Physical activity is associated with clinically important differences in health-related quality of life among rural and small-town breast cancer survivors.
The primary purpose of this study was to examine differences in health-related quality of life and fatigue between rural and small-town (RST) breast cancer survivors meeting and not meeting public health physical activity (PA) recommendations. Using a retrospective survey design, RST breast cancer survivors (N = 524) residing in Southern Alberta, Canada completed a mailed questionnaire assessing self-reported prediagnosis, on treatment, and current PA behavior, and current health-related quality of life and fatigue. Analyses indicated 44.1%, 13.7%, and 34.7% of RST breast cancer survivors met public health PA recommendations during prediagnosis, on treatment, and post-treatment (i.e., current) time periods, respectively. Multivariate analyses of variance suggested indicated survivors currently meeting PA recommendations reported clinically advantageous differences in health-related quality of life and fatigue symptoms than survivors not currently meeting PA recommendations. Repeated measures analyses also indicated significant differences in PA behavior across the three cancer-related time periods (all p < 0.01). The results of this study provide evidence that RST breast cancer survivors have similar PA behavior estimates across the cancer trajectory to urban survivors. Being physically active was associated with clinically important advantages with respect to health-related quality of life and fatigue. Strategies designed to facilitate PA behavior in the RST breast cancer survivor population are warranted.


The efficacy of color duplex sonography in preoperative assessment of anterolateral thigh flap.
The anterolateral thigh (ALT) flap has become a workhorse in reconstructive surgery of the head and neck region and the extremities. However, its inconsistent vascular anatomy and frequent intramuscular course of perforators often cause difficulties during the dissection of this versatile flap. Hence, reliable preoperative perforator mapping and identification of vascular anomalies may render the raising of the flap easier and safer. The aim of this study was to evaluate the use of Color Duplex sonography and whether it allows the distinction between septocutaneous and musculocutaneous perforators. For this purpose, the thighs of 13 patients undergoing reconstruction with ALT flaps were examined preoperatively, and results were compared to intraoperative findings. A total of 30 perforators could be detected preoperatively, of which 29 were confirmed during flap dissection. Preoperative Color Duplex sonography correctly predicted the course of all perforators as either running through the vastus lateralis muscle or the intermuscular septum. In our investigations, Color Doppler sonography had a 96.7% positive predictive value and a 96.7% true positive rate in detecting perforators. Color Duplex sonography is a highly reliable tool in the preoperative assessment of ALT flaps. Localization and course of perforators can be determined accurately and vascular anomalies can be identified.


[Substance P is not involved in SII descending modulation of the nucleus centrum medianum of the thalamus in cats].
It was investigated that the effects of electrical stimulation of the somatosensory area II (SII) of the cerebral cortex and electroacupuncture on substance P (SP) concentration in the perfusate from the nucleus centrum medianum (CM) of the thalamus, in order to probe into if SP participates in the SII descending modulation of the nucleus CM and this mechanism of acupuncture analgesia. Adult cats were randomly divided into three groups: control, electroacupuncture and electrical stimulation of SII. Push-pull perfusion technique was used to collect the perfusate from the nucleus CM. SP contents in the perfusate were determined by radioimmunoassay. The results showed that SP contents in the perfusate have not statistically significant changes before and after the electrical stimulation of SII or electroacupuncture, suggesting that the SP release from the nucleus CM was not influenced by the stimulation of SII or electroacupuncture. It is indicated that SP may not associate with the SII descending modulation of the nucleus CM and this mechanism of acupuncture analgesia.


Phlorizin binding to renal outer cortical brush-border membranes of cadmium-injected rabbits.
The effect of cadmium injection on the high-affinity phlorizin binding to renal outer cortical brush-border membranes was studied in rabbits. Animals received subcutaneous injections of CdCl2 at a dose of 3 mg Cd/kg.day for about 3 weeks. Brush-border membranes were isolated from renal outer cortex by Percoll gradient centrifugation and magnesium precipitation. Cadmium injection resulted in a marked increase in membrane cadmium content and decrease in Na(+)-dependent phlorizin binding. The latter effect was attributed to a reduction in the number of binding sites (N0) and not to changes in the dissociation constant (Kd). Similar results were observed in normal membrane vesicles directly exposed to cadmium in vitro. These results suggest that one mechanism of the cadmium-induced glycosuria is a loss of active Na(+)-glucose cotransport carrier in the proximal tubular brush-border membrane by direct interaction with free cadmium.


[Ovarian neoplasms and tumor markers].
This is an experience about the utility of CA125 in diagnosis, staging, prognosis, and therapeutic response of ovarian cancer. The patients were 21 (the ages range was 38-66). They had an epithelial cancer (10 serous, 3 mucinous, 2 endometrioid, 6 non specific). The quantitative test of CA125 was performed with purified monoclonal antibody OC125 pre and post antineoplastic treatment. The reduction of CA125 was in connection with the neoplastic regression. Perservering or increasing values were related to neoplastic stasis or to non-responsive neoplasia, respectively. Even if the method we used was specific its sensibility is lower in patients with smallest residue disease.


[Evaluation of nasal patency].
The subjective estimation of nasal breathing, the flow in anterior rhinomanometry, nasal peak flow and the results of acoustic rhinometry have been investigated in 30 patients before and after decongestion of the nasal mucosa. The aim of this study was to compare the different methods in view of their results. The effect of decongestion can be seen in all methods. A regression analysis showed no significant correlation between these methods. We found the best correlation between subjective estimation and the flow in anterior rhinomanometry at 75 Pa on the side of the better flow. The decisive drawback of the acoustic rhinometry is the fitting between nosepiece and nostril. Because of the influence of extranasal factors on the results of the peak flow measurement, anterior rhinomanometry seems to be the most reliable method to assess nasal air flow.


Hypothyroidism and cerebral vein thrombosis--a possible association.
There are many systemic illnesses that constitute risk factors for cerebral vein thrombosis (CVT). Hypothyroidism was never associated with CVT, despite growing evidence supporting a possible etiopathogenic link. We report two patients with CVT in whom hypothyroidism was concomitantly diagnosed. Cases were women 21 and 52 years old. They both presented with intracranial hypertension syndrome and symptomatic focal epilepsy. CVT was diagnosed with MRI and MR venography. Hypothyroidism was diagnosed in the acute phase of CVT. Both had an autoimmune thyroiditis. None of the patients had diffuse goitre. Other risk factors for CVT were oral contraceptives and elevated homocysteine in one and hormonal replacement therapy in the other. Both were treated with anticoagulation, anti-epileptic drugs and thyroid replacement therapy, with good clinical outcome. The association found between untreated hypothyroidism and CVT in these patients may result from chance. However, several haemostatic and fibrinolytic parameters have been demonstrated to be disturbed in hypothyroidism suggesting a possible role of this disease in CVT pathogenesis. In addition, indirect evidence also supports possible endothelial dysfunction and venous stasis in hypothyroidism, further emphasizing the physiopathological link between the two conditions. More research is needed to determine a possible causal role of hypothyroidism on CVT. We suggest that thyroid function should be included in the usual workup of CVT patients.


Does a medial retraction blade transmit direct pressure to pharyngeal/esophageal wall during anterior cervical surgery?
A prospective study of 25 patients who underwent anterior cervical surgery. To assess retraction pressure and the exposure of pharyngeal/esophageal (P/E) wall to the medial retractor blade to clarify whether medial retraction causes direct pressure transmission to the P/E wall. Retraction pressure on P/E walls has been used to explain the relation between the retraction pressure and dysphagia or the efficacies of new retractor blades. However, it is doubtful whether the measured pressure represent real retraction pressure on the P/E wall because exposure of the P/E in the surgical field could be reduced by the shielding effect of thyroid cartilage. Epi- and endoesophageal pressures were serially measured using online pressure transducers 15 minutes before retraction, immediately after retraction, and 30 minutes after retraction. To measure the extent of P/E wall exposure to pressure transducer, we used posterior border of thyroid cartilage as a landmark. Intraoperative radiograph was used to mark the position of the posterior border of thyroid cartilage. We checked out the marked location on retractors by measuring the distance from distal retractor tip. The mean epiesophageal pressure significantly increased after retraction (0 mmHg: 88.7 ± 19.6 mmHg: 81.9 ± 15.3 mmHg). The mean endoesophageal pressure minimally changed after retraction (9.0 ± 6.6 mmHg: 15.7 ± 13.8 mmHg: 17.0 ± 14.3 mmHg). The mean location of the posterior border of thyroid cartilage was 7.3 ± 3.5 mm on the retractor blade from the tip, which means epiesophageal pressure was measured against the posterior border of thyroid cartilage, not against the P/E wall. We suggest that a medial retraction blade does not transmit direct pressure on P/E wall due to minimal wall exposure and intervening thyroid cartilage. Our result should be considered when measuring retraction pressure during anterior cervical surgery or designing novel retractor systems.


Combining a symptom index, CA125 and HE4 (triple screen) to detect ovarian cancer in women with a pelvic mass.
To assess a simple algorithm of CA125, HE4 and Symptom Index to predict ovarian cancer in women with a pelvic mass. This was a prospective study of women referred to a gynecologic oncology clinic for surgical evaluation of a pelvic mass. Preoperatively, women completed a SI and had serum markers drawn. Results were correlated with pathology. A triple screen was considered positive if at least 2 of the 3 markers were abnormal (positive SI, CA125≥35U/mL, HE4≥140pmol/L). 218 patients enrolled in the study. 66 patients (30%) had ovarian or fallopian tube cancer (97% epithelial), 124 (57%) had benign masses, 17 (8%) had borderline tumors, and 11 (5%) had metastatic disease. The SI, CA125 and HE4 were positive in 87.9%, 74.2% and 60.6% of ovarian cancer patients, respectively. Of the 112 women with a positive SI 58 (52%) had ovarian cancer and 75 (67%) had non-benign masses. Excluding borderline and metastatic cancers the sensitivity of the triple screen was 79%; specificity 91%, PPV 83% and NPV 89%. CA125 alone had a sensitivity, specificity, PPV and NPV of 79%, 76%, 63% and 87% respectively. Requiring only one of the three tests to be abnormal resulted in a sensitivity of 97% but specificity dropped to 50%. An algorithm using SI, CA125 and HE4 has good performance statistics for predicting cancer in women with pelvic masses. The triple screen has higher specificity and PPV than CA125 alone but similar sensitivity and NPV for predicting ovarian cancer.


Influence of alcohol on cognitive performance during mild hypoglycaemia; implications for Type 1 diabetes.
Alcohol and hypoglycaemia independently affect cognitive function. This may be relevant for insulin-treated diabetic patients who drive motor vehicles. The aim of this study was to examine the effect of mild hypoglycaemia (2.8 mmol/l) with modest alcohol intoxication (levels below UK driving limits) on intellectual performance in patients with Type 1 diabetes. A hyperinsulinaemic glucose clamp (60 mU/m2) was used to study 17 subjects [age 35 +/- 8 years, HbA1c 8.1 +/- 1.4% (mean +/- sd)] on four occasions: (A) euglycaemia (4.5 mmol/l) with placebo, (B) euglycaemia with alcohol, (C) hypoglycaemia (2.8 mmol/l) with placebo, and (D) hypoglycaemia with alcohol. Cognitive performance was assessed using four-choice reaction time (4CRT, primary outcome), measurements of general intellectual skills [trail making B (TMB) and digit symbol substitution (DSST)], and visual information processing [visual change detection (VCD)]. A test related to driving performance (hazard perception) was also used. In experiments B and D the average blood alcohol level was 43 mg/dl. This was associated with deterioration in 4CRT [+ 35 ms [95% confidence interval (CI) 20, 50]] and TMB, whereas hypoglycaemia without alcohol increased 4CRT only [+ 39 ms (95% CI 5, 73)]. However, when alcohol was combined with hypoglycaemia, there was marked deterioration in all the cognitive function tests [4CRT 74 ms (95% CI 35, 113), TMB, DSST and VCD]. Hazard perception was not affected. The effect of alcohol was no different in euglycaemia than in hypoglycaemia, i.e. there was no interaction. Whereas hypoglycaemia did not reduce the likelihood that the subjects would drive, alcohol did. The cumulative effect of alcohol and hypoglycaemia on cognitive function together has implications for driving in patients with Type 1 diabetes. Both independently impair cognitive function and together the effects are additive. Patients with Type 1 diabetes should be educated about hypoglycaemia and driving and should avoid alcohol completely if planning to drive.


Isolation and Characterization of a Novel Tembusu Virus Circulating in Muscovy Ducks in South China.
Duck Tembusu virus (DTMUV) is an infectious pathogen that can cause epidemics in egg-laying ducks. Here, we isolated and characterized a DTMUV, designated GDLH01, thought to be responsible for the noticeable egg drop in Muscovy duck flocks in South China since 2011. The genome sequence of GDLH01 shared 97-99% homology with other avian-origin Tembusu viruses, and 99.5% homology with the mosquito-borne strain SDMS recently reported in China. Phylogenetic analysis based on the nucleotide sequence of the entire open reading frame confirmed that the isolate was of avian origin and closely related to a mosquito-borne strain. Our findings characterize a novel Tembusu virus circulating in Muscovy ducks in South China and emphasize the importance of reinforcing biosecurity measures and developing vaccines to prevent the spread of this viral pathogen.


Selective late sodium current blockade with GS-458967 markedly reduces ischemia-induced atrial and ventricular repolarization alternans and ECG heterogeneity.
Ischemic heart disease is associated with dual risk for atrial and ventricular arrhythmias. We examined whether selectively targeting late sodium channel current (INa) with GS-458967 (hereafter GS967) can reduce cardiac electrical instability and compared its effects to a clinically relevant dose of flecainide. Electrode catheters were positioned on the left atrial appendage and left ventricle of anesthetized pigs to monitor repolarization alternans and electrocardiographic heterogeneity before and during left circumflex coronary artery stenosis (75% flow reduction) before and after GS967 (0.4 mg/kg, intravenously [IV]) or flecainide (1 mg/kg, IV, bolus over 2 minutes followed by 1 mg/(kg·h), IV, for 1 hour) administration. Left circumflex coronary artery stenosis increased atrial repolarization alternans by 520% (from 9.4 ± 1.2 to 58.3 ± 11.3 μV; P = .029) and T-wave alternans by 1038% (from 30.7 ± 8.2 to 349.3 ± 103.8 μV; P = .049). GS967 prevented ischemia-induced increases in alternans in the left atrium (19.3 ± 5.6 μV vs 58.3 ± 11.3 μV; P = .023) and left ventricle (217.9 ± 95.8 μV vs 349.3 ± 103.8 μV; P < .001) (n = 7). GS967 reduced ischemia-induced increases in depolarization heterogeneity (atrium: from 45% to 28%; ventricle: from 92% to 51%) and repolarization heterogeneity (atrium: 43% to 23%; ventricle: 137% to 91%). GS967 did not alter heart rate, arterial blood pressure, PR and QT intervals, or QRS duration, but it mildly decreased contractility (left ventricular dP/dt) during ischemia, which was consistent with late INa inhibition. Flecainide (n = 7) amplified ischemia-induced increase in atrial and ventricular repolarization alternans, electrocardiographic heterogeneity, and ventricular fibrillation incidence. Selective late INa inhibition with GS967 exerts potent protective effects against ischemia-induced depolarization and repolarization abnormalities in both atria and ventricles.


[Recombinant protein folding and production].
The biotechnology of recombinant protein production is now entering its most advanced stage, and the growth of industrial protein pharmaceuticals provides solid proof of this evolution. However, the systematic conversion of genetic information into a biologically active protein is constantly confronted by the fundamental problem of protein folding in cells, and many recombinant proteins are not produced in their native state. Instead, they aggregate into a biologically inactive state. Although this aggregation reaction has some practical advantages, in vitro renaturation of recombinant proteins, after solubilization of cellular aggregates, is still an empiric and random process. Thus, it is better to control cellular expression conditions to minimize this problem inside the cells. The most attractive approach is certainly the development of high throughput genetic screens to monitor efficient protein folding.


Continuous wavelet transform-based feature selection applied to near-infrared spectral diagnosis of cancer.
Spectrum is inherently local in nature since it can be thought of as a signal being composed of various frequency components. Wavelet transform (WT) is a powerful tool that partitions a signal into components with different frequency. The property of multi-resolution enables WT a very effective and natural tool for analyzing spectrum-like signal. In this study, a continuous wavelet transform (CWT)-based variable selection procedure was proposed to search for a set of informative wavelet coefficients for constructing a near-infrared (NIR) spectral diagnosis model of cancer. The CWT provided a fine multi-resolution feature space for selecting best predictors. A measure of discriminating power (DP) was defined to evaluate the coefficients. Partial least squares-discriminant analysis (PLS-DA) was used as the classification algorithm. A NIR spectral dataset associated to cancer diagnosis was used for experiment. The optimal results obtained correspond to the wavelet of db2. It revealed that on condition of having better performance on the training set, the optimal PLS-DA model using only 40 wavelet coefficients in 10 scales achieved the same performance as the one using all the variables in the original space on the test set: an overall accuracy of 93.8%, sensitivity of 92.5% and specificity of 96.3%. It confirms that the CWT-based feature selection coupled with PLS-DA is feasible and effective for constructing models of diagnostic cancer by NIR spectroscopy.


Estimation of polymeric IgA in human serum: an assay based on binding of radiolabeled human secretory component with applications in the study of IgA nephropathy, IgA monoclonal gammopathy, and liver disease.
Binding of 125I-human secretory component (SC) to human polymeric immunoglobulin A (pIgA) was employed to measure quantitatively the pIgA present in human sera. Interference by IgM in some sera was prevented by removal of IgM with glutaraldehyde polymerized anti-IgM antibodies. 125I-SC complexed to pIgA was measured by precipitation with anti-IgA antibodies and the quantity of pIgA in human serum was estimated by comparing the quantity of 125I-SC bound by several dilutions of human serum to that bound by standard quantities of human monoclonal pIgA proteins. The assay was specific for pIgA because heat-aggregated monomeric IgA or hypogammaglobulinemic serum did not bind 125I-SC greater than a precipitate formed with human monoclonal IgG and anti-IgG. Moreover, analysis of a series of IgA myeloma sera indicated no correlation between the IgA content of the serum and the quantity of pIgA measured. The quantity of pIgA found in 30 normal human sera was 0.13 +/- 0.08 mg/ml (1S.D.), which consisted of 11.3 +/- 5.3% (1 SD) of the total IgA. Patients with IgA monoclonal gammopathy were most often found to have predominantly monomeric IgA. Patients with IgA nephropathy also showed an elevation of pIgA, but this appeared to be a consequence of an overt IgA elevation. IgA nephropathy patients with elevated serum IgA in fact showed a significant elevation of monomeric IgA. Selective elevation of pIgA was observed in patients with primary biliary cirrhosis and alcoholic liver disease. A comparison of this assay with other assays to measure pIgA is discussed.


Pattern formation in a two-dimensional reaction-diffusion channel with Poiseuille flow.
We study stationary patterns arising from a combination of flow and diffusion in a two-dimensional (2D) reaction-diffusion system in a channel with Poiseuille flow. Both transverse and longitudinal modes are investigated and compared with numerical computations.


Native-born versus foreign-born patients' perception of communication and care in Swedish dental service.
Like many other countries Sweden is becoming more multicultural and many residents do not fully master the national language and are not completely familiar with national norms and habits. The key to good interaction between dentists and patients is communication. Therefore this study aimed to examine whether there are differences in the experience of communication and care between native-born (NB) and foreign-born (FB) patients in the Swedish Public Dental Service (PDS). Consecutive patients at four PDS clinics in a major Swedish city (Gothenburg) were asked to complete the Dental Visit Satisfaction Scale (DVSS), eight additional items concerning communication and care, and a questionnaire eliciting background information.The questionnaires were available in English, Swedish, Arabic and Farsi. The response rate was 74% (204 patients, mean age: 42 years, range 18-86). Of the participants, 96 (47%) were NB and 108 (53%) were FB; 80 (40%) were men and 121 (60%) women. The NB group was significantly older, had higher education and more regular dental care habits, and reported higher dental fear than the FB group. Fewer FB than NB patients thought the dentist treated them in the same manner as he or she would treat other patients and this applied particularly to those who had lived in Sweden for more than 5 years. FB patients were as satisfied with the information and communication they received from the dentist as those born in Sweden, but they were more sceptical about the dentist's technical competence. The differences between the two groups were otherwise smaller than might have been expected in view of probable language difficulties and differences in dental care background.


[The role of tissue steroids in benign hyperplasia and prostate cancer].
This paper presents a large body of data relating to benign prostatic hyperplasia, which have been derived from fundamental endocrinological research. For the urologist, the data open up interesting aspects of the pathomorphology of prostatic hyperplasia. The most interesting findings can be summed up as follows: 1. Testosterone is the circulating androgenic prohormone that mediates the intracellular message leading to androgen secretion, though by way of its metabolite dihydrotestosterone, which is really the active substance. 2. This metabolic conversion is catalyzed by 5 alpha-reductase, which is predominantly a stromal enzyme. 3. The estrogen metabolism in the stromal cells of the prostate may be associated with the abnormal growth of the prostate. 4. In the presence of benign prostatic hyperplasia dihydrotestosterone and 17 beta-estradiol accumulate in the nuclei of the stromal cells. 5. Adrenal androgens are also metabolized in the human prostate, yielding some substances with androgenic and some with estrogenic potency. 6. Changes in sex hormone binding globulins (SHBG) are found with age whether benign prostatic hyperplasia is present or not. It is therefore questionable whether it has any influence on the development of prostatic hyperplasia. 7. Although in some cases it is not yet possible to determine whether the findings presented in this paper have any causal significance, the data can be used as a rational basis for hormonal treatment of prostatic disease.


Foamy gland carcinoma of the prostate in needle biopsy: incidence, Gleason grade, and comparative α-methylacyl-CoA racemase vs. ERG expression.
Foamy gland carcinoma is a variant of prostatic acinar adenocarcinoma characterized by abundant, foamy cytoplasm, frequently showing small, pyknotic nuclei. The incidence and Gleason grade of foamy gland carcinoma in a large prostate needle biopsy series have not been established. Foamy gland carcinoma may be deceptively benign appearing and missed on needle biopsy. Immunohistochemical staining for basal cells and α-methylacyl-CoA racemase (AMACR) can support a diagnosis of foamy gland carcinoma, but the sensitivity of AMACR for foamy gland carcinoma has been reported to be lower than that for usual acinar carcinoma. The utility of ERG immunohistochemistry in the diagnosis of foamy gland carcinoma has not been explored. The aim of this study was to characterize the incidence and Gleason grade of foamy gland carcinoma in a large consecutive series of prostate needle biopsy cases. We also assessed ERG expression in foamy gland carcinoma, in comparison with AMACR expression, to determine whether ERG expression provides added diagnostic value beyond AMACR expression. We evaluated a consecutive series of 476 prostatic adenocarcinoma needle core biopsy cases for presence, linear extent, and Gleason grade of foamy gland carcinoma. A selected block from each case containing foamy gland carcinoma was evaluated for AMACR and ERG expression by immunohistochemistry. Of the 476 cases, 17% contained a foamy gland carcinoma component, with 2% of the cases showing pure foamy gland carcinoma. Two cases of pure foamy gland carcinoma had a total linear extent of <3 mm. The majority (80%) of cases had a Gleason score 3+3=score of 6. Sensitivity of AMACR for foamy gland carcinoma was 92%, and sensitivity of ERG was 42%. No AMACR-negative case was ERG positive. Low AMACR expression was detected in 24 of 72 cases (33%), and of these cases ERG was positive in 5 (21%). In summary, foamy gland carcinoma features are relatively common in prostate needle core biopsies, the foamy gland carcinoma is admixed with usual acinar carcinoma in the majority of cases, and is usually not of high Gleason grade, although 20% are Gleason score 7 or greater. ERG immunohistochemistry did not provide added value beyond AMACR expression in most cases, suggesting that it need not be initially utilized in addition to basal cell markers and AMACR when immunohistochemistry is needed to substantiate a diagnosis of foamy gland malignancy. This is an important consideration in this era of cost-consciousness in application of immunohistochemistry. Sensitivity of AMACR for foamy gland carcinoma was comparable to that seen in studies of usual acinar carcinoma and is an excellent marker for foamy gland carcinoma of the prostate. ERG immunohistochemistry could be considered in a second round of immunostaining of select difficult cases of foamy gland carcinoma with low AMACR expression.


Estimation of pressure pulse amplification between aorta and brachial artery using stepwise multiple regression models.
The pressure pulse is amplified between the aorta and peripheral sites. This study compares two methods to estimate pressure pulse amplification (PPA) between the aorta and the brachial artery. Method 1: PPA was determined from a multi-parameter linear regression of subject parameters (gender, age, height, weight, heart rate (HR), brachial systolic pressure (BSP), diastolic pressure (BDP), mean pressure (MP)). Method 2: PPA was calculated from central aortic pressure waveforms (CW) estimated from the same subject parameters. The sample population (1421 male, 992 female) was selected from a database where aortic pressure was estimated by mathematical transformation of a peripheral (radial) pulse calibrated to sphygmomanometric BSP and BDP. The two methods were consistent in showing HR and MP as the most important parameters to estimate PPA. Correlation coefficients (R2) of 0.48 (method 1) and 0.44 (method 2) were obtained using height, weight, HR, BSP, BDP and age. Inclusion of MP increased R2 to 0.77 (method 1) and 0.71 (method 2). This study shows that databases containing peripheral and central aortic pressure waveforms can be used to construct multiple regression models for PPA estimation. These models could be applied to studies of similar subject groups where peripheral waveforms may not be available.


[Estimation of the phantom scatter factor (Sp) of rectangular fields].
This study proposes a method to accurately estimate the phantom scatter factor (Sp) of arbitrary rectangular fields. We measured output doses in water and air; these measured values were based on square fields and a limited number of symmetric rectangular fields using 4 MV and 10 MV X-rays of a Varian Clinac-iX. We calculated Sp from these measured values. Then, using these Sp values, we estimated equations of Sp on square fields consisting of the primary dose, Day's scatter, and forward scatter. This equation may be used to estimate the Sp value on a square field, but it cannot estimate the Sp value on a rectangular field. We investigated the calculation method for an equivalent square of a rectangular field. As a result, this study's calculation method for an equivalent square, the area ratio correction method, was more accurate than the conventional Bjärngard's method. Therefore, when using the approximate equation of Sp on a square field and the equivalent square calculated by the area ratio correction method, a Sp value of an arbitrary rectangular field may be accurately estimated.


The use of endothelial progenitor cells combined with barrier membrane for the reconstruction of peri-implant osseous defects: an animal experimental study.
The aim of this research was to study the efficacy of endothelial progenitor cells (EPC) with ß tri-calcium phosphate (β-TCP) and barrier in the treatment of experimental peri-implantitis. Thirty implants were placed in five American foxhounds. Following osseointegration, ligature-induced peri-implantitis was initiated. EPC were isolated from peripheral blood. Two months later, open flap debridement was performed and implants' surface was decontaminated with 24% EDTA. The sites were grafted with β-TCP and collagen membrane (β-TCP group) or β-TCP loaded with EPC and covered with membrane (EPC group) or left un-grafted (OFD group). At 3 months, animals were killed and specimens sent for histomorphometric and micro-CT analysis. Bone height and %BIC served as primary and secondary outcomes. EPC group showed shorter distance to first BIC (3.29 ± 0.69 mm) compared to 4.2 ± 0.92 mm (β-TCP) and 3.82 ± 0.73 mm (OFD). Mean histological BIC was 2-3 folds higher in the EPC group (17.65 ± 3.3%) compared with OFD (7.55 ± 2.24%, p = 0.01) and β-TCP (5.68 ± 2.91%, p = 0.05). BIC greater than 25% was found only in the EPC group. The distance between the implant shoulder to 1st BIC was 2.51 ± 0.7 mm (lingual sites) compared to 3.64 ± 0.8 mm for buccal sites (p < 0.0001). β-TCP loaded with EPC and covered with a membrane-enhanced bone formation around previously contaminated dental implants in an experimental peri-implantitis canine model.


Coherent information structure in complex computation.
We have recently presented a framework for the information dynamics of distributed computation that locally identifies the component operations of information storage, transfer, and modification. We have observed that while these component operations exist to some extent in all types of computation, complex computation is distinguished in having coherent structure in its local information dynamics profiles. In this article, we conjecture that coherent information structure is a defining feature of complex computation, particularly in biological systems or artificially evolved computation that solves human-understandable tasks. We present a methodology for studying coherent information structure, consisting of state-space diagrams of the local information dynamics and a measure of structure in these diagrams. The methodology identifies both clear and "hidden" coherent structure in complex computation, most notably reconciling conflicting interpretations of the complexity of the Elementary Cellular Automata rule 22.


Comparison of composition of atherosclerotic plaques in saphenous veins used as aortocoronary bypass conduits with plaques in native coronary arteries in the same men.
This study describes quantitatively the components of atherosclerotic plaques in saphenous vein grafts used for aortocoronary bypass and compares the findings with the plaques in the native coronary arteries in the same men. A total of 607 five-mm segments of saphenous veins and 797 five-mm segments of native coronary arteries were examined by computerized planimetric technique in 19 men, aged 39 to 82 years (mean 61), who had survived bypass operation for > 1 year. Comparison of the mean percentages of the plaque components in saphenous vein grafts in place for 14 to 26 months with those of the native coronary arteries revealed significant differences: cellular fibrous tissue, 86 vs 7%; dense fibrous tissue, 13 vs 82%; p < 0.05. As survival time after the bypass operation increased, composition of the plaques in the saphenous veins changed so that by approximately 80 months the amounts of cellular and dense fibrous tissue in both saphenous vein grafts and native coronary arteries were similar: 10 vs 16%, and 75 vs 71%; p = not significant. Thus, by about 7 years after a coronary bypass operation the composition of plaques in saphenous vein grafts is similar to that in the native coronary arteries of the same patients.


Ultrastructural degradation of the carotid body in the aged rat: is there a role for atherosclerosis in the main carotid arteries?
In this study we examined the potential role of atherosclerosis in the main arteries supplying blood to the carotid body in the organ's morphological degradation with age. We addressed this issue by comparing the ultrastructural picture of carotid bodies and of fragments of the carotid artery bifurcation in two age-extreme groups of rats: young - 3 months old and senescent - 24 months old. Tissues were excised under surgical anesthesia, fixed in aldehydes, and processed for transmission electron microscopy. We found that the old carotid body parenchyma exhibited profound degenerative changes. Chemoreceptor cells were at various stages of atrophy, ranging from swollen mitochondria and fewer secretory vesicles to dark dehydrated cells. In contrast, the senescent carotid artery bifurcation was little different from that in young rats. Particularly, endothelial cells were in perfect condition. There were some changes in deeper arterial wall layers such as breaks in the continuity of elastic bands or a subtly different phenotype of smooth muscle cells. No foam cells or calcium build-ups were found in the arterial walls. Such changes correspond to the process of arterial wall stiffening in old age rather than to the outright atherosclerosis. Lack of atherosclerosis in the common carotid arteries, which could hamper blood flow, argues against its playing a role in the morphological age-changes in the carotid bodies.


Phenotype description of a Dutch otosclerosis family with suggestive linkage to OTSC7.
This study reports on a clinical investigation of a Dutch family that shows suggestive linkage to OTSC7. Cross-sectional as well as longitudinal analyses of audiometric data were performed. Also, high-resolution computed tomography (CT) images of the temporal bones from genetically affected family members were obtained to study the incidence and extent of otospongiotic foci. Audiometric data showed a considerable degree of phenotypic variability. Cross-sectional regression analysis did not show age-dependent progression of bone conduction (BC), air conduction (AC), and air-bone gap (ABG) levels. Longitudinal analysis of audiometric follow-up data of one family member showed age-dependent progression of AC, BC, and ABG levels. High-resolution CT images revealed an otospongiotic focus in six of six (100%) clinically affected individuals that carried the disease haplotype. In none of the clinically unaffected family members that showed linkage to OTSC7, an otospongiotic focus was detected by CT. In conclusion, hearing impairment in the present otosclerosis family seems to be variable in terms of onset age and level of progression. Long-term audiometric data of one patient proved to be valuable in understanding progression of hearing impairment in this individual. The detection rate of otospongiotic foci in our study group is similar compared to previous reports on CT data in consecutive otosclerosis patients who had stapes replacing surgery.


Radiological outcomes of pinless navigation in total knee arthroplasty: a randomized controlled trial.
This study aimed to investigate the accuracy of pinless navigation (BrainLAB(®) VectorVision(®) Knee 2.5 Navigation System) as an intra-operative alignment guide in total knee arthroplasty (TKA). The authors hypothesized that pinless navigation would reduce the proportion of outliers in conventional TKA, without a significant increase in the duration of surgery. Between 2011 and 2012, 100 patients scheduled for a unilateral primary TKA were randomized into two groups: pinless navigation and conventional surgery. All TKAs were performed with the surgical aim of achieving neutral coronal alignment with a 180° mechanical axis. The primary outcomes of this study were post-operative radiographic assessment of lower limb alignment using hip-knee-ankle angle (HKA) and components placement using coronal femoral-component angle (CFA) and coronal tibia-component angle (CTA). There was a smaller proportion of outliers for HKA, CFA and CTA at 10, 2 and 2 % respectively, in the pinless navigation group, compared to 32, 16 and 16 %, respectively, in the conventional group (p = 0.013, p = 0.032 and p = 0.032, respectively). The mean CFA was also more accurate at 90° in the pinless navigation group compared to 91° in the conventional group (p = 0.002). There was no difference in the duration of surgery between the two groups (n.s.). Pinless navigation improves lower limb alignment and components placement without a significant increase in the duration of surgery. The authors recommend the use of pinless navigation to verify the coronal alignments of conventional cutting blocks in TKA before the bone cuts are made. I.


[Ultrastructure of the epithelium of the major pancreatic duct in sheep].
Light-and electron-microscopic and some histochemical investigations on the epithelium or the ductus pancreaticus major were carried out in sheep. At least six different cell types are recognizable: (1) nondifferentiated duct cells; (2) cells containing apical secretory granules; (3) goblet cells; the mucosubstances of type 2 and 3 are PAS- and Alcian-blue-positive, also reacting wih methenamine silver; (4) ciliated cells, containing a single cilium with the microtubular pattern 9+2; (5) tuft cells with extremely long and wide microvilli and a pear-shaped cell body; (6) migrating cells, mainly lymphocytes and some assumed eosinophils, showing reaction to Mg++-activated ATPase.


Could Short-Term Perioperative High-Dose Atorvastatin Offer Antiarrhythmic and Cardio-Protective Effects in Rheumatic Valve Replacement Surgery?
To evaluate the role of prophylactic high-dose atorvastatin for prevention of postoperative atrial fibrillation (POAF), inflammatory response attenuation, and myocardial protection after valve replacement cardiac surgery. Randomized controlled trial. Assiut University Hospitals. Sixty-four adult patients undergoing cardiac valve replacement surgery. The participants were equally divided into 2 groups. Group S received 80 mg of atorvastatin (oral tablets), 12 and 2 hours preoperatively, and on the 2nd, 3rd, 4th, and 5th postoperative days. Control group C received placebo at the same time periods. The incidence of POAF, postoperative white blood cell count, serum C-reactive protein, interleukin 6, and troponin I. Group S patients showed a lower incidence of POAF compared with the placebo group (p = 0.031). The white blood cell count showed significant reductions in group S compared with group C on the second, third, fourth, and fifth postoperative days. The C-reactive protein level showed significant reductions on the third, fourth, and fifth postoperative days in group S compared with group C (p = 0.001, 0.001, and 0.001, respectively). The serum level of interleukin 6 showed a significant reduction on the fifth postoperative day in group S compared with group C (p = 0.001). There was no significant difference between the 2 groups regarding the troponin I level and inotropic score. Prophylactic use of high dose atorvastatin can decrease the incidence of POAF and attenuate the inflammatory process in adult patients undergoing isolated rheumatic cardiac valve replacement surgery.


Unexpected white matter changes in an early treated PKU case and improvement after dietary treatment.
We report a case of classic phenylketonuria (PKU) treated by dietary restriction until the age of 5 years. At the age of 18 years, she developed anxious-depressive symptoms and deterioration of school performance. Neurophysiological investigations showed changes in VEPs and BAEPs and brain MRI showed white matter abnormalities. The return to a diet low in phenylalanine reduced psychiatric disturbances and reversed neurophysiological and MRI changes. Our data confirm previous observations of white matter involvement in PKU and the utility of lifelong dietary therapy to prevent neurological and/or psychiatric deterioration.


Haemodynamic phenotypes and survival in patients with systemic sclerosis: the impact of the new definition of pulmonary arterial hypertension.
In this study, we investigated the impact of the new haemodynamic definition of pulmonary arterial hypertension (PAH) as proposed by the 6th PH World Symposium on phenotypes and survival in patients with systemic sclerosis (SSc). In SSc patients who were prospectively and consecutively screened for PAH including right heart catheterisation in Heidelberg or Zurich, haemodynamic and clinical variables have been reassessed according to the new PAH definition. Patients have been followed for 3.7±3.7 (median 3.4) years; Kaplan-Meier survival analysis was performed. Patients with significant lung or left heart disease were excluded from comparative analyses. The final dataset included 284 SSc patients, 146 patients (49.2%) had mean pulmonary arterial pressure (mPAP) ≤20 mm Hg, 19.3% had mPAP 21-24 mm Hg and 29.4% had mPAP ≥25 mm Hg. In the group of mildly elevated mPAP, only four patients (1.4% of the whole SSc cohort) had pulmonary vascular resistance (PVR) values ≥3 Wood Units (WU) and could be reclassified as manifest SSc-APAH. Twenty-eight (9.8%) patients with mPAP of 21-24 mm Hg and PVR ≥2 WU already presented with early pulmonary vascular disease with decreased 6 min walking distance (6MWD) (p<0.001), TAPSE (p=0.004) and pulmonary arterial compliance (p<0.001). A PVR ≥2 WU was associated with reduced long-term survival (p=0.002). PVR and 6MWD were independent prognostic predictors in multivariate analysis. The data of this study show that a PVR threshold ≥3 WU is too high to enable an early diagnosis of PAH. A PVR threshold ≥2 WU was already associated with pulmonary vascular disease, significantly reduced survival and would be more appropriate in SSc patients with mild PAH.


Magnet assisted fabrication of microtubule arrays.
Magnetic fields were used to fashion permanently aligned microtubule arrays allowing formation of highly ordered platforms for assembly, separation, and single molecule motor studies.


Granulomatous peritonitis and pleuritis in interferon-gamma gene knockout mice naturally infected with mouse hepatitis virus.
To investigate a disease outbreak in a colony of laboratory mice with targeted disruption of the gene for interferon-gamma. FORMAT: A case report based on necropsy, histopathology, serology and immunohistochemistry. Affected mice exhibited depression and variable ascites. Necropsy revealed a granulomatous peritonitis and pleuritis with extensive adhesions although parenchymal lesions were minimal. Serum samples had high concentrations of antibody to mouse hepatitis virus and immunohistochemical examination revealed the presence of mouse hepatitis virus antigen in granuloma macrophages. Sero-logical testing for other infectious agents and bacterial culture were negative and wild type mice kept in the same facility remained healthy. Despite the association between the disease and mouse hepatitis virus infection, the precise role played by mouse hepatitis virus was not determined. While the disease is superficially similar to feline infectious peritonitis (another coronavirus-induced serositis), differences exist between the histopathological findings in these two conditions. This unusual disease process illustrates how new diagnostic challenges can arise in novel mouse genotypes created through molecular genetics. Furthermore, the association between the disease and mouse hepatitis virus illustrates the importance of maintaining laboratory animals under specific-pathogen free conditions.


En-Face Optical Coherence Tomography of Acute Syphilitic Posterior Placoid Chorioretinopathy.
To report a unique case series of acute syphilitic posterior placoid chorioretinopathy (ASPPC) correlating en-face optical coherence tomography (OCT) with standard imaging modalities. In this retrospective case series, multimodal imaging was performed in three ASPPC patients at the time of disease presentation. Clinical and laboratory findings were consistent with the diagnosis of ASPPC. In all the study patients, multiple hyperreflective dot-like lesions distributed in the macular area and observed with en-face OCT at the level of retinal pigment epithelium (RPE) corresponded to the nodular RPE elevations on cross-sectional OCT and to the hyperautoﬂuorescent spots on fundus autofluorescence. In addition, the cross-sectional OCT scans showed disorganization of the outer retinal bands and punctate choroidal hyperreﬂectivity. By combining en-face OCT with multimodal imaging analysis, we propose that a primary inflammation at the level of the choroid may be the pathogenic mechanism for the occurrence of outer retinal band abnormalities.


Interaction of receptor for advanced glycation end products with advanced oxidation protein products induces podocyte injury.
Chronic kidney disease (CKD) is characterized by progressive decline in renal function. Podocyte dropouts contribute to the pathogenesis of diabetic and nondiabetic CKD. Zhou and colleagues demonstrate that the association between advanced oxidation protein products (AOPPs) and receptor for advanced glycation end products (RAGE) elicited podocyte injuries, using cultured podocytes and mice injected with AOPPs. This study suggests that the blockade of RAGE is preventive and therapeutic against podocyte apoptosis caused by oxidative stress-related AOPPs in CKD.


Effect of the cathode material on the removal of nitrates by electrolysis in non-chloride media.
In this work, the effect of the cathode material (conductive diamond, stainless steel, silicon carbide, graphite or lead) and the current density (150-1400 A m(-2)) on the removal of nitrates from aqueous solutions is studied by electrolysis in non-divided electrochemical cells equipped with conductive diamond anodes, using sodium sulphate as the electrolyte. The results show that the cathode material very strongly influences both the process performance and the product distribution. The main products obtained are gaseous nitrogen (NO, N(2)O and NO(2)) and ammonium ions. Nitrate removal follows first order kinetics, which indicates that the electrolysis process is controlled by mass transfer. Furthermore, the stainless steel and graphite cathodes show a great selectivity towards the production of ammonium ions, whereas the silicon carbide cathode leads to the highest formation of gaseous nitrogen, which production is promoted at low current densities.


Developing an easy-to-apply model for identifying relevant pathogen pathways into surface waters used for recreational purposes.
Swimming in inner-city surface waters is popular in the warm season, but can have negative consequences such as gastro-intestinal, ear and skin infections. The pathogens causing these infections commonly enter surface waters via several point source discharges such as the effluents from wastewater treatment plants and sewer overflows, as well as through diffuse non-point sources such as surface runoff. Nonetheless, the recreational use of surface waters is attractive for residents. In order to save financial and organizational resources, local authorities need to estimate the most relevant pathways of pathogens into surface waters. In particular, when detailed data on a local scale are missing, this is quite difficult to achieve. For this reason, we have developed an easy-to-apply model using the example of Escherichia coli and intestinal enterococci as a first approach to the local situation, where missing data can be replaced by data from literature. The model was developed based on a case study of a river arm monitored in western Germany and will be generalized for future applications. Although the limits of the EU Bathing Water Directive are already fulfilled during dry weather days, we showed that the effluent of wastewater treatment plants and overland flow had the most relevant impact on the microbial surface water quality. On rainy weather days, combined sewer overflows are responsible for the highest microbial pollution loads. The results obtained in this study can help decision makers to focus on reducing the relevant pathogen sources within a catchment area.


Supracondylar humeral fractures in children: current concepts for management and prognosis.
Supracondylar humeral fractures are the most common elbow fractures in children and represent 3 % of all paediatric fractures. The most common cause is a fall onto an outstretched hand with the elbow in extension, resulting in an extension-type fracture (97-99 % of cases). Currently, the Gartland classification is used, which has treatment implications. Diagnosis is based on plain radiographs, but accurate imaging could be limited due to patient pain. Based on fracture type, the definitive treatment could be either non-operative (type I) or operative (type III/IV); however, when handling type II fractures controversy remains. Neither pin configuration have shown higher efficacy over the other. Complications are ~1 %, the most common being pin migration, with compartment syndrome as the most devastating. Overall, functional outcomes are good, and physical therapy does not appear to be necessary.


Age-adjusted treatment of cervical intraepithelial 1 lesions by superficial or regular loop excision of transformation zone.
The loop electrosurgical excision procedure (LEEP) is one of the treatments for cervical intraepithelial neoplasia 1 (CIN1). One of the risks of LEEP is preterm birth. We evaluated final pathological diagnoses following LEEP as treatment for CIN1 lesions, for procedures in which cone height was determined by patients' age. A retrospective study of 329 women diagnosed with CIN1 on a cervical biopsy and treated by LEEP. In patients under age 35 years, a thin LEEP COIN was performed, and in women over 35 years, a regular LEEP was performed. The final pathological diagnosis was CIN2 and CIN3 in 14.6% of the women. The average excision height was 0.64 cm in women aged under 35 years, 0.82 cm in women aged 36-45 years, and 0.96 cm in women older than 46 (P<0.0001). Comparing excision height less than 0.8 cm to excision height above 0.9 cm, complications of the procedure, positive margins rates and recurrence rates were similar. Among women of childbearing age, the performance of a LEEP procedure with smaller cone height appeared equivocal in achieving correct pathological diagnoses and low recurrence. To avoid increasing the risk of premature delivery, the excisional depth should be adjusted to age and fertility status.


Local recurrence of breast cancer: conventionally fractionated partial external beam re-irradiation with curative intention.
To assess the outcome of breast cancer patients with local recurrence who underwent partial external beam re-irradiation (re-RT) either as part of a second breast-conserving therapy or following mastectomy. Between 03/2004 and 10/2016, 83 breast cancer patients with local recurrence were treated with surgery followed by re-RT. The re-RT schedules were 45 Gy (1.8 Gy per fraction) administered either to the partial breast (n = 42) or mastectomy scar (n = 41). The patients and tumor characteristics predictive of local control, distant control, and survival (overall and breast-cancer specific) were evaluated by univariate and multivariate analyses. The median follow-up was 35 months (range 3-143 months). The median time interval between the first irradiation and re-RT was 117 months (range 16-357 months). The prognostic factors for favorable overall survival rates were younger age (p = 0.045), lower T‑category (p = 0.019), and N0 category (p = 0.005). N0 was also superior to N+ with respect to outfield recurrences (p = <0.001) and breast cancer-specific survival (p = 0.025). Acute and late skin toxicity was generally low (<grade 3). Re-RT with 45 Gy (1.8 Gy per fraction) for partial breast or mastectomy scar after the second surgery resulted in high local control rates and tolerable skin toxicity.


Smoking habits of final-year Galician medical students.
Smoking habits among final-year Galician medical students have been studied using a questionnaire complying with the recommendations of the W.H.O. and the U.I.C.C. Aspects reported include the prevalence of the smoking habit, the characteristics of smoker, drug and habit, and health problems attributed to smoking. The prevalence rate was high (61.9%); average consumption by smokers was 16 cigarettes/day; most smokers smoked cigarettes with medium-to-high nicotine and medium-to-low tar contents; and the proportion of ex-smokers was small. Smokers were found to be well aware of the dangers of smoking, and their failure to relinquish the habit is attributed to lack of social support. The role of Medical Faculties in the fight against smoking is discussed, and it is suggested that priority should be given to anti-smoking campaigns among secondary school students (14-17 year-olds) and university undergraduates, since 60% of smokers acquired the habit during the former period and 21% during the latter.


RPP25 is developmentally regulated in prefrontal cortex and expressed at decreased levels in autism spectrum disorder.
Dysfunction of cerebral cortex in autism is thought to involve alterations in inhibitory neurotransmission. Here, we screened, in prefrontal cortex (PFC) of 15 subjects diagnosed with autism and 15 matched controls the expression of 44 transcripts that are either preferentially expressed in gamma-aminobutyric acidergic interneurons of the mature cortex or important for the development of inhibitory circuitry. Significant alterations in the autism cohort included decreased expression (-45%) of RPP25 (15q24.1), which is located within the autism susceptibility locus, 15q22-26. RPP25, which encodes the 25 kDa subunit of ribonuclease P involved in tRNA and pre-ribosomal RNA processing, was developmentally regulated in cerebral cortex with peak levels of expression during late fetal development (human) or around birth (mouse). In the PFC, RPP25 chromatin showed high levels of histone H3-lysine 4 trimethylation, an epigenetic mark associated with transcriptional regulation. Unexpectedly, and in contrast to peripheral tissues, levels of RPP25 protein remained undetectable in fetal and adult cerebral cortex. Taken together, these findings suggest a potential role for the RPP25 gene transcript in the neurobiology of developmental brain disorders.


Management of head injury. Neurobehavioral outcome.
Recent research on overall recovery from closed head injury has focused on improving the prediction of outcome and the influence of age. The aspects of long-term neurobehavioral sequelae and recovery, memory deficit after closed head injury, and language and speech disturbance after head injury are covered in this article.


Evaluation of 18F-FDG PET in patients with advanced, metastatic, or recurrent gastric cancer.
PET with 18F-FDG has been widely used in oncology, but its application for stomach neoplasms has been limited. The aim of this study was to evaluate the visual diagnostic accuracy of (18)F-FDG PET for advanced, metastatic, or recurrent gastric cancer and to generate semiquantitative values for lesions. 18F-FDG PET scans were obtained on 42 patients (29 men, 13 women; age, 27-78 y; median age, 63 y): 20 patients with a PT931/04 scanner and 22 patients with a SET2400W scanner. The PT931/04 has a spatial resolution of 6.0 mm at full width at half maximum (FWHM) and covers 15 cm above and below the targeted lesion, and the SET2400W has a spatial resolution of 3.9 mm at FWHM and images the entire body. All PET images were interpreted visually, and tracer uptakes were quantitated as standardized uptake values (SUVs) on SET2400W images. The sensitivity, specificity, and accuracy as a whole were as follows: 71%, 74%, and 73%, respectively, with the SET2400W scanner and 47%, 79%, and 62%, respectively, with the PT931/04 scanner. Values were high for primary lesions, liver, lymph node, and lung metastases, but were low for bone metastases, ascites, peritonitis, and pleuritis carcinomatoses. SUVs were 8.9 +/- 4.2 (primary lesions, 19 patients/19 lesions), 6.5 +/- 2.2 (liver, 9/55), 6.1 +/- 2.5 (lymph nodes, 14/38), 6.5 +/- 1.8 (abdominal wall, 4/7), 3.9 +/- 2.0 (bone, 3/27), and 4.7 +/- 2.6 (lung, 2/3). Comparing SUVs and histologic findings for 17 untreated patients, values for well-differentiated and moderately differentiated adenocarcinomas versus poorly differentiated adenocarcinomas and signet ring cell carcinomas were 13.2 +/- 6.3 (4/4) versus 7.7 +/- 2.6 (13/13) (P < 0.05) for the primary lesions, 7.0 +/- 2.4 (5/39) versus 5.6 +/- 2.8 (2/2) for the liver, and 5.5 +/- 1.9 (9/28) versus 8.8 +/- 3.3 (3/8) (P < 0.05) for the lymph nodes. Our results indicate that 18F-FDG PET is a useful diagnostic modality for advanced, metastatic, or recurrent gastric cancer but not for detecting bone metastases, peritonitis, or pleuritis carcinomatoses. 18F-FDG uptake by gastric cancers is relatively high but does not parallel histopathologic features of malignancy.


[Evaluation of venom specific IgE and total serum IgE among forest administration workers].
We used a questionnaire to investigate Hymenoptera hypersensitivity in 323 forest administration workers and measured total serum IgE and venom specific IgE antibodies against yellow jackets and paper wasps. The results were as follows. 1) Most of the workers, including 69 (21.8%) hypersensitive workers, had been exposed to stings by yellow jackets or wasps. 2) The titer of RAST (p less than 0.05) and RAST positive rate (p less than 0.01) were higher in the hypersensitive workers than in the non-hypersensitive ones. 3) There was a correlation between venom specific IgE titers to yellow jackets and paper wasps (rs = 0.818). 4) The titer of venom specific IgE increases with the frequency of sting exposure, and decreased gradually with the passage of time. 5) The higher the venom specific IgE titer, the higher the total serum IgE titer. 6) The titer of venom specific IgE, total serum IgE and atopy had no relation to the severity of clinical symptoms.


[Amino acid makeup of beef].
Studies were carried out both on the quantitative and qualitative composition of aminoacids in the proteins of m. longissimus dorsi from cattle of the "Bulgarian Brown" breed with the help of an automatic aminoanalyzer Hd 1200 E, made in Czechoslovakia. Hydroxyproline and triptophane were determined at different analytical speeds. It was established that in the proteins of the muscle investigated are contained the following aminoacids, expressed in g/16 g N: lysine--7.77; treonine--4.09, valine--5.12, methyonine--2.50, isoleucine--4.67, leucine--8.42, phenylalanine--4.34, triptophane--1.40, histidine--3.37, arginine--6.17, aspartic acid--7.92, serine--3.31, glutamine acid--13.30, proline--3.73, glycine--4.79, alanine--4.99, tirosine--3.84 and hydroxyproline--0.59. The quantity of the essential aminoacids in the proteins of the muscle investigated from cattle, except the value of methyonine and cystine (the method we implemented does not secure the determination of cystine), surpasses the norm for their contents in the proteins suggested by FAO/WHO.


The Efficacy of Emotionally Focused Couples Therapy and Behavioral Couples Therapy: A Meta-Analysis.
Behavioral couple therapy (BCT) and emotionally focused couples therapy (EFCT) are well-established treatments to reduce couple distress. This meta-analysis summarizes the current state of knowledge on the efficacy of these two therapy methods by focusing on randomized controlled trials only. A literature search revealed 33 suitable primary studies (2,730 participants in total), all of them measuring relationship satisfaction. Robust-variance random-effects meta-analysis revealed medium effect sizes at post-test (overall: g = 0.60; BCT: g = 0.53; EFCT: g = 0.73) and small effect sizes of 6 months after treatment (overall: g = 0.44; BCT: g = 0.35; EFCT: g = 0.66), but these gains were not maintained after 12 months (BCT only: g = 0.06). Between the two therapy methods, no significant effect size differences could be found. Results have to be interpreted with caution due to potential publication bias.


Efficacy of terazosin in the treatment of essential hypertension in blacks.
The antihypertensive effects of the selective alpha 1-adrenoceptor antagonist, terazosin, in black patients with uncomplicated, mild to moderate essential hypertension were examined retrospectively in seven randomized, double-blind, placebo-controlled trials conducted in the United States. Following 4 to 13 weeks of treatment with terazosin (2-40 mg, once daily), supine and standing systolic and diastolic blood pressures were decreased significantly from baseline, and these decreases were significantly greater than those observed in the placebo group (P less than 0.05). Blood pressure changes in the black and white patient subgroups were comparable. Terazosin was generally well tolerated with a low incidence of serious side effects. We conclude that terazosin is a safe and effective antihypertensive agent in black patients with essential hypertension.


[The role of cells originating from seminal vesicles in aspiration biopsy smears of the prostate (author's transl)].
328 (30.7%) of 1068 prostatic aspirates obtained from 874 patients contained cells of seminal vesicle origin. Cells originating from the seminal vesicles were recognized in aspirates obtained from 27.6% of the untreated patients and in aspirates from 60.4% of the treated patients. Patients of the latter group had received hormonal treatment or radation therapy, or both, or had been surgically treated by prostatectomy. The occurrence of cells derived from seminal vesicles was due to the site of the needled prostatic lesion in 21% of the aspirates obtained, to treatment in 21% and to incorrect biopsy technique in the remaining 58%. A false cytologic report was made in the case of 6 aspirates (1.6%).


Diving accidents in sports divers in Orkney waters.
Scapa Flow in Orkney is one of the major world centres for wreck diving. Because of the geography of Orkney and the nature of the diving, it is possible to make relatively accurate estimates of the number of dives taking place. The denominator of dive activity allows the unusual opportunity of precise calculation of accident rates. In 1999, one in every 178 sports divers visiting Orkney was involved in a significant accident, in 2000 the figure was one in 102. Some of these accidents appear to have been predictable and could be avoided by better education and preparation of visiting divers.


The central role of diminishing sea ice in recent Arctic temperature amplification.
The rise in Arctic near-surface air temperatures has been almost twice as large as the global average in recent decades-a feature known as 'Arctic amplification'. Increased concentrations of atmospheric greenhouse gases have driven Arctic and global average warming; however, the underlying causes of Arctic amplification remain uncertain. The roles of reductions in snow and sea ice cover and changes in atmospheric and oceanic circulation, cloud cover and water vapour are still matters of debate. A better understanding of the processes responsible for the recent amplified warming is essential for assessing the likelihood, and impacts, of future rapid Arctic warming and sea ice loss. Here we show that the Arctic warming is strongest at the surface during most of the year and is primarily consistent with reductions in sea ice cover. Changes in cloud cover, in contrast, have not contributed strongly to recent warming. Increases in atmospheric water vapour content, partly in response to reduced sea ice cover, may have enhanced warming in the lower part of the atmosphere during summer and early autumn. We conclude that diminishing sea ice has had a leading role in recent Arctic temperature amplification. The findings reinforce suggestions that strong positive ice-temperature feedbacks have emerged in the Arctic, increasing the chances of further rapid warming and sea ice loss, and will probably affect polar ecosystems, ice-sheet mass balance and human activities in the Arctic.


[Sudden newborn infant death in maternity. Anatomo-clinical study of 31 cases].
All cases of sudden and unexpected death occurring in maternity were studied over a period of 6 years (1985-1991). Anamnestic data, results of clinical examination of the body and findings of bacterial screening of body fluids or tissues were collected. The results at necropsy were also collected following the protocol used, with parental consent, in all cases of sudden infant death syndrome. There were 31 cases of sudden and unexpected death. Of these, 48% occurred before the 24th hour of life, 68% before the 36th hour and 84% before the 72nd hour. The majority of death occurred at night (55% between midnight and 6 AM, 90% between 9 PM and 9 AM). Analysis of the data provided a precise cause of death in 25 cases (81%), and a probable cause in 4 cases (13%). The major causes were perinatal anoxia, generally associated with massive amniotic inhalation (16 cases), and maternal-fetal infection (9 cases). No cause was found in 2 cases. Despite the fact that the death occurred unexpectedly, half of the newborns showed warning signs, some hours before the event. These signs were either not detected or ignored. The incidence of sudden death in neonates is 0.15 to 0.36/1,000 live births. Its causes are generally correlated with common neonatal diseases. Its occurrence at night and the existence of warning signs raise questions concerning the care of neonates in maternity.


Frequency-dependent learning achieved using semiconducting polymer/electrolyte composite cells.
Frequency-dependent learning has been achieved using semiconducting polymer/electrolyte composite cells. The cells composed of polymer/electrolyte double layers realized the conventional spike-rate-dependent plasticity (SRDP) learning model. These cells responded to depression upon low-frequency stimulation and to potentiation upon high-frequency stimulation and presented long-term memory. The transition threshold θm from depression to potentiation varied depending on the previous stimulations. A nanostructure resembling a bio-synapse in its transport passages was demonstrated and a random channel model was proposed to describe the ionic kinetics at the polymer/electrolyte interface during and after stimulations with various frequencies, accounting for the observed SRDP.


[Mechanisms of onset and signs of latent mastoiditis in patients with exudative otitis media].
Tympanomastoidotomy was performed in 42 patients with exudative otitis media running from 4 to 8 weeks. Large size of the antral cells and high pneumatization of the translabyrinthine tract cells contribute to the onset of latent antritis; large size of the apical cells and hyperpneumatization of the cells of the inferior labyrinthine tract predispose to emergence of isolated apical mastoiditis in patients with exudative otitis media at early stages. Latent mastoiditis and mucoperiostitis in the region of perifacial and perilabyrinthine cells in patients with exudative otitis media are evidenced by early atypical cochleovestibular complaints, mixed hypoacusis and variability of tympanograms.


Diabetic kidney lesions of GIPRdn transgenic mice: podocyte hypertrophy and thickening of the GBM precede glomerular hypertrophy and glomerulosclerosis.
Diabetic nephropathy is the leading cause of end-stage renal disease and the largest contributor to the total cost of diabetes care. Rodent models are excellent tools to gain more insight into the pathogenesis of diabetic nephropathy. In the present study, we characterize the age-related sequence of diabetes-associated kidney lesions in GIPR(dn) transgenic mice, a novel mouse model of early-onset diabetes mellitus. Clinical-chemical analyses as well as qualitative and quantitative morphological analyses of the kidneys of GIPR(dn) transgenic animals and nontransgenic littermate controls were performed at 3, 8, 20, and 28 wk of age. Early renal changes of transgenic mice consisted of podocyte hypertrophy, reduced numerical volume density of podocytes in glomeruli, and homogenous thickening of the glomerular basement membrane, followed by renal and glomerular hypertrophy as well as mesangial expansion and matrix accumulation. At 28 wk of age, glomerular damage was most prominent, including advanced glomerulosclerosis, tubulointerstitial lesions, and proteinuria. Real-time PCR demonstrated increased glomerular expression of Col4a1, Fn1, and Tgfb1. Immunohistochemistry revealed increased mesangial deposition of collagen type IV, fibronectin, and laminin. The present study shows that GIPR(dn) transgenic mice exhibit renal changes that closely resemble diabetes-associated kidney alterations in humans. Data particularly from male transgenic mice indicate that podocyte hypertrophy is directly linked to hyperglycemia, without the influence of mechanical stress. GIPR(dn) transgenic mice are considered an excellent new tool to study the mechanisms involved in onset and progression of diabetic nephropathy.


Solid-state 19F MAS NMR study on the conformation and molecular mobility of poly(chlorotrifluoroethylene).
The temperature dependence of molecular mobility and conformational changes of poly(chlorotrifluoro- ethylene) (PCTFE) have been investigated by solid-state (19)F magic angle spinning (MAS) NMR spectroscopy. The pulse techniques of dipolar-filter and T(1rho)-filter allow selective observation of the amorphous and crystalline domains, respectively. The temperature dependence of T(1rho) (F) revealed that the segmental motion in the amorphous domain becomes vigorous above ca 80 degrees C, which is well above the glass transition (T(g)) temperature (52 degrees C) and more close to the beta-relaxation temperature (95 degrees C). On the other hand, vigorous molecular motions in the crystalline domain occur above 120 degrees C, which is much below the melting temperature (212 degrees C). This indicates that the polymer chains in the PCTFE crystallites are more mobile than those of typical semicrystalline fluoropolymers like poly(vinylidene fluoride) (PVDF), which can be associated with structural imperfections in the crystallites. In addition, the density functional theory (DFT) calculations of (19)F magnetic shielding suggest that the high-frequency shifts observed for the crystalline signals above 80 degrees C can be ascribed to the conformational change around meso diads toward more twisted and/or helical conformations in the main chain.


Differential tissue regulation of insulin-like growth factor binding proteins in experimental diabetes mellitus in the rat.
The expression and regulation of IGF-I is tissue-specific in diabetes mellitus in the rat. These studies were designed to examine if similar tissue specificity exists for IGF-BPs in the diabetic milieu. Diabetes mellitus was induced by a single i.p. injection of STZ (100 mg/kg body weight). Rats were treated with either vehicle--insulin, vanadate, or phlorizin for 7-14 days. Tissues were analyzed for IGF-BPs by ligand blotting and by affinity cross-linking and immunoprecipitation. In liver tissue from nondiabetic control rats, multiple forms of IGF-BPs were noted, ranging from 48,000 to 25,000 M(r). In diabetic rat liver tissue, the 25,000-M(r) form was unchanged, whereas the higher M(r) forms (48,000-42,000 M(r)) were decreased, and the 30,000-M(r) form was increased. Insulin therapy of diabetic rats decreased all forms to below control levels. In the kidney tissue of control rats, faint IGF-BP bands were seen at 30,000 and 25,000 M(r). In diabetic rat kidney tissue, the 30,000-M(r) form again was increased (as in liver) and restored to control levels with insulin therapy. In contrast, only a 30,000-M(r) band was seen in control pituitary tissue, which was slightly increased in the diabetic rats and also was decreased below control levels by insulin. In hypothalamus and cerebral cortex tissue, bands at 30,000 and 25,000 M(r) were noted, and neither was altered by diabetes or insulin treatment. Treatment of diabetic rats with vanadate and phlorizin resulted in comparable blood glucose levels, which were only slightly higher than those achieved with insulin therapy.(ABSTRACT TRUNCATED AT 250 WORDS)


Risky business: emotion, decision-making, and addiction.
Although metabolic abnormalities in the orbitofrontal cortex have been observed in substance dependent individuals (SDI) for several years, very little attention was paid to the role of this brain region in addiction. However, patients with damage to the ventromedial (VM) sector of the prefrontal cortex and SDI show similar behaviors. (1) They often deny, or they are not aware, that they have a problem. (2) When faced with a choice to pursue a course of action that brings an immediate reward at the risk of incurring future negative consequences, they choose the immediate reward and ignore the future consequences. Studies of patients with bilateral lesions of the VM prefrontal cortex support the view that the process of decision-making depends in many important ways on neural substrates that regulate homeostasis, emotion, and feeling. Parallel lines of study have revealed that VM cortex dysfunction is also evident in subgroups of individuals who are addicted to substances. Thus, understanding the neural mechanisms of decision-making has direct implications for understanding disorders of addiction and pathological gambling, and the switch from a controlled to uncontrolled and compulsive behavior. On the clinical front, the approach to treat addictive disorders has been dominated by a diagnostic system that focuses on behaviors, physical symptoms, or choice of drugs. The article emphasizes the concept of using neurocognitive criteria for subtyping addictive disorders. This is a significant paradigm shift with significant implications for guiding diagnosis and treatment. Using neurocognitive criteria could lead to more accurate subtyping of addictive disorders, and perhaps serve as a guide for more specific, and potentially more successful, behavioral and pharmacological interventions.


Drug treatment of heart failure.
The objectives of treatment for patients with chronic heart failure are the prevention of the initial occurrence, the alleviation of signs and symptoms, the delay of the progression of damage to heart muscle and the reduction of the mortality rate. Many drugs are used in severe heart failure. Current controversy is concerned with which drugs to use in patients with mild heart failure or with left ventricular dysfunction. There is a trend towards the earlier introduction of an angiotensin-converting enzyme inhibitor combined with a diuretic.


[Role of the autonomic nervous system in early arrhythmias in acute myocardial infarct in the rabbit].
In order to evaluate the influence of the autonomic nervous system in the incidence and characteristics of the early arrhytmias that follows myocardial infarction, we have developed an experimental myocardial infarction in rabbits by acute occlusion of the left ventricular artery. The influence of adrenergic and cholinergic suppression over rhythm disorders and hemodynamics changes after experimental infarction in the rabbit was also studied. We found that after the acute experimental infarction in the rabbit heart, arose an early stage of rhythm disorders in 60% of the animals. In a group of animals that were injected with Practolol before coronary occlusion, the incidence of arrhythmias was 25% and in a group of animals with vagotomy prior to occlussion none of them developed rhythm disorders. It was concluded that the model is highly steemed for the study of early arrhytmias and that automatic nervous system has an important role in the incidence of such arrhythmias.


Emergency medical services assessment and treatment of children with special health care needs before and after specialized paramedic training.
This study evaluates whether a continuing education program for paramedics, focusing on Children with Special Health Care Needs, improved paramedics' assessment and management. Emergency Medical Services responses for children, 21 years of age or younger, with a congenital or acquired condition or a chronic physical or mental illness, were identified. The responses before and after the specialized education program were reviewed by a multidisciplinary team to evaluate assessment and management of the children. Interreviewer agreement between the nurses on the team and between the physicians on the team was assessed. We also evaluated whether there was an improvement in assessment and care by paramedics completing our education program. Significant improvement was seen in appropriate assessment and overall care by paramedics who completed our specialized education program. Reviewers also noted an appropriate rating for the initial assessment category more often for responses involving paramedics who had the training. Agreement on whether assessment and treatment was appropriate for all five reviewers varied considerably, ranging from 32% to 93%. Overall there was a high percentage of agreement (>70%) between the nurses and between the physicians on most items. However, kappa statistics did not generally reflect good agreement except for most of the focused assessment items and some treatment and procedure items. Most of the documentation on the EMS records indicated appropriate assessment and treatment during all responses for Children with Special Health Care Needs. Nevertheless, the results indicate that paramedics may improve their assessment and management of these children after specialized continuing education.


The bacteriology of obstructive pneumonitis. A prospective study using ultrasound-guided transthoracic needle aspiration.
Obstructive pneumonitis, the opacity that develops distal to an obstructing endobronchial lesion or external compression, is actually a combination of atelectasis, bronchiectasis with mucus plugging, and true parenchymal inflammation. In the majority of cases, it is usually not possible to determine whether infection is present or not from the radiographic findings alone. The aim of this study was to evaluate the bacteriology of obstructive pneumonitis and the influence of this result on the treatment of patients. From March 1992 to February 1993, 26 consecutive patients (20 men and six women) with obstructive pneumonitis were investigated. The obstructive pneumonitis had been caused by malignant tumors in 24 and benign lesions in two. Chest ultrasound (US) and US-guided percutaneous transthoracic aspirations were undergone to obtain specimens for microbiologic examination. Microorganisms were isolated from seven of nine febrile patients and two of 17 nonfebrile patients. A total of 16 bacterial strains are detected in obstructive pneumonitis (Pseudomonas aeruginosa, Klebsiella pneumoniae, viridant streptococci, Bacteroides fragilis, two Peptostreptococcus species, Mycobacterium tuberculosis, Pseudomonas maltophilia, Streptococcus sanguis, Staphylococcus aureus, Bacteroides thetaiotamomicrons, Bacteroides intermedius, Bacteroides species, Veillonella species, aerobic gram-positive bacilli, and Escherichia coli). In five cases the isolates were monobacteriae, and in the remaining four cases, cultures yielded more than one bacteria. The results of aspirate cultures led to changes in the initial antibiotic trial in seven of nine patients, and fever subsided thereafter. Pneumothorax occurred in one cases as the sole complication. The pathogen causing obstructive pneumonitis is very heterogeneous, and polymicrobial infection is common.(ABSTRACT TRUNCATED AT 250 WORDS)


The effect of a penetrating biodegradable implant on the epiphyseal plate: an experimental study on growing rabbits with special regard to polyglactin 910.
A polyglactin 910 rod 3.2 mm in diameter and 25 mm in length was driven in a drill hole in the intercondylar portion of the right femur across the central portion of the growth plate in 20 5-week-old rabbits. The follow-up times were 3, 6, 12, and 24 weeks. The distal femoral growth plates of both femurs were analyzed by radiographic, microradiographic, and oxytetracycline fluorescence, histological, and histomorphometric studies. Histomorphometric studies showed clear changes at injury site and appeared to be an excellent means of exact numerical description of the different cellular areas of the growth plate. Six weeks after implantation, a polyglactin 910 implant resulted in a growth disturbance similar to that of a drill hole of equal bore.


Correlation of lymphatic vessel density and vascular endothelial growth factor with nodal metastasis in papillary thyroid microcarcinoma.
The aim of this study was to investigate not only the intratumoral and peritumoral lymphatic vessel density (ILD and PLD) but also the expression of vascular endothelial growth factors (VEGFs) and to test their correlation with regional lymph nodal metastases in papillary thyroid microcarcinoma (PTMC). A clinicopathologic data review was performed in 60 patients with PTMC treated with total thyroidectomies involving neck dissections. The patterns of lymphatic vessels, the expression of VEGFs, and their correlation with neck metastases were assessed. PLD was significantly higher than ILD (p < .001). Patients with high PLD (>8.0) showed higher rates of neck metastases than low PLD (≤ 8.0) (74.0% vs 46.8%, p = .03). Univariate and multivariate analyses revealed high PLD as the only independent variable predictive of neck metastasis. The expression of VEGFs did not correlate with either lymphatic density or neck metastasis. PLD may be of potential benefit in the prediction of neck metastasis in PTMC.


Patient characteristics and success in day treatment.
This study examined the ability of seven patient characteristics to predict success (remaining, benefiting) in a day treatment program for psychiatric outpatients. The sample consisted of 165 patients, most with affective and personality disorders, who participated in an intensive psychodynamically and group-oriented program within a controlled clinical trial. Two patient personality characteristics (psychological mindedness, quality of object relations) emerged as the strongest predictors. Other variables that contributed to the predictions, either singly or in an interaction with quality of object relations, were age, marriage, presence of a personality disorder, and previous psychiatric hospitalization. The patient's initial level of symptomatic disturbance was not a significant predictor. The advantage of using predictors that are relevant to the theoretical and technical orientation of a program is emphasized.


[Radiologic aspects of myxoma of the jaws].
Four cases of jaw bones myxoma are described, laying special stress on the radiological appearance. Conventional radiogram showed a typical multilocular osteolytic lesion thinning and expanding the cortical bone. This allowed the authors to correctly diagnose the affection. On the contrary CT, showing a unilocular lesion, offered a far less typical representation of the tumor in the two patients who underwent this examination.


High cell density culture with S. cerevisiae CEN.PK113-5D for IL-1β production: optimization, modeling, and physiological aspects.
Saccharomyces cerevisiae CEN.PK113-5D, a strain auxotrophic for uracil belonging to the CEN.PK family of the yeast S. cerevisiae, was cultured in aerated fed-batch reactor as such and once transformed to express human interleukin-1β (IL-1β), aiming at obtaining high cell densities and optimizing IL-1β production. Three different exponentially increasing glucose feeding profiles were tested, all of them "in theory" promoting respiratory metabolism to obtain high biomass/product yield. A non-structured non-segregated model was developed to describe the performance of S. cerevisiae CEN.PK113-5D during the fed-batch process and, in particular, its capability to metabolize simultaneously glucose and ethanol which derived from the precedent batch growth. Our study showed that the proliferative capacity of the yeast population declined along the fed-batch run, as shown by the exponentially decreasing specific growth rates on glucose. Further, a shift towards fermentative metabolism occurred. This shift took place earlier the higher was the feed rate and was more pronounced in the case of the recombinant strain. Determination of some physiological markers (acetate production, intracellular ROS accumulation, catalase activity and cell viability) showed that neither poor oxygenation nor oxidative stress was responsible for the decreased specific growth rate, nor for the shift to fermentative metabolism.


Multi-modal MRI classifiers identify excessive alcohol consumption and treatment effects in the brain.
Robust neuroimaging markers of neuropsychiatric disorders have proven difficult to obtain. In alcohol use disorders, profound brain structural deficits can be found in severe alcoholic patients, but the heterogeneity of unimodal MRI measurements has so far precluded the identification of selective biomarkers, especially for early diagnosis. In the present work we used a combination of multiple MRI modalities to provide comprehensive and insightful descriptions of brain tissue microstructure. We performed a longitudinal experiment using Marchigian-Sardinian (msP) rats, an established model of chronic excessive alcohol consumption, and acquired multi-modal images before and after 1 month of alcohol consumption (6.8 ± 1.4 g/kg/day, mean ± SD), as well as after 1 week of abstinence with or without concomitant treatment with the antirelapse opioid antagonist naltrexone (2.5 mg/kg/day). We found remarkable sensitivity and selectivity to accurately classify brains affected by alcohol even after the relative short exposure period. One month drinking was enough to imprint a highly specific signature of alcohol consumption. Brain alterations were regionally specific and affected both gray and white matter and persisted into the early abstinence state without any detectable recovery. Interestingly, naltrexone treatment during early abstinence resulted in subtle brain changes that could be distinguished from non-treated abstinent brains, suggesting the existence of an intermediate state associated with brain recovery from alcohol exposure induced by medication. The presented framework is a promising tool for the development of biomarkers for clinical diagnosis of alcohol use disorders, with capacity to further inform about its progression and response to treatment.


Polygonum multiflorum Radix extract protects human foreskin melanocytes from oxidative stress in vitro and potentiates hair follicle pigmentation ex vivo.
To examine the ability of an extract from traditional Chinese medicine, Polygonum multiflorum Radix, to protect melanocyte viability from oxidative stress, a key mechanism in the initiation and progression of hair greying. To assess the antioxidant capacity of Polygonum multiflorum Radix extract, primary human foreskin melanocytes were treated with a commercially available Polygonum multiflorum Radix extract added to culture medium and exposed to hydrogen peroxide (H2 O2 ), using intracellular reactive oxygen species concentrations and glutathione/protein ratios as endpoints. To improve solubility for cosmetic uses, a new Polygonum multiflorum Radix extract was derived. As hair greying is the consequence of melanocyte disappearance in an oxidative stress environment, we checked whether the antioxidant capacity of the new Polygonum multiflorum Radix extract could preserve melanocyte viability in response to H2 O2 -induced oxidative stress, and preserve pigmentation within ex vivo human hair follicles. In vitro treatment of primary human foreskin melanocytes with traditional available Polygonum multiflorum Radix extract resulted in decreased intracellular ROS accumulation in response to H2 O2 exposure with a concomitant preservation of glutathione-to-protein ratio, consistent with a protective response against H2 O2 exposure and demonstrating the promise of this extract for protecting melanocytes against oxidative stress. Melanocytes treated with the improved Polygonum multiflorum Radix extract exhibited attenuated H2 O2 -induced cell death, demonstrating a clear cytoprotective effect. Treatment of ex vivo human hair follicles with the improved Polygonum multiflorum Radix extract resulted in a higher level of melanin compared to vehicle-treated controls, demonstrating an ex vivo protective effect on hair pigmentation. Polygonum multiflorum Radix extract protects in vitro primary human foreskin melanocytes from the deleterious effects of H2 O2 exposure and improves pigmentation within ex vivo human hair follicles, demonstrating the utility of Polygonum multiflorum Radix extract as a potential active ingredient for the protection of melanocytes against premature death. This data provides in vitro mechanistic evidence consistent with existing in vivo studies for the use of Polygonum multiflorum Radix extract as a strategy for the prevention of oxidative stress-induced hair greying, in line with traditional Polygonum multiflorum Radix uses.


The development of a sialic acid specific lectin-immunoassay for the measurement of human chorionic gonadotrophin glycoforms in serum and its application in normal and Down's syndrome pregnancies.
We have developed and validated a lectin-immunoassay for the recognition of sialic acid residues on hCG glycoforms in serum. This assay employs a hCG specific capture antibody and a sialic acid specific lectin (Wheat Germ Agglutinin) labelled with horse radish peroxidase. The standard curve covered hCG concentrations of 0-4000 IU/l (3rd IS for hCG, 75/537) with an analytical sensitivity of 1.0 IU/l. The within and between batch coefficient of variation was < 7% for all doses. Cross-reactivity of < 1% with TSH, LH, FSH, hCGalpha, hCGbeta and desialylated hCG confirmed assay specificity. Dilutions of serum of < 10% final concentration were parallel to the standard curve (within and between batch CV, < 6%). The assay working range was 100 - > 500 000 IU/l and the recovery of hCG from serum was in the range of 94.5% to 115.4%, with a mean value of 102.1%. The assay detected a time dependent change in hCG sialylation during normal pregnancy with the relative abundance of sialylated hCG declining after week 9 and increasing after week 15 of gestation. In addition preliminary studies showed that maternal serum hCG concentrations measured with the lectin-immunoassay were elevated in high risk Down's pregnancies (as defined by conventional screening tests between weeks 16-18 gestation, median multiple of median, 3.14; range 1.81-19.12, P < 0. 001) and low risk (1.57, 0.49-6.14, P = 0.034) compared to normal (1. 00, 0.32-3.20) pregnancies. Furthermore, the lectin immunoassay had greater discriminatory power compared to conventional immunoassay of hCG and hCGbeta between normal and both low and high risk Down's pregnancies. This assay will allow analysis of serum samples for the investigation of sialylated variants of hCG glycoforms in various pathological and physiological situations.


Nursery practices and detection of jaundice after newborn discharge.
To investigate nursery practices regarding outpatient recognition of neonatal jaundice. Descriptive survey. Random sample of nursery head nurses and pediatricians from national lists. Nurseries with more than 100 births per year and pediatricians responsible for newborn discharges. Head nurses from 204 nurseries and 200 pediatricians were surveyed, with 62% of head nurses and 55% of pediatricians responding. Almost half of the head nurses (45%) reported lack of a written neonatal jaundice protocol. Twenty-seven percent of head nurses and pediatricians reported that no system is in place to track jaundiced newborns after discharge. Forty percent of head nurses and 26% of pediatricians reported from higher-risk nurseries, defined as nurseries where more than 25% of mothers did not have a high school diploma or more than 50% of infants were born to single-parent families. These nurseries were no more likely to have a protocol for jaundice management or to use a system to track newborns after discharge. Discharge of most newborns before 36 hours of age was common (70% of head nurses, 62% of pediatricians) and some respondents discharged most newborns before 24 hours of age (16% of head nurses, 12% of pediatricians). For newborns discharged before 24 hours of age, more than half of the nurseries surveyed scheduled follow-up within 2 to 3 days (53% of head nurses, 62% of pediatricians). The likelihood of such follow-up did not differ by type of health care insurance, level of maternal education, percentage of single-parent families, predominance of minority patients, or higher risk as defined above. In our sample, many nurseries lack parent education, neonatal jaundice protocols, and neonatal jaundice tracking systems. Newborns discharged before 48 hours of age are often not scheduled to be seen by a health care provider within 2 to 3 days, despite American Academy of Pediatrics guidelines recommending such follow-up.


Prolactin reduction after combined therapy for prolactin macroadenomas.
The ability of surgery or bromocriptine to produce endocrine control of a prolactin macroadenoma decreases as the prolactin level increases. Guidelines for the use of multimodality therapy have not been developed for tumors associated with markedly elevated prolactin levels. We reviewed the records of 21 patients with prolactin levels greater than 200 ng/ml treated by transsphenoidal surgery and postoperative radiotherapy with or without a dopamine agonist. Values before and after treatment were available for 19 patients (13 men and 6 women). The mean basal prolactin level before treatment for the entire group was 2410 ng/ml. Surgery and radiotherapy resulted in a 90% reduction and serum prolactin levels within normal limits in 0 of 7 patients, versus the combination of surgery, radiotherapy, and dopamine agonist, which resulted in a 99.5% reduction and values within the normal range in 12 of 12 patients. Spontaneous physiological improvement was not often observed. One woman and two men were able subsequently to have children. A plan for these patients is discussed.


Mevalonate kinase deficiency associated with ataxia and retinitis pigmentosa in two brothers with MVK gene mutations.
To report the clinical and molecular genetic findings in two brothers with retinitis pigmentosa (RP) and mevalonate kinase deficiency (MKD). The brothers were examined clinically and with fundus autofluorescence, near-infrared autofluorescence, and spectral domain optical coherence tomography. Targeted resequencing was done with a custom designed gene panel containing 78 genes associated with RP. Mutations were confirmed by direct Sanger sequencing. Both brothers, aged 46 and 47 years, were found to carry compound heterozygous mutations in the MVK gene (c.59A>C, c.1000G>A) encoding mevalonate kinase. They presented with severe ataxia, pseudophakia due to early onset cataract, and progressed retinitis pigmentosa. In one brother with cystoid macular edema, treatment with dorzolamide was beneficial. Serum IgD levels were markedly increased in both brothers and mevalonic acid blood and urine levels were markedly increased in the one brother who could be examined. The disease severity differed between the brothers-one had more severe ataxia and less severe visual deficiency compared to the other. MKD can be associated with RP and early onset cataract. Most MKD patients developing RP carry the (p.Ala334Thr) mutation. Macular edema can be treated using local dorzolamide.