Quantitative spectroscopy of single molecule interaction times.

Single molecule fluorescence tracking provides information at nanometer-scale and millisecond-temporal resolution about the dynamics and interaction of individual molecules in a biological environment. While the dynamic behavior of isolated molecules can be characterized well, the quantitative insight is more limited when interactions between two indistinguishable molecules occur. We address this aspect by developing a theoretical foundation for a spectroscopy of interaction times, i.e., the inference of interaction from imaging data. A non-trivial crossover between a power law to an exponential behavior of the distribution of the interaction times is highlighted, together with the dependence of the exponential term upon the microscopic reaction affinity. Our approach is validated with simulated and experimental datasets.

EPILEPTIC SEIZURES AS THE FIRST MANIFESTATION OF FAHR'S SYNDROME.

INTRODUCTION: Hypoparathyroidism is a rare endocrine disorder, leading to complications affecting the kidneys, the eyes, the cerebrum (Fahr's syndrome, epilepsy, parkinsonism, cognitive impairment), and the heart. CASE REPORT: We present the case of a 24-year old male that presented to our clinic for generalized tonic-clonic seizures increasing in frequency for the last year or so. Furthermore, he was diagnosed with subcapsular cataract of both eyes and had intraocular lens implant surgery 12 years ago. CT scan performed at admission showed calcium deposits on the dentate nuclei, basal ganglia, thalamus, cerebellum and bilateral subcortical fronto-parietal white matter compatible with Fahr's disease. The results of the laboratory tests were normal except for hypocalcemia, hyperphosphoremia and low intact parathormone (iPTH). The patient was diagnosed with primary hypoparathyroidism which led to Fahr's syndrome. The patient was prescribed oral medication including calcium carbonate, calcidiol, magnesium orotate and levetiracetam. The follow-up after three months revealed a seizure free status and normalization of magnesium, calcium, and phosphorus levels. CONCLUSION: Fahr's syndrome can be a cause of epileptic seizures and should be considered in the clinical approach to an epileptic patient, especially in children, teenagers, and young adults.

PATIENTS TREATED WITH INSULIN AND SULPHONYLUREA ARE AT INCREASED MORTALITY RISK AS COMPARED WITH THOSE TREATED WITH INSULIN PLUS METFORMIN.

AIMS: To investigate the effect of sulphonylurea (SU) treatment on all-cause and cardiovascular mortality as compared with metformin (MET), when used in combination with insulin (INS) in type 2 diabetes. METHODS: All type 2 diabetes patients aged ≥40 years were included at their first prescription of INS+MET or INS+SU, during 2001-2008. They were considered at risk until death or December 31st, 2011. Mortality rates were calculated per 1000 person-years. Crude and adjusted rate ratios (RR) were calculated using time dependent analysis with INS+MET as reference. RESULTS: There were 7122 patients (60.8% women) included in the analysis, with a mean age at baseline of 62.0±9.9 years. During the 11 years of study, patients on INS+MET contributed 13620 person-years and 330 deaths (mortality rate 24, CI95% 22-27), while those on INS+SU contributed 8720 person-years and 393 deaths (mortality rate 45, CI95% 41-50). Adjusted all-cause mortality RR were: SU 1.6 (CI95% 1.21-2.11, p<0.001), glimepiride 1.18 (CI95% 0.73-1.91, p=0.51), gliclazide 1.78 (CI95% 1.07-2.95, p=0.024), glibenclamide 1.66 (CI95% 0.71-3.88, p=0.23), glipizide 1.24 (CI95% 0.68-2.27, p=0.49), and gliquidonum 2.32 (CI95% 1.54-3.50, p=0.001). CONCLUSIONS: When combined with insulin as dual therapy, patients treated with SU were at increased mortality risk as compared with insulin + MET.

25 Gbps direct modulation and 10 km data transmission with 1310 nm waveband wafer fused VCSELs.

Direct modulation at >25 Gbps is achieved with 1310 nm wavelength wafer fused VCSELs by adjusting the strain in the quantum well active region and the cavity photon lifetime. 25 + Gbps large signal modulation with 10-12 BER at 1310 nm across 10 km of standard single mode fiber is demonstrated.

Polarization mode control of long-wavelength VCSELs by intracavity patterning.

Polarization mode control is enhanced in wafer-fused vertical-cavity surface-emitting lasers emitting at 1310 nm wavelength by etching two symmetrically arranged arcs above the gain structure within the laser cavity. The intracavity patterning introduces birefringence and dichroism, which discriminates between the two polarization states of the fundamental transverse modes. We find that the cavity modifications define the polarization angle at threshold with respect to the crystal axes, and increase the gain anisotropy and birefringence on average, leading to an increase in the polarization switching current. Experimental measurements are explained using the spin-flip model of VCSEL polarization dynamics.

8.5 W VECSEL output at 1270 nm with conversion efficiency of 59%.

We report on 1270 nm vertical-external-cavity surface-emitting lasers (VECSELs) with up to 59% conversion efficiency and maximum output power of 8.5 W (pump limited), at 5°C heat sink temperature. These VECSELs comprised wafer-fused gain mirrors in the flip-chip (thin-disk) heat dissipation scheme. The reflected pump light from the gain mirror surface was found to depend considerably on temperature and pump power.

West Nile virus circulation in South-Eastern Romania, 2011 to 2013.

Lineage 2 West Nile virus (WNV), previously found only in sub-Saharan Africa and Madagascar, was identified in Hungary in 2004 and has rapidly expanded in Europe in the past decade. Following a significant outbreak of West Nile fever with neurological cases caused by lineage 1 WNV in Romania in 1996, scattered cases have been recorded in the south-east of the country in each transmission season. Another outbreak, affecting a larger area and caused by lineage 2 WNV, was recorded in 2010. We analysed human sera from neuroinvasive West Nile fever cases and mosquitoes, sampled in south-eastern Romania between 2011 and 2013, for the presence of WNV genome, and obtained partial NS5 and envelope glycoprotein sequences. Human- and mosquito-derived WNV sequences were highly similar (99%) to Volgograd 2007 lineage 2 WNV and differed from isolates previously detected in central and southern Europe. WNV was detected in one pool of Culex pipiens s.l. males, documenting vertical transmission. Lineage 4 WNV, of unknown pathogenicity to mammals, was found in the amphibian-feeding mosquito Uranotaenia unguiculata from the Danube Delta. Our results present molecular evidence for the maintenance of the same isolates of Volgograd 2007-like lineage 2 WNV in south-eastern Romania between 2011 and 2013.

Increasing single mode power of 1.3-µm VCSELs by output coupling optimization.

We report on the single mode emission power enhancement of 1.3-µm VCSELs by adjusting the reflectivity of the top GaAs-based DBR for output coupling optimization using selective removal of Bragg reflector layers. Devices with record single mode power of 6.8-mW at room temperature and 2.8-mW at 80°C, with more than 30 dB single mode suppression ratio, have been obtained.

Optical injection locking of transverse modes in 1.3-µm wavelength coupled-VCSEL arrays.

Optical injection locking of 1.3-µm phase-locked VCSEL arrays defined by patterned tunnel junctions and wafer fusion is investigated experimentally and theoretically. The impact of the overlap between the master laser injection beam and the injected modes is demonstrated and explained with a rate equation model that incorporates the spatial variations.

Laparoscopic sleeve gastrectomy improves reproductive hormone levels in morbidly obese males -- a series of 28 cases.

BACKGROUND: Obese males frequently present with low androgen levels that may improve after weight loss achieved by bariatric surgery. Laparoscopic sleeve gastrectomy (LSG) has been used often in the last decade as treatment for morbid obesity. The aim of this study was to evaluate modifications in the male reproductive hormone profile after LSG. PATIENTS AND METHODS: The prospective study included 28 males with body mass index (BMI) 35 kg m2 who underwent LSG.Total Testosterone (TT), Sex Hormone Binding Globulin(SHBG) and Luteinizing hormone (LH), together with biochemical and anthropometric data, were evaluated at baseline and after LSG. RESULTS: Baseline patients had a mean BMI of 50.10 (+-11.19)kg m2, SHBG 23.37 (+-17.47) nmol L, LH 3.83 (+-1.76)mUI ml and TT 8.31 (+-3.24) nmol L. After LSG, patients showed a mean BMI of 35.87 (+-7.02) kg m2 (p 0.001),SHBG 37.81 (+-18.95) nmol L (p 0.05), LH 4.76 (+-2.49)mUI ml (p 0.05), whereas mean TT was 12.7 (Â+-3.8) nmol L(p 0.001). The percentage of excess body weight loss (%EBL)was 43.07 (+-9.56) and metabolic syndrome prevalence decreased significantly from 75% to 25% (p 0.001). CONCLUSIONS: Beyond BMI loss, LSG significantly improved reproductive hormone levels in morbidly obese males.

14XX nm-wavelength electrically-pumped VECSELs fabricated by wafer fusion.

We report on the design, fabrication and characterization of electrically pumped vertical external cavity surface emitting lasers (EP-VECSELs) emitting at 1470 nm. We demonstrate 6.2 mW of CW output power, which represents the highest power value reported so far for EP-VECSELs in the 14XX nm and 15XX nm wavelength bands.

Association of serum adiponectin and insulin-like growth factor I levels with parameters of cardiac remodeling in severely obese patients.

BACKGROUND: Obesity is associated with various changes in cardiac geometry and this process involves both hemodynamic and non-hemodynamic factors, among which adipocitokines and growth factors may play an important role. The aim of this study was to identify the extent and pattern of cardiac remodeling in a group of severely obese patients and analyze the relationship between adiponectin, IGFI and cardiac parameters reflecting obesity-associated structural changes. SUBJECTS AND METHODS: Our study included 344 patients (104 men) with severe obesity [mean body mass index (BMI)= 45.7 ± 8.5 kg/m(2)], extensively evaluated clinically and biologically (complete metabolic tests, serum adiponectin, and IGF-I measurements). Left ventricular (LV) mass index (LVMI), left atrium (LA) size, and LV geometry were determined by means of cardiac ultrasound. RESULTS: The most prevalent pattern of LV geometry was eccentric hypertrophy (28.7% of patients). In a gender-, age-, BMI-, diabetes- and hypertension-adjusted general linear model, patients with concentric or eccentric hypertrophy had significantly lower values of adiponectin than those with normal geometry (6.75 ± 0.41, 6.96 ± 0.53, vs 9.04 ± 0.42 mg/l, p<0.05). In multivariate analysis, independent determinants for LVMI were BMI (ß=0.364, p<0.001), systolic blood pressure (BP) (ß=0.187, p=0.004), age (ß=0.246, p<0.001), adiponectin (ß=-0.151, p=0.012), and IGF-I z-score (ß=0.134, p=0.025) while factors independently related to LA size were systolic BP (ß=0.218, p<0.001), BMI (ß=0.194, p<0.001), age (ß=0.273, p<0.001), gender (ß=-0.195, p<0.001), and adiponectin (ß=-0.180, p=0.005). CONCLUSIONS: In patients with severe obesity, IGF-I z score and adiponectin correlate with parameters of cardiac remodeling independently of anthropometric, hemodynamic or metabolic factors.

Adiponectin, body mass index and hepatic steatosis are independently associated with IGF-I status in obese non-diabetic women.

OBJECTIVE: Low IGF-I levels have been associated with obesity, insulin resistance, hepatic steatosis, and were shown to predict cardiovascular mortality. Adiponectin, on the other hand, was proved to have an important protective role against metabolic and cardiovascular diseases. This study investigates the relation between hepatic steatosis, adiponectin and IGF-I levels in a group of non-diabetic obese Romanian women. DESIGN: This cross-sectional study included 201 obese non-diabetic women, with mean age of 41.1±11.9 years and mean body mass index (BMI) of 44.1±8.3 kg/m(2), consecutively admitted to the Endocrinology Department of a University Hospital to be evaluated as candidates for bariatric surgery. Main measured parameters included total adiponectin (detected by ELISA method), insulin, C reactive protein (CRP), and IGF-I (all by chemiluminescence methods). Insulin sensitivity was assessed using the Quantitative Insulin Sensitivity Check Index (QUICKI). Patients were considered IGF-deficient if IGF-I z score was ≤2 standard deviations from mean for age. Hepatic ultrasound was used to determine the presence of significant steatosis (SS+). RESULTS: Significant steatosis was observed in 60.7% of our patients and this feature was associated with reduced total adiponectin levels (p<0.001) and lower IGF-I z scores (p<0.001). IGF-I z score negatively correlated with BMI (r=-0.283, p<0.001), alanine aminotransferase (ALT) (r=-0.130, p=0.032), gamma glutamyltransferase (GGT) (r=-0.158, p=0.018) and logarithmic transformed (log) CRP (r=-0.232, p=0.001) and positively correlated with QUICKI (r=0.148, p=0.023) and log adiponectin (r=0.216, p=0.003). The relationship between IGF-I z score and log adiponectin remained significant after adjusting for age, BMI, ALT, QUICKI and log CRP (r=0.183, p=0.012). IGF-I deficiency was present in 33.3% of these obese women. In multivariate logistic analysis, BMI (p<0.001), ALT (p=0.003), log adiponectin (p<0.001) and SS (p=0.043) proved to be independently associated with IGF-I deficiency. CONCLUSIONS: Adiponectin is significantly correlated with IGF-I z scores and, along with BMI, ALT and significant steatosis, is independently associated with IGF-I deficiency in obese non-diabetic women.

Six months results of laparoscopic sleeve gastrectomy in treatment of obesity and its metabolic complications.

BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) has become a popular bariatric surgical procedure, with proven results in achieving weight loss, however data regarding its effectiveness on metabolic syndrome (MetS) components are scarce. The aims of the present study were to assess the outcomes of LSG on weight loss and obesity associated metabolic complications at six months following intervention. PATIENTS AND METHODS: This was a retrospective study on 124 consecutive obese patients (29.8% men), who had undergone LSG between 01/01/2008 and 12/31/2010, in a highly specialized clinic. The dynamic of anthropometric and biochemical data between baseline and six months following LSG were evaluated. We also determined the change in MetS prevalence and used logistic regression to estimate predictors of MetS remission RESULTS: 6 months after LSG, the body mass index (BMI) decreased from 46.84 +/- 8.62 to 33.81 +/- 7.04 kg/m2 (p < 0.001). Mean excess BMI loss (EBL) was 65.24 +/- 25.16%. The best results on weight loss were observed in young patients, not affected by MetS, with lower initial BMI. Lipids profile suffered a significant improvement (HDL cholesterol increased, while LDL, total cholesterol, triglycerides decreased, p < 0.05 for each). HOMA-IR values decreased by 75.2%, from 5.24 +/- 4.49 to 1.30 +/- 1.22 (p < 0.001). MetS prevalence was reduced from 74.3% to 18.4% (p < 0.001). In multivariate analysis, % EBL remained the only significant predictor of MetS remission, the risk for lack of a MetS remission being practically 3 times higher in patients with EBL < 50%, compared to those with EBL > 50% (OR: 2.97, CI: 1.1-10.23, p < 0.05). CONCLUSIONS: As early as 6 months after LSG we recorded a significant weight loss and improvement in insulin resistance and lipids metabolism, as well as an impressive reduction in metabolic syndrome prevalence.

Outbreak of West Nile virus infection in humans, Romania, July to October 2010.

A total of 57 cases of West Nile virus infection (54 with neuroinvasive infection and three with fever) were identified in Romania between July and October 2010.The median age of the cases was 53.4 years, with the highest incidence in the age group 60­69 years.The case fatality rate was 8.8%. Cases were distributed in 19 districts in the southern, western, central and eastern parts of the country. Molecular investigation revealed lineage 2 West Nile virus, related to the Volgograd 2007 strain.

1.38-µm mode-locked Raman fiber laser pumped by semiconductor disk laser.

A mode-locked Raman fiber laser pumped by 1.3 µm semiconductor disk laser is demonstrated. Direct Watt-level core-pumping of the single-mode fiber Raman lasers and amplifiers with low-noise disk lasers is demonstrated to represent a highly practical solution as compared with conventional scheme using pumping by Raman wavelength convertors. Raman laser employing passive mode-locking by nonlinear polarization evolution in normal dispersion regime produces stable pedestal-free 1.97 ps pulses at 1.38 µm. Using semiconductor disk lasers capable of producing high power with diffraction-limited beam allows Raman gain to be obtained at virtually any wavelength of interest owing to spectral versatility of semiconductor gain materials and wafer-fusing technology.

Raman fiber laser pumped by a semiconductor disk laser and mode locked by a semiconductor saturable absorber mirror.

A 1.6µm mode-locked Raman fiber laser pumped by a 1480nm semiconductor disk laser is demonstrated. Watt-level core pumping of the single-mode fiber Raman lasers with low-noise disk lasers together with semiconductor saturable absorber mirror mode locking represents a highly practical solution for short-pulse operation.