A 3-Gene-Based Diagnostic Signature in Alzheimer's Disease.
Alzheimer's disease (AD) is a chronic neurodegenerative disease. In this study, potential diagnostic biomarkers were identified for AD. All AD samples and healthy samples were collected from 2 datasets in the GEO database, in which differentially expressed genes (DEGs) were analyzed by using the limma package of R language. GO and KEGG pathway enrichment was conducted basing on the DEGs via the clusterProfiler package of R. And, the PPI network construction and gene prediction were performed using the STRING database and Cytoscape. Then, a logistic regression model was constructed to predict the sample type. Bioinformatic analysis of GEO datasets revealed 2,063 and 108 DEGs in GSE5281 and GSE4226 datasets, separately, and 15 overlapping DEGs were found. GO and KEGG enrichment analysis revealed terms associated with neurodevelopment. Then, we built a logistic regression model based on the hub genes from the PPI network and optimized the model to 3 genes (ALDOA, ENC1, and NFKBIA). The values of area under the curve of the training set GSE5281 and testing set GSE4226 were 0.9647 and 0.7857, respectively, which implied the efficacy of this model. The comprehensive bioinformatic analysis of gene expression in AD patients and the effective logistic regression model built in our study may provide promising research value for diagnostic methods of AD.


[The results of clinical trials and the prospects of using the Soviet preparation of human recombinant interferon alpha-2 (reaferon) in medical practice].
The results of the clinical trials of human recombinant interferon alpha-2 (reaferon) make it possible to come to the conclusion that the preparation is well-tolerated and produces a pronounced therapeutic effect in a number of viral and oncological diseases. The Pharmacological Committee of the USSR has recommended reaferon for use in acute hepatitis B, hairy cell leukemia, renal cancer at stage IV, disseminated sclerosis, ocular herpes. The use of reaferon has been found to be promising in the treatment of papillomatosis of the larynx, Kaposi's sarcoma, mycosis fungoides, chronic myeloleukemia.


A model for assessing the sensitivity and specificity of tests subject to selection bias. Application to exercise radionuclide ventriculography for diagnosis of coronary artery disease.
A probabilistic model was developed which allows one to estimate sensitivity and specificity of diagnostic tests for coronary artery disease without reference to angiography. The feasibility of the model was evaluated first in a series of computer simulations, and the model was then applied to the assessment of ejection fraction in 933 patients without prior myocardial infarction who underwent exercise radionuclide ventriculography. In 196 patients who were referred to angiography, the conventional abnormal ejection fraction criterion--an absolute rise of less than 0.05 with exercise--had a sensitivity of 79% and a specificity of 68% when referenced to coronary angiography. In 737 patients who were not referred for angiography and who were analyzed instead by our probabilistic model, sensitivity was 63% (p = 0.004 compared to that in the 119 angiographically diseases patients) and specificity was 79% (p = 0.036 compared to that in the 77 angiographic normals). Both the higher sensitivity and lower specificity in the catheterized patients are consistent with a preferential referral of positive test responders to angiography, and of negative test responders away from angiography. The distortion of test sensitivity and specificity which results from this selection bias can be circumvented by substituting a probabilistic estimate of disease for conventional angiographic ascertainment.


Evidence for the catabolism of polychlorinated biphenyl-induced cytochrome P-448 by microsomal heme oxygenase, and the inhibition of delta-aminolevulinate dehydratase by polychlorinated biphenyls.
Polychlorinated biphenyls (PCB) are potent inducers of hepatic microsomal CO-binding hemoprotein P-448 (P1-450) and of delta-aminolevulinate synthetase (ALAS) activity. Inorganic cobalt was able to block PCB induction of cytochrome P-448 and to modify the PCB effect on ALAS activity in a time-dependent manner. PCB were also found to decrease the activity of delta-aminolevulinic acid dehydratase (ALAD) in liver. Pretreatment of rats with cobalt (30 min) produced the following changes in PCB actions on heme metabolism in liver: (a) augmentation of the porphyrinogenic effect of PCB, as determined by the total porphyrin content and ALAS activity; (b) augmentation of PCB inhibition of ALAD activity; and (c) blockade of induction of microsomal hemoprotein (cytochrome P-448). PCB did not interfere with cobalt induction of hepatic heme oxygenase activity. The sequence of administration of the metal and the PCB was important in relation to the changes produced in hepatic ALAS activity and microsomal hemoprotein and heme contents. When cobalt was administered 24 h after PCB treatment, the magnitude of induction of ALAS by PCB was lowered, and there was a great reduction in microsomal hemoprotein and heme contents. The renal response to PCB was different than that of the liver. In the kidney, PCB blocked the induction of heme oxygenase and depletion of cellular heme produced by cobalt. Furthermore, renal microsomal heme content was increased by PCB treatment alone or in combination with cobalt. It is concluded that (a) the heme moiety of microsomal cytochrome P-448 is metabolized by the heme oxygenase system, and it is suggested that for this catabolism to take place, the hemoprotein must be first converted to the denatured form of the hemoprotein, cytochrome P-420; (b) that the synthesis of heme in the kidney and the liver are regulated through different mechanisms; and (c) that ionic cobalt controls activity of ALAS by first inhibiting synthesis of the enzyme followed by the indirect induction of the enzyme as a result of the catabolism of heme, the physiological repressor of ALAS, by the metal-induced heme oxygenase. Thus microsomal heme oxygenase may be viewed as having an overall regulatory role in relation to mictochondrial ALAS by virtue of its ability to catabolize endogenous heme.


Deficit of state-dependent risk attitude modulation in gambling disorder.
Gambling disorder (GD) is often considered as a problem of trait-like risk preference. However, the symptoms of GD cannot be fully understood by this trait view. In the present study, we hypothesized that GD patients also had problem with a flexible control of risk attitude (state-dependent strategy optimization), and aimed to investigate the mechanisms underlying abnormal risk-taking of GD. To address this issue, we tested GD patients without comorbidity (GD group: n=21) and age-matched healthy control participants (HC group: n=29) in a multi-step gambling task, in which participants needed to clear 'block quota' (required units to clear a block, 1000-7000 units) in 20 choices, and conducted a task-functional magnetic resonance imaging (fMRI) experiment. Behavioral analysis indeed revealed a less flexible risk-attitude change in the GD group; the GD group failed to avoid risky choice in a specific quota range (low-quota condition), in which risky strategy was not optimal to solve the quota. Accordingly, fMRI analysis highlighted diminished functioning of the dorsolateral prefrontal cortex (dlPFC), which has been heavily implicated in cognitive flexibility. To our knowledge, the present study provided the first empirical evidence of a deficit of state-dependent strategy optimization in GD. Focusing on flexible control of risk attitude under quota may contribute to a better understanding of the psychopathology of GDs.


Sibutramine improves fat distribution and insulin resistance, and increases serum adiponectin levels in Korean obese nondiabetic premenopausal women.
The aim of this study was to evaluate the effects of sibutramine on body composition and fat distribution, insulin resistance, and serum adiponectin levels in obese women. A total of 28 obese, premenopausal women (mean age, 34.5 +/- 13.7 years; BMI, 31.00 +/- 4.10 kg/m2) was studied before and after 12-week-course of sibutramine (10mg/day). Sibutramine treatment reduced body mass index (P < 0.05) and total body fat (P < 0.05). Abdominal subcutaneous and visceral fat areas (ASFA and AVFA) and mid-thigh low density muscle areas (LDMA) measured by computed-tomography decreased significantly (all, P < 0.05). Insulin resistance (IR) calculated from the homeostasis model assessment (HOMA) method decreased (P < 0.05) and serum adiponectin levels increased significantly (P < 0.05). In our sequential data, the changes of fasting serum insulin levels and the HOMA-IR scores, serum free fatty acids and triglyceride levels, serum adiponectin levels and the mid-thigh LDMA preceded significant changes of body weight, total body fat, and abdominal fat distribution, suggesting sibutramine might improve insulin sensitivity directly by alterations of fatty acid metabolism or secondarily by increasing serum adiponectin levels. Conclusively, sibutramine improved fat distribution and insulin resistance, and increased serum adiponectin levels in Korean obese nondiabetic premenopausal women.


What mechanisms drive cell migration and cell interactions in Pleurodeles?
Embryogenesis implies a strict control of cell interaction and cell migration. The spatial and temporal regulation of morphogenetic movements occurring during gastrulation is directly dependent on the early cell interactions that take place in the blastula. The newt Pleurodeles waltl is a favorable model for the study of these early morphogenetic events. The combination of orthotopic grafting and fluorescent lineage tracers has led to precise early gastrula mesoderm fate maps. It is now clear that there are no sharp boundaries between germ layers at the onset of gastrulation but rather diffuse transition zones. The coordination of cell movements during gastrulation is closely related to the establishment of dorsoventral polarity. Ventralization by U.V. irradiation or dorsalization by lithium treatment modifies the capacity for autonomous migration on the fibronectin coated substratum of marginal zone cells accordingly. It is now firmly established that mesodermal cells need to adhere to a fibrillar extracellular matrix (ECM) to undergo migration during gastrulation. Extracellular fibrils contain laminin and fibronectin (FN). Interaction of cells with ECM involves receptors of the beta 1 integrin family. A Pleurodeles homolog of the alpha v integrin subunit has been recently identified. Protein alpha v expression is restricted to the surface of mesodermal cells during gastrulation. Integrin-mediated interactions of cells with FN are essential for ECM assembly and mesodermal cell migration. Intracellular injection of antibodies to the cytoplasmic domain of beta 1 into early cleavage embryos causes inhibition of FN fibril formation. Intrablastocoelic injections of several probes including antibodies to FN or integrin alpha 5 beta 1, competitive peptides to the major cell binding site of FN or the antiadhesive protein tenascin all block mesodermal cell migration. This results in a complete arrest of gastrulation indicating that mesodermal cell migration is a major driving force in urodele gastrulation. It is now possible to approach the role of fibroblast growth factor (FGF) during cell interactions taking place in urodele embryos. Four different FGF receptors (FGFR) have been cloned in Pleurodeles. Each of them has a unique mRNA expression pattern. FGFR-1, FGFR-3, and the variant of FGFR-2 containing the IIIb exon are maternally expressed and might be involved in mesodermal induction. During gastrulation, FGFR-3 and FGFR-4 have a restricted pattern of expression, whereas FGFR-1 mRNA is nearly uniformly distributed. Splicing variants FGFR-2IIIb and FGFR-2IIIc have exclusive expression patterns during neurulation. IIIb is expressed in epidermis and IIIc in neural tissue, suggesting a function in the differentiation of ectodermal derivatives.


[Epidemiologic monitoring of human rabies in an endemic canine rabies area in the Ivory Coast].
The objective of this study was to analyze the epidemiologic monitoring of human rabies in the rabies medical center of Abidjan. A cross-sectional study was undertaken based on files of patients having consulted in the rabies center after exposure and suspicion of human rabies between January 2001 and June 2009. Twenty-six cases of human rabies were reported in 10,706,136 inhabitants (annual incidence of 0.028 cases per 100,000). The number of detected cases increased considerably after reinforcing the monitoring of the disease. Most cases occurred in an urban environment and concerned both sexes. The most concerned age range was under 31 years. The patients' were mostly school children and housewives. In all cases, the rabid animal was a dog and the type of exposure was a bite. Fifty-six percent of the victims had not received any local treatment and almost all no post-exposure prophylaxis. The mean delay before the first symptoms was 49.5 days after exposure and for death, 4 days after the onset of symptoms. Virological diagnosis was made in four cases. In spite of the increase of cases observed since 2006, certainly due to reinforcement of the monitoring network, improvement is needed to assess the real incidence of rabies in the Ivory Coast.


[Fine motor and self-development assessment of preschool children with epilepsy].
Objective. To assess fine motor and self-care skills in preschool children with epilepsy. Material and methods. The study included 22 children, 12 girls (54.5%) and 10 boys (45.5%), mean age 41.5±19.9 months. Children were tested with DISC and Munchen tests. Results and conclusion. Among preschool children with epilepsy, 50% have impaired and 22.7% - delayed development of fine motor skills. The mean coefficient of fine motor skills was 59.0±28.1. Among preschool children with epilepsy, 36.4% have impaired and 45.5% - delayed development of self-development skills. The coefficient of self-care skills was 57.8±26.1. DISC and Munchen tests for evaluation of small motor and self-care skills are equivalent for assessment in children with epilepsy (p<0.001). Self-care skills were more often disturbed (p<0.05) among children older than 3 years and among boys. Children with psychiatric and movement disorders (72.7%) more frequently have both impaired self-care and fine motor skills (p<0.05).


Development and utilization of a psychometric instrument for measuring quality of life in burn patients, 1976 to 1996.
Our Burn Specific Health Scale was initially developed in 1978. Using a number of existing health scales, including the sickness impact profile, a depression scale, and the activities of daily living scale, and a large number of burn specific items derived from staff and patients, we eventually developed an 80 item instrument. This instrument was divided into four domains each containing 20 items of equal weight. The instrument was validated sequentially with intrarater, interrater and global validation systems, and subsequently compared with a number of other health and mental scales during which it performed very well. We now have longitudinal data which link this measurement system of quality of life to pre-injury educational level, to post-injury, stress disorder and predictability of return to work. The results indicate that total burn size has little to do with quality of life after recovery, and that a number of other factors play a bigger role, which will be presented.


Relationships among resonant frequency changes on a coated quartz crystal microbalance, thickness changes, and resistance responses of polymer-carbon black composite chemiresistors
The relationships among frequency changes on a film-coated quartz crystal microbalance, thickness changes, and dc resistance changes have been investigated for carbon black-insulating polymer composite vapor detectors. Quartz crystal microbalance (QCM) measurements and ellipsometry measurements have been performed simultaneously on polymer films that do not contain carbon black filler to relate the QCM frequency change and the ellipsometrically determined thickness change to the analyte concentration in the vapor phase. In addition, quartz crystal microbalance measurements and dc resistance measurements on carbon black composites of these same polymers have been performed simultaneously to relate the QCM frequency change and dc electrical resistance response to the analyte concentration in the vapor phase. The data indicate that the dc resistance change is directly relatable to the thickness change of the polymers and that a variety of analytes that produce a given thickness change produce a constant resistance change for each member of the test set of polymers investigated in this work.


Are Fast-Bowlers Prone to Back Injuries? Prevalence of Lumbar Spine Injuries in Fast-Bowlers: Review of MRI-Based Studies.
Fast-bowlers in cricket subject their spines to repetitive stress. The aim of this study was to review the prevalence of lumbar spine injuries among fast-bowlers. Medline and embase searches were performed. Further, the authors canvassed the reference list of available articles and used other search engines such as Google Scholar to identify a total of nine studies. The prevalence of lumbar disc degeneration in fast-bowlers ranges from 21-65% with an incidence rate of 15% per year, and the prevalence of lumbar spine bony abnormalities ranges from 24-81%. Factors associated with lumbar spine injury in fast-bowlers are classified into un-modifiable (age) and modifiable (more intense bowling workload and mixed-bowling technique). Fast-bowlers have a high prevalence of lumbar spine injuries. Appropriate interventions, such as educational sessions, may be able to modify risk factors such as bowling workload and bowling technique and thus reduce injury prevalence.


The synthesis and immunogenicity of varicella-zoster virus glycoprotein E and immediate-early protein (IE62) expressed in recombinant herpes simplex virus-1.
In order to evaluate the conditions for optimal expression and immunogenicity of varicella-zoster virus (VZV) proteins in a herpes simplex virus-1 (HSV-1) vector, we selected the VZV glycoprotein E (gE), encoded by ORF 68 and the VZV product of ORF 62, an immediate-early major tegument protein (IE62). Three HSV/VZV recombinants were generated: (1) VZV gE protein coding sequences along with the promoter region were inserted into the thymidine kinase (TK) gene of HSV-1 strain KOS; (2) VZV gE expressed from the HSV-1 ICP4 promoter was inserted into the glycoprotein C (gC) gene of HSV-1 strain F; and (3) VZV IE62 protein coding sequences under the control of the HSV-1 ICP4 promoter were inserted into the gC gene of HSV-1 strain F. Immunoblot analysis and immunoperoxidase staining of infected cell monolayers demonstrated vector expression of VZV proteins. Following intracranial inoculation in mice, both VZV gE-HSV (TK) and VZV IE62-HSV (gC) induced an IgG response against VZV gE or VZV IE62. When tested in cytotoxicity assays using T-lymphocytes from VZV immune human donors, the range of precursor frequencies for T-lymphocytes that recognized VZV gE or VZV IE62 was similar whether these proteins were expressed by HSV-1 or a vaccinia vector. These experiments demonstrate that HSV-1 is a competent vector for expression of these VZV proteins and support the feasibility of engineering a combined vaccine for these closely related alpha-herpesviruses.


CCL3L1 gene copy number in individuals with and without HIV-associated neurocognitive disorder.
CCL3L1 copy number variation has been implicated as a marker for susceptibility and immunity to human immunodeficiency virus (HIV)-1 infection and its pathogenic sequelae. Some of these findings have been confirmed in several, but not all, subsequent independent cohort studies. A three-fold risk for the development of HIV-associated dementia was reported in individuals possessing a CCL3L1 copy number below the ethnic group median combined with a detrimental CCR5 genotype. With the availability of antiretroviral therapy since 1996, there has been a significant decline in HIV-associated dementia, and milder forms of HIV-associated neurocognitive impairment (HAND) are now most prevalent. Moreover, patients are living longer with HIV-1 infection and it is recognized that aging may be a contributory factor to the development of cognitive disorder. Thus, the need for biomarkers that can be used in clinical practice to identify and provide optimal treatment for those at increased risk for HAND is great. HAND affects 20%-30% of HIV-infected individuals, and several genetic loci which have been shown to confer susceptibility to HIV infection may also modulate the development of neurocognitive disorder. The aim of this study was to determine whether CCL3L1 chemokine gene copy number in self-defined ethnic groups could differentiate HIV-infected individuals with and without HAND. Genomic DNA was isolated from buccal swabs or peripheral blood mononuclear cells obtained from HIV-infected patients with or without a diagnoses of neurocognitive dysfunction in the Northeast AIDS Dementia Cohort and National NeuroAIDS Tissue Consortium. To maintain a uniform standard, a quantitative polymerase chain reaction design similar to previous studies using Taqman probes and fixed input DNA between 2 ng and 10 ng was used to determine a CCL3L1 copy number. Standard curves with two-fold dilutions from 25 ng to 1.56 ng were generated. CCL3L1 copy number was determined in triplicate in 262 subjects using quantitative polymerase chain reaction and the relative quantitation method. Data were analyzed using analysis of variance, with significance defined as P < 0.05 and Bonferroni post hoc tests. Significant differences as determined by analysis of variance in CCL3L1 copy number between African-Americans and Caucasians (P < 0.0001) were found, highlighting ethnic group differences in the copy number of this gene. However, there were no differences in CCL3L1 copy number across the neurocognitive groups within each ethnic group. The median CCL3L1 copy number in African-Americans of two and Caucasians of one in this study was significantly lower than the previously reported ethnic group means of two and four copies, respectively. A higher prevalence of abnormal cognition with a relative risk of four was seen in African-Americans versus Caucasians. Based on this nested case-control study, CCL3L1 copy number alone may not be useful for distinguishing between individuals at risk for mild or severe neurocognitive disorder. Additional larger cohort studies are required to determine whether CCL3L1 copy number in combination with polymorphisms in other genes known to contribute to HIV risk will be useful in identifying those at increased risk for HAND.


Health sector demand-side financial incentives in low- and middle-income countries: a systematic review on demand- and supply-side effects.
Demand-side financial incentive (DSF) is an emerging strategy to improve health seeking behavior and health status in many low- and middle-income countries. This narrative synthesis assessed the demand- and supply-side effects of DSF. Forty one electronic data bases were searched to screen relevant experimental and quasi-experimental study designs. Out of the 64 selected papers, 28 were eligible for this review and they described 19 DSF initiatives across Asia, Africa and Latin America. There were three categories of initiatives, namely long-run multi-sectoral programs or LMPs (governmental); long-run health-exclusive programs (governmental); and short-run health-exclusive initiatives (both governmental and non-governmental). Irrespective of the nature of incentives and initiatives, all DSF programs could achieve their expected behavioral outcomes on healthcare seeking and utilization substantially. However, there existed a few negative and perverse outcomes on health seeking behavior and DSF's impact on continuous health seeking choices (e.g. bed net use and routine adult health check-ups) was mixed. Their effects on maternal health status, diarrhea, malaria and out-of-pocket expenditure were under-explored; while chronic non-communicable diseases were not directly covered by any DSF programs. DSF could reduce HIV prevalence and child deaths, and enhance nutritional and growth status of children. The direction and magnitude of their effects on health status was elastic to the evaluation design employed. On health system benefits, despite prioritizing on vulnerable groups, DSF's substantial effect on the poorest of the poor was mixed compared to that on the relatively richer groups. Though DSF initiatives intended to improve service delivery status, many could not optimally do so, especially to meet the additionally generated demand for care. Causal pathways of DSF's effects should be explored in-depth for mid-course corrections and cross-country learning on their design, implementation and evaluation. More policy-specific analyses on LMPs are needed to assess how 'multi-sectoral' approaches can be cost-effective and sustainable in the long run compared to 'health exclusive' incentives.


Ca(2+)-induced Ca(2+) release via inositol 1,4,5-trisphosphate receptors is amplified by protein kinase A and triggers exocytosis in pancreatic beta-cells.
Hormones, such as glucagon and glucagon-like peptide-1, potently amplify nutrient stimulated insulin secretion by raising cAMP. We have studied how cAMP affects Ca(2+)-induced Ca(2+) release (CICR) in pancreatic beta-cells from mice and rats and the role of CICR in secretion. CICR was observed as pronounced Ca(2+) spikes on top of glucose- or depolarization-dependent rise of the cytoplasmic Ca(2+) concentration ([Ca(2+)](i)). cAMP-elevating agents strongly promoted CICR. This effect involved sensitization of the receptors underlying CICR, because many cells exhibited the characteristic Ca(2+) spiking at low or even in the absence of depolarization-dependent elevation of [Ca(2+)](i). The cAMP effect was mimicked by a specific activator of protein kinase A in cells unresponsive to activators of cAMP-regulated guanine nucleotide exchange factor. Ryanodine pretreatment, which abolishes CICR mediated by ryanodine receptors, did not prevent CICR. Moreover, a high concentration of caffeine, known to activate ryanodine receptors independently of Ca(2+), failed to mobilize intracellular Ca(2+). On the contrary, a high caffeine concentration abolished CICR by interfering with inositol 1,4,5-trisphosphate receptors (IP(3)Rs). Therefore, the cell-permeable IP(3)R antagonist 2-aminoethoxydiphenyl borate blocked the cAMP-promoted CICR. Individual CICR events in pancreatic beta-cells were followed by [Ca(2+)](i) spikes in neighboring human erythroleukemia cells, used to report secretory events in the beta-cells. The results indicate that protein kinase A-mediated promotion of CICR via IP(3)Rs is part of the mechanism by which cAMP amplifies insulin release.


Modulation by hyperpolarization-activated cationic currents of voltage responses in human rods.
We used the whole-cell patch-clamp recording technique on surgically excised human retina to examine whether human rod photoreceptors express hyperpolarization-activated cationic currents (I(h)) and to analyze the effects of I(h) on rod's voltage responses. Hyperpolarizing voltage steps from a holding potential of -60 mV evoked a slow inward-rectifying current in both rods in retinal slices and isolated rods. The slow inward-rectifying currents induced by hyperpolarization were markedly reduced by 3 mM Cs(+) (a blocker of I(h)) in the bath, but not by 3 mM Ba(2+) (an anomalous rectifier K(+) current blocker) or 1 mM SITS (a Cl(-) current blocker). A concentration-response curve for block by Cs(+) of the inward currents could be fitted by the Hill equation with a half-blocking concentration (IC(50)) of 41 microM and a Hill coefficient of 0.91. The time course of the inward current activation was well described at all recorded voltages by the sum of two exponentials. Under current-clamp conditions, injection of steps of current, either hyperpolarizing or depolarizing, elicited an initial rapid voltage change that was followed by a gradual decay in the voltage response. The decay in the voltage responses was eliminated by bath application of 3 mM Cs(+). The voltage dependence, pharmacology, and kinetics of the slow inward-rectifying currents described above suggest that human rods express I(h). We suggest that I(h) becomes activated in the course of large hyperpolarizations generated by bright-light illumination and may modify the waveform of the photovoltage in human rods.


Radiological-pathological correlation in diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH): imaging and histopathology.
To review histologically confirmed diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) cases and carry out a detailed pathological-radiological correlation to see if computed tomography (CT) can be used to confidently identify DIPNECH. Twenty-three histologically confirmed DIPNECH patients in the shared database of two NHS Trusts were reviewed. CT images were reviewed by two independent radiologists, each of them with >10 years of experience in thoracic imaging. All histological specimens were reviewed by a single pathologist with >25 years of experience. The diagnosis of DIPNECH was made according to the current World Health Organization (WHO) definition included in the WHO 2015 classification of pulmonary tumours. The results on histology were compared to the presence of nodules and air trapping on CT. Demographic information and, when available, molecular imaging studies and pulmonary function tests were also considered. There are prototypal clinical and radiological findings reflecting the presence of underlying histological DIPNECH: middle-aged women with multiple small and scattered nodules due to the clustering and proliferation of neuroendocrine cells. At least one larger, dominant, lung nodule reflecting a carcinoid tumour is very common and mosaic attenuation/air trapping is seen approximately in 50% of cases in inspiratory scans. Airflow obstruction is rarely associated with histological bronchial or peribronchial fibrosis, which suggests other mechanisms must be involved in its development. CT can be used to predict pathological DIPNECH in the appropriate clinical setting. It is important to consider DIPNECH to avoid overdiagnosis of more sinister conditions such as lung cancer or metastases.


Comprehensiveness in the perspective of public health: pathways for the training of the nurse.
to present an academic practice experienced by professors in a curricular unit of the public health field entitled "Comprehensive health care", offered in the undergraduate nursing course of a public university. experience report of dialogic activities between professors and undergraduates. it was possible to discuss nursing care from the perspective of comprehensiveness, which allowed the understanding of the need to broaden the scope regarding the practices conducted in primary care and enabled the attribution of new meanings to the actions experienced by undergraduate students in their curricular internships; thus, contributing to the training of a professional with critical and creative capacity. the students were able to understand that quality care should go beyond complaint-behavior, providing care based on a networked health service structure aligned with SUS policies and programs.


More than the terrible twos: the nature and severity of behavior problems in clinic-referred preschool children.
The primary goals of this study are to describe the nature and severity of disruptive behavior problems in clinic-referred preschoolers from low-income environments and to explore the validity of DSM-IV disruptive disorders for young children. We examine the relation between DSM-IV symptoms, standardized behavior checklists, and observational ratings as a means of exploring measurement validity in this age group. Seventy-nine clinic-referred preschoolers (ages 2 through 5 years) from low-income environments were assessed. To examine whether clinic-referred preschool children have symptoms that are consistent with DSM-IV disruptive behavior disorders, parents were administered a semistructured diagnostic interview, modified for developmentally appropriate usage. In addition, parents completed the Child Behavior Checklist (CBCL) and children's behavior problems were assessed with observational ratings during parent-child interaction. Nearly half of the sample met criteria for conduct disorder, and three quarters met criteria for oppositional defiant disorder. Preliminary evidence for the validity of DSM-IV disruptive disorders in preschool children was demonstrated through association with CBCL scores, behavior ratings, and significant levels of impairment. Future efforts aimed at validating these diagnoses in preschoolers and implications for prevention are discussed.


Retrospective Analysis of the Safety and Efficacy of Sugammadex Versus Neostigmine for the Reversal of Neuromuscular Blockade in Children.
Sugammadex, with its novel mechanism of action of encapsulation and noncompetitive binding of aminosteroid neuromuscular-blocking agents (rocuronium and vecuronium), may offer distinct advantage to pediatric patients where residual neuromuscular blockade may be poorly tolerated. Data describing its use in the pediatric population are limited, and no large-scale studies are available evaluating the occurrence of adverse event across the full spectrum of ages. We sought to measure the occurrence of adverse events, assess the severity and clinical significance of the events, and quantify a surrogate measure of efficacy of sugammadex compared to neostigmine in a large population and in the full age range of children. Beginning in September 2016 through initiation of data collection, we identified from our data warehouse that all patients were treated with sugammadex for reversal of neuromuscular blockade, from birth through adolescence, and retrospectively matched, by case type and age group, to historical neostigmine-treated controls. From subsequent chart review, we quantified occurrence of adverse events and administration of medications to treat adverse events. All cases in the originally identified cohort treated with epinephrine after administration of sugammadex underwent chart review to elicit the cause, in the event that an infrequently occurring event was not captured after the case-matching process. "End-Interval Time," the time from administration of reversal agent to time out of the procedure room, was measured as an indirect assessment of efficacy. Fewer cases of bradycardia were observed in the sugammadex group compared to the neostigmine group in the overall cohort (P < .001) and in the subgroups of older children (P < .001) and adolescents (P < .001). End-interval time, the time measured from administration of neuromuscular blockade (NMB) reversal agent to time out of the operating room, was significantly shorter in sugammadex-treated groups in the overall cohort (mean difference, 2.8; 95% CI, 1.85-3.77; P < .001) and all age groups except for first year (31 days through 12 months). This observation was most pronounced in the neonatal subgroup (mean difference, 11.94 minutes; 95% CI, 4.79-19.1; P < .001). No other adverse events measured were found to be different between treatment groups. This study provides data supporting the safe and effective use of sugammadex for reversal of neuromuscular blockade throughout the entire range of ages in the pediatric population. Within age groups, sugammadex demonstrates faster completion of operation compared with neostigmine, with the greatest difference observed in the neonatal population.


Percutaneous and mucocutaneous exposures in nursing students: an Italian observational study.
To investigate occupational exposures to biological material potentially infected by blood-borne viruses in nursing student population during the course years. An observational retrospective study was designed. Data were collected in May 2007. Two-thousand-two-hundred-fifteen nursing students from the 3 years of degree course were enrolled in the four Italian universities. A structured questionnaire was constructed and was given out unannounced to nursing students in four universities on a randomly chosen day. The likelihood of association between nursing student exposure and certain assumed risk factors was measured. The exposure risk is associated with each study year of nursing students. Specifically, the probability of accidental exposure is reduced significantly with the increase of clinical skills during the training period. The risk for exposure in the 1st year students appears significantly higher than in those of the next years (odds ratio [OR] 1.465; 95% confidence interval [CI] 1.105-1.943). Data highlighted a gradual increase of bio-safety knowledge in nursing students from the 1st to the 3rd years of study. However, a statistically significant association exists only between awareness of a correct use of gloves and exposure risk (OR 0.435; 95%CI 0.227-0.834). Mucocutaneous exposures are more frequent than percutaneous exposures (62.2%), and the hollow-bore needle is the device most often involved. In 42.5% of cases, accidental exposures occurred when nursing students are working alone in a medical ward or surgery area. During their clinical training, nursing students can encounter a real risk for percutaneous and mucocutaneous exposures to blood potentially infected with blood-borne viruses. However, this risk is reduced with an increase in clinical skills. Results show that some new strategies are necessary for exposure risk reduction such as development of simulation laboratories for nursing practice and the adequate presence of tutors in clinical training education.