Application of simple photobleaching microscopy techniques for the determination of the balance between anterograde and retrograde axonal transport

The directionality of axonal transport represents an important question in neurophysiological and neuropathological research. Various approaches such as videomicroscopy, radioisotopic and fluorescence-based techniques are used. Recently, a novel FRAP-based (fluorescent recovery after photobleaching) technique using synaptophysin-EGFP expression in primary neurons was applied, allowing reliable and sensitive evaluation of gross axonal transport changes using confocal live-imaging microscopy. Here, we describe a novel FLIP-based (fluorescence loss in photobleaching) approach using a synaptophysin-EGFP probe that allows the differential evaluation of the ante- and retrograde transport parameters. Furthermore, we improved the sensitivity of the probe by substituting EGFP with an ECFP/VenusYFP fusion FRET (fluorescence resonance energy transfer) pair. The use of this FRET couple improves the precision of axonal transport measurements by combining FLIP and FLAP (fluorescence localization after photobleaching) techniques and eliminating the need for pre-bleaching images and thus pixel shifts between various exposures, and by reducing the deleterious effect of photobleaching.     

A 15-year longitudinal follow-up study of heart rate and heart rate variability in healthy elderly persons

BACKGROUND: Few researchers have conducted heart rate (HR) studies in healthy very elderly subjects aged 70 years or older, and there are no longitudinal follow-up studies in this population. The objective of this study was to evaluate long-term changes in HR and heart rate variability (HRV) with aging in healthy elderly persons by means of comparison between two Holter monitor recordings obtained at an interval of 15 years. METHODS: The study population consisted of 15 healthy elderly persons (10 women and 5 men) aged 64 to 80 years (mean 70 +/- 4.1) at the first recording, and 79 to 95 years old (mean 85 +/- 4.1 years) at the second recording 15 years later. Nighttime (midnight to 5 AM) and daytime (noon to 5 PM) HR and HRV were obtained, and paired t tests were performed to assess the differences in each parameter of nighttime and daytime HR and HRV between the two (15-year interval) Holter monitor recordings. RESULTS: The results of the t-test comparisons were as follows: there was a significant increase in minimal, maximal, and average HRs (nighttime, p < .01; daytime, p < .05, respectively). On the other hand, with regard to HRV, there was a significant nighttime decrease in the SDNN index (mean of standard deviations of normal RR intervals between adjacent QRS complexes resulting from sinus node depolarizations for all 5-minute segments) (p = .0086), and a significant daytime increase in the NN50 (number of adjacent normal RR intervals >50 milliseconds) per hour (p = .0425). Moreover, there was a significant decrease in the low-frequency (LF) component (nighttime, p = .0151; daytime, p = .0032), and a significant decrease in the LF/HF ratio (nighttime, p = .0270; daytime, p = .0371), but there was no significant change in the nighttime or daytime high-frequency (HF) component. CONCLUSIONS: HR increased with age over the 15-year period in the healthy elderly persons. As for concurrent changes in HRV, however, the parameters of sympathetic modulation decreased, and the parameters of parasympathetic modulation were unchanged or slightly increased.     

Serum hepatitis B surface antigen correlates with fibrosis and necroinflammation: A multicentre perspective in China

The kinetics of serum hepatitis B surface antigen (HBsAg) during the natural history of hepatitis B virus (HBV) infection has been studied, but the factors affecting them remain unclear. We aimed to investigate the factors affecting HBsAg titres, using data from multicentre, large‐sized clinical trials in China. The baseline data of 1795 patients in 3 multicentre trials were studied, and the patients were classified into 3 groups: hepatitis B early antigen (HBeAg)‐positive chronic HBV infection (n = 588), HBeAg‐positive chronic hepatitis B (n = 596), and HBeAg‐negative chronic hepatitis B (n = 611). HBsAg titres in the different phases were compared, and multiple linear progression analyses were performed to investigate the implicated factors. HBsAg titres varied significantly in different phases (P = .000), with the highest (4.60 log10 IU/mL [10%‐90% confidence interval: 3.52 log10 IU/mL‐4.99 log10 IU/mL]) in patients with HBeAg‐positive chronic HBV infection. In all phases, age and HBV DNA were correlated with serum HBsAg level. In HBeAg‐positive chronic hepatitis B patients, a negative correlation between HBsAg titres and fibrosis stage was observed. Alanine amonitransferase or necroinflammatory activity was also correlated with HBsAg titres in HBeAg‐negative chronic hepatitis B patients. In conclusion, decreased HBsAg titres may be associated with advancing fibrosis in HBeAg‐positive chronic hepatitis B patients or increased necroinflammation in those with HBeAg‐negative chronic hepatitis B. Our findings may help clinicians better understand the kinetics of HBsAg and provide useful insights into the management of this disease.     

Evaluation of internal reliability in the presence of inconsistent responses

Background  

We aimed to assess the impact of inconsistent responses on the internal reliability of a multi-item scale by developing a procedure to adjust Cronbach's alpha.     

Waist Circumference Reference Values for Screening Cardiovascular Risk Factors in Chinese Children and Adolescents

Objectives To explore the optimal threshold values of waist circumference （WC） for detecting cardiovascular （CV） risk factors among Chinese children and adolescents. Methods Association of WC with CV risk factors was studied among 65 898 children aged 7-18 years whose data were pooled from nine previous studies in China. CV risk factors in this study included hypertension （blood pressure above 95 percentile levels）, dyslipidemia （with one or more of the following three indexes： TG ≥ 1.7 mmol/L, TC ≥ 5.18 mmol/L, and HDL-C ≤ 1.04 mmol/L） and elevated glucose level （fasting plasma glucose ≥5.6 mmol/L）. Receive-operating characteristic analysis （ROC） and logistic regression were employed to derive optimal age- and sex-specific waist circumference references for predicting CV risk factors. Results A slight increasing trend of CV risk factors was observed starting from the 75th percentile of waist circumference in the study population, while a remarkable increasing trend occurred from the 90th percentile. The optimal waist circumference thresholds for predicting high blood pressures were at the 75th percentile for both boys and girls, which was at the 90th percentiles for detecting at least two of the above three CV risk factors. In comparison with children with waist circumference below the 75th percentile, the odds ratio of two CV risk factors doubled among children with waist circumference between the 75th and the 90th percentile, and increased by 6 times among children with waist circumference above the 90th percentile. The trend of high blood pressure increasing with waist circumference remained significant after having been stratified by BMI category. Conclusion The 75th and the 90th percentiles of WC are the optimal cut-off points for predicting an increased and a substantially increased risk of CV factors in Chinese children and adolescents, respectively.     

Amaryl (glimepiride) in patients with type 2 diabetes mellitus

The purpose of the present study was to investigate the effect of the first third-generation sulphonylurea drug glimepiride (Amaryl, Aventis) in the treatment of patients with type 2 diabetes mellitus in an open 6-month clinical trial. The study included 19 patients with type 2 diabetes mellitus (7 men and 12 women, aged 53.6 +/- 2.43 years, mean duration of diabetes 7.79 +/- 1.45 years). The body mass index (BMI) of the patients was x = 30.157 +/- 1.63 which is at the borderline between overweight and obesity. The patients started at a baseline dosage of 1 mg which was then it was gradually adjusted according to the blood sugar level. The dosage of the drug varied between 1 and 6 mg (mean daily dosage 2.03 mg). The metabolic control parameters that were calculated included fasting and 2-hour postprandial blood sugar concentration, total cholesterol, serum triglycerides, HbA1c, and microproteinuria. They were measured at baseline, at 3 and 6 months. The results showed that the fasting blood glucose decreased significantly (P<0.05 at 3 months and P<0.001 at 6 months). Statistically significant lower postprandial glycemia was also observed in the patients (the decrease was not significant at 3 months but highly significant at 6 months, P<0.01). The overall evaluation was based on the values of HbA1c--they were statistically significantly lower at 6 months (P<0.01) which suggests the steady improving tendency of the metabolic control in type 2 diabetes patients treated with Amaryl (glimepiride). The improvement of the metabolic control was also manifested by the lower serum triglycerides levels (P<0.05) and the BMI remaining nearly without change. It is concluded that Amaryl (glimepiride) is an efficacious oral sulphonylurea preparation which can be used as an appropriate substitute of the other beta cell stimulators. Glimepiride once daily provides a good compliance of patients which reduces to minimum the skipped doses. It is associated with a reduced risk of hypoglycemia and causes no weight gain.     

Psychopathology and psychosocial causes in adult deliberate self-poisoning in Plovdiv region, Bulgaria

INTRODUCTION: The percentage of deliberate self-poisoning among acute intoxications continues to be high in the medical practice worldwide; in Plovdiv region it reaches 64% of all acute poisoning cases. MATERIAL AND METHODS: A representative retrospective study of 311 acute deliberate self-poisoning cases over 14 years of age, treated in the Regional toxicological center of Plovdiv region between 01.01.1990 and 31.12.1998 was carried out. The following factors were studied: gender, age, type of poisoning, psychiatric diagnosis and psychosocial stressors. The classification criteria of Diagnostic and Statistical Manual--4th edition (DSM-IV) of the American Psychiatric Association were applied. RESULTS: We identified a first attempt of deliberate self-poisoning in 237 patients (71.6%) and a second consecutive attempt in 62 patients (18.7%). Thirty two (9.7%) of the attempts were committed in a state of alcohol intoxication. The percentage of women was statistically significantly higher. The age group of 14-19 years represented the highest percentage (27%). In 168 patients (50.8%) a psychiatric disorder was diagnosed. Adjustment disorder (53.57%) and depressive and schizophrenic disorders (26.79%) were the leading diagnoses among adults committing deliberate self-poisoning. The problems with primary support group (in 61.8% as a single stressor and in 13.71% in combination with other stressors) were the most common psychosocial factors for deliberate self-poisoning. CONCLUSIONS: To reduce the number of adult deliberate self-poisonings, measures including harmonization of the relationships in the primary support group and active treatment of patients with depressive and schizophrenic disorders are needed.     

Automatic adjustment of biphasic pulse duration in transthoracic defibrillation

Many studies have proven that biphasic defibrillation pulses are more efficient than the damped sinusoid monopolar waveform. Transthoracic resistance was shown to change during the two phases. On the other hand, it was proven that transthoracic resistance plays an important role in the defibrillation process, yielding the current for selected energy or voltage. Pre-shock measurement of the resistance may lead to improved selection. Stabilized current defibrillators are of low stored-to-delivered energy ratio. Therefore, automatic dynamic adjustment of some defibrillator parameters with respect to transthoracic resistance changes seems rational. An approach is known for modifying the pulse duration, in order to deliver a selected energy. A method is proposed here and an experimental defibrillator is developed for dynamic pulse duration adjustment with the purpose of obtaining a desired optimal time-course of the cardiac cell transmembrane potential.     

Left ventricular aneurysm without coronary artery disease, incidence and clinical features: clinical analysis of 11 cases

OBJECTIVE: To examine the incidence, underlying disease and clinical features of left ventricular aneurysm (LVA) not related to coronary artery occlusion. METHODS: Retrospective review of consecutive patients who underwent both left ventriculography and coronary angiography. PATIENTS: LVA was confirmed in 11 of 2,348 consecutive patients (0.47%). RESULTS: The location of LVA was mainly in the apical region (81.8%). In five of the 11 patients (45.5%), the underlying heart disease was hypertrophic cardiomyopathy (HCM), including 4 patients of dilated phase and one patient of midventricular type. The serial ECG changes from left ventricular hypertrophy to abnormal Q wave and endomyocardial biopsy were useful for the differential diagnosis of these cases against myocardial infarction. The underlying disease of the remaining patients was: myocarditis (2 patients), arrhythmogenic right ventricular dysplasia (1 patient), Chagas' disease (1 patient), glycogen storage disease (1 patient), and sarcoidosis (1 patient). Ventricular tachycardia appeared in 9 of 11 cases (81.8%) including 2 patients with sustained ventricular tachycardia. CONCLUSION: LVA formation without coronary artery disease was a rare phenomenon. The underlying disease was varied but the incidence of hypertrophic cardiomyopathy in the dilated phase was comparatively high. Ventricular tachycardia was a significant complication in these patients.