The health of Antillean migrants in the Netherlands: a comparison with the health of non-migrants in both the countries of origin and destination.
This article examines risk factor and health differences between Antillean migrants in the Netherlands and Antillean and Dutch non-migrants, and relates these findings to four commonly used explanations for migrant health disparities. Nationally representative data from the 2012 Dutch Public Health Monitor and the 2013 National Health Survey Curaçao was used. The weighted rates were calculated and significance assessed using the χ2 test. Logistic regression analyses were used to compare health behaviours and outcomes between Antillean migrants and the non-migrant populations. Overall, Antillean migrants had poorer physical and mental health than Antillean and Dutch non-migrants. For overweight/obesity and tobacco and alcohol use, Antillean migrants had rates in-between those of the Antillean and Dutch non-migrants. The poor health of Antillean migrants persisted in the second generation, who were born in the Netherlands. Patterns of differences in physical and mental health among the study populations were suggestive of a 'stressful environment' effect. The poorer health of Antillean migrants may be partly determined by host-country-specific stressors, such as perceived discrimination, spatial concentration in multi-ethnic neighbourhoods and reduced social mobility.


Novel Model of Pulmonary Artery Banding Leading to Right Heart Failure in Rats.
Congenital heart diseases often involve chronic pressure overload of the right ventricle (RV) which is a major cause of RV dysfunction. Pulmonary artery (PA) banding has been used to produce animal models of RV dysfunction. We have devised a new and easier method of constricting the PA and compared it directly with the partial ligation method. Eight-week-old male Sprague-Dawley rats (240-260 g) were divided into three groups: sham operation, partial pulmonary artery ligation (PAL) procedure, and pulmonary artery half-closed clip (PAC) procedure. RV function and remodeling were determined by echocardiography and histomorphometry. Surgical mortality was significantly lower in the PAC group while echocardiography revealed significantly more signs of RV dysfunction. At the 8th week after surgery RV fibrosis rate was significantly higher in the PAC group. This procedure of pulmonary artery banding in rats is easier and more efficient than partial ligation.


New insights on anion recognition by isomers of a calix pyrrole derivative.
Two isomeric structures of meso-tetramethyltetrakis(3-hydroxyphenyl)calix[4]pyrrole, 4-alphaalpha betabeta and 4-alphabeta alphabeta, have been isolated and characterized by 1H NMR in different solvents (CD3CN, CD3OD, and DMSO-d6) at 298 K. Standard Gibbs energies of solution derived from solubility data in various solvents were used to calculate the transfer Gibbs energy, delta(t)G(o), of these ligands using acetonitrile as the reference solvent. These results are consistent with the 1H NMR studies in different media that show chemical shift changes observed in the resonances of the NH and the OH protons of these ligands. Solvate formation was observed when these isomers were exposed to saturated atmosphere of N,N-dimethylformamide, dimethyl sulfoxide and propylene carbonate. Anion interaction involving 4-alphaalpha betabeta and 4-alphabeta alphabeta was investigated by 1H NMR in CD3CN while the complex composition was assessed through conductance measurements. Significant differences are observed in the affinity of these ligands for anions as well as in the composition of the fluoride complexes. Thus 4-alphaalpha betabeta shows selectivity for H2PO4(-) in acetonitrile while its isomer 4-alphabeta alphabeta is selective for the fluoride anion. Again the complex composition is altered for the fluoride anion when complexed with 4-alphaalpha betabeta in acetonitrile (1:1 complex) relative to 4-alphabeta alphabeta in the same solvent. The latter isomer shows an enhanced hosting ability for this anion. Thus two anions are taken up per unit of ligand. The thermodynamics of complexation of H2PO4(-) and these ligands in acetonitrile is discussed, and the results are compared with those involving calix[4]pyrrole and this anion in this solvent. It is shown that the isomers interact with two H2PO4(-) anions while one calix[4]pyrrole unit interacts with this anion. This paper demonstrates for the first time that the enthalpy parameter may be a suitable reporter of the number of hydrogen bonds formed when calix[4]pyrrole and its derivatives interact with the dihydrogen phosphate anion in acetonitrile. In moving from acetonitrile to N,N-dimethylformamide, 4-alphaalpha betabeta is unable to enter complexation with most anions, except fluoride, with which the formation of a 1:2 (ligand:anion) complex is demonstrated. The rather versatile behavior of these receptors for anions is explained on the basis of 1H NMR evidence and solvation effects. These investigations highlight the importance of the medium effect on the stability of the complex and reflect the inherent nature of the solvent and its highly significant involvement in the complexation process.


Quantifying uncertainty in brain-predicted age using scalar-on-image quantile regression.
Prediction of subject age from brain anatomical MRI has the potential to provide a sensitive summary of brain changes, indicative of different neurodegenerative diseases. However, existing studies typically neglect the uncertainty of these predictions. In this work we take into account this uncertainty by applying methods of functional data analysis. We propose a penalised functional quantile regression model of age on brain structure with cognitively normal (CN) subjects in the Alzheimer's Disease Neuroimaging Initiative (ADNI), and use it to predict brain age in Mild Cognitive Impairment (MCI) and Alzheimer's Disease (AD) subjects. Unlike the machine learning approaches available in the literature of brain age prediction, which provide only point predictions, the outcome of our model is a prediction interval for each subject.


Restraining expansion of the peak envelope in H/D exchange-MS and its application in detecting perturbations of protein structure/dynamics.
Hydrogen/deuterium exchange (H/DX) mass spectrometry (MS) is increasingly applied to problems in protein structural biology in order to map protein dynamics and identify sites of interactions. In theory, an MS-based readout of deuterium label incorporation can overcome the concentration, size, purity, and complexity limitations inherent in NMR-based measurements of exchange; however, in practice, these advantages are reduced due to spectral interference and dilution of the sample in deuterium oxide (D 2O). In this study, we demonstrate that popular H/DX labeling strategies aggravate the interference problem and that significant recovery of spectral capacity may be achieved with a "minimalist" strategy. Simulations of peptide deuteration justify large reductions in the level of D 2O used in labeling experiments, as well as reduced numbers of peaks used in making relative labeling measurements between biochemical states of a protein. To demonstrate the utility of a minimalist approach, calmodulin was interrogated in a bottom-up H/DX-MS workflow, and sensitivity to the addition of Ca (2+) as a structural perturbation was measured as a function of % D 2O and the number of peaks used in quantitating deuteration level. It is shown that high sensitivity to change is preserved with deuteration levels of 5.0 +/- 1.1 (apo-CaM) and 1.4 +/- 1.3% (holo-CaM) using 10% D 2O in the labeling experiment. Further, only two peaks of a peptide peak distribution are needed to sensitively monitor changes in protein structure, dynamics, or both.


Socioeconomic determinants of intrauterine growth retardation.
This paper reviews the evidence bearing on socioeconomic determinants of intrauterine growth retardation (IUGR). The primary focus is on those factors with a quantitatively important impact from a public health perspective, as indicated by their large etiologic fraction (population attributable risk). In developed countries in which a sizeable proportion of women smoke during pregnancy, cigarette smoking is associated with the largest etiologic fraction (by far), followed by low gestational weight gain (primarily due to low energy intake) and low prepregnancy body mass index (BMI). In developing countries where undernutrition is prevalent and pregnant women do not smoke, low maternal weight gain and BMI assume even greater importance, as does short maternal stature. A major section of the paper concerns the large within-country socioeconomic disparities in IUGR and the possible mechanisms underlying these disparities. In developed countries, differences in cigarette smoking explain a large part of the disparity; low weight gain and short stature may also be important mediators in some settings. Future etiologic studies should assess a wide scope of potential determinants and will require large sample sizes to control for their mutually confounding effects.


Women's autonomy in household decision-making: a demographic study in Nepal.
How socio-demographic factors influence women's autonomy in decision making on health care including purchasing goods and visiting family and relatives are very poorly studied in Nepal. This study aims to explore the links between women's household position and their autonomy in decision making. We used Nepal Demographic Health Survey (NDHS) 2006, which provided data on ever married women aged 15-49 years (n = 8257). The data consists of women's four types of household decision making; own health care, making major household purchases, making purchase for daily household needs and visits to her family or relatives. A number of socio-demographic variables were used in multivariable logistic regression to examine the relationship of these variables to all four types of decision making. Women's autonomy in decision making is positively associated with their age, employment and number of living children. Women from rural area and Terai region have less autonomy in decision making in all four types of outcome measure. There is a mixed variation in women's autonomy in the development region across all outcome measures. Western women are more likely to make decision in own health care (1.2-1.6), while they are less likely to purchase daily household needs (0.6-0.9). Women's increased education is positively associated with autonomy in own health care decision making (p < 0.01), however their more schooling (SLC and above) shows non-significance with other outcome measures. Interestingly, rich women are less likely to have autonomy to make decision in own healthcare. Women from rural area and Terai region needs specific empowerment programme to enable them to be more autonomous in the household decision making. Women's autonomy by education, wealth quintile and development region needs a further social science investigation to observe the variations within each stratum. A more comprehensive strategy can enable women to access community resources, to challenge traditional norms and to access economic resources. This will lead the women to be more autonomous in decision making in the due course.


Intratumoral hemorrhage of mammary phyllodes tumor after menstrual induction: a puzzling presentation.
Mammary phyllodes tumor is an uncommon stromal-epithelial neoplasm with a reported incidence of 0.3% to 0.5% of female breast tumors. Sudden, rapid growth of a mammary phyllodes tumor with intratumoral hemorrhage was noted in a 45-year-old woman after menstrual induction with progesterone and norethindrone acetate. This case is presented here to highlight the possibility of such an onset of phyllodes tumor in order to facilitate its prompt diagnosis. A 45-year-old woman suffered from missed periods for 2 months and received progesterone for menstrual induction. After treatment, rapid enlargement of her left breast was noted. Tracing the history of the patient, we found that she had already felt an about 3 cm painless lump in her left breast 5 months before this episode. Sonography of the left breast showed a large cystic lesion with some echogenic content and about 150 mL of old blood was obtained by aspiration. Surprisingly, follow-up breast sonography 3 weeks later revealed a large irregular solid mass and a small amount of peripheral cystic content with markedly increased vascularity. Surgery was suggested. A large encapsulated mass consisting of heterogeneous yellow soft tissue and a cystic component measuring 10 x 8 cm was totally excised. Microscopically, the sections revealed branching and cystically dilated glands lined by cuboidal to columnar epithelial cells in a myxoid hypercellular fibroblastic stroma with hyperchromatic nuclei and frequent mitotic figures. The final histological diagnosis was malignant phyllodes tumor. Progesterone for menstrual induction may cause rapid growth of a phyllodes tumor with resultant internal hemorrhage. Only with the awareness of this entity can a prompt diagnosis be made and optimal treatment be given.


Embryo disposal practices in IVF clinics in the United States.
The moral status of the human embryo is particularly controversial in the United States, where one debate has centered on embryos created in excess at in vitro fertilization (IVF) clinics. Little has been known about the disposal of these embryos. We mailed anonymous, self-administered questionnaires to directors of 341 American IVF clinics. 217 of 341 clinics (64 percent) responded. Nearly all (97 percent) were willing to create and cryopreserve extra embryos. Fewer, but still a majority (59 percent), were explicitly willing to avoid creating extras. When embryos did remain in excess, clinics offered various options: continual cryopreservation for a charge (96 percent) or for no charge (4 percent), donation for reproductive use by other couples (76 percent), disposal prior to (60 percent) or following (54 percent) cryopreservation, and donation for research (60 percent) or embryologist training (19 percent). Qualifications varied widely among those personnel responsible for securing couples' consent for disposal and for conducting disposal itself. Some clinics performed a religious or quasi-religious disposal ceremony. Some clinics required a couple's participation in disposal; some allowed but did not require it; some others discouraged or disallowed it. The disposal of human embryos created in excess at American IVF clinics varies in ways suggesting both moral sensitivity and ethical divergence.


Enhanced rectal potassium secretion in chronic renal insufficiency: evidence for large intestinal potassium adaptation in man.
The role of the large intestine in K+ excretion in chronic renal insufficiency was studied with a rectal dialysis technique in 14 normal subjects and eight normokalaemic, normotensive patients with chronic renal insufficiency. At initial intraluminal K+ concentrations of 10, 20, 30 and 45 mmol/l, net K+ secretion in patients with renal insufficiency was significantly greater than in normal subjects by approximately 1.8 mumol h-1 cm-2. The increase in net K+ secretion was more marked in those patients with creatinine clearances of less than 10 ml/min. In contrast, there were no significant differences in net Na+ and water transport, transmucosal potential difference and plasma aldosterone concentrations between the two groups. With an initial intraluminal K+ concentration of 30 mmol/l, the addition of amiloride (final concentration 1 mmol/l) to the rectal lumen decreased net Na+ absorption and transmucosal potential difference in normal subjects by 69% (P less than 0.005) and 31% (P less than 0.005) respectively, and in patients with renal insufficiency by 75% (P less than 0.05) and 36% (P less than 0.05) respectively, but there was no change in net K+ secretion in either group. These results indicate that the K+ secretory capacity of the rectal mucosa increases in chronic renal insufficiency, and the large intestine may therefore contribute to the maintenance of K+ homoeostasis as renal K+ excretion declines. Increased rectal K+ secretion in renal insufficiency occurs independently of changes in plasma K+ and aldosterone concentrations, net Na+ absorption and transmucosal potential difference, and may reflect stimulation of an active K+ secretory process.


Mild intraoperative hypothermia during surgery for intracranial aneurysm.
Surgery for intracranial aneurysm often results in postoperative neurologic deficits. We conducted a randomized trial at 30 centers to determine whether intraoperative cooling during open craniotomy would improve the outcome among patients with acute aneurysmal subarachnoid hemorrhage. A total of 1001 patients with a preoperative World Federation of Neurological Surgeons score of I, II, or III ("good-grade patients"), who had had a subarachnoid hemorrhage no more than 14 days before planned surgical aneurysm clipping, were randomly assigned to intraoperative hypothermia (target temperature, 33 degrees C, with the use of surface cooling techniques) or normothermia (target temperature, 36.5 degrees C). Patients were followed closely postoperatively and examined approximately 90 days after surgery, at which time a Glasgow Outcome Score was assigned. There were no significant differences between the group assigned to intraoperative hypothermia and the group assigned to normothermia in the duration of stay in the intensive care unit, the total length of hospitalization, the rates of death at follow-up (6 percent in both groups), or the destination at discharge (home or another hospital, among surviving patients). At the final follow-up, 329 of 499 patients in the hypothermia group had a Glasgow Outcome Score of 1 (good outcome), as compared with 314 of 501 patients in the normothermia group (66 percent vs. 63 percent; odds ratio, 1.14; 95 percent confidence interval, 0.88 to 1.48; P=0.32). Postoperative bacteremia was more common in the hypothermia group than in the normothermia group (5 percent vs. 3 percent, P=0.05). Intraoperative hypothermia did not improve the neurologic outcome after craniotomy among good-grade patients with aneurysmal subarachnoid hemorrhage.


S100A8/A9 stimulates keratinocyte proliferation in the development of squamous cell carcinoma of the skin via the receptor for advanced glycation-end products.
Squamous cell carcinoma (SCC) is the most common neoplasm in organ transplant recipients (OTR) on long-term immunosuppression and occurs 60- to 100-fold more frequently than in the general population. Here, we present the receptor for advanced glycation end products (RAGE) and S100A8/A9 as important factors driving normal and tumor keratinocyte proliferation. RAGE and S100A8/A9 were transcriptionally upregulated in SCC compared to normal epidermis, as well as in OTR compared to immunocompetent patients (IC) with SCC. The proliferation of normal and SCC keratinocytes was induced by exposure to exogenous S100A8/A9 which in turn was abolished by blocking of RAGE. The migratory activities of normal and SCC keratinocytes were also increased upon exposure to S100A8/A9. We demonstrated that exogenous S100A8/A9 induces phosphorylation of p38 and SAPK/JNK followed by activation of ERK1/2. We hypothesize that RAGE and S100A8/A9 contribute to the development of human SCC by modulating keratinocyte growth and migration. These processes do not seem to be impaired by profound drug-mediated immunosuppression in OTR.


Granulocyte macrophage colony-stimulating factor expression in human herpetic stromal keratitis: implications for the role of neutrophils in HSK.
Granulocyte macrophage colony-stimulating factor (GM-CSF) is thought to play a key role in chronic inflammatory diseases by governing the survival and function of infiltrating neutrophils. The objective of this study was to determine the putative role of GM-CSF in the pathogenesis of human herpetic stromal keratitis (HSK). Primary human corneal fibroblast (HCF) cultures and a telomerase-immortalized human corneal epithelial (HCE) cell line representative of native HCE were stimulated with the known HSK-inducing cytokines interferon (IFN)-gamma, interleukin (IL)-1beta, and tumor necrosis factor (TNF)-alpha. Alternatively, the T-cell cytokine IL-17 was added solely or simultaneously. Human neutrophils were incubated with conditioned medium (CM) of the HCF and HCE stimulated with the aforementioned cytokines, or recombinant GM-CSF, and their viability or activation status was determined by flow cytometry. GM-CSF and IL-8 secretion levels in the CM were determined by ELISA. The antibody-dependent cellular cytotoxicity (ADCC) of neutrophils toward herpes simplex virus (HSV)-infected HCFs was determined by flow cytometry. The expression of GM-CSF was determined in HSK and control corneal buttons by real-time RT-PCR and immunohistology. Compared with IFN-gamma, CM of either cell type stimulated with IL-1beta, or in the case of HCE cells, stimulated with TNF-alpha or IL-17, delayed neutrophil apoptosis significantly. Only in HCFs did IL-17 exhibit a synergistic effect with TNF-alpha. The antiapoptotic activity was attributable in part to the GM-CSF secreted by the activated HCFs and HCE cells. GM-CSF stimulation of neutrophils induced their activation and the secretion of IL-8. GM-CSF did not increase significantly the ADCC reaction of neutrophils toward HSV-infected HCFs. Finally, GM-CSF was expressed in corneas of the patients with HSK but not in control subjects. The data suggest that GM-CSF, expressed by cornea-resident cells such as HCFs and HCE cells, may play a role in the immunopathogenesis of HSK by prolonging the survival and modulating the effector function of corneal infiltrating neutrophils.


Dissecting the mechanisms of tissue transglutaminase-induced cross-linking of alpha-synuclein: implications for the pathogenesis of Parkinson disease.
Tissue transglutaminase (tTG) has been implicated in the pathogenesis of Parkinson disease (PD). However, exactly how tTG modulates the structural and functional properties of alpha-synuclein (alpha-syn) and contributes to the pathogenesis of PD remains unknown. Using site-directed mutagenesis combined with detailed biophysical and mass spectrometry analyses, we sought to identify the exact residues involved in tTG-catalyzed cross-linking of wild-type alpha-syn and alpha-syn mutants associated with PD. To better understand the structural consequences of each cross-linking reaction, we determined the effect of tTG-catalyzed cross-linking on the oligomerization, fibrillization, and membrane binding of alpha-syn in vitro. Our findings show that tTG-catalyzed cross-linking of monomeric alpha-syn involves multiple cross-links (specifically 2-3). We subjected tTG-catalyzed cross-linked monomeric alpha-syn composed of either wild-type or Gln --> Asn mutants to sequential proteolysis by multiple enzymes and peptide mapping by mass spectrometry. Using this approach, we identified the glutamine and lysine residues involved in tTG-catalyzed intramolecular cross-linking of alpha-syn. These studies demonstrate for the first time that Gln(79) and Gln(109) serve as the primary tTG reactive sites. Mutating both residues to asparagine abolishes tTG-catalyzed cross-linking of alpha-syn and tTG-induced inhibition of alpha-syn fibrillization in vitro. To further elucidate the sequence and structural basis underlying these effects, we identified the lysine residues that form isopeptide bonds with Gln(79) and Gln(109). This study provides mechanistic insight into the sequence and structural basis of the inhibitory effects of tTG on alpha-syn fibrillogenesis in vivo, and it sheds light on the potential role of tTG cross-linking on modulating the physiological and pathogenic properties of alpha-syn.


Prenatal exposure to a farm environment modifies atopic sensitization at birth.
Previous cross-sectional surveys have suggested that maternal exposure to animal sheds during pregnancy exerted a protective effect on atopic sensitization in children lasting until school age. We sought to evaluate the effects of maternal exposure to animal sheds and other farm-related exposures during pregnancy on cord blood IgE levels in a prospective birth cohort. Pregnant women living in rural areas in Austria, Finland, France, Germany, and Switzerland were recruited in the third trimester of pregnancy. Information on maternal farm-related exposures, nutrition, and health during pregnancy was obtained by means of interviews. Specific IgE levels for food and common inhalant allergens were assessed in cord blood of 922 children and peripheral blood samples of their mothers. Different sensitization patterns in cord blood of farm and nonfarm children were observed. In multivariable analysis consumption of boiled, but not unboiled, farm milk during pregnancy was positively associated with specific IgE to cow's milk independently from maternal IgE. In contrast, there was an inverse relationship between maternal exposure to animal sheds and cord blood IgE levels against seasonal allergens (adjusted odds ratio, 0.38; 95% CI, 0.21-0.70). This association was not confounded by maternal IgE levels. Maternal contact with hay enhanced the protective effect of exposure to animal sheds on IgE levels to grass pollen in cord blood. Maternal exposure during pregnancy influences atopic sensitization patterns in cord blood. The (microbial) context of allergen contact possibly modifies the risk of atopic sensitization.


Structure and function in human and primate social networks: implications for diffusion, network stability and health.
The human social world is orders of magnitude smaller than our highly urbanized world might lead us to suppose. In addition, human social networks have a very distinct fractal structure similar to that observed in other primates. In part, this reflects a cognitive constraint, and in part a time constraint, on the capacity for interaction. Structured networks of this kind have a significant effect on the rates of transmission of both disease and information. Because the cognitive mechanism underpinning network structure is based on trust, internal and external threats that undermine trust or constrain interaction inevitably result in the fragmentation and restructuring of networks. In contexts where network sizes are smaller, this is likely to have significant impacts on psychological and physical health risks.


Challenges in design of multicenter trials: end points assessed longitudinally for change and monotonicity.
Assessing clinimetric performance of diabetic sensorimotor polyneuropathy (DSPN) end points in single and multicenter trials. Assessed were placebo-treated patients with DSPN in the Viatris and Eli Lilly trials and an epidemiologic cohort. Test reproducibility in clinical trial cohorts (r(I) approximately 0.7-0.85) approached that in the epidemiologic cohort (r(I) approximately 0.85-0.95). Associations between pairs of end points explained <10% of the variability of data (sometimes 15-35%), being higher in the epidemiologic cohort and the Viatris trial than in the Lilly trial. Most end points did not show monotonic worsening over 4 years. However, sural nerve amplitude and peroneal motor conduction velocity did. A nerve conduction score (Sigma 5 NC nds [5 attributes of nerve conduction expressed as normal deviates]) did not show monotonic worsening in established DSPN. In the epidemiologic cohort followed for 9.5 years, monotonic worsening of small magnitude occurred for sural amplitude, vibration detection threshold, and especially for composite quantitative sensation. The main reason why it is difficult to demonstrate monotonic worsening of neuropathic end points appears to be a very slow worsening of DSPN, a placebo effect for symptoms and signs, and measurement noise. Demonstrating disease progression in controlled trials of DSPN is more likely when 1) patients with developing rather than established DSPN are selected, 2) type 1 diabetic patients are preferentially recruited, 3) patients are selected who cannot or will not achieve ideal glycemic control, 4) end points chosen are known to show monotonic worsening, and 5) a restricted number of centers and expert examiners (trained, certified, using standard approaches, and reference values and interactive surveillance of tests) are used.


Influence of place of residence in access to specialized cancer care for African Americans.
Disparities in cancer care for rural residents and for African Americans have been documented, but the interaction of these factors is not well understood. The authors examined the simultaneous influence of race and place of residence on access to and utilization of specialized cancer care in the United States. Access to specialized cancer care was measured using: (1) travel time to National Cancer Institute (NCI) Cancer Centers, academic medical centers, and any oncologist for the entire continental US population, and (2) per capita availability of oncologists for the entire United States. Utilization was measured as attendance at NCI Cancer Centers, specialized hospitals, and other hospitals in the Surveillance, Epidemiology, and End Results (SEER) program Medicare population from 1998-2004. In urban settings, travel times were shorter for African Americans compared with Caucasians for all three cancer care settings, but they were longer for rural African Americans traveling to NCI Cancer Centers. Per capita oncologist availability was not significantly different by race or place of residence. Urban African American patients were almost 70% more likely to attend an NCI Cancer Center than urban Caucasian patients (OR = 1.66; 95% CI 1.51-1.83), whereas rural African American patients were 58% less likely to attend an NCI Cancer Center than rural Caucasian patients (OR = 0.42; 95% CI 0.26-0.66). Urban African Americans have similar or better access to specialized cancer care than urban Caucasians, but rural African Americans have relatively poor access and lower utilization compared with all other groups.


On the molecular basis of the recognition of angiotensin II (AII). NMR structure of AII in solution compared with the X-ray structure of AII bound to the mAb Fab131.
The high-resolution 3D structure of the octapeptide hormone angiotensin II (AII) in aqueous solution has been obtained by simulated annealing calculations, using high-resolution NMR-derived restraints. After final refinement in explicit water, a family of 13 structures was obtained with a backbone RMSD of 0.73 +/- 0.23 A. AII adopts a fairly compact folded structure, with its C-terminus and N-terminus approaching to within approximately 7.2 A of each other. The side chains of Arg2, Tyr4, Ile5 and His6 are oriented on one side of a plane defined by the peptide backbone, and the Val3 and Pro7 are pointing in opposite directions. The stabilization of the folded conformation can be explained by the stacking of the Val3 side chain with the Pro7 ring and by a hydrophobic cluster formed by the Tyr4, Ile5 and His6 side chains. Comparison between the NMR-derived structure of AII in aqueous solution and the refined crystal structure of the complex of AII with a high-affinity mAb (Fab131) [Garcia, K.C., Ronco, P.M., Verroust, P.J., Brunger, A.T., Amzel, L.M. (1992) Science257, 502-507] provides important quantitative information on two common structural features: (a) a U-shaped structure of the Tyr4-Ile5-His6-Pro7 sequence, which is the most immunogenic epitope of the peptide, with the Asp1 side chain oriented towards the interior of the turn approaching the C-terminus; (b) an Asx-turn-like motif with the side chain aspartate carboxyl group hydrogen-bonded to the main chain NH group of Arg2. It can be concluded that small rearrangements of the epitope 4-7 in the solution structure of AII are required by a mean value of 0.76 +/- 0.03 A for structure alignment and approximately 1.27 +/- 0.02 A for sequence alignment with the X-ray structure of AII bound to the mAb Fab131. These data are interpreted in terms of a biological "nucleus" conformation of the hormone in solution, which requires a limited number of structural rearrangements for receptor-antigen recognition and binding.


Microsomal binding sites for antioestrogens in rat liver. Properties and detergent solubilization.
The properties of an antioestrogen binding site (AEBS), which has high affinity and specificity for nonsteroidal antioestrogens and structurally related compounds, have been studied in rat liver microsomes. When subcellular organelles were separated on Percoll density gradients the distribution of the AEBS paralleled that of NADPH-cytochrome c reductase, indicating that the AEBS is associated with the endoplasmic reticulum. Saturation analysis showed that [3H]tamoxifen was bound to a single class of saturable binding sites in liver microsomes with a KD of 0.9 +/- 0.1 nM at 0 degrees C. The equilibrium KD was not significantly different at 22 degrees C. The KD calculated from the association and dissociation rate constants for [3H]tamoxifen binding at 0 degrees C and 22 degrees C was compatible with the KD measured at equilibrium. Ligand specificity studies using tamoxifen analogues showed qualitatively similar structure-affinity relationships for the AEBS from both rat liver and the MCF 7 breast cancer cell line. In general structural modifications caused correspondingly greater changes in affinity for rat liver AEBS than for MCF 7 AEBS. The AEBS was solubilized from microsomal membranes with sodium cholate. This was the only detergent of nine tested that solubilized the site in high yield without loss of activity. Solubilization using cholate was more effective in the presence of 1 M-NaCl. In the solubilized state there was an apparent loss of [3H]tamoxifen binding activity which could be restored by dilution of the detergent. Gel filtration indicated an Mr of 440,000-490,000 for the AEBS-cholate complex. These studies demonstrate that rat liver contains high concentrations of a microsomal AEBS which has similar properties and specificity to the AEBS previously described in human breast cancer cells. This site can be solubilized by sodium cholate to supply material suitable for further purification.


Development of Pathotype-Specific SCAR Markers for Detection of Verticillium albo-atrum Isolates from Hop.
Rapid polymerase chain reaction (PCR) assays were developed for the identification and detection of Verticillium albo-atrum hop pathotypes PG1 and PG2 from Slovenia. Of 17 pathotype-linked amplified fragment length polymorphism (AFLP) markers, 11 were cloned successfully and sequenced. To convert polymorphic AFLP markers into pathotype-specific sequence-characterized amplified region (SCAR) markers, 22 PG2- and 10 PG1-specific primer pairs were designed from 16 sequences. When primer specificity was tested on a wide range of Verticillium isolates, 10 PG2- and 6 PG1-specific primer pairs retained amplification specificity for V. albo-atrum Slovene hop isolates, but also amplified sequences in V. albo-atrum and V. dahliae hop isolates from different hop production areas in Europe, as well as in some isolates from other hosts. Primer combinations obtained from the AFLP-9-1 marker were specific only for V. albo-atrum PG2 isolates. The highly specific primers were used in multiplex PCR and a nested PCR to detect the V. albo-atrum PG2 pathotype in xylem tissue of hop plants. These new SCAR markers provide a valuable tool for rapid identification of V. albo-atrum PG1 and PG2 hop pathotypes.


Improving the network management of integrated primary mental healthcare for older people in a rural Australian region: protocol for a mixed methods case study.
An integrated approach to the mental healthcare of older people is advocated across health, aged care and social care sectors. It is not clear, however, how the management of integrated servicing should occur, although interorganisational relations theory suggests a reflective network approach using evaluation feedback. This research will test a network management approach to help regional primary healthcare organisations improve mental health service integration. This mixed methods case study in rural South Australia will test facilitated reflection within a network of health and social care services to determine if this leads to improved integration. Engagement of services will occur through a governance group and a series of three 1-day service stakeholder workshops. Facilitated reflection and evaluation feedback will use information from a review of health sector and local operational policies, a network survey about current service links, gaps and enablers and interviews with older people and their carers about their help seeking journeys. Quantitative and qualitative analysis will describe the policy enablers and explore the current and ideal links between services. The facilitated reflection will be developed to maximise engagement of senior management in the governance group and the service staff at the operational level in the workshops. Benefit will be assessed through indicators of improved service coordination, collective ownership of service problems, strengthened partnerships, agreed local protocols and the use of feedback for accountability. Ethics approval will deal with the sensitivities of organisational network research where data anonymity is not preserved. The benefit will be the tested utility of a facilitated reflective process for a network of health and social care services to manage linked primary mental healthcare for older people in a rural region. Dissemination will make use of the sectoral networks of the governance group.


Does hospital occupancy impact discharge rates?
To understand what impact hospital inpatient occupancy levels have on patient throughput by analysing one hospital's occupancy levels and the rate of patient discharge. A four-stage model was fit to hospital admission and separation data and used to analyse the per-capita separation rate according to the patient load and the impact of hospital over-census actions. Per-capita separation rates are significantly higher on days when the hospital declares an over-census due to emergency department crowding. Per-capita separation rates are also higher or lower on days with 8-10% higher or lower patient loads, respectively, but the response is not nearly as strong as the response to an over-census declaration, and is limited to patients with an elapsed stay of 10 days or more. Within the medical division there is an increase in per-capita separation rates on over-census days, but no significant difference in per-capita release rates for different patient loads. Within the surgical division there is no significant difference in per-capita separation rates on over-census days compared with other days, but the patient load does make a significant difference. Staff do discharge a greater proportion of long-stay patients when the hospital is experiencing high demand and a lower proportion when occupancy is low, but the reasons driving those changes remains unclear.


Penile Bead Implantation in Relation to HIV Infection in Male Heroin Users in Taiwan.
Recent reports indicate that injection risk behavior has declined among injection drug users (IDUs) but sexual risk behavior continues. RuJu, classified as a form of body modification, is the practice of permanently inserting beads beneath the foreskin of the penis. A man who has penis beads does not comfortably use a condom while having sex. This study examined the possible association of RuJu with human immunodeficiency virus (HIV) infection among IDUs in Taiwan. Of 644 eligible male heroin users who agreed to participate in the study, 573 (89%) completed consent forms and a questionnaire between June and August 2008. Clinical characteristics (HIV, hepatitis C, and RuJu) were retrieved from their medical files. Multinomial logistic regression was performed to examine the association of RuJu and HIV seropositivity, with drug risk behavior and sexual risk behavior controlled for. 206 respondents (36%) were HIV positive, 428 (75%) were HCV positive, and 232 (40%) had RuJu beads. 21% reported condom use at last sex and 34% reported multiple sexual partners during the last 6 months. 88% reported that they had injected heroin within the last 6 months, 18% shared a needle at last injection, and 26% shared rinses at last injection. Multinomial logistic regression analysis revealed that HIV-positive IDUs were more likely than HIV-negative IDUs to have HIV/AIDS knowledge, to have had RuJu and an IDU partner, and to have used a condom at last sex and shared needles and rinse water at last heroin use. Prevalence rates of HIV, HCV, and RuJu are high among IDUs seen at Taiwan drug detention centers. The results show that RuJu is highly associated with HIV seropositivity. Practitioners who seek to prevent HIV in male IDUs should be aware of the RuJu culture. More research on the role of RuJu in HIV infection is suggested.


A meta-analysis of coffee intake and risk of urolithiasis.
Epidemiologic studies have reported various results relating coffee to urolithiasis. A meta-analysis of cohort and case-control studies was conducted to pool the relative risk (RR) estimates of the association between coffee and urolithiasis. Eligible studies were retrieved via both computer searches and review of references. We analyzed abstracted data with random effects models to obtain the summary RR estimates. A dose-response meta-analysis was performed for studies reporting categorical RR estimates for a series of exposure levels. A total of 6 studies (2 cohort and 4 case-control studies) on coffee intake were included in the meta-analysis. The pooled odds ratio (OR) showed a significant influence of the highest coffee consumption (OR = 0.70, 95% confidence interval 0.60-0.82) on the risk of urolithiasis. Coffee exhibited an inverse dose-response relationship with urolithiasis. In stratified analysis, a significant inverse association between coffee and urolithiasis was observed in study design, geographical region and gender subgroup. The overall current literature suggests that coffee intake is associated with a decreased risk of urolithiasis. Further efforts should be made to clarify the underlying biological mechanisms.


Predicting Carriers of Ongoing Selective Sweeps without Knowledge of the Favored Allele.
Methods for detecting the genomic signatures of natural selection have been heavily studied, and they have been successful in identifying many selective sweeps. For most of these sweeps, the favored allele remains unknown, making it difficult to distinguish carriers of the sweep from non-carriers. In an ongoing selective sweep, carriers of the favored allele are likely to contain a future most recent common ancestor. Therefore, identifying them may prove useful in predicting the evolutionary trajectory--for example, in contexts involving drug-resistant pathogen strains or cancer subclones. The main contribution of this paper is the development and analysis of a new statistic, the Haplotype Allele Frequency (HAF) score. The HAF score, assigned to individual haplotypes in a sample, naturally captures many of the properties shared by haplotypes carrying a favored allele. We provide a theoretical framework for computing expected HAF scores under different evolutionary scenarios, and we validate the theoretical predictions with simulations. As an application of HAF score computations, we develop an algorithm (PreCIOSS: Predicting Carriers of Ongoing Selective Sweeps) to identify carriers of the favored allele in selective sweeps, and we demonstrate its power on simulations of both hard and soft sweeps, as well as on data from well-known sweeps in human populations.


Mortality among silicotics in Genoa, Italy, from 1961 to 1987.
A historical cohort mortality study conducted among 515 silicotic subjects revealed higher than expected risks for all causes [standardized mortality ratio (SMR) 1.89], respiratory tract diseases (SMR 8.89), silicotuberculosis (SMR 27.00), respiratory tract cancers (SMR 3.14), and lung cancer (SMR 3.50). Mortality from cardiovascular diseases was lower than that expected (SMR 0.51). Lung cancer risk increased with duration of occupational exposure (SMR 2.80, 2.99, and 5.02 for 14, 15-29, and 30 years of employment, respectively). Lung cancer risk was higher for the silicotics without tuberculosis (SMR 3.72) than for those with tuberculosis (SMR 2.83). Indirect adjustment for smoking habits, including number of cigarettes smoked per day, showed that smoking would have been responsible for a maximum risk of 1.77. Thus smoking may have explained 50% of the observed excess mortality from lung cancer.


Intestinal Activation of pH-Sensing Receptor OGR1 [GPR68] Contributes to Fibrogenesis.
pH-sensing ovarian cancer G-protein coupled receptor-1 [OGR1/GPR68] is regulated by key inflammatory cytokines. Patients suffering from inflammatory bowel diseases [IBDs] express increased mucosal levels of OGR1 compared with non-IBD controls. pH-sensing may be relevant for progression of fibrosis, as extracellular acidification leads to fibroblast activation and extracellular matrix remodelling. We aimed to determine OGR1 expression in fibrotic lesions in the intestine of Crohn's disease [CD] patients, and the effect of Ogr1 deficiency in fibrogenesis. Human fibrotic and non-fibrotic terminal ileum was obtained from CD patients undergoing ileocaecal resection due to stenosis. Gene expression of fibrosis markers and pH-sensing receptors was analysed. For the initiation of fibrosis in vivo, spontaneous colitis by Il10-/-, dextran sodium sulfate [DSS]-induced chronic colitis and the heterotopic intestinal transplantation model were used. Increased expression of fibrosis markers was accompanied by an increase in OGR1 [2.71 ± 0.69 vs 1.18 ± 0.03, p = 0.016] in fibrosis-affected human terminal ileum, compared with the non-fibrotic resection margin. Positive correlation between OGR1 expression and pro-fibrotic cytokines [TGFB1 and CTGF] and pro-collagens was observed. The heterotopic animal model for intestinal fibrosis transplanted with terminal ileum from Ogr1-/- mice showed a decrease in mRNA expression of fibrosis markers as well as a decrease in collagen layer thickness and hydroxyproline compared with grafts from wild-type mice. OGR1 expression was correlated with increased expression levels of pro-fibrotic genes and collagen deposition. Ogr1 deficiency was associated with a decrease in fibrosis formation. Targeting OGR1 may be a potential new treatment option for IBD-associated fibrosis.


Effects of source spatial partial coherence on temporal fade statistics of irradiance flux in free-space optical links through atmospheric turbulence.
The temporal covariance function of irradiance-flux fluctua-tions for Gaussian Schell-model (GSM) beams propagating in atmospheric turbulence is theoretically formulated by making use of the method of effective beam parameters. Based on this formulation, new expressions for the root-mean-square (RMS) bandwidth of the irradiance-flux temporal spectrum due to GSM beams passing through atmospheric turbulence are derived. With the help of these expressions, the temporal fade statistics of the irradiance flux in free-space optical (FSO) communication systems, using spatially partially coherent sources, impaired by atmospheric turbulence are further calculated. Results show that with a given receiver aperture size, the use of a spatially partially coherent source can reduce both the fractional fade time and average fade duration of the received light signal; however, when atmospheric turbulence grows strong, the reduction in the fractional fade time becomes insignificant for both large and small receiver apertures and in the average fade duration turns inconsiderable for small receiver apertures. It is also illustrated that if the receiver aperture size is fixed, changing the transverse correlation length of the source from a larger value to a smaller one can reduce the average fade frequency of the received light signal only when a threshold parameter in decibels greater than the critical threshold level is specified.


Regulation of Cdc42 expression and signaling is critical for promoting corneal epithelial wound healing.
Cdc42, a member of Rho GTPases (guanosine triphosphatases), participates in cytokine- and growth factor-controlled biological functions in mammalian tissues. Here, we examined Cdc42 role in corneal epithelial wound healing and the influence of hepatocyte, keratinocyte, and epidermal growth factor (HGF, KGF, and EGF)-mediated signaling on Cdc42. Epithelial wounds were created on the corneas of live rabbits by complete debridement and in rabbit corneal epithelial primary cultures through scratch injury. Cdc42 expression in cultures was suppressed using Cdc42 siRNA. Cdc42 activation was determined by pull-down assays with PAK-agarose beads. Cdc42 expression was analyzed by immunoblotting and immunofluorescence. Association of Cdc42 with cell-cycle proteins was identified by immunoprecipitation. In rabbit corneas, significant increase in Cdc42 expression that occurred 2 to 4 days after the injury coincided with wound closure, and by 8 days the expression reached near basal levels. Silencing of Cdc42 expression in cultures caused inhibition of wound closure as a result of 60% to 75% decrease in epithelial migration and growth. HGF, KGF, and EGF increased Cdc2 expression, activation, and its phosphorylation on ser71. Inhibition of growth factor-mediated PI-3K signaling resulted in the downregulation of Cdc42 expression and its phosphorylation. Increased association of cell-cycle proteins p27(kip) and cyclin-dependent kinase 4 (CDK4) with Cdc42; and phosphorylated Cdc42 with plasma membrane leading edges was also observed in the presence of growth factors. Cdc42 is an important regulator of corneal epithelial wound repair. To promote healing, Cdc42 may interact with receptor tyrosine kinase-activated signaling cascades that participate in cell migration and cell-cycle progression.


Canoe slalom--competition analysis reliability.
The aim of this study was to assess intra-observer and inter-observer reliability of data gathered from a lapsed-time time-motion analysis of canoe slalom competition. The data were collected using a definition set developed in conjunction with elite canoe slalom coaches. Competition runs from four national-standard paddlers in a national selection race were analysed in random order three times by three observers. For each run, observers identified various events specific to canoe slalom, including time taken between gates, touched and missed gates, turn times, major and minor avoidance, rolls, paddle in and out of water times, and stroke classification. The error of measurement was determined for each of these variables. For time taken between gates and turn times, the error was < or = 0.21 and < or = 0.39 s for intra-observer and inter-observer analysis, respectively. The error for stroke in and out of water times was < or = 0.08 and < or = 0.13 s for intra-observer and inter-observer analysis, respectively. Analysis of stroke classification identification for intra-observer comparisons revealed that 91% of the time identical stroke identification occurred. Inter-observer analysis revealed identical stroke identification was achieved 81% of the time. These reliability data compare favourably with previous time-motion analysis in other sports using fewer variables.


Ultrasound assessment of selected peripheral nerve pathologies. Part III: Injuries and postoperative evaluation.
The previous articles of the series devoted to ultrasound diagnostics of peripheral nerves concerned the most common nerve pathologies, i.e. entrapment neuropathies. The aim of the last part of the series is to present ultrasound possibilities in the postoperative control of the peripheral nerves as well as in the diagnostics of the second most common neuropathies of peripheral nerves, i.e. posttraumatic lesions. Early diagnostics of posttraumatic changes is of fundamental importance for the course of treatment and its long-term effects. It aids surgeons in making treatment decisions (whether surgical or conservative). When surgical treatment is necessary, the surgeon, based on US findings, is able to plan a given type of operative method. In certain cases, may even abandon the corrective or reconstructive surgery of the nerve trunk (when there are extensive defects of the nerve trunks) and instead, proceed with muscle transfers. Medical literature proposes a range of divisions of the kinds of peripheral nerve injuries depending on, among others, the mechanism or degree of damage. However, the most important issue in the surgeon-diagnostician communication is a detailed description of stumps of the nerve trunks, their distance and location. In the postoperative period, ultrasound is used for monitoring the operative or conservative treatment effects including the determination of the causes of a persistent or recurrent neuropathy. It facilitates decision-making concerning a repeated surgical procedure or assuming a wait-and-see attitude. It is a difficult task for a diagnostician and it requires experience, close cooperation with a clinician and knowledge concerning surgical techniques. Apart from a static assessment, a dynamic assessment of possible adhesions constitutes a crucial element of postoperative examination. This feature distinguishes ultrasound scanning from other methods used in the diagnostics of peripheral neuropathies.


SymB and SymC, two membrane associated proteins, are required for Epichloë festucae hyphal cell-cell fusion and maintenance of a mutualistic interaction with Lolium perenne.
Cell-cell fusion in fungi is required for colony formation, nutrient transfer and signal transduction. Disruption of genes required for hyphal fusion in Epichloë festucae, a mutualistic symbiont of Lolium grasses, severely disrupts the host interaction phenotype. They examined whether symB and symC, the E. festucae homologs of Podospora anserina self-signaling genes IDC2 and IDC3, are required for E. festucae hyphal fusion and host symbiosis. Deletion mutants of these genes were defective in hyphal cell fusion, formed intra-hyphal hyphae, and had enhanced conidiation. SymB-GFP and SymC-mRFP1 localize to plasma membrane, septa and points of hyphal cell fusion. Plants infected with ΔsymB and ΔsymC strains were severely stunted. Hyphae of the mutants colonized vascular bundles, were more abundant than wild type in the intercellular spaces and formed intra-hyphal hyphae. Although these phenotypes are identical to those previously observed for cell wall integrity MAP kinase mutants no difference was observed in the basal level of MpkA phosphorylation or its cellular localization in the mutant backgrounds. Both genes contain binding sites for the transcription factor ProA. Collectively these results show that SymB and SymC are key components of a conserved signaling network for E. festucae to maintain a mutualistic symbiotic interaction within L. perenne.


Supersaturating drug delivery systems: The potential of co-amorphous drug formulations.
Amorphous solid dispersions (ASDs) are probably the most common and important supersaturating drug delivery systems for the formulation of poorly water-soluble compounds. These delivery systems are able to achieve and maintain a sustained drug supersaturation which enables improvement of the bioavailability of poorly water-soluble drugs by increasing the driving force for drug absorption. However, ASDs often require a high weight percentage of carrier (usually a hydrophilic polymer) to ensure molecular mixing of the drug in the carrier and stabilization of the supersaturated state, often leading to high dosage volumes and thereby challenges in the formulation of the final dosage form. As a response to the shortcomings of the ASDs, the so-called co-amorphous formulations, which are amorphous combinations of two or more low molecular weight components, have emerged as an alternative formulation strategy for poorly-soluble drugs. While the current research on co-amorphous formulations is focused on preparation and characterization of these systems, more detailed research on their supersaturation and precipitation behavior and the effect of co-formers on nucleation and crystal growth inhibition is needed. The current status of this research is reviewed in this paper. Furthermore, the potential of novel preparation methods for co-amorphous systems with respect to the current preparation methods are discussed.


Internal and near-surface electromagnetic fields for a spheroidal particle with arbitrary illumination.
A theoretical procedure in which a spheroidal coordinate separation-of-variables solution is used is developed for the determination of the internal and the near-surface electromagnetic fields for an arbitrary monochromatic field that is incident upon a homogeneous spheroidal particle. Calculations are presented for both the prolate and the oblate geometries, demonstrating the effects of particle size, particle axis ratio, and the orientation and character (plane-wave and focused Gaussian beam) of the incident field on the resultant internal and near-surface electromagnetic-field distributions.


The VIPER elements of trypanosomes constitute a novel group of tyrosine recombinase-enconding retrotransposons.
VIPER was initially characterized as a 2326bp LTR-like retroelement associated to SIRE, a short interspersed repetitive element specific of Trypanosoma cruzi. It carried a single ORF that coded for a putative reverse transcriptase-RNAse H protein, suggesting that it could be a truncated copy of a longer retroelement. Herein we report the identification and characterization of a complete 4480bp long VIPER in the T. cruzi genome. The complete VIPER harbored three non-overlapped domains encoding for a GAG-like, a tyrosine recombinase and a reverse transcriptase-RNAse H proteins. VIPER elements were also found in the genomes of Trypanosoma brucei and Trypanosoma vivax, but not in Leishmania sp. On the basis of its reverse transcriptase phylogeny, VIPER was classified as an LTR retroelement. However, VIPER was structurally related to the tyrosine recombinase encoding retroelements, DIRS and Ngaro. Phylogenetic analysis showed that VIPER's tyrosine recombinase grouped with the transposases RCI1 of Escherichia coli and Ye24 and Ye72 of Haemophilus influenzae within a major branch of prokaryotic recombinases. Taken together, VIPER's structure, the nature of its tyrosine recombinase, the unique features of its reverse transcriptase catalytic consensus motif and the fact that it was found in Trypanosomes, an early branching eukaryote, suggest that VIPER may be the closest relative of the founder element of the tyrosine recombinase encoding retrotransposons known up to date. Our analysis revealed that tyrosine recombinase-encoding retroelements were originated as early in evolution as non-LTR retroelements and suggests that VIPER, Ngaro and DIRS elements may constitute a third group of retrotransposons, distinct from both LTR and non-LTR retroelements.


The Effect of Spinopelvic Parameters on the Development of Proximal Junctional Kyphosis in Early Onset: Mean 4.5-Year Follow-up.
Proximal junctional kyphosis (PJK) is a major complication after posterior spinal surgery. It is diagnosed radiographically based on a proximal junctional angle (PJA) and clinically when proximal extension is required. We hypothesized that abnormal spinopelvic alignment will increase the risk of PJK in children with early-onset scoliosis (EOS). A retrospective study of 135 children with EOS from 2 registries, who were treated with distraction-based implants. Etiologies included 54 congenital, 10 neuromuscular, 37 syndromic, 32 idiopathic, and 2 unknown. A total of 89 rib-based and 46 spine-based surgeries were performed at a mean age of 5.3±2.83 years. On sagittal radiographs, spinopelvic parameters were measured preoperatively and at last follow-up: scoliosis angle (Cobb method, CA), thoracic kyphosis (TK), lumbar lordosis (LL), pelvic incidence (PI), pelvic tilt (PT), sacral slope and PJA. Radiographic PJK was defined as PJA≥10 degrees and PJA≥10 degrees greater than preoperative measurement. The requirement for the proximal extension of the upper instrumented vertebrae was considered a proximal junctional failure (PJF). Analysis of risk factors for the development of PJK and PJF was performed. At final follow-up (mean: 4.5±2.6 y), CA decreased (P<0.005), LL (P=0.029), and PI (P<0.005) increased, whereas PI-LL (pelvic incidence minus lumbar lordosis) did not change (P=0.706). Overall, 38% of children developed radiographic PJK and 18% developed PJF. Preoperative TK>50 degrees was a risk factor for the development of radiographic PJK (relative risk: 1.67, P=0.04). Children with high postoperative CA [hazard ratio (HR): 1.03, P=0.015], postoperative PT≥30 degrees (HR: 2.77, P=0.043), PI-LL>20 degrees (HR: 2.92, P=0.034), as well as greater preoperative to postoperative changes in PT (HR: 1.05, P=0.004), PI (HR: 1.06, P=0.0004) and PI-LL (HR: 1.03, P=0.013) were more likely to develop PJF. Children with rib-based constructs were less likely to develop radiographic PJK compared with children with spine-based distraction constructs (31% vs. 54%, respectively, P=0.038). In EOS patients undergoing growth-friendly surgery for EOS, preoperative TK>50 degrees was associated with increased risk for radiographic PJK. Postoperative PI-LL>20 degrees, PT≥30 degrees, and overcorrection of PT and PI-LL increased risk for PJF. Rib-based distraction construct decreased the risk for radiographic PJK in contrast with the spine-based constructs. Level III.


How should we measure arm exercise capacity in patients with COPD? A systematic review.
There are no recommendations on how to measure arm exercise capacity in individuals with COPD. The objectives of this study were (1) to synthesize the literature on measures of arm exercise capacity in individuals with COPD, (2) to describe the psychometric properties and the target construct of each measure, and (3) to make recommendations for clinical practice and research. Studies conducted in patients with COPD that included a measure of arm exercise capacity were identified after searches of five electronic databases (PubMed, CINAHL, EMBASE, PEDro, and Cochrane Library) and reference lists of pertinent articles. One reviewer performed data extraction, and two assessed the quality of the studies that described measurement properties, using the Consensus-based Standards for the Selection of Health Status Measurement Instruments (COSMIN) checklist. Of 654 reports, 41 met the study criteria. Five types of arm exercise tests were identified: arm ergometry, ring shifts, dowel lifts, proprioceptive neuromuscular facilitation, and activities of daily living. Four studies assessed the measurement properties of the unsupported upper-limb exercise test (UULEX), the 6-min pegboard and ring test (6PBRT), a test involving weight shifts, and the grocery-shelving task (GST). Validity studies were of fair to good quality, whereas reliability studies were of poor quality. Arm ergometry may be the best method for measuring peak supported arm exercise capacity and endurance. The UULEX, 6PBRT, and GST may better reflect activities of daily living and should be the tests of choice to measure peak unsupported arm exercise capacity (UULEX) and arm function (6PBRT and GST).


Plant-Based Nutrition: An Essential Component of Cardiovascular Disease Prevention and Management.
This review aims to summarize and discuss the role of plant-based nutrition as an adjunct to the management of cardiovascular disease (CVD). Discussion of nutrition and the benefits of a plant-based diet should be highlighted during healthcare provider visits as an essential part of the overall CVD prevention and management care plan. Evidence from prospective cohort studies indicates that a high consumption of predominantly plant-based foods, such as fruit and vegetables, nuts, and whole grains, is associated with a significantly lower risk of CVD. The protective effects of these foods are likely mediated through their multiple beneficial nutrients, including mono- and polyunsaturated fatty acids, omega-3 fatty acids, antioxidant vitamins, minerals, phytochemicals, fiber, and plant protein. In addition, minimizing intake of animal proteins has been shown to decrease the prevalence of CVD risk factors. Substantial evidence indicates that plant-based diets can play an important role in preventing and treating CVD and its risk factors. Such diets deserve more emphasis in dietary recommendations.


The effect of ultrasound treatment on microbial and physicochemical properties of Iranian ultrafiltered feta-type cheese.
Pasteurization failures in the dairy industry have been reported in many previous studies. Hence, ultrasound, as a nonthermal alternative to pasteurization, has been studied in recent years. In this research, retentate of ultrafiltered milk was pasteurized, inoculated with Escherichia coli O157:H7, Staphylococcus aureus, Penicillium chrysogenum, or Clostridium sporogenes, and then treated with ultrasound for 20 min at frequencies of 20, 40, and 60 kHz and intensity of 80%. Microbial and physicochemical properties of the subsequently produced ultrafiltered white cheeses were investigated throughout 60 d of ripening. Sonication at 20, 40, and 60 kHz reduced counts of E. coli O157:H7, S. aureus, P. chrysogenum, and Cl. sporogenes by 4.08, 4.17, and 4.28 log; 1.10, 1.03, and 1.95 log; 1.11, 1.07, and 1.11 log; and 2.11, 2.03, and 2.17 log, respectively. Sonication improved the acidity of ripened cheese, and sonicated samples had lower pH values than control samples at the end of storage. Sonication did not affect fat in dry matter or the protein content of cheese during ripening, but it did accelerate lipolysis and proteolysis; the highest rates of lipolysis index (free fatty acid content) and proteolysis index (water-soluble nitrogen) were observed on d 60 of ripening for samples sonicated at 60 kHz. Sonication did not affect cohesiveness or springiness of cheese samples, but hardness and gumminess increased in the first 30 d and then decreased until 60 d of storage. Furthermore, ultrasound treatment improved organoleptic properties of the cheese. In terms of overall acceptance, samples sonicated at 60 kHz received the highest sensorial scores. Results showed that sonication can improve microbial, physicochemical, and sensorial properties of ultrafiltered white cheese.


Dressed for sex: red as a female sexual signal in humans.
In many non-human primate species, a display of red by a female serves as a sexual signal to attract male conspecifics. Red is associated with sex and romance in humans, and women convey their sexual interest to men through a variety of verbal, postural, and behavioral means. In the present research, we investigate whether female red ornamentation in non-human primates has a human analog, whereby women use a behavioral display of red to signal their sexual interest to men. Three studies tested the hypothesis that women use red clothing to communicate sexual interest to men in profile pictures on dating websites. In Study 1, women who imagined being interested in casual sex were more likely to display red (but not other colors) on their anticipated web profile picture. In Study 2, women who indicated interest in casual sex were more likely to prominently display red (but not other colors) on their actual web profile picture. In Study 3, women on a website dedicated to facilitating casual sexual relationships were more likely to prominently exhibit red (but not other colors) than women on a website dedicated to facilitating marital relationships. These results establish a provocative parallel between women and non-human female primates in red signal coloration in the mating game. This research shows, for the first time, a functional use of color in women's sexual self-presentation, and highlights the need to extend research on color beyond physics, physiology, and preference to psychological functioning.


Adaptive Data Gathering in Mobile Sensor Networks Using Speedy Mobile Elements.
Data gathering is a key operator for applications in wireless sensor networks; yet it is also a challenging problem in mobile sensor networks when considering that all nodes are mobile and the communications among them are opportunistic. This paper proposes an efficient data gathering scheme called ADG that adopts speedy mobile elements as the mobile data collector and takes advantage of the movement patterns of the network. ADG first extracts the network meta-data at initial epochs, and calculates a set of proxy nodes based on the meta-data. Data gathering is then mapped into the Proxy node Time Slot Allocation (PTSA) problem that schedules the time slots and orders, according to which the data collector could gather the maximal amount of data within a limited period. Finally, the collector follows the schedule and picks up the sensed data from the proxy nodes through one hop of message transmissions. ADG learns the period when nodes are relatively stationary, so that the collector is able to pick up the data from them during the limited data gathering period. Moreover, proxy nodes and data gathering points could also be timely updated so that the collector could adapt to the change of node movements. Extensive experimental results show that the proposed scheme outperforms other data gathering schemes on the cost of message transmissions and the data gathering rate, especially under the constraint of limited data gathering period.


Antigen-induced aggregation and modulation of receptors on hapten-specific B lymphocytes.
Mouse spleen cells were subjected to a fractionation procedure designed to enrich for 4-hydroxy-3-iodo-5-nitro-phenylacetyl (NIP)- or DNP-specific B lymphocytes, which depended on adherence of specific cells to a layer of hapten-gelatin at 4 degrees C, recovery of bound cells by melting, and digestion of adherent antigen by collagenase. A population of cells resulted which contained 90% typical B cells and 37% of cells capable of binding a fluorescent, haptenated polymeric protein. Fractionated cells were reacted in vitro with fluorescent conjugates of the specific haptens with polymerized flagellin [NIP-polymerized flagellin (POL)-tetramethylrhodamine isothiocyanate conjugate or DNP-POL-fluorescein isothiocyanate conjugate] under a variety of conditions, with the aim of investigating the behavior of Ig receptors on B lymphocytes after exposure to antigen; Experiments were performed with immunogenic and tolerogenic concentrations of antigen. Furthermore, four experimental designs were used, namely: (a) brief labeling with fluorescent antigen followed by culture without antigen (pulse design); (b) culture in the continuous presence of fluorescent antigen (continuous-labeling design); (c) culture in the continuous presence of nonlabeled antigen followed by labeling of unoccupied receptors by fluorescent antigen (receptor status design); and (d) culture with nonlabeled antigen for 2 h followed by incubation without further antigen for 20 h and labeling with fluorescent antigen (modulation design). Further insight into receptor occupancy and distribution was gained by the use of fluorescent antihapten and antiglobulin reagents. It was found that both immunogenic and tolerogenic antigen concentrations caused rapid patching and capping of the receptors to which they attached, followed by endocytosis and probably some shedding of Ig receptors. However, a proportion of cells continued to bear some cell surface antigen for 24 h. The immunogenic antigen concentration failed to completely remove the receptor coat from the cell surface. At all stages of immunogenesis, plentiful unoccupied receptors could be demonstrated. The tolerogenic concentration nearly saturated available receptors, and in its continuous presence, only few unoccupied or antigen-occupied surface receptors could be detected after 24 h of culture. Experiments of the modulation design showed that brief incubation with the tolerogenic concentration appeared to suppress receptor resynthesis, as few new receptors could be demonstrated after 20 h of further culture without antigen. Experiments were performed to determine whether fractionated cells prepared from spleens of 8-day-old mice showed an unusual tendency for modulation, even with immunogenic antigen concentrations. They were found to behave essentially like adult fractionated cells. The results are discussed in the framework of current theories of B-lymphocyte activation and tolerization.


Deep eutectic solvents: similia similibus solvuntur?
Deep eutectic solvents, mixtures of an organic compound and a salt with a deep eutectic melting point, are promising cheap and eco-friendly alternatives to ionic liquids. Ab initio molecular dynamics simulations of reline, a mixture consisting of urea and choline chloride, reveal that not solely hydrogen bonds allow similar interactions between both constituents. The chloride anion and the oxygen atom of urea also show a similar spatial distribution close to the cationic core of choline due to a similar charge located on both atoms. As a result of multiple similar interactions, clusters migrating together cannot be observed in reline which supports the hypothesis similia similibus solvuntur. In contrast to previous suggestions, the interaction of the hydroxyl group of choline with a hydrogen bond acceptor is overall rigid. Fast hydrogen bond acceptor dynamics is facilitated by the hydrogen atoms in the trans position to the carbonyl group of urea which contributes to the low melting point of reline.


The in vitro effect of manuka honeys on growth and adherence of oral bacteria.
Honey has been used since ancient times and more recently, for the healing of wounds and against infectious diseases. The aim of our study was to investigate the effect of two manuka honeys showing different potencies of their antibacterial activity, on potentially pathogenic oral bacteria. The antimicrobial activity was examined by determining the MIC and MBC using the macro dilution broth technique. The effect on the adherence was tested on growing cells of Streptococcus mutans on a glass surface and on a multi-species biofilm grown on saliva-coated hydroxyapatite discs. As expected, the antibacterial activity of manuka 1 (with higher potency of antibacterial activity) was the most important. The two tested honeys weakly inhibited the adherence of S.mutans cells to a glass surface at sub-MIC concentration. Manuka 1 showed a total inhibition of multi-species biofilm at the concentration of 200 μg/ml manuka 2 inhibited biofilm formation weakly at the concentration of 200 μg/ml but firmly at the concentration of 500 μg/ml. Our findings suggest that manuka honeys might be able to reduce oral pathogens within dental plaque. These two honeys appear to be able to control dental biofilm deposit.


The amphipod crustacean Parhyale hawaiensis: An emerging comparative model of arthropod development, evolution, and regeneration.
Recent advances in genetic manipulation and genome sequencing have paved the way for a new generation of research organisms. The amphipod crustacean Parhyale hawaiensis is one such system. Parhyale are easy to rear and offer large broods of embryos amenable to injection, dissection, and live imaging. Foundational work has described Parhyale embryonic development, while advancements in genetic manipulation using CRISPR-Cas9 and other techniques, combined with genome and transcriptome sequencing, have enabled its use in studies of arthropod development, evolution, and regeneration. This study introduces Parhyale development and life history, a catalog of techniques and resources for Parhyale research, and two case studies illustrating its power as a comparative research system. This article is categorized under: Comparative Development and Evolution > Evolutionary Novelties Adult Stem Cells, Tissue Renewal, and Regeneration > Regeneration Comparative Development and Evolution > Model Systems Comparative Development and Evolution > Body Plan Evolution.


A formal, one-pot β-chlorination of primary alcohols and its utilization in the transformation of terpene feedstock and the synthesis of a C2-symmetrical terminal bis-epoxide.
A one-pot transformation of alkan-1-ols into 2-chloroalkan-1-ols is described. As a practical application, terpene-derived primary alcohols were converted into semiochemicals such as olfactory lactones (aerangis lactone, whisky lactone, and cognac lactone) and pheromones (cruentol and ferrugineol). Using heptane-1,7-diol as a bifunctional substrate, the corresponding bis-epoxide was synthesized by bidirectional synthesis in good yield and high enantioselectivity.


High prevalence of haemoglobin S in the closed Egyptian community of Siwa Oasis.
Sickle cell haemoglobinopathy, the most frequent of the hereditary anomalies of haemoglobin, occurs most commonly in individuals of African descent. With a population of about 23 000, Siwa Oasis is situated in the Western Desert of Egypt, close to the Libyan border. It is Egypt's most remote oasis town and the Siwans have developed their own distinct Berber culture. Siwans represent a closed isolated community suffering from various health problems, among which is haemolytic anaemia. This study aimed at screening primary school children of Siwa Oasis for abnormal haemoglobin (Hb) profiles and determining the prevalence of Hb S among them. This descriptive and analytic study included 349 primary school children of both sexes, 153 males and 196 females with a male to female ratio of 1:1.3. Their ages ranged between 6 and 12 years. All subjects were screened for abnormal Hbs using complete blood counts and capillary Hb electrophoresis. Out of a total of 349 primary school children screened, 22% (77/349) were having abnormal Hb profiles, of whom 88% (68/77) had Hb S (ie, sickle cell disorder) constituting 20% of the total population studied. 94% of those having Hb S (64/68) had sickle cell trait (ie, Hb S less than 50%) constituting 18% of the total population screened, while 6% had sickle cell disease, having more than 50% Hb S. The closed Egyptian community in Siwa Oasis has a high frequency of Hb S carriers and so represents one of the targets of prevention programmes to be implemented in Egypt in order to reduce the economic burden of health services for treating patients with sickle cell disease. 1-25/15-1-2014.


Molecular identification and typing of lactobacilli isolated from kefir grains.
Seventeen heterofermentative lactobacilli isolated from kefir grains were characterized by molecular methods. Bacterial isolates were identified by amplification of 16S rRNA gene and analysis by Amplified Ribosomal DNA Restriction Analysis (ARDRA), using the restriction enzymes Hae III, Dde I, and Hinf I. ARDRA analysis of lactobacilli isolates showed, for each enzyme used, a same banding pattern between the heterofermentative lactobacilli and the reference strains Lactobacillus kefir JCM 5818 and Lb. kefir ATCC 8007. Other reference lactobacilli and one homofermentative isolate showed differences in at least one of these patterns. The 16S-23S rRNA spacer region was also used to discriminate the bacterial isolates at the species level. The data obtained from the analysis of spacer region confirmed that sequencing of this genome region is a good tool for a reliable identification of members of Lb. kefir species. Genotyping of isolates was performed by Random Amplified Polymorphic DNA (RAPD-PCR) analysis using M13, Coc, ERIC-2 and 1254 primers. Patterns obtained allowed the differentiation of isolates in three groups. The three clusters showed by RAPD-PCR analysis could be correlated with at least three different strains of Lb. kefir species in the group of heterofermentative lactobacilli isolates obtained from Argentinian kefir grains.


Modelling mixing within the dead space of the lung improves predictions of functional residual capacity.
Routine estimation of functional residual capacity (FRC) in ventilated patients has been a long held goal, with many methods previously proposed, but none have been used in routine clinical practice. This paper proposes three models for determining FRC using the nitrous oxide concentration from the entire expired breath in order to improve the precision of the estimate. Of the three models proposed, a dead space with two mixing compartments provided the best results, reducing the mean limits of agreement with the FRC measured by whole body plethysmography by up to 41%. This moves away from traditional lung models, which do not account for mixing within the dead space. Compared to literature values for FRC, the results are similar to those obtained using helium dilution and better than the LUFU device (Dräger Medical, Lubeck, Germany), with significantly better limits of agreement compared to plethysmography.


Pattern of deliberate self-harm in young people in Karachi, Pakistan.
Globally, suicide remains one of the leading causes of death among individuals aged 10 to 64 years and it ranks between second and fourth among those age 10 to 45 years. Data on suicidal behavior from Pakistan is sparse, especially for children and adolescents. A retrospective descriptive case note study was carried out of all patients under the age of 18 years (n = 69) admitted with deliberate self-harm (DSH) to a university hospital in Karachi, Pakistan. Females (63.8%) outnumbered males by 1.7:1. The mean age of the group was 16 years (+/- 2.2). The most frequent method used was benzodiazepine overdose (30.4%). "Family conflicts" was the main stressor reported by 66.7%. The most frequent diagnosis made was major depressive disorder in 18%. Despite the fact that 98% of our sample was Muslims and suicide is strictly forbidden in Islam, 76.8% expressed their intent to die. Multivariate logistic regression found current stressor to be significantly associated with an intention to die. Patients with nonfatal suicidal behavior form a pool for future suicides. Preventive efforts should be directed at this group. School based programs would be an effective way of addressing this.


Diabrotica virgifera virgifera (Coleoptera: Chrysomelidae) larval feeding behavior on transgenic maize (MON 863) and its isoline.
Diabrotica species (Coleoptera: Chrysomelidae) larval behavior studies have posed a challenge to researchers because of the subterranean life cycle of this pest. To fully understand how the western corn rootworm, Diabrotica virgifera virgifera LeConte, injures the maize, Zea mays L., root system, its behavior must be studied. For example, larvae that can detect an area of the root that has a lower amount of toxin, whether from an insecticide or a transgenic maize plant, have an increased chance of survival. This study assessed D. v. virgifera larval feeding behavior on rootworm-susceptible maize and maize containing a biotechnology-derived trait (MON 863) with resistance to D. v. virgifera first instar feeding. Maize plants were grown in a medium that allowed for direct observation and measurements during feeding of larval stadia. Neonates were placed on maize seedlings, and data were taken at 3, 6, 9, and 12 d postinfestation on resistant and susceptible maize. On rootworm-susceptible maize, neonate larvae aggregated at the root tips and began actively feeding, and then they moved to older root tissue. Conversely, some larvae that ingested Cry 3Bb1 from the resistant maize exhibited no movement. Other larvae on the resistant maize moved continuously, sampling root hairs or root tissue but not actively feeding. The continuously moving larvae had visibly empty guts, suggesting possible nonpreference for the resistant root. This study contributes to our understanding of D. v. virgifera larval behavior and provides insight into questions surrounding the potential evolution of behavioral and biochemical resistance to Cry3Bb1.


Genetic Basis of Positive and Negative Symptom Domains in Schizophrenia.
Schizophrenia is a highly heritable disorder, the genetic etiology of which has been well established. Yet despite significant advances in genetics research, the pathophysiological mechanisms of this disorder largely remain unknown. This gap has been attributed to the complexity of the polygenic disorder, which has a heterogeneous clinical profile. Examining the genetic basis of schizophrenia subphenotypes, such as those based on particular symptoms, is thus a useful strategy for decoding the underlying mechanisms. This review of literature examines the recent advances (from 2011) in genetic exploration of positive and negative symptoms in schizophrenia. We searched electronic databases PubMed, Web of Science, and Cumulative Index to Nursing and Allied Health Literature using key words schizophrenia, symptoms, positive symptoms, negative symptoms, cognition, genetics, genes, genetic predisposition, and genotype in various combinations. We identified 115 articles, which are included in the review. Evidence from these studies, most of which are genetic association studies, identifies shared and unique gene associations for the symptom domains. Genes associated with neurotransmitter systems and neuronal development/maintenance primarily constitute the shared associations. Needed are studies that examine the genetic basis of specific symptoms within the broader domains in addition to functional mechanisms. Such investigations are critical to developing precision treatment and care for individuals afflicted with schizophrenia.


Power Enhancement in High Dimensional Cross-Sectional Tests.
We propose a novel technique to boost the power of testing a high-dimensional vector H : θ = 0 against sparse alternatives where the null hypothesis is violated only by a couple of components. Existing tests based on quadratic forms such as the Wald statistic often suffer from low powers due to the accumulation of errors in estimating high-dimensional parameters. More powerful tests for sparse alternatives such as thresholding and extreme-value tests, on the other hand, require either stringent conditions or bootstrap to derive the null distribution and often suffer from size distortions due to the slow convergence. Based on a screening technique, we introduce a "power enhancement component", which is zero under the null hypothesis with high probability, but diverges quickly under sparse alternatives. The proposed test statistic combines the power enhancement component with an asymptotically pivotal statistic, and strengthens the power under sparse alternatives. The null distribution does not require stringent regularity conditions, and is completely determined by that of the pivotal statistic. As specific applications, the proposed methods are applied to testing the factor pricing models and validating the cross-sectional independence in panel data models.


Permeation of limonene through disposable nitrile gloves using a dextrous robot hand.
The purpose of this study was to investigate the permeation of the low-volatile solvent limonene through different disposable, unlined, unsupported, nitrile exam whole gloves (blue, purple, sterling, and lavender, from Kimberly-Clark). This study utilized a moving and static dextrous robot hand as part of a novel dynamic permeation system that allowed sampling at specific times. Quantitation of limonene in samples was based on capillary gas chromatography-mass spectrometry and the internal standard method (4-bromophenol). The average post-permeation thicknesses (before reconditioning) for all gloves for both the moving and static hand were more than 10% of the pre-permeation ones (P≤0.05), although this was not so on reconditioning. The standardized breakthrough times and steady-state permeation periods were similar for the blue, purple, and sterling gloves. Both methods had similar sensitivity. The lavender glove showed a higher permeation rate (0.490±0.031 μg/cm2/min) for the moving robotic hand compared to the non-moving hand (P≤0.05), this being ascribed to a thickness threshold. Permeation parameters for the static and dynamic robot hand models indicate that both methods have similar sensitivity in detecting the analyte during permeation and the blue, purple, and sterling gloves behave similarly during the permeation process whether moving or non-moving.


[Carrión's disease complicated with severe acute leptospirosis: a case report].
The case of an adult, 56 year old male is reported, from Sihuas (Ancash) who presented at Hospital Nacional Dos de Mayo with fever, jaundice and anemia. In three days of hospitalization, he developed severe anemia (Hb: 11.8 to 6.7 g / dL) and generalized myalgias associated with a sudden worsening jaundice correlated with elevated bilirubin (TB 3.2 to 19.6 mg / dL direct dominance) and general deterioration. Microbiological smear and culture were positive for Bartonella bacilliformis. Subsequent serology (microagglutination) was positive for Lesptospira serovar Pomona. The patient was given specific antibiotic therapy (ceftriaxone and ciprofloxacin), transfused two units of packed red blood cells, improved clinically and was discharged.


Understanding the role of alcohol during rape: the perfect storm of attention, emotion, & expectancies.
Sex offenders and violent offenders in general that were intoxicated at the time of their offense often claim that they were too intoxicated to know 1) what they were doing at the time of the offense and 2) therefore unable to recall the details of the offense situation the next day. What the literature has to say contradicts the claims of sex offenders or violent offenders who claim they were "out of control" and that they do not recall what they did in the offense situation. Alcohol use (mild to moderate consumption) appears to result in 1) alcohol myopia; 2) increased attentional focus on the more salient emotions (whether negative or positive); 3) improved creative thinking and improved attention to the activity at hand; 4) decreased frontal lobe activity (e.g., lack of concern about consequences or morals); 5) is impacted by alcohol expectancies; and 6) does not prevent an individual from being able to recall activity that occurred while intoxicated when provided cues.


α3β1 Integrin Suppresses Prostate Cancer Metastasis via Regulation of the Hippo Pathway.
Existing anticancer strategies focused on disrupting integrin functions in tumor cells or tumor-involved endothelial cells have met limited success. An alternative strategy is to augment integrin-mediated pathways that suppress tumor progression, but how integrins can signal to restrain malignant behavior remains unclear. To address this issue, we generated an in vivo model of prostate cancer metastasis via depletion of α3β1 integrin, a correlation observed in a significant proportion of prostate cancers. Our data describe a mechanism whereby α3β1 signals through Abl family kinases to restrain Rho GTPase activity, support Hippo pathway suppressor functions, and restrain prostate cancer migration, invasion, and anchorage-independent growth. This α3β1-Abl kinase-Hippo suppressor pathway identified α3 integrin-deficient prostate cancers as potential candidates for Hippo-targeted therapies currently under development, suggesting new strategies for targeting metastatic prostate cancer based on integrin expression. Our data also revealed paradoxical tumor suppressor functions for Abl kinases in prostate cancer that may help to explain the failure of Abl kinase inhibitor imatinib in prostate cancer clinical trials. Cancer Res; 76(22); 6577-87. ©2016 AACR.


Structure and dynamics of the multi-domain resuscitation promoting factor RpfB from Mycobacterium tuberculosis.
RpfB is multidomain protein that is crucial for Mycobacterium tuberculosis resuscitation from dormancy. This protein cleaves cell wall peptidoglycan, an essential bacterial cell wall polymer formed by glycan chains of β-(1-4)-linked-N-acetylglucosamine (GlcNAc) and N-acetylmuramic acid (MurNAc) cross-linked by short peptide stems. RpfB is structurally complex being composed of five distinct domains, namely a catalytic, a G5 and three DUF348 domains. Here, we have undertaken a combined experimental and computation structural investigations on the entire protein to gain insights into its structure-function relationships. CD spectroscopy and light scattering experiments have provided insights into the protein fold stability and into its oligomeric state. Using the available structure information, we modeled the entire protein structure, which includes the two DUF348 domains whose structure is experimentally unknown, and we analyzed the dynamic behavior of RpfB using molecular dynamics simulations. Present results highlight an intricate mutual influence of the dynamics of the different protein domains. These data provide interesting clues on the functional role of non-catalytic domains of RpfB and on the mechanism of peptidoglycan degradation necessary to resuscitation of M. tuberculosis.


Native microbiome impedes vertical transmission of Wolbachia in Anopheles mosquitoes.
Over evolutionary time, Wolbachia has been repeatedly transferred between host species contributing to the widespread distribution of the symbiont in arthropods. For novel infections to be maintained, Wolbachia must infect the female germ line after being acquired by horizontal transfer. Although mechanistic examples of horizontal transfer exist, there is a poor understanding of factors that lead to successful vertical maintenance of the acquired infection. Using Anopheles mosquitoes (which are naturally uninfected by Wolbachia) we demonstrate that the native mosquito microbiota is a major barrier to vertical transmission of a horizontally acquired Wolbachia infection. After injection into adult Anopheles gambiae, some strains of Wolbachia invade the germ line, but are poorly transmitted to the next generation. In Anopheles stephensi, Wolbachia infection elicited massive blood meal-induced mortality, preventing development of progeny. Manipulation of the mosquito microbiota by antibiotic treatment resulted in perfect maternal transmission at significantly elevated titers of the wAlbB Wolbachia strain in A. gambiae, and alleviated blood meal-induced mortality in A. stephensi enabling production of Wolbachia-infected offspring. Microbiome analysis using high-throughput sequencing identified that the bacterium Asaia was significantly reduced by antibiotic treatment in both mosquito species. Supplementation of an antibiotic-resistant mutant of Asaia to antibiotic-treated mosquitoes completely inhibited Wolbachia transmission and partly contributed to blood meal-induced mortality. These data suggest that the components of the native mosquito microbiota can impede Wolbachia transmission in Anopheles. Incompatibility between the microbiota and Wolbachia may in part explain why some hosts are uninfected by this endosymbiont in nature.


Sea otter dental enamel is highly resistant to chipping due to its microstructure.
Dental enamel is prone to damage by chipping with large hard objects at forces that depend on chip size and enamel toughness. Experiments on modern human teeth have suggested that some ante-mortem chips on fossil hominin enamel were produced by bite forces near physiological maxima. Here, we show that equivalent chips in sea otter enamel require even higher forces than human enamel. Increased fracture resistance correlates with more intense enamel prism decussation, often seen also in some fossil hominins. It is possible therefore that enamel chips in such hominins may have formed at even greater forces than currently envisaged.


Ear acupoint detection before and after hysteroscopy: is it possible to clarify the representation of the uterus on the outer ear?
In the auricular maps introduced over the past 50 years by the French and Chinese schools, most organs and systems overlap consistently. One exception is the reproductive system, which shows a markedly different somatotopic representation-for example, for the uterus and the ovary. To identify the distribution of points with increased tenderness to pressure or with reduced electrical resistance, on the outer ear of a group of women undergoing hysteroscopy. For diagnostic purposes the auricles of 78 women were examined before and after hysteroscopy using a pain-pressure test and electrical skin resistance test. The points identified were transcribed onto a graphic system called Sectogram. Spatial cluster analysis was used to identify the statistically significant clusters of sectors with a higher concentration of points appearing after hysteroscopy. The points identified after hysteroscopy tend to be concentrated in specific areas not previously recognised and which only partially overlap with the French and Chinese representation of the uterus. When auricular acupuncture is applied to reduce discomfort during hysteroscopy, particular attention must be paid when choosing the points/areas to be stimulated, which are not only those indicated in the Chinese or French maps.


Splicing-factor oncoprotein SRSF1 stabilizes p53 via RPL5 and induces cellular senescence.
Splicing and translation are highly regulated steps of gene expression. Altered expression of proteins involved in these processes can be deleterious. Therefore, the cell has many safeguards against such misregulation. We report that the oncogenic splicing factor SRSF1, which is overexpressed in many cancers, stabilizes the tumor suppressor protein p53 by abrogating its MDM2-dependent proteasomal degradation. We show that SRSF1 is a necessary component of an MDM2/ribosomal protein complex, separate from the ribosome, that functions in a p53-dependent ribosomal-stress checkpoint pathway. Consistent with the stabilization of p53, increased SRSF1 expression in primary human fibroblasts decreases cellular proliferation and ultimately triggers oncogene-induced senescence (OIS). These findings underscore the deleterious outcome of SRSF1 overexpression and identify a cellular defense mechanism against its aberrant function. Furthermore, they implicate the RPL5-MDM2 complex in OIS and demonstrate a link between spliceosomal and ribosomal components, functioning independently of their canonical roles, to monitor cellular physiology and cell-cycle progression.