Modification of the adenylate cyclase activity of bovine thyroid plasma membranes by manipulating the ganglioside composition with a nonspecific lipid transfer protein.
Gangliosides (GM1, GT1b, GD3) were incorporated in bovine thyroid plasma membranes using the nonspecific lipid transfer protein from beef liver. The transfer of GT1b or GD3 in the presence of 16 units of transfer protein was twice as high as that of GM1. However, taking into account the spontaneous exchange (approximately 8% for GT1b or GD3 and 1% for GM1) the transfer protein seemed to be more effective for GM1. Incorporation of these gangliosides in bovine thyroid plasma membranes caused a concentration dependent inhibition of the TSH-stimulated adenylate cyclase activity. The forskolin-stimulated adenylate cyclase activity was not significantly affected by ganglioside modification of the plasma membranes, indicating that the gangliosides do not act at the level of the catalyst of adenylate cyclase. Binding experiments on the other hand revealed that TSH binding to bovine thyroid plasma membranes was inhibited with the same order of efficacy (GT1b greater than GD3 greater than GM1) and to the same extent as their inhibitory effect on TSH stimulation. Therefore, this indicates that the ganglioside induced drop in TSH binding might be an important factor in the decrease in TSH-stimulated adenylate cyclase activity. Incorporation of GT1b or GD3 (approximately 11 nmol) in bovine thyroid plasma membranes, however, also induced a substantial decrease in cholera toxin-stimulated adenylate cyclase activity (approximately 30%) and to a lesser degree a decrease in NaF-stimulated activity (approximately 17%), whereas GM1 incorporation did not significantly affect these stimulated activities. These latter inhibitory effects were paralleled by changes in fluorescence steady-state anisotropy: GT1b modification of the plasma membranes provoked a slight increase in TMA-DPH anisotropy, whereas the anisotropy of DPH was substantially enhanced after incorporation of GD3 or GT1b. These results suggest that gangliosides might also interfere with the coupling between the alpha-subunit of the stimulatory GTP-binding regulatory protein and the catalyst of the adenylate cyclase system by affecting the membrane fluidity.


Passive Q switching of a solar-pumped Nd:YAG laser.
Passive Q switching is a preferable choice for switching the Q factor of a solar-pumped laser because it requires neither a driver nor an electrical power supply. The superior thermal characteristics and durability of Cr(4+):YAG single crystals as passive Q switches for lamp and diode-pumped high-power lasers has been demonstrated. Here we report on an average power of 37 W and a switching efficiency of 80% obtained by use of a solar-pumped Nd:YAG laser Q switched by a Cr(4+):YAG saturable absorber. Concentration of the pumping solar energy on the laser crystal was obtained with a three-stage concentrator, composed of 12 heliostats, a three-dimensional compound parabolic concentrator (CPC) and a two-dimensional CPC. The water-cooled passive Q switch also served as the laser rear mirror. Repetition rates of as much as 50 kHz, at pulse durations between 190 and 310 ns (FWHM) were achieved. From the experimental results, the saturated single-pass power absorption of the Cr(4+):YAG device was estimated as 3 ? 1%.


Anti-tumor necrosis factor monoclonal antibody therapy for gastrointestinal Behçet's disease: a case report.
Behçet's disease (BD) is a multisystem immune-mediated inflammatory disorder that involves the intestine in 3%-26% of cases. Corticosteroids, 5-aminosalicylic acid derivatives, immunomodulators, and more recently thalidomide and pentoxifylline have been used to treat BD with varying degrees of success. Tumor necrosis factor (TNF)-alpha is believed to play a pivotal role in this T helper cell type 1 (Th1)-mediated disease. Infliximab, a chimeric monoclonal antibody to TNF-alpha, has been demonstrated to be an effective therapy for Crohn's disease and rheumatoid arthritis, 2 other Th1-mediated disorders. We describe a patient with chronically active, steroid-dependent BD involving the gastrointestinal tract who received 4 doses of infliximab during a 6-month period. Because most of her symptoms were gastrointestinal, the Crohn's Disease Activity Index (CDAI) was used to assess response. A rapid and dramatic improvement in both gastrointestinal and extraintestinal symptoms was observed. The CDAI score decreased from 270 points (preinfusion) to 13 points by week 2, and remission was sustained despite complete withdrawal of steroids. Colonoscopy performed 10 weeks after the first infusion showed marked endoscopic and histologic improvement. This report suggests that infliximab may be an effective new therapy for gastrointestinal BD, and perhaps other manifestations of BD as well.


Pregnancy complications, sick leave and service needs of women who experience perinatal distress, weak social support and dissatisfaction in their partner relationships.
Although perinatal distress is acknowledged as a burdening condition for pregnant women, its effects on pregnancy are not well known. This study was conducted to increase knowledge regarding the effects of distress on pregnancy-related problems. The study also assessed women's need for sick leave and increased prenatal care due to distress, and the effects of weak social support and dissatisfaction with their partner relationships. In total, 2523 women were screened for perinatal distress three times during pregnancy in this quantitative cohort study. Structured psychiatric interviews were conducted following the screening, with 562 of the participants. Data from participants' pregnancy records were also analysed. The study was conducted in primary healthcare centres in Iceland after receiving approval from the Icelandic National Bioethical Committee. The main outcome measures were pregnancy problems, sick leave issued and prenatal service needs. Data from 503 women were analysed. The perinatal distress group (PDG) was significantly more likely than was the nondistressed group (NDG) to experience fatigue, vomiting and pelvic pain after controlling for background variables. Distressed women who reported weak family support experienced symptoms of nausea and heartburn. The PDG needed more frequent prenatal care than did the NDG and was issued sick leave for up to 42 days longer. Dissatisfaction in the partner relationship and with the division of household tasks and childcare was strongly associated with distress, the development of complications and the need for sick leave. Identification of perinatal distress by midwives and other healthcare professionals is important, since distress may be linked to women's complaints of fatigue, vomiting, pelvic pain and need for prolonged sick leave, and additional prenatal care services will be needed. Perceived dissatisfaction in the partner relationship and with the division of household tasks should also form part of clinical practice and assistance provided.


Effects of colon to antrum transposition on gastrin release and antral G-cell proliferation.
To investigate the effects of colonic mucosa on antral G-cell activity and proliferation, a colonic patch was transposed to the antrum. Thirty-nine rats were divided into 3 equal groups and underwent the following surgical procedures: Group 1: sham operation. Group 2: a standard portion (1 cm2) of the anterior surface of the antrum, including the pyloric sphincter, was removed and the defect was closed using a 10 mm segment of transverse colon shaped as a patch. Group 3 (control group): an identical procedure was carried out, closing the gastric defect with a gastro-duodenal suture. Three months after surgery, serum gastrin levels were determined by radioimmunoassay, both in fasting and freely fed animals. The antrum was then removed and examined for: counts of antral G-cell number by an immunoperoxidase method; evaluation of the cytoplasmic G-cell granule distribution (assumed as an index of gastrin turnover) by transmission electron microscopy investigation. The colon to antrum transposition significantly increased the antral G-cell density. By contrast, fasting serum gastrin levels and gastrin turnover were reduced after colon to antrum transposition, as compared with the relevant control procedure.


Total synthesis of (-)-borrelidin.
The total synthesis of borrelidin has been achieved. The best feature of our synthetic route is SmI(2)-mediated intramolecular Reformatsky-type reaction for macrocyclization after esterification between two segments. The two key segments were synthesized through chelation-controlled carbotitanation, chelation-controlled hydrogenation, stereoselective Reformatsky reaction, and MgBr(2).Et(2)O-mediated chelation-controlled allylation. [reaction: see text]


Primary health care theory to practice: experience of first-year nursing students in Hong Kong.
In the past, nursing education in Hong Kong has focused on acute illness care, and institutions providing nursing education have been slow to modify the illness-focused curriculum to a health-based curriculum. The nursing curriculum at the University of Hong Kong is unique in that it focuses on primary health care, and these concepts are introduced in both theory and practice in the first year of the baccalaureate program. In the second semester of the first year, students are required to develop and implement a primary health care project in a community setting. This article outlines the process and outcomes of the experience of 8 first-year nursing students who developed and implemented a primary health care project with older adults in a Hong Kong community. The Generalized Model for Program Development (McKenzie & Smeltzer) was used to guide the students in their practicum activities. The students demonstrated a high degree of competency in relation to health assessment skills; analysis of individual and community needs; development of appropriate health promotion sessions in relation to coronary artery disease, diabetes mellitus, and arthritis; and evaluation strategies to demonstrate effectiveness of the intervention. This experience early in the program provided a strong foundation for the students in primary heath care and grounded their nursing practice in scientific-based evidence.


Rho-regulated signals induce apoptosis in vitro and in vivo by a p53-independent, but Bcl2 dependent pathway.
Rho proteins are a branch of GTPases that belongs to the Ras superfamily which are critical elements of signal transduction pathways leading to a variety of cellular responses. This family of small GTPases has been involved in diverse biological functions such as cytoskeleton organization, cell growth and transformation, cell motility, migration, metastasis, and responses to stress. We report that several human Rho proteins including Rho A, Rho C and Rac 1, are capable of inducing apoptosis in different cell systems like murine NIH3T3 fibroblasts and the human erythroleukemia K562 cell line. Since K562 cells are devoid of p53, apoptosis induced by Rho in this system is independent of p53. Rho-dependent apoptosis is mediated by the generation of ceramides, and it is drastically inhibited by ectopic expression of Bcl2, both under in vitro and in vivo conditions. Furthermore, the human oncogenes vav and ost that have been shown to function as guanine exchange factors for Rho proteins, were also able to induce apoptosis under similar conditions. Finally, we also report that the levels of endogenous Rho proteins are increased when U937 myeloid leukemia cells are exposed to apoptosis-inducing conditions such as TNF alpha treatment. Furthermore, TNF alpha-induced apoptosis in these cells is inhibited by expression of a dominant negative mutant of Rac 1 but it is not affected by a similar mutant of Rho A. These results suggest that Rho proteins play an important role in the physiological regulation of the apoptotic response to stress-inducing agents.


Excitation spectrum and effective mass of the even-fraction quantum hall liquid
To probe the nature of the even-fraction quantum Hall system, we have investigated the low-lying excitation spectrum by exact diagonalization for finite systems. We have found (i) a striking one-to-one correspondence (i.e., a shell structure) between the spectrum and those for free (composite) fermions, (ii) a surprisingly straight scaling plot for the excitation energy that gives a zero gap (metal) in the thermodynamic limit, (iii) the effective mass evaluated from the scaling becoming heavier for nu = 1/2,1/4,1/6, but (iv) some deviations from the single-mode or the Hartree-Fock composite fermion approximation.


Defeating feature fatigue.
Consider a coffeemaker that offers 12 drink options, a car with more than 700 features on the dashboard, and a mouse pad that's also a clock, calculator, and FM radio. All are examples of "feature bloat", or "featuritis", the result of an almost irresistible temptation to load products with lots of bells and whistles. The problem is that the more features a product boasts, the harder it is to use. Manufacturers that increase a product's capability--the number of useful functions it can perform--at the expense of its usability are exposing their customers to feature fatigue. The authors have conducted three studies to gain a better understanding of how consumers weigh a product's capability relative to its usability. They found that even though consumers know that products with more features are harder to use, they initially choose high-feature models. They also pile on more features when given the chance to customize a product for their needs. Once consumers have actually worked with a product, however, usability starts to matter more to them than capability. For managers in consumer products companies, these findings present a dilemma: Should they maximize initial sales by designing high-feature models, which consumers consistently choose, or should they limit the number of features in order to enhance the lifetime value of their customers? The authors' analytical model guides companies toward a happy middle ground: maximizing the net present value of the typical customer's profit stream. The authors also advise companies to build simpler products, help consumers learn which products suit their needs, develop products that do one thing very well, and design market research in which consumers use actual products or prototypes.


Colonoscopic decompression for pseudo-obstruction of the colon.
The purpose of this report was to review the authors' experience with colonoscopy as a method of treating patients with acute colonic distention. For the period 1981-1987, 19 patients at two teaching hospitals met the selection criteria for this study. In terms of measurable decompression of a colon distention, colonoscopy was successful in 89 per cent of patients, although 41 per cent required repeat endoscopic decompression during their hospital stay. The procedure failed in two patients (11%) and operative decompression was necessary. The authors have found that colonoscopy is a useful procedure for determining the cause of progressive colon distention and for providing safe and effective treatment.


Effect of cigarette smoke on hepatic and pulmonary cytochromes P450 in mouse: evidence for CYP2E1 induction in lung.
Pulmonary and liver microsomes of male NMRI mice were used to study the inductive effect of cigarette smoke on various cytochrome P450 isoforms implicated in precarcinogen and premutagen bioactivation. The enzymatic activities catalyzed by CYP1A1, CYP2B, CYP2C, CYP2D, CYP2E1 and CYP3A were induced in liver microsomes. Immunoquantification of lung and liver CYP1A1, 2E1 and 3A demonstrated that 1) CYP1A1 was induced in lung and liver, 2) CYP3A subfamily was induced in liver and not detected in lung, 3) CYP2E1 was slightly induced in liver whereas its pulmonary expression was more largely increased (6.8 fold) than CYP1A1 (2.0 fold). This latter data suggests that CYP2E1, which is known to be expressed in human lung, could actively participate in pulmonary carcinogenesis induced by cigarette smoke.


Is soil dressing a way once and for all in remediation of arsenic contaminated soils? A case study of arsenic re-accumulation in soils remediated by soil dressing in Hunan Province, China.
The investigation of arsenic (As) re-accumulation in an area previously remediated by soil dressing will help in sustainable controlling the risks of As to local ecosystems and should influence management decisions about remediation strategies. In this study, As content in an area remediated by soil dressing and the possible As accumulation risk in agricultural products were investigated. The results indicated that after 7 years of agricultural activities, the average As content (24.6 mg kg(-1)) in surface soil of the investigated area increased by 83.6% compared with that (13.4 mg kg(-1)) in clean soil. Of the surface soil samples (n = 88), 21.6% had As levels that exceeded the limits of the Environmental Quality Standard for Soils of China (GB 15618-1995) and 98.9% of the surface soil samples with As contents exceeding that in clean soil was observed. Soil dressing might be not a remediation method once and for all in some contaminated areas, even though no significant difference in available As content was found between clean (0.18 mg kg(-1)) and surface (0.22 mg kg(-1)) soils. The foreign As in surface soil of the investigated area mainly specifically sorbed with soil colloid or associated with hydrous oxides of Fe and Al, or existed in residual fraction. The upward movement of contaminated soil from the deeper layers and the atmospheric deposition of slag particles might be responsible for the re-accumulation of As in the investigated area. Decreases in soil pH in the investigated soils and the fact that no plant samples had As levels exceeding the limits of the National Food Safety Standards for Contaminants of China (GB 2762-2012) were also observed.


Reduced antegrade flow in the coronary sinus is a predictor of coronary artery stenosis in hypertensive patients.
The purpose of this study was to evaluate the feasibility of assessing blood flow in the coronary sinus by transthoracic Doppler echocardiography for detecting coronary artery stenosis in hypertensive patients. Flow in the coronary sinus was studied in 105 participants who all had undergone coronary angiography: 35 nonhypertensive patients, 34 hypertensive patients without coronary artery disease (CAD), and 36 hypertensive patients with CAD. The antegrade phase of flow in the coronary sinus was analyzed and compared among the groups. Multivariate analysis for blood flow and coronary artery stenosis was done. Compared with the nonhypertensive patients, the hypertensive patients without CAD had significantly higher blood flow (9.36 ± 5.94 vs 5.84 ± 2.91 mL/stroke and 584.45 ± 177.32 vs 327.68 ± 125.48 mL/min, respectively; P < .001) in the coronary sinus. Compared with the hypertensive patients without CAD, those with CAD had significantly lower blood flow (5.18 ± 0.72 vs 9.36 ± 5.94 mL/stroke and 352.51 ± 156.18 vs 584.45 ± 177.32 mL/min; P < .001) and a lower velocity time integral (13.14 ± 2.51 vs 19.85 ± 4.89 cm; P < .01). Stepwise multiple regression analysis indicated that the coronary sinus diameter, velocity time integral, and heart rate significantly correlated with the blood flow per minute in the coronary sinus in each group, and the flow per minute was the independent determinant of the percent stenosis diameter. The sensitivity, specificity, and accuracy for the prediction of severe stenosis (>70%) in the left coronary artery were 91.07%, 87.76%, and 88.49% for blood flow of less than 220 mL/min in the coronary sinus. Transthoracic Doppler echocardiography can effectively depict blood flow changes in the coronary sinus, and reduced antegrade flow is a sensitive and specific predictor of coronary artery stenosis in hypertensive patients.


Diagnostic features associated with culture of Mycobacterium tuberculosis among young children in a vaccine trial setting.
To identify diagnostic features associated with culture of Mycobacterium tuberculosis (MTB), the standard for tuberculosis (TB) diagnosis, to inform clinical end point definitions for new TB vaccine trials. Children <2 years of age (n = 1445) were screened and investigated for TB during a Bacille Calmette Guerin vaccine trial in South Africa. Standardized clinical, radiologic, and microbiologic data were collected, including paired gastric lavage and induced sputum for MTB liquid culture. Adjusted odds ratios (AORs) were calculated using a multivariate logistic regression model. Adjusted odds of positive MTB culture increased by 90% with history of wheezing (AOR, 1.9) and by 4% with each 1-mm increase in Mantoux diameter (AOR, 1.04). Odds of positive MTB culture doubled if the chest radiograph was suggestive of pulmonary TB (AOR, 2.16) and more than tripled if lower chest retraction was observed clinically (AOR, 3.37). Fever, night sweats, and presence of lymphadenopathy were negatively associated with MTB culture (AOR: 0.5, 0.62, and 0.2, respectively). Persistent cough, weight loss, and failure to thrive were not significantly associated with MTB culture in this study population. Wheezing and lower chest retraction, consistent with intrathoracic airway obstruction; chest radiography suggestive of pulmonary tuberculosis; and Mantoux diameter were predictive of positive MTB culture. These variables should be considered for inclusion in composite clinical end point definitions for infant TB vaccine trials. Several clinical features, commonly used for TB diagnosis in older children, were not associated with positive MTB culture among children younger than 2 years.


Plasma leptin in children: relationship to puberty, gender, body composition, insulin sensitivity, and energy expenditure.
Leptin has been demonstrated to reflect body fat mass (FM) in humans, but the regulation of leptin levels during childhood growth and development is poorly understood. We studied the relation between plasma leptin, fasting insulin, insulin sensitivity, and resting energy expenditure in 22 healthy prepubertal children and 27 adolescents. Body composition was assessed by the H2(18)O-dilution principle, insulin sensitivity by a hyperinsulinemic (40 mU/m2/min)-euglycemic clamp, and energy expenditure by indirect calorimetry. Plasma leptin in prepubertal children (9.3 +/- 2.0 ng/mL) was not different from that in pubertal adolescents (10.9 +/- 2.2 ng/mL). Plasma leptin correlated with FM (r = .77, P < .001). There were no gender differences in leptin after controlling for FM differences. In prepubertal and pubertal subjects, plasma leptin correlated with fasting insulin independently of FM (r = .60, P < .001), but did not correlate with insulin sensitivity independently of body fat content. Leptin showed no relationship to resting energy expenditure after adjusting for body composition. The present cross-sectional evaluation of normal children shows that (1) plasma leptin reflects body fat content, (2) leptin concentrations are similar between prepubertal children and pubertal adolescents, (3) there are no gender differences in leptin independent of adiposity, and (4) leptin correlates with fasting insulin but not with insulin sensitivity. Contrary to animal data, our cross-sectional results in healthy children do not suggest a role for leptin in puberty or a female-related leptin resistance as reported in adults. It remains to be determined at which stage of human development the sexual dimorphism in leptin becomes evident.


Immunopathogenesis of abdominal sepsis.
Sepsis is an unsolved problem worldwide, with a 30-50 % mortality rate. The recent failures of anti-TLR4, recombinant activated protein C, and anti-TNF in clinical trials indicate a need to rethink our current understanding of sepsis’s pathophysiology. While the initial immune response is crucial for effective clearance of invading pathogens, an overly exuberant host response to infection can cause septic shock, tissue damage, and death. Profuse inflammation in sepsis is frequently followed by global immunosuppression that increases susceptibility to viral and bacterial infections. Despite the dangers of immune over-response, the immune system’s anti-inflammatory activities are likely necessary to reduce the initial over-activation of the immune system. With this review, we want to illuminate the different aspects of immune response to sepsis and provide insight to the ongoing difficulties currently present within sepsis research. Future treatment strategies for sepsis should focus on maintaining balance between pro- and anti-inflammatory immune actions in a timely manner.


Implications of patient-borne costs associated with pediatric neurosurgical care in eastern Africa.
OBJECTIVE Pediatric neurosurgery can be highly cost-effective even in the developing world, but delivery of these services is hampered by resource limitations at the levels of both health care infrastructure and individual patients. Few studies have evaluated costs borne by neurosurgical patients in the developing world and their potential implications for efficient and effective delivery of care in this population. METHODS The families of 40 pediatric neurosurgery patients were surveyed in February 2015 at the AIC Kijabe Hospital in Kijabe, Kenya. Costs associated with obtaining inpatient care were assessed. RESULTS Patient families were charged an average of US $539.44 for neurosurgical services, representing 132% of their annual income. Indirect expenses (transport, food and lodging, lost wages) constituted US $79.37, representing 14.7% of the overall cost and 19.5% of their annual income. CONCLUSIONS Expansion of pediatric neurosurgical services throughout the developing world necessitates increased attention to seemingly insignificant expenses that are absorbed by patients and their families. Even when all direct costs are covered at the institutional or national level, without additional assistance, some patients may be too poor to obtain even "free" neurosurgical care.


Laboratory-confirmed invasive meningococcal disease: effect of the Hajj vaccination policy, Saudi Arabia, 1995 to 2011.
Saudi Arabia (SA) experienced two large invasive meningococcal disease (IMD) outbreaks during the 2000 and 2001 Hajj pilgrimages. In 2002, polysaccharide quadrivalent ACWY vaccines became mandatory for Mecca and Medina pilgrims/residents older than two years. This study aimed to analyse IMD surveillance data among citizens, residents and pilgrims in SA from 1995 to 2011, focusing on changes before and after the new vaccination policy. For all laboratory-confirmed IMD cases in the national surveillance database from 1995 to 2011, serogroup and age were retrieved. The cases' seasonal distribution as well as the case fatality ratios (CFR) were obtained. For Saudi citizens/residents and Hajj pilgrims, annual rates were calculated using mid-year population estimates. The Student's t-test was used to compare means between the pre-epidemic (1995-1999) and post-epidemic (2002-2011) periods, excluding outbreak years. From 1995 to 2011, laboratories notified 1,103 cases. Between the pre- and post-epidemic periods, mean annual IMD rates decreased from 0.20 (standard deviation (SD): 0.1) to 0.06 cases/100,000 (SD: 0.06; p=0.02), mean numbers of Hajj-related cases from 13 (SD: 9.3) to 2 cases/year (SD: 2.3; p=0.02) and the mean age from 31 (SD: 1.3) to 18 years (SD: 1.4; p<0.01). The CFR in Saudi citizens (10.4) was lower than among foreign pilgrims (28.9) and decreased from 19.3% (SD: 1.8) in the pre-epidemic to 11.4% (SD: 7.0; p=0.04) in the post-epidemic phase. The decrease of annual IMD rates, CFR and Hajj-related cases between the pre- and post- vaccine era suggests a possible positive effect of the mandatory ACWY vaccination for pilgrims/residents in Mecca and Medina. Regular surveillance with an annual data analysis is necessary to monitor trends and circulating serotypes and to implement appropriate public health measures to avoid new IMD epidemics during upcoming Hajj seasons.


Desensitization by histamine of H2 receptor-mediated adenylate cyclase activation in the human gastric cancer cell line HGT-1.
Short-term treatment of cultured HGT-1 cells with histamine produced a time-dependent (half-life: 20 min) and homologous desensitization of histamine H2 receptor activity mediating cAMP generation in HGT-1 cells and gastric acid secretion in normal gastric mucosa. Histamine treatment resulted in loss of response of the adenylate cyclase to histamine in purified plasma membranes, but had no effect on basal, vasoactive intestinal peptide (VIP)- or NaF-stimulated enzyme activities. We propose that the desensitization of gastric histamine H2 receptor by histamine evidenced in cellular or subcellular preparations from HGT-1 cells could be involved in the physiological regulation and pharmacological control of gastric cell function in man.


Outpatient parenteral antibiotic therapy. Management of serious infections. Part II: Amenable infections and models for delivery. Osteomyelitis.
Osteomyelitis is one of the most common and well-established indications for outpatient parenteral antibiotic therapy. Because patients are usually otherwise healthy and therapy is prolonged (four to six weeks), this infection is especially suited to outpatient management. While most gram-negative infections in adults can be treated with an oral quinolone, others usually require IV therapy.


Exposure to elevated temperatures and risk of preterm birth in Valencia, Spain.
Prematurity is the second-leading cause of death in children under the age of 5 worldwide. It is predicted that the future climate will have more intense, longer lasting and frequent extreme heat episodes, and so the temperature effect on the risk of preterm birth is generating considerable interest in the public health field. Our aim was to explore the potential short-term effects of elevated temperatures on the risk of preterm birth in Valencia (Spain). All singleton natural births born in the metropolitan area of Valencia during the warm season (May-September, 2006-2010) were included (N=20,148). We applied time-series quasi-Poisson generalized additive models to evaluate the risk of preterm birth at different maximum apparent and minimum temperature values (50th, 90th and 99th percentiles of the warm season) up to 3 weeks before delivery (reference: overall annual median value). In addition, three temperature-interval-specific estimates were obtained for changes between each of these temperature values. We took into account the pregnancies at risk adjusted by the gestational age distribution of the set in each day. We used distributed-lag non-linear models with a flexible function in the shape of the relationship and lag structure. Risk of preterm birth increased up to 20% when maximum apparent temperature exceeded the 90th percentile two days before delivery and 5% when minimum temperature rose to the 90th percentile in the last week. Differences between interval-specific risk estimates across lags were observed. Exposure to elevated temperatures was associated with an increased risk of preterm birth in the following three weeks.


Cardiac and behavioural responses of mussels to risk of predation by dogwhelks.
We used noninvasive, infrared phototransducers to record continuously the heartbeat of common mussels, Mytilus edulis, experiencing successive phases of interaction with the predatory gastropod Nucella lapillus, from initial threat to attack and consumption. Coupling physiological monitoring with behavioural analysis allowed us to investigate in detail the responses of mussels to predation threat. Compared to values of normal feeding activity, heart rate increased significantly when mussels were in the presence of effluent from dogwhelks. When attacked by dogwhelks, mussels increased their heart rate further, together with the rate of valve gaping. Considering the heart rate as a reliable estimator of respiratory function, these cardiac responses might be a mechanism to compensate for increased energy demand in order to cope with predation hazard. If so, the theoretical importance of trading off energy balance against risk of predation is supported by our results. Cardiac and behavioural responses varied throughout the attack according to the penetration method adopted by dogwhelks. When mussels were attacked through a drilled hole, heart rate tended to increase and periods of cardiac pausing appeared close to the point of death. In contrast, mussels attacked by penetration between the valves showed decreasing heart rate throughout the attack, together with relatively earlier cessation of valve gaping and appearance of cardiac pausing. These differences clearly support the hypothesis that dogwhelks penetrating between the valves are able to induce muscular paralysis of prey by injecting toxins. Copyright 1999 The Association for the Study of Animal Behaviour.


The HMG-14/-17 chromosomal protein family: architectural elements that enhance transcription from chromatin templates.
Chromosomal proteins HMG-14 and HMG-17 enhance the transcriptional potential of chromatin when incorporated into nucleosomes during, but not after, chromatin assembly on replicating DNA. Two molecules of either HMG-14 or HMG-17 can bind to nucleosome cores, independently of the underlying DNA sequence, in a cooperative fashion to limit nucleosome mobility and stabilize the structure of the nucleosome core without stabilizing the higher order chromatin structure. By modifying the structure of nucleosomes, the proteins affect the local structure of the chromatin fiber leading to an increase in the rate of transcriptional elongation but not initiation. We suggest that HMG-14/-17 are architectural elements which assist in the assembly of an unfolded chromatin fiber thereby decreasing the repressive activity of histones and facilitating transcriptional processes.


Animal models of psychiatric disease.
Animal models of psychiatric diseases are useful tools for screening new drugs and for investigating the mechanisms of those disorders. Despite the difficulties inherent in modelling human psychiatric phenotypes in animals, there has been recent success identifying mutations in mice that give rise to some of the characteristic features of anxiety, depression, schizophrenia, autism, obsessive-compulsive disorder and bipolar disorder. In some cases these models have the additional strength that drugs used to treat the human condition alleviate the symptoms in mice. Robust genetic evidence of the involvement of multiple susceptibility genes in psychiatric disease will enable future studies to move from single-gene models to models with multiple modified loci, with the promise of better representing the complexity of the human diseases.


Comparative effectiveness of antibiotics for uncomplicated urinary tract infections: network meta-analysis of randomized trials.
The efficacies and adverse effects of different antibiotics for uncomplicated urinary tract infections (UTIs) have been studied by standard meta-analytic methods using pairwise direct comparisons of antimicrobial treatments: the effects of one treatment are compared to those of either another treatment or placebo. However, for clinical decisions, we need to know the effectiveness of each possible treatment in comparison with all relevant alternatives, not with just one. To compare the efficacies and adverse effects of all relevant antibiotics for UTI treatment simultaneously by performing a network meta-analysis using direct and indirect treatment comparisons. Using logistic regression analysis, we performed a network meta-analysis of randomized controlled trials (RCTs) published after 1999 that compared different oral antibiotic or placebo regimens for UTI treatment in general practice or outpatient settings. We looked at five binary outcomes: early clinical, early bacteriological, late clinical and late bacteriological outcomes, as well as adverse effects. Consequently, a ranking of the antibiotic regimens could be composed. Using a network structure, we could compare and rank nine treatments from 10 studies. Overall, ciprofloxacin and gatifloxacin appeared the most effective treatments, and amoxicillin-clavulanate appeared the least effective treatment. In terms of adverse effects, there were no significant differences. Network meta-analysis shows some clear efficacy differences between different antibiotic treatments for UTI in women. It provides a useful tool for clinical decision making in everyday practice. Moreover, the method can be used for meta-analyses of RCTs across primary care and beyond.


[Surfactants in amniotic fluids: a comparision between biomechanical and biochemical analyses (author's transl)].
44 specimens of amniotic fluid from the 25 week's gestation onwards were tested in a modified Wilhelmy-Langmuir surface balance. In addition percentage of lecithin in total phospholipids, total phospholipd phosphorus concentration and fatty acid composition of lecithin was determined. Lecithin, total phospholipid-phosphorus and palmitic acid show significant rises in concentration with gestational progress. The results of the surface tension measurements are significantly correlated with the biochemical analysis. Therefore, fetal lung maturity seems to be well estimated by the biomechanical method.


Effects of cerium on key enzymes of carbon assimilation of spinach under magnesium deficiency.
The mechanism of the fact that cerium improves the photosynthesis of plants under magnesium deficiency is poorly understood. The main aim of the study was to determine the role of cerium in the amelioration of magnesium deficiency effects in CO(2) assimilation of spinach. Spinach plants were cultivated in Hoagland's solution. They were subjected to magnesium deficiency and to cerium chloride administered in the magnesium-present Hoagland's media and magnesium-deficient Hoagland's media. The results showed that the chlorophyll synthesis and oxygen evolution was destroyed, and the activities of Rubisco carboxylasae and Rubisco activase and the expression of Rubisco large subunit (rbcL), Rubisco small subunit (rbcS), and Rubisco activase subunit (rca) were significantly inhibited, then plant growth was inhibited by magnesium deficiency. However, cerium promotes the chlorophyll synthesis, the activities of two key enzymes in CO(2) assimilation, and the expression of rbcL, rbcS, and rca, thus leading to the enhancement of spinach growth under magnesium-deficient conditions.


Urosdeoxycholic acid in primary sclerosing cholangitis: a meta-analysis and systematic review.
Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease with no proven effective medical therapy. Ursodeoxycholic acid (UDCA) was proposed as a potential treatment for this disorder. However, several randomised controlled trials reported conflicting results regarding the usefulness of UDCA. The aim of this meta-analysis and systematic review is to investigate the efficacy of UDCA in PSC. Literature review was performed to include randomised controlled trials and non-randomised studies comparing UDCA to a placebo in PSC. The included controlled trials were assigned a quality score. Random effects model was used. Outcomes were measured with Weight Mean Difference, Risk Ratio or Risk Difference. Heterogeneity was measured by I(2) measure of inconsistency. Seven RCTs satisfied the inclusion criteria with a total number of 553 patients. Low dose UDCA was used in 4 studies, high dose UDCA (17-30mg/kg) was used in three studies. UDCA did not decrease the risk of mortality compared to placebo (RR=1.04, 95% CI 0.46-2.35) or the need for liver transplant (RR=1.22, 95% CI 0.7-2.12). UDCA also had no effect on the clinical symptoms. Liver Function Tests (LFTs) were significantly improved in the UDCA treated patients. UDCA did not decrease the incidence of cholangiocarcinoma. UDCA had no beneficial effect on the patients' survival, liver histology, prevention of cholangiocarcinoma, or improvement of clinical symptoms. High dose UDCA was associated with increased mortality in one of the large randomised trial included in this analysis.


Toll-like receptor system and endometriosis.
Endometriosis is an estrogen-dependent chronic inflammatory condition associated with variable degrees of pelvic pain and infertility. Studies have showed that the growth and progression of endometriosis continue even in ovariectomized animals. This indicates that besides ovarian steroid hormones, the growth of endometriosis can be regulated by the innate immune system in the pelvic environment. As a component of innate immune system, increased infiltration of macrophages has been described in the intact tissue and peritoneal fluid of women with endometriosis. Different immune cells and dendritic cells express Toll-like receptors (TLR) and exhibit functional activity in response to microbial products. In this review article, we discuss the role of the TLR system in endometrium and endometriosis and outline the involvement of cytokines/endotoxin in causing adverse reproductive outcome. In the first part of this review article, the fundamentals of innate immune system, functional characteristics of TLR and signaling pathways of TLR4 are discussed for easy understanding by the readers.


The risk of preterm birth following treatment for precancerous changes in the cervix: a systematic review and meta-analysis.
Studies investigating the association between treatment for precancerous changes in the cervix and risk of preterm birth have used a variety of comparison groups. To investigate whether treatment for precancerous changes in the cervix is associated with preterm birth (<37 weeks) and to examine the impact of the type of comparison group on estimates of risk. PubMed, Embase and CENTRAL were searched for studies pubished between 1950 and 2009. Eligible studies were those that reported preterm birth outcomes for excisional and ablative treatments separately and included a comparison group. Pooled relative risks (RR) and 95% confidence intervals were computed using a random effects model. Thirty eligible studies were located. Excisional treatment was associated with an increased odds of preterm birth, when compared with an external (RR 2.19, 95% CI 1.93-2.49) or internal (RR 1.96, 95% CI 1.46-2.64) comparison group. In comparison with women who were assessed but not treated, the risk estimate was smaller (RR 1.25, 95% CI 0.98-1.58). Ablative treatment was associated with an increased risk of preterm birth when an external comparison group (RR 1.47, 95% CI 1.24-1.74) but not an internal comparison group (RR 1.24, 95% CI 0.73-2.10) or untreated comparison group (RR 1.03, 95% CI 0.90-1.18) was used. Excisional treatment was associated with a significantly increased risk of preterm birth. It provides new evidence that some types of ablative treatment may also be associated with a small increased risk. The type of comparison group used is an important consideration when comparing the outcomes of studies.


Assessing the need for knowledge on injury management among high school athletic coaches in South Dakota.
A lack of health coverage at athletic competitions and practices poses concern over the knowledge coaches have in providing adequate health care to high school (HS) athletes. Therefore, the purpose of this study was to determine the need for education of coaches in the prevention, assessment and management of sports-related injuries in South Dakota (SD). Survey link e-mailed to 1,050 HS athletic head coaches in SD; 247 (23.5 percent) completed the prospective, web-based survey. Of the respondents, 74.91 percent reported HS enrollments less than 300, with 79.36 percent in rural/frontier counties and 28.74 percent in medically underserved areas. Coaches from 14 sports responded. The majority indicated they were responsible for the immediate medical care of athletes at practices (89.07 percent) and competitions (74.90 percent); and 79.76 percent of coaches agreed or strongly agreed they needed more injury management education. Results also indicated less than 50.00 percent had current certifications in CPR/BLS (46.65 percent) and first aid (47.4 percent). Due to the demand placed on head coaches to be the initial caregivers for injured athletes, there is a need for increased education of SD coaches related to the management of acute sports injuries. Additionally, policy changes may be indicated to address the lack of medical personnel available during HS athletic competitions and practices.


Transcriptional accessibility for genes of multiple tissues and hematopoietic lineages is hierarchically controlled during early hematopoiesis.
Hematopoietic stem cells (HSCs) maintain hematopoiesis by giving rise to all types of blood cells. Recent reports suggest that HSCs also possess the potential to generate nonhematopoietic tissues. To evaluate the underlying mechanisms in the commitment of HSCs into multitissue and multihematopoietic lineages, we performed oligonucleotide array analyses targeting for prospectively purified HSCs, multipotent progenitors (MPPs), common lymphoid progenitors (CLPs), and common myeloid progenitors (CMPs). Here we show that HSCs coexpress multiple nonhematopoietic genes as well as hematopoietic genes; MPPs coexpress myeloid and lymphoid genes; CMPs coexpress myeloerythroid, but not lymphoid genes, whereas CLPs coexpress T-, B-, and natural killer-lymphoid, but not myeloid, genes. Thus, the stepwise decrease in transcriptional accessibility for multilineage-affiliated genes may represent progressive restriction of developmental potentials in early hematopoiesis. These data support the hypothesis that stem cells possess a wide-open chromatin structure to maintain their multipotentiality, which is progressively quenched as they go down a particular pathway of differentiation.


[Earstructures in one case of anencephalie (author's transl)].
According to the majority of cases under observation the following anomalies could be found: extended, separated or manifold developed crura of the stapes, reduction in the circular windings of the cochlea down to 1 1/2 with a normal development of Corti's organum, reduction of the nerve structures of the nervus cochlearis to a munimum and an open facial canal.


Effect Of Diets With Different Lipid's Sources On Serum And Brain Fatty Acids Profile. Experimental Model.
It´s widely accepted and recognized the importance of diet in maintaining health. Diet lipid profile is important to prevent chronic diseases and improve the quality of individual's life. The objective of this report is to analyze the effect of different sources of dietary lipids with standard and high concentration on growing rats. Experimental diets contained 15 or 42% kcal of fat, provided by butter (B), olive oil (O), high oleic sunflower oil (HO) and sunflower oil (S). Control diet (C) was normocaloric with 15%kcal of fat provided by soy oil. All diets were complete in the other nutrients according to AIN 1993 and were administered for 40 days. Daily intake was similar in all groups. The administration of these diets provoked changes in serum fatty acid profile in response to the differences sources of dietary lipids used; no changes were observed in brain´s fatty acids. These results would suggest that the organism tries first to supply brain´s fatty acid needs at the expense of its modification in serum.


Pretreatment with oral contraceptives in infertile anovulatory patients with polycystic ovary syndrome who receive gonadotropins for controlled ovarian stimulation.
This study was intended to assess the effects of oral contraceptives given before treatment in infertile anovulatory patients with polycystic ovary syndrome who receive gonadotropins for controlled ovarian stimulation. Pretreatment with oral contraceptives increased the mono-ovulatory cycles, the duration of stimulation for noncanceled cycles, and the number of vials of gonadotropins used. It also reduced the number of dominant follicles and the peak E(2) levels for dominant follicles. No effect was observed in rates of cycle cancellation, pregnancy, abortion, live birth, multiple pregnancies, and ovarian hyperstimulation syndrome.


An arthroscopic-plus-open method of repair for combined tears of the subscapularis, supraspinatus, and infraspinatus tendons.
Tears involving the subscapularis and posterosuperior rotator cuff comprise a distinct clinical entity. An aggressive treatment involving operative repair has demonstrated superior results compared with delayed intervention, yet there is no consensus as to the optimal method of repair. Various methods are evolving, but they are not without their pitfalls. Methods of fixation, patient positioning, and biceps management are emerging as points of contention. In this technical note, we describe an arthroscopic-plus-open approach in which arthroscopic repair of the posterosuperior rotator cuff is followed by an open subscapularis repair. Advantages of this method include ability to address concomitant pathology, relative ease of repair, and creation of a strong, reliable construct. The interval-splitting approach affords minimal additional morbidity and does not preclude use of allograft or biological augmentation for salvage procedures. Overall, this method is an effective, efficient technique that yields reproducible, reliable repair of these combined rotator cuff tears.


[Role of ultrasonics in the diagnosis of subclinical carcinoma of the breast].
The authors report the results of a retrospective multicentric study concerning the sonographic diagnosis of subclinical breast cancer, 11,254 patients were examined by means of mammography, with last-generation mammographic equipment, and by means of real-time US with 7.5-10 MHz transducer. Fifty-seven subclinical breast cancers were identified and histologically confirmed. US detected 30/57 neoplastic lesions, versus mammography 47/57; in particular, US identified 10 cancers missed at mammography, while the latter detected 27 malignant lesions missed at US. Mammographic accuracy in the early detection of breast cancers was 82.4%, while US accuracy was 52.6%. Mammographic false negatives were due to opacity of the glandular parenchyma. US false negatives presented at mammography as microcalcifications (67%), lesions less than 1 cm phi (22%), and indirect signs (11%). The results of this study demonstrate the important role of US in women with radiographically-dense parenchymal patterns, but confirm the superiority of mammography in the detection of subclinical breast cancer.


A numerical study on flow and pollutant transport in Singapore coastal waters.
Intensive economic and shipping activities in Singapore Strait have caused Singapore coastal waters to be under high risk of water pollution. A nested three-dimensional unstructured-grid SUNTANS model is applied to Singapore coastal waters to simulate flow and pollutant transport. The small domain (~50m resolution) Singapore coastal model is nested within a large domain (~200m resolution) regional model. The nested model is able to predict water surface elevations and velocities with high R(2) values of 0.96 and 0.91, respectively. Model results delineate the characteristics of circulation pattern in Singapore coastal waters during the Northeast and Southwest monsoons. The pollutants are modeled as passive tracers, and are released at six key sailing locations Points 1-6 in Singapore coastal waters and are named as Passive Tracers 1-6, respectively. Our results show that the rate of dispersion is twice as large for the Northeast monsoon compared to the Southwest monsoon due to differences in large-scale monsoons and small-scale local winds. The volume averaged concentration (VAC) diminishes faster and the local flushing time is shorter during the Northeast monsoon than the Southwest monsoon. Dispersion coefficients K and the VAC decreasing rate are maximum for Tracers 2 and 3 with shortest local flushing time due to the strong surrounding currents and abrupt bathymetry changes near Senang and St. John Islands. Dispersion coefficients K and the VAC decreasing rate are minimum for Tracer 1 due to weak currents induced by the semi-enclosed coastline near Tuas. It is found that both the lateral dispersion coefficient Ky and the compound dispersion coefficient K obey a "4/3-law", which defines a linear correlation between dispersion coefficients and 4/3-power of selected length scale.


Collegiate alcohol/drug treatment programs in the United States.
A random sample of 400 U.S. colleges and universities provided data on the existence, type, structure, and philosophy of campus alcohol/drug treatment programs. Although many institutions reported service provision, a variety of approaches were described in the questionnaires. The results uncover important issues on administrative structure, licensure, treatment models, assessment procedures, and confidentiality.


Could Slackline Training Complement the FIFA 11+ Programme Regarding Training of Neuromuscular Control?
The current study compared changes in neuromuscular control between slackline training and the stabilization training elements of the FIFA 11+ programme. Twenty-five students in 2 groups performed a 12-unit training programme. The slackline training group (n = 13) exclusively trained with a slackline. The stabilization training group (n = 12) practised exercises as described in the second part of the FIFA 11+ programme. Improvements in balance were assessed using three tests for dynamic, quasi-static, and perturbed postural control: the star excursion balance test (SEBT), the closed-eye single-leg stance, and the MFT S3-Check. Both groups significantly improved the stability and sensorimotor index of the MFT S3-Check (p < .001), their range on the SEBT (p < .001), and the duration of closed-eye single-leg stance (p < .001). The group × training interaction was significant for the MFT S3-Check (stability index: p = .042; sensorimotor index: p = .004) and the SEBT (dominant leg: p = .003; averaged both legs: p = .016), with the slackline training group showing a larger training effect than the stabilization training group. The results of the present study suggest that slackline training offers similar - or better - improvements in neuromuscular control as the FIFA 11+ warm-up programme. If compliance with the FIFA 11+ programme is declining, then slacklining might offer an alternative approach to reach the training goals of improved sensorimotor control.


[Effect of signal transduction inhibitors on human endometrial carcinoma cells with differential PTEN gene expression].
To investigate the apoptotic and proliferation effects of signal transduction inhibitors on human endometrial carcinoma cells with different PTEN gene expression. PTEN antisense oligonucleotide and pcDNA3.1/PTEN vector contained PTEN gene were transfected into endometrial carcinoma cells (HEC-1A and Ishikawa). The expression of PTEN protein was detected by confocal spectral microscopy. The endometrial carcinoma cells (HEC-1A, HEC-1A-PTEN-null, Ishikawa, Ishikawa-PTEN) were treated with signal transduction inhibitors, RG-14620, SB203580 (SB) and rapamycin, respectively. Cell apoptosis morphology, cell apoptosis and cell cycle were detected by Hoechst 33258 staining and flow cytometry. Cell viability was determined by methyl thiazolyl tetrazolium assay. The PTEN protein expression in two endometrial carcinoma cells (Ishikawa, HEC-1A) was exchanged by PTEN antisense oligonucleotide blocked and pcDNA3.1/PTEN stable transfected. After treated with RG-14620, SB and rapamycin, marked morphological changes of apoptosis were observed in HEC-1A-PTEN-null and Ishikawa cells. The cell apoptosis of HEC-1A-PTEN-null and Ishikawa cells exposed to SB were significantly increase [(31.6 +/- 0.8)% and (37.8 +/- 0.8)%, respectively], the G(1) phase cells were increased to (84.1 +/- 3.2)% and (87.5 +/- 1.9)%. While cell viability was significantly decreased in HEC-1A-PTEN-null and Ishikawa cells, the cell viability of HEC-1A-PTEN-null and Ishikawa cells exposed to SB were (54.0 +/- 2.1)% and (49.0 +/- 1.7)%. Loss of PTEN in endometrial carcinoma cells may improve the G(1) phase cells and apoptotic effects, inhibit the cell proliferation, which due to the sensitivity of cells to related signal transduction inhibitors.


Synergism between hepatitis B virus and aflatoxin in hepatocellular carcinoma.
Epidemiological data have suggested that environmental factors play a major role in hepatocellular carcinoma (HCC). Such factors include hepatitis B virus (HBV), infection, chemical carcinogens and parasites. The available data provide compelling evidence of the causative association of HBV with HCC but its exact role has not been defined. Similarly, field studies have indicated the importance of aflatoxin contamination of foodstuffs in areas with high prevalence rates of HCC. The precise role of this mycotoxin has been the subject of debate. The hypothesis that aflatoxin and HBV can interact and cause HCC synergistically has been challenged by those who postulate that aflatoxin merely suppresses cell-mediated immunity, thereby permitting persistence of HBV in the liver.


Lipid and lipoprotein changes associated with oral contraceptive use: a randomized clinical trial.
To determine the effects of oral contraceptives on lipids and lipoproteins over a six-month period, we randomized 266 women into four oral contraceptive groups: ethinyl estradiol 35 micrograms plus ethynodiol diacetate 1 mg, ethinyl estradiol 30 micrograms plus levonorgestrel 0.15 mg, ethinyl estradiol 35 micrograms plus norethindrone 1 mg, and ethinyl estradiol 35 micrograms plus norethindrone 0.5 and 1 mg (biphasic). For all groups, total cholesterol increased 5.9-9.1% from baseline values over the six months. Triglycerides increased with all preparations, with the ethynodiol diacetate group (37.6%) and the biphasic norethindrone group (45.3%) showing the greatest increase. Low-density lipoprotein cholesterol increased 10-15.6% among the groups; low-density lipoprotein-apolipoprotein B changed proportional to the low-density lipoprotein cholesterol increases. All groups except the ethynodiol diacetate group showed a decrease of high-density lipoprotein cholesterol, with the levonorgestrel group (8.7%) and biphasic norethindrone group (4.5%) showing the largest declines. Apolipoprotein A-1 increased in all groups, with the ethynodiol diacetate preparation (19.3%) showing the greatest increase and the levonorgestrel preparation (3.2%) showing the smallest increase from baseline values. The changes in apolipoprotein A-1 were out of proportion to the changes in high-density lipoprotein cholesterol, suggesting that the high-density lipoprotein particle may be undergoing some type of metabolic alteration.


Effect of brain serotoninergic stimulation on sodium appetite of euthyroid and hypothyroid rats.
The aim of the present work was to investigate the role of the serotoninergic system in the control of sodium appetite of hypothyroid rats (HTR) by administering drugs that affect the serotoninergic activity, and to compare the same homeostatic behaviour in euthyroid rats (ETR) also given these drugs. Fenfluramine (FEN; 5.0 mg x kg(-1), I.P.), which releases serotonin in the brain, significantly reduced the intake of 1.8 % NaCl in HTR subjected to water and sodium depletion (depleted) or water, sodium and food deprivation (deprived) by 31 and 45 %, respectively, 120 min after FEN injection, compared to HTR that received vehicle alone. Similarly, administration of FEN to ETR reduced 1.8 % NaCl intake in depleted and deprived rats by 64 and 46 %, respectively. The presynaptic serotonin reuptake inhibitor fluoxetine (20.0 mg x kg(-1), I.P.) led to the inhibition of sodium appetite in HTR during the initial 30 min in depleted rats and for up to 60 min post-injection in deprived rats, while sodium appetite inhibition persisted for longer periods in ETR. The 5HT2C receptor agonist mCPP (5.0 mg x kg(-1), I.P.) caused a drastic reduction in sodium appetite in HTR and ETR in depleted and deprived rats, respectively, after 120 min. Prior administration of the 5HT2C receptor antagonist LY53857 (5.0 mg x kg(-1), I.P.) completely blocked the inhibitory action of mCPP on sodium appetite in both HTR and ETR. In summary, our results suggest that the recruitment of serotoninergic neurons involved in the modulation of sodium appetite seems to be decreased in hypothyroidism due to a probable deficiency in the cerebral signalling pathway.


Tailoring electronic transparency of twin-plane 1D superlattices.
The structural properties of twin-plane superlattices in InP nanowires are systematically analyzed. First, we employ molecular dynamics simulations to determine the strain fields in nanowires grown in the [111] direction. These fields are produced by the formation of twin-planes and by surface effects. By using the stress tensor obtained from molecular dynamics simulations, we are able to describe changes on the electronic structure of these nanowires. On the basis of the resulting electronic structure, we confirm that a one-dimensional superlattice is indeed formed. Furthermore, we describe the transport properties of both electrons and holes in the twin-plane superlattices. In contrast to the predicted transparency of Γ-electrons in heterolayered III-V semiconductor superlattices, we verify that surface effects in 1D systems open up possibilities of electronic structure engineering and the modulation of their transport and optical responses.


Preferential transcription of Paracoccidioides brasiliensis genes: host niche and time-dependent expression.
Paracoccidioides brasiliensis causes infection through inhalation by the host of airborne propagules from the mycelium phase of the fungus. This fungus reaches the lungs, differentiates into the yeast form and is then disseminated to virtually all parts of the body. Here we review the identification of differentially-expressed genes in host-interaction conditions. These genes were identified by analyzing expressed sequence tags (ESTs) from P. brasiliensis cDNA libraries. The P. brasiliensis was recovered from infected mouse liver as well as from fungal yeast cells incubated in human blood and plasma, mimicking fungal dissemination to organs and tissues and sites of infection with inflammation, respectively. In addition, ESTs from a cDNA library of P. brasiliensis mycelium undergoing the transition to yeast were previously analyzed. Together, these studies reveal significant changes in the expression of a number of genes of potential importance in the host-fungus interaction. In addition, the unique and divergent representation of transcripts when the cDNA libraries are compared suggests differential gene expression in response to specific niches in the host. This analysis of gene expression patterns provides details about host-pathogen interactions and peculiarities of sites within the host.


Best Practice Recommendations for Diagnosis and Management of Helicobacter pylori-Synthesizing the Guidelines.
Purpose of review Three guidelines on Helicobacter pylori have been published recently with recommendations that differ from past guidelines. In this review, we summarize the Toronto consensus statement, the Maastricht V/Florence consensus report and the American College of Gastroenterology guidelines on H. pylori, comparing and contrasting the recommendations. We also provide a proposed approach integrating the information from all three guidelines. Findings Increasing antibiotic resistance has decreased the effectiveness of past treatment regimens for H. pylori. The recommended treatment approach should be based on local and individual antibiotic resistance patterns. Empiric first-line therapy should be a 14-day course of bismuth- or antibiotic-based quadruple therapy. Clarithromycin triple therapy is not recommended unless the local clarithromycin resistance rate is less than 15%. Second-line therapy should be influenced by the failed first-line therapy. Quadruple bismuth-based therapy or levofloxacin-based therapy are suggested regimens. Testing for antibiotic resistance is recommended after multiple failed treatments. Summary Therapy of H. pylori should be based on the knowledge of local antibiotic resistance patterns. Unfortunately, these are often not available. Additional efforts are needed to define local antibiotic resistance to allow susceptibility-based treatment. In the meantime, 14-day quadruple therapy with bismuth or concomitant antibiotics is the recommended as an empiric first-line treatment approach.


Reactive astroglia support primary dendritic but not axonal outgrowth from mouse cortical neurons in vitro.
Reactive astrocytes are thought to be impediments to axon regrowth following injury to the mammalian central nervous system. Axon and dendrite growth, however, appear to be differently controlled by normal astrocytes in vitro. To determine whether reactive astrocytes differ in their ability to support axons or dendrites, embryonic (E18) mouse cortical neurons were cocultured with P4 and P12 rat astroglial cells derived from normal or lesioned cortex. After 5 days in vitro, axon and dendrite outgrowth from isolated neurons was quantified with double-labeling immunohistochemical techniques. Reactive astrocytes were able to maintain primary dendrite growth, principally primary dendrite number. Axon elongation, however, was significantly reduced on both neonatal and more mature reactive astrocytes. These results indicate that reactive astrocytes may exhibit separate mechanisms to control dendrite and axon growth.


Age interacts with the expression of steroid and HER-2 receptors in operable invasive breast cancer.
The negative association between the oestrogen receptor (ER) and the human epidermal growth factor receptor 2 (HER-2) in breast cancer travels in both directions. ER+ tumours are less likely HER-2+ and HER-2+ tumours are less likely ER+. We studied the age-related immunohistochemical (IHC) expression of ER, progesterone receptor (PR) and HER-2 in 2,227 tumours using age as a continuous variable. Steroid receptors were considered positive for any nuclear staining of invasive cancer cells and for HER-2, either for strong expression by IHC (score 3+) or gene amplification by fluorescence in situ hybridisation (FISH). Based on nonparametric regression, the age-related association between steroid receptors and HER-2 was presented as likelihood curves. The association between ER or PR and HER-2 is age-related. The age-related expression of ER and PR is HER-2 dependent. In HER-2(-) cases, the odds ratio (OR) for being ER+ was 2.594 (95% CI = 1.874-3.591) up to age 50 and age-independent thereafter; for PR-expression the OR was 2.687 (95% CI = 1.780-4.057) up to age 45 and 0.847 (95% CI = 0.761-0.942) thereafter. In HER-2+ cases, the OR was 0.806 (95% CI = 0.656-0.991) to be ER+ and 0.722 (95% CI = 0.589-0.886) to be PR+. The age-related OR for breast cancers to be HER-2+ is steroid receptor dependent. Taking together, ER+PR+HER-2+ breast cancers appear on average 5.4 years earlier than breast cancers of any other ER/PR/HER-2 phenotype (95% CI = 3.3-7.5; P < 0.0001). There is a qualitative interaction between age and expression of steroid and HER-2 receptors. Our findings suggest a strong age-related selective growth advantage for breast tumour cells belonging to the ER+PR+HER-2+ subgroup.


Challenges and benefits of international clinical placements in public health nursing.
International clinical placements offer interested nursing students unique opportunities for development of nursing expertise and cultural competence skills. The authors review the professional literature regarding nursing student experiences in international sites, describe the development of international clinical sites in a required baccalaureate public health nursing course, and summarize challenges and benefits of the program.


Effect of hydration on bond strength of a silane-bonded composite to porcelain after seven months.
Presence of moisture reduced the strength of the silane bond between each of three resin composites and porcelain significantly. The tests were run in a moist environment in vitro for seven months. Porcelain repairs in vivo are exposed to variations in temperatures and saliva. This study indicates that thermocycling alone may not be sufficient to stimulate intraoral conditions before testing shear strength of materials.


Metals in sediments and mangrove oysters (Crassostrea rhizophorae) from the Caroni Swamp, Trinidad.
Metals can have significant impacts on inhabitants of mangrove swamps as well as consumers of mangrove-associated fauna. Yet, for several Caribbean islands, assessments regarding the impact of metals on such ecosystems are particularly sparse. The present study investigated the distribution and potential impact of Cd, Cr, Cu, Ni, Pb and Zn in the Caroni Swamp, Trinidad and Tobago's largest mangrove ecosystem. Surface sediments and mangrove oysters (Crassostrea rhizophorae) from 10 sites in the swamp were analysed for the 6 identified metals. The concentration ranges (in μg/g dry wt.) of metals in sediments from Caroni Swamp were: Zn (113.4-264.6), Cr (27-69.7), Ni (10.7-41.1) and Cu (11-40.7). Based on Canadian Sediment Quality Guidelines (CSQGs), metals in sediments posed a low to medium risk to aquatic life. The concentration ranges (in μg/g wet wt.) for metals in Crassostrea rhizophorae tissues were: Zn (123.2-660), Cu (4.2-12.3), Ni (0.1-5.5), Pb (0.1-0.9), Cr (0.2-0.3) and Cd (0.1-0.2). Multiple evaluations indicated that zinc posed a potential threat to the health of oyster consumers. Information from this study is vital for managing the Caroni Swamp, safeguarding the health of consumers of shellfish on this Caribbean island and serving as a useful baseline for future local and regional risk assessments.


The purine-cytosine permease gene of Saccharomyces cerevisiae: primary structure and deduced protein sequence of the FCY2 gene product.
A 2.1 kb DNA segment carrying the purine-cytosine permease gene (FCY2) of Saccharomyces cerevisiae was sequenced, the primary structure of the protein (533 amino acids) deduced and a folding pattern in the membrane is proposed for the permease protein. Expression of the FCY2 gene product requires a functional secretory pathway and is reduced in mnn9, a mutant strain deficient in outer chain glycosylation. The FCY2 gene was mapped on the right arm of chromosome V close to the HIS1 gene.


Molecular mapping of vernalization requirement and fertility restoration genes in carrot.
Carrot (Daucus carota L.) is a cool-season vegetable normally classified as a biennial species, requiring vernalization to induce flowering. Nevertheless, some cultivars adapted to warmer climates require less vernalization and can be classified as annual. Most modern carrot cultivars are hybrids which rely upon cytoplasmic male-sterility for commercial production. One major gene controlling floral initiation and several genes restoring male fertility have been reported but none have been mapped. The objective of the present work was to develop the first linkage map of carrot locating the genomic regions that control vernalization response and fertility restoration. Using an F(2) progeny, derived from the intercross between the annual cultivar 'Criolla INTA' and a petaloid male sterile biennial carrot evaluated over 2 years, both early flowering habit, which we name Vrn1, and restoration of petaloid cytoplasmic male sterility, which we name Rf1, were found to be dominant traits conditioned by single genes. On a map of 355 markers covering all 9 chromosomes with a total map length of 669 cM and an average marker-to-marker distance of 1.88 cM, Vrn1 mapped to chromosome 2 with flanking markers at 0.70 and 0.46 cM, and Rf1 mapped to chromosome 9 with flanking markers at 4.38 and 1.12 cM. These are the first two reproductive traits mapped in the carrot genome, and their map location and flanking markers provide valuable tools for studying traits important for carrot domestication and reproductive biology, as well as facilitating carrot breeding.


Serum cholesterol levels and the risk of multiple system atrophy: a case-control study.
Cholesterol in brain membranes may modulate the conformational state and accumulation of alpha-synuclein in alpha-synucleinopathies.We examined the association between serum cholesterol and the risk of multiple system atrophy (MSA), one of the alpha-synucleinopathies. We enrolled 142 patients with probable MSA from two tertiary referral hospitals and 155 age- and gender-matched healthy people with no neurological disease. The levels of total cholesterol, low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) were significantly lower in MSA patients than in controls (total cholesterol: 172.7 vs. 196.3 mg/dL, P < 0.001; LDL-C: 104.0 vs. 115.3 mg/dL, P = 0.001; HDL-C: 47.3 vs. 54.2 mg/dL, P < 0.001). After adjusting for age, gender, use of cholesterol-lowering drugs, and histories of hypertension, diabetes mellitus, and smoking, the odds ratios was 5.9 (95% CI = 2.3-11.5, P < 0.001) for MSA patients in the lowest quartile of total cholesterol and 2.6 (95% CI = 1.2-5.5, P = 0.016) for those in the lowest quartile of HDL-C, compared with the highest quartiles. Levels of serum cholesterol did not significantly correlate with disease duration or severity. Our data suggest that lower levels of total cholesterol and HDL may be associated with an increased risk of MSA.


Beyond the best interest of the child: ten years later.
The book "Beyond the Best Interest of the Child" advocated major changes in understanding and implementing child placements, through general principles and guidelines and through specific recommendations. After ten years of clinical experience with child placements, a reassessment of the book is attempted. It is felt that the main principles and guidelines espoused are useful and are an improvement over the previous guidelines. However, the specific recommendations were felt to be less useful and are not necessarily the logical consequences of the principles and guidelines.


Cervical cancer screening with papanicolaou smear plus speculoscopy by nurse practitioners in a health maintenance organization.
We set out to evaluate the utility of a magnified chemiluminescent screening examination (speculoscopy) as an adjunct to the Papanicolaou (Pap) smear in detection of cervical pathological processes by nurse practitioners and midwives in a health maintenance organization setting. Patients who presented for routine screening (N = 689) received a Pap smear and speculoscopy examination. If the Pap smear or speculoscopy result was positive, colposcopy was performed and biopsies were obtained from women with positive colposcopies. Data were analyzed using McNemar's adaptation of the chi-square test for correlated proportions. In 80 patients from whom biopsies were obtained, Pap smear alone detected 67% of (6 of 9) and speculoscopy alone detected 77% of (7 of 9) high-grade squamous intraepithelial lesions (HGSILs). Pap smear alone detected 26% of low-grade squamous intraepithelial lesions (LGSILs) (10 of 38) whereas speculoscopy alone detected 84% (32 of 38) (p < .001). Combined use of Pap smear and speculoscopy showed a trend (p = .073) toward enhanced detection of HGSIL compared with either the Pap smear alone or speculoscopy alone. Speculoscopy can be included in a nurse practitioner- and midwife-based cervical screening program, and the addition of this modality enhances the sensitivity of cervical screening by finding more high-grade and low-grade cervical disease than does pap smear alone.


The histological characteristics of clinically normal mucosa adjacent to oral cancer.
The 'field cancerization' theory tries to explain the risk of local recurrences and development of second primary tumors in oral sqamous cell carcinoma (OSCC) patients. According to this theory it is assumed that clinically normal mucosa adjacent to oral cancer, except molecular, has already developed certain premalignant histopathological changes. The aim of this study was to determine histological characteristics of clinically normal-looking mucosa at different distances from the apparent tumor lesion margins in OSCC patients. Normal-appearing oral mucosa biopsy specimens were obtained from 30 new (untreated) oral cancer patients from sites at a distance of 10 mm and 20 mm from the tumor lesion margins and were compared with normal oral mucosa from 30 control patients with benign oral lesions. A total of 21 patients (70%) in the OSCC group demonstrated histological abnormalities under microscopic examination versus 7 (23.3%) control patients (P<0.01). Seventeen oral cancer patients (57%) showed significant difference in incidence and type of histological changes of normal-looking mucosa at a distance of 10 mm from the tumor lesion; 8 (27%) demonstrated reactive changes, 6 (20%) mild dysplasia and 3 (10%) squamous cell carcinoma, compared to histological abnormalities registered in 11 (OSCC) patients (36%) at a distance of 20 mm from the tumor; 10 (33%) displayed reactive changes and 1 (3%) mild dysplasia. Histological abnormalities of clinically normal-looking oral mucosa taken at different distances from the tumor lesion indicated the existence of subclinical field change and represent an important parameter during the assessment of the adequacy of surgical resection margins in oral cancer management.


Endogenous digitalis-like factor as a stimulator of endothelin secretion from endothelial cells.
Effects of human urine-derived endogenous digitalis-like factor (EDLF) and ouabain on endothelin (ET) secretion were examined in cultured endothelial cells. ET was secreted in a linear fashion over 5 hours from bovine pulmonary artery endothelium into serum-free medium. EDLF stimulated ET secretion in a dose-dependent manner. In contrast, ouabain did not affect ET secretion at the concentration of 10(-9)-10(-5) M. These results indicate that human urine-derived EDLF is distinct from plant-derived ouabain and act as a stimulator of ET secretion by endothelial cells.


The resident strikes back: invader-induced switching of resident attractor.
The aim of this paper is two-fold: (a) by way of example, we elucidate the phenomenon of invader-induced switches in a resident attractor; (b) we expose in detail how resonance and phase have a strong impact when semelparous organisms (as, e.g. Pacific salmon) with different life-cycle lengths compete in a self-induced periodically fluctuating environment. We analyse a simple model for the competition between annuals and biennials, focusing on the situation that the annual population in isolation converges to a two-cycle. Well-timed biennial mutants sample the periodically varying environment more efficiently than the annual resident. They can invade successfully even when they are inferior to the resident, in the sense that they have lower viability and/or fertility. Successful invasion can lead to resonance-mediated coexistence if the invader is rather inferior to the resident. Remarkably, for mutants that are less inferior to the resident, successful invasion by a mutant strategy will inevitably be followed by the extinction of the former invader and concurrent re-establishment of the resident. The expulsion of the invader is brought about by an invasion-induced phase shift or attractor switch. We call this phenomenon "the resident strikes back" and say that the resident strategy is invasible, yet invincible. After the resident has struck back, other mutants can successfully invade again. On a longer time-scale, this might lead to an intermittent occurrence of ultimately inferior strategies. The results show that even in a deterministic setting, successful invasion does not necessarily lead to establishment and that mutual invasibility is not always sufficient for coexistence.


Theta rhythm of the hippocampus: subcortical control and functional significance.
The theta rhythm is the largest extracellular synchronous signal that can be recorded from the mammalian brain and has been strongly implicated in mnemonic processes of the hippocampus. We describe (a) ascending brain stem-forebrain systems involved in controlling theta and nontheta (desynchronization) states of the hippocampal electroencephalogram; (b) theta rhythmically discharging cells in several structures of Papez's circuit and their possible functional significance, specifically with respect to head direction cells in this same circuit; and (c) the role of nucleus reuniens of the thalamus as a major interface between the medial prefrontal cortex and hippocampus and as a prominent source of afferent limbic information to the hippocampus. We suggest that the hippocampus receives two main types of input: theta rhythm from ascending brain stem- diencephaloseptal systems and information bearing mainly from thalamocortical/cortical systems. The temporal convergence of activity of these two systems results in the encoding of information in the hippocampus, primarily reaching it from the entorhinal cortex and nucleus reuniens.


Risk of disordered eating at the intersection of gender and racial/ethnic identity among U.S. high school students.
Gender and racial/ethnic disparities in disordered eating among youth exist, although whether having multiple marginalized identities disproportionately increases risk is unclear. Therefore, we aimed to quantify the risk of disordered eating associated with intersecting gender and racial/ethnic identities of U.S. adolescents. We analyzed data from 11,514 U.S. high school students identifying as White, Black/African American, or Hispanic/Latino who participated in the 2013 National Youth Risk Behavior Surveillance System. Age-adjusted relative risks (RR) of purging, fasting, diet pill use, and any disordered eating were estimated using log-binomial models. Relative excess risk due to interaction (RERI) was estimated to evaluate the degree to which the combined effect of marginalized gender and racial/ethnic identity was larger than the sum of their individual effects. Disordered eating was prevalent (girls: 20.4% Black/African American, 29.2% Hispanic/Latina, 21.4% White; boys: 13.4% Black/African American, 12.4% Hispanic/Latino; 8.1% Whites). Girls of all racial/ethnic identities and racial/ethnic minority boys had elevated risks of purging, fasting, and any disordered eating compared to White boys (RR range = 1.57-7.43); Hispanic/Latina and White girls also had elevated risk of diet pill use (RR range = 1.98-3.20). Among Hispanic/Latina girls, positive interaction between gender and race/ethnicity produced excess risk of any disordered eating and purging (RERI: any = 0.42 (95% confidence interval (CI) = -0.02, 0.87); purging = 1.74 (95% CI = 0.06, 3.42). Findings illustrate the advantages of adopting an intersectional approach to disordered eating research. Future research should investigate the mechanisms of these disparities.


Effects of a structured heart failure program on quality of life and frequency of hospital admission in Saudi Arabia.
To compare the quality of life (QOL) and frequency of hospital admission (FHA) in the past 4 months between congestive heart failure (CHF) patients involved in a structured heart failure program (HFP) compared with waitlisted controls. This study, employing an ex-post-facto comparative cross-sectional design, involved 80 patients with CHF (40 in the HFP and 40 controls). Those in the HFP had been enrolled for at least 4 months. Controls were waiting to be enrolled in the program. Participants completed a questionnaire assessing demographic, social/cultural, psychological, and CHF-related physical health characteristics, along with the primary dependent variables, QOL and FHA. Bivariate and multivariate analyses assessed differences between those in the HFP and controls. Congestive heart failure patients in the HFP were significantly less likely than the control group to score below the median on heart failure-specific QOL, controlling for other variables (OR=0.83, 95% CI: 0.82-0.95, p=0.007). Those in the HFP were also significantly less likely than controls to be hospitalized within the past 4 months (OR=0.78, 95% CI: 0.69-0.88, p less than 0.001). Multivariate analyses indicated that CHF patients in the HFP were 95% less likely than controls to be admitted to the hospital during that period, independent of other risk factors for hospital admission. Involvement by patients with CHF in a structured HFP at King Abdulaziz University in Jeddah, Kingdom of Saudi Arabia, is associated with significantly higher quality of life and lower likelihood of being hospitalized compared to CHF patients not involved.


The relationship between emotionality and dominance in the hooded rat.
Hooded rodents were tested in an emotionality condition and two competitive "dominance" conditions. It was found that stable rankings of subjects within the test groups could be established for each of the three conditions. Significant negative correlations were also found between a subject's "emotionality" ranked in a group and his ranking in the group in relation to either condition of competitive dominance, while a significant positive correlation was found between a subject's ranking in both of the competitive dominance conditions. These data are taken as evidence for a debilitating effect of high emotionality on one's success in competition.


The effects of S-nitrosoglutathione on platelet activation, hypertension, and uterine and fetal Doppler in severe preeclampsia.
To determine the effects of the platelet-specific nitric oxide donor S-nitrosoglutathione on women with severe preeclampsia. Ten women with severe preeclampsia or preeclampsia with severe fetal compromise at 21-33 weeks' gestation each received a 60-90-minute intravenous infusion of 50-250 micrograms/minute of S-nitrosoglutathione. Each was hypertensive, despite conventional oral antihypertensive therapy in eight. Maternal blood pressure, heart rate, platelet activation, uterine artery, and fetal Doppler indices were measured during the infusion. A dose-dependent reduction in mean arterial pressure from 125 mmHg (95% confidence interval [CI] 117-133) to 103.5 (95% CI 97-111) (P < .005) and an increase in pulse rate from 73.7 beats per minute (95% CI 64.3-84.5) to 89.1 (95% CI 81.2-97.8) (P < .02) was observed during the infusion. Mean uterine artery resistance index fell from 0.76 (95% CI 0.73-0.81) to 0.70 (95% CI 0.65-0.75) (P < .009). Platelet activation measured by P-selectin expression was reduced from 3.02% (95% CI 2.09-4.36) to 1.22% (95% CI 0.94-1.58) (P < .01). Fetal Doppler indices (umbilical artery, middle cerebral artery, and thoracic aorta) showed no significant changes during the infusion. S-nitrosoglutathione infusion reduced material mean arterial pressure, platelet activation, and uterine artery resistance without further compromising fetal Doppler indices. This study suggests that platelet-specific nitric oxide donors may prove beneficial in the management of severe preeclampsia.


Novel α-actinin 2 variant associated with familial hypertrophic cardiomyopathy and juvenile atrial arrhythmias: a massively parallel sequencing study.
Next-generation sequencing might be particularly advantageous in genetically heterogeneous conditions, such as hypertrophic cardiomyopathy (HCM), in which a considerable proportion of patients remain undiagnosed after Sanger. In this study, we present an Italian family with atypical HCM in which a novel disease-causing variant in α-actinin 2 (ACTN2) was identified by next-generation sequencing. A large family spanning 4 generations was examined, exhibiting an autosomal dominant cardiomyopathic trait comprising a variable spectrum of (1) midapical HCM with restrictive evolution with marked biatrial dilatation, (2) early-onset atrial fibrillation and atrioventricular block, and (3) left ventricular noncompaction. In the proband, 48 disease genes for HCM, selected on the basis of published reports, were analyzed by targeted resequencing with a customized enrichment system. After bioinformatics analysis, 4 likely pathogenic variants were identified: TTN c.21977G>A (p.Arg7326Gln); TTN c.8749A>C (p.Thr2917Pro); ACTN2 c.683T>C (p.Met228Thr); and OBSCN c.13475T>G (p.Leu4492Arg). The novel variant ACTN2 c.683T>C (p.Met228Thr), located in the actin-binding domain, proved to be the only mutation fully cosegregating with the cardiomyopathic trait in 18 additional family members (of whom 11 clinically affected). ACTN2 c.683T>C (p.Met228Thr) was absent in 570 alleles of healthy controls and in 1000 Genomes Project and was labeled as Damaging by in silico analysis using polymorphism phenotyping v2, as Deleterious by sorts intolerant from tolerant, and as Disease-Causing by Mutation Taster. A targeted next-generation sequencing approach allowed the identification of a novel ACTN2 variant associated with midapical HCM and juvenile onset of atrial fibrillation, emphasizing the potential of such approach in HCM diagnostic screening.


Cytochemical and immunocytochemical study of nuclear structures of Lacandonia schismatica.
The interphase nucleus of the cells of several tissues of Lacandonia schismatica was studied using electron microscopy cytochemical and immunocytochemical methods. The EDTA staining procedure, preferential for RNP, contrasted the Lacandonia granules and perichromatin fibrils. These granules were found to be relatively resistant to RNAse hydrolysis, but they were easily digested if RNAse treatment was carried out after a short hydrolysis with pronase. Bismuth oxynitrate stained granular structures about 17 nm in diameter and the periphery of a few Lacandonia granules. The anti-snURNPs bound to RNP-containing fibrils in the perichromatin and interchromatin space and also to the periphery of some Lacandonia granules. Immunolabeling of DNA demonstrated numerous filaments of extended chromatin in the perichromatin and interchromatin spaces which were closely related to Lacandonia granules. These observations suggested that Lacandonia granules are equivalent to Balbiani ring granules of nuclei with polytene chromosomes and to perichromatin granules of other plant and animal nuclei. The small number of Lacandonia granules labeled in their periphery by anti-snURNP mAb were interpreted as being immature granules in the process of formation. The external or annular part of the ring-shaped structures is heavily labeled by anti-URNP mAbs but scarcely stained by the EDTA procedure. These features indicate that this region contains abundant proteins associated with snURNAs but probably little snURNAs. The synaptonemal-like complexes previously found in the interphase nuclei of Lacandonia are formed by two parallel masses of compact chromatin, which react with anti-DNA, and a central clear space crossed by fiber.(ABSTRACT TRUNCATED AT 250 WORDS)


Locus of control and delinquency.
A sample of delinquent and nondelinquent male adolescents was assessed with respect to locus of control and intellectual achievement responsibility. Data were also gathered concerning age, family size, birth order, socioeconomic status, race, and school grade. Results were subjected to a multivariate analysis and showed support for a multidimensional model of locus of control. There was no difference in expectancy of control for negative academic events between delinquents and nondelinquents. In general, birth order and delinquency were the two most important determinants of locus of control. Results are discussed in terms of previous literature on locus of control with particular consideration paid to expectations of control.


The Self in the Spectrum: A Closer Look at the Temporal Stability of Self-Disorders in Schizophrenia.
Self-disorders are temporally persisting, experiential anomalies of subjective experiences that index liability to schizophrenia. They impact on the temporal unfolding of concomitant, diagnostic symptoms and can be suitably characterized through the Examination of Anomalous Self Ex periences (EASE). Capitalizing on the results of a recent longitudinal study, we explored the relevant patterns of interaction within self-disorders' descriptive dimensions (i.e., stream of consciousness, presence, corporeality, demarcation, and solipsism). The results indicated that after a 5-year follow-up the interconnection across SD dimensions tightened, confirming that EASE domains are interdependent aspects of an overarching structural change of subjectivity.


[Central cancer of the lung in MR image].
The paper analyzes the authors' own material based on the data of chest magnetic resonance imaging (MRI) in 48 patients with verified central cancer of the lung. The algorithm of chest MRI optimized by the authors is presented. The MRI signs of lung cancer in exo- and peribronchial forms of cancer are systematized. The MRI semiotics of chest structural damages are given in the extent of a tumor when progressing, and a metastatic lesion. The MRI signs of complications of this disease are specified.


SET nuclear proto-oncogene gene expression is associated with microsatellite instability in human colorectal cancer identified by co-expression analysis.
Microsatellite instability (MSI) is one of the promising biomarkers in human colorectal cancers (CRCs), and it is influenced by an intricate gene interaction network. Hence, we aimed to identify and validate hub genes associated with MSI CRC and to illustrate its underlying mechanisms. Weighted gene co-expression network analysis (WGCNA) was used to investigate potential regulatory targets and relationships between key modules and hub genes associated with MSI CRC. In the red module (r = 0.83), SET nuclear proto-oncogene (SET) was selected due to its high intra-modular connectivity and module membership. In the test sets, SET expression was downregulated in MSI CRCs compared to that in microsatellite stability (MSS) CRCs. SET expression level had a good performance in stratifying patients into MSI or MSS CRCs (area under the curve = 0.953). Moreover, the BRAF V600E mutation was highly associated with SET expression, and MSI/HLA- samples showed lower levels of SET mRNA expression than MSS/HLA- samples. Finally, gene set enrichment analysis (GSEA) indicated that patients in the SET low expression group were enriched in base excision repair. SET was identified and validated as a novel potential biomarker in MSI CRCs, and SET probably acts through regulating the base excision repair pathway.


Towards understanding the role of insulin in the brain: lessons from insulin-related signaling systems in the invertebrate brain.
Insulin is a molecule that has played a key role in several of the most important landmarks in medical and biological research. It is one of the most extensively studied protein hormones, and its structure and function have been elucidated in many vertebrate species, ranging from man to hagfish and turkey. The structure, function as well as tissue of synthesis of vertebrate insulins are strictly conserved. The structural identification of insulin-related peptides from invertebrates has disrupted the picture of an evolutionary stable peptide hormone. Insulin-related peptides in molluscs and insects turned out to be a structurally diverse group encoded by large multi-gene families that are uniquely expressed in the brain and serve functions different from vertebrate insulin. In this review, we discuss invertebrate insulins in detail. We examine how these peptides relate to the model role that vertebrate insulin has played over the years; however, more importantly, we discuss several unique principles that can be learned from them. We show how diversity of these peptides is generated at the genetic level and how the structural diversity of the peptides is linked to the exclusive presence of a single type of neuronal insulin receptor-related receptor. We also discuss the fact that the invertebrate peptides, in addition to a hormonal role, may also act in a synaptic and/or nonsynaptic fashion as transmitters/neuromodulators on neurons in the brain. It can be expected that the use of well-defined neuronal preparations in invertebrates may lead to a further understanding of these novel functions and may act as guide preparations for a possible role of insulin and its relatives in the vertebrate brain.


Billing for inpatient hospital care.
Pharmacy personnel billing patients for services rendered is discussed. Billing for services is a critical function for maintaining the financial viability of health care institutions. Poor understanding of the system can lead to incorrect documentation, which can result in a claim rejection. The UB-92 provides hospitals with the proper format to request reimbursement for services provided. To ensure proper reimbursement, appropriate coding of International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) codes for diagnosis, procedures, and services provided is necessary. Ancillary services, such as pharmacy, play a crucial role in the completion of the bill by ensuring that the charge-master accurately represents the service provided. This information includes identification, charge, cost, and revenue codes. Hospital billing agents must also account for any outpatient visits that may have occurred within three days of admission, since these charges may need to be included on the hospital bill. In order for the billing process to be effective, it is important that all personnel have a thorough understanding of the billing process and be able to effectively communicate with each other.


Differences between the Lewis and Sprague-Dawley rats in chronic inflammation induced norepinephrine sensitivity of cutaneous C-fiber nociceptors.
We investigated whether there are any differences between the Lewis and Sprague-Dawley (SD) rats in chronic inflammation-induced norepinephrine (NE) sensitivity of nociceptors. Activities of C-fiber nociceptors innervating rat hairy hindpaw skin were recorded in an in vitro skin-nerve preparation. Sixty-five percent of C-fibers from inflamed Lewis rats were excited by NE (10 microM), against only 38% of C-fibers from inflamed SD rats. The average of the total impulses evoked in response to NE was also significantly higher in Lewis rats. The alpha2-adrenoceptor antagonist CH 38083 (10 microM) and yohimbine (10 microM) consistently blocked the NE-excitation of both strains. These results show that after chronic inflammation, C-fiber nociceptors of Lewis strain rats have a stronger sensitivity to NE, and that alpha2-adrenoceptors are predominately involved in the NE-sensitivity of inflamed rats in both strains.