Antimicrobial Resistance Patterns and Risk Factors Associated with ESBL-Producing and MDR Escherichia coli in Hospital and Environmental Settings in Lusaka, Zambia: Implications for One Health, Antimicrobial Stewardship and Surveillance Systems.
Antimicrobial resistance (AMR) is a public health problem threatening human, animal, and environmental safety. This study assessed the AMR profiles and risk factors associated with Escherichia coli in hospital and environmental settings in Lusaka, Zambia. This cross-sectional study was conducted from April 2022 to August 2022 using 980 samples collected from clinical and environmental settings. Antimicrobial susceptibility testing was conducted using BD PhoenixTM 100. The data were analysed using SPSS version 26.0. Of the 980 samples, 51% were from environmental sources. Overall, 64.5% of the samples tested positive for E. coli, of which 52.5% were from clinical sources. Additionally, 31.8% were ESBL, of which 70.1% were clinical isolates. Of the 632 isolates, 48.3% were MDR. Most clinical isolates were resistant to ampicillin (83.4%), sulfamethoxazole/trimethoprim (73.8%), and ciprofloxacin (65.7%) while all environmental isolates were resistant to sulfamethoxazole/trimethoprim (100%) and some were resistant to levofloxacin (30.6%). The drivers of MDR in the tested isolates included pus (AOR = 4.6, CI: 1.9-11.3), male sex (AOR = 2.1, CI: 1.2-3.9), and water (AOR = 2.6, CI: 1.2-5.8). This study found that E. coli isolates were resistant to common antibiotics used in humans. The presence of MDR isolates is a public health concern and calls for vigorous infection prevention measures and surveillance to reduce AMR and its burdens.


Regression of transplant coronary artery disease during chronic HELP therapy: a case study.
This report concerns a heart transplant patient with hypercholesterolemia who showed rapid development of a severe transplant coronary artery disease. The patient received 10 mg pravastatine per day. Quantitative coronary angiography analyses of 4 serial angiograms clearly demonstrated that in the first 2.5 years following surgery, there was a rapid simultaneous progression in both the transplant coronary disease, involving the entire coronary system, and the development of segmental stenotic lesions. During one year of weekly heparin-mediated extracorporeal LDL-cholesterol precipitation (HELP) therapy in addition to diet and pravastatine therapy, the serum low density lipoprotein (LDL), lipoprotein (a) (Lp(a)), and fibrinogen levels could be reduced from 185 +/- 45 mg/dl, 138 mg/dl and 248 mg/dl, respectively, to interval values of 136 +/- 17 mg/dl, 48 +/- 15 mg/dl, and 185 +/- 44 mg/dl, respectively [interval value = (the concentration after HELP + the concentration before the next HELP treatment):2]. This therapy halted further progression of coronary diameter throughout the whole coronary system and brought about marked regression of segmental obstructive lesions.


Enhancing the physicochemical properties and functional performance of starch-based films using inorganic carbon materials: A review.
Sustainable film-forming materials are being explored as potential replacements for petroleum-based plastics with the aim of reducing their adverse impacts on the environment. Starch is a highly abundant, renewable, and inexpensive natural polymer with good film-forming properties. However, the weak mechanical strength, poor barrier properties, and high moisture sensitivity of starch-based films currently limit their ability to replace plastics. Inorganic carbon materials (ICMs) can be incorporated to improve the physicochemical properties and functional performance of starch-based films due to their excellent properties. Herein, we provide a summary of the different kinds of ICMs that can be used for this purpose. We then discuss the impact of incorporating these ICMs into starch-based films on their physicochemical and functional properties. Additionally, the potential application of ICM-loaded starch composite films as active and intelligent food packaging materials is highlighted. Finally, the challenges and future perspectives of starch-based films with ICMs are described.


Quality Perceptions and Choice of Public Health Facilities: A Mediation Effect Analysis of Outpatient Experience in Rural China.
Outpatients have choices of providers in the hierarchical health service delivery system of China. Understanding how quality perceptions and outpatient experience affect the choice of health facility would help inform decisions about priorities for action aimed at guiding the use of primary care. This study examines how quality perceptions of outpatient service affect the facility level choice in rural China. Household surveys were conducted in 2011, 2012 and 2015 in Ningxia Hui Autonomous Region, China. We selected 968 respondents as the study sample, who had at least two outpatient visits to the public health facilities during each survey period. Prior quality perceptions of the outpatient service at the village clinics, township centers, and county hospitals were reported on an 8-item Quality Indicator questionnaire. Experienced quality perception from the first outpatient visit was also reported. The outcome of interest was outpatients' facility level choices. We used regression and mediation analysis to explore whether and how outpatient experience at a specific health facility would mediate the relationship between prior quality perceptions and the facility level choice. Overall, the quality perception was positively and significantly associated with outpatients' staying at the same or lower levels of care (β=0.265, P=0.007). This effect was fully mediated by experienced quality perception (z=2.985, P=0.003). The indirect effect was significant for three particular dimensions, including quality perceptions of the environment (β=0.075, P=0.025), doctor-patient communication (β=0.065, P=0.022), and physician ability (β=0.062, P=0.021). Outpatient quality perceptions-especially positive perceptions regarding environment, doctor-patient communication, and physician ability-could contribute to minimizing upward referral via improvement in outpatient experience. Policymakers and health care providers may need to therefore optimize outpatient experience as they push to develop a more locally responsive primary care system.


Distribution, quantification and biological activity of messenger RNA coding for human chorionic somatomammotropin during normal pregnancy.
Synthesis of hCS by RNA fractions from human placentas obtained at different stages of pregnancy was estimated either by immunological or electrophoretical methods in wheat-germ and reticulocyte cell-free systems. hCS synthesis is preferentially associated with polyribosomes bound to the membrane of the endoplasmic reticulum, as is assumed for a secreted protein. In both translational systems we determined only one precursor form of this hormone of a molecular weight near 24 000. Full-term placentas synthesize hCS as the major protein. This conveniently allowed us to isolate the messenger RNA coding for the hormone and to synthesize a specific hCS complementary DNA which we used as a probe for quantifying sequences of RNA coding for hCS during pregnancy. In placentas from first-trimester pregnancy, the concentration of hCS mRNA was 4 times less than in the full-term organs, and the hCS synthesis per microgram of RNA added into the translational medium was diminished in the same order of magnitude. In placentas from second-trimester pregnancy, the concentration of hCS mRNA was similar to that obtained at term, and in vitro the hCS synthesis per microgram of translated RNA was also similar to that observed at the end of pregnancy. However, the hCS mRNA content per placenta from mid-term pregnancy was much lower than from full-term gestation. We established a good parallelism, as pregnancy progressed, between the hCS mRNA content, its capacity of hCS synthesis in vitro and the maternal plasma hCS level, indicating that hCS production is controlled essentially by the biological active mass of the placenta.


Admissions, patterns of utilization and disposition of cases of acute stroke in Brisbane hospitals.
In a population of slightly-more than one million persons, all cases of acute admission to hospital for cerebrovascular disease during 1984 were studied. Of the 2676 hospital admissions, 91% were of public-hospital patients. Of the 1908 patients who were aged more than 25 years and whose conditions were assigned the International classification of diseases' (ICD-9) codes (430-437) for cerebrovascular accidents, 1264 (1.8 patients per 1000 population of older than 25 years of age) cases were completed strokes, and 644 (1.0 patients per 1000 population of older than 25 years of age) cases were transient ischaemic attacks. There was no significant difference between the specific aetiological types of stroke that were diagnosed neuroradiologically and those that were diagnosed clinically. Among the cases of completed strokes, 54% of cases were thrombotic, 11% of cases were embolic, and 15% of cases were haemorrhagic, while nearly 20% of cases were unclassified. Twenty-one per cent of patients who were admitted to hospital with completed strokes died within two weeks of their admission, 28% of such patients were discharged home, 8% of such patients were transferred to full-maintenance care, and the remaining 43% of such patients were transferred for inpatient rehabilitation. The median length of stay for patients with completed strokes was 11.8 days compared with 6.2 days for patients with transient ischaemic attacks.


Efficacy and toxicity of 2-Chlorodeoxyadenosine (Cladribine)--2 h infusion for 5 days--as first-line treatment for advanced low grade non-Hodgkin's lymphoma.
2-Chlorodeoxyadenosine (Cladribine) is a new purine analogue with high activity in pretreated low grade non-Hodgkin's lymphoma (NHL). To evaluate the efficacy of this drug in untreated patients with advanced NHL, we performed a prospective multicentre trial. Cladribine (0.12 mg/kg) was administered intravenously daily for 5 consecutive days in an out-patient setting. The treatment was repeated every 28 days for four cycles. Included were patients with a histological diagnosis of low grade NHL according to the Kiel classification and stage III or IV disease. Stage II patients were included when radiotherapy had failed. 55 patients were entered into the study. 50 patients were evaluable. The remission rate was 44/50 (88%; 95% confidence interval 82-100%), including complete remissions (CR) in 14 (28%) patients. Only 2 patients showed progression while on Cladribine treatment. The estimated overall survival, and time to treatment failure (TTF) were 85% and 51%, respectively, after a median observation time of 92 weeks. 11 (22%) patients showed grade 3 or 4 toxicity according to the WHO grading. Haematological toxicity was responsible for 86% of the overall toxicity and 100% of grade 3 and 4 toxicity. 7 patients (14%) had an infection, two of which were opportunistic. 12 (24%) patients did not experience any toxicity during the treatment. The results of this study clearly demonstrate the safety and considerable activity of this regimen. Cladribine is very effective even at lower doses than have been used so far.


One-step seed dispersion polymerisation in supercritical carbon dioxide.
A single step seed dispersion polymerisation is reported for the first time, in which scCO2 is used simultaneously as both an antisolvent and a polymerisation medium to create polymer-C60 composite microparticles providing additional proof for the mechanism of dispersion polymerisation in scCO2.


Efficacy of platelet-rich plasma injections in patients with adhesive capsulitis of the shoulder.
The goal of this study is to investigate whether platelet-rich plasma (PRP) injections are effective in the management of adhesive capsulitis of the shoulder (AC). A triple-blind, randomized controlled trial was designed and conducted in a medical school hospital. 32 adult patients with adhesive capsulitis (21 female, 11 male with a mean age of 57, ranging from 23 to 70) were included in this study. Patients had to have shoulder pain and restrictions in movements (at least 25% when compared to the other side, and at least in two directions) for three months minimum and nine months maximum. Patients were randomized to two groups, and one group took PRP injections for three times every two weeks, while the other group took saline injections in same frequency and volume. A standardized exercise program was also applied to all patients. Patients were evaluated with Shoulder Pain and Disability Index (SPADI), Visual Analogue Scales for pain and disability, ranges of movements, and use of analgesics in before, after, and third month after the initiation of the therapy. Baseline comparisons between groups showed no differences. SPADI and ranges of motion in all directions showed significant improvements with therapy, and the group which took PRP injections showed better improvements when compared to the control group (p < 0.05). Visual Analogue Scale was found to be better for the PRP group after therapy and third month, and not for the control group (0.4 ± 1.06 and 0.17 ± 0.72 vs. 2.5 ± 2.6 and 2 ± 2.2, respectively, p < 0.05). Use of analgesics was not found to be significant for both groups (p > 0.05). PRP injections were found to be effective in both pain and disability, and showed improvements in a restricted shoulder due to adhesive capsulitis. These findings might point out PRP as a therapeutic option in the management of adhesive capsulitis.


CT-Based Radiogenomics of P4HA3 Expression in Clear Cell Renal Cell Carcinoma.
The sequencing of the renal cell carcinoma (RCC) genome identified several mutations with prognostic significance. Genomic analysis, collected in The Cancer Genome Atlas Research Network, revealed several clear cell renal cell carcinoma (ccRCC) gene mutations and gene expressions. Radiogenomics is a new branch of diagnostic imaging based on the association between imaging phenotypes and genomics of diseases. P4HA3 expression has recently been shown to correlate with increased aggressiveness of ccRCC, with poor prognosis, proliferation, migration, invasion, and metastases, suggesting P4HA3 as a prognostic marker and therapeutic target in ccRCC. The aim of this study is to investigate the computed tomography (CT) imaging phenotype of P4HA3 expression in ccRCC patients. In this retrospective study we enrolled 196 ccRCC patients divided into two groups: ccRCC patients with P4HA3 expression (n = 13) and ccRCC patients without P4HA3 expression (n = 183). Several imaging features were evaluated on preoperative CT scan. The statistical significance threshold was set at P < .05. A statistically significant association was found with larger primary tumor size (P = .033), tumor infiltration (P = .023), ill-defined tumor margins (P = .025), and advanced tumor stage American Joint Committee of Cancer (P = .014). This study demonstrates CT imaging features associated with P4HA3 expression in ccRCC. These results could contribute to better understand P4HA3 expression with a noninvasive approach and could be applied to the development of targeted therapies.


TGF-β1 29T/C polymorphism and breast cancer risk: a meta-analysis involving 25,996 subjects.
Transforming growth factor β1 (TGF-β1) is a cytokine, playing an important role in controlling cell proliferation and differentiation involved in breast cancer. It was reported the 29T/C polymorphism in TGF-β1 has been implicated in breast cancer risk. However, studies on the association between this polymorphism and breast cancer remain conflicting. To derive a more precise estimation of the relationship, a meta-analysis of 10,341 cases and 15,655 controls from fifty published case-control studies was performed. Our analysis suggested that 29T/C has no association with a trend of breast cancer risk when using both dominant [odds ratio (OR) = 1.01, 95% confidence intervals (CI) 0.96-1.07] and recessive models (OR = 0.98, 95% CI 0.89-1.08) to analyze the data. In ethnic subgroups analysis, 29T/C also did not appear to be risk factors for breast cancer. However, larger scale primary studies are required to further evaluate the interaction of TGF-β1 29T/C polymorphism and breast cancer risk in specific populations.


Retracted: Analysis of Landscape Ecological Planning Based on the High-Order Multiwavelet Neural Network Algorithm.
[This retracts the article DOI: 10.1155/2021/9420532.].


Reassessment of the assumed A-V oxygen content difference in the shunt calculation.
A study was undertaken in 15 patients to compare measured and assumed arteriovenous oxygen (A-V O2) content differences and their effects on resultant shunt calculations. All patients were on volume ventilators and demonstrated a stable cardiovascular state. Simultaneous measurements of the O2 content of a pulmonary artery (PA) and of a superior vena cava (SVC) sample were compared. A mean A-V 02 content difference of 3.5 plus or minus 0.8 volumes percent was obtained from the PA and 2.6 plus or minus 1.1 volumes percent from the SVC. The resultant shunt calculations derived from measured A-V 02 content differences were compared with the calculation based on an assumed A-V O2 content difference of 5 volumes percent. A method for extrapolating a "true" A-V 02 content difference from an SVC blood sample was obtained. The extrapolated value resulted in a more representative "true shunt" calculation in 13 of the 15 patients.


Near perfect classification of cardiac biomarker Troponin-I in human serum assisted by SnS2-CNT composite, explainable ML, and operating-voltage-selection-algorithm.
The high worldwide mortality and disproportionate impact of cardiovascular diseases have emerged as the most significant global health burden, unfortunately, unmet by the traditional detection methods. Therefore, developing a rapid, sensitive, selective, and rugged biosensor for the precise classification/quantification of cardiac biomarkers is a stepping stone for the future generation of cardiac healthcare. We demonstrate a facile, time-efficient, and scalable biosensor for classifying the FDI approved gold standard cardiac biomarker Troponin-I (cTnI) in untreated human serum matrix, built-on 2-D SnS2 and 1-D MWCNT composite transducer and decision-tree based explainable machine learning (ML) algorithm. The proposed methodology is further enhanced using an inimitable Operating-Voltage-Selection-Algorithm (OVSA), which boosts ML accuracy to ∼100%. The near-perfect classification is realized by strategically incorporating this two-step algorithm-first the OVSA, then the heuristic and ML approaches on the selected dataset. Dynamic concentrations of the biomarker (100 fg/mL to 100 ng/mL) are estimated with high sensitivity, ∼71 (ΔR/R) (ng/mL)-1cm-2 and low limit of detection (0.02 fg/mL), aiding to the prediction and prognosis of acute myocardial infarction. The hyperparameter tuning and feature engineering improve the decision process of the ML algorithm, fostering robustness against data variability. Feature importance indices, namely the Gini index, Permutation Importance, and SHAP values, portray 'Voltage' as the most important feature, further justifying our insight into the OVSA. The biosensor's specificity, selectivity, reproducibility and stability are effectively demonstrated with the sampling to result reporting time of just 20 min, establishing it as a potential candidate for clinical testing.


p53 expression in skin carcinogenesis and its relationship to cell proliferation and tumour growth.
The immunoreactivity of p53 protein was studied in relation to tumour development, histopathological characteristics, cell proliferation, and basement membrane organisation following the induction of skin carcinogenesis in tumour-sensitive and -resistant mouse strains by ultraviolet (UV) irradiation or 7,12-dimethylbenz(a)anthracene (DMBA). In non-neoplastic skin exposed to UV irradiation or DMBA, p53 immunoreactivity was observed in nearly 50% of the basal layer cells. These cells were morphologically and histochemically indistinguishable from the p53-negative cells, occurring similarly in the tumour-producing and the tumour-negative mouse strains and regardless of subsequent tumour formation. In induced epidermal hyperplasia and in benign tumours, p53-positive and proliferating cells constituted 40-50% of all cells in the basal layer, while superficial cells were p53 negative. In dysplastic epidermis, p53-positive cells and proliferating cells were seen in all cell layers. In the case of squamous cell carcinomas, p53-positive proliferating cells in differentiated neoplasms were localised close to the basement membrane and, more frequently, in border areas showing invasion and basement membrane destruction. In horn cysts, centrally located cells were non-proliferating and p53 negative. In moderately differentiated neoplasms, proliferating cells were located closer to the basement membrane, while p53-positive cells were distributed diffusely in the neoplasm. In poorly differentiated neoplasms, p53-positive cells were more common than proliferating cells and were arranged in a diffuse pattern. The results showed that the number and location of p53-positive cells depended upon histology, with a close relationship to tumour type and degree of malignancy, but not on the mode of induction, nor on the animal strain or the relationship to subsequent tumour formation.


Use of technetium-99m albumin colloid to assess competency of hemidiaphragms in children.
Three cases are presented in which the intraperitoneal injection of radiopharmaceutical is used to assess diaphragmatic competency.


Training attention-switching ability in adults with ADHD.
Children with ADHD show attention-switching impairment. The present study assessed attention-switching ability in adults with ADHD, the extent to which this ability can be improved via targeted training, and the degree to which training extends to novel tasks of attention-switching. Adults with ADHD (n = 16) and adults without ADHD (n = 18) were divided into training and non-training groups. Training groups performed six blocks of four different attention-switching tasks, while non-training groups completed non-switching, "filler" tasks. Lastly, the four groups were tested on two novel attention-switching tasks. Adults with ADHD showed impaired attention-switching, relative to non-ADHD adults, but training significantly improved attention-switching in both ADHD and non-ADHD training groups. Finally, training effects transferred to new tasks of attention-switching. Adults with ADHD show attention-switching impairments, but deficits may be ameliorated with short-term, targeted training. Research has implications for cognitive training in ADHD.


Overlapping association signals in the genetics of hair-related phenotypes in humans and their relevance to predictive DNA analysis.
Genetic prediction of different hair phenotypes can help reconstruct the physical appearance of an individual whose biological sample is analyzed in criminal and identification cases. Up to date, forensic prediction models for hair colour, hair shape, hair loss and hair greying have been developed, but studies investigating predictability of hair thickness and density traits are missing. First data suggesting overlapping associations in various hair features have emerged in recent years, suggesting partially common genetic basis and molecular mechanisms, and this knowledge can be used for predictive purposes. Here we aim to broaden our understanding of the genetics underlying head, facial and body hair thickness and density traits and examine the association for a set of literature SNPs. We characterize the overlap in SNP association for various hair phenotypes, the extent of genetic interactions and the potential for genetic prediction. The study involved 999 samples from Poland, genotyped for 240 SNPs with targeted next-generation sequencing. Logistic regression methods were applied for association and prediction analyses while entropy-based approach was used for interaction testing. As a result, we refined known associations for monobrow and hairiness (PAX3, 5q13.2, TBX) and identified two novel association signals in IGFBP5 and VDR. Both genes were among top significant loci, showed broad association with different hair-related traits and were implicated in multiple interaction effects. Overall, for 14.7% of SNPs previously associated with head hair loss and/or hair shape, a positive signal of association was revealed with at least one hair feature studied in the current research. Overlap in association with at least two hair-related traits was demonstrated for 24 distinct loci. We showed that the associated SNPs explain ∼5-30% of the variation observed in particular hair traits and allow moderate accuracy of prediction. The highest accuracy was achieved for hairiness level prediction in females (AUC = 0.69 for the "none", 0.69 for the "low" and 0.76 for the "excessive" hairiness category) and monobrow (AUC = 0.69 for the "none", 0.62 for the "slight" and 0.70 for the "significant" monobrow category) with 33% of the variation in hairiness level in females explained by 7 SNPs and age, and 20% of the variation in monobrow captured by 7 SNPs and sex. Our study presents clear evidence of pleiotropy and epistasis in the genetics of hair traits. The acquired knowledge may have practical application in forensics, as well as in the cosmetic industry and anthropological research.


Impact of the reduction of the prescription charge in Wales on the prescribing of non-sedating antihistamines in primary care.
Determine the impact of the phased reduction of the prescription charge in Wales on prescriptions for non-sedating antihistamines. Prescription items for non-sedating antihistamines dispensed in 22 Local Health Boards (LHBs) in Wales and 15 Primary Care Trusts in the South East of England were analysed between October 2001 and September 2006. There was an increase in percent change (median (interquartile range [IQR])) in prescription items for non-sedating antihistamines dispensed in Wales in the 24 months after the first reduction of the prescription charge in October 2004 compared to the 24 months prior to this (13.7 [10.9-17.1] vs. 7.3 [5.0-10.7], p<0.001). In the South East of England there was no change over the same periods (4.4 [3.4-7.5] vs. 4.5 [0.8-7.9], p=0.73). In the five least deprived LHBs the percent change in prescriptions for non-sedating antihistamines increased in the 24 months after the reduction of the prescription charge compared to the previous 24 months (14.3 [11.5-19.4] vs. 9.0 [9.1-13.5], p=0.04). In contrast there was no change over the two periods in the five most deprived LHBs (13.1 [10.9-17.5] vs. 9.5 [2.9-10.4], p=0.08]. The phased reduction of the prescription charge in Wales coincided with an increase in the number of non-sedating antihistamines dispensed in Wales. This was only evident in the least deprived LHBs.


The use of cross-correlation function for the alignment of ECG waveforms and rejection of extrasystoles.
The cross-correlation function for alignment of ECG waveforms and rejection of artifacts was studied. ECG waveforms were recorded and digitized (10-bit resolution) at 1.28 KHz and were processed with a CDC 6600 computer. The cross-correlation function was calculated using the cross spectrum and the fast Fourier transform algorithm. The maximum value of the cross-correlation function and the time location of that value were searched for (a) the similarity between the waveforms (for elimination of extrasystoles), and (b) measuring the relative time delay (for the waveform's alignment in the averaging process) between the ECG waveforms. Prior to the correlation procedure each of the ECG waveforms was filtered through a nonrecursive digital bandpass filter. Experiments with various filters indicated that when low-frequency cutoff at 30 Hz and high-frequency cutoff at 250 Hz were used the maximum value of the cross-correlation function was higher than 0.9 for most of our recorded waveforms and more accurate results were obtained.


Future Cardiovascular Disease Risk for Women With Gestational Hypertension: A Systematic Review and Meta-Analysis.
Background Inconsistent findings have been found among studies evaluating the risk of cardiovascular disease for women who have had pregnancies complicated by gestational hypertension (the new onset of high blood pressure without proteinuria during pregnancy). We provide a comprehensive review of studies to quantify the association between gestational hypertension and cardiovascular events in women. Methods and Results We conducted a systematic search of PubMed, Embase, and Web of Science in March 2019 for studies examining the association between gestational hypertension and any cardiovascular event. Two reviewers independently assessed the abstracts and full-text articles. Study characteristics and the relative risk (RR) of cardiovascular events associated with gestational hypertension were extracted from the eligible studies. Where appropriate, the estimates were pooled with inverse variance weighted random-effects meta-analysis. A total of 21 studies involving 3 60 1192 women (127 913 with gestational hypertension) were identified. Gestational hypertension in the first pregnancy was associated with a greater risk of overall cardiovascular disease (RR, 1.45; 95% CI, 1.17-1.80) and coronary heart disease (RR, 1.46; 95% CI, 1.23-1.73), but not stroke (RR, 1.26; 95% CI, 0.96-1.65) or thromboembolic events (RR, 0.88; 95% CI, 0.73-1.07). Women with 1 or more pregnancies affected by gestational hypertension were at greater risk of cardiovascular disease (RR, 1.81; 95% CI, 1.42-2.31), coronary heart disease (RR, 1.83; 95% CI, 1.33-2.51), and heart failure (RR, 1.77; 95% CI, 1.47-2.13), but not stroke (RR, 1.50; 95% CI, 0.75-2.99). Conclusions Gestational hypertension is associated with a greater risk of overall cardiovascular disease, coronary heart disease, and heart failure. More research is needed to assess the presence of a dose-response relationship between gestational hypertension and subsequent cardiovascular disease. Registration URL: https://www.crd.york.ac.uk/prospero/; Unique identifier: CRD42018119031.


A mixture of experts network structure for breast cancer diagnosis.
Mixture of experts (ME) is a modular neural network architecture for supervised learning. This paper illustrates the use of ME network structure to guide diagnosing of breast cancer. Expectation-maximization (EM) algorithm was used for training the ME so that the learning process is decoupled in a manner that fits well with the modular structure. Diagnosis tasks are among the most interesting activities in which to implement intelligent systems. Specifically, diagnosis is an attempt to accurately forecast the outcome of a specific situation, using as input information obtained from a concrete set of variables that potentially describe the situation. The ME network structure was implemented for breast cancer diagnosis using the attributes of each record in the Wisconsin breast cancer database. To improve diagnostic accuracy, the outputs of expert networks were combined by a gating network simultaneously trained in order to stochastically select the expert that is performing the best at solving the problem. For the Wisconsin breast cancer diagnosis problem, the obtained total classification accuracy by the ME network structure was 98.85%. The ME network structure achieved accuracy rates which were higher than that of the stand-alone neural network models.


A quality control system for the optimized sperm penetration assay.
To develop a quality control system for the optimized sperm penetration assay (SPA) and to use this system to monitor interassay variability and stability over time. Four semen donors were tested consecutively for a period of weeks (7 to 139 weeks) with the SPA. Their average semen analyses and SPA scores were evaluated to monitor natural biologic variation. Intra-assay variation was obtained by dividing 11 semen samples into three aliquots and testing each separately in the SPA. A single ejaculate from seven individuals was aliquoted and frozen to be used as a control. They were tested on different assay days in 1986 and subsequently in 1991 to evaluate the assay stability over time. Results were expressed as a sperm capacitation index (mean number of sperm penetrations per ovum). Consecutive weekly semen analyses and SPAs on donors exhibited coefficients of variation ranging from 20% to > 40%. In contrast, these variations were much greater than intra-assay variability. Analysis of frozen semen specimens tested in several SPAs also displayed a low coefficient of variation. When aliquots of these frozen samples were tested in the SPA 5 years later, there were no differences in the observed values, showing the remarkable stability of this assay over time. The lower limit of the normal fertile range did not change over a period of 2 years. Results show that using fresh semen samples as a positive control in the SPA is inadequate. This deficiency has been overcome with the use of frozen semen controls. With frozen semen for quality control, the optimized SPA developed in this laboratory is a highly reproducible assay that meets the strict criteria required for clinical laboratory certification.


3D cardiac microtissues encapsulated with the co-culture of cardiomyocytes and cardiac fibroblasts.
Cardiac tissue engineering has major applications in regenerative medicine, disease modeling and biological studies. Despite the significance, numerous questions still need to be explored to enhance the functionalities of engineered tissue substitutes. In this study, 3D cardiac microtissues are developed through encapsulation of cardiomyocytes and cardiac fibroblasts, as the main cellular constituents of native myocardium. The geometries of the constructs are precisely controlled and assessed for their role on synchronous contraction of the cells. Cardiomyocytes exhibit a native-like phenotype when co-cultured with cardiac fibroblasts as compared to the monoculture condition. Particularly, elongated F-actin fibers with abundance of sarcomeric α-actinin and troponin-I are observed within all layers of the constructs. Higher expressions of connexin-43 and integrin-β1 indicate improved cell-cell and cell-matrix interactions. Amongst co-culture conditions, 2:1 (cardiomyocytes: cardiac fibroblasts) ratio exhibits enhanced functionalities, whereas decreasing the construct size adversely affects the synchronous contraction of the cells. Overall, the study here indicates that the cell-cell ratio and the construct geometry are crucial parameters, which need to be optimized to enhance the functionalities of the engineered tissue substitutes.


A heavy metal tolerant novel bacterium, Bacillus malikii sp. nov., isolated from tannery effluent wastewater.
The taxonomic position of a Gram-stain positive and heavy metal tolerant bacterium, designated strain NCCP-662(T), was investigated by polyphasic characterisation. Cells of strain NCCP-662(T) were observed to be rod to filamentous shaped, motile and strictly aerobic, and to grow at 10-50 °C (optimum 30-37 °C) and at pH range of 6-10 (optimum pH 7-8). The strain was found to be able to tolerate 0-12 % NaCl (w/v) and heavy metals (Cr 1200 ppm, Pb 1800 ppm and Cu 1200 ppm) in tryptic soya agar medium. The phylogenetic analysis based on the 16S rRNA gene sequence of strain NCCP-662(T) showed that it belongs to the genus Bacillus and showed high sequence similarity (98.2 and 98.0 %, respectively) with the type strains of Bacillus niabensis 4T19(T) and Bacillus halosaccharovorans E33(T). The chemotaxonomic data showed that the major quinone is MK-7; the predominant cellular fatty acids are anteiso-C15 :0, iso-C14:0, iso-C16:0 and C16:0 and iso-C15:0; the major polar lipids are diphosphatidylglycerol, phosphatidylglycerol along with several unidentified glycolipids, phospholipids and polar lipids. The DNA G+C content was determined to be 36.9 mol%. These data also support the affiliation of strain NCCP-662(T) with the genus Bacillus. The level of DNA-DNA relatedness between strain NCCP-662(T) and B. niabensis JCM 16399(T) was 20.5 ± 0.5 %. On the basis of physiological and biochemical characteristics, phylogenetic analyses and DNA-DNA hybridization data, strain NCCP-662(T) can be clearly differentiated from the validly named Bacillus species and thus represents a new species, for which the name Bacillus malikii sp. nov. is proposed with the type strain NCCP-662(T) (= LMG 28369(T) = DSM 29005(T) = JCM 30192(T)).


Operating temperature prediction and comparison for rooftop PV arrays in coastal climates of India.
This article predicts the operational temperature of a 1-MWp rooftop photovoltaic (PV) system installed on buildings of GITAM University, Andhra Pradesh, India, using various temperature models. In the process of photovoltaic conversion, the operating temperature plays a key role, where the module efficiency and output power of the PV module are linearly dependent on temperature. Various temperature models are presented in the literature with simplified working formulas to find the module temperature involving environment and PV system parameters. This study adopts four models NOCT (normal operating cell temperature), Fiaman, Scandia and arbitrary mounting model (AMM), to assess the power, module temperature of the photovoltaic plant and identify the best model to suit the present study location. Their precision is evaluated on a seasonal day (winter, summer, monsoon and autumn) from the measured data. It is observed that winter, summer, monsoon and autumn days have hourly average module temperatures of 45.4 °C, 48.1 °C, 48.2 °C and 45.3 °C, respectively. Results show the highest average DC voltage of 231.2 kW on a summer day with an hourly module temperature of 48.1 °C recorded. The slightest error values of 3.71% MBE, 5.8% NRMSE, 1.89% TS and 0.03% WMBE are noted with the arbitrary mounting temperature model. This study is helpful to validate that the AMM model is best suited for PV simulation in coastal regions.


Availability of toxic trace metals to the conceptus.
Energy production releases numerous toxic metals into the environment. Among those metals which have been shown to be toxic to the conceptus are cadmium, lead, mercury, plutonium and vanadium. This paper reviews the results from the authors' studies of pregnant rats exposed to these metals by parenteral administration, inhalation or gastric intubation. In addition, direct measurements were made of maternal blood flow and clearance of metals across the guinea pig placenta to serve as conceptual examples of factors which regulate the effects of the metals on the fetus. Discussion includes the influence of route of maternal exposure and subsequent absorption, gestational age at exposure, metal behavior in the maternal bloodstream, movement of metals across the placenta, and distribution of metals in the products of conception.


Enhanced antitumor effects of bleomycin and moderate hyperthermia by additional use of ethanol.
The combined effects of moderate local hyperthermia, bleomycin and ethanol were investigated with Lewis lung carcinoma tumors in female C57BL/6 mice. Different combinations of treatments were performed on days 4 and 7 after tumor implantation. Combined treatment of 41 degrees C hyperthermia and bleomycin resulted in mild reductions of tumor growth. Hyperthermia plus bleomycin led to marked reduction in tumor growth under the condition of a 43 degrees C temperature. The antitumor effects of 41 degrees C hyperthermia combined with bleomycin were enhanced by the additional use of ethanol, and these effects were more remarkable than those of 43 degrees C hyperthermia and bleomycin. A possible application of these findings to clinical therapy for advanced esophageal cancer was discussed.


What Would Jaws Do? The Tyranny of Film and the Relationship between Gaze and Higher-Level Narrative Film Comprehension.
What is the relationship between film viewers' eye movements and their film comprehension? Typical Hollywood movies induce strong attentional synchrony-most viewers look at the same things at the same time. Thus, we asked whether film viewers' eye movements would differ based on their understanding-the mental model hypothesis-or whether any such differences would be overwhelmed by viewers' attentional synchrony-the tyranny of film hypothesis. To investigate this question, we manipulated the presence/absence of prior film context and measured resulting differences in film comprehension and eye movements. Viewers watched a 12-second James Bond movie clip, ending just as a critical predictive inference should be drawn that Bond's nemesis, "Jaws," would fall from the sky onto a circus tent. The No-context condition saw only the 12-second clip, but the Context condition also saw the preceding 2.5 minutes of the movie before seeing the critical 12-second portion. Importantly, the Context condition viewers were more likely to draw the critical inference and were more likely to perceive coherence across the entire 6 shot sequence (as shown by event segmentation), indicating greater comprehension. Viewers' eye movements showed strong attentional synchrony in both conditions as compared to a chance level baseline, but smaller differences between conditions. Specifically, the Context condition viewers showed slightly, but significantly, greater attentional synchrony and lower cognitive load (as shown by fixation probability) during the critical first circus tent shot. Thus, overall, the results were more consistent with the tyranny of film hypothesis than the mental model hypothesis. These results suggest the need for a theory that encompasses processes from the perception to the comprehension of film.


Maternal knowledge on early childhood caries and barriers to seek dental treatment in Jordan.
To assess maternal knowledge, attitudes and beliefs of Early Childhood Caries (ECC) risk factors and to determine barriers in seeking dental treatment among children with ECC. A total of 600 mothers of healthy children, aged 3-5 years, with ECC attending maternity and child health centres in Jordan completed a questionnaire using face-to-face interviews. ECC was diagnosed clinically by the chief investigator, based on the diagnostic criteria suggested by American Academy of Paediatric Dentistry (AAPD), and caries was recorded using dmft index. The majority of the children had poor oral health status (99.2%) with a dmft index of 6.04 (± 1.2). Less than third (25.7%) of the mothers believed that their child had poor oral health with more than half (53.3%) not being aware that their child had dental caries. Most of the mothers had poor knowledge, attitudes and beliefs regarding their children's oral health (82%). Participants` oral health knowledge was significantly associated with mothers` level of education and profession (p < 0.05). In addition, there was delay in seeking dental treatment for their children by the majority (65.9%) of mothers. Maternal profession, family income and time needed to reach a nearby health centre were found to be significant barriers in seeking dental treatment (p < 0.05). The majority of the mothers of children in Jordan with ECC had poor knowledge about their children's oral health status. Moreover, seeking dental treatment was delayed by a large number of mothers of children with ECC.


Idiopathic hemochromatosis presenting as amenorrhea and arthritis.
Idiopathic hemochromatosis in young adults has been increasingly recognized over the last three decades. Younger patients with hemochromatosis frequently have presenting problems other than diabetes, cirrhosis, and hyperpigmentation. A young woman with idiopathic hemochromatosis is described. Arthritis and secondary amenorrhea developed at age 20, and liver biopsy showed hemochromatosis at age 29. Further work-up revealed that the amenorrhea was due to underproduction of pituitary gonadotropins. The patient was treated with phlebotomy. Estrogen and progesterone replacement was begun because of severe osteoporosis. Serum iron studies may be useful in young patients with unexplained amenorrhea and/or arthropathy.


Acute skin GVHD following syngeneic BMT for CLL.
A 41-year-old woman received a syngeneic BMT for CLL and subsequently developed acute skin GVHD. Transfusion-related allogeneic GVHD was excluded on the basis of an unchanged HLA type in circulating lymphocytes. Short tandem repeat PCR was used to confirm syngeneicity between donor and recipient. The patient had a personal and family history of autoimmune disease which may have made her particularly susceptible to development of syngeneic GVHD. The distinction between allogeneic and syngeneic or autologous GVHD is important because of therapeutic implications.


Posttraumatic and postoperative cardiac luxation: computed tomography findings in nine patients.
Posttraumatic and postoperative cardiac luxation represents a serious complication of pericardial rupture, and early diagnosis is important. The purpose of this study is to determine signs of left cardiac luxation on computed tomography (CT). CT scans in nine patients with pericardial rupture and cardiac luxation after blunt chest trauma (n = 7) and postoperatively after extended left pneumectomy (n = 2) were reviewed for abnormalities. We analyzed the clinical history, clinical findings, and the imaging findings. Dislocation of the heart to the left and pneumopericardium were seen in nine patients. Five of these nine patients revealed "entrapment" of the left heart between the proximal ascending aorta and the descending aorta. All patients underwent a pneumopericardium. All patients with a history of trauma showed a left-sided pneumothorax but no pericardial effusion. CT plays a key role for early diagnosis of cardiac luxation. Dislodgment of the heart, entrapment of the left atrium and ventricle, and pneumopericardium associated with pneumothorax are the most important CT findings.


Intensity- and time-matched acute interval and continuous endurance exercise similarly induce an anti-inflammatory environment in recreationally active runners: focus on PD-1 expression in Tregs and the IL-6/IL-10 axis.
Acute exercise elicits a transient anti-inflammatory state during the early recovery period. Since recent studies reported on regimen-specific effects on immune-related humoral factors and cellular subsets, this study compared the effects of intensity- and time-matched acute interval and continuous exercise on peripheral anti-inflammatory cellular and humoral immune parameters with a particular focus on the PD-1 expression in CD4+ regulatory T cells (Tregs). Twenty-four recreationally active runners (age: 29.7 ± 4.3 years, BMI: 22.2 ± 2.4, VO2peak: 56.6 ± 6.4 ml × kg-1 × min-1) participated in this crossover RCT. Each subject conducted a moderate continuous (MCE) and a high-intensity interval exercise (HIIE) session in a counterbalanced design. Blood was drawn before, immediately after, and 1 h after exercise. Treg subsets and levels of PD-1 and Foxp3 were assessed by flow cytometry. Serum levels of IL-10 and IL-6 were quantified by ELISA. PD-1 levels on Tregs increased within the recovery period after HIIE (p < .001) and MCE (p < 0.001). Total counts of Tregs (HIIE: p = 0.044; MCE: p = .021), naïve Tregs (HIIE: p < 0.001; MCE: p < 0.001), and PD-1+ effector Tregs (eTregs) (HIIE: p = .002) decreased 1 h after exercise. IL-10 increased 1 h after HIIE (p < 0.001) and MCE (p = 0.018), while IL-6 increased immediately after both HIIE (p = 0.031) and MCE (p = 0.021). Correlations between changes in IL-6 and IL-10 (p = 0.017, r = 0.379) and baseline VO2peak and Treg frequency (p = 0.002, r = 0.660) were identified. This is the first study that investigates PD-1 expression in circulating Tregs after acute exercise, revealing an increase in PD-1 levels on eTregs during the early recovery period after intensity- and time-matched HIIE and MCE. Future studies are needed to investigate the PD-1 signalosome in eTregs, together with the expression of key effector molecules (i.e., IL-10, TGF-β, IL-35, CTLA-4) to elucidate PD-1-dependent changes in cellular function. Based on changes in serum cytokines, this study further reveals a regimen-independent establishment of an anti-inflammatory milieu and underpins the role of the IL-6/IL-10 axis.


The PECAn image and statistical analysis pipeline identifies Minute cell competition genes and features.
Investigating organ biology often requires methodologies to induce genetically distinct clones within a living tissue. However, the 3D nature of clones makes sample image analysis challenging and slow, limiting the amount of information that can be extracted manually. Here we develop PECAn, a pipeline for image processing and statistical data analysis of complex multi-genotype 3D images. PECAn includes data handling, machine-learning-enabled segmentation, multivariant statistical analysis, and graph generation. This enables researchers to perform rigorous analyses rapidly and at scale, without requiring programming skills. We demonstrate the power of this pipeline by applying it to the study of Minute cell competition. We find an unappreciated sexual dimorphism in Minute cell growth in competing wing discs and identify, by statistical regression analysis, tissue parameters that model and correlate with competitive death. Furthermore, using PECAn, we identify several genes with a role in cell competition by conducting an RNAi-based screen.


Interaction between neuropeptide FF and opioids in the ventral tegmental area in the behavioral response to novelty.
Considerable evidence has focused on the interaction between endogenous opioid peptides and the dopaminergic mesocorticolimbic system in behavioral responses to stress. Recently, it has been proposed that the CNS synthesizes and secretes neuropeptides that act as part of a homeostatic system to attenuate the effects of morphine or endogenous opioid peptides. Among these antiopioids, neuropeptide FF (NPFF) is particularly interesting since both NPFF immunoreactive-like terminals and NPFF binding sites are located in the vicinity of the dopaminergic cell bodies within the ventral tegmental area (VTA) suggesting an interaction at this level. The purpose of the present study was to evaluate the respective implication of opioid and antiopioid peptides at the level of the VTA in the locomotor response to novelty in rats. The results indicate that s.c. naloxone pretreatment, an opiate receptor antagonist, reduced locomotor activity in rats placed in a novel environment without having any effect in a familiar environment. This effect takes place in the VTA since intra-VTA administration of naloxone methobromide diminished similarly and dose-dependently the motor response to novelty. This effect is mainly dependent on opioid peptides released at VTA level since local injections of thiorphan, an inhibitor of enkephalin degradation, strongly increased locomotor response to novelty and this effect is completely prevented by the co-administration of naloxone methobromide. When injected in the VTA, NPFF is acting as an antiopioid compound, i.e. it reduces the locomotor activity triggered by exposure to novelty to the level recorded in a familiar environment. Moreover, NPFF decreased dose-dependently the potentiation of novelty-induced locomotor response produced by VTA injection of thiorphan. Taken together, these results suggest that NPFF neurons may participate at the level of the VTA to a homeostatic regulating process counteracting opioid effects induced by a mild stress such as novelty.


Understanding bruxism in children and adolescents.
Screening for the various forms of bruxism in children and adolescents requires a sound knowledge of the physiopathology of this parafunction in addition to the etiologic and associated factors and comorbidities. The international literature contains various suggestions for suitable treatment. The optimal therapeutic approach often involves multidisciplinary management of these young patients. Sleep bruxism (SB) is a common sleep disorder which can cause serious problems to the stomatognathic system such as damaged teeth, headaches, muscle pain and TMD. Dental professionals are responsible for the detection and prevention of these harmful impacts on the patient's oral health. However, SB is much more than a question of worn teeth. Patients with SB consult for other medical comorbidities such as nighttime breathing problems, insomnia, attention deficit hyperactivity disorder, depression, moodiness and gastroesophogeal reflux before any course of treatment is initiated. If a comorbidity is diagnosed, the treatment approach will be aimed in the first instance at the medical disorder, while concurrently managing the repercussions of SB. On the other hand, in as far as the majority of young bruxers cease to grind their teeth before adolescence or adulthood, it is feasible to adopt wait-and-see and non-interventionist strategies for young children. However, it is preferable to have a better understanding of SB, notably on account of its potential association with psychological disorders during childhood. Daytime bruxism is characterized by teeth clenching (TC). First-line treatment involves encouraging patients to monitor their harmful parafunctional behavior and, consequently, change and cease it. This protocol is not always easy to apply, particularly in younger children. In such cases, cognitive-behavioral treatments and biofeedback techniques can also be used in daytime bruxism.


Supramolecular Iron Metallocubanes Exhibiting Site-Selective Thermal and Light-Induced Spin-Crossover.
Treatment of Fe[BF4]2·6H2O with 4,6-di(pyrazol-1-yl)-1H-pyrimid-2-one (HL1) or 4,6-di(4-methylpyrazol-1-yl)-1H-pyrimid-2-one (HL2) affords solvated crystals of [{FeIII(OH2)6}⊂FeII8(μ-L)12][BF4]7 (1, HL = HL1; 2, HL = HL2). The centrosymmetric complexes contain a cubic arrangement of iron(II) centers, with bis-bidentate [L]- ligands bridging the edges of the cube. The encapsulated [Fe(OH2)6]3+ moiety templates the assembly through 12 O-H···O hydrogen bonds to the [L]- hydroxylate groups. All four unique iron(II) ions in the cages are crystallographically high-spin at 250 K, but they undergo a gradual high → low spin-crossover on cooling, which is predominantly centered on one iron(II) site and its symmetry-related congener. This was confirmed by magnetic susceptibility data, light-induced excited spin state trapping (LIESST) effect measurements, and, for 1, Mössbauer spectroscopy and diffuse reflectance data. The clusters are stable in MeCN solution, and 1 remains high-spin above 240 K in that solvent. The cubane assembly was not obtained from reactions using other iron(II) salts or 4,6-di(pyrazol-1-yl)pyrimidine ligands, highlighting the importance of hydrogen bonding in templating the cubane assembly.


Human cytomegalovirus US2 causes similar effects on both major histocompatibility complex class I and II proteins in epithelial and glial cells.
The human cytomegalovirus (HCMV) glycoprotein US2 specifically binds to major histocompatibility complex (MHC) class I heavy chain (HC) and class II proteins DRalpha and DMalpha, triggering their degradation by proteasomes. Effects of US2 on class II proteins were originally characterized in HCMV- or adenovirus vector-infected U373 astroglioma cells. Here, we have extended characterization of US2-mediated degradation of class II DRalpha to two other cell lines, including biologically relevant epithelial cells. Comparison of the effects of US2 in cells expressing both class I and II proteins demonstrated only a slight preference for class I HC. Moreover, US2 caused degradation of DRalpha and DMalpha when these proteins were expressed by transfection without DRbeta, invariant chain (Ii), or DMbeta. Therefore, US2 binds to alpha chains of DR and DM and triggers endoplasmic reticulum degradation without formation of class II DR alphabeta/Ii or DM alphabeta complexes. Similar levels of degradation of class II alpha were observed in cells expressing vastly different amounts of class II, suggesting that cellular factors, other than class II, were limiting. We concluded that US2 has broad effects in a variety of cells that express both class I and II proteins and is relevant to HCMV infection in vivo.


Differentiation of proactivator from tissue plasminogen activator with low molecular weight in the paranasal mucous membrane.
It has been shown that large amounts of fibrinolytic enzyme are contained in tissue extracts of the paranasal mucous membrane in patients with chronic sinusitis. However, the fibrinolytic enzyme in the tissue extracts has not yet been characterized by biochemical techniques. In the present study, proactivator was differentiated from tissue plasminogen activator with low molecular weight in extracts of the paranasal mucous membrane and the existence of the proactivator was thus demonstrated in tissue extracts. By analogy with the proactivator in antrochoanal polyps, this proactivator may play an important role in the proliferation and enlargement of the paranasal mucous membrane.


Return of individual research results and incidental findings in the clinical trials cooperative group setting.
The National Cancer Institute (NCI)-funded cooperative group cancer clinical trial system develops experimental therapies and often collects samples from patients for correlative research. The cooperative group bank (CGB) system maintains biobanks with a current policy not to return research results to individuals. An online survey was created, and 10 directors of CGBs completed the surveys asking about understanding and attitudes in changing policies to consider return of incidental findings (IFs) and individual research results (IRRs) of health significance. The potential impact of the 10 consensus recommendations of Wolf et al. presented in this issue are examined. Reidentification of samples is often not problematic; however, changes to the current banking and clinical trial systems would require significant effort to fulfill an obligation of recontact of subjects. Additional resources, as well as a national advisory board would be required to standardize implementation.


Internet and healthcare in Brazil: the role of the Working Group for Healthcare (GT Saúde).
This paper introduces the GT Saúde initiative in Brazil. The group is part of the Brazilian Internet project, which goals are to depict how Internet can be useful to the society. The mission of the GT Saúde group is to foster Internet applications on the healthcare area. The main projects currently under development are presented: Multicom-21, using large bandwidth connections on telemedicine; the Unified Health Record, using Internet and smart-cards for a national minimum patient data set; the Brazilian Virtual Hospital, that presents a large amount of useful information and links for healthcare professionals and people in general; the National Healthcare Information Network (RNIS), that uses Internet as a medium for data exchange among the state secretaries and publishing statistics from the national healthcare system (SUS) for general public access; and finally the virtual university proposal, which uses Internet for education and is offering its first course on nutrition. The heterogeneity of the projects is meant and is part of the group's task, which is to cover the subject as widely as possible. Through this 'demonstration' projects the group is trying to prove the usefulness and benefits of using Internet technologies, even (or mainly) on a developing country with an inadequate healthcare situation. In its short existence the GT Saúde group has achieved several of its original goals. The most relevant accomplishments are: putting together different groups, eliciting synergy across the projects and encompassing a broad spectrum of applications (the 'demonstration factor').


Similarity information versus relational information: differences in the time course of retrieval.
Two experiments are reported that examine the time course of retrieval in a sentence matching procedure. Subjects learned lists of active and passive sentences and were tested with sentences in active or passive, correct or incorrect versions; for example, if "John hit Bill" was a studied sentence, "Bill hit John" would be an incorrect active test sentence. A response signal procedure was used so that accuracy could be measured as a function of time. The data show that sentences containing words from studied sentences are discriminable early in processing from sentences containing all new words, but discrimination of correct from incorrect versions of studied sentences occurs only later in processing (after 600-700 ms). These results demonstrate that different kinds of information are available at different points during the time course of retrieval and so suggest that modifications are required of models that provide only a unitary value for the amount of match between a test probe and information in memory. Early in processing, the growth of accuracy can be explained by a simple model that assumes independent contributions to total amount of match for each of the content words of a sentence, but this independent processing model cannot account for discrimination later in processing. Several, more general, memory models are examined with respect to their abilities to produce independent item information early in processing and relational information later in processing.


Progression from idiopathic portal hypertension to incomplete septal cirrhosis with liver failure requiring liver transplantation.
We report the case of a 30-year-old male patient suffering from what was initially thought to be end-stage cryptogenic cirrhosis with portal hypertension and liver failure, who underwent liver transplantation. Histological examination of the surgical specimen showed incomplete septal cirrhosis. At the age of 17 this patient had presented pancytopenia and splenomegaly, which were treated by splenectomy. The surgeon discovered portal hypertension. Re-examination of the wedge liver biopsy taken at this time revealed features of idiopathic portal hypertension. This case clearly shows that incomplete septal cirrhosis may be a late manifestation of idiopathic portal hypertension. The presence of sinusoidal dilatation and peliosis as well as early evidence of fibrosis which are already visible on the initial biopsy and are still present on the late specimen, are indirect evidence of a continuous process which ultimately led to incomplete cirrhosis with liver failure.


Is it safe to switch between efavirenz and nevirapine in the event of toxicity?
The non-nucleoside reverse transcriptase inhibitors (NNRTIs) efavirenz and nevirapine are chemically distinct, but both may cause cutaneous hypersensitivity and hepatotoxicity. We reviewed the literature to assess the evidence for cross-reactivity between nevirapine and efavirenz. All papers, abstracts, or presentations, regardless of study design, that made reference to the response of patients who were switched from one NNRTI to another as a result of an adverse drug reaction were included. Most of the studies were retrospective. Recurrent reactions occurred in 30 (12.6%) of 239 reported patients with rash who were switched from nevirapine to efavirenz, compared with eight (50%) of 16 patients switched from efavirenz to nevirapine. Hepatitis did not recur in either the 11 reported patients switched from nevirapine to efavirenz, or in the single reported patient who was switched from efavirenz to nevirapine. Substituting efavirenz for nevirapine following hepatotoxicity or cutaneous hypersensitivity appears to be reasonable, providing that the adverse reaction to nevirapine was not life-threatening. There is insufficient evidence to recommend substituting nevirapine for efavirenz following either hepatotoxicity or cutaneous hypersensitivity.


Synbiotics: a New Route of Self-production and Applications to Human and Animal Health.
Synbiotics are preparations in which prebiotics are added to probiotics to achieve superior performance and benefits on the host. A new route of their formation is to induce the prebiotic biosynthesis within the probiotic for synbiotic self-production or autologous synbiotics. The aim of this review paper is first to overview the basic concept and (updated) definitions of synergistic synbiotics, and then to focus particularly on the prebiotic properties of probiotic wall components while describing the environmental factors/stresses that stimulate autologous synbiotics, that is, the biosynthesis of prebiotic-forming microcapsule by probiotic bacteria, and finally to present some of their applications to human and animal health.


Postnatal laboratory timers of antenatal hypoxemic-ischemic brain damage.
Markers were sought to identify the antenatal starting times and rates at which brain damage advanced in children with hypoxemic-ischemic cerebral palsy. Fetal bradycardia's onset marked the damage's start. Using this baseline, the following were tested as additional timers of the damage's onset: serial blood counts of neonates' normoblasts, platelets, lymphocytes,differences at birth between base excess values in umbilical arterial and venous bloods,brain damage patterns. Each timer had a broad antenatal time frame within which it could identify specific damage starting times. The broad time frames are as follows: Blood lymphocyte counts: 0.45 to 13.8 hours before birth, blood normoblast counts: 0.45 to 55.0 hours before birth, blood platelet counts: 0.5 to >72 hours before birth. Brain damage patterns: 0.4 to >0.7 hour before birth. Hyperventilating and hyperoxygenating neonates greatly accelerated the damage's advance. Commonly obtained laboratory values and brain images can identify when such brain damage began and the rate at which it advanced.


Biochemical, cellular and structural characterization of novel and selective ERK3 inhibitors.
Triazolo[4,5-d]pyrimidin-5-amines were identified from kinase selectivity screening as novel ERK3 inhibitors with sub-100 nanomolar potencies in a biochemical assay using MK5 as substrate and with an attractive kinase selectivity profile. ERK3 crystal structures clarified the inhibitor binding mode in the ATP pocket with impact on A-loop, GC-loop and αC-helix conformations suggesting a potential structural link towards MK5 interaction via the FHIEDE motif. The inhibitors also showed sub-100 nM potencies in a cellular ERK3 NanoBRET assay and with excellent correlation to the biochemical IC50s. This novel series provides valuable tool compounds to further investigate the biological function and activation mechanism of ERK3.


Effects of weightlessness on bone mass and osteoclast number in pregnant rats after a five-day spaceflight (COSMOS 1514).
Five pregnant growing rats were orbited for 5 days aboard the Soviet COSMOS 1514 biologic satellite. The bone effects of weightlessness were studied and compared to those of five pregnant rats kept in vivarium and five pregnant conditioned rats. Bone histomorphometric studies were performed to investigate the early effects of weightlessness in loaded (tibia-femur) and unloaded (thoracic and lumbar vertebrae) bones. A short exposure to weightlessness does not induce any change in bone mass and inner structure in either type of bone. In unloaded bones, the number of osteoclasts per square millimeter of the trabecular surface significantly increased when measured after histochemical demonstration of tartrate-resistant acid phosphatase. It is likely that a stimulation of bone resorption activity occurs in the trabeculae of unloaded bones during the early phase of a spaceflight. In tibia, osteoid seam thickness and total osteoclastic resorption surfaces at the endosteal level were not modified.


Disruption of the left anterior ventrolateral temporal cortex along with the inferior longitudinal fasciculus impairs the ability to retrieve famous face names: Evidence from three longitudinal case studies.
The cortical distribution of the proper name (PN) retrieval network has been widely studied contrary to its connectional anatomy. Here, we report the case of three patients with a low-grade glioma damaging the mid-to-anterior part of the left temporal lobe. A longitudinal behavioural assessment showed that the surgery caused a long-lasting decline in PN retrieval performances in all patients. Furthermore, a detailed analysis of surgery-related structural disconnections revealed that interruption of the inferior longitudinal fasciculus was the unique common denominator.


Heterogeneity of Multimedia Exposures to Neurotoxic Elements (Al, As, Cd, Pb, Mn, and Hg) in Breastfed Infants from Porto Velho, Brazil.
Infant exposure to neurotoxic elements is a public health issue that needs monitoring with regard to breast milk composition. We studied six neurotoxic elements in breast milk samples at different stages of lactation in mothers from Porto Velho, Brazil. We used a flow-injection mercury system (FIMS) to determine total Hg concentrations and an inductively coupled plasma optical emission spectrometer (ICP-OES) to determine the concentrations of Al, As, Cd, Pb, and Mn in 106 donors of a human milk bank. Association rules analyses were applied to determine the pattern of binary and ternary mixtures of the measured exposants. The metal concentration was mostly below the limit of detection (LOD) for Cd (99%), Pb (84%), and Hg (72%), and it was above the LOD for As (53%), Mn (60%), and Al (82%), respectively. Median concentrations (dry weight) of Al, As, Hg, Mn, and Pb were 1.81 μg/g, 13.8 ng/g, 7.1 ng/g, 51.1 ng/g, and 0.43 μg/g, respectively. Al is singly the most frequent element to which infants are exposed. Occurring binary combination (> LOD) was 56% for Al-Mn, 41% for Al-As, 22% for Al-Hg, and 13% for Al-Pb. In 100% of neonates, exposure to Al-ethylmercury (EtHg) occurred through immunization with thimerosal-containing vaccines (TCV). Association rules analysis revealed that Al was present in all of the multilevel combinations and hierarchical levels and that it showed a strong link with other neurotoxic elements (especially with Mn, As, and Hg). (a) Nursing infants are exposed to combinations of neurotoxicants by different routes, dosages, and at different stages of development; (b) In breastfed infants, the binary exposures to Al and total Hg can occur through breast milk and additionally through TCV (EtHg and Al);


Aminopyrine--an effective modifier of liver and serum gamma glutamyl transpeptidase.
Serum activities of gamma glutamyl transpeptidase, alanine and aspartate aminotransferases, and alkaline phosphatase were determined in children on long-term treatment with aminopyrine. Gamma glutamyl transpeptidase activity was increased up to 15 times above the upper normal limit in children, who received aminopyrine for two weeks or longer. Livers of rats treated with aminopyrine (600 mg/kg/day for 18 to 25 days) had an exceedingly increased activity of gamma glutamyl transpeptidase and a slightly elevated microsomal cytochrome P-450 content. Apparently isolated enhancement of serum gamma glutamyl transpeptidase during aminopyrine medication represents a drug-induced increase of microsomal liver enzymes without clinical relevance and without evidence of damage of liver cells.


Responses of subtidal benthos of the Strait of Georgia, British Columbia, Canada to ambient sediment conditions and natural and anthropogenic depositions.
Patterns in infaunal biota in the Strait of Georgia are explored relative to water depth, substrate type, organic content of sediments and sedimentation characteristics. The analyses are based on geographically-diverse grab and core data collected over a 19-year period. Infaunal abundance and biomass were not predictable by sediment particle size, organic content or water depth. While organic flux was a reasonable predictor of biotic factors, quality of organic material, relative proportions of organic and inorganic input and source of inputs were also important in this regard. Areas with high accumulation of sediment and high organic flux rates from terrestrial (riverine) sources supported the highest macro-infaunal abundance and biomass found to date in the Strait of Georgia, and were dominated by bivalves. Polychaetes dominated in low organic deposition conditions, and where anthropogenic organic deposition was high. However, biota were severely impoverished in sediments with high organic content from marine deposition, due to low fluxes and poor quality of organic material. Taxa number was related to percent total nitrogen and to the ratio of organic/inorganic flux, both in background conditions and where there was labile organic enrichment. Faunal communities from the Fraser River delta, which experiences considerable bottom-transported riverine material, were very different in composition from those that proliferate in habitats with high deposition and organic flux from the water column.


FAP-retargeted Ad5 enables in vivo gene delivery to stromal cells in the tumor microenvironment.
Fibroblast activation protein (FAP) is a cell surface serine protease that is highly expressed on reactive stromal fibroblasts, such as cancer-associated fibroblasts (CAFs), and generally absent in healthy adult tissues. FAP expression in the tumor stroma has been detected in more than 90% of all carcinomas, rendering CAFs excellent target cells for a tumor site-specific adenoviral delivery of cancer therapeutics. Here, we present a tropism-modified human adenovirus 5 (Ad5) vector that targets FAP through trivalent, designed ankyrin repeat protein-based retargeting adapters. We describe the development and validation of these adapters via cell-based screening assays and demonstrate adapter-mediated Ad5 retargeting to FAP+ fibroblasts in vitro and in vivo. We further show efficient in vivo delivery and in situ production of a therapeutic payload by CAFs in the tumor microenvironment (TME), resulting in attenuated tumor growth. We thus propose using our FAP-Ad5 vector to convert CAFs into a "biofactory," secreting encoded cancer therapeutics into the TME to enable a safe and effective cancer treatment.


[Coma and communication].
Communication around a comatose patient is a touchy subject. In the event of a breakdown in this interaction, there is a risk of a strained relationship being established between the nurses, the patient and their family, a source of conflicts or value judge ments. The objective of appropriate communication is to place the patient back at the centre of the relationship.


Intensity-modulated radiation therapy for definitive treatment of cervical cancer: a meta-analysis.
To compare the efficacies and toxicities of intensity-modulated radiotherapy (IMRT) with three-dimensional conformal radiotherapy (3D-CRT) or conventional two-dimensional radiotherapy (2D-RT) for definitive treatment of cervical cancer. A meta-analysis was performed using search engines, including PubMed, Cochrane Library, Web of Science, and Elsevier. In the meta-analysis, odds ratios (ORs) were compared for overall survival (OS), disease-free survival (DFS), and acute and chronic toxicities. Included data were analysed using RevMan 5.2 software. Six studies encompassing a total of 1008 patients who received definitive treatment (IMRT = 350, 3-DCRT/2D-RT = 658) were included in the analysis. A comparison of 3-year OS and 3-year DFS revealed no significant differences between IMRT and 3D-CRT or 2D-RT (3-year OS: OR = 2.41, 95% confidence interval [CI]: 0.62-9.39, p = 0.21; 3-year DFS: OR = 1.44, 95% CI: 0.69-3.01, p = 0.33). The incidence of acute gastrointestinal (GI) toxicity and genitourinary (GU) toxicity in patients who received IMRT was significantly lower than that in the control group (GI: Grade 2: OR = 0.5, 95% CI: 0.28-0.89, p = 0.02; Grade 3 or higher: OR = 0.55, 95% CI: 0.32-0.95, p = 0.03; GU: Grade 2: OR = 0.41, 95% CI: 0.2-0.84; p = 0.01; Grade 3 or higher: OR = 0.31, 95% CI: 0.14-0.67, p = 0.003). Moreover, the IMRT patients experienced fewer incidences of chronic GU toxicity than did the control group (Grade 3: OR = 0.09, 95% CI: 0.01-0.67, p = 0.02). IMRT and conventional radiotherapy demonstrated equivalent efficacy in terms of 3-year OS and DFS. Additionally, IMRT significantly reduced acute GI and GU toxicities as well as chronic GU toxicity in patients with cervical cancer.


Chemotherapy extravasation: a consequence of fibrin sheath formation around venous access devices.
To describe, using two case studies, chemotherapy drug extravasation as a consequence of fibrin sheath formation. Journal articles, textbooks, medical records, and personal experiences. Fibrin sheath formation around venous access devices (VADs) frequently leads to persistent withdrawal occlusion (PWO). While PWO often is easily managed with small doses of thrombolytic therapy (e.g., urokinase), it may result in a more serious complication, such as chemotherapy extravasation. Chemotherapy should not be administered through a VAD unless a free-flowing blood return can be demonstrated. Careful nursing assessment of all VADs is important to identify complications such as fibrin sheath formation. To rule out fibrin sheath formation, nurses must obtain catheter dye studies when fibrinolytic therapy fails to restore catheter function.


Biomarkers of Immunosuppression.
It is now recognized that sepsis is not a uniformly proinflammatory state. There is a well-recognized counter anti-inflammatory response that occurs in many patients. The timing and magnitude of this response varies considerably and thus makes its identification and manipulation more difficult. Studies in animals and humans have now identified a small number of biologic responses that characterize this immunosuppressed state, such as lymphocyte death, HLA receptor downregulation, and monocyte exhaustion. Researchers are now trying to use these as markers of individual immunosuppression to predict outcomes and identify patients who would and would not benefit from new immune stimulatory therapies.


Implementing AORN Recommended Practices for Laser Safety.
Lasers used in the OR pose many risks to both patients and personnel. AORN's "Recommended practices for laser safety in perioperative practice settings" identifies the potential hazards associated with laser use, such as eye damage and fire- and smoke-related injuries. The practice recommendations are intended to be used as a guide for establishing best practices in the workplace and to give perioperative nurses strategies for implementing the recommended safety measures. A laser safety program should include measures to control access to laser use areas; protect staff members and patients from exposure to the laser beam; provide staff members and patients with the appropriate safety eyewear for use in the laser use area; and protect staff members and patients from surgical smoke, electrical, and fire hazards. Measures such as using a safety checklist or creating a laser cart can help perioperative nurses successfully incorporate the practice recommendations. Patient scenarios are included as examples of how to use the document in real-life situations.


Detection of specific murine anti-tumour immunity and serum factors by the indirect E-rosette augmentation assay.
The spontaneous interaction of sheep erythrocytes and human lymphocytes results in the formation of aggregates known as E-rosettes. The antigen reactivity of murine T-lymphocytes can be detected indirectly by the production of a lymphokine that augments the E-rosette-forming ability of human lymphocytes. An indirect E-rosette augmentation (ERA) assay was used to study cellular reactivity and tumour-related serum reactions in mice bearing methylcholanthrene (MCA)-induced tumours. The assay was used to demonstrate the antigenic specificity of two tumours and to detect blocking factors in tumour-bearer serum. Blocking factors were shown to be tumour-specific and to act on lymphocytes at an early stage before exposure to antigen.


Expression of highly polysialylated neural cell adhesion molecule in rat subventricular zone with exposure to repeated kindled seizures.
Immunoreactive highly polysialylated neural cell adhesion molecule (PSA-NCAM) expression was examined in the rat with repeated exposure to amygdaloid kindled generalized seizures (GS). In the sham control brain, PSA-NCAM staining was slightly observed in the subventricular zone (SVZ) of the striatum. The number of PSA-NCAM positive cells increased four times in the bilateral SVZ after three consecutive GS, with a further increase after 30 consecutive GS. As PSA-NCAM is involved in neural plasticity as well as migration of neural stem cells (NSC), expression of PSA-NCAM in the SVZ suggests that the recurrent GS may mainly contribute to reconstruction of synaptic network and could also contribute to NSC migration after kindling.


Detection of Vibrio parahaemolyticus in shellfish using polymerase chain reaction-enzyme-linked immunosorbent assay.
This study evaluated the application of polymerase chain reaction-enzyme-linked immunosorbent assay (PCR-ELISA) for the detection of Vibrio parahaemolyticus in shellfish. The PCRs were selected to amplify a species-specific sequence region. In particular, internal tl biotin-labelled oligonucleotide probe was used to capture the DIG-labelled PCR products. Next, the probe PCR product hybrids, immobilized on a streptavidin-coated microtiter plate, were detected with peroxidase-conjugated anti-digoxigenin antibody (anti-DIG-POD) and the colorimetric peroxidase substrate ABTS [2,2'-azino-bis(3-ethylbenzthiazoline-6-sulphonic acid)] using an ELISA plate reader. The PCR-ELISA system described is a feasible, sensitive method for the direct and specific detection of V. parahaemolyticus in shellfish samples. Compared with gel-based detection methods, PCR-ELISA in this study increased sensitivity by 100-fold for V. parahaemolyticus. The PCR-ELISA described may be used for potential rapid detection in routine shellfish analysis for the seafood industry. The sector requires simultaneous large-scale sample screenings to monitor contamination levels in processing plants and evaluate the performance of the hazard analysis and critical control point (HACCP) system. PCR-ELISA also proved to be economical, with a cost of about 9 Euros per sample, and the quick assay taking 8 h to complete starting from DNA extraction.


Study on the primary visual cortex of visually impaired subjects by means of 123I-IMP SPECT and MRI.
We conducted a study of rCBF in the primary visual cortex of visually impaired subjects who have not been subjected to external stimulation for a long period, by means of 123I-IMP SPECT and MRI. The four subjects had lost their sight due to brain tumors (n = 2), glaucoma (n = 1) and trauma (n = 1). 123I-IMP SPECT showed no differences between the visually impaired group and a visually sound control group on visual analysis as well as semiquantitative analysis. MRI of the visually impaired subjects showed no organic changes, such as atrophy, in the occipital cortex. In conclusion, visually impaired subjects have no decrease in rCBF and no anatomical changes in the primary visual cortex.


Toxicity of gossypol at antifertility dosages in male rats: statistical analysis of lethal rates and body weight responses.
The lethal rates and body weight responses of male Wistar rats following oral treatment with gossypol acetic acid (GAA) at dosages of 2.5-30 mg/kg were analysed by various statistical procedures. Daily treatment with GAA for 10 weeks was associated with lethal rates significantly different from placebo groups in both the low dose (2.5, 5.0, and 7.5 mg/kg, p less than 0.05) and high dose groups (15, 20 and 30 mg/kg, p less than 0.01). The pronounced mean body weight gain observed in placebo groups, was suppressed in the GAA-treated groups at each dose level after 10 weeks. This indicates decreased appetite and/or lessened feed utilisation caused by GAA activity. GAA administration at a dose of 30 mg/kg every other day exerted identical deleterious effects as daily treatment. As derived from the antifertility responses of the GAA treatment groups it was evident that the toxic activity of GAA was not related to its antifertility efficacy. It is concluded that GAA has remarkable toxicity at antifertility dosages in rats.


Endoluminal thoracic aortic repair: does the parachute need to be randomized?
Development of endoluminal repair has substantially reduced mortality and morbidity associated with repair of the thoracic aorta. It has significant advantages over conventional surgical repair, particularly in the management of acute dissection and thoracic aortic injury. Despite these perceived advantages it is important to realize that no level 1 data are available to prove safety and/or efficacy. Because the advantages are perceived to be so great these data are unable to be accrued and it is important that clinicians involved with this procedure keep rigorous data and undertake ongoing evaluation to ensure that clinical perceptions are eventually underpinned by robust data.


Endotracheal metallic stent removal: A novel ABC (airway balloon collapse) technique.
To illustrate a previously unreported method of tracheal stent removal that appears to cause less mucosal injury we present a case of a 9-year-old Down syndrome patient with a history of tracheoesophageal fistula, brought to our attention after recurrent bouts of exacerbating cough and tracheo-bronchitis. Endoscopic examination under general anesthesia noted the presence of severe tracheomalacia with inspiratory collapse, and a 10-mm balloon expandable metallic stent (BEMS) was deployed and symptomatic improvement was noted. The initial stent was then removed to consider a definitive procedure using the typical grasping fashion with an alligator forceps and expected mucosal excoriation was noted. Due to symptom recurrence, the patient underwent placement of a second BEMS stent. Initial improvement was noted followed by recurrent episodes of respiratory distress due to granulation tissue formation and stent compression and a decision to remove the stent was made. A new method of stent removal deemed ABC (airway balloon collapse) method was utilized where an expandable airway balloon is placed outside the stent between the stent and tracheal wall and then inflated to collapse the stent, facilitating easy removal.


Primary structures of hemagglutinin-esterase and spike glycoproteins of murine coronavirus DVIM.
Diarrhea virus of infant mice (DVIM) is a member of murine hepatitis viruses (MHVs). The nucleotide sequences of the genes encoding the hemagglutinin-esterase (HE) and the spike (S) glycoproteins from DVIM were determined and compared with those of other MHVs. The deduced amino acid sequence of the HE protein was most similar to that of MHV-S strain (94% identity), and the S protein sequence was most similar to that of MHV-Y strain (90% identity). The DVIM HE protein has a unique N-linked glycosylation site in addition to other glycosylation sites common to many MHV strains. Unlike in some typical MHV strain, such as MHV-A59 and MHV-JHM, the vast majority of the S glycoprotein molecules in DVIM exist an uncleaved form probably due to several amino acid substitutions around the cleavage site.


The significance of the ratio of blood to marrow hematopoietic progenitors (CFU-GM and CFU-GEMM) in relation to disease state of patients with acute lymphoblastic leukemia.
We studied a total of 143 patients with 231 assays of CFU-GM, of these, 45 patients were studied with 58 simultaneous assays of CFU-GEMM in an attempt to correlate progenitor colony growth with disease state. Blood and marrow leukocytes were cultured in a standard methylcellulose culture system using normal human leukocyte colony stimulating activity. Results are expressed as natural logarithm of the ratio of blood colonies to marrow colonies. A high ratio of blood to marrow (greater than 1) was seen in active disease while a low ratio occurred during remission. Eighty-seven per cent of CFU-GM matched pair samples with active disease had high ratios while less than 1% of remission samples were high. In addition, patients with suspected relapse or relapse up to 14 months after this test often had high ratios indicating this test could be of prognostic value. It is not known if this effect of ALL is unique to ALL or if it occurs as a reaction to any hematopoietic stress.


Noninvasive measurement of systemic arterial blood pressure in the conscious beagle dog.
The objectives of this study were to evaluate a technique for routine, noninvasive measurement of systemic arterial blood pressure and heart rate (HR) in conscious Beagle dogs for toxicologic research. HR, systolic, diastolic, and mean arterial (MAP) pressures were measured with a DINAMAP research monitor (Model 1255, Critikon, Inc.) as follows: Dogs were restrained in a Harvard dog sling, a neonatal cuff was wrapped around the base of the tail, and blood pressure and HR were determined once a minute. Initially, normal values were obtained, 5-10 trials/session, one to three sessions/day for 15 days in six dogs. The day to day, session to session, and trial variabilities were determined and found to be minimal. The day to day diastolic pressure ranged from 74 +/- 18 to 91 +/- 13 mm Hg, systolic pressure from 125 +/- 25 to 156 +/- 22 mm Hg, MAP from 94 +/- 20 to 113 +/- 15 mm Hg, and HR from 111 +/- 21 to 126 +/- 24 beats/minute (bpm). The effects of various drugs on these parameters were determined. Norepinephrine increased diastolic, systolic, and MAP by 75 to 110 mm Hg and decreased HR by half. Epinephrine increased HR by 20 bpm. Phentolamine decreased diastolic, systolic, and MAP by up to 25 mm Hg. Isoproterenol increased HR by up to 130 bpm and decreased diastolic, systolic, and MAP by 20 mm Hg. In addition, the effect of a classic drug interaction on these parameters was determined. When dogs pretreated with the monoamine oxidase inhibitor tranylcypromine were challenged with tyramine, diastolic, systolic, and MAP pressures were increased, whereas HR was decreased.(ABSTRACT TRUNCATED AT 250 WORDS)


Evaluating rates of reporting symptoms of Parkinson's disease psychosis: provider versus targeted questionnaire.
A targeted questionnaire may help increase rates of reporting Parkinson's disease psychosis (PDP) symptoms. Despite the need for a rapid patient- and/or caregiver-administered screening tool for PDP symptoms, an appropriate tool is not yet available. This study developed a targeted PDP questionnaire and examined rates of reporting psychosis symptoms in response to the questionnaire compared to rates of reporting symptoms to healthcare providers during a routine visit. This was a single-center, cross-sectional observational study of patients at an outpatient neurology practice. Medical charts were screened for eligibility, and patients were contacted by telephone for informed consent. A total of 25 patients (24%, N = 104) newly reported PDP symptoms in response to the targeted questionnaire. The frequency of reporting new symptoms in response to the questionnaire was statistically significantly greater compared to frequency of reporting symptoms without use of a targeted questionnaire (p < 0.0001). A targeted questionnaire increases rates of reporting PDP symptoms, and based on frequency, severity, and distress ratings, may allow for capture of PDP symptoms earlier in the course of the disease. By using a questionnaire, patients reported symptom onset an average of 1.4 years earlier than patients who reported symptoms to their providers according to patient medical records.


[Congenital pulmonary lymphangiectasia revealed by cardiac arrest].
Congenital pulmonary lymphangiectasia is a rare cause of respiratory distress in the neonatal period. Cardiac arrest may be its first manifestation. We report the case of a full term newborn who suffered at 30 min of life a sudden cardiac arrest. Despite intensive support, the patient died 5 h later. Lung examination showed pulmonary lymphangiectasia. Congenital pulmonary lymphangiectasia may be revealed by a sudden neonatal cardiac arrest. Pulmonary lymphangiectasia should be suspected in any newborn who develops early in life an unexplained refractory hypoxemia with radiographic reticulonodular images and uni or bilateral pneumothorax. The diagnosis is established at lung microscopy.


Disruption of Brca2 increases the spontaneous mutation rate in vivo: synergism with ionizing radiation.
The breast cancer predisposition gene BRCA2 encodes a protein involved in the repair of DNA double-strand breaks, which arise spontaneously and following exposure to ionizing radiation (IR). To develop a mouse model that examines the effect of BRCA2 mutation and IR exposure on in vivo somatic mutation acquisition, we crossed mice with targeted disruption of Brca2 with a LacZ transgenic mutation reporter strain. Loss of both wild-type Brca2 alleles caused a 2.3-fold increase, equivalent to an extra 100 mutations per cell, in the in vivo acquisition of spontaneous somatic mutation by 2 weeks gestation. IR (4 Gy) had a disproportionate effect on animals homozygous for Brca2 disruption, inducing 3.4-fold more mutations compared with wild-type animals. These data provide the first evidence that loss of Brca2 increases in vivo somatic mutation acquisition and synergizes with IR exposure, with potential attendant implications for mammographic screening and therapeutic IR in mutation carriers.


A role for epigenetics in hearing: Establishment and maintenance of auditory specific gene expression patterns.
Epigenetics is a large and diverse field encompassing a number of different mechanisms essential to development, DNA stability and gene expression. DNA methylation and histone modifications work individually and in conjunction with each other leading to phenotypic changes. An overwhelming amount of evidence exists demonstrating the essential nature of epigenetics to human biology and pathology. This field has spawned a vast array of knowledge, techniques and pharmaceuticals designed to investigate and manipulate epigenetic phenomena. Despite its centricity to molecular biology, little work has been conducted examining how epigenetics affects hearing. In this review, we discuss both the basic tenets of epigenetics and highlight the most recent advances in this field. We discuss its importance to human development, genomic stability, gene expression, epigenetic modifying agents as well as briefly introduce the expansive field of cancer epigenetics. We then examine the evidence of a role for epigenetics in hearing related processes and hearing loss. The article concludes with a discussion of areas of epigenetic research that could be applied to hearing research.


A unified mathematical model to quantify performance impairment for both chronic sleep restriction and total sleep deprivation.
Performance prediction models based on the classical two-process model of sleep regulation are reasonably effective at predicting alertness and neurocognitive performance during total sleep deprivation (TSD). However, during sleep restriction (partial sleep loss) performance predictions based on such models have been found to be less accurate. Because most modern operational environments are predominantly characterized by chronic sleep restriction (CSR) rather than by episodic TSD, the practical utility of this class of models has been limited. To better quantify performance during both CSR and TSD, we developed a unified mathematical model that incorporates extant sleep debt as a function of a known sleep/wake history, with recent history exerting greater influence. This incorporation of sleep/wake history into the classical two-process model captures an individual's capacity to recover during sleep as a function of sleep debt and naturally bridges the continuum from CSR to TSD by reducing to the classical two-process model in the case of TSD. We validated the proposed unified model using psychomotor vigilance task data from three prior studies involving TSD, CSR, and sleep extension. We compared and contrasted the fits, within-study predictions, and across-study predictions from the unified model against predictions generated by two previously published models, and found that the unified model more accurately represented multiple experimental studies and consistently predicted sleep restriction scenarios better than the existing models. In addition, we found that the model parameters obtained by fitting TSD data could be used to predict performance in other sleep restriction scenarios for the same study populations, and vice versa. Furthermore, this model better accounted for the relatively slow recovery process that is known to characterize CSR, as well as the enhanced performance that has been shown to result from sleep banking.


Diagnostic, Prognostic, and Predictive Role of Next-Generation Sequencing in Mature Lymphoid Neoplasms.
Lymphoma is a clinically and biologically heterogeneous disease. Next-generation sequencing (NGS) has expanded our understanding of this heterogeneity at the genetic level, refining disease classification, defining new entities, and providing additional information that can be used in diagnosis and management. This review highlights some of the NGS findings in lymphoma and how they can be used as genetic biomarkers to aid diagnosis and prognosis and guide therapy.


Layer by layer self-assembly of poly[2-(methacryloyloxy) ethyl phosphorylcholine] multilayer via the ionic complexation with zirconium.
Zirconium-phosphonate (Zr-P) ionic complexation chemistry is explored as a new approach to fabricate poly[2-(methacryloyloxy) ethyl phosphorylcholine] (PMPC) multilayer film by layer-by-layer self-assembly method. Quartz crystal microbalance with dissipation (QCM-D) and optical ellipsometry measurements demonstrated that PMPC layer can be fully absorbed on each Zr(4+) layer. The thickness of the multilayer film with a good linear relationship was followed by the ellipsometry in situ adlayer characterization. The influence of pH of the PMPC and Zr(4+) solutions on the multilayer deposition were investigated by optical ellipsometry. QCM-D results indicated that the multilayer film is stable in a PBS flowing chamber at a high flow rate of 5.2×10(-3)m/s. The ellipsometry data demonstrated that 67.2% of the film still remained on the silicon wafer after being strong shaken in PBS at 80 rpm for 12h. The adsorption of bovine serum albumin (BSA) and fetal bovine serum (FBS) on the PMPC surface was monitored by the QCM-D and spectroscopic ellipsometry, and the results showed the multilayer film have excellent protein resistance.