A Walnut-Enriched Diet Reduces Lipids in Healthy Caucasian Subjects, Independent of Recommended Macronutrient Replacement and Time Point of Consumption: a Prospective, Randomized, Controlled Trial.
Studies indicate a positive association between walnut intake and improvements in plasma lipids. We evaluated the effect of an isocaloric replacement of macronutrients with walnuts and the time point of consumption on plasma lipids. We included 194 healthy subjects (134 females, age 63 ± 7 years, BMI 25.1 ± 4.0 kg/m²) in a randomized, controlled, prospective, cross-over study. Following a nut-free run-in period, subjects were randomized to two diet phases (8 weeks each). Ninety-six subjects first followed a walnut-enriched diet (43 g walnuts/day) and then switched to a nut-free diet. Ninety-eight subjects followed the diets in reverse order. Subjects were also randomized to either reduce carbohydrates (n = 62), fat (n = 65), or both (n = 67) during the walnut diet, and instructed to consume walnuts either as a meal or as a snack. The walnut diet resulted in a significant reduction in fasting cholesterol (walnut vs. -8.5 ± 37.2 vs. -1.1 ± 35.4 mg/dL; p = 0.002), non-HDL cholesterol (-10.3 ± 35.5 vs. -1.4 ± 33.1 mg/dL; p ≤ 0.001), LDL-cholesterol (-7.4 ± 32.4 vs. -1.7 ± 29.7 mg/dL; p = 0.029), triglycerides (-5.0 ± 47.5 vs. 3.7 ± 48.5 mg/dL; p = 0.015) and apoB (-6.7 ± 22.4 vs. -0.5 ± 37.7; p ≤ 0.001), while HDL-cholesterol and lipoprotein (a) did not change significantly. Neither macronutrient replacement nor time point of consumption significantly affected the effect of walnuts on lipids. Thus, 43 g walnuts/d improved the lipid profile independent of the recommended macronutrient replacement and the time point of consumption.


Network Science and Group Fusion Similarity-Based Searching to Explore the Chemical Space of Antiparasitic Peptides.
Antimicrobial peptides (AMPs) have appeared as promising compounds to treat a wide range of diseases. Their clinical potentialities reside in the wide range of mechanisms they can use for both killing microbes and modulating immune responses. However, the hugeness of the AMPs' chemical space (AMPCS), represented by more than 1065 unique sequences, has represented a big challenge for the discovery of new promising therapeutic peptides and for the identification of common structural motifs. Here, we introduce network science and a similarity searching approach to discover new promising AMPs, specifically antiparasitic peptides (APPs). We exploited the network-based representation of APPs' chemical space (APPCS) to retrieve valuable information by using three network types: chemical space (CSN), half-space proximal (HSPN), and metadata (METN). Some centrality measures were applied to identify in each network the most important and nonredundant peptides. Then, these central peptides were considered as queries (Qs) in group fusion similarity-based searches against a comprehensive collection of known AMPs, stored in the graph database StarPepDB, to propose new potential APPs. The performance of the resulting multiquery similarity-based search models (mQSSMs) was evaluated in five benchmarking data sets of APP/non-APPs. The predictions performed by the best mQSSM showed a strong-to-very-strong performance since their external Matthews correlation coefficient (MCC) values ranged from 0.834 to 0.965. Outstanding MCC values (>0.85) were attained by the mQSSM with 219 Qs from both networks CSN and HSPN with 0.5 as similarity threshold in external data sets. Then, the performance of our best mQSSM was compared with the APPs prediction servers AMPDiscover and AMPFun. The proposed model showed its relevance by outperforming state-of-the-art machine learning models to predict APPs. After applying the best mQSSM and additional filters on the non-APP space from StarPepDB, 95 AMPs were repurposed as potential APP hits. Due to the high sequence diversity of these peptides, different computational approaches were applied to identify relevant motifs for searching and designing new APPs. Lastly, we identified 11 promising APP lead candidates by using our best mQSSMs together with diversity-based network analyses, and 24 web servers for activity/toxicity and drug-like properties. These results support that network-based similarity searches can be an effective and reliable strategy to identify APPs. The proposed models and pipeline are freely available through the StarPep toolbox software at http://mobiosd-hub.com/starpep.


The initial effects of orthopedic forces: a study of alterations in the craniofacial complex of a macerated human skull owing to high-pull headgear traction.
The initial reaction of components of the craniofacial skeleton of a macerated human skull was studied after high-pull headgear traction. The applied forces were increased step by step from 0.5 N to 3.25 N per side (1N = 100 grams). Laser holography was used for measuring displacements in three dimensions in seventeen indicator points on the skull. These points were located near sutures or on the outer surface of individual bones. The skull was observed from the right frontal and from the left lateral side. Results indicate that displacements range from 0 micrometer to 17.0 micrometers, depending on force magnitude and on the location of the observed point. Individual components of the craniofacial skeleton were mostly displaced in a horizontal backward direction when the skull was viewed from the frontal aspect. Various compression and shearing patterns were observed in the craniofacial sutures, apparently depending on their spatial locations and intersutural surface morphology.


Smoking cessation counseling in dentistry: attitudes of Nigerian dentists and dental students.
The study was aimed at assessing the awareness, attitude, practices, willingness, and perceived barriers of dental students and dentists in Lagos University Teaching Hospital, Lagos, Nigeria, in relation to smoking cessation in the dental care setting. An anonymous self-administered questionnaire that contained questions relating to attitudes, views, and perceived barriers to smoking cessation activities in the dental clinic was hand-delivered to all dentists and clinical dental students in 2007. One hundred and thirty-six respondents took part in the study (response rate=81.9 percent). Although 95 percent of the respondents believed that smoking affects the dental management of the patient, only 65 percent always ask their patients about their smoking habits, and only 30 percent have heard about smoking cessation programs. A significantly higher proportion of students always ask patients about their smoking habits compared with dentists (p=0.0017). Also, a significantly higher proportion of dentists (97 percent) advised their patients against tobacco use compared with 77 percent of students (p=0.0000). Only 2 percent and 3 percent agreed that it is their professional responsibility to educate or encourage patients to quit smoking, respectively. Also, 98 percent strongly disagreed that it is within the scope of dental practice to ask about tobacco use, and 86 percent disagreed that tobacco counseling can be effective in helping patients quit tobacco use. Perceived barriers reported were lack of time (88 percent), lack of necessary materials (81 percent), and lack of knowledge of smoking cessation (74 percent). However, 81 percent of the respondents said they are willing to undergo training in tobacco use cessation. Since most of the dentists and dental students had poor attitudes and negative perceptions of smoking cessation activities, possibly due to lack of training and resources to carry it out in the clinics, there is need to include smoking cessation training in the dental curriculum in Nigeria.


Robust image-adaptive data hiding using erasure and error correction.
Information-theoretic analyses for data hiding prescribe embedding the hidden data in the choice of quantizer for the host data. In this paper, we propose practical realizations of this prescription for data hiding in images, with a view to hiding large volumes of data with low perceptual degradation. The hidden data can be recovered reliably under attacks, such as compression and limited amounts of image tampering and image resizing. The three main findings are as follows. 1) In order to limit perceivable distortion while hiding large amounts of data, hiding schemes must use image-adaptive criteria in addition to statistical criteria based on information theory. 2) The use of local criteria to choose where to hide data can potentially cause desynchronization of the encoder and decoder. This synchronization problem is solved by the use of powerful, but simple-to-implement, erasures and errors correcting codes, which also provide robustness against a variety of attacks. 3) For simplicity, scalar quantization-based hiding is employed, even though information-theoretic guidelines prescribe vector quantization-based methods. However, an information-theoretic analysis for an idealized model is provided to show that scalar quantization-based hiding incurs approximately only a 2-dB penalty in terms of resilience to attack.


Controlled trial of oligoantigenic treatment in the hyperkinetic syndrome.
76 selected overactive children were treated with an oligoantigenic diet, 62 improved, and a normal range of behaviour was achieved in 21 of these. Other symptoms, such as headaches, abdominal pain, and fits, also often improved. 28 of the children who improved completed a double-blind, crossover, placebo-controlled trial in which foods thought to provoke symptoms were reintroduced. Symptoms returned or were exacerbated much more often when patients were on active material than on placebo. 48 foods were incriminated. Artificial colorants and preservatives were the commonest provoking substances, but no child was sensitive to these alone.


Changes in numbers of pancreatic acinar cell nuclei and in DNA content during raw soya flour feeding in mice.
Nuclei of pancreatic cells were isolated by trypsin-detergent digestion of fresh tissue and stained with propidium iodide, and nuclear DNA was measured by flow cytometry. Samples were isolated from mice fed either chow or raw soya flour (RSF) for periods ranging from 1 day to 48 weeks, beginning at 4 weeks of age. In chow-fed mice, the pancreas contained about 80% diploid (2N) and 20% tetraploid (4N) cells at the start of the study, but tetraploidy gradually increased to about 40% 2 weeks later (6 weeks of age) and remained at this level from that time onwards. Low levels of octaploid nuclei (8N) were also present in some animals after 2 weeks. In RSF-fed mice, about 20% tetraploid nuclei were also present for 1 and 2 days after starting RSF, but by 4 days tetraploidy had increased significantly to 40% and by 14 days had further increased to 50%. This level was significantly higher than that seen in chow-fed animals and was maintained for up to 48 weeks. Significantly higher numbers of octaploid nuclei were also present in the RSF-fed animals. In both chow- and RSF-fed mice, most cells were mononuclear, averaging 70% in chow-fed and 64% in RSF-fed animals. This difference was significant. This study shows that the mouse pancreas differs from the rat pancreas in the absence of a large population of binucleate acinar cells and the presence of considerable nuclear tetraploidy. Raw soya flour feeding leads to significant changes in these features, but in this species these changes do not appear to predispose to neoplasia.


Rhode Island Department of Health Foodborne Illness Complaint System: A Descriptive and Performance Analysis.
Foodborne illnesses create a large impact on both the health and economy of the United States. Early detection of an outbreak is essential to preventing additional illnesses. Foodborne illnesses are commonly identified through foodborne illness complaint systems, and it is vital that public health agencies ensure their systems are functioning effectively for successful detection of foodborne outbreaks. The purpose of this study was to provide a descriptive summary of foodborne illness complaint data in Rhode Island and to evaluate the Rhode Island Department of Health (RIDOH) foodborne illness complaint system's ability to detect foodborne outbreaks using the Council to Improve Foodborne Outbreak Response (CIFOR) target performance measures. Data were collected from all foodborne illness complaints reported to RIDOH by the public from 1 January 2010 to 31 December 2017. During this period, 1,218 foodborne illness complaints in total were reported to RIDOH; 85% of complainants reported their illness within 7 days of symptom onset. Most complainants (73%) did not seek medical attention. There were 54 outbreaks, 80% of which were identified by the complaint system. Most pathogens that were identified during an outbreak detected by the complaint system were nonreportable (69%). CIFOR metrics indicate that the complaint system is functioning (i) at an acceptable level of illness complaints expected based on population size and (ii) at preferable levels for metrics related to outbreak detection. This review of the RIDOH foodborne illness complaint system provides evidence for the vital role of complaint systems in detecting foodborne illness outbreaks. In addition, it demonstrates that complaint systems can detect illnesses in a timely manner, likely preventing further illnesses. This was the first multiyear evaluation of Rhode Island's illness complaint surveillance system and will serve as a baseline for future analyses to monitor trends in performance.


Transcatheter Aortic Valve Replacement in Patients With or Without Active Cancer.
Background Data on clinical outcomes after transcatheter aortic valve replacement (TAVR) in specific cancer types or the presence of metastatic disease remain sparse. This study aimed to investigate the impact of active cancer on short-term mortality, complications, and readmission rates after TAVR across different cancer types. Methods and Results The authors assessed the Nationwide Readmissions Database for TAVR cases from 2012 to 2019. Patients were stratified by specific cancer types. Primary outcome was in-hospital mortality. Secondary outcomes included bleeding requiring blood transfusion and readmissions at 30, 90, and 180 days after TAVR. Overall, 122 573 patients undergoing TAVR were included in the analysis, of whom 8013 (6.5%) had active cancer. After adjusting for potential confounders, the presence of active cancer was not associated with increased in-hospital mortality (adjusted odds ratio [aOR], 1.06 [95% CI, 0.89-1.27]; P=0.523). However, active cancer was associated with an increased risk of readmission at 30, 90, and 180 days after TAVR and increased risk of bleeding requiring transfusion at 30 days. Active colon and any type of metastatic cancer were individually associated with readmissions at 30, 90, and 180 days after TAVR. At 30 days after TAVR, colon (aOR, 2.51 [95% CI, 1.68-3.76]; P<0.001), prostate (aOR, 1.40 [95% CI, 1.05-1.86]; P=0.021), and any type of metastatic cancer (aOR, 1.65 [95% CI, 1.23-2.22]; P=0.001) were individually associated with an increased risk of bleeding requiring transfusion. Conclusions Patients with active cancer had similar in-hospital mortality after TAVR but higher risk of readmission and bleeding requiring transfusion, the latter depending on certain types of cancer.


Signs of Inequality? Variations in Providing Home Health Care Across Care Organizations and Across European Countries in the IBenC Study.
Most countries aim to allocate home health care to those in need in a fair and equal way. Equal allocation implies that the amount of home care a person receives would reflect the level of health impairment and the need for resources. It is not clear whether countries succeed in attaining this. Our objective was to explore signs of (un)equal home health care provisioning across care organizations and across European health countries. We used data of the IBenC study collected from 2718 older community care recipients from 33 organizations in 6 Western European countries (www.ibenc.eu). We benchmarked differences of provided and expected formal care time across organizations and countries. Expected formal care hours were estimated by multiplying the overall sample's mean formal hours with recipients' case mix weights from interRAI's resources utilization group profiles. We found substantial variations in provided formal care time among organizations both within and across countries that could not be explained by the case mix differences of recipients. This implied presence of inequality of home care provisioning. These findings may alert professionals and policy makers striving for equal home health care provisioning for dependent older persons.


Contrast-Enhanced Digital Mammography in the Surgical Management of Breast Cancer.
Contrast-enhanced digital mammography (CEDM) is a new breast imaging technique. The role of CEDM in the surgical management of breast cancer has not yet been characterized. A retrospective review of prospective breast surgery and breast imaging databases for patients who underwent CEDM and had breast cancer surgery. A total of 351 patients had CEDM; 128 had malignant lesions, and 101 of these underwent surgery with 105 malignancies identified. The mean age was 62 years (range 25-85 years). The histology was 65 % invasive ductal carcinoma, 16 % invasive lobular carcinoma, 11 % ductal carcinoma-in situ, 3 % mixed invasive ductal carcinoma/invasive lobular carcinoma, and 5 % other histologies. After excluding two lesions that had been removed before the examination, CEDM identified 98 % (n = 101/103) of the index lesions. The two lesions not identified were Paget disease only and a parasternal lesion too medial to include in the field of view. CEDM led to additional biopsies in 12 % (n = 12) of patients. Of these, 67 % (n = 8) proved to be invasive carcinoma and 33 % (n = 4) were benign. CEDM changed surgical management in 20 % (n = 20) of cancer patients with a 4 % (n = 4) rate of conversion to mastectomy. Among patients undergoing surgical therapy for breast cancer, CEDM was highly sensitive, had size measurements that correlated well with histologic size, and produced a relatively low rate of false-positive additional biopsy findings. CEDM appears to be promising as an alternative to magnetic resonance imaging in the surgical planning of these patients.


Increased cytokine response of rhinovirus-infected airway epithelial cells in chronic obstructive pulmonary disease.
Airway inflammation is a central feature of chronic obstructive pulmonary disease (COPD). COPD exacerbations are often triggered by rhinovirus (RV) infection. We hypothesized that airway epithelial cells from patients with COPD maintain a proinflammatory phenotype compared with control subjects, leading to greater RV responses. Cells were isolated from tracheobronchial tissues of 12 patients with COPD and 10 transplant donors. Eight patients with COPD had severe emphysema, three had mild to moderate emphysema, and one had no emphysema. All had moderate to severe airflow obstruction, and six met criteria for chronic bronchitis or had at least one exacerbation the previous year. Cells were grown at air-liquid interface and infected with RV serotype 39. Cytokine and IFN expression was measured by ELISA. Selected genes involved in inflammation, oxidative stress, and proteolysis were assessed by focused gene array and real-time polymerase chain reaction. Compared with control subjects, cells from patients with COPD demonstrated increased mRNA expression of genes involved in oxidative stress and the response to viral infection, including NOX1, DUOXA2, MMP12, ICAM1, DDX58/RIG-I, STAT1, and STAT2. COPD cells showed elevated baseline and RV-stimulated protein levels of IL-6, IL-8/CXCL8, and growth-related oncogene-alpha/CXCL1. COPD cells demonstrated increased viral titer and copy number after RV infection, despite increased IL-29/IFN-lambda1, IL-28A/IFN-lambda2, and IFN-inducible protein-10/CXCL10 protein levels. Finally, RV-infected COPD cultures showed increased mRNA expression of IL28A/IFNlambda2, IL29/IFNlambda1, IFIH1/MDA5, DDX58/RIG-I, DUOX1, DUOX2, IRF7, STAT1, and STAT2. Airway epithelial cells from patients with COPD show higher baseline levels of cytokine expression and increased susceptibility to RV infection, despite an increased IFN response.


Hierarchical Bayesian modeling of the relationship between task-related hemodynamic responses and cortical excitability.
Investigating the relationship between task-related hemodynamic responses and cortical excitability is challenging because it requires simultaneous measurement of hemodynamic responses while applying noninvasive brain stimulation. Moreover, cortical excitability and task-related hemodynamic responses are both associated with inter-/intra-subject variability. To reliably assess such a relationship, we applied hierarchical Bayesian modeling. This study involved 16 healthy subjects who underwent simultaneous Paired Associative Stimulation (PAS10, PAS25, Sham) while monitoring brain activity using functional Near-Infrared Spectroscopy (fNIRS), targeting the primary motor cortex (M1). Cortical excitability was measured by Motor Evoked Potentials (MEPs), and the motor task-related hemodynamic responses were measured using fNIRS 3D reconstructions. We constructed three models to investigate: (1) PAS effects on the M1 excitability, (2) PAS effects on fNIRS hemodynamic responses to a finger tapping task, and (3) the correlation between PAS effects on M1 excitability and PAS effects on task-related hemodynamic responses. Significant increase in cortical excitability was found following PAS25, whereas a small reduction of the cortical excitability was shown after PAS10 and a subtle increase occurred after sham. Both HbO and HbR absolute amplitudes increased after PAS25 and decreased after PAS10. The probability of the positive correlation between modulation of cortical excitability and hemodynamic activity was 0.77 for HbO and 0.79 for HbR. We demonstrated that PAS stimulation modulates task-related cortical hemodynamic responses in addition to M1 excitability. Moreover, the positive correlation between PAS modulations of excitability and hemodynamics brought insight into understanding the fundamental properties of cortical function and cortical excitability.


Microsporidia, amitochondrial protists, possess a 70-kDa heat shock protein gene of mitochondrial evolutionary origin.
An intronless gene encoding a protein of 592 amino acid residues with similarity to 70-kDa heat shock proteins (HSP70s) has been cloned and sequenced from the amitochondrial protist Encephalitozoon cuniculi (phylum Microsporidia). Southern blot analyses show the presence of a single gene copy located on chromosome XI. The encoded protein exhibits an N-terminal hydrophobic leader sequence and two motifs shared by proteobacterial and mitochondrially expressed HSP70 homologs. Phylogenetic analysis using maximum likelihood and evolutionary distances place the E. cuniculi sequence in the cluster of mitochondrially expressed HSP70s, with a higher evolutionary rate than those of homologous sequences. Similar results were obtained after cloning a fragment of the homologous gene in the closely related species E. hellem. The presence of a nuclear targeting signal-like sequence supports a role of the Encephalitozoon HSP70 as a molecular chaperone of nuclear proteins. No evidence for cytosolic or endoplasmic reticulum forms of HSP70 was obtained through PCR amplification. These data suggest that Encephalitozoon species have evolved from an ancestor bearing mitochondria, which is in disagreement with the postulated presymbiotic origin of Microsporidia. The specific role and intracellular localization of the mitochondrial HSP70-like protein remain to be elucidated.


Molecular characterization of medically important viruses of the genus Orthobunyavirus.
We have characterized the full-length S segment RNA sequences of five human pathogens of the virus family Bunyaviridae, genus Orthobunyavirus. S segment sequences of Fort Sherman, Shokwe and Xingu viruses of the Bunyamwera serogroup, as well as those of Bwamba and Pongola viruses of the Bwamba serogroup, are described. S segment sequences of Bwamba and Pongola viruses represent the first nucleotide sequences characterized for viruses of the Bwamba serogroup. The described molecular and phylogenetic analyses of these and other selected viruses of the genus Orthobunyavirus reveal that a close sequence similarity is shared between the African Bwamba and the predominantly North American and European California serogroups of the genus Orthobunyavirus.


Influence of guanethidine on the nicotinic effects of acetylcholine in atropinized dogs.
The influence of guanethidine on the nicotinic effects of acetylcholine was studied in anaesthetized atropinized dogs. Guanethidine (5 mg/kg i.v.) reversed the initial nicotinic pressor reaction, abolished the accompanying femoral vasoconstriction and reduced the increase of mean aortic flow. Therefore, nicotinic hypotension after guanethidine was due to a decrease of the peripheral vascular resistance. The height of the second pressor reaction was hardly affected by guanethidine. This drug inhibited the increases in mean aortic flow and heart rate but not the elevation of peripheral resistance, occurring at the secone nicotinic pressor phase. The present findings support the assumption that the initial hypertension is due to increased sympathetic outflow towards heart and vessels, whereas the second hypertension is due to adrenal medullary stimulation. The neurogenic femoral vasodilation at the onset of the second nicotinic pressor phase was blocked by guanethidine, which also inhibited the catecholamine-induced neurogenic vasodilation. These antagonisms may result from the interference of guanethidine with noradrenaline re-uptake.


[Stratification of risk in infarcts without Q wave: role of echocardiography at rest and during exertion].
To assess the relation between the extent of myocardial necrosis and the presence of myocardium at risk in myocardial infarction without Q waves (NQMI) we studied by echocardiography the prevalence of jeopardized myocardium in a group of NQMI stratified on the basis of left ventricular wall motion (akinesis, hypokinesis, normal kinesis). We have studied 60 consecutive patients with non-Q myocardial infarction. Patients were examined by 2D echo at rest (V-VI day from the acute episode) and during symptoms limited bicycle ergometric test (ExT) (XX-XXX day). Regional left ventricular wall motion was evaluated as normal or asynergic (severe hypokinetic, akinetic) and the ExT was considered positive in case of new asynergic areas or ECG criteria. 2D echo at rest was technically satisfactory in 56 patients, 19 showed almost an akinetic segment (Aci) 17 had hypokinetic areas (Ipo) and 20 had normal left ventricle kinesis (Norc). Wall motion abnormalities were localized more frequently in the apex and lateral areas. During exercise 2D echo was performed in 46 patients (82%) with 23 positive tests (50%). Stratifying the population on the basis of left ventricle wall motion we observed a major number of positive tests in the group of patients with normal wall motion in comparison with those with asynergic areas at rest (Norc 66.6%, Ipo 35.7%, Aci 42.6% p less than 0.05 Nore vs Ipo and Nore vs Aci) despite the same CAD extension. These data show the heterogeneity of the NQMI that likely includes patients with transmural (asynergy group) and subendocardial MI (normal kinesis group), the latter with a higher degree of myocardium at risk.


Extrathoracic airway stability during resistive loading in preterm infants.
Extrathoracic airway (ETA) stability was tested in 10 preterm infants during sleep with a drop in intraluminal pressure produced by the application of an external inspiratory flow-resistive load (IRL, 125 cmH2O.1-1.s at 1 l/min). An increase in total pulmonary resistance was sought as the measure of airway narrowing. The role of the ETA in the increased pulmonary resistance with loading was examined by testing the same infants while endotracheally intubated and after extubation. Total pulmonary resistance decreased with loading during the intubated studies (102.5 +/- 41.2 to 82.4 +/- 33.3 cmH2O.1-1.s, P less than 0.05), whereas a significant increase in pulmonary resistance was seen with loading in the extubated studies (101 +/- 58.1 to 128 +/- 68.6 cmH2O.1-1.s, P less than 0.01). Intraluminal pressure in the ETA, measured by the lowest proximal airway pressure, fell significantly with loading in both conditions, with values changing from -0.7 +/- 0.3 to -4.7 +/- 2.7 cmH2O in the intubated infants and from -0.9 +/- 0.3 to -4.6 +/- 0.9 cmH2O) in the extubated infants (P less than 0.01). The results suggest ETA narrowing with loading in extubated infants despite the absence of overt obstructive apnea. Measurements of total pulmonary resistance with IRL can be used as a simple test of ETA stability.


Smart devices for the management of pediatric asthma: a scoping review protocol.
The objective of this scoping review is to identify the scope of literature published on the use of smart devices for interventions in pediatric asthma, including low income and culturally diverse populations. Childhood asthma results in substantial morbidity and costs that pose a significant burden to families and healthcare systems. Low-income and culturally diverse pediatric populations have increased rates of morbidity and mortality compared to higher income families. Smart devices have the potential to improve pediatric asthma health outcomes and reduce health disparities. This scoping review will consider studies with participants who are children, adolescents and young adults with the diagnosis of asthma (ages zero to 26 years). Studies of children and adolescents and young adults with asthma may include adult participants who manage and/or supervise asthma care or provide asthma instruction. This scoping review will be conducted using the Ovid MEDLINE, Embase, Cochrane Library, CINAHL, Web of Science, PsycINFO, ERIC, and both Compendex and Inspec through Engineering Village databases. Gray literature searches will also be conducted. Studies will be reviewed independently by two reviewers, with any conflicts adjudicated by a third member. Data extracted will be presented in a tabular format with an accompanying narrative.


[Pseudoaneurysm in the radial artery after catheterization].
Eleven days after surgery to remove an olfactory groove meningioma, a woman developed a pulsatile swelling and localized elevation of temperature in the radial artery catheterized to monitor arterial pressure. Pseudoaneurysm of the radial artery was diagnosed and the patient was returned to the operating room for ligation and biopsy of the vessel under regional anesthesia. Her condition worsened in spite of the resection and 48 hours after repair of the arterial pseudoaneurysm she was admitted to the intensive care unit with septic shock. Radial artery catheterization is a safe, frequently performed procedure but it is not free of risk. The most common complication is thrombosis. Much more rare are pseudoaneurysms, lesions that are observed late after catheterization (7-40 days) and are associated with vessel wall alterations, repeated puncture attempts, and catheter infection. The usual therapeutic approach involves surgical resection and ligature of the vessel, although other measures have been suggested.


[Diagnosis of bacterial allergy in patients with diseases of the nose and paranasal sinuses].
A comprehensive allergological examinations of 92 patients with lesions of the nose and paranasal cavities and 20 essentially healthy subjects was carried out, using skin tests and neutrophil tests. Half of the patients showed sensitization to Staphylococcus aureus and Streptococcus pyogenes allergens, which occurred more frequently in patients with chronic purulent sinusitis. It is recommended to expose such patients to allergological examinations and to prescribe, if indicated, desensitization therapy.


Abuse Potential and Pharmacodynamic Characteristics of Oral and Intranasal Eluxadoline, a Mixed μ- and κ-Opioid Receptor Agonist and δ-Opioid Receptor Antagonist.
Drugs with μ-opioid receptor (OR) activity can be associated with abuse and misuse. The peripherally acting mixed μ-OR and κ-OR agonist and δ-OR antagonist eluxadoline is approved in the United States for the treatment of irritable bowel syndrome with diarrhea. In two separate crossover studies, we evaluated the oral and intranasal abuse potential of eluxadoline versus placebo and the active control oxycodone. Healthy recreational opioid users received eluxadoline 100, 300, and 1000 mg, oxycodone 30 and 60 mg, and placebo (oral study), or eluxadoline 100 and 200 mg, oxycodone 15 and 30 mg, and placebos matched to eluxadoline and oxycodone (intranasal study). In the oral study, Drug Liking Visual Analog Scale (VAS) peak (maximum) effect (Emax) score (primary endpoint) was significantly greater with eluxadoline 300 and 1000 mg versus placebo, but scores were significantly lower versus oxycodone. Following intranasal insufflation of eluxadoline, Drug Liking VAS Emax scores were not statistically different versus placebo, and were significantly lower versus oxycodone. Across other subjective measures, eluxadoline was generally similar to or disliked versus placebo. Pupillometry indicated no or minimal central effects with oral and intranasal eluxadoline, respectively. Adverse events of euphoric mood were reported with oral and intranasal eluxadoline but at a far lower frequency versus oxycodone. These data demonstrate that eluxadoline has less abuse potential than oxycodone in recreational opioid users.


Scratchcard gambling among adolescent males.
Playing instant scratchcards has become a popular activity among a significant minority of the UK population since their introduction by the National Lottery operators (Camelot) on March 21, 1995. This study examined scratchcard gambling in a group of adolescent males. A total of 204 boys from two secondary schools in Birmingham (aged 11 to 16 years; mean age 13.6 years) were administered a questionnaire on their scratchcard gambling behaviour. Ten classes (five in each school) took part in the survey with one class from each year group selected at random by the headteacher. Within each class almost all the children took part. Forty-two percent of the sample (n=86) had bought their own scratchcards since their introduction in March 1995. Ten children (12% of the gamblers who had bought scratchcards themselves) met an adapted version of the DSM-IV criteria for pathological gambling on scratchcards. Furthermore, a significant relationship was found between parents buying scratchcards and the child's scratchcard purchasing behaviour.


Identification of functional networks of estrogen- and c-Myc-responsive genes and their relationship to response to tamoxifen therapy in breast cancer.
Estrogen is a pivotal regulator of cell proliferation in the normal breast and breast cancer. Endocrine therapies targeting the estrogen receptor are effective in breast cancer, but their success is limited by intrinsic and acquired resistance. With the goal of gaining mechanistic insights into estrogen action and endocrine resistance, we classified estrogen-regulated genes by function, and determined the relationship between functionally-related genesets and the response to tamoxifen in breast cancer patients. Estrogen-responsive genes were identified by transcript profiling of MCF-7 breast cancer cells. Pathway analysis based on functional annotation of these estrogen-regulated genes identified gene signatures with known or predicted roles in cell cycle control, cell growth (i.e. ribosome biogenesis and protein synthesis), cell death/survival signaling and transcriptional regulation. Since inducible expression of c-Myc in antiestrogen-arrested cells can recapitulate many of the effects of estrogen on molecular endpoints related to cell cycle progression, the estrogen-regulated genes that were also targets of c-Myc were identified using cells inducibly expressing c-Myc. Selected genes classified as estrogen and c-Myc targets displayed similar levels of regulation by estrogen and c-Myc and were not estrogen-regulated in the presence of siMyc. Genes regulated by c-Myc accounted for 50% of all acutely estrogen-regulated genes but comprised 85% (110/129 genes) in the cell growth signature. siRNA-mediated inhibition of c-Myc induction impaired estrogen regulation of ribosome biogenesis and protein synthesis, consistent with the prediction that estrogen regulates cell growth principally via c-Myc. The 'cell cycle', 'cell growth' and 'cell death' gene signatures each identified patients with an attenuated response in a cohort of 246 tamoxifen-treated patients. In multivariate analysis the cell death signature was predictive independent of the cell cycle and cell growth signatures. These functionally-based gene signatures can stratify patients treated with tamoxifen into groups with differing outcome, and potentially identify distinct mechanisms of tamoxifen resistance.


Immune-mediated myelopathies.
This article presents data about inflammatory myelopathies, also referred to as transverse myelitis. While the idiopathic form of this condition is rare, the prevalence of transverse myelitis is relatively common when including all of the secondary causes, such as multiple sclerosis (MS). Thus, clinicians and researchers should be familiar with the presentations, diagnostic algorithms, treatment options, and long-term symptom management for patients with transverse myelitis. This review presents data about the idiopathic and secondary forms of transverse myelitis. As research has expanded, the presentations of transverse myelitis have been clarified and the secondary causes explored. With the identification of the aquaporin-4 (AQP4) antibody, more patients with transverse myelitis have been categorized as having neuromyelitis optica (NMO), and more variable presentations have been published. A growing experience with various treatment options has expanded the therapeutic approaches to acute inflammatory myelopathies beyond standard corticosteroid intervention regimens. Transverse myelitis can occur in isolation or as part of a larger systemic condition. An empiric approach to patient evaluation can accelerate diagnosis of secondary conditions. Mounting evidence suggests that an aggressive approach to therapy can improve patient outcomes, but large-scale prospective trials are lacking.


Effect of phenytoin and age on gingival fibroblast enzymes.
The alteration of cytokine balance is stated to exert greater influence on gingival overgrowth compared to the direct effect of the drug on the regulation of extracellular matrix metabolism. The current study evaluated the effect of phenytoin on the regulation of collagen, lysyl oxidase and elastin in gingival fibroblasts. Normal human gingival fibroblasts (HGFs) were obtained from 4 healthy children and 4 adults. Samples were cultured with phenytoin. MTT test was used to evaluate the proliferation and ELISA was performed to determine the level of IL1β and PGE2 production by HGFs. Total RNA of gingival fibroblasts was extracted and RT-PCR was performed on samples. Mann-Whitney U test was used to analyze the data with an alpha error level less than 0.05. There was a significant difference in the expression of elastin between the controls and treated samples in both adult and pediatric groups and also in the lysyl oxidase expression of adult controls and treated adults. No significant difference was found between collagen expression in adults. The significant difference in elastin and lysyl oxidase expression between adult and pediatric samples indicates the significant effect of age on their production.


Vitamin D deficiency and airflow limitation in the Baltimore Longitudinal Study of Ageing.
Vitamin D deficiency is common in patients with chronic obstructive pulmonary disease (COPD) and has also been linked to comorbidities often present in COPD. The aim of this study was to investigate whether vitamin D deficiency was related specifically to airflow limitation or whether vitamin D deficiency was determined by conditions that frequently coexist with COPD: insulin resistance, hypertension, anaemia, obesity and hypercholesterolaemia. For this cross-sectional analysis, we included 897 subjects from the Baltimore Longitudinal Study of Aging. Subjects taking vitamin D supplements were excluded. Airflow limitation was defined as FEV1 /FVC < lower limit of normal. Logistic regression was used to assess the association between vitamin D deficiency (25-hydroxy vitamin D < 20 ng/mL) and possible determinants. Vitamin D deficiency was not specific for subjects with airflow limitation. Body mass index (BMI) (OR: 1.05, P < 0.03) and obesity (BMI > 30 kg/m(2)) (OR: 1.9, P < 0.002) were significantly associated with vitamin D deficiency in the adjusted multivariate regression analysis. Physical activity was associated with a decreased risk of vitamin D deficiency. Airflow limitation was not an independent determinant of vitamin D deficiency. The effect of weight loss and increased physical activity on vitamin D levels should be investigated further in intervention studies.


How intracranial aneurysm rupture damages the brain.
Intracranial aneurysm rupture causes arterial bleeding into the subarachnoid space (SAH). In the acute stage lasting around 5 minutes intracranial pressure (ICP) rises rapidly up to the level between systolic and diastolic blood pressures, which slows down the outflow of blood, facilitates clot formation in the site of rupture and leads to arrest of bleeding. Increased ICP lowers cerebral perfusion pressure, causing brain ischemia, which is unevenly distributed throughout the brain as a result of interhemispheric pressure gradients, arterial spasms and other factors. No-reflow phenomenon in the capillaries following temporary arrest or considerable slowing of circulation produces areas of hypoperfusion and reduced capacity of blood flow autoregulation scattered irregularly in the brain in the subacute stage up to 30 minutes following haemorrhage. Disturbed regional cerebral blood flow is accompanied by spots of damaged blood brain barrier resulting in brain oedema. After SAH the brain remains vulnerable to reduction of blood flow and hypoxaemia, which explains greater brain damage after secondary haemorrhage, and in some cases persistent neurological deficits or global brain dysfunction.


Sex differences in risk of lung cancer: Expression of genes in the PAH bioactivation pathway in relation to smoking and bulky DNA adducts.
It is controversial whether women have a higher lung cancer susceptibility compared to men. We previously reported higher levels of smoking-related bulky DNA adducts in female lungs. In a pilot study (27 cases), we also found a higher level of female lung cytochrome P4501A1 (CYP1A1) gene expression. In the present extended study we report on the pulmonary expression of several genes involved in polycyclic aromatic hydrocarbon bioactivation in relation to sex, smoking and DNA adducts. CYP1A1, CYP1B1, aryl hydrocarbon receptor and microsomal epoxide hydrolase gene expression was measured by quantitative real-time reverse transcriptase-PCR in 121 normal lung tissue samples. The expression of CYP1A1 and CYP1B1 was significantly higher among current smokers compared to ex-smokers and never-smokers. Among current smokers, females had a 3.9-fold higher median level of CYP1A1 compared to males (p = 0.011). CYP1B1 expression was not related to sex. Lung DNA adducts (measured by 32P-postlabeling) were highly significantly related to CYP1A1 (p < 0.0001) irrespective of smoking-status. Our results are consistent with the hypothesis that CYP1A1 plays a significant role in lung DNA adduct formation and support a higher susceptibility to lung cancer among females.


Quantitative oximetry of breast tumors: a near-infrared method that identifies two optimal wavelengths for each tumor.
We present a noninvasive optical method to measure the oxygen saturation of hemoglobin in breast lesions. This method introduces the novel concept that the best choice of near-infrared wavelengths for noninvasive tumor oximetry consists of a wavelength pair (lambda1, lambda2) within the range 680-880 nm, where the specific values of lambda1 and lambda2 depend on the optical properties of the specific tumor under examination. Our method involves two steps: (1) identify the optimal wavelength pair for each tumor and (2) measure the tumor oxygenation using the optical data at the two selected wavelengths. We have tested our method by acquiring experimental optical data from turbid media containing cylindrical or irregularly shaped inhomogeneities and by computing theoretical data for the case of spherical lesions embedded in a highly scattering medium. We have found that our optical method can provide accurate and quantitative measurements of the oxygenation of embedded lesions without requiring knowledge of their size, shape, and depth.


Use of orthogonal serine integrases to multiplex plasmid conjugation and integration from E. coli into Streptomyces.
Some major producers of useful bioactive natural products belong to the genus Streptomyces or related actinobacteria. Genetic engineering of these bacteria and the pathways that synthesize their valuable products often relies on serine integrases. To further improve the flexibility and efficiency of genome engineering via serine integrases, we explored whether multiple integrating vectors encoding orthogonally active serine integrases can be introduced simultaneously into Streptomyces recipients via conjugal transfer and integration. Pairwise combinations of Escherichia coli donors containing vectors encoding orthogonal serine integrases were used in each conjugation. Using donors containing plasmids (of various sizes) encoding either the φBT1 or the φC31 integration systems, we observed reproducible simultaneous plasmid integration into Streptomyces coelicolor and Streptomyces lividans at moderate frequencies after conjugation. This work demonstrated how site-specific recombination based on orthogonal serine integrases can save researchers time in genome engineering experiments in Streptomyces .


[Computed tomography in the diagnosis of salivary gland neoplasms].
To evaluate the efficiency of computed tomography (CT) in the diagnosis of salivary neoplasms, 68 patients (50 with benign tumors of the salivary glands, 10 with theirs malignant tumors, 8 with salivary cysts) were examined. The authors revealed the high informative value of CT in the diagnosis of salivary bulky lesions. CT defined the site of a tumor, the benign or malignant pattern of its growth, the extent of tumorous invasion. The diagnostic value of CT in the diagnosis of salivary glands was as follows: its sensitivity, specificity, and accuracy were 97.0, 81.8, and 94.9%, respectively.


[Polymer chain with eliminated volume in an exterior field].
The problem of the behaviour of a polymer chain with excluded volume in an external attractive potential field was considered. It was found that the phase transition (the capture of a polymer by a potential pit), is the phase transition of the second kind; the excluded volume affects neither the temperature, nor the kind of phase transition, but it influences essentially the structure of the system after capture. An analysis of this structure was undertaken; the dependence of the critical temperature on the parameters of the pit was calculated.


PALM and STORM: Into large fields and high-throughput microscopy with sCMOS detectors.
Single Molecule Localization Microscopy (SMLM) techniques such as Photo-Activation Localization Microscopy (PALM) and Stochastic Optical Reconstruction Microscopy (STORM) enable fluorescence microscopy super-resolution: the overcoming of the resolution barrier imposed by the diffraction of light. These techniques are based on acquiring hundreds or thousands of images of single molecules, locating them and reconstructing a higher-resolution image from the high-precision localizations. These methods generally imply a considerable trade-off between imaging speed and resolution, limiting their applicability to high-throughput workflows. Recent advancements in scientific Complementary Metal-Oxide Semiconductor (sCMOS) camera sensors and localization algorithms reduce the temporal requirements for SMLM, pushing it toward high-throughput microscopy. Here we outline the decisions researchers face when considering how to adapt hardware on a new system for sCMOS sensors with high-throughput in mind.


Novel strategies to minimize progeny inbreeding while maximizing genetic gain using genomic information.
In this study, 3 strategies for controlling progeny inbreeding in mating plans were compared. The strategies used information from pedigree inbreeding coefficients, genomic relationships, or shared runs of homozygosity. The strategies were compared for the reduction in genetic gain and progeny inbreeding that would be expected from selected matings, and for the decrease of homozygosity of deleterious recessive alleles. Using real pedigree, genotype [43,115 single nucleotide polymorphism (SNP) markers], and estimated breeding value data from Holstein cattle, mating plans were derived for herds of 300 cows with 20 sires available for mating, replicated 50 times. Each of the 300 individuals allocated as dams were matched to 1 of 20 sires to maximize genetic merit minus the penalty for estimated progeny inbreeding, and given the restriction that the sire could not be mated to more than 10% of the cows. The strategy that used a genomic relationship matrix (GRM) was the most effective in reducing average progeny inbreeding; this strategy also resulted in fewer homozygous SNP out of 1,000 low-frequency SNP compared with the strategy using pedigree information. In the future, large numbers of cattle may be genotyped for low-density SNP panels. A GRM constructed using 3,123 SNP produced results similar to a GRM constructed using the full 43,115 SNP. These results demonstrate that using GRM information, a 1% reduction in progeny inbreeding (valued at around $5 per cow) can be made with very little compromise in the overall breeding objective. These results and the availability of low-cost, low-density genotyping make it attractive to apply mating plans that use genomic information in commercial dairy herds.


[Effects of Chinese herbal medicine Pingchuan Formula on airway inflammation, interferon-γ and interleukin-4 in mice with asthma].
To observe the changes of interferon-γ (IFN-γ) and interleukin-4 (IL-4), factors related to T helper 1/T helper 2 (Th1/Th2), in airway inflammation in an asthmatic model of mice and the effects of Pingchuan Formula (PCF), a compound traditional Chinese herbal medicine. Eighty BALB/c mice were randomly divided into normal group, model group, dexamethasone group and PCF group, with 20 mice in each group. For inducing asthma, the BALB/c mice were sensitized by intraperitoneal injection of mixed ovalbumin, and then activated by inhaling ovalbumin. After 2 weeks of sensitizing, asthmatic mice were intragastrically administered with the drugs once a day for four weeks. Bronchoalveolar lavage fluid (BALF) and lung tissue were collected respectively after 7-day activation or 2 weeks after activation. The general histological changes were observed by hematoxylin and eosin staining and collagen staining, meanwhile the levels of IFN-γ and IL-4 in BALF were detected by enzyme-linked immunosorbent assay. After 7 d of activation, compared with the normal group, significant decrease in IFN-γ and increase in IL-4 were detected in the model group; compared with the model group, IL-4 level of the two treated groups was decreased and the IFN-γ/IL-4 ratio was increased significantly; no significant difference was found between the two treated groups. Two weeks after activation, compared with the normal group, IFN-γ was decreased, IL-4 was increased, and the IFN-γ/IL-4 ratio was decreased in the model group; compared with the model group, IL-4 level in the dexamethasone group was significantly decreased and IFN-γ/IL-4 ratio was significantly elevated, while the level of IL-4 in the PCF group was significantly decreased, the level of IFN-γ was increased simultaneously, and the IFN-γ/IL-4 ratio was significantly elevated. There was no significant difference between the two treated groups in IFN-γ and IL-4 levels, nor in the IFN-γ/IL-4 ratio. The area of collagen fiber in airway wall epithelium in the model group was smaller than that in the normal group, and those in the treated groups were lower than that in the model group; there was no significant difference between the two treated groups. PCF has regulating function in correcting the imbalance of Th1/Th2 so as to improve airway inflammation. The therapeutic effects of PCF are basically similar to dexamethasone.


The surface concentration of H-2 antigens on mouse pancreatic beta-cells and islet cell transplantation.
Measurement of the concentration of H-2 complex antigens in the surface membrane of mouse pancreatic beta-cells by a quantitative immunoferritin-labeling technique revealed that the antigens were present in very small amounts on the beta-cells of five strains. A comparison of the labeling densities in the five strains suggested that beta-cells from C57BL/10Sn congenic strains have about half the H-2 antigen density of BALB/c and C3H/HeJ cells. In C57BL/10Sn mice the antigen density on beta-cells was slightly greater than that on erythrocytes, about 20% of that on thymocytes, and about 2.5% of that present on peritoneal macrophages. Intraperitoneal allografts of c57BL/10Sn islets were uniformly rejected by B10.BR/SgSn diabetic recipients only when the islets were accompanied by 10(7) peritoneal lymphoid cells. When transplanted without peritoneal cells, C57BL/10Sn islets were only marginally rejectable. In a group of nine such allografts, three diabetic recipients were permanently cured and three others showed rejection times of about 30 days. Sensitization of the three mice showing permanent cures, using 10(7) allogeneic peritoneal cells at about 40 days after the transplant, did not cause rejection of the allografts. Isogeneic transplantation of cell suspensions from dissociated islets of Langerhans was markedly less effective in controlling diabetes than intact islets, and dissociation did not obviously improve the rate of allograft survival. However, 5/19 diabetic mice receiving allografts of dissociated islet cells showed long-term reversals of diabetes that were unaffected by administration of 10(7) peritoneal cells at about 100 days after the transplant. Recipient mice whose diabetes was reversed by islet allografts and unaffected by specific sensitization had pancreatic insulin concentrations characteristic of diabetic mice. Our reversals of diabetes with untreated islet allografts may be due to the cleanliness of islet preparations obtained with a modified isolation technique, and to the very low density of H-2 complex antigens on C57BL/10Sn beta-cells.


RDX binds to the GABA(A) receptor-convulsant site and blocks GABA(A) receptor-mediated currents in the amygdala: a mechanism for RDX-induced seizures.
Hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) is a high-energy, trinitrated cyclic compound that has been used worldwide since World War II as an explosive in both military and civilian applications. RDX can be released in the environment by way of waste streams generated during the manufacture, use, and disposal of RDX-containing munitions and can leach into groundwater from unexploded munitions found on training ranges. For > 60 years, it has been known that exposure to high doses of RDX causes generalized seizures, but the mechanism has remained unknown. We investigated the mechanism by which RDX induces seizures. By screening the affinity of RDX for a number of neurotransmitter receptors, we found that RDX binds exclusively to the picrotoxin convulsant site of the γ-aminobutyric acid type A (GABA(A)) ionophore. Whole-cell in vitro recordings in the rat basolateral amygdala (BLA) showed that RDX reduces the frequency and amplitude of spontaneous GABA(A) receptor-mediated inhibitory postsynaptic currents and the amplitude of GABA-evoked postsynaptic currents. In extracellular field recordings from the BLA, RDX induced prolonged, seizure-like neuronal discharges. These results suggest that binding to the GABA(A) receptor convulsant site is the primary mechanism of seizure induction by RDX and that reduction of GABAergic inhibitory transmission in the amygdala is involved in the generation of RDX-induced seizures. Knowledge of the molecular site and the mechanism of RDX action with respect to seizure induction can guide therapeutic strategies, allow more accurate development of safe thresholds for exposures, and help prevent the development of new explosives or other munitions that could pose similar health risks.


A 24 hour plastic envelope method for isolating and identifying Gardnerella vaginalis (PEM-GVA)
A new plastic envelope culture test that is selective for Gardnerella vaginalis was compared with a conventional method. Vaginal specimens from 92 women were cultured. Results from both methods were compared with the results of pelvic examinations and clinic screening tests used to diagnose bacterial vaginosis (BV). G vaginalis was isolated more often in the envelope than by the conventional method from patients with BV and those without, though the difference was not significant. Isolation and identification of G vaginalis was completed in 18-24 hours by the envelope method; the conventional method took a mean of 72 hours (range two to six days). Polymorphonuclear leucocytes (PMNLs) occurred significantly more in specimens from the patients without BV than from those with BV. Both clue cells and a positive amine test reaction were found significantly more in specimens from patients with BV than from those without BV. Clue cells and G vaginalis isolation correlated best with BV (in 47 women), followed by clue cells and positive amine test results (in 39). Adherence of G vaginalis in the envelope also correlated more with BV, clue cells, and positive amine test results (32) than with patients without BV (14). When there were no clue cells and amine test results were negative the results correlated totally with a prediction of no BV. The use of the rapid envelope culture test would have confirmed BV in 20% of the cases where clue cell and amine test results were discordant.


Contribution of β-adrenergic receptors to exercise-induced bronchodilatation in healthy humans.
Exercise in healthy subjects is usually associated with progressive bronchodilatation. Though the decrease in vagal tone is deemed to be the main underlying mechanism, activation of bronchial β(2)-receptors may constitute an additional cause. To examine the contribution of β(2)-adrenergic receptors to bronchodilatation during exercise in healthy humans, we studied 15 healthy male volunteers during maximum exercise test at control conditions and after a non-selective β-adrenergic blocker (carvedilol 12.5mg twice a day until heart rate decreased at least by 10beats/min) and inhaled β(2)-agonist (albuterol 400μg). Airway caliber was estimated from the partial flow at 40% of control forced vital capacity (V˙(part40)) and its changes during exercise from the slope of linear regression analysis of V˙(part40) values against the corresponding minute ventilation during maximal exercise until exhaustion. At control, V˙(part40) increased progressively and significantly with exercise. After albuterol, resting V˙(part40) was significantly larger than at control increased but did not further increase during exercise. After carvedilol, V˙(part40) was similar to control but its increase with exercise was significantly attenuated. These findings suggest that β(2)-adrenergic system plays a major role in exercise-induced bronchodilation in healthy subjects.


A minimal standardization setting for language mapping tests: an Italian example.
During awake surgery, picture-naming tests are administered to identify brain structures related to language function (language mapping), and to avoid iatrogenic damage. Before and after surgery, naming tests and other neuropsychological procedures aim at charting naming abilities, and at detecting which items the subject can respond to correctly. To achieve this goal, sufficiently large samples of normed and standardized stimuli must be available for preoperative and postoperative testing, and to prepare intraoperative tasks, the latter only including items named flawlessly preoperatively. To discuss design, norming and presentation of stimuli, and to describe the minimal standardization setting used to develop two sets of Italian stimuli, one for object naming and one for verb naming, respectively. The setting includes a naming study (to obtain picture-name agreement ratings), two on-line questionnaires (to acquire age-of-acquisition and imageability ratings for all test items), and the norming of other relevant language variables. The two sets of stimuli have >80 % picture-name agreement, high levels of internal consistency and reliability for imageability and age of acquisition ratings. They are normed for psycholinguistic variables known to affect lexical access and retrieval, and are validated in a clinical population. This framework can be used to increase the probability of reliably detecting language impairments before and after surgery, to prepare intraoperative tests based on sufficient knowledge of pre-surgical language abilities in each patient, and to decrease the probability of false positives during surgery. Examples of data usage are provided. Normative data can be found in the supplementary materials.


The role of national registries in improving patient safety for hip and knee replacements.
The serious adverse events associated with metal on metal hip replacements have highlighted the importance of improving methods for monitoring surgical implants. The new European Union (EU) device regulation will enforce post-marketing surveillance based on registries among other surveillance tools. Europe has a common regulatory environment, a common market for medical devices, and extensive experience with joint replacement registries. In this context, we elaborate how joint replacement registries, while building on existing structure and data, can better ensure safety and balance risks and benefits. Actions to improve registry-based implant surveillance include: enriching baseline and diversifying outcomes data collection; improving methodology to limit bias; speeding-up failure detection by active real-time monitoring; implementing risk-benefit analysis; coordinating collaboration between registries; and translating knowledge gained from the data into clinical decision-making and public health policy. The changes proposed here will improve patient safety, enforce the application of the new legal EU requirements, augment evidence, improve clinical decision-making, facilitate value-based health-care delivery, and provide up-to-date guidance for public health.


Genome diversity of Pseudomonas aeruginosa isolates from cystic fibrosis patients and the hospital environment.
Pseudomonas aeruginosa is a gram-negative rod that is ubiquitous in nature. P. aeruginosa is also the quintessential opportunistic pathogen, causing a wide variety of infections in compromised hosts. In cystic fibrosis patients, P. aeruginosa is the leading cause of death. In this study, the evolutionary genetic relationships among 17 P. aeruginosa isolates were examined by comparative sequence analysis of the housekeeping gene encoding malate dehydrogenase and the chaperone groEL. The P. aeruginosa isolates examined included the sequenced strain PAO1, 11 strains recovered from cystic fibrosis patients in Ireland, 4 environmental isolates recovered from a hospital environment, and 1 isolate recovered from a plant rhizosphere. Phylogenetically, clinical and environmental isolates clustered together with one another on the mdh gene tree. At the groEL locus, among the 17 isolates examined, only two polymorphic sites were observed, highlighting the close genetic relationship between isolates from these different environments. Phenotypic analysis of 12 traits among our isolates, however, found that only clinical isolates produced phenazines and elastase. Furthermore, molecular analysis of the distribution of 15 regions associated with virulence showed that two of the environmental isolates examined lacked the majority of regions. Among the clinical isolates examined, the 15 virulence regions were variably present. The distribution of two prophages (Bacto1, Pf1) was also determined, with most isolates encoding both these regions. Of the four genomic islands (the flagellum island and PAGI-1, -2, and -3) examined, only two isolates contained the flagellum island, and PAGI-1, -2, and -3 were absent from all isolates tested. Our data demonstrate the significant role horizontal gene transfer and recombination, together with gene loss, play in the evolution of this important human pathogen.


The free-flight response of Drosophila to motion of the visual environment.
In the present study we investigated the behavioural strategies with which freely flying fruit flies (Drosophila) control their flight trajectories during active optomotor stimulation in a free-flight arena. We measured forward, turning and climbing velocities of single flies using high-speed video analysis and estimated the output of a 'Hassenstein-Reichardt' elementary motion detector (EMD) array and the fly's gaze to evaluate flight behaviour in response to a rotating visual panorama. In a stationary visual environment, flight is characterized by flight saccades during which the animals turn on average 120 degrees within 130 ms. In a rotating environment, the fly's behaviour typically changes towards distinct, concentric circular flight paths where the radius of the paths increases with increasing arena velocity. The EMD simulation suggests that this behaviour is driven by a rotation-sensitive EMD detector system that minimizes retinal slip on each compound eye, whereas an expansion-sensitive EMD system with a laterally centred visual focus potentially helps to achieve centring response on the circular flight path. We developed a numerical model based on force balance between horizontal, vertical and lateral forces that allows predictions of flight path curvature at a given locomotor capacity of the fly. The model suggests that turning flight in Drosophila is constrained by the production of centripetal forces needed to avoid side-slip movements. At maximum horizontal velocity this force may account for up to 70% of the fly's body weight during yaw turning. Altogether, our analyses are widely consistent with previous studies on Drosophila free flight and those on the optomotor response under tethered flight conditions.


Uptake of water by an acid-base nanoparticle: theoretical and experimental studies of the methanesulfonic acid-methylamine system.
The effect of water on the growth of dry nano-size acid-base particles is not yet known. In this paper, we investigate the uptake of water by nano-size particles composed of methanesulfonic acid (MSA) and methylamine (MA) using a combination of quantum chemical calculations and laboratory experiments. Calculations were performed on the (MSA-MA)4 cluster as the dry nanoparticle model, which forms a pseudo-cubic structure, to which twelve water molecules were added successively. Theoretical results show that the hydrated clusters (MSA-MA)4-(H2O)n, n = 1 to 12 are thermodynamically stable. In ab initio dynamic simulations, no loss of water or significant changes of structure are seen for at least 10 picoseconds. In all the clusters studied, most of the water molecules lie on the face of the (MSA-MA)4 initial dry unit, and water is found to be incorporated inside the initial unit for n ranging from five to twelve. Sizes of hydrated clusters exceed significantly that of the dry cluster only for n ≥ 6. These theoretical results suggest that dry MSA-MA clusters cannot dissociate in small quantities of water. Calculations of hydrated cluster distributions at steady state show that the cluster compositions studied, with up to 12 water molecules, encompass all the hydrated clusters under the experimental conditions (RH ∼ 19%, 300 K). Experiments performed in a glass flow reactor showed no changes in size or number concentration when particles formed from MSA-MA were subsequently exposed to water vapor, in contrast to increases in both size and number when water was present during particle formation. Thus, the results seem to imply for both experiment and theory that growth in size of a particle due to uptake of water requires the previous presence of some level of hydration. These results illustrate the importance for atmospheric models of understanding on a molecular basis the mechanisms of particle formation in air.


Membrane and synaptic actions of halothane on rat hippocampal pyramidal neurons and inhibitory interneurons.
A relatively small number of inhibitory interneurons can control the excitability and synchronization of large numbers of pyramidal neurons in hippocampus and other cortical regions. Thus, anesthetic modulation of interneurons could play an important role during anesthesia. The aim of this study was to investigate effects of a general anesthetic, halothane, on membrane and synaptic properties of rat hippocampal interneurons. GABA receptor-mediated IPSCs were recorded with whole-cell patch-clamp techniques in visually identified CA1 pyramidal cells and interneurons located at the border of stratum lacunosum-moleculare and stratum radiatum. Halothane (0.35 mm congruent with 1.2 vol%) depressed evoked IPSC amplitudes recorded from both pyramidal cells and inhibitory interneurons. Also, halothane considerably prolonged the decay time constant of evoked IPSCs in pyramidal cells and interneurons. The frequencies of miniature IPSCs were increased by halothane (two- to threefold) in both types of neuron. On the other hand, halothane effects on resting membrane potentials were variable but minimal in both types of neurons. In current-clamp recordings, halothane depressed EPSP amplitudes and increased IPSP amplitudes recorded from both types of neurons. In addition, halothane increased the failure rate of synaptically evoked action potentials. Taken together, these data provide evidence that halothane increases GABA(A) receptor-mediated synaptic inhibition between synaptically connected interneurons and depresses excitatory transmission, similar to effects observed in pyramidal neurons.


The Current State of U.S. Regulation of Electronic Monitoring to Combat Elder Abuse and Its Future.
The incidence of elder abuse has led to a growing trend of states taking various methods to regulate the use of electronic monitoring in institutional settings through programs, guidelines, regulations, and laws. This article attempts evaluate how the regulation of electronic monitoring has evolved and may be advanced in the future with the anticipated increase of elder abuse.


Potential anticancer effects of statins: fact or fiction?
Deregulation of any of the steps in cell growth, proliferation and apoptosis may result in its malignant transformation. Statins, along with their lipid-lowering potential, modify several processes in the cell cycle. These agents inhibit cell proliferation and arrest cell cycle progression by interrupting growth-promoting signals. Statins selectively induce proapoptotic protential in tumor cells and synergistically enhance proapoptotic potential of several cytotoxic agents. Statins alter angiogenic potential of cells by modulating apoptosis inhibitory effects of VEGF and decrease secretion of metalloproteases. Statins also alter adhesion and migration of tumor cells, thereby inhibiting tumor invasion and metastasis. Statins suppress rate of activation of multiple coagulation factors and thus prevent coagulation-mediated angiogenesis. Statins have been shown to have anti-tumor activity in experimental models. Various anti-neoplastic properties of statins are probably a result of inhibition of posttranslational modifications of growth regulatory proteins. Molecular mechanisms of antiproliferative, proapoptotic and antiangiogenic effects of statins are reviewed in this chapter.


Eco-evolutionary dynamics induced by massive mortality events.
An eco-genetic model tuned on a population of marble trout Salmo marmoratus subject to periodic flood events was used to explore how the evolution of growth rates interacting with density-dependent processes can modify size at age and population structure and in turn influence the resilience of populations. Fish with greater growth potential were assumed to have higher mortality rates. The results of simulations were compared between two scenarios, one in which populations may evolve growth rates and the other one in which the distribution of growth rates within a population is kept fixed. Evolving populations had a greater proportion of age 1 year individuals in the population, greater median length at age 3 years (the typical age at sexual maturity for S. marmoratus) and lower population sizes. The slightly smaller population sizes did not affect realized extinction risk. Resilience, defined as the number of years necessary to rebound from flood-induced population collapse, was on average from 2 to 3 years in both scenarios, with no significant difference between them. Moderate heritability of growth, relaxation of density-dependent processes at low densities and rapid recovery to a safe population size combine to limit the capacity to evolve faster recovery after flood-induced population collapses via changing growth rates.


[Benefit of the implementation of on-call neurology physicians in a general hospital].
Most Spanish hospitals have no oncall neurologist (OCN) for emergency patients. This study was designed to highlight the benefits in patient management when an OCN system is implemented. We conducted a prospective study in the University Hospital of Albacete during the first year of OCN implementation (2004). We also compared stroke patients admissions from emergency department (ED) in 2004 with respect to 2003. OCN attended 2,745 patients (7.6 per day), 73.1% of these calls coming from ED between 3 PM and 10 PM. Acute stroke was the most frequent consultation. A total of 118 calls were made to determine the need for thrombolytic therapy and 323 emergency neurosonologic examinations were performed by the OCN during the duty. A total of 44.8% of the attended patients were admitted and 30.1% were referred to outpatient clinics. Our hospital had a significant decrease (12.3%) in stroke patients admissions over 2004 compared with 2003 despite an actual increase of total admissions in the neurological ward. The mean hospital stay of stroke patients was shorter in the neurology department than in the internal medicine one. OCN improves the quality of attention to the neurological patient, reduces the number of unnecessary hospital admissions and increases the status of the neurological department. Implementation of on-call neurology physicians for 24 hours is necessary in all those sites that provide care to emergency patients and have neurology services.


Exercise for children with chronic kidney disease and end-stage renal disease.
It is well known that adults suffering from chronic kidney disease (CKD) experience muscle wasting and excessive fatigue, which results in a reduced exercise capacity and muscle weakness compared to their healthy counterparts, but research suggests that this can be improved through exercise. There is very limited data available regarding exercise tolerance in children with CKD and even less on the effects of exercise training programs. However, the available evidence does suggest that like adults, children also suffer from poor exercise capacity and reduced muscle strength, although the reasons for these limitations remain unclear. Studies that have attempted to implement exercise training programs in pediatric CKD populations have experienced high dropout rates, suggesting that the approach used to implement such programs in children needs to be different from the approach used for adults. This review summarizes the current knowledge regarding exercise capacity and muscle strength in children with CKD, the methods used to perform these assessments, and the possible causes of physical limitations. The results of exercise training studies, and the potential reasons as to why training programs have proved relatively unsuccessful are also discussed.


Regression of human kidney cancer following allogeneic stem cell transplantation is associated with recognition of an HERV-E antigen by T cells.
Transplanted donor lymphocytes infused during hematopoietic stem cell transplantation (HSCT) have been shown to cure patients with hematological malignancies. However, less is known about the effects of HSCT on metastatic solid tumors. Thus, a better understanding of the immune cells and their target antigens that mediate tumor regression is urgently needed to develop more effective HSCT approaches for solid tumors. Here we report regression of metastatic renal cell carcinoma (RCC) in patients following nonmyeloablative HSCT consistent with a graft-versus-tumor effect. We detected RCC-reactive donor-derived CD8(+) T cells in the blood of patients following nonmyeloablative HSCT. Using cDNA expression cloning, we identified a 10-mer peptide (CT-RCC-1) as a target antigen of RCC-specific CD8(+) T cells. The genes encoding this antigen were found to be derived from human endogenous retrovirus (HERV) type E and were expressed in RCC cell lines and fresh RCC tissue but not in normal kidney or other tissues. We believe this to be the first solid tumor antigen identified using allogeneic T cells from a patient undergoing HSCT. These data suggest that HERV-E is activated in RCC and that it encodes an overexpressed immunogenic antigen, therefore providing a potential target for cellular immunity.


Management of stroke-related seizures.
Although general guidelines exist for the diagnosis and the treatment of epilepsy, no specific recommendations are available concerning the management of seizures related to cerebrovascular disease. The incidence of seizures after stroke was found to be 8.9% in the only published prospective study. This is an underestimation as seizures occurring at stroke onset were not taken in to account and non-convulsive spells are rarely recognized as such. Risk factors, diagnosis, management and treatment will be different according to the time of onset of the seizures in relation to the stroke. As, on one hand, repeated seizures and status epilepticus worsen the neurological and the mental condition of stroke patients and, on the other hand, antiepileptic drugs (AEDs) can also increase cognitive impairment, the main questions to be answered are for which patients AEDs should be prescribed and which drug should be preferred.


Low-Intensity Pulsed Ultrasound Counteracts Advanced Glycation End Products-Induced Corpus Cavernosal Endothelial Cell Dysfunction via Activating Mitophagy.
Injury to corpus cavernosal endothelial cells (CCECs) is an important pathological basis of diabetes mellitus-induced erectile dysfunction (DMED), while low-intensity pulsed ultrasound (LIPUS) has been shown to improve erectile function in DMED. To further understand its therapeutic mechanism of action, in this study, we first demonstrated increased apoptosis and shedding in the CCECs of DMED patients, accompanied by significant mitochondrial injury by immunohistochemistry and electron microscopy of corpus cavernosum tissue. Next, we used advanced glycation end products (AGEs) to simulate the diabetic environment in vitro and found that AGES damaged mitochondria and inhibited angiogenesis in CCECs in a dose-dependent manner, while LIPUS treatment significantly reversed its effects. Mechanistic studies based on transcriptome sequencing showed that LIPUS significantly up-regulated LC3 and PARKIN protein levels in mitochondria, promoted mitophagy, and affected mitochondrial dynamics and reactive oxygen species (ROS) production. In addition, the protective effects of LIPUS were abrogated when mitophagy was inhibited by 3-methyladenine. In summary, LIPUS exerted potent inhibitory effects on AGES-induced CCEC failure via mitophagy, providing a theoretical basis for DMED treatment that encompasses the protection of endothelial structure and function.


Generation of specific helper cells and suppressor cells in vitro for the IgE and IgG antibody responses.
Normal splenic lymphocytes from BDF1 mice were cultured on ovalbumin (OA)-bearing syngeneic peritoneal adherent cells for 5 days and their subsequent helper function was tested by an adoptive transfer technique. Lymphocytes harvested from the culture were mixed with DNP-KLH-primed spleen cells and transferred into irradiated syngeneic mice followed by challenge with DNP-OA. The results showed that the cultured lymphocytes has helper function for both IgE and IgG anti-DNP antibody responses. Depletion of mast cells and T cells in the peritoneal adherent cell preparations did not affect the generation of helper cells in the culture. The helper function of the cultured lymphocytes was abolished by the treatment with anti-theta antiserum and complement and was specific for ovalbumin. The OA-specific helper T cells were generated in vitro by the culture of a T cell-rich fraction of normal spleen on T cell-depleted OA-bearing peritoneal cells. If the normal splenic lymphocytes or T cell-rich fraction were cultured with 10 mug/ml of OA in the absence of macrophages, cultured lymphocytes lacked helper function. The transfer of splenic lymphocytes or splenic T cells cultured with soluble OA to normal non-irradiated mice, however, suppressed both IgG and IgE antibody responses of the recipients to subsequent immunization with DNP-OA. The suppressor cells were sensitive to anti-theta antiserum and complement and their activity was specific for OA. The cultured cells transferred into normal mice did not suppress anti-hapten antibody response to DNP-KLH. Normal lymphocytes cultured on OA-bearing macrophages and had helper function in adoptive transfer experiments failed to suppress antibody response of non-irradiated recipients to DNP-OA. The results indicate that OA-bearing macrophages primed T cells and generated helper T cells, whereas the culture of normal lymphocytes with soluble OA in the absence of macrophages generated suppressor T cells.


The ATP-dependent Lon protease of Mus musculus is a DNA-binding protein that is functionally conserved between yeast and mammals.
The ATP-dependent Lon protease is a multi-functional enzyme that is conserved from archae to mammalian mitochondria, which not only degrades protein substrates but also binds DNA. As a starting point toward understanding Lon function in development, the mouse Lon cDNA was cloned and the encoded protein was characterized in cultured mammalian cells, in yeast and in vitro. Mouse Lon shows 87, 40 and 33% amino acid similarity with the human, yeast and bacterial homologs, respectively. Expression of a single mouse Lon transcript is detected in liver>heart>kidney>testis and is present during early embryonic development. Endogenous as well as transiently overexpressed mouse Lon co-localize with mitochondrial markers and have half-lives greater than 24 h as determined by pulse-chase studies. Enzymatically active mouse Lon that hydrolyses ATP and degrades protein and peptide substrates in an ATP-dependent manner also specifically binds to single-stranded but not to double-stranded DNA oligonucleotides. We propose that binding to TG-rich DNA sequences has been conserved between the mouse and human proteins. In addition, the evolutionary conservation of mitochondrial Lon function is demonstrated by the ability of mouse Lon to substitute for the yeast protein in vivo.


[The trichomes of pericarp in Juglans (Juglandaceae): scanning microscopy, fluorescent microscopy amd histochemistry].
Four types of glandular and non-glandular trichomes of pericarp in four Juglans species (J. ailanthifolia, J. cordiformis, J. mandshurica and J. regia) from Juglandaceae were studied by scanning electron microscopy, fluorescent light microscopy and histochemistry. The capitate trichomes on short stalk, the capitate trichomes on long stalk and the peltate trichomes belong to glandular trichomes; the simple hairs concern to non-glandular trichomes. The investigated species differ one from another in dimensions and distribution oftrichomes as well as the chemical content and the mechanism of secretion. The fluorescent markers and histochemical tests show the presence of flavonoids, tannins and polyphenols in trichomes on short and long stalk. In peltate trichomes the flavonoids and tannins were found in lesser quantity and the polyphenols are absent. In simple hairs the phenolic substances have not been recognized. It has been come out with the suggestion about a functional role of each type of trichomes.


Haplotype-based allele mining in the Japan-MAGIC rice population.
Multi-parent advanced generation inter-cross (MAGIC) lines have broader genetic variation than bi-parental recombinant inbred lines. Genome-wide association study (GWAS) using high number of DNA polymorphisms such as single-nucleotide polymorphisms (SNPs) is a popular tool for allele mining in MAGIC populations, in which the associations of phenotypes with SNPs are investigated; however, the effects of haplotypes from multiple founders on phenotypes are not considered. Here, we describe an improved method of allele mining using the newly developed Japan-MAGIC (JAM) population, which is derived from eight high-yielding rice cultivars in Japan. To obtain information on the haplotypes in the JAM lines, we predicted the haplotype blocks in the whole chromosomes using 16,345 SNPs identified via genotyping-by-sequencing analysis. Using haplotype-based GWAS, we clearly detected the loci controlling the glutinous endosperm and culm length traits. Information on the alleles of the eight founders, which was based on the effects of mutations revealed by the analysis of next-generation sequencing data, was used to narrow down the candidate genes and reveal the associations between alleles and phenotypes. The haplotype-based allele mining (HAM) proposed in this study is a promising approach to the detection of allelic variation in genes controlling agronomic traits in MAGIC populations.


Does Heart Valve Team Risk Assessment Predict Outcomes after Transcatheter Aortic Valve Replacement?
Consideration for transcatheter aortic valve replacement (TAVR) necessitates an integrated risk assessment by members of the Heart Valve Team. The utility of the integrated risk assessment for predicting TAVR outcomes is not established. This article aims to compare the utility of the integrated risk assessment to that of the Society of Thoracic Surgeons Predicted Risk of Mortality (STS-PROM) score for predicting patient outcomes after TAVR. A total of 274 patients who underwent TAVR from January 2016 to August 2017 were included in this study. Patients were deemed intermediate or high risk by two surgeons on the Heart Valve Team based on an integrated risk assessment that incorporates the STS-PROM score, fragility measures, end-organ dysfunction, and surgeon evaluation. Patients were also deemed low, intermediate, or high risk based solely on their STS-PROM scores of <3%, ≥3% to <8%, and ≥8%, respectively. Differences in postoperative outcomes between intermediate- and high-risk groups as categorized by the integrated risk assessment versus STS-PROM were compared. There were no statistically significant differences in postoperative outcomes between patients who were deemed high and intermediate risk by the Heart Valve Team risk assessment. In contrast, postoperative complication rates were significantly higher in patients deemed high risk as compared with intermediate risk by STS-PROM. Integrated risk assessment by the Heart Valve Team is not superior to STS-PROM in predicting postoperative outcomes in patients undergoing TAVR.


Endoscopic Delayed Breast Reconstruction With Expanders and Implants via the Axillary Incision Made for Sentinel Lymph Node Biopsy or Lymphadenectomy.
Classic techniques of delayed prosthetic breast reconstruction use the mastectomy scar as an access route. As a result, the filling of the expander must be postponed until the wounds have healed. This creates an asymmetry between the breasts with the volume changes caused by the filling of the expander, which may occur over several weeks and cause considerable discomfort. Delayed breast reconstruction was performed via the axillary incision made for sentinel lymph node biopsy or lymphadenectomy with endoscopic assistance and detachment of the pectoralis major muscle. The filling of the expander and symmetrization with the contralateral breast was performed in the first stage.The expander was replaced with the definitive prosthesis 3 months later, after endoscopic capsulotomy. Fat grafting was performed to create a lipobed around the implant and to improve tissue quality. Sixty-two patients underwent surgery. Mean follow-up was 19 months. There were no major complications in the reconstructed breast. One case of hematoma in a contralateral breast reduction and an oil cystic mass secondary to fat grafting were recorded. In all cases, the filling of the expander with the definitive volume was possible during the first stage. Endoscopic delayed breast reconstruction with insertion of implants through the axillary incision for sentinel node biopsy or lymphadenectomy is safe and feasible. It achieves complete intraoperative expansion, symmetry between the volumes of the breasts during the first stage, and avoids problems with the scar and the risk of extrusion, as the scar is placed remotely in the axilla.


Mechanistic issues concerning cancer prevention by tea catechins.
The cancer preventive activities of tea (Camellia sinensis, Theaceae) have been demonstrated in animal models for cancers at different organ sites and suggested by some epidemiological studies. Many mechanisms for cancer prevention have been proposed based on studies in cell lines, which demonstrated the modulation of signal transduction and metabolic pathways by (-)-epigallocatechin-3-gallate (EGCG), the most abundant and active polyphenol in green tea. These molecular events may result in cellular changes, such as enhancement of apoptosis, suppression of cell proliferation, and inhibition of angiogenesis. Nevertheless, it is not known whether these are the molecular mechanisms of inhibition of carcinogenesis in animals and humans. This article discusses the key issues involved in extrapolating results from cell line studies to mechanistic information in vivo and in translating animal studies to human cancer prevention.


Neonatologists' practices and experiences in arranging retinopathy of prematurity screening services.
Neonatologists play a central role in identifying infants who require screening for retinopathy of prematurity and in coordinating screening and treatment when necessary. No previous study has evaluated neonatologists' practices or experiences related to these activities. A national mail survey of a random sample of 300 neonatologists was conducted from September to November 2006. The response rate was 62%. Nearly all (98%) of the respondents considered gestational age to identify infants for retinopathy of prematurity screening. However, only 19% used the currently recommended gestational age criterion of 30 weeks; instead, 6% used a lower, more-restrictive criterion, and 74% used a higher, more-inclusive criterion. Fewer respondents (77%) considered birth weight to identify infants for retinopathy of prematurity screening, most of whom (86%) used the current criterion of < or = 1500 g. Although more than one half (67%) of the respondents reported that pediatric ophthalmologists usually screen infants for retinopathy of prematurity in their NICU, nearly one half (46%) reported that retinal specialists provide treatment. Some (36%) reported that they have been unable to transfer a child to a NICU of lower acuity or closer to the child's home because there are no specialists available there for retinopathy of prematurity screening. Some (34%) also reported that they have needed to delay discharge because outpatient follow-up for either screening or treatment of retinopathy of prematurity is not available near the family's home. We found variations in how children are identified for retinopathy of prematurity screening and how screening and treatment are provided. Future research is needed to understand how these variations affect visual outcomes and costs of care. Such work must also consider the impact of regional pediatric eye care workforce shortages on retinopathy of prematurity screening and treatment strategies.


[Use of medicines by the elderly in Santa Rosa, Rio Grande do Sul State, Brazil].
Medicines are one of the most important health care items for the elderly, who are particularly prone to use multiple drugs with a higher number of adverse reactions. The current study aimed to assess the profile of pharmaceutical consumption by the elderly. A cross-sectional epidemiological study used household interviews in a random sample of 294 elderly living in Santa Rosa, Rio Grande do Sul State, Brazil. The elderly represent 9% of the local population. The results showed a mean consumption of 2.79 medicines per individual. The prevalence rate for use of medicines in the previous week was 82%, and of the 827 medicines used by the elderly, 794 (96%) had been prescribed. The most widely used pharmacological classes were anti-hypertensives (21.3%) and diuretics (11.3%). Prevalence of pharmaceutical use was comparable to the results from other studies, thus confirming the importance of medicines in the health of the elderly. The percentage of medicines used without a medical prescription was low. The most frequently reported medicines and formulations were those usually prescribed and dispensed free of cost in the municipal basic health care system, which has been organized for more than 10 years, with coverage of nearly 100%.


[Hormones of adipose tissue in diabetes mellitus and its complications (review of literature and the authors'own data)].
The contemporary ideas on endocrine function of the adipose tissue and its role in pathogenesis of diabetes mellitus and insulin resistance associated with it and the metabolic syndrome are shown in the review. A change in the life style (excessive and irrational nutrition, insufficient physical loading, psychological disorders) and also the reduction of genetic and immunologic controlling mechanisms contribute to the development of obesity, that is now considered as low-grade inflammation. An increased number of small size adipocytes and macrophages of the adipose tissue begin to secrete an increase number of proinflammatory adipocytokines and chemokines that result in the inflammatory and metabolic stress accompanied by the stimulation of signal pathways, leading to increased insulin requirement, on the one hand, and promoting to the beta-cell death, on the other hand. The role of some adipocytokines such as IL-6, TNF-alpha, leptin, adiponectin, visfatin and resistin was demonstrated in these processes.


The effectiveness of an educational intervention in changing nursing practice and preventing catheter-related infection for patients receiving total parenteral nutrition.
Catheter-related infections are one of the most serious complications of TPN therapy. Nurses have important responsibilities in the care of patients who are receiving TPN. This quasi-experimental study was conducted for the purpose of investigating the effectiveness of an educational intervention on changing nursing practice and preventing catheter-related infections in patients receiving total parenteral nutrition. The nurses' practice and the colonisation rate of control and comparative group patients in the surgical clinics of Hacettepe University Hospital (Turkey), and related variables were examined before and after an educational intervention. The findings of the study indicate that the intervention was successful in improving appropriate nursing practice, mean scores of nurses' practices were 45.7 before and 66.5 after the intervention (p<0.05). The rate of microorganism colonisation was also decreased but statistical analysis demonstrated no association between nursing practices and microorganism colonisation of catheter cultures.