfected with the WT and the (p.T550I) mutant showed an intermediate response suggesting a possible dominant negative effect. CONCLUSION: This case report presents a not-yet-described mutation in the cysteine-rich region of the CASR extracellular domain, a mutation with a possible dominant negative effect.

Ultrasound Brain Tissue Pulsatility is decreased in middle aged and elderly type 2 diabetic patients with depression.

We used Tissue Pulsatility Imaging (TPI) to compare the Brain Tissue Pulsatility (BTP) in depressed (n=11) and non-depressed (n=13) type-2 diabetic non-demented patients aged 50 years and older. Both maximum and mean BTP were significantly decreased in depressed diabetic subjects compared to non-depressed diabetic subjects.

Trends in the quality of care for elderly people with type 2 diabetes: the need for improvements in safety and quality (the 2001 and 2007 ENTRED Surveys).

AIM: This study aimed to characterize the sociodemographic data, health status, quality of care and 6-year trends in elderly people with type 2 diabetes. METHODS: This study used two French cross-sectional representative surveys of adults of all ages with all types of diabetes (Entred 2001 and 2007), which combined medical claims, and patient and medical provider questionnaires. The 2007 data in patients with type 2 diabetes aged 65 years or over (n=1766) were described and compared with the 2001 data (n=1801). RESULTS: Since 2001, obesity has increased (35% in 2007; +7 points since 2001) while written nutritional advice was less often provided (59%; -6 points). Mean HbA(1c) (7.1%; -0.2%), blood pressure (135/76 mmHg; -4/-3 mmHg) and LDL cholesterol (1.04 g/L; -0.21 g/L) declined, while the use of medication increased: at least two OHAs, 34% (+4 points); OHA(s) and insulin combined, 10% (+4 points); antihypertensive treatment, 83% (+4 points); and statins 48% (+26 points). Severe hypoglycaemia remained frequent (10% had an event at least once a year). The overall prevalence of complications increased. Renal complications were not monitored carefully enough (missing value for albuminuria: 42%; -4.5 points), and 46% of those with a glomerular filtration rate less than 60 mL/min/1.73 m² were taking metformin. CONCLUSION: Elderly people with type 2 diabetes are receiving better quality of care and have better control of cardiovascular risk factors than before. However, improvement is still required, in particular by performing better screening for complications. In this patient population, it is important to carefully monitor the risks for hypoglycaemia, hypotension, malnutrition and contraindications related to renal function.

Low high density lipoprotein cholesterol: prevalence and associated risk-factors in a large French population.

PURPOSE: High density lipoprotein-cholesterol (HDL-C) is a strong predictor of cardiovascular risk. We investigated the distribution of HDL-C in a French general population according to age, sex, and the risk factors associated with low HDL-C values. METHODS: A group of 18,483 men and 22,047 women 16-79 years of age were investigated during a medical check-up. Relevant parameters were studied in three groups according to age and gender-specific percentile classes (≤5th [HDL5] median and >95th). Gender-specific logistic regression models selected variables associated with HDL5. RESULTS: Using the National Cholesterol Education Program Adult Treatment Panel III criteria (threshold: 40 mg/dL in men, 50 mg/dL in women) the prevalence of low HDL-C was 11.1% and 26.4% in men and women and it decreased with age. Mean HDL-C levels increased with age. HDL5 was positively associated with a sedentary lifestyle and deprivation (p < 0.00001) even after adjustment on alcohol consumption and smoking. Abdominal obesity, smoking, hypertriglyceridemia, hyperleucocytosis, and low alcohol consumption were associated with HDL5 for both genders. CONCLUSIONS: The prevalence of low HDL-C was similar to that observed in other Europeans but lower than in the United States. HDL5 was associated with cardiovascular risk factors, metabolic syndrome, and social deprivation. A prevention policy to increase HDL-C levels should focus on reducing smoking and abdominal obesity, particularly in deprived subjects.

[BRAF V600E mutation in papillary thyroid carcinoma: prevalence and detection in fine needle aspiration specimens]. / Mutation BRAF V600E et carcinomes papillaires de la thyroïde : prévalence et faisabilité de la détection sur produits de cytoponction.

UNLABELLED: BRAF V600E mutation in papillary thyroid carcinoma (PTC): prevalence and detection in fine needle aspiration (FNA) specimens. BACKGROUND AND OBJECTIVE: The activating mutation of the BRAF gene, T1799A, is the most common and specific genetic alteration in PTC. In the present study, our aims were to confirm these data and investigate the feasibility of BRAF mutation detection in FNA specimens. METHODS: In a retrospective study, we examined paraffin-embedded surgical samples of 57 PTC and 51 non-PTC thyroid tumors for the presence of BRAF mutation by dideoxy sequencing. We analyzed thyroid aspirates (drop and washed-out solution) and smears from 31 patients who underwent thyroidectomy, before intraoperative frozen sections, and 25 archival thyroid FNA smears. RESULTS: The BRAF mutation was present in 58 % of PTC. Among non-PTC thyroid tumors, only one medullary thyroid carcinoma contained the BRAF mutation. BRAF mutation was correctly detected from the FNA-derived materials. Considering the search of BRAF mutation in preoperative FNA smears, the diagnosis of PTC would have been affirmed in 31 % (4/13) of indeterminate and suspicious FNA. CONCLUSION: BRAF mutation detection in FNA specimens is feasible and could be used as an adjunct tool for preoperative diagnosis of PTC classified as indeterminate and suspicious with conventional cytology (categories 3, 4 and 5 according to NCI/Bethesda 2008 terminology).