Genome-Wide Copy Number Variant and High-Throughput Transcriptomics Analyses of Placental Tissues Underscore Persisting Child Susceptibility in At-Risk Pregnancies Cleared in Standard Genetic Testing.
Several studies have shown that children from pregnancies with estimated first-trimester risk based on fetal nuchal translucency thickness and abnormal maternal serum pregnancy protein and hormone levels maintain a higher likelihood of adverse outcomes, even if initial testing for known genetic conditions is negative. We used the Finnish InTraUterine cohort (ITU), which is a comprehensively characterized perinatal cohort consisting of 943 mothers and their babies followed throughout pregnancy and 18 months postnatally, including mothers shortlisted for prenatal genetic testing but cleared for major aneuploidies (cases: n = 544, 57.7%) and control pregnancies (n = 399, 42.3%). Using genome-wide genotyping and RNA sequencing of first-trimester and term placental tissue, combined with medical information from registry data and maternal self-report data, we investigated potential negative medical outcomes and genetic susceptibility to disease and their correlates in placenta gene expression. Case mothers did not present with higher levels of depression, perceived stress, or anxiety during pregnancy. Case children were significantly diagnosed more often with congenital malformations of the circulatory system (4.12 (95% CI [1.22−13.93]) higher hazard) and presented with significantly more copy number duplications as compared to controls (burden analysis, based on all copy number variants (CNVs) with at most 10% frequency, 823 called duplications in 297 cases versus 626 called duplications in 277 controls, p = 0.01). Fifteen genes showed differential gene expression (FDR < 0.1) in association with congenital malformations in first-trimester but not term placenta. These were significantly enriched for genes associated with placental dysfunction. In spite of normal routine follow-up prenatal testing results in early pregnancy, case children presented with an increased likelihood of negative outcomes, which should prompt vigilance in follow-up during pregnancy and after birth.


Rapid Characterization and Modeling of Natural and Undefined Charge-Regulated Surfaces in Aqueous Systems.
The surfaces of most materials in aqueous systems are charged due to the ionization of surface functional groups. When these surfaces interact, the surface charge, electrostatic potential, and pH will vary as a function of separation distance, and this process is termed the charge-regulation effect. Charge regulation is a controlling factor in the adhesion and transport of colloids and microorganisms in aqueous systems, and its modeling requires representation of the pH-charge response of the surfaces, typically provided as the equilibrium constants (K) and site densities (N) of the dominant surface functional groups. Existing methods for obtaining these parameters demonstrate shortcomings when applied to many natural and man-made materials, such as weathered materials, materials with undefined or complex surface structures, and permeable materials, and for materials that do not provide the requisite high surface area in suspension due to small sample sizes. This hinders inclusion of the charge-regulation effect in colloid and microbial transport studies, and most studies of colloidal and microbial surface interactions use simplifying assumptions; a key example is the routine use of the constant potential assumption in DLVO modeling. Here we present a robust method that overcomes these issues and provides a rapid means to characterize charge-regulated surfaces using zeta potential data, without requiring a priori knowledge of the material composition. Applying a combined charge-regulation and Gouy-Chapman model, K and N values are obtained that accurately represent the electrostatic response of a charge-regulated surface. This method is demonstrated using activated carbon, aluminum oxide, iron (hydr)oxide, feldspar, and silica sand. The resulting K and N values are then used to show the variations in surface charge, electrostatic potential, and pH that can occur as these charge-regulated surfaces interact. This method provides a readily applied experimental approach for characterizing charge-regulated surfaces, with the overall goal to promote the inclusion of charge-regulated interactions into adhesion and transport studies with natural and undefined materials.


Glaucoma Surgery in Pregnancy: A Case Series and Literature Review.
Glaucoma management in pregnant patients is a real challenge, especially when the glaucoma is not controlled with medications. We report the results of 6 incisional glaucoma surgeries for the management of medically uncontrolled glaucoma patients during pregnancy. This retrospective, case series was conducted on the 6 eyes of 3pregnant patients with uncontrolled glaucoma using maximum tolerable medications. Details of the glaucoma surgical management of these patients as well as their postoperative care and pregnancy and clinical outcomes on longitudinal follow-up are discussed. All 3 patients had juvenile open-angle glaucoma and were on various anti-glaucoma medications, including oral acetazolamide. The first case described underwent trabeculectomy without antimetabolites in both eyes because of uncontrolled intraocular pressure with topical medications. The surgery was done with topical lidocaine jelly and subconjunctival lidocaine during the second and third trimesters. The second patient had an Ahmed valve implantation in both eyes during the second and third trimesters because of uncontrolled IOP with topical medications and no response to selective laser trabeculoplasty. Surgery was done with topical tetracaine and subconjunctival and sub-Tenon's lidocaine. The third case had a Baerveldt valve implantation under general anesthesia in the second trimester. In selected pregnant glaucoma patients with medically uncontrolled intraocular pressure threatening vision, incisional surgery may lead to good outcomes for the patient with no risk for the fetus.


Dural sinus filling defect: intrasigmoid encephalocele.
Filling defects of dural venous sinuses are considered to be a challenging problem especially in case of symptomatic patients. Many lesions have to be ruled out such as sinus thrombosis, arachnoid granulations and tumours. Encephalocele into dural sinus is also a rare cause of these filling defects of dural sinuses. Here, we report an extremely rare case with spontaneous occult invagination of temporal brain tissue into the left sigmoid sinus and accompanying cerebellar ectopia.


Protein metabolism in skeletal muscle, diaphragm, and heart of diabetic rats.
Rates of protein synthesis were measured in several muscle types in young streptozotocin-diabetic rats at different times after withdrawal of insulin therapy. Protein synthesis decreased in all types of muscle studied. In muscles with a substantial proportion of fast-twitch fibers (gastrocnemius and extensor digitorum longus), this decline was associated with falls in both protein synthesis-to-RNA and RNA-to-protein ratio, but in soleus and heart the effect could be explained entirely in terms of decreased ribosome concentration. Rates of protein degradation were calculated for heart, diaphragm, and gastrocnemius muscle from the changes in protein synthesis and protein content and were found in all cases to be elevated by 4 days of insulin withdrawal. However, measurements of protein synthesis and protein mass in the gastrocnemius muscle of a group of chronically diabetic rats indicated that in this condition, unlike in acute diabetes, the rate of protein degradation was depressed.


Nonsteroidal anti-inflammatory drugs (NSAIDs) and paracetamol do not affect 6-month mood-stabilizing treatment outcome among 482 patients with bipolar disorder.
Many mood disorder patients need analgesics due to increased pain sensitivity. Recent studies have suggested that nonsteroidal anti-inflammatory drugs (NSAIDs) may inhibit antidepressant treatment, which requires replication before clinical recommendations. The Clinical and Health Outcomes Initiatives in Comparative Effectiveness for Bipolar Disorder Study randomized participants to 6 months lithium or quetiapine treatment. Use of NSAIDs and paracetamol was assessed throughout the study period and psychopathology measured with the Clinical Global Impression Scale for Bipolar Disorder (CGI-BP) and Bipolar Inventory of Symptoms Scale (BISS). The effects of NSAIDs and paracetamol on treatment outcome were examined using mixed effects linear regression adjusted for age, gender, body mass index, smoking status, exercise, and somatic diseases. Among 482 participants, 177 (36.7%) used NSAIDs and/or paracetamol during the study. NSAID and paracetamol users did not differ from nonusers with respect to treatment outcome with lithium or quetiapine at any time point during 6 months treatment on the overall CGI-BP (β = 0.001 (95% CI = -0.01 to -0.01), P = .87), the BISS (β = 0.01 (95% CI = -0.17 to 0.15), P = .91), nor the CGI-BP subscales for depression or mania. Users of NSAIDs only (n = 76), paracetamol only (n = 62), and users of both NSAIDs and paracetamol (n = 39) showed no statistical difference compared to nonusers (all P > .3). This is the first trial to show that use of NSAIDs and paracetamol, alone or in combination, does not affect lithium- or quetiapine-based bipolar disorder mood-stabilizing treatment outcomes. Prior studies have suggested that NSAIDs may inhibit antidepressant treatment, whereas our results support findings indicating no detrimental effects of NSAIDs or paracetamol on affective disorder treatment.


Exercise-induced asthma and the use of hypertonic saline aerosol as a bronchial challenge.
Exercise induced asthma is a common complaint and the prevalence appears to be increasing worldwide. Once confined to the research domain of university teaching hospitals, the study of EIA has extended into the school playground, defence force establishments and sports institutions. Standardized protocols have been developed to study EIA in the laboratory and in the field. A surrogate challenge using eucapnic or isocapnic hyperventilation with dry air is becoming popular because it has advantages over exercise, at least for adults. The stimulus that leads the airways to narrow is caused by the inhalation of dry air during hyperventilation and exercise, during which water is evaporated from the airways in order to condition the inspired air. The mechanism whereby the airways narrow is thought to be due to the dehydrating effects of water loss, particularly in relation to its potential to cause the airways to become hyperosmolar. Mast cell mediators such as histamine and the leucotrienes are probably involved in EIA because specific antagonists reduce severity. As a result of the osmotic theory of EIA, studies were carried out to determine whether subjects with EIA were sensitive to the effects of increasing airway osmolarity by inhalation of hyperosmolar aerosols of sodium chloride. A challenge protocol using an aerosol of 4.5% sodium chloride, generated from an ultrasonic nebulizer, has been used to identify persons with asthma and to assess response to drug therapy. There are many similarities between responses to exercise, hyperventilation and hypertonic saline in the physiological and biochemical responses and the responses to drugs. Challenge with hypertonic saline is easier and cheaper to use because expensive equipment and a source of dry air is not required as with exercise or hyperventilation. The ability to obtain a dose-response curve rather than a single response and the ability to collect inflammatory cells at the same time make challenge with hypertonic saline an attractive technique to study patients suspected of having asthma.


Maternal control and eating styles in children: The mediating role of emotion differentiation.
Introduction: Theoretical accounts and empirical research suggest that mother-child interactions significantly influence the child's eating styles (emotional, external, and restrained eating). However, little or no research has explored the association between maternal psychological control and eating styles and whether other mechanisms may be involved in such association. To address this shortcoming, the present study aimed to investigate the mediating role of difficulties in differentiating emotions between maternal control and eating styles.Methods: Participants were 324 elementary school children (Girls = 172, 53.1%) aged between 8 and 11 years (Mage = 9.13, SD = .89) assessed through self-report measures. Parents provided information about weight and height.Results: Path analysis model showed an acceptable fit to the data (χ2 (3) = 3.966, p = .256; RMSEA = .032; CFI = .990; TLI = .911; SRMR = .018). Difficulties in differentiating emotions significantly mediated the relationship between maternal control and emotional eating (β = -.071, 95%CI [-.094, -.052]; p < .001). The model was invariant across genders.Conclusions: Our findings support the importance of dyadic interaction in enhancing the risk for dysfunctional eating style during infancy, showing that emotion differentiation deficits may be particularly salient in such relationship. Clinical and practical implications of these findings are discussed.


Metabolic regulation of photosynthesis.
Photosynthesis is fundamental to biomass production, but is a dynamic process sensitive to environmental constraints. In recent years, approaches to increase biomass and grain yield by altering photosynthetically related processes in the plant have received considerable attention. However, improving biomass yield requires a predictive understanding of the molecular mechanisms that allow photosynthesis to be adjusted. The important roles of metabolic reactions external to those directly involved in photosynthesis are highlighted in this review; however, our major focus is on the routes taken to improve photosynthetic carbon assimilation and to increase photosynthetic efficiency and consequently biomass yield.


Early and long-term improvement in left ventricular performance following coronary bypass surgery.
Changes in left ventricular performance after coronary artery bypass grafting (CABG) have been variable. Earlier studies based on contrast left ventriculography have shown occasional improvement in left ventricular function in patients with unstable angina or abnormal preoperative ventricular performance, but for the most part repeat cardiac catheterization several months after operation has shown no significant changes in global left ventricular contraction. In the past few years, advances in radiopharmaceutical technology have made the characterization of left ventricular wall motion accurate and highly reproducible. Since prognosis in patients with coronary artery disease and survival after CABG have been related to global ejection fraction (EF), we employed prospectively on analysis of short-term and long-term changes in EF after CABG utilizing multidose hypothermic potassium crystalloid cardioplegia as the method of myocardial protection. Concomitantly, newer techniques in anesthesia and perioperative patient management were employed to minimize myocardial damage in these patients. Postoperative scintigraphic evaluation showed a transient (2-hour) depression in left ventricular function, followed by recovery to preoperative levels at 24 hours and significant improvement in EF at 7 days. From 7 days to 8 months postoperatively, there was no further change in resting EF, but there was another significant exercise-induced increase in EF at the long-term examination. Thus, present advances in the multidisciplinary management of patients with coronary artery disease are associated with improvement in resting and exercise-related EF postoperatively.


Neural Progenitor Cell Terminology.
Since descriptions of neural precursor cells (NPCs) were published in the late 19th century, neuroanatomists have used a variety of terms to describe these cells, each term reflecting contemporary understanding of cellular characteristics and function. As the field gained knowledge through a combination of technical advance and individual insight, the terminology describing NPCs changed to incorporate new information. While there is a trend toward consensus and streamlining of terminology over time, to this day scientists use different terms for NPCs that reflect their field and perspective, i.e., terms arising from molecular, cellular, or anatomical sciences. Here we review past and current terminology used to refer to NPCs, including embryonic and adult precursor cells of the cerebral cortex and hippocampus.


Early life undernutrition and adolescent pregnancy outcome in rural India.
In poor communities of the Third World, adolescent pregnancy outcomes are likely to be worse in view of the prevailing chronic undernutrition. The study examined the confounding effect of early life undernutrition on adolescent pregnancy outcome in rural India. Retrospective information on socio-economic, demographic and anthropometric variables, gynaecological and obstetric history, pregnancy outcome and birth weight was obtained on 326 primigravid young married rural girls during 1998-2001. Prevalence of pregnancy wastage (stillbirths and abortions) reduced significantly (p < 0.01) with increase in age at first conception. The risk for pregnancy wastage observed (OR = 1.95, 95% CI = 0.91-4.21) in mothers with early conception (<17.25 years) increased significantly to 4.24 (95% CI = 1.4-12.86) in case of girls with delayed menarcheal age (>or=14.5 years) or to 14.2 (95% CI = 1.17-173.2) if they had higher post-menarcheal stature growth (>or=4 cm). Similarly, risk for preterm delivery (OR = 2.18, 95% CI = 0.88-5.42) observed among mothers with early conception increased to 36.6 (95% CI = 3.57-374.0) if they had significant post-menarche gain in height. Our findings thus indicate that pregnancy outcome was adversely affected by early conception and prolonged adolescent growth, which are the features of biological immaturity in undernourished populations. Our findings indicate that in view of prevailing socio-cultural conditions, good nutrition in early life for girls is essential to prevent post-menarcheal height growth while health education programmes are essential to prevent early conception in rural India. These observations have wider implications for similar rural settings especially in other developing countries.


Evidence suggesting that a novel guanine nucleotide regulatory protein couples receptors to phospholipase C in exocrine pancreas.
The initial response of many cells to 'Ca2+-mobilizing' agonists is phospholipase C-mediated hydrolysis of phosphatidylinositol bisphosphate to inositol trisphosphate (IP3) and diacylglycerol. It has been suggested, by analogy with receptor regulation of adenylate cyclase, that 'Ca2+-mobilizing' receptors may interact with a guanine nucleotide-binding protein (G protein) to regulate phospholipase C activity. Here we report increased accumulation of IP3 in response to caerulein or carbachol in electrically permeabilized rat pancreatic acinar cells. The stable analogues of GTP (guanosine 5'-[gamma-thio]trisphosphate and guanosine 5'-[beta, gamma-imido]triphosphate) stimulate IP3 accumulation and potentiate the effects of caerulein and carbachol. This synergism demonstrates an interaction between receptors, a G protein and phospholipase C. These responses are unaffected by pretreatment of the cells with pertussis or cholera toxins under conditions that produce substantial covalent modification of Gi and Gs, the proteins that couple receptors to adenylate cyclase. We therefore conclude that the G protein that couples receptors to phospholipase C in exocrine pancreas is probably neither Gi nor Gs; instead, we propose that a different G protein mediates this effect.


Melanoma and the problem of malignancy.
Of the overt biological properties exhibited by malignant cells two appear to command particular attention; these are (1) the transmigratory ability which empowers these cells to invade surrounding tissues and results in their metastatic and destructive potential, and (2) their ability to evade detection by the immune system of the host. Both of these characteristics may well involve several disparate mechanisms. However, it may be that there are some metabolic features that are common to malignant neoplasms which could go some way to explaining one of these behavioural anomalies. It is proposed that abnormalities of oxidative metabolism of cancer cells, resulting in the generation of reactive oxygen species, are responsible for the inhibition of the functions of vicinal antigen-presenting cells and, thus, the failure of the immune system to recognize tumour-specific antigens likely to be expressed by malignant cells as part of their transmigratory capability.


Perspectives and Experiences of Smartphone Overuse among University Students in Umm Al-Qura University (UQU), Saudi Arabia: A Qualitative Analysis.
Smartphone overuse and addiction is a growing concern worldwide. However, there are limited studies about smartphone addiction and its impacts on university students in Saudi Arabia. This qualitative study aimed to elicit students' and university staff's perspectives and experiences about smartphone overuse/addiction in Umm Al-Qura University (UQU), Saudi Arabia. Fifteen undergraduate students and 18 university staff (13 lecturers and five professionals) were recruited for the purpose of this study. The study data were collected using semi-structured interviews and analysed using thematic analysis. The qualitative data comprising 33 participants (students and staff) identified four major themes including the perception of smartphone use; causes of smartphone overuse; negative impacts of smartphone overuse; and strategies to reduce the overuse of smartphone. The overall findings confirmed that students and staff alike held both positive and negative perceptions about using a smartphone. Potential factors leading to smartphone overuse included personal factors (extended free time and low self-confidence, irresponsibility/escaping certain social gatherings/passing the time); smartphone factors (reasonable price, attractive advertisements (ads), and engaging smartphone Apps); and social factors (social pressure and fear of losing a connection). The main negative impacts of smartphone overuse were found to be related to low academic productivity, poor physical health (body pain, lack of sleep, and low exercise), compromised mental well-being (stress and negative emotions), and decreased socialisation (social isolation and a reduction in face-to-face communication). Our findings suggested that awareness campaigns about smartphone overuse, promoting family and social events, encouraging physical activities, and limiting internet use can reduce smartphone usage among university students. This finding has significant implications for decision-makers.


Childhood Physical Neglect Is Associated With Exaggerated Systemic and Intracellular Inflammatory Responses to Repeated Psychosocial Stress in Adulthood.
Experiences of child maltreatment are associated with a host of adverse mental and physical health outcomes in adulthood. Altered reactivity to psychosocial stress exposure may partially explain known associations between early experiences of maltreatment and later life health. The present study focuses on examining whether experiences of child maltreatment are associated with physiological reactions to initial and repeated psychosocial stress in adulthood. To this end, 44 healthy adults (52% male, aged 18-65) completed the Childhood Trauma Questionnaire to provide information about exposure to child maltreatment and completed the Trier Social Stress Test (TSST) on 2 consecutive days. Peripheral blood was collected prior to as well as 30 and 120 min following the TSST on each day. Plasma Interleukin-6 (IL-6) and gene expression of IL-6, IL-1β, nuclear factor-kB (NF-kB), and inhibitor of kB (IkB) were measured from each blood sample. Total CTQ scores were unrelated to plasma IL-6 and gene expression (ps > .10) but a history of childhood physical neglect was associated with increased interleukin-1β (β =.35; p =.02; R2 =.19) and nuclear factor-kB (β =.30; p =.046; R2 =.13) expression following initial stress. Following repeated exposure to the TSST, childhood physical neglect was associated with increased plasma IL-6 reactivity (β =.34; p =.02; R2 =.16) and increased expression of nuclear factor-kB (β =.31; p =.04; R2 =.08). Finally, childhood physical neglect was associated with decreased habituation following repeated exposure to the TSST. Other CTQ subscales were not related to plasma IL-6 and gene expression when considered individually. Results from this study are suggestive of a unique effect of childhood physical neglect on the physiological stress response following initial and repeated exposure to a common psychosocial stressor. This provides important directions for future research because the effect of childhood physical neglect on long-term neglect are not well understood and in need of further investigation.


Water/alcohol soluble electron injection material containing azacrown ether groups: synthesis, characterization and application to enhancement of electroluminescence.
Using an environmentally stable metal as the cathode in a polymer light-emitting diode (PLED) is an essential requirement for its practical application. We present the preparation of a water/alcohol soluble copoly(p-phenylene) (P1) containing pendant azacrown ether and ethylene glycol ether groups as a highly efficient electron injection layer (EIL) for PLEDs, allowing the use of environmentally stable aluminum as the cathode. Multilayer PLEDs [ITO/PEDOT:PSS/PF-Green-B/EIL/Al] using P1 as EIL exhibit significantly enhanced device performance, particularly in the presence of K2CO3 or Cs2CO3. The maximum luminous power efficiency and maximum luminance of the device with Cs2CO3-doped P1 as EIL were enhanced to 9.16 lm W(-1) and 17,050 cd m(-2), respectively, compared with those without EIL (0.16 lm W(-1), 890 cd m(-2)). The turn-on voltage was also significantly reduced from 5.7 V to 3.7 V simultaneously. The performance enhancement has been attributed to improved electron injection which has been confirmed by the rise in open-circuit voltage (Voc) obtained from photovoltaic measurements. The incorporation of such an electron injection layer significantly enhances device performance for PLEDs with an environmentally stable metal as the cathode.


Who makes the decision regarding the treatment of clinically localized prostate cancer--the patient or physician?: results from a population-based study.
The current study examined how patients' sociodemographic, cancer-related, and subjective affective factors impacted their role in treatment decision-making. The patient sample (N = 788) was taken from a prospective follow-up study of a population-based cohort. Participants included 343 African American and 445 Caucasian-American patients with clinically localized prostate cancer. Multinomial logistic regression was used to investigate relations between the explanatory variables and the nominal 3-level decision-making variable: patient-only, patient-physician shared, and physician-only. Approximately 41% of patients reported patient-only decision-making, 45% reported shared decision-making, and 13% reported physician-only decision-making. The odds of patient-only over physician-only decision-making were greater for younger men (vs those aged ≥ 65 years) (odds ratio [OR], 1.68; 95% confidence interval [95% CI], 1.03-2.74), and were less for men with high (vs low) cancer aggressiveness (OR,0.29; 95% CI, 0.15-0.55). The odds of shared over physician-only decision-making were less for men with high (vs low) cancer aggressiveness (OR, 0.40; 95% CI, 0.22-0.73). Greater odds of patient-only and shared decision-making also were found to be associated with greater concerns about the physical impact of treatment and having enough time for decision-making and lower scores of receiving advice from others. The findings of the current study indicate that, to facilitate a more patient-oriented decision-making process regarding treatment in those with clinically localized prostate cancer, clinicians need to tailor their interventions according to patient age and cancer aggressiveness, help reduce patient concerns and misconceptions regarding the physical impact of treatments, allow sufficient time for patients to consider treatment options, and assist patients in balancing advice and information received from different sources.


Heat shock reduces stalled RNA polymerase II and nucleosome turnover genome-wide.
Heat shock rapidly induces expression of a subset of genes while globally repressing transcription, making it an attractive system to study alterations in the chromatin landscape that accompany changes in gene regulation. We characterized these changes in Drosophila cells by profiling classical low-salt-soluble chromatin, RNA polymerase II (Pol II), and nucleosome turnover dynamics at single-base-pair resolution. With heat shock, low-salt-soluble chromatin and stalled Pol II levels were found to decrease within gene bodies, but no overall changes were detected at transcriptional start sites. Strikingly, nucleosome turnover decreased genome-wide within gene bodies upon heat shock in a pattern similar to that observed with inhibition of Pol II elongation, especially at genes involved in the heat-shock response. Relatively high levels of nucleosome turnover were also observed throughout the bodies of genes with paused Pol II. These observations suggest that down-regulation of transcription during heat shock involves reduced nucleosome mobility and that this process has evolved to promote heat-shock gene regulation. Our ability to precisely map both nucleosomal and subnucleosomal particles directly from low-salt-soluble chromatin extracts to assay changes in the chromatin landscape provides a simple general strategy for epigenome characterization.


Contributors of water intake in US children and adolescents: associations with dietary and meal characteristics--National Health and Nutrition Examination Survey 2005-2006.
Little is known about the association of contributors of total water intake with dietary characteristics in US children. We examined intakes of total water and its contributors and their associations with diet and meal reporting in children and adolescents. Dietary data for children 2-19 y of age (n = 3978) from the National Health and Nutrition Examination Survey 2005-2006 were used to compute usual intake of total water. The association of total water and its contributors with sociodemographic characteristics and dietary and meal attributes was examined by using multiple regression analysis. The adjusted mean intakes of total water in Americans aged 2-5, 6-11, and 12-19 y were 1.4, 1.6, and 2.4 L, respectively. The mean usual intake of total water was generally less than the Adequate Intake; overall, more boys reported intakes of at least the Adequate Intake. The percentage of total water intake from plain water increased with age. Plain water intake was inversely associated with the intake of beverage moisture and the energy density of foods; conversely, beverage moisture was positively associated with dietary energy, fat, and the energy density of foods. Associations of water contributors with meal patterns (number of eating occasions, reporting of breakfast or snack) were inconsistent across age groups. Nearly 80% of food moisture, >66% of beverage moisture, and ≈30% of plain water were reported with main meals. Intake of total water over 24 h from different contributors varied by age. Qualitative differences in dietary intake in association with the amount of plain water and beverage moisture in the recalls were observed. American children and adolescents consumed more than two-thirds of their daily beverages with main meals.


The end of life: informal care for dying older people and its relationship to place of death.
This study examined the features of informal end-of-life care of older people living in the community and the association between informal care characteristics and dying at home. Retrospective data were obtained from interviews and self-administered questionnaires of 56 persons who had been primary caregivers of older relatives in the last three months of their lives. Results showed that informal caregivers of terminally ill older people living in the community provided a considerable amount of personal, household, and management care. Secondary informal caregivers and formal caregivers assisted resident primary caregivers less often than nonresident primary caregivers. Primary caregivers who felt less burdened, who gave personal care more intensively, and/or who were assisted by secondary caregivers, were more likely to provide informal end-of-life care at home until the time of death. Our study showed that informal care at the end of life of older people living in the community is complex, since the care required is considerable and highly varied, and involves assistance from secondary informal caregivers, formal home caregivers as well as institutional care. Burden of informal care is one of the most important factors associated with home death. More attention is needed to help ease the burden on informal caregivers, specifically with regard to resident caregivers and spouses. Since these resident caregivers were disadvantaged in several respects (i.e., health, income, assistance from other carers) compared to nonresident caregivers, interventions by formal caregivers should also be directed towards these persons, enabling them to bear the burden of end-of-life care.


An electromyographic study of post retraction orthodontic patients.
19 patients treated by the Begg technique 7 patients treated by the Edgewise technique and 15 cases treated by a functional technique who had been at from 1-10 years without any form of retention were recorded electromyographically and their patterns of activity compared with those of patients who had a normal occlusion and who had not received orthodontic treatment. In the interocclusal position the patients who had received functional treatment had a balanced activity and were similar to those with a normal occlusion but this was not so when biting on cardboard 0.5 mm thick. The Begg cases were balanced but the amount of activity was reduced by half; the Edgewise cases were balanced when biting on cardboards and were then similar to those with a normal occlusion.


Cardiac abnormalities associated with pheochromocytoma and other adrenal tumors.
To study the specific cardiac abnormalities associated with pheochromocytoma and to suggest a strategy for evaluating cardiac function in patients with pheochromocytoma. In this case-control study, we reviewed pathology records of patients seen at Cedars-Sinai Medical Center between 1997 and 2007; patients with adrenal or extra-adrenal pheochromocytoma and those with nonfunctioning benign or malignant adrenal tumors were identified. Patients with functioning adrenal adenomas that secreted cortisol or aldosterone were excluded. Clinical history, imaging, pathology, biochemical test results, electrocardiographic findings, and echocardiographic findings were compared between patients with pheochromocytoma and patients with nonfunctioning adrenal tumors. The charts of 22 patients with pheochromocytoma and 35 patients with nonfunctioning adrenal tumors were included. No perioperative mortality was observed. The average age of patients with pheochromocytoma was similar to that of control patients (51.9 +/- 3.9 years vs 60.2 +/- 2.5 years, respectively), as was the number of patients with known cardiovascular diseases (2 [9%] in the pheochromocytoma group vs 5 [14%] in the control group). Two patients with pheochromocytoma (9%) exhibited myocardial damage. Abnormal electrocardiographic findings were present in 16 patients with pheochromocytoma (73%) and in 17 control patients (49%) (P = .1). QTc was prolonged in patients with pheochromocytoma compared with control patients (448.3 +/- 9.7 ms vs 424.7 +/- 4.5 ms, respectively; P = .02) and was correlated with levels of norepinephrine and normetanephrine, but not with levels of epinephrine and metanephrine or tumor size. ST-T abnormalities were present in 11 patients with pheochromocytoma (50%) and in 8 control patients (23%) (P = .04). Echocardiographic findings were normal in most patients with pheochromocytoma; abnormal left ventricular wall motion was documented in 3 patients with long QTc. The specific electrocardiographic findings in patients with pheochromocytoma are prolonged QTc and ST-T abnormalities. Performing an electrocardiogram in patients with pheochromocytoma would be prudent. Echocardiography would be useful to examine LV wall motion in patients with long QTc. Coronary artery disease should be excluded in patients with significant ST-T changes.


Strategies for hearing in noise: peripheral control over auditory sensitivity in the bushcricket sciarasaga quadrata (Austrosaginae: tettigoniidae)
The carrier frequency of the call of the Australian bushcricket Sciarasaga quadrata is unusually low for tettigoniids at 5 kHz. The sound transmission measured in the habitat of the insect reflects the advantages of producing low- rather than high-frequency signals; attenuation is explained almost entirely by the spherical spreading of sound. The natural vibration frequency of the wings is controlled by size and stiffness. The small tegmina are unusually fleshy, with an order-of-magnitude higher water content than in comparable sagine species. Reduced stiffness allows the insect to call at low carrier frequencies, albeit at lower intensity levels (60 dB SPL at 1 m), than bushcrickets of comparable size (80-90 dB SPL). The responses of the tympanic nerve and a first-order interneurone (omega neurone) in the afferent auditory pathway showed that the hearing system is most sensitive to frequencies of 15-20 kHz, an effective mismatch to the conspecific call resulting in a reduced sensitivity of approximately 20 dB at the carrier frequency of the call. S. quadrata can occlude its spiracular opening, which increases the sensitivity of the ear to lower frequencies. Under such conditions, the best frequency of the ear matched that of the carrier frequency of the call. We measured the activity of auditory neurones in the field, noting the ability of the open and partially closed ear to filter out potentially masking calls of congenerics. At the same time, the directionality of the system was only slightly reduced in the closed relative to the open spiracle status. We discuss the evolutionary advantages of an insect both calling with a low carrier frequency and having the ability to close down the tracheal system to avoid the effects of masking. In addition, we consider the advantages of such a signalling system in avoiding the most significant predator of the male, the ormine fly Homotrixa alleni. <P>


Radical surgery in ovarian cancer.
While there is an ongoing debate regarding the timing of the maximal surgical effort in epithelial ovarian cancer, it is well established that patients with suboptimal tumor debulking derive no benefit from the surgical procedure. The amount of residual disease after cytoreductive surgery has been repeatedly identified as a strong predictor of survival, and accordingly, the surgical effort to achieve the goal of complete gross tumor resection has been constantly evolving. Centers that have adopted the concept of radical surgery in patients with advanced ovarian cancer have reported improvements in their patients' survival. In addition to the expected improvements in the pharmacologic treatment of this disease, some of the next challenges in the surgical management of ovarian cancer include the preoperative prediction of suboptimal debulking, improving the drug delivery to the tumor, and increasing access to centers of excellence in ovarian cancer regardless of geographical, financial, or other social barriers. This review will discuss an update on the role of surgery in the treatment of primary epithelial ovarian cancer as it has evolved since the emergence of the concept of surgical cytoreduction.


On-Surface Debromination of 2,3-Bis(dibromomethyl)- and 2,3-Bis(bromomethyl)naphthalene: Dimerization or Polymerization?
We describe the on-surface dehalogenative homocoupling of benzylic bromides, namely bis-bromomethyl- and bis-gem-(dibromomethyl) naphthalene as a potential route to either hydrocarbon dimers or conjugated polymers on Au(111). While bis-gem-(dibromomethyl) naphthalene affords different dimers with naphthocyclobutadiene as the key intermediate, bis-bromomethyl naphthalene furnishes a poly(o-naphthylene vinylidene) as a non-conjugated polymer which undergoes dehydrogenation toward its conjugated derivative poly(o-naphthylene vinylene) upon mild annealing. A combination of scanning tunneling microscopy, non-contact atomic force microscopy and density functional theory calculations provides deep insights into the prevailing mechanisms.


Vertical and temporal variation in phytoplankton assemblages correlated with environmental conditions in the Mundaú reservoir, semi-arid northeastern Brazil.
The goal of this study was to analyse the vertical structure of the phytoplankton community at the Mundaú reservoir, located in the semi-arid region of northeastern Brazil, and to correlate it to environmental conditions over two distinct seasons, dry and rainy. Samples were collected bimonthly at eight depths in the dry and rainy season for analyses of the physical and chemical variables of the water, as well as density, abundance, dominance, species diversity index and equitability of the community. Analysis of variance (ANOVA-two way) was used to analyse the vertical and seasonal differences, and Canonical Correspondence Analysis (CCA) was used to assess associations between phytoplankton and environmental variables Cylindrospermopsis raciborskii (Woloszynska) Seenaya and Subba Raju was the only dominant species and Geitlerinema amphibium (C. Agardh) Anagnostidis, Merismopedia punctata Meyen and Synedra rumpens Kützing. Others six taxa were abundant in at least one of the samples. Distinct vertical distribution patterns were observed for the abundant taxa between depths and seasons. The cyanobacteria, with the exception of C. raciborskii, showed similar seasonal patterns, with higher densities in the dry season. The CCA showed a strong correlation between the density of the phytoplanktonic species and abiotic variables. The vertical changes in abundant taxa revealed distinct patterns regulated by the variation in the environmental factors that were directly linked to seasonality, with the success of one or more species being dependent on their life strategies and ecological needs. The present study restates the importance of environmental and seasonal factors for phytoplankton composition and distribution in a freshwater tropical reservoir through a vertical gradient.


[NO-ergic innervation of digestive tract of Japanese anchovy (Engraulis japonicus)].
This investigation was aimed at the study of distribution, localization and morphological peculiarities of NO-ergic cells and fibers in the digestive tract of Japanese anchovy Engraulis japonicus. Using the histochemical method developed by B.T. Hope and S.R. Vincent (1989), NO-ergic cells and fibers were demonstrated in the intermuscular plexus and in the circular layer of the muscular tunic in all the digestive tract organs studied. Single No-ergic cells were located in the longitudinal layer of the muscular tunic in the esophagus and stomach. In the submucosal plexus NO-ergic neurons were detected only in the stomach. The greatest density of NO-ergic cell distribution was characteristic to the posterior portion of the intestine and stomach.


Predictors and prognosis for complex coronary lesions in patients with acute myocardial infarction: data from RICO survey.
We aimed to investigate the determinants and outcomes of multiple complex lesions (MCLs) on coronary angiography in patients with an acute myocardial infarction. One thousand one hundred fifty-two consecutive nonselected myocardial infarction patients who underwent coronary angiography within 24 hours after admission were analyzed. A complex lesion was defined by the presence of thrombus, ulceration, irregular plaque, and flow impairment. Patients with < or = 1 complex lesion were considered with single complex lesion (SCL), and patients with > 1 complex lesions with MCLs. Multiple complex lesions were identified in 360 patients (31%). Patients from the MCL group were older and had a higher rate of cardiovascular risk factors but were less likely to be smokers when compared with the SCL group. Patients with MCLs were more likely to have altered left ventricular ejection fraction and multivessel disease and showed a trend toward an increased median time delay to revascularization (360 vs 285 minutes; P = .070). Moreover, the C-reactive protein (CRP) plasma levels increased with the number of CLs. By multivariate analysis, multivessel disease and CRP level were associated with the presence of MCLs. When compared with the SCL group, patients with MCLs had a higher risk of inhospital cardiogenic shock (18% vs 11%; P = .005) and 30-day mortality (11% vs 6%; P = .002). At 1-year follow-up, the presence of MCLs was an independent predictive factor of death. This study shows that the presence of MCLs is associated with worse outcomes and that risk factors such as CRP are able to identify patients at a high risk for MCLs.


[Complex neuroradiological diagnosis in case of atherosclerotic lesion of the carotid arteries].
The diagnostic arsenal for extracranial stenosis includes both ultrasound techniques, such as transcranial Doppler and duplex sonography, which are not only screening methods, but also are used at surgery, and high-tech neuroradiological techniques, such as spiral computed tomographic and magnetic resonance angiography, which can visualize structural changes in the vessel walls and qualitatively and functionally evaluate blood flow in the vascular bed. The purpose of this investigation was to determine the efficacy of non-invasive diagnostic methods, such as magnetic resonance angiography, including phase-contrast magnetic resonance angiography and spiral computed tomographic angiography, in the detection and comprehensive evaluation of stenoses and to compare the feasibilities of noninvasive procedures with the gold standard--selective angiography.


Recurrent disseminated encephalomyelitis: A case report and literature review.
Acute disseminated encephalomyelitis has been understood as a monophasic, often post-infectious illness that predominantly affects the pediatric population. Though that describes the majority of cases, exceptions do exist. In this case report, we present an adult case of recurrent disseminated encephalomyelitis (DEM) and review the available literature on this clinical entity. PubMed search performed using the terms "MDEM" and "Recurrent ADEM" in April 2018. A total of 23 items resulted for the first search and another 142 for the second. We selected articles that described cases of recurrent ADEM with a preference for those publications describing adult cases and those written in English language. Recurrent disseminated encephalomyelitis is a distinct clinical entity that has features which overlap with multiple sclerosis, making it imperative to distinguish the two. Our case presentation and accompanying literature review highlights the limited scope of data available on recurrent DEM and the need for further study.


Recall-promoting physician behaviors in primary care.
Effective treatments can be rendered useless by poor patient recall of treatment instructions. Studies suggest that patients forget a great deal of important information and that recall can be increased through recall-promoting behaviors (RPBs) like repetition or summarization. To assess how frequently RPBs are used in primary care, and to reveal how they might be applied more effectively. Recordings of 49 unannounced standardized patient (SP) visits were obtained using hidden audiorecorders. All SPs presented with typical gastroesophageal reflux disease symptoms. Transcripts were coded for treatment recommendations and RPBs. Forty-nine primary care physicians. Of 1,140 RPBs, 53.7% were repetitions, 28.2% were communication of the rationale for a treatment, 11.7% were categorizations of treatments (i.e., stating that a treatment could be placed into a treatment category, such as medication-related or lifestyle-related categories), and 3.8% were emphasis of a recommendation's importance. Physicians varied substantially in their use of most RPBs, although no physicians summarized or asked patients to restate recommendations. The number of RPBs was positively correlated with visit length. Primary care physicians apply most RPBs inconsistently, do not utilize several RPBs that are particularly helpful, and may use RPBs inefficiently. Simple principles guiding RPB use may help physicians apply these communication tools more effectively.


Ablate and pace revisited: long term survival and predictors of permanent atrial fibrillation.
To assess long term mortality and identify factors associated with the development of permanent atrial fibrillation after atrioventricular (AV) node ablation for drug refractory paroxysmal atrial fibrillation. Retrospective cohort study. UK tertiary centre teaching hospital. Patients admitted to the University Hospital Birmingham between January 1995 and December 2000. AV node ablation and dual chamber mode switching pacing. Long term mortality and predictors of permanent atrial fibrillation, assessed through Kaplan-Meier curves and logistic regression. 114 patients (1995-2000) were included: age (mean (SD)), 65 (9) years; 55 (48%) male; left atrial diameter 4 (1) cm; left ventricular end diastolic diameter 5 (1) cm; ejection fraction 54 (17)%. Indications for AV node ablation were paroxysmal atrial fibrillation in 95 (83%) and paroxysmal atrial fibrillation/flutter in 19 (17%). The survival curve showed a low overall mortality after 72 months (10.5%). Fifty two per cent of patients progressed to permanent atrial fibrillation within 72 months. There was no difference in progression to permanency between paroxysmal atrial fibrillation and paroxysmal atrial fibrillation/flutter (log rank 0.06, p = 0.8). Logistic regression did not show any association between the variables collected and the development of permanent atrial fibrillation, although age over 80 years showed a trend (p = 0.07). Ablate and pace is associated with a low overall mortality. No predictors of permanent atrial fibrillation were identified, but 48% of patients were still in sinus rhythm at 72 months. These results support the use of dual chamber pacing for paroxysmal atrial fibrillation patients after ablate and pace.


Cellular mechanisms associated with spontaneous and ciliary neurotrophic factor-cAMP-induced survival and axonal regeneration of adult retinal ganglion cells.
We have shown previously that intraocular elevation of cAMP using the cAMP analog 8-(4-chlorophenylthio)-cAMP (CPT-cAMP) failed to promote axonal regeneration of axotomized adult retinal ganglion cells (RGCs) into peripheral nerve (PN) grafts but significantly potentiated ciliary neurotrophic factor (CNTF)-induced axonal regeneration. Using the PN graft model, we now examine the mechanisms underlying spontaneous and CNTF/CPT-cAMP-induced neuronal survival and axonal regrowth. We found that blockade of the cAMP pathway executor protein kinase A (PKA) using the cell-permeable inhibitor KT5720 did not affect spontaneous survival and axonal regeneration but essentially abolished the CNTF/CPT-cAMP-induced RGC survival and axonal regeneration. Blockade of CNTF signaling pathways such as phosphotidylinositol 3-kinase (PI3K)/akt by 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one (LY294002), mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) by 2-(2-diamino-3-methoxyphenyl-4H-1-benzopyran-4-one (PD98059), or Janus kinase (JAK)/signal transducer and activators of transcription (STAT3) by tyrphostin AG490 also blocked the CNTF/CPT-cAMP-dependent survival and regeneration effects. PKA activity assay and Western blots showed that KT5720, LY294002, and PD98059 almost completely inhibited PKA, PI3K/akt, and MAPK/ERK signal transduction, respectively, whereas AG490 substantially decreased JAK/STAT3 signal transduction. Intraocular injection of CPT-cAMP resulted in a small PKA-dependent increase in CNTF receptor alpha mRNA expression in the retinas, an effect that may facilitate CNTF action on survival and axonal regeneration. Surprisingly, in the absence of CNTF/CPT-cAMP, LY294002, PD98059, and AG490, but not KT5720, significantly enhanced spontaneous RGC survival, suggesting differential roles of these pathways in RGC survival under different conditions. Our data suggest that CNTF/CPT-cAMP-induced RGC survival and axonal regeneration are a result of multiple pathway actions, with PKA as an essential component, but that these pathways can function in an antagonistic manner under different conditions.


[Regenerative processes of the internal structures of the knee joint following meniscectomy. Experimental study of the knee joint of the rabbit].
In an experimental study of thirty rabbits, processes of repairing of the inner structures in the knee joint after meniscectomy were examined: Three operational methods were used: The total, partial and sub-partial menisectomy. Macroscopic, microscopic and electron microscopic examinations of the inner structure of the knee joint were made after intervals of one, three, six, nine and twelve weeks after meniscectomy. Processes of adaptation in the articulating parts of the joints were detected after total and sub-total menisectomy. These were in the form of marginally located chrondo-osteophytic deposits. Very little change or no change at all could be found in the tibia and the femur, where a sub-total meniscectomy had been performed. A regenerative development took place in the capsular part of the resection line of the meniscus and/or the anterior part of the meniscus. The regeneration consisted of connective tissue rich in collagen fibres. No cartilage tissue could be found. There was no regenerative development in evidence after performing a sub-total menisectomy. Closure of the lesion/defect to the original half moon shape was not observed. The inner edge of the meniscus base showed itself to be unchanged. Intermediate cartilage structures remaining in the joint after the performance of partial and sub-total meniscectomy showed evidence of changes in connective tissue composition. Microscopy showed changes in its connective tissue through increased layering of collagen tissue in the cartilaginous tissue matrix. Adaptation processes in the tibia and the femur after total and partial meniscectomy indicate a low functional regenerative efficiency.


Best practice in fall prevention: roles of informal caregivers, health care providers and the community.
Falls are an important public health problem for older adults, resulting in significant morbidity and mortality, as well as healthcare costs. Evidence supports the assessment of older adults' fall risks and implementation of interventions to reduce these risks. Older adults are the key stakeholder in preventing falls, but need the support of their informal caregivers, healthcare providers, and community groups. This article addresses the roles of these additional stakeholders in providing and supporting best practices in fall prevention. Together these stakeholders can assist older adults in self-management of fall prevention, based on the preferences of the individual, local resources, and available programmes and healthcare services.


Association of type 2 diabetes and an inflammatory marker with incident bone fracture among a Japanese cohort.
There are various causes of incident bone fracture. Not only aging, low bone mineral density and history of previous fracture, but also diabetes mellitus and inflammation are regarded as risk factors for fracture. The purpose of the present study was to verify the association of glycemic control or one inflammatory marker with incident fracture in a large-scale Japanese cohort. The present study was carried out at the Hiroshima Atomic Bomb Casualty Council and included 6,556 participants (2,785 men and 3,771 women, aged 55-87 years) who underwent annual health examinations and were followed for 7.4 years. Information about incident fractures was collected at interviews. Participants were classified into three groups: normal, borderline and diabetes mellitus according to glycohemoglobin levels (treated diabetes patients were included in the diabetes mellitus group). Furthermore, participants were classified into four additional groups by glycemic control (diabetes mellitus or non-diabetes mellitus) and C-reactive protein (CRP) levels (low or high). Hazard ratios (HRs) of diabetes mellitus, CRP and their combined risk of incident fracture were evaluated. After adjusting for age, bone mineral density and previous fracture, CRP was associated with increased fracture risk (in men HR 1.04, 95% confidence interval [CI]: 1.003-1.06; in women HR 1.07, 95% CI: 1.03-1.13), and diabetes mellitus predicted fracture risk in men (HR 1.31, 95% CI: 1.02-1.51). Fracture risk was significantly higher among the diabetes mellitus with high CRP group compared with the non-diabetes mellitus with low CRP group (in men HR 1.47, 95% CI: 1.02-1.98; in women HR 1.41, 95% CI: 1.04-1.92). Among a Japanese cohort, CRP measurements were helpful to detect high fracture risk in patients with type 2 diabetes mellitus.


Parenteral treatment of episodic tension-type headache: a systematic review.
Tension-type headache is highly prevalent in the general population and is a consistent if not frequent cause of visits to acute care settings. Analgesics such as nonsteroidal anti-inflammatory drugs, acetaminophen, and salicylates are considered first-line therapy for treatment of tension-type headache. For patients who present to an acute care setting with persistent tension-type headache despite analgesic therapy, it is not clear which parenteral agent should be administered. We performed a systematic review of the medical literature to determine whether parenteral therapies other than salicylates or nonsteroidals are efficacious for acute tension-type headache. We performed a systematic review of Medline, EMBASE, CINAHL, Google scholar, and the Cochrane Central Registry of Controlled Trials from inception through August, 2012 using the search terms "tension-type headache" and "parenteral or subcutaneous or intramuscular or intravenous." Our goal was to identify randomized trials in which one parenteral treatment was compared to another active comparator or to placebo for the acute relief of tension-type headache. Parenteral was defined as intravenous, intramuscular, or subcutaneous administration. We only included studies that distinguished tension-type headache from other primary headache disorders, such as migraine. The primary outcome for this review was measures of efficacy one hour after medication administration. Data abstraction was performed by two authors. Disagreements were resolved by a third author. We assessed the internal validity of trials using the Cochrane Collaboration risk of bias tool. Because of the small number of trials identified, and the substantial heterogeneity among study design and medications, we decided that combining data and reporting summary statistics would serve no useful function. The results of individual studies are presented using Number Needed to Treat (NNT) with 95%CI when dichotomous outcomes were available and continuous outcomes otherwise. Our search returned 640 results. One hundred eighty-seven abstracts were reviewed, and 8 studies involving 486 patients were included in our analysis. The most common reasons for exclusion of abstracts were no assessment of acute pain relief, use of nonparenteral medications only, and no differentiation of headache type. Risk of bias ranged from low to high. The following medications were more effective than placebo for acute pain (NNT, 95%CI): metamizole (4, 2-26), chlorpromazine (4, 2-26), and metoclopramide (2, 1-3). The combination of metoclopramide + diphenhydramine was superior to ketorolac (4, 2-8) The following medications were not more effective than placebo: mepivacaine, meperidine + promethazine, and sumatriptan. Various parenteral medications other than salicylates or nonsteroidals provide acute relief of tension-type headache. Comparative efficacy studies are needed.


Diagnostic specificity and mental health service utilization among veterans with newly diagnosed anxiety disorders.
This study examined rates of specific anxiety diagnoses (posttraumatic stress disorder, generalized anxiety disorder, panic disorder, obsessive-compulsive disorder, social anxiety disorder, and specific phobia) and anxiety disorder not otherwise specified (anxiety NOS) in a national sample of Veterans and assessed their mental health service utilization. This study used administrative data extracted from Veteran Health Administration outpatient records to identify patients with a new anxiety diagnosis in fiscal year 2010 (N = 292,244). Logistic regression analyses examined associations among diagnostic specificity, diagnostic location, and mental health service utilization. Anxiety NOS was diagnosed in 38% of the sample. Patients in specialty mental health were less likely to receive an anxiety NOS diagnosis than patients in primary care (odds ratio [OR] = 0.36). Patients with a specific anxiety diagnosis were more likely to receive mental health services than those with anxiety NOS (OR = 1.65), as were patients diagnosed in specialty mental health compared with those diagnosed in primary care (OR = 16.29). Veterans diagnosed with anxiety NOS are less likely to access mental health services than those with a specific anxiety diagnosis, suggesting the need for enhanced diagnostic and referral practices, particularly in primary care settings.


Miniaturization of free space optical systems.
Coherent illumination enables not only integrated optics, but also miniaturized free-space optics that takes advantage of the amplitude and phase control afforded by optical microelectromechanical systems (MEMS) and photonic crystals. These technologies also provide a practical and cost-effective means for integration and packaging of optical systems. The properties of miniaturized optical systems based on optical MEMS and photonic crystals are described, and efficient analysis and design approaches to miniaturized optical scanners and tunable diffractive optical elements are demonstrated. The impact of photonic crystals on free-space micro-optics is discussed.


Slowing down in spatially patterned ecosystems at the brink of collapse.
Predicting the risk of critical transitions, such as the collapse of a population, is important in order to direct management efforts. In any system that is close to a critical transition, recovery upon small perturbations becomes slow, a phenomenon known as critical slowing down. It has been suggested that such slowing down may be detected indirectly through an increase in spatial and temporal correlation and variance. Here, we tested this idea in arid ecosystems, where vegetation may collapse to desert as a result of increasing water limitation. We used three models that describe desertification but differ in the spatial vegetation patterns they produce. In all models, recovery rate upon perturbation decreased before vegetation collapsed. However, in one of the models, slowing down failed to translate into rising variance and correlation. This is caused by the regular self-organized vegetation patterns produced by this model. This finding implies an important limitation of variance and correlation as indicators of critical transitions. However, changes in such self-organized patterns themselves are a reliable indicator of an upcoming transition. Our results illustrate that while critical slowing down may be a universal phenomenon at critical transitions, its detection through indirect indicators may have limitations in particular systems.


Ten simple rules for managing laboratory information.
Information is the cornerstone of research, from experimental (meta)data and computational processes to complex inventories of reagents and equipment. These 10 simple rules discuss best practices for leveraging laboratory information management systems to transform this large information load into useful scientific findings.


Lactic acidosis in a patient with cancer.
Lactic acidosis is commonly associated with tissue hypoperfusion and gives rise to concern regarding hypoxia or underlying hypotension. In the cancer patient, especially one undergoing chemotherapy, there is always concern for sepsis; however, in the otherwise clincially stable patient with cancer, type B lactic acidosis can also be related to their underlying malignancy. It is considered a haematological emergency given its high mortality rate. However, despite the urgency to treat type B lactic acidosis in these circumstances, treatment options beyond treatment of the malignancy are limited, and its presence portends a poor prognosis. This case highlights our current understanding of type B lactic acidosis and an approach to lactic acidosis evaluation in the cancer patient.


Automated Detection of Substance-Use Status and Related Information from Clinical Text.
This study aims to develop and evaluate an automated system for extracting information related to patient substance use (smoking, alcohol, and drugs) from unstructured clinical text (medical discharge records). The authors propose a four-stage system for the extraction of the substance-use status and related attributes (type, frequency, amount, quit-time, and period). The first stage uses a keyword search technique to detect sentences related to substance use and to exclude unrelated records. In the second stage, an extension of the NegEx negation detection algorithm is developed and employed for detecting the negated records. The third stage involves identifying the temporal status of the substance use by applying windowing and chunking methodologies. Finally, in the fourth stage, regular expressions, syntactic patterns, and keyword search techniques are used in order to extract the substance-use attributes. The proposed system achieves an F1-score of up to 0.99 for identifying substance-use-related records, 0.98 for detecting the negation status, and 0.94 for identifying temporal status. Moreover, F1-scores of up to 0.98, 0.98, 1.00, 0.92, and 0.98 are achieved for the extraction of the amount, frequency, type, quit-time, and period attributes, respectively. Natural Language Processing (NLP) and rule-based techniques are employed efficiently for extracting substance-use status and attributes, with the proposed system being able to detect substance-use status and attributes over both sentence-level and document-level data. Results show that the proposed system outperforms the compared state-of-the-art substance-use identification system on an unseen dataset, demonstrating its generalisability.


Effect of rimonabant on carotid intima-media thickness (CIMT) progression in patients with abdominal obesity and metabolic syndrome: the AUDITOR Trial.
The aim of this trial was to determine whether obese patients benefit from treatment with rimonabant in terms of progression of carotid atherosclerosis. Rimonabant, a selective cannabinoid-1 receptor blocker, reduces body weight and improves cardiometabolic risk factors in patients who are obese. A prospective, double-blind, placebo-controlled trial (Atherosclerosis Underlying Development assessed by Intima-media Thickness in patients On Rimonabant (AUDITOR)) randomised 661 patients with abdominal obesity and metabolic syndrome to rimonabant or placebo for 30 months of treatment. The absolute change in the average value for six segments of far wall carotid intima-media thickness from baseline to month 30 was 0.010 ± 0.095 mm in the rimonabant group and 0.012 ± 0.091 mm in the placebo group (p=0.67). The annualised change was an increase of 0.005 ± 0.042 mm for the rimonabant-treated group and 0.007 ± 0.043 mm for the placebo-treated group (p=0.45). There was no difference in atherosclerosis progression between patients receiving rimonabant for 30 months and those receiving placebo for the primary efficacy measure (absolute change in carotid intima-media thickness). These findings are consistent with a similar study using coronary intravascular ultrasound and another study evaluating the occurrence of cardiovascular events. Our findings suggest that a 5% loss of body weight over a 30-month period with rimonabant is insufficient to modify atherosclerosis progression in the carotid artery in obese patients with metabolic syndrome. Clinical trial registration information clinicaltrials.gov Identifier: NCT00228176.


Neural Circuitry of Reward Prediction Error.
Dopamine neurons facilitate learning by calculating reward prediction error, or the difference between expected and actual reward. Despite two decades of research, it remains unclear how dopamine neurons make this calculation. Here we review studies that tackle this problem from a diverse set of approaches, from anatomy to electrophysiology to computational modeling and behavior. Several patterns emerge from this synthesis: that dopamine neurons themselves calculate reward prediction error, rather than inherit it passively from upstream regions; that they combine multiple separate and redundant inputs, which are themselves interconnected in a dense recurrent network; and that despite the complexity of inputs, the output from dopamine neurons is remarkably homogeneous and robust. The more we study this simple arithmetic computation, the knottier it appears to be, suggesting a daunting (but stimulating) path ahead for neuroscience more generally.


Developmental toxicity of inhaled ethylene oxide in rats following short-duration exposure.
The developmental toxicity of ethylene oxide (EtO) was examined in Sprague-Dawley rats following inhalation exposure during Days 6 to 15 of gestation. Two different exposure regimens were used: (1) exposure for 0.5 hr once a day to 0, 400, 800, or 1200 ppm EtO; or (2) exposure for 0.5 hr three times a day to 0, 200, or 400 ppm EtO or 0, 800, or 1200 ppm EtO. Repeated brief exposures (3 x 0.5 hr/day) to EtO caused fetal toxicity indicated by reduced fetal weight at 800 and 1200 ppm, and overt maternal toxicity manifested as reduced body weight gain at 1200 ppm. Neither embryolethality nor teratogenicity occurred following any exposure regimen.


Genome contact map explorer: a platform for the comparison, interactive visualization and analysis of genome contact maps.
Hi-C experiments generate data in form of large genome contact maps (Hi-C maps). These show that chromosomes are arranged in a hierarchy of three-dimensional compartments. But to understand how these compartments form and by how much they affect genetic processes such as gene regulation, biologists and bioinformaticians need efficient tools to visualize and analyze Hi-C data. However, this is technically challenging because these maps are big. In this paper, we remedied this problem, partly by implementing an efficient file format and developed the genome contact map explorer platform. Apart from tools to process Hi-C data, such as normalization methods and a programmable interface, we made a graphical interface that let users browse, scroll and zoom Hi-C maps to visually search for patterns in the Hi-C data. In the software, it is also possible to browse several maps simultaneously and plot related genomic data. The software is openly accessible to the scientific community.


Facilitators and Barriers of Implementing a Measurement Feedback System in Public Youth Mental Health.
This study examines implementation facilitators and barriers of a statewide roll-out of a measurement feedback system (MFS) in a youth public mental health system. 76 % of all state care coordinators (N = 47) completed interviews, which were coded via content analysis until saturation. Facilitators (e.g., recognition of the MFS's clinical utility) and barriers (e.g., MFS's reliability and validity) emerged paralleling the Exploration, Adoption/Preparation, Implementation, and Sustainment framework outlined by Aarons et al. (Adm Policy Mental Health Mental Health Serv Res, 38:4-23, 2011). Sustainment efforts may leverage innovation fit, individual adopter, and system related facilitators.


Dihydroxyacetone-induced oscillations in cytoplasmic free Ca2+ and the ATP/ADP ratio in pancreatic beta-cells at substimulatory glucose.
Glucose stimulation of pancreatic beta-cells causes oscillatory influx of Ca2+, leading to pulsatile insulin secretion. We have proposed that this is due to oscillations of glycolysis and the ATP/ADP ratio, which modulate the activity of ATP-sensitive K+ channels. We show here that dihydroxyacetone, a secretagogue that feeds into glycolysis below the putative oscillator phosphofructokinase, could cause a single initial peak in cytoplasmic free Ca2+ ([Ca2+]i) but did not by itself cause repeated oscillations in [Ca2+]i in mouse pancreatic beta-cells. However, in the presence of a substimulatory concentration of glucose (4 mm), dihydroxyacetone induced [Ca2+]i oscillations. Furthermore, these oscillations correlated with oscillations in the ATP/ADP ratio, as seen previously with glucose stimulation. Insulin secretion in response to dihydroxyacetone was transient in the absence of glucose but was considerably enhanced and somewhat prolonged in the presence of a substimulatory concentration of glucose, in accordance with the enhanced [Ca2+]i response. These results are consistent with the hypothesized role of phosphofructokinase as the generator of the oscillations. Dihydroxyacetone may affect phosphofructokinase by raising the free concentration of fructose 1,6-bisphosphate to a critical level at which it activates the enzyme autocatalytically, thereby inducing the pulses of phosphofructokinase activity that cause the metabolic oscillations.


Stereocomplexes Formed From Select Oligomers of Polymer d-lactic Acid (PDLA) and l-lactate May Inhibit Growth of Cancer Cells and Help Diagnose Aggressive Cancers-Applications of the Warburg Effect.
It is proposed that select oligomers of polymer d-lactic acid (PDLA) will form a stereocomplex with l-lactate in vivo, producing lactate deficiency in tumor cells. Those cancer cells that utilize transport of lactate to maintain electrical neutrality may cease to multiply or die because of lactate trapping, and those cancer cells that benefit from utilization of extracellular lactate may be impaired. Intracellular trapping of lactate produces a different physiology than inhibition of LDH because the cell loses the option of shuttling pyruvate to an alternative pathway to produce an anion. Conjugated with stains or fluorescent probes, PDLA oligomers may be an agent for the diagnosis of tissue lactate and possibly cell differentiation in biopsy specimens. Preliminary experimental evidence is presented confirming that PDLA in high concentrations is cytotoxic and that l-lactate forms a presumed stereocomplex with PDLA. Future work should be directed at isolation of biologically active oligomers of PDLA.


[New diagnostic technologies in peripheral nerve injuries].
Based on experience of examination of about 300 patients with n. medianus and n. ulnaris injuries there are generalized new methodic possibilities in anatomical and functional approaches to diagnostics in peripheral neural trunks injuries. It is worth to include into the complex of diagnostic measures not only ENMG, but a set of other effective methods of investigation also. The use of modern clinical anatomical technologies (ultrasonography) permits as to detect areas of damage of the nerves, the sizes of diastasis and the location of the ends of the nerve, the presence and sizes of neuroma, as to evaluate the state of surrounding tissues, to reveal associated pathology. The application new clinical functional technologies (laser Doppler flowmetry with computer wavelet analysis of blood flow oscillations, computer thermography) allows to estimate the condition of the fine autonomous and sensor neural fibers. It empowers as diagnostics of functional condition of the nerve after trauma, as early detection the signs of tissue reinnervation after reconstruction of nerves and choice of the adequate tactics of management of such patients.


Spatial variability of different fractions of particulate matter within an urban environment and between urban and rural sites.
The spatial variability of different fractions of particulate matter (PM) was investigated in the city of Basel, Switzerland, based on measurements performed throughout 1997 with a mobile monitoring station at six sites and permanently recorded measurements from a fixed site. Additionally, PM10 measurements from the following year, which were concurrently recorded at two urban and two rural sites, were compared. Generally, the spatial variability of PM4, PM10, and total suspended particulates (TSP) within this Swiss urban environment (area = 36 km2) was rather limited. With the exception of one site in a street canyon next to a traffic light, traffic density had only a weak tendency to increase the levels of PM. Mean PM10 concentration at six sites with different traffic densities was in the range of less than +/- 10% of the mean urban PM10 level. However, comparing the mean PM levels on workdays to that on weekends indicated that the impact of human activities, including traffic, on ambient PM levels may be considerable. Differences in the daily PM10 concentrations between urban and more elevated rural sites were strongly influenced by the stability of the atmosphere. In summer, when no persistent surface inversions exist, differences between urban and rural sites were rather small. It can therefore be concluded that spatial variability of annual mean PM concentration between urban and rural sites in the Basel area may more likely be caused by varying altitude than by distance to the city center.


Two new dammarane-type saponins from the leaves of Panax ginseng.
Two new dammarane-type saponins, named ginsenoside Ki (1a) and ginsenoside Km (1b), along with 15 known ones (2-16), were isolated from the leaves of Panax ginseng. Their structures were elucidated on the basis of chemical and spectroscopic methods.


International public opinion on the environment.
This article analyzes public opinion data on environmental issues collected in two major surveys. The data reveal substantial concern about the environment in both developing and industrial countries along with perceptions that the quality of the environment has declined and will continue to decline. Developing country respondents rate their local and national environmental quality lower than do industrial country respondents, whereas both groups rate global environmental quality about the same. The data also reveal considerable willingness among the developing and industrial countries to accept responsibility for the world's environmental problems and recognition of the importance of governments in addressing local and national environmental issues and of strong international agencies in addressing transnational issues.


Crystal structure of the thiamin diphosphate-dependent enzyme pyruvate decarboxylase from the yeast Saccharomyces cerevisiae at 2.3 A resolution.
The crystal structure of pyruvate decarboxylase (EC 18.104.22.168), a thiamin diphosphate-dependent enzyme isolated from Saccharomyces cerevisiae, has been determined and refined to a resolution of 2.3 A. Pyruvate decarboxylase is a homotetrameric enzyme which crystallizes with two subunits in an asymmetric unit. The structure has been refined by a combination of simulated annealing and restrained least squares to an R factor of 0.165 for 46,787 reflections. As in the corresponding enzyme from Saccharomyces uvarum, the homotetrameric holoenzyme assembly has approximate 222 symmetry. In addition to providing more accurate atomic parameters and certainty in the sequence assignments, the high resolution and extensive refinement resulted in the identification of several tightly bound water molecules in key structural positions. These water molecules have low temperature factors and make several hydrogen bonds with protein residues. There are six such water molecules in each cofactor binding site, and one of them is involved in coordination with the required magnesium ion. Another may be involved in the catalytic reaction mechanism. The refined model includes 1074 amino acid residues (two subunits), two thiamin diphosphate cofactors, two magnesium ions associated with cofactor binding and 440 water molecules. From the refined model we conclude that the resting state of the enzyme-cofactor complex is such that the cofactor is already deprotonated at the N4' position of the pyrimidine ring, and is poised to accept a proton from the C2 position of the thiazolium ring.


Temperature-dependent transmission of rotavirus in Great Britain and The Netherlands.
In Europe, rotavirus gastroenteritis peaks in late winter or early spring suggesting a role for weather factors in transmission of the virus. In this study, multivariate regression models adapted for time-series data were used to investigate effects of temperature, humidity and rainfall on reported rotavirus infections and the infection-rate parameter, a derived measure of infection transmission that takes into account population immunity, in England, Wales, Scotland and The Netherlands. Delayed effects of weather were investigated by introducing lagged weather terms into the model. Meta-regression was used to pool together country-specific estimates. There was a 13 per cent (95% confidence interval (CI), 11-15%) decrease in reported infections per 1 degrees C increase in temperature above a threshold of 5 degrees C and a 4 per cent (95% CI, 3-5%) decrease in the infection-rate parameter per 1 degrees C increase in temperature across the whole temperature range. The effect of temperature was immediate for the infection-rate parameter but delayed by up to four weeks for reported infections. There was no overall effect of humidity or rainfall. There is a direct and simple relationship between cold weather and rotavirus transmission in Great Britain and The Netherlands. The more complex and delayed temperature effect on disease incidence is likely to be mediated through the effects of weather on transmission.


Postoperative hyponatremia. A prospective study.
In the present study, we found that at least 4.4% of 1,088 prospectively studied patients developed postoperative hyponatremia (plasma sodium concentration less than 130 mEq/L). Most patients (42%) were normovolemic. Edematous states (21%), hyperglycemia (21%), volume depletion (8%), and renal failure (8%), however, were also common settings of postoperative hyponatremia. Plasma arginine vasopressin was present in all patients in whom it was measured and 94% of the patients were receiving hypotonic fluid at the time of development of hyponatremia. Hyponatremia was not associated with significant neurologic deterioration in the 48 postoperative patients in the present study. In eight patients, however, the positive water balance that resulted in hyponatremia was associated with development of pulmonary vascular congestion. We conclude that hyponatremia commonly occurs following all types of surgical procedures and is due to hypotonic fluid administration in the presence of nonosmotic secretion of arginine vasopressin.


LC-MS Approach to Decipher a Light Chain Chromatographic Peak Splitting of a Monoclonal Antibody.
Monoclonal antibodies (mAbs), like other protein therapeutics, are prone to various forms of degradation, some of which are difficult to distinguish from the native form yet may alter potency. A generalizable LC-MS approach was developed to enable quantitative analysis of isoAsp. In-depth understanding of product quality attributes (PQAs) enables optimization of the manufacturing process, better formulation selection, and decreases risk associated with product handling in the clinic or during shipment. Reversed-phase chromatographic peak splitting was observed when a mAb was exposed to elevated temperatures. Multiple LC-MS based methods were applied to identify the reason for peak splitting. The approach involved the use of complementary HPLC columns, multiple enzymatic digestions and different MS/MS ion dissociation methods. In addition, mAb potency was measured by enzyme-linked immunosorbent assay (ELISA). The split peaks had identical masses, and the root cause of the peak splitting was identified as isomerization of an aspartic acid located in the complementarity-determining region (CDR) of the light chain. And the early eluting and late eluting peaks were collected and performed enzymatic digestion to confirm the isoAsp enrichment in the early eluting peak. In addition, decreased potency was observed in the same heat-stressed sample, and the increased isoAsp levels in the CDR correlate well with a decrease of potency. Liquid chromatography-mass spectrometry (LC-MS) has been utilized extensively to assess PQAs of biological therapeutics. In this study, a generalizable LC-MS-based approach was developed to enable identification and quantitation of the isoAsp-containing peptides.


Ethical quandaries around expanded carrier screening in third-party reproduction.
Although current screening methods of gamete donors are capable of reducing the incidence of genetic anomalies in donor offspring below general population levels, targeted screening for a large number of conditions (expanded carrier screening or ECS) could be considered as part of the routine selection procedure for gamete donors. There are, however, important drawbacks to its practical implementation. Excluding all carriers of severe recessive monogenic pediatric disorders would disqualify virtually all donors, and other approaches negatively affect cost (and therefore access), present dilemmas in regard to disclosure of genetic findings, and/or overburden the intended parents. In all of the scenarios considered, adequate genetic counseling will be of central importance. Besides looking at benefits and drawbacks of possible ways of implementing ECS, we also examine whether a moral obligation exists to adopt ECS at all and on whose shoulders such an alleged obligation would rest: policymakers, medical staff at fertility clinics, sperm and egg banks, the intended parents? We argue that given the small risk reduction brought about by ECS, the possible negative effects of its implementation, and the absence of widespread preconception carrier screening in the general population, it is inconsistent to argue that there is a moral obligation to perform ECS in the context of donor conception. Finally, implications for the donors are discussed.


Acquiring 4D thoracic CT scans using a multislice helical method.
Respiratory motion degrades anatomic position reproducibility during imaging, necessitates larger margins during radiotherapy planning and causes errors during radiation delivery. Computed tomography (CT) scans acquired synchronously with the respiratory signal can be used to reconstruct 4D CT scans, which can be employed for 4D treatment planning to explicitly account for respiratory motion. The aim of this research was to develop, test and clinically implement a method to acquire 4D thoracic CT scans using a multislice helical method. A commercial position-monitoring system used for respiratory-gated radiotherapy was interfaced with a third generation multislice scanner. 4D cardiac reconstruction methods were modified to allow 4D thoracic CT acquisition. The technique was tested on a phantom under different conditions: stationary, periodic motion and non-periodic motion. 4D CT was also implemented for a lung cancer patient with audio-visual breathing coaching. For all cases, 4D CT images were successfully acquired from eight discrete breathing phases, however, some limitations of the system in terms of respiration reproducibility and breathing period relative to scanner settings were evident. Lung mass for the 4D CT patient scan was reproducible to within 2.1% over the eight phases, though the lung volume changed by 20% between end inspiration and end expiration (870 cm3). 4D CT can be used for 4D radiotherapy, respiration-gated radiotherapy, 'slow' CT acquisition and tumour motion studies.


Healthcare Provider-Patient Communication: A Satisfaction Study in the Outpatient Clinic at Hospital Kuala Lumpur.
There is growing interest in research on patient satisfaction with healthcare provider (HCP) communication as a measure of healthcare quality and HCPs' communication competency. This study aimed to determine the levels of patient satisfaction with healthcare provider-patient communication (HCP-PC) and its associated factors at the outpatient clinic at Hospital Kuala Lumpur. A cross-sectional study was conducted on a convenience sample in July 2012 using self-administered questionnaires for the data collection. Both overall and domain-specific satisfaction were measured, with the three domains being exchanging information (EI), socio-emotional behaviour (SB), and communication style (CS). The findings show that 92.8% of the 283 respondents were satisfied with overall HCP-PC, 89.5% with EI, 91.3% with SB, and 72.2% with CS. Satisfaction was statistically higher among Malays for CS and higher among those with low education and poor health for EI, SB and CS. EI and overall communication satisfaction were also higher among patients who reported short wait times, and patients who were in gender concordance with their HCPs showed higher SB satisfaction. Basic and continuous communication skills training and patient activation programs should be established to increase patient satisfaction. Health information technology use should be actively promoted to allow for structured and standardised information exchange between HCPs and patients.


Signature murders: a report of the 1984 Cranbrook, British Columbia cases.
Two females, Denean Worms and Brenda Hughes, were murdered in separate events in Cranbrook, British Columbia in 1984 within three months of each other. Terrence Wayne Burlingham was found guilty of both murders and he appealed. The Supreme Court of Canada granted Burlingham a new trial in the Worms case, but no evidence from Burlingham's confession nor the murder weapon could be used. The Crown counsel requested an evaluation of the two murders to determine if they were committed by the same person. The analyses of those murders revealed that they were linked by a personal "signature" of the killer. The murder cases reported here demonstrate a control-oriented signature. The killer used a .410 shotgun as his method of control and death, engaged in overkill of each victim by shooting them twice in the head, and left the victims in sexually degrading positions. Another signature feature was the absence of typical wounds to the victims which would be expected from a serial sex offender. All of these characteristics, in combination, accounted for this killer's personal expression.


[Lateralization of secondary lesions of the brain stem in stroke by the method of short-latency auditory evoked potentials].
Twenty-seven patients with acute cerebral circulation disorders (ACCD) in large hemispheres and 4 patients with ACCD in the cerebellum were examined by means of short-latent acoustic evoked potentials (SAEP). The signs of the secondary stem syndrome were recorded in the neurological status of all the patients. Computer-aided tomography discovered displacement of the median structures of varying degree and deformation of cisternal spaces of the stem. The data obtained allowed a conclusion about a possibility of lateralization of the side of a greater injury to the stem by means of SAEP. As a rule, it was made ipsilaterally to the supratentorial focus. Provided the focus is seated subtentorially, a special pattern of SAEP may occur, namely primary changes in 1-3 components till complete disappearance of the evoked response.


A Division of Labor between YAP and TAZ in Non-Small Cell Lung Cancer.
Lung cancer is the leading cause of cancer-related deaths worldwide. The paralogous transcriptional cofactors Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ, also called WWTR1), the main downstream effectors of the Hippo signal transduction pathway, are emerging as pivotal determinants of malignancy in lung cancer. Traditionally, studies have tended to consider YAP and TAZ as functionally redundant transcriptional cofactors with similar biological impact. However, there is growing evidence that each of them also possesses distinct attributes. Here we sought to systematically characterize the division of labor between YAP and TAZ in non-small cell lung cancer (NSCLC), the most common histological subtype of lung cancer. Representative NSCLC cell lines as well as patient-derived data showed that the two paralogs orchestrated nonoverlapping transcriptional programs in this cancer type. YAP preferentially regulated gene sets associated with cell division and cell-cycle progression, whereas TAZ preferentially regulated genes associated with extracellular matrix organization. Depletion of YAP resulted in growth arrest, whereas its overexpression promoted cell proliferation. Likewise, depletion of TAZ compromised cell migration, whereas its overexpression enhanced migration. The differential effects of YAP and TAZ on key cellular processes were also associated with differential response to anticancer therapies. Uncovering the different activities and downstream effects of YAP and TAZ may thus facilitate better stratification of patients with lung cancer for anticancer therapies. SIGNIFICANCE: Thease findings show that oncogenic paralogs YAP and TAZ have distinct roles in NSCLC and are associated with differential response to anticancer drugs, knowledge that may assist lung cancer therapy decisions.


Rice-Associated Rhizobacteria as a Source of Secondary Metabolites against Burkholderia glumae.
Various diseases, including bacterial panicle blight (BPB) and sheath rot, threaten rice production. It has been established that Burkholderia glumae (B. glumae) is the causative agent of the above mentioned pathologies. In the present study, antagonistic activity, growth promotion, and the metabolite profiles of two rhizobacteria, isolated in different paddy fields, were assessed against B. glumae. Strains were identified based on 16S rRNA gene sequences, and the phylogenetic analyses showed that both strains belong to the genus Enterobacter, with high similarity to the strain Enterobacter tabaci NR146667.2 (99%). The antagonistic activity was assessed with the disc diffusion method. Active fractions were isolated through a liquid/liquid extraction with ethyl acetate (EtOAc) from the fermentation media, and their antibacterial activities were evaluated following the Clinical and Laboratory Standards Institute (CLSI) guidelines. The Pikovskaya modified medium was used to test the ability of in vitro inorganic phosphorus solubilization, and BSB1 proved to be the best inorganic phosphorus solubilizer, with a solubilization index (SI) of 4.5 ± 0.2. The glass-column fractionation of the EtOAc extracted from BCB11 produced an active fraction (25.9 mg) that inhibited the growth of five B. glumae strains by 85-95%. Further, metabolomic analysis, based on GC-MS, showed 3-phenylpropanoic acid (3-PPA) to be the main compound both in this fraction (46.7%), and in the BSB1 extract (28.6%). This compound showed antibacterial activity against all five strains of B. glumae with a minimum inhibitory concentration (MIC) of 1000 mg/L towards all of them. The results showed that rice rhizosphere microorganisms are a source of compounds that inhibit B. glumae growth and are promising plant growth promoters (PGP).


A comparison of 4-week peptic ulcer healing rates following treatment with antacids and ranitidine.
Eighty-eight patients with endoscopically proven gastric and duodenal ulceration were treated with ranitidine ( Zantac ; Glaxo) or an antacid preparation containing aluminium hydroxide and magnesium trisilicate ( Gelusil ; Warner) over a 4-week period to assess healing. Clinical, haematological and biochemical assessment and endoscopy were performed at the beginning and at the end of this period. Of the duodenal ulcers, 74% healed on ranitidine therapy and 63% on Gelusil . This difference was not statistically significant (chi 2(1) = 0,55). Of the gastric ulcers 58% healed on ranitidine therapy and 35% on Gelusil , but this difference did not reach statistical significance (chi 2(1) = 1,79). There was no significant difference between the two therapies with regard to symptomatic relief in the duodenal ulcer group, but ranitidine produced significantly better results in the gastric ulcer group. No side-effects were noted in either group.


Cholestasis secondary to Hodgkin's disease: report of 2 cases of vanishing bile duct syndrome.
Only a small percentage of patients with Hodgkin's disease become clinically Jaundiced during their disease. This Jaundice may be secondary to biliary obstruction, hemolysis, direct hepatic infiltration by the disease, drug toxicity or viral hepatitis. Vanishing bile duct syndrome secondary to Hodgkin's disease is a rare cause of cholestasis in these patients, only 13 cases having been reported so far. The authors describe 2 patients who developed severe Jaundice secondary to Hodgkin's disease due to vanishing bile duct syndrome affecting small intrahepatic bile ducts.