Predicting perceived risk of crime: a multilevel study.
With a sample of Italians selected from 71 Italian counties (N = 1,868), we performed two multilevel analyses aimed at predicting the perceived risk of crime at local (i.e., in the participants' county of residence) and at societal (i.e., in the context of Italian society) levels. A significant proportion of the variation in local risk perception was at the county level. The following individual variables predicted higher levels of this variable: indirect victimization, the perception of social and physical disorder, being a woman, being poorly educated, and being an older person. Among the ecological predictors, the crime rate and unemployment rate predicted higher levels of local crime risk perception, while the immigrant rate did not. Perceived risk of crime at the societal level did not show significant variation at the county level. Education, being a man, trusting people, and adhesion to post-materialistic values predicted lower levels of societal crime risk perception, while number of sons/daughters and exposure to television news increased it. The limitations and possible development of this study are discussed.


Human-derived Acellular Dermal Matrix Grafts for Treatment of Diabetic Foot Ulcers: A Systematic Review and Meta-analysis.
Treating diabetic foot ulcers (DFUs) requires thorough understanding of available surgical tools. This meta-analysis compares human-derived acellular dermal matrices (H-ADMs) with standard of care (SOC) to evaluate the number of healed ulcers at 12 and 16 weeks and number of days to complete healing. As a secondary outcome, the efficacy of 3 H-ADM subtypes are studied. Two researchers searched PubMed, EMBASE, and The Cochrane Central Register of Controlled Trials for relevant titles from inception through July 2018. Inclusion criteria indicated articles be randomized controlled trials investigating the effects on neuropathic, nonischemic DFUs. Data from 312 DFUs in total were included in the meta-analysis. The results show H-ADMs are more effective in healing patients within a 12-week (3.14; range, 2.04-4.83) and 16-week period (2.35; range, 1.25-4.43) in comparison with SOC. Further, the mean time to complete healing was shorter in the H-ADM group (-2.31 days; range, -2.67 to -1.95 days) in comparison with SOC. Within the subgroups, 2 H-ADMs were associated with a higher likelihood of complete healing within 12 weeks when compared with SOC. The third H-ADM had a point estimate, which suggested superiority over SOC. This study shows H-ADMs are associated with a higher likelihood of complete healing and fewer days to complete healing within a 12-week and 16-week periods when compared with SOC. Also, the commercial products performed similarly.


Lymphokine-like factors produced by human lymphoid cell lines with B or T cell surface markers.
In the present series of experiments we examined the ability of eight continuous cell lines derived from human lymphocytes to release lymphokines into their culture media. We have demonstrated that all could produce a macrophage migration inhibitory factor and a neutrophil chemotactic factor. This ability was independent of the B or T cell origin of the cell lines. As a further extension of previous reports, we report that the migration inhibitory effect does not seem to be due to cytotoxic effects as judged by trypan blue exclusion studies, and more important by the demonstration that the inhibition is reversible. The demonstration that neutrophil chemotactic activity is removable by treatment with a previously described and characterized anti-lymphokine antiserum suggests that this factor may be chemically similar to some of the lymphokines (migration inhibitory factor or chemotactic factor for macrophages) produced by antigen-activated guinea pig lymphocyte cultures. The failure to effect similar removal or inactivation of the macrophage migration inhibitory factor may simply reflect greater interspecies heterogeneity in this factor, or more interestingly, that this does not correspond to "classic" MIF. These results extend previous observations by defining further the capacity of lymphoid cell lines in continuous culture to produce mediators and by characterizing their relationship to conventional lymphokines produced by antigen or mitogen-activated lymphocytes.


A novel model of intracranial meningioma in mice using luciferase-expressing meningioma cells. Laboratory investigation.
Meningioma research has been hindered by the inability to sequentially measure intracranial tumor growth in a cost-effective, efficient manner. Recently, the luciferase gene has been transfected into cancer lines to obtain cells that express the luciferase enzyme, which oxidizes luciferin in a reaction that releases photon energy that can be measured noninvasively by bioluminescence imaging (BLI) systems. The authors describe a mouse model of intracranial meningioma that uses this novel BLI system. The immortal meningioma cell lines CH-157-MN and IOMM-Lee were transfected with luciferase and neomycin phosphotransferase (LucNeo) and selected with G418. These cells were stereotactically implanted at skull base and cerebral convexity locations in nude mice. Animals were imaged for bioluminescence biweekly, and 5 mice underwent magnetic resonance (MR) imaging. Tumors were harvested for immunohistochemical and ultrastructural analysis. The CH-157-MN-LucNeo and IOMM-Lee-LucNeo cell lines were successfully implanted intracranially in mice. The tumor induction rate for CH-157-MN-LucNeo skull base tumors was 90% (36 of 40 procedures). Statistical analysis of CH-157-MN-LucNeo skull base tumor volume measured on MR imaging correlated with the results of BLI showed an R value of 0.900. The tumors exhibited characteristics of aggressive meningiomas by insinuating along arachnoid planes and invading brain. Noninvasive BLI was successfully used to image intracranial meningiomas in mice. The tumors grew in a fashion similar to that of aggressive meningiomas in humans, and exhibited the microscopic, immunohistochemical, and ultrastructural features characteristic of meningiomas. This animal model overcomes the main obstacle in studying intracranial meningiomas by enabling sequential noninvasive tumor measurement in a cost-effective manner.


Vasopressin potentiates mineralocorticoid selectivity by stimulating 11 beta hydroxysteroid deshydrogenase in rat collecting duct.
Arginine vasopressin (AVP) and corticosteroid hormones are involved in sodium reabsorption regulation in the renal collecting duct. Synergy between AVP and aldosterone has been well documented, although its mechanism remains unclear. Both aldosterone and glucocorticoid hormones bind to the mineralocorticoid receptor (MR), and mineralocorticoid selectivity depends on the MR-protecting enzyme 11 beta hydroxysteroid deshydrogenase (11-HSD), which metabolizes glucocorticoids into derivatives with low affinity for MR. We have investigated whether the activity of 11-HSD could be influenced by AVP and corticosteroid hormones. This study shows that in isolated rat renal collecting ducts, AVP increases 11-HSD catalytic activity. This effect is maximal at 10(-8) M AVP (a concentration clearly above the normal physiological range of AVP concentrations) and involves the V2 receptor pathway, while activation of protein kinase C or changes in intracellular calcium are ineffective. The stimulatory effect of AVP on 11-HSD is largely reduced after adrenalectomy, and is selectively restored by infusion of aldosterone, not glucocorticoids. We conclude that this synergy between AVP and aldosterone in controlling the activity of 11-HSD is likely to play a pivotal role in resetting mineralocorticoid selectivity, and hence sodium reabsorption capacities of the renal collecting duct.


[Fetal pseudohypoaldosteronism: a rare cause of hydramnios].
PHA is a rare cause of hydramnios, characterized by increased amniotic fluid levels of aldosterone and sodium. Two distinct genetic entities (PHA type I and PHA type II) are included. Both are stemmed by a target organ defect with diminished renal tubular responsiveness to aldosterone. The AA present a case in which pregnancy resulted in a preterm infant with severe hydramnios, metabolic acidosis, hyponatriemia, hyperkaliemia. Salt and fluid replacement significantly improved clinical and metabolic condition. However a growth deficiency (-2 SDS) persists at follow-up.


Computed Tomography Findings of Ruptured Hepatic Hydatid Cyst into the Pericardial Space: A Case Report.
Hydatidosis, is a parasitic infestation caused by Echinococcus granulosus. Although the disease most commonly affects liver and lungs, almost all organ and tissue involvements are documented. Rupture into pericardial space which may lead to pericardial effusion, pericarditis and pericardial tamponade, can be seen especially in the patients with cardiac hydatidosis. But rupture of a hepatic hydatid cyst into the pericardial space through a transdiaphragmatic fistula is very rare. In this report, we present imaging findings of a type III hepatic hydatid cyst lesion which ruptured spontaneously into pericardial space and caused pericardial effusion.


Radioligand binding, autoradiographic and functional studies demonstrate tachykinin NK-2 receptors in dog urinary bladder.
Tachykinin receptors in the dog bladder were characterized using radioligand binding, functional and autoradiographic techniques. In detrusor muscle homogenates, specific binding of [125l]iodohistidyl neurokinin A (INKA) and [125l]Bolton Hunter eledoisin was reversible, saturable and, to a single class of sites of Kd, 3,6 and 27 nM, respectively. No specific binding of [125l]Bolton Hunter[Sar9, Met (O2)11] substance P occurred. INKA binding was reduced by the peptidase inhibitor bacitracin. The rank potency order of agonists competing for binding of both radioligands indicated interaction at NK-2 sites. NK-2-selective antagonists also competed for INKA binding, with SR 48968, GR 94800, MDL 29913 and the selective agonist [Lys5, MeLeu9, Nle10]-NKA(4-10) showing biphasic binding profiles. Autoradiographic studies revealed specific binding of INKA and [125l]Bolton Hunter eledoisin over detrusor muscle and small arteries. [125l]Bolton Hunter [Sar9, Met (O2)11] SP labeled the intima of arteries and arterioles, but not the detrusor muscle. Tachykinins contracted detrusor muscle strips, with potency order at the carbachol EC15 NKA = kassinin > [Lys5, MeLeu9, Nle10]-NKA(4-10) = neuropeptide gamma = neuropeptide K = NKB > > MDL 28564, with [Sar9, Met(O2)11]-SP ineffective. Shallow concentration-response curves, variable efficacies and inhibition by atropine and mepyramine suggest that other mechanisms may influence contractile responses. Responses to [Lys5, MeLeu9, Nle10]-NKA(4-10) were inhibited competitively by MDL 29913 and MEN 10207 (pA2 values: 6.4 and 5.3, respectively). Antagonism by SR 48968 and GR 94800 was noncompetitive (both pK8 values 8.9). In summary, NK-2-preferring ligands showed superior potency as both binding competitors and contractile agonists, demonstrating that NK-2 receptors mediate detrusor muscle contraction, similar to the human detrusor. Tachykinins may play important roles in the micturition reflex and in regulating detrusor muscle blood flow in the dog.


Effect of industrial processing and storage procedures on oxysterols in milk and milk products.
Oxysterols are products of enzymatic and/or chemical cholesterol oxidation. While some of the former possess broad antiviral activities, the latter mostly originate from the deterioration of the nutritional value of foodstuff after exposure to heat, light, radiation and oxygen, raising questions about their potential health risks. We evaluated the presence of selected oxysterols in bovine colostrum and monitored the evolution of their cholesterol ratio throughout an entire industrial-scale milk production chain and after industrially employed storage procedures of milk powders. We report here for the first time the presence of high levels of the enzymatic oxysterol 27-hydroxycholesterol (27OHC) in concentrations of antiviral interest in bovine colostrum (87.04 ng mL-1) that decreased during the first postpartum days (56.35 ng mL-1). Of note, this oxysterol is also observed in milk and milk products and is not negatively affected by industrial processing or storage. We further highlight an exponential increase of the non-enzymatic oxysterols 7β-hydroxycholesterol (7βOHC) and 7-ketocholesterol (7KC) in both whole (WMPs) and skimmed milk powders (SMPs) during prolonged storage, confirming their role as reliable biomarkers of cholesterol oxidation over time: after 12 months, 7βOHC reached in both SMPs and WMPs amounts that have been found to be potentially toxic in vitro (265.46 ng g-1 and 569.83 ng g-1, respectively). Interestingly, industrial processes appeared to affect the generation of 7βOHC and 7KC differently, depending on the presence of fat in the product: while their ratios increased significantly after skimming and processing of skimmed milk and milk products, this was not observed after processing whole milk and milk cream.


Protection by butyrylcholinesterase against organophosphorus poisoning in nonhuman primates.
Butyrylcholinesterase (BuChE) was examined as an in vivo exogenous scavenger for highly toxic organophosphorus (OP) poisons. Protection studies with equine BuChE were carried out in rhesus monkeys trained to perform a Serial Probe Recognition task. The pharmacokinetics of equine BuChE administered i.v. in rhesus monkeys revealed an elimination T1/2 of approximately 620 hr. Animals given 503 nmol of BuChE i.v. and then challenged with 220 to 260 nmol of soman (two LD50; a lethal dose in untreated animals) all survived with no clinical signs of OP poisoning. Serial Probe Recognition performance was depressed after enzyme administration and at 1 hr postsoman. However, all monkeys performed the task at base-line levels at 8 hr after soman and throughout the remainder of the experimental period. Two different monkeys each were given two doses of sarin, 183 nmol/dose (one LD50) after 460 nmol of BuChE. No signs were observed. A third group of monkeys given 253 or 340 nmol (three and four LD50, respectively) of soman after 460 nmol of BuChE required 1 mg/kg of atropine i.v. 10 min postsoman, but recovered completely within 24 hr. Our results indicate that BuChE has the required properties to function as a biological scavenger to protect against the pharmacological and behavioral toxicity of OP poisons.


Unintentional Injuries in the Three References Laboratories: Sana'a, Yemen.
The aim is to determine the incidence rate of unintentional injuries and its associated factors and determine the pattern of these injuries among laboratory staff in three reference laboratories in Sana'a, Yemen. A cross-sectional study was conducted among laboratory staff in the three reference laboratories in Sana'a, Yemen. A pretested structured questionnaire was used to collect data on the unintentional injuries during the past 12 months including the type of injury. A total of 93 technicians responded and filled the questionnaires. Of the 93 technicians, 51 (54.8%) technicians reported that they had been injured in the past 12 months. Of all injuries, 38% of technicians were caused by needle sticks, 21% by sharp materials other than needles, 15% by hot materials, 15% by exposure to chemicals, and 11% of them by other exposures. Only 18% of injuries were reported to safety officer in the laboratory. Those who had an experience of <5 years were more likely to experience injury in the past 12 months than those who had 5 years of experience or more (odds ratio = 8.3; 95% confidence interval: 2.2, 27.4; P < 0.005). About half of laboratory technicians in Yemen reported that they had been injured in the past 12 months, with the needle stick being the most common cause of injury. Therefore, there is a need for targeted interventions to laboratory technicians to increase their awareness on the risk of injuries in the laboratory. Bio-safety training among laboratory technicians deemed very necessary.


Debugging the intestinal microbiota in IBD.
Besides its role in repelling enteropathogenic infections, the gastrointestinal tract is in intimate contact with commensal microbiota. Tremendous advances have been made in determining the pivotal role of the microbiota in both tissue homeostasis and metabolism, as well as in the initiation and maintenance of inflammatory lesions in inflammatory bowel diseases. A better understanding of human gut microbiota could provide innovative targets for treating and/or curing such common immunopathologies of the gastrointestinal tract.


beta-Glucans in promoting health: prevention against mutation and cancer.
The polysaccharides beta-glucans occur as a principal component of the cellular walls. Some microorganisms, such as yeast and mushrooms, and also cereals such as oats and barley, are of economic interest because they contain large amounts of beta-glucans. These substances stimulate the immune system, modulating humoral and cellular immunity, and thereby have beneficial effect in fighting infections (bacterial, viral, fungal and parasitic). beta-Glucans also exhibit hypocholesterolemic and anticoagulant properties. Recently, they have been demonstrated to be anti-cytotoxic, antimutagenic and anti-tumorogenic, making them promising candidate as pharmacological promoters of health.


Defining early SIV replication and dissemination dynamics following vaginal transmission.
Understanding HIV transmission is critical to guide the development of prophylactic interventions to prevent infection. We used a nonhuman primate (NHP) model with a synthetic swarm of sequence-tagged variants of SIVmac239 ("SIVmac239X") and scheduled necropsy during primary infection (days 3 to 14 after challenge) to study viral dynamics and host responses to the establishment and dissemination of infection following vaginal challenge. We demonstrate that local replication was initiated at multiple sites within the female genital tract (FGT), with each site having multiple viral variants. Local replication and spread in the FGT preceded lymphatic dissemination. Innate viral restriction factors were observed but appeared to follow viral replication and were ineffective at blocking initial viral establishment and dissemination. However, major delays were observed in time to dissemination in animals and among different viral variants within the same animal. It will be important to assess how phenotypic differences affect early viral dynamics.


BC-PROM: validation of a patient-reported outcomes measure for patients with breast cancer.
Key issues of treatment for patients with breast cancer such as patient satisfaction with treatments, compliance, and some side effects are essential for evaluating quality of life by patient-reported outcomes in clinical trials. The study aimed to develop and evaluate a specific patient-reported measure which included physical, psychological, social, and therapeutic domain for assessing the survival of patients with breast cancer.The pool of items was drafted after a theoretical revision and cognitive interviews with women with breast cancer. The draft scale was formed after the adjustment of the items and dimensions, and the selected items were submitted to expert's judgments. Five statistical methods were used to select these items by 2 validation samples. The final scale was administered to a sample of 417 patients from 8 hospitals and 135 controls for reliability, validity, and responsive analyses.The final BC-PROM consisted of 52 items, 13 subdomains, and 4 domains, being developed after preexamination and formal examination. Cronbach alpha coefficient was 0.902 and 0.712 for the full scale and therapeutic domain. The structural validity results showed that the multidimensional measurement of the scale fulfilled expectations. Differences in the BC-PROM mean scores were significant between cancer patients and healthy participants in 13 subdomains (P < .05), indicating good responsiveness. Among the sample survey of patients, the scale copy acceptance rate was 98.2%, completion rate 94.6%, and average filling time 10 minutes.The new and reliable BC-PROM was developed in patients with breast cancer and applied to clinical treatment evaluation and clinical trials for such patients.


Molecular studies on bromovirus capsid protein. II. Functional analysis of the amino-terminal arginine-rich motif and its role in encapsidation, movement, and pathology.
The N-terminal region of the brome mosaic bromovirus (BMV) coat protein (CP) contains an arginine-rich motif that is conserved among plant and nonplant viruses and implicated in binding the RNA during encapsidation. To elucidate the functional significance of this conserved motif in the BMV CP, a series of deletions encompassing the arginine-rich motif was introduced into a biologically active clone of BMV RNA3, and their effect on replication, encapsidation, and infection in plants was examined. Analysis of infection phenotypes elicited on Chenopodium quinoa revealed the importance of the first 19 N-proximal amino acids of BMV CP in encapsidation and pathogenicity. Inoculation of C. quinoa with three viable variants of BMV RNA3 lacking the first 11, 14, and 18 N-terminal amino acids of the CP resulted in the development of necrotic local lesions and restricted the spread of infection to inoculated leaves. Progeny analysis from symptomatic leaves revealed that, in each case, virus accumulation was severely affected by the introduced mutations and each truncated CP differed in its ability to package genomic RNA. In contrast to these observations in C. quinoa, none of the CP variants was able to establish either local or systemic infections in barley plants. The intrinsic role played by the N-terminal arginine-rich motif of BMV CP in packaging viral RNAs and the interactions between the host and the truncated CPs in modulating symptom expression and movement are discussed.


Maintenance of fetal murine pulmonary microvasculature in heart-lung en bloc whole organ culture.
The authors have previously shown that murine fetal lungs can be maintained in serum-free whole organ culture and that airway ligation accelerates lung development. In spite of extensive use of lung organ culture systems, the vasculature of the unperfused lung in organ culture has not been studied. The aim of the present study was to compare organ cultures of heart-lung blocks with continuous perfusion of the pulmonary vasculature to those without perfusion, ie, whole lungs cultured without the attached heart. Time-dated pregnant CD-1 mice were killed on gestational day (Gd) 14. The fetuses were removed via laparotomy. Heart-lung blocks and whole lungs without the heart were excised under sterile conditions and cultured in BGJb media. Some of the heart-lungs and whole lungs underwent tracheal ligation whereas others were left with the trachea unligated allowing free egress of airway fluid. After 7 days, the cultured organs were processed for histology, ultrastructural analysis, and immunohistochemistry. (1) Lungs were fixed in 10% formalin, paraffin embedded, and processed for routine H&E staining. (2) Lungs were fixed in 2.5% glutaraldehyde in cacodylate buffer and processed for transmission electron microscopy. (3) Lungs were embedded in CRYOform and flash frozen for immunohistochemical localization of PECAM-1 (CD31) (PECAM-1, Platelet endothelial cell adhesion molecule-1, a selective endothelial cell marker). Our daily observations of the cultured organs showed that the heart maintained synchronized beating for all 7 days in culture. Perfusion of the pulmonary microvasculature was demonstrated. Light microscopically, H&E sections showed that fresh fetal Gd14 pseudoglandular lungs (time-zero) had a defined capillary network, which was more centrally localized and peripherally less developed. The presence of more numerous lung capillaries in the cultured heart-lung blocks was noted when compared with cultured lungs alone. Ultrastructurally, endothelial cells with intact structural integrity were identified only in cultured whole lungs with hearts. Immunohistochemical staining of the whole lungs with rat antimurine PECAM-1 monoclonal antibody performed on cryosections showed the presence of vasculature by specific PECAM-1 localization on endothelial cells. PECAM-1 labeling of capillaries was noted in Gd14 (time-zero) lungs. In addition, the lungs cultured with hearts, ie, perfused lungs, showed more well defined, distinct capillary networks stained with PECAM-1 antibody than unperfused lungs without hearts. Our results showed that microvasculature is present in murine fetal lungs at Gd14. After 7 days in organ culture, the maintenance of lung microvasculature was confirmed histologically, ultrastructurally, and immunohistochemically. The microvasculature in whole lungs cultured as perfused/beating heart-lung blocks was better maintained than the microvasculature of unperfused whole lungs cultured without hearts. A perfused whole lung organ culture model is attractive because the lung architecture is better maintained and may be useful in lung developmental studies as it mimics the in situ heart-lung functional physiological relationship.


Surveillance by oral fluid of drugs subject to misuse among individuals under arrest.
Background: Between 1988 and 2013 the U.S. government conducted surveillance of national drug misuse use trends by collecting voluntary urine specimens from individuals under arrest in major counties. It was discontinued for financial reasons. The program was the only national survey that used a bioassay to measure drug use. Other national drug surveys continue to be based entirely on self-reports of drug use.Objective: Given the current opioid and incipient methamphetamine epidemics, this study aimed to demonstrate the feasibility of surveilling drugs subject to misuse among individuals under arrest using oral fluid collected anonymously by jail staff in one U.S. county. This method has never been previously employed with an offender population.Methods: The subjects were adults arrested for any reason and booked in one Midwest county jail in the U.S. between July 2019 - January 2020 (N = 196; 145 males). Oral fluid specimens were provided for research purposes voluntarily and anonymously.Results: 79% of individuals approached consented to participation. The most frequently detected drugs were cannabis (53%), methamphetamine (27%), cocaine (9%) and opioids (11%). Further, 74% tested positive for at least one drug; 36% tested positive for at least one illegal drug, 10% tested positive for at least one possibly illegal drug, and 54% tested positive for at least one legal drug (predominantly cannabis). (Tests for nicotine and ethanol were not included.)Conclusion: The feasibility of collecting oral fluid from individuals under arrest in a jail setting to measure the prevalence of drugs subject to misuse was demonstrated.


Juicy fruit and creepy crawlies: an electrophysiological study of the implicit Go/NoGo association task.
The Go/NoGo association task (GNAT) has been used in behavioral studies to measure the strength of association between different category groups and two poles of an evaluative dimension. However, reaction time data do not provide information about the neural time course of such associative information. We investigated event-related brain potentials (ERPs) elicited when participants were required to respond (Go) or withhold a response (NoGo) according to task instructions. Task instructions paired words from one of two taxonomic categories (fruit/bugs) with either pole of an evaluative dimension (good/bad). Within a given run, Go responses were assigned to one of the categories and one evaluative dimension. ERPs showed an increased negativity over frontal sites to NoGo as compared to Go responses. Moreover, NoGo minus Go difference waves showed that the N200 effect was delayed in trials within incongruent blocks (e.g., "Press if a bug word or a good word") as compared to trials within congruent blocks (e.g., "Press if a bug word or a bad word"). These results suggest that such associative attitude information is available at a very early stage of processing, less than 250 ms after seeing a fruit or a bug word. This finding is further discussed with respect to alternative explanations of the behavioral effect.


The innervation of taste buds in the soft palate and circumvallate papilla of the rat as revealed by the zinc iodide-osmium tetroxide technique.
The taste buds in the soft palate and the circumvallate papillae of the rat were investigated by the zinc iodide-osmium tetroxide technique. In addition, electron micrographs of taste buds stained with this method were presented for the first time. Differences in taste bud structures were found between the examined regions. The taste buds of the soft palate showed a complicated plexus of intragemmal nerve fibers. Some fibers exhibited terminal polymorphic swellings. Single branches could be traced close to the space of the taste pore. In the soft palate, the taste bud cells remained unstained, whereas in the circumvallate papillae of the tongue, a subpopulation of taste bud cells could be selectively stained and the intragemmal nerve fibers were characterized by large varicosities. The morphological dissimilarities between the taste buds of the investigated regions might be explained by their functional characteristics, or possibly their varying affinities to the taste qualities. Electron microscopic investigation of the stained circumvallate papillae revealed that the electron-dense reaction product had primarily accumulated in a subpopulation of light cells. Dark cells exhibited only a slight labelling. In detail, the precipitate was found loosely distributed in the cytoplasm as well as the nuclei of the cells, and particularly concentrated at the membranes of light vacuoles, this probably being profiles of dilated endoplasmic reticulum. A few roundish accumulations of precipitate were seen in the cytoplasm of taste bud cells, which showed no intensive light microscopic staining. Labelled material was also found within the taste pores outside the apical processes of the cells. The present findings indicate that the zinc iodide-osmium tetroxide technique is applicable to neuroanatomical studies of taste buds.


Predicting Risk for Suicide: A Preliminary Examination of Non-Suicidal Self-Injury and the Acquired Capability Construct in a College Sample.
The interpersonal psychological theory of suicide provides a useful framework for considering the relationship between non-suicidal self-injury and suicide. Researchers propose that NSSI increases acquired capability for suicide. We predicted that both NSSI frequency and the IPTS acquired capability construct (decreased fear of death and increased pain tolerance) would separately interact with suicidal ideation to predict suicide attempts. Undergraduate students (N = 113) completed self-report questionnaires, and a subsample (n = 66) also completed a pain sensitivity task. NSSI frequency significantly moderated the association between suicidal ideation and suicide attempts. However, in a separate model, acquired capability did not moderate this relationship. Our understanding of the relationship between suicidal ideation and suicidal behavior can be enhanced by factors associated with NSSI that are distinct from the acquired capability construct.


Stroke patients in nursing homes: eating, feeding, nutrition and related care.
The purpose of this study was to explore eating, feeding and nutrition among stroke patients in nursing homes as described by their nurses and by assessments. Registered Nurses were interviewed about an individual stroke patient's state of health, care needs and nursing care received and nursing records were reviewed. Information on eating, feeding and nutrition was extracted from the interviews and nursing records. A comprehensive instrument, the Resident Assessment Instrument, was also used to assess these patients' state of health. The domains of eating, feeding and nutrition were focused on in this study. Manifest content analysis was used. The results showed that more than 80% of the stroke patients in nursing homes were assessed as having some sort of dependence in eating. According to the Registered Nurses, 22 out of 40 patients demonstrated different eating disabilities. The number of eating disabilities in individual patients ranged from 1 to 7, which emphasized the complexity of eating disabilities in stroke patients. Dysphagia was reported in almost one-fourth of the patients and 30% were described and/or assessed as having a poor food intake or poor appetite. The Registered Nurses' descriptions of the eating disabilities, nutritional problems and their care were often vague and unspecific. Only six weights were documented in the nursing records and there were no nutritional records. The findings highlight the importance of making careful observations and assessments, and of maintaining documentation about eating and nutrition early after a patient's arrival in the nursing home to enable appropriate care and promotion of health.


Delineating ion-ion interactions by electrostatic modeling for predicting rhizotoxicity of metal mixtures to lettuce Lactuca sativa.
Effects of ion-ion interactions on metal toxicity to lettuce Lactuca sativa were studied based on the electrical potential at the plasma membrane surface (ψ0 ). Surface interactions at the proximate outside of the membrane influenced ion activities at the plasma membrane surface ({M(n+)}0). At a given free Cu(2+) activity in the bulk medium ({Cu(2+)}b), additions of Na(+), K(+), Ca(2+), and Mg(2+) resulted in substantial decreases in {Cu(2+)}0. Additions of Zn(2+) led to declines in {Cu(2+)}0, but Cu(2+) and Ag(+) at the exposure levels tested had negligible effects on the plasma membrane surface activity of each other. Metal toxicity was expressed by the {M(n+)}0 -based strength coefficient, indicating a decrease of toxicity in the order: Ag(+) > Cu(2+) > Zn(2+). Adsorbed Na(+), K(+), Ca(2+), and Mg(2+) had significant and dose-dependent effects on Cu(2+) toxicity in terms of osmolarity. Internal interactions between Cu(2+) and Zn(2+) and between Cu(2+) and Ag(+) were modeled by expanding the strength coefficients in concentration addition and response multiplication models. These extended models consistently indicated that Zn(2+) significantly alleviated Cu(2+) toxicity. According to the extended concentration addition model, Ag(+) significantly enhanced Cu(2+) toxicity whereas Cu(2+) reduced Ag(+) toxicity. By contrast, the response multiplication model predicted insignificant effects of adsorbed Cu(2+) and Ag(+) on the toxicity of each other. These interactions were interpreted using ψ0, demonstrating its influence on metal toxicity.


Neurohistologic observations of the Cebus apella monkeys soft palate mucosa.
A neurohistological observation was done in the solf palate mucosa of the Cebus apella monkey. Six mucosa were employed and were removed after perfusion of each animal, with 10% formalin solution, through the external carotid artery of the right side. The mucosa was removed together with the muscular layer and salivary glands. The histologic analysis was performed and therefore the pieces were prepared by the "De Castro" technic of silver impregnation. The material was embedded in the vertical sense to allow frontal sections with the thickness of 8 micra. Our findings allow the following conclusions: a) the mucosa innervation of the soft palate is essencially done by the branches of the lesser palatine nerve; b) the free nerve endings of the soft palate mucosa have a great variation in the form and size and are abundant; c) the superficial fibres are related to the general sensibility and the deepest are directly connected to the innervation of the salivary glands.


Hereditary hemorrhagic telangiectasia: two distinct ENG deletions in one family.
Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disorder characterized by aberrant vascular development. Mutations in endoglin (ENG) or activin A receptor type II-like 1 (ACVRL1) account for around 90% of HHT patients, 10% of those are large deletions or duplications. We report here the first observation of two distinct, large ENG deletions segregating in one pedigree. An ENG exon 4-7 deletion was observed in a patient with HHT. This deletion was identified in several affected family members. However, some affected family members had an ENG exon 3 deletion instead. These deletions were detected by multiplex ligation-dependent probe amplification and confirmed by mRNA sequencing and an oligo-CGH array. Linkage analysis revealed that one individual with the exon 3 deletion inherited the same chromosome from his mother who has the exon 4-7 deletion. This finding has important clinical implications because it shows that targeted family-specific mutation analysis for exon deletions could have led to the misdiagnosis of some affected family members.


Channel defect detection in food packages using integrated backscatter ultrasound imaging.
Hermetically-sealed flexible food packages require very effective seal integrity testing to extend the shelf stability of thermally processed food. The initial goal of this study was to estimate the detection limits of laboratory-generated channels which simulate defects in food packages using pulse-echo ultrasonic imaging techniques. Packages with well characterized (via transmission optical microscopy) laboratory-generated channels that simulate defects with diameters between 9 and 325 microm in the seal plane traversing the major axis of the heat seal were generated in heat-sealed microwavable retort-pouch plastic film (trilaminate). Pulse-echo techniques in the 13-17 MHz center frequency range were investigated. The samples were examined with a conventional B-mode imaging technique, which was found to be inadequate for subwavelength imaging of the types of typical channel defects found in shelf-stable food packages. Based on conventional B-mode image features, a new goal of this study was established to develop and evaluate an imaging technique which would exhibit subwavelength imaging capabilities. The new imaging technique called backscattered amplitude integral (BAI) is introduced here. It was observed that BAI-mode imaging has the ability for subwavelength detection of channel defects, e.g., detection of a 10-microm diameter channel defect at a center frequency of 13.1 MHz (lambda=182 microm).


APC Moonlights to Prevent Wnt Signalosome Assembly.
The scaffold protein APC has a well-known function in ensuring β-catenin destruction. In this issue of Developmental Cell, Saito-Diaz et al. (2018) uncover another role for APC in Wnt signaling: to prevent clathrin-dependent signalosome formation in the absence of ligand.


Tips of the trade #36. Measurement of intramedullary rod distal locking screws.
A technique that is used to measure the length of intramedullary rod distal locking screws is described. This procedure does not require the use of standard depth gauges.


Rationing access to care to the medically uninsured: the role of bureaucratic front-line discretion at large healthcare institutions.
Medically uninsured patients seeking nonemergency care are not guaranteed access to services at most healthcare institutions. They must first register with a clerk who could require a deposit and/or payment on an outstanding debt. This study examines the factors that influence whether nonmedical bureaucratic staff sign in or turn away uninsured patients who cannot meet prepayment requirements. The study was conducted at a for-profit, a not-for-profit, and a public healthcare institution in a metropolitan area. The authors explored the relevant policy environment through interviews with senior administrators and a review of documents pertaining to the management of self-pay patients. Then they examined how policies affecting access were implemented through in-depth, semistructured, audiotaped interviews with 55 front-line clerical personnel. At all 3 institutions, policies were ambiguous about what to do when uninsured patients cannot afford required prepayments. Seventy-one percent of staff reported they do not turn patients away; the remainder stated that on occasion they do. A variety of rationales were provided for how decisions are made. Those with the lowest-level positions were significantly more likely to be sympathetic to indigent patients and less likely to report turning patients away. Consistent with other studies of front-line bureaucracies indicating that low-level personnel who interface with clients make discretionary decisions, particularly when organizations pursue potentially conflicting priorities, this preliminary investigation found that nonmedical personnel play a significant role in decisions affecting access to care for medically indigent patients.


[Noradrenaline concentration and monoamine oxidase activity in regions of the brain and the livers of hyperoxic rats].
Content of noradrenaline and the activity of mitochondrial monoamineoxidase (MAO) were studied in cerebral cortex, hypothalamus, mesencephalon, medulla oblongata and liver tissue after the oxygen treatment under pressure (4 atm) within 1 hr. Content of noradrenaline was decreased in all the brain and liver tissues studied. The most distinct decrease was found in hypothalamus and the less marked one -- in liver tissue. The MAO activity was increased slightly in hypothalamus; it was unaltered in cerebral cortex (as compared with control), decreased distinctly in mesencephalon and inhibited by 100% in medulla oblongata. In the general brain preparation the MAO activity was considerably decreased. The decrease of the enzyme was less pronounced in liver tissue as compared with brain.


Social escape behaviors in children with fragile X syndrome.
Social escape behavior is a common behavioral feature of individuals with fragile X syndrome (fraX). In this observational study, we examined the effect of antecedent social and performance demands on problem behaviors in four conditions: face-to-face interview, silent reading, oral reading and a singing task. Results showed that problem behaviors were significantly more likely to occur during the interview and singing conditions. Higher levels of salivary cortisol were predictive of higher levels of fidgeting behavior and lower levels of eye contact in male participants. There were no associations between level of FMRP expression and social escape behaviors. These data suggest that specific antecedent biological and environmental factors evoke social escape behaviors in fragile X syndrome.


Conduction Electrohydrodynamics with Mobile Electrodes: A Novel Actuation System for Untethered Robots.
Electrohydrodynamics (EHD) refers to the direct conversion of electrical energy into mechanical energy of a fluid. Through the use of mobile electrodes, this principle is exploited in a novel fashion for designing and testing a millimeter-scale untethered robot, which is powered harvesting the energy from an external electric field. The robot is designed as an inverted sail-boat, with the thrust generated on the sail submerged in the liquid. The diffusion constant of the robot is experimentally computed, proving that its movement is not driven by thermal fluctuations, and then its kinematic and dynamic responses are characterized for different applied voltages. The results show the feasibility of using EHD with mobile electrodes for powering untethered robots and provide new evidences for the further development of this actuation system for both mobile robots and compliant actuators in soft robotics.


Prostate cancer treatment for economically disadvantaged men: a comparison of county hospitals and private providers.
The authors compared the types of treatments prostate cancer patients received from county hospitals and private providers as part of a statewide public assistance program. This was a cohort study of 559 men enrolled in a state-funded program for low-income patients known as Improving Access, Counseling, and Treatment for Californians With Prostate Cancer (IMPACT). Multinomial regression was used to compare types of treatments patients received from different providers. Between 2001 and 2006, 315 (56%) participants received treatment from county hospitals and 244 (44%) from private providers. There were no significant between-group differences with respect to age (P = .22), enrollment year (P = .49), Charlson comorbidity index (P = .47), Gleason sum (P = .33), clinical T stage (P = .36), prostate-specific antigen (P = .39), or D'Amico risk criteria (P = .45). Participants treated by private providers were more likely than those treated in county hospitals to be white (35% vs 10%, P < .01) and less likely to undergo surgery (29% vs 54%, P < .01). Multinomial regression analyses showed that participants treated by private providers were nearly 2(1/2) times more likely than those treated by public providers to receive radiotherapy (odds ratio [OR], 2.36; 95% confidence interval [CI], 1.37-4.07) and >4(1/2) times more likely to receive primary androgen deprivation (OR, 4.71; 95% CI, 2.15-10.36) than surgery. In this economically disadvantaged cohort, prostate cancer treatments differed significantly between county hospitals and private providers. These data reveal substantial variations in treatment patterns between different types of healthcare institutions that-given the implications for health policy and quality of care-merit further scrutiny.


Muscle-specific function of the centronuclear myopathy and Charcot-Marie-Tooth neuropathy-associated dynamin 2 is required for proper lipid metabolism, mitochondria, muscle fibers, neuromuscular junctions and peripheral nerves.
The ubiquitously expressed large GTPase Dynamin 2 (DNM2) plays a critical role in the regulation of intracellular membrane trafficking through its crucial function in membrane fission, particularly in endocytosis. Autosomal-dominant mutations in DNM2 cause tissue-specific human disorders. Different sets of DNM2 mutations are linked to dominant intermediate Charcot-Marie-Tooth neuropathy type B, a motor and sensory neuropathy affecting primarily peripheral nerves, or autosomal-dominant centronuclear myopathy (CNM) presenting with primary damage in skeletal muscles. To understand the underlying disease mechanisms, it is imperative to determine to which degree the primary affected cell types require DNM2. Thus, we used cell type-specific gene ablation to examine the consequences of DNM2 loss in skeletal muscle cells, the major relevant cell type involved in CNM. We found that DNM2 function in skeletal muscle is required for proper mouse development. Skeletal muscle-specific loss of DNM2 causes a reduction in muscle mass and in the numbers of muscle fibers, altered muscle fiber size distributions, irregular neuromuscular junctions (NMJs) and isolated degenerating intramuscular peripheral nerve fibers. Intriguingly, a lack of muscle-expressed DNM2 triggers an increase of lipid droplets (LDs) and mitochondrial defects. We conclude that loss of DNM2 function in skeletal muscles initiates a chain of harmful parallel and serial events, involving dysregulation of LDs and mitochondrial defects within altered muscle fibers, defective NMJs and peripheral nerve degeneration. These findings provide the essential basis for further studies on DNM2 function and malfunction in skeletal muscles in health and disease, potentially including metabolic diseases such as diabetes.


Transition metals-incorporated zeolites as environmental catalysts for indoor air ozone decomposition.
The present study aimed to prepare catalysts of Fe- and Cu-loaded zeolite via ion-exchange technique using dilute solutions of metal nitrate precursors followed by calcination at 600°C in the air for 4 h. Commercial zeolite ZSM-5 with specific surface area of 400 m2/g and diameter particle of 1.2-2 mm was used as a parent support. The prepared catalysts were characterized by Fourier transform infrared spectroscopy analysis. The IR absorbed bands of Cu-ZSM-5 and Fe-ZSM-5 revealed a shift in the frequency and a reduction in the intensity framework. This indicates that both catalysts have a significant change in the number of the zeolite structure bonds. The catalytic activity of the prepared materials compared to the parent zeolite was evaluated for the catalytic ozone decomposition. The ozone stream of the initial concentration (13 g/m3) with air flow rate (Q) of 0.18 m3/h was passed through a glass jacket column reactor filled with a fixed bed of 40 g zeolites. It was showed that the ozone removal efficiency by Cu-ZSM-5 and Fe-ZSM-5 was obviously higher than that found with the parent ZSM-5. In terms of O3 removal efficiency, zeolite samples could be ranked as follows: Fe-ZSM-5 > Cu-ZSM-5> parent ZSM-5. The results revealed about 90% O3 removal efficiency for Fe-ZSM-5 and 70% for Cu-ZSM-5 as compared to nearly 40% for the parent zeolite. Consequently, the incorporation of Fe and Cu metals onto the zeolite surface plays a key role for enhancing the gaseous ozone elimination.


An exceptional cause of polyuria-polydipsia syndrome in a 10-year-old boy.
Polyuria-polydipsia syndrome is a frequent symptom in pediatrics, primarily attributed to diabetes mellitus. In the context of diabetes insipidus, this syndrome can stem from central or nephrogenic factors. Sjögren's syndrome, an uncommon autoimmune disease in children, can affect multiple organs. Kidney involvement as described in adults is usually related to glomerular or tubular impairment, often linked to distal tubular acidosis. As a kidney involvement during childhood, Sjögren's syndrome has rarely been reported. Hereby, we present the case of Sjögren's syndrome revealed by polyuria-polydipsia syndrome in a 10-year-old boy.


MTA-enriched nanocomposite TiO(2)-polymeric powder coatings support human mesenchymal cell attachment and growth.
The objective of the study described in this paper was the development of novel polymer/ceramic nanocomposite coatings for implants through the application of ultrafine powder coating technology. Polyester resins were combined with µm-sized TiO(2) (25%) as the biocompatibility agent, nTiO(2) (0.5%) as the flow additive and mineral trioxide aggregates (ProRoot® MTA, 5%) as bioactive ceramics. Ultrafine powders were prepared and applied to titanium to create continuous polymeric powder coatings (PPCs) through the application of electrostatic ultrafine powder coating technology. Energy dispersive x-ray analysis confirmed that MTA had been incorporated into the PPCs, and elemental mapping showed that it had formed small clusters that were evenly distributed across the surface. Scanning electron microscopy (SEM) revealed continuous and smooth, but highly textured surface coatings that contrasted with the scalloped appearance of commercially pure titanium (cpTi) controls. Atomic force microscopy revealed intricate nano-topographies with an abundance of submicron-sized pits and nano-projections, evenly dispersed across their surfaces. Inverted fluorescence microscopy, SEM and cell counts showed that human embryonic palatal mesenchymal cells attached and spread out onto PPC and MTA-enriched PPCs within 24 h. Mitochondrial enzyme activity measured viable and metabolically active cells on all of the surfaces. After 72 h of growth, cell counts and metabolic activity were significantly higher (P < 0.05) on the grey-MTA enriched PPC surfaces, than on unmodified PPC and cpTi. The novel polymer/ceramic nanocomposites that were created with ultrafine powder coating technology were continuous, homogenous and nano-rough coatings that enhanced human mesenchymal cell attachment and growth.


Pathomechanic determinants of posttraumatic arthritis.
The etiology of posttraumatic arthritis is poorly understood. One possible mechanism involves a mechanical insult to the cartilage matrix that affects chondrocyte function. To better understand the etiology of posttraumatic arthritis, pathomechanic changes in articular contact mechanics resulting from injury during physiologic motion and loading need to be determined. Previous studies of injury-associated changes in articular contact mechanics, using static testing methods, have measured relatively modest increases in contact stresses. Static testing cannot measure transient loads associated with motion or loading rates. This testing method poorly simulates normal viscoelastic cartilage properties, and accounts for contact stress changes in a single or limited number of joint positions. In this study, time-variant contact stresses in two ankles with an anterolateral stepoff were measured during quasiphysiologic motion and loading. Contact stresses were integrated over the entire range of motion to estimate pathomechanic loads that accumulate over the entire motion cycle. Numerical techniques were applied to time-variant contact stress data to calculate contact stress directional gradients and contact stress rates of change. Contact stress directional gradients and rates of change were integrated over the complete motion cycle to estimate whole-cycle accumulation of these potential pathomechanic parameters.


Elevation of pro-inflammatory cytokine levels following anti-resorptive drug treatment is required for osteonecrosis development in infectious osteomyelitis.
Various conditions, including bacterial infection, can promote osteonecrosis. For example, following invasive dental therapy with anti-bone resorptive agents, some patients develop osteonecrosis in the jaw; however, pathological mechanisms underlying these outcomes remain unknown. Here, we show that administration of anti-resorptive agents such as the bisphosphonate alendronate accelerates osteonecrosis promoted by infectious osteomyelitis. Potent suppression of bone turnover by these types of agents is considered critical for osteonecrosis development; however, using mouse models we found that acceleration of bone turnover by teriparatide injection did not prevent osteonecrosis but rather converted osteoclast progenitors to macrophages expressing inflammatory cytokines, which were required for osteonecrosis development. In fact, we demonstrate that TNFα-, IL-1α/β- or IL-6-deficient mice as well as wild-type mice administered a TNFα-inhibitor were significantly resistant to development of osteonecrosis accompanying infectious myelitis, even under bisphosphonate treatment. Our data provide new insight into mechanisms underlying osteonecrosis and suggest new ways to prevent it.


Chemotherapy prior to hepatic resection for colorectal liver metastases: helpful until harmful?
Improved efficacy of chemotherapy for treatment of colorectal liver metastases (CLM) has renewed interest in the use of systemic treatment as part of a 'potentially curative' treatment plan for patients with CLM. Controversy exists regarding potential hepatotoxicity of therapy delivered before liver resection. Medline reports of pathologic changes in liver and tumor, specific chemotherapy types and clinical outcomes were examined. Hepatic steatosis without inflammation (simple steatosis) may occur with chemotherapy treatment, but hepatic resection can be performed safely even in patients with severe (>30%) steatosis. Steatohepatitis is associated with irinotecan therapy and an increased risk for liver failure and death after hepatic resection. Hepatic sinusoidal obstruction can occur with oxaliplatin treatment and appears to increase in severity with prolonged treatment (>6 cycles). Bevacizumab can be used safely when discontinued >5 weeks before liver resection. Importantly, bevacizumab decreases the incidence and severity of sinusoidal injury with oxaliplatin therapy. Pathologic response is improved with the addition of bevacizumab and is evolving as an independent predictor of long-term survival. Chemotherapy-related liver injuries are regimen-specific. Targeted therapy combined with cytotoxic therapy is safe and most effective. With the use of limited chemotherapy combining appropriately selected agents, the risk of surgical complications can be minimized and the overall effect and benefits of treatment optimized.


Toward a model for assessing level of personality functioning in DSM-5, part I: a review of theory and methods.
Personality disorders are associated with fundamental disturbances of self and interpersonal relations, problems that vary in severity within and across disorders. This review surveyed clinician-rated measures of personality psychopathology that focus on self-other dimensions to explore the feasibility and utility of constructing a scale of severity of impairment in personality functioning for DSM-5. Robust elements of the instruments were considered in creating a continuum of personality functioning based on aspects of identity, self-direction, empathy, and intimacy. Building on preliminary findings (Morey et al., 2011 /this issue), the proposed Levels of Personality Functioning will be subjected to extensive empirical testing in the DSM-5 field trials and elsewhere. The resulting version of this severity measure is expected to have clinical utility in identifying personality psychopathology, planning treatment, building the therapeutic alliance, and studying treatment course and outcome.


No clinical effect of prosthesis-patient mismatch after transcatheter versus surgical aortic valve replacement in intermediate- and low-risk patients with severe aortic valve stenosis at mid-term follow-up: an analysis from the NOTION trial.
Prosthesis-patient mismatch (PPM) after surgical aortic valve replacement (SAVR) for severe aortic valve stenosis (AVS) is common, but less common after transcatheter aortic valve replacement (TAVR) in patients considered at high risk for death after surgery. The objectives of this study were to determine incidence and clinical effect of PPM after SAVR and TAVR in a primarily low-risk patient group. Patients 70 years or older with severe isolated AVS, regardless of predicted operative mortality risk, were consecutively randomized 1:1 to TAVR using a self-expandable bioprosthesis (n = 145) or SAVR (n = 135). Post-procedure PPM was graded after 3 months as follows: Not present-mild, if indexed effective orifice area (iEOA) >0.85 cm2/m2, moderate, if 0.65 cm2/m2 < iEOA ≤ 0.85 cm2/m2 and severe, if iEOA ≤0.65 cm2/m2. Outcomes were major adverse cardiac and cerebrovascular events (MACCE, e.g. composite rate of all-cause death, stroke, myocardial infarction or valve reintervention), cardiac-related hospitalizations and New York Heart Association (NYHA) functional class after 2 years. The incidence and the severity of PPM were significantly lower after TAVR compared with SAVR (severe, moderate, none-mild 14.0, 35.5, 50.4 vs 33.9, 36.7, 29.4%; P<0.001). PPM resulted in similar higher mean valve gradients at 3 months for both groups. Baseline characteristics related to severe PPM were younger age, absence of diabetes mellitus, lower mortality-risk score for TAVR, and younger age and higher body mass index for SAVR. At 2 years, there were numerical but no statistically significant differences between both TAVR and SAVR patients with severe and no severe PPM for MACCE (0.0 vs 12.8% for TAVR; P = 0.13, and 13.5 vs 7.0% for SAVR; P = 0.27), number of cardiac-related hospitalizations (mean ± standard deviation 0.4 ± 0.6 vs 0.6 ± 0.8; P = 0.23, and 0.4 ± 0.8 vs 0.5 ± 0.9; P = 0.70) and NYHA functional class (Class I/II/III/IV: 64.7/29.4/5.9/0.0 vs 62.1/34.7/3.2/0.0%, respectively; P = 0.91, and 71.4/25.7/2.9/0.0 vs 72.9/22.9/4.3/0.0%, respectively; P = 0.92). The incidence of PPM was lower and less severe after TAVR compared with SAVR in intermediate- and low-risk patients with severe AVS. There were no significant differences in MACCE, cardiac-related hospitalizations or NYHA class after 2 years for patients with versus those without severe PPM.


Ecological pathways to prevention: How does the SASA! community mobilisation model work to prevent physical intimate partner violence against women?
Intimate partner violence (IPV) against women is a global public health concern. While community-level gender norms and attitudes to IPV are recognised drivers of IPV risk, there is little evidence on how interventions might tackle these drivers to prevent IPV at the community-level. This secondary analysis of data from the SASA! study explores the pathways through which SASA!, a community mobilisation intervention to prevent violence against women, achieved community-wide reductions in physical IPV. From 2007 to 2012 a cluster randomised controlled trial (CRT) was conducted in eight communities in Kampala, Uganda. Cross-sectional surveys of a random sample of community members, aged 18-49, were undertaken at baseline (n = 1583) and 4 years post intervention implementation (n = 2532). We used cluster-level intention to treat analysis to estimate SASA!'s community-level impact on women's past year experience of physical IPV and men's past year perpetration of IPV. The mediating roles of community-, relationship- and individual-level factors in intervention effect on past year physical IPV experience (women)/perpetration (men) were explored using modified Poisson regression models. SASA! was associated with reductions in women's past year experience of physical IPV (0.48, 95 % CI 0.16-1.39), as well as men's perpetration of IPV (0.39, 95 % CI 0.20-0.73). Community-level normative attitudes were the most important mediators of intervention impact on physical IPV risk, with norms around the acceptability of IPV explaining 70 % of the intervention effect on women's experience of IPV and 95 % of the effect on men's perpetration. The strongest relationship-level mediators were men's reduced suspicion of partner infidelity (explaining 22 % of effect on men's perpetration), and improved communication around sex (explaining 16 % of effect on women's experience). Reduced acceptability of IPV among men was the most important individual-level mediator (explaining 42 % of effect on men's perpetration). These results highlight the important role of community-level norm-change in achieving community-wide reductions in IPV risk. They lend strong support for the more widespread adoption of community-level approaches to preventing violence. ClinicalTrials.gov, NCT00790959 . Registered 13th November 2008. The study protocol is available at: http://www.trialsjournal.com/content/13/1/96.


Investigating the Protective Role of Mastery Imagery Ability in Buffering Debilitative Stress Responses.
Mastery imagery has been shown to be associated with more positive cognitive and emotional responses to stress, but research is yet to investigate the influence of mastery imagery ability on imagery's effectiveness in regulating responses to acute stress, such as competition. Furthermore, little research has examined imagery's effectiveness in response to actual competition. This study examined (a) whether mastery imagery ability was associated with stress response changes to a competitive stress task, a car racing computer game, following an imagery intervention, and (b) the effects of different guided imagery content on pre-task cognitive and emotional responses. In Session 1, 78 participants (M age = 20.03 years, SD = 1.28) completed ratings of pre-task anxiety intensity and direction, confidence, and perceived control. Imagery ability was also assessed before completing the task. In Session 2, participants were randomly allocated to an imagery condition (positive mastery, negative mastery, relaxation) or control group (no imagery) before completing the task and outcome measures again. For the negative mastery group, greater positive mastery imagery ability was associated with greater perceived control and perceiving anxiety as more facilitative. Furthermore, mastery imagery ability moderated the relationship between anxiety intensity and direction. Altogether, results suggest that positive mastery imagery ability may act as a potential buffer against the effects of negative images.


Uterine crowding in the sow affects litter sex ratio, placental development and embryonic myogenin expression in early gestation.
Uterine crowding in the pig results in intrauterine growth restriction (IUGR), and permanently affects fetal muscle fibre development, representing production losses for the commercial pig herd. The present study sought to understand how different levels of uterine crowding in sows affects muscle fibre development in the early embryo at the time of muscle fibre differentiation and proliferation. Sows either underwent surgical, unilateral oviduct ligation (LIG; n = 10) to reduce the number of embryos in the uterus, or remained as intact, relatively-crowded controls (CTR; n = 10). Embryos and placentae were collected at Day 30 of gestation, and myogenic regulatory factor (MRF) transcript abundance was determined using real-time PCR for both myogenin (MYOG) and myoblast differentiation 1 (MYOD1). Unilateral tubal ligation resulted in lower numbers of embryos in utero, higher placental weights and a higher male : female sex ratio (P < 0.05). Relative MYOD1 expression was not different, but MYOG expression was higher (P < 0.05) in the LIG group embryos; predominantly due to effects on the male embryos. Relatively modest uterine crowding therefore affects MRF expression, even at very early stages of embryonic development, and could contribute to reported differences in fetal muscle fibre development, birthweight and thus post-natal growth performance in swine.


The bactericidal effect of silver nanoparticles.
Nanotechnology is expected to open new avenues to fight and prevent disease using atomic scale tailoring of materials. Among the most promising nanomaterials with antibacterial properties are metallic nanoparticles, which exhibit increased chemical activity due to their large surface to volume ratios and crystallographic surface structure. The study of bactericidal nanomaterials is particularly timely considering the recent increase of new resistant strains of bacteria to the most potent antibiotics. This has promoted research in the well known activity of silver ions and silver-based compounds, including silver nanoparticles. The present work studies the effect of silver nanoparticles in the range of 1-100 nm on Gram-negative bacteria using high angle annular dark field (HAADF) scanning transmission electron microscopy (STEM). Our results indicate that the bactericidal properties of the nanoparticles are size dependent, since the only nanoparticles that present a direct interaction with the bacteria preferentially have a diameter of approximately 1-10 nm.


[Left ventricular mural thrombus in acute anterior myocardial infarct].
Fifty-six consecutive patients with acute anterior infarction were studied by two-dimensional echocardiography to determine the incidence and complications of left-ventricular thrombosis. Mean follow-up period was 4.4 months. Left-ventricular thrombus was demonstrated in 14 patients (25%) between 25 and 54 days after infarction (group A), in 42 patients (group B) it was not demonstrated. Apical and septal dyskinesis, and Forrester's hemodynamic subset-III were significantly (P less than 0.02) associated with thrombus development. Ten patients of group A received heparin (6.6 days mean); the remaining four patients received aspirin and dipyridamole. Thrombi formation were not significantly prevented with both treatments (chi 2 = 0.635). During follow-up period, thrombus persisted in 6 patients of group A, all of them with apical and septal dyskinesis. Three patients had a cerebrovascular accident (5.3%), one of them of group A; no heparin anticoagulation was administered in two. We conclude that apical and septal dyskinesis during acute anterior infarction is generally associated with mural thrombi development. Due to the embolic risk therapeutic anticoagulation must be considered in these patients.


Guidelines for investigating causality of sequence variants in human disease.
The discovery of rare genetic variants is accelerating, and clear guidelines for distinguishing disease-causing sequence variants from the many potentially functional variants present in any human genome are urgently needed. Without rigorous standards we risk an acceleration of false-positive reports of causality, which would impede the translation of genomic research findings into the clinical diagnostic setting and hinder biological understanding of disease. Here we discuss the key challenges of assessing sequence variants in human disease, integrating both gene-level and variant-level support for causality. We propose guidelines for summarizing confidence in variant pathogenicity and highlight several areas that require further resource development.


Dextrose Prolotherapy for Chronic Shoulder Pain: A Case Report.
Context • Shoulder pain is one of the most common pain complaints reported by patients. Consensus is lacking on its ideal treatment, and many different treatments are available and used. Prolotherapy is an injection-based therapy that has shown significant results in treating many common musculoskeletal pain conditions, including osteoarthritis, lateral epicondylosis, and low-back pain. Objective • The study intended to evaluate the use of dextrose prolotherapy in the treatment of shoulder pain. Design • The research team performed a case study. Setting • The study occurred at the Medical Center at Southwest College of Naturopathic Medicine (Tempe, AZ, USA). Participant • The participant was a middle-aged male with a long-term history of untreated shoulder pain. Intervention • Injections were placed in the patient's glenohumeral joint space, the acromioclavicular joint, the subacromial space, and the insertion of the supraspinatus. Each location was injected with a solution of 50% dextrose diluted with 1% lidocaine, 0.25% bupivacaine, and 1 mg methylcobalamin. The final concentration of dextrose in the solution was approximately 22.8%. Outcome Measures • The patient completed questionnaires (numerical rating scale, verbally reported at the beginning of each visit) indicating his level of pain on a scale of 0 to 10, with 0 = no pain and 10 = worst pain. Results • Following 3 sessions of prolotherapy, the patient reported a 90% reduction in pain and full restoration of normal activity. Conclusions • The findings suggest that dextrose prolotherapy may be an effective treatment for chronic shoulder pain and may be an alternative to surgery or other more costly and invasive interventions.


Selective ophthalmic artery chemosurgery (SOAC) for retinoblastoma: fluoroscopic time and radiation dose parameters. A baseline study.
To evaluate fluoroscopic time and radiation dose parameters, and factors affecting these parameters, during selective ophthalmic artery chemosurgery (SOAC) for retinoblastoma. Retrospective review from the prospective database of all patients with retinoblastoma treated with SOAC over a 5-year period (September 2009-January 2015) at a single institution after receiving institutional review board approval. Patient demographics, arterial approach, access device, side of treatment, number of SOAC cycles/patient, number of drugs/SOAC, and radiation parameters (outcome variables), including the fluoroscopic time, dose-area product (DAP), and total radiation dose, were obtained from the database. Generalized linear regression was used for univariate and multivariate analysis of the outcome variables. In 218 patients (M:F=94:124), 272 eyes were treated by 833 SOAC infusions during 792 procedures. Mean age, weight, SOAC cycle/patient, and drugs/cycle were 19±19.5 months, 11.4±6.4 kg, 2.72±1.6, and 2.48±0.8, respectively. Mean fluoroscopic time, DAP, and doses were 10.2±8.4 min, 218.7±240.8 cGy.cm2, and 42.3±41.4 mGy, respectively. Radiation parameters (fluoroscopic time, DAP, and dose) were significantly lower (p<0.001) for the ophthalmic artery (OA) approach (7.5±5.4; 147.7±138.4; 28.5±29.4) than with middle meningeal artery (13.4±5.6; 242±138; 51.4±27) and balloon-assisted infusion in the internal carotid artery (ICA; 17.8±11.5; 449.8±361; 81.8±63.3). Radiation parameters for microcatheter access (8.6±7.1; 193.4±181.3; 42.3±37) were significantly lower (p<0.001) than with the ICA (17.8±11.5; 449.8±361; 81.8±63.3). Radiation parameters for bilateral IA chemotherapy (IAC; 16.8±11.6; 320.7±268.7; 60.8±45.6) were significantly higher (p<0.001) than for unilateral IAC (8.9±6.6; 212.7±247; 42±41). In SOAC for retinoblastoma, the OA approach, microcatheter access, and unilateral treatment were associated with significantly lower radiation parameters. We established benchmark radiation parameters for retinoblastoma SOAC in our patient cohort.


Stability of cachet phakic intraocular lens position during 6-months follow-up.
To evaluate the position stability of a phakic intraocular lens (Cachet pIOL; Alcon, Laboratories, Inc., Fort Worth, TX) in the anterior chamber (AC) during a 6-months follow-up. Thirty eyes of 16 subjects underwent a Cachet pIOL implantation for the correction of high myopia from -6.50 to -16.00 D with plano targeted refraction. The position stability of the Cachet pIOL was evaluated using an Anterior Segment-OCT (AS-OCT, Carl Zeiss AG, Oberkochen, Germany) at 1- and 6-months postoperatively. Three measurements have been taken into account: 1) the minimum distance between the anterior surface of the Cachet pIOL optic disk and the central corneal endothelium; 2) the minimum distance between the optic disk's edges of the pIOL and the endothelium; 3) the minimum distance between the posterior surface of the pIOL optic disk and the anterior surface of the crystalline lens. The endothelial cell density (ECD) was also recorded. No statistically significant changes of the Cachet pIOL position in the AC were found during follow-up. The average changes were ≤0.1 mm between 1- and 6-months postoperatively (P>0.05). At the end of follow-up, The mean ECD loss was 0.7 % (from 2794 ± 337 cell/mm(2) to 2776 ± 388 cell/mm(2); P>0.05). A high position stability of the Cachet pIOL in the anterior chamber was shown during a 6-months follow-up.


Effect of Lateral Decubitus Body Posture on Anterior Chamber Angle in Healthy Subjects: An Anterior Segment Optical Coherence Tomography Study.
To investigate the effect of the lateral decubitus (LD) position on the anterior chamber (AC) angle in healthy subjects. Twenty-three healthy young subjects were included in this prospective observational study. We measured AC angle parameters in the sitting and the left LD positions using anterior segment optical coherence tomography (Visante OCT): trabecular-iris angle (TIA), angle opening distance (AOD500), trabecular-iris space area (TISA500), anterior chamber width, lens vault, and anterior chamber depth. The Wilcoxon signed-rank test was used to compare the parameters between different body positions. Interobserver reproducibility of AC angle measurements was assessed by intraclass correlation coefficients. Postural alterations from sitting to the left LD position significantly reduced the AC angle on the temporal side in right eyes (TIA: 39.53±2.38 to 38.31±3.47 degrees; AOD500: 0.72±0.13 to 0.65±0.08; TISA500: 0.25±0.06 to 0.22±0.04; all P<0.05), whereas no significant changes were noted on the nasal side. Contrastingly, a significant decrease in the AC angle on the nasal side was noted for left eyes (TIA: 39.49±2.24 to 38.17±2.76 degrees; AOD500: 0.68±0.09 to 0.64±0.10; TISA500: 0.23±0.04 to 0.21±0.03; all P<0.05). Anterior chamber width and anterior chamber depth were unaffected by postural alterations, but lens vault significantly was reduced following a shift to the left LD position. The AC angle parameters on the nondependent side of the eye in the LD position were significantly reduced compared with those in the sitting position. Therefore, postural shift from sitting to the LD position may induce alterations in the AC angle.


Multivariate logistic regression for familial aggregation of two disorders. II. Analysis of studies of eating and mood disorders.
Family studies have suggested that eating disorders and mood disorders may coaggregate within families. Previous studies, however, have been limited by use of univariate modeling techniques and failure to account for the correlation of observations within families. To provide a more efficient analysis and to illustrate multivariate logistic regression models for familial aggregation of two disorders, the authors analyzed pooled data from two previously published family studies (conducted in Massachusetts in 1984-1986 and 1986-1987) by using multivariate proband predictive and family predictive models. Both models demonstrated a significant familial aggregation of mood disorders and familial coaggregation of eating and mood disorders. The magnitude of the coaggregation between eating and mood disorders was similar to that of the aggregation of mood disorders. Similar results were obtained with alternative models, including a traditional univariate proband predictive model. In comparison with the univariate model, the multivariate models provided greater flexibility, improved precision, and wider generality for interpreting aggregation effects.


Increased glycosylation capacity in regenerating rat liver is paralleled by decreased activities of CMP-N-acetylneuraminate hydrolase and UDP-galactose pyrophosphatase.
In regenerating rat liver the activities of CMP-N-acetylneuraminate hydrolase and UDP-galactose pyrophosphatase were decreased to 40-50% of control values within 35 h after partial hepatectomy. In the same time period the activities of sialyltransferase and galactosyltransferase were increased, and the initial sharp decrease in the carbohydrate content of liver and serum glycoproteins was largely restored. The antiparallel nature of these events is suggestive of an involvement of nucleotide-sugar-hydrolysis enzymes in rat liver glycoprotein biosynthesis.


Deficiency of vitamin D and vitamin C in the pathogenesis of bronchial asthma.
Epidemiology of bronchial asthma (BA) indicates a marked paradox: rapid rise in the prevalence.Simultaneous decline in mortality is mostly related to improvement in the diagnosis and therapy. In many economically developed countries the BA affects more than 10 per cent of the population, while mortality related to this respiratory disorder is below 1/100,000. Factors favorably influencing mortality of BA include new more effective medications, decline in smoking and also improved nutrition, based on awareness of protective role of vitamins. Vitamin D deficiency has a number of biological effects that are potentially instrumental in the pathogenesis and severity of BA. Increased number of randomized, controlled, interventional studies is showing positive effects of vitamin D supplementation in pediatric and in adult BA. Oxidative stress is potentially an important pathogenic factor in the progression of BA. Vitamin C (ascorbic acid) belongs to the most effective nutritional antioxidants. By counteracting oxidants, reducing generation of reactive oxygen species, vitamin C may inhibit external attacks in the respiratory tract, thus modulating the development of BA (Fig. 2, Ref. 15).


Effect of ADH on chloride reabsorption in the loop of Henle of the Brattleboro rat.
Both in vivo superficial loop segment microperfusion and in vitro perfusion of isolated medullary thick ascending limb segments were used to assess the effect of vasopressin on loop of Henle chloride absorption in the Brattleboro rat. Superficial loop segments were perfused between the latest proximal and earliest distal tubule in vivo at 19.2 +/- 0.4 nl/min (mean +/- SE) with an artificial tubule fluid. Under control conditions, absolute chloride reabsorption was 1,596 +/- 61 pmol/min and increased to 1,876 +/- 102 after intravenous infusion of vasopressin (P less than 0.005). Distal tubule fluid chloride concentration decreased 4.6 +/- 1.5 meq/liter (P less than 0.05), and fractional chloride reabsorption increased 4.8 +/- 2.0% (P less than 0.05). For in vitro perfusion, medullary thick ascending limb segments were bathed and perfused (9-15 nl/min) with phosphate-buffered solutions at 38 degrees C. Under control conditions, transepithelial voltage was +2.4 +/- 0.3 mV, lumen positive, and the net chloride flux was 147 +/- 24 pmol X min-1 X mm-1 in the absorptive direction. Addition of vasopressin to the bathing solution increased net chloride reabsorption to 342 +/- 56 pmol X min-1 X mm-1 (P less than 0.02) and transepithelial voltage to 3.0 +/- 0.3 mV (P less than 0.002). An additional group of tubules was examined under identical conditions; however, vasopressin was removed from the bathing medium during a subsequent recovery period. In these experiments, net chloride flux and transepithelial voltage significantly increased compared with the control period and returned to control values upon removal of vasopressin from the bath.(ABSTRACT TRUNCATED AT 250 WORDS)


Hepatotoxicity associated to synthetic cannabinoids use.
Synthetic cannabinoids (SCs) are psychotropic compounds, chemically created in laboratory to mimic cannabinergic brain activity of delta-9 tetrahydrocannabinol. The consumption of these compounds for recreational purposes can lead to a variety of adverse effects on health including overdose and deaths. Increasingly popular as substances of abuse since the 2000s, SCs were produced initially to bind and study cannabinoid receptors (they also can be called synthetic cannabimimetics) failing in eliminating the psychoactive effects. Currently, SCs are misused by students and young adults as "natural products" because of their herbal aspect. Actually, these apparently innocuous recreational substances hide toxic effects to health. Reported side effects are cardiovascular, gastrointestinal, neurological, renal, metabolic, ophthalmologic, pulmonary and psychoactive including dependence and withdrawal. A few cases of SCs ingestion have also been associated with liver failure. We herein review the recent literature on the SCs toxicity with particular attention to liver damage aspects.


Posteroventral medial pallidotomy in levodopa-unresponsive parkinsonism.
Parkinsonism in a 42-year-old patient, which was presumably related to peripheral trauma, did not respond to levodopa therapy. We treated the patient with microelectrode-guided unilateral posteroventral medial pallidotomy and followed up with magnetic resonance imaging and prospective clinical evaluation. Pallidotomy resulted in marked improvement of right-sided parkinsonian symptoms and functional disability at 4.5 months after surgery. Microelectrode recording during pallidotomy revealed discharge patterns that were similar to those seen in patients with Parkinson disease. Postoperative magnetic resonance imaging confirmed the location of the lesion in the posteroventral medial pallidum. Posteroventral pallidotomy usually has limited benefit in patients with degenerative atypical parkinsonism who do not respond to levodopa therapy. Nevertheless, pallidotomy can be an effective treatment for other levodopa-unresponsive parkinsonian disorders.


Charge resonance character in the charge transfer state of bianthryls: effect of symmetry breaking on time-resolved near-IR absorption spectra.
We study the effects of symmetry breaking on the photogenerated intramolecular charge transfer (CT) state of 9,9'-bianthryl (BA) with femtosecond time-resolved near-IR spectroscopy. The time-resolved near-IR spectra are measured in acetonitrile for a symmetric substituted derivative of 10,10'-dicyano-9,9'-bianthryl (DCBA) and asymmetric substituted derivatives of 10-cyano-9,9'-bianthryl (CBA) and 9-(N-carbazolyl)anthracene (C9A), as well as nonsubstituted BA. The transient near-IR absorption spectrum of each compound at 0 ps has a locally excited (LE) absorption band, which agrees with the transient absorption band of the corresponding monomer unit. At 3 ps after the photoexcitation, the symmetric compounds show a broad charge transfer (CT) absorption band, whereas no absorption peak appears in the spectra of the asymmetric compounds. The broad CT absorption at 1250 nm only observed for the symmetric compounds can be attributed to the charge resonance transition associated with two equivalent charge separated states.


Expectation-Maximization Model for Substitution of Missing Values Characterizing Greenness of Organic Solvents.
Organic solvents are ubiquitous in chemical laboratories and the Green Chemistry trend forces their detailed assessments in terms of greenness. Unfortunately, some of them are not fully characterized, especially in terms of toxicological endpoints that are time consuming and expensive to be determined. Missing values in the datasets are serious obstacles, as they prevent the full greenness characterization of chemicals. A featured method to deal with this problem is the application of Expectation-Maximization algorithm. In this study, the dataset consists of 155 solvents that are characterized by 13 variables is treated with Expectation-Maximization algorithm to predict missing data for toxicological endpoints, bioavailability, and biodegradability data. The approach may be particularly useful for substitution of missing values of environmental, health, and safety parameters of new solvents. The presented approach has high potential to deal with missing values, while assessing environmental, health, and safety parameters of other chemicals.


[Preliminary progress in the study of the relationship between COVID-19 infection and partial arterial or venous diseases].
Vascular complications are commonly associated with COVID-19 infection. Increasing reports suggest a close relationship between COVID-19 and venous thromboembolic diseases, including deep vein thrombosis and pulmonary embolism. Furthermore, COVID-19 has been linked to various aortic diseases such as aortic valve stenosis, aortic thrombosis, abdominal aortic aneurysm, aortic dissection, and limb ischemia. Consequently, understanding the causes and treatment of these vascular complications has become a critical aspect of comprehensive COVID-19 management. This article provides a review of aortic diseases and venous thromboembolic diseases that may be associated with COVID-19, aiming to explore potential mechanisms underlying the development of these vascular conditions and discuss strategies for preventing thrombosis in COVID-19 patients.


PIN1 is an E2F target gene essential for Neu/Ras-induced transformation of mammary epithelial cells.
Oncogenes Neu/HER2/ErbB2 and Ras can induce mammary tumorigenesis via upregulation of cyclin D1. One major regulatory mechanism in these oncogenic signaling pathways is phosphorylation of serines or threonines preceding proline (pSer/Thr-Pro). Interestingly, the pSer/Thr-Pro motifs in proteins exist in two completely distinct cis and trans conformations, whose conversion is catalyzed specifically by the essential prolyl isomerase Pin1. By isomerizing pSer/Thr-Pro bonds, Pin1 can regulate the conformation and function of certain phosphorylated proteins. We have previously shown that Pin1 is overexpressed in breast tumors and positively regulates cyclin D1 by transcriptional activation and posttranslational stabilization. Moreover, in Pin1 knockout mice, mammary epithelial cells fail to undergo massive proliferation during pregnancy, as is the case in cyclin D1 null mice. These results indicate that Pin1 is upregulated in breast cancer and may be involved in mammary tumors. However, the mechanism of Pin1 overexpression in cancer and its significance in cell transformation remain largely unknown. Here we demonstrate that PIN1 expression is mediated by the transcription factor E2F and enhanced by c-Neu and Ha-Ras via E2F. Furthermore, overexpression of Pin1 not only confers transforming properties on mammary epithelial cells but also enhances the transformed phenotypes of Neu/Ras-transformed mammary epithelial cells. In contrast, inhibition of Pin1 suppresses Neu- and Ras-induced transformed phenotypes, which can be fully rescued by overexpression of a constitutively active cyclin D1 mutant that is refractory to the Pin1 inhibition. Thus, Pin1 is an E2F target gene that is essential for the Neu/Ras-induced transformation of mammary epithelial cells through activation of cyclin D1.


Specificity of the combined dexamethasone suppression and TRH/TSH tests in melancholia.
Subjects for this study were 61 acute psychiatric inpatients. Forty two (42) qualified for a RDC diagnosis of Major Depressive Disorder (MDD) and 19 for other disorders. After a 7-10 days drug withdrawal period patients were subjected to the dexamethasone suppression and TRH/TSH tests. TSH was measured using a RIA. Cortisol was measured using a CPB technique. Eighteen (18) of the 42 MDD patients and 1 of the 19 others had an abnormal DST (sensitivity 43%, specificity 94%). Twenty two (22) depressed patients and 4 others had a blunted TSH response (sensitivity 52%, specificity 79%). Thirteen (13) depressives and none of the others had abnormal responses to both tests (sensitivity 31%, specificity 100%). DST nonsuppression alone and blunted TSH response alone were not a function of severity of illness, sex, age of onset, family history or RDC subtype. The 13 MDD patients with the combined neuroendocrine abnormality were more severely depressed, had longer episodes of illness, were older and had a later age of onset of their first episode. Our results add support to the suggestion that serial neuroendocrine challenge studies might be of particular relevance and significance in the diagnosis and management of elderly psychotic depressed patients.


Whole exome analysis identifies frequent CNGA1 mutations in Japanese population with autosomal recessive retinitis pigmentosa.
The purpose of this study was to investigate frequent disease-causing gene mutations in autosomal recessive retinitis pigmentosa (arRP) in the Japanese population. In total, 99 Japanese patients with non-syndromic and unrelated arRP or sporadic RP (spRP) were recruited in this study and ophthalmic examinations were conducted for the diagnosis of RP. Among these patients, whole exome sequencing analysis of 30 RP patients and direct sequencing screening of all CNGA1 exons of the other 69 RP patients were performed. Whole exome sequencing of 30 arRP/spRP patients identified disease-causing gene mutations of CNGA1 (four patients), EYS (three patients) and SAG (one patient) in eight patients and potential disease-causing gene variants of USH2A (two patients), EYS (one patient), TULP1 (one patient) and C2orf71 (one patient) in five patients. Screening of an additional 69 arRP/spRP patients for the CNGA1 gene mutation revealed one patient with a homozygous mutation. This is the first identification of CNGA1 mutations in arRP Japanese patients. The frequency of CNGA1 gene mutation was 5.1% (5/99 patients). CNGA1 mutations are one of the most frequent arRP-causing mutations in Japanese patients.


Photovoltachromic device with a micropatterned bifunctional counter electrode.
A photovoltachromic window can potentially act as a smart glass skin which generates electric energy as a common dye-sensitized solar cell and, at the same time, control the incoming energy flux by reacting to even small modifications in the solar radiation intensity. We report here the successful implementation of a novel architecture of a photovoltachromic cell based on an engineered bifunctional counter electrode consisting of two physically separated platinum and tungsten oxide regions, which are arranged to form complementary comb-like patterns. Solar light is partially harvested by a dye-sensitized photoelectrode made on the front glass of the cell which fully overlaps a bifunctional counter electrode made on the back glass. When the cell is illuminated, the photovoltage drives electrons into the electrochromic stripes through the photoelectrochromic circuit and promotes the Li(+) diffusion towards the WO3 film, which thus turns into its colored state: a photocoloration efficiency of 17 cm(2) min(-1) W(-1) at a wavelength of 650 nm under 1.0 sun was reported along with fast response (coloration time <2 s and bleaching time <5 s). A fairly efficient photovoltaic functionality was also retained due to the copresence of the independently switchable micropatterned platinum electrode.


The many faces of fear: a synthesis of the methodological variation in characterizing predation risk.
Predators affect prey by killing them directly (lethal effects) and by inducing costly antipredator behaviours in living prey (risk effects). Risk effects can strongly influence prey populations and cascade through trophic systems. A prerequisite for assessing risk effects is characterizing the spatiotemporal variation in predation risk. Risk effects research has experienced rapid growth in the last several decades. However, preliminary assessments of the resultant literature suggest that researchers characterize predation risk using a variety of techniques. The implications of this methodological variation for inference and comparability among studies have not been well recognized or formally synthesized. We couple a literature survey with a hierarchical framework, developed from established theory, to quantify the methodological variation in characterizing risk using carnivore-ungulate systems as a case study. Via this process, we documented 244 metrics of risk from 141 studies falling into at least 13 distinct subcategories within three broader categories. Both empirical and theoretical work suggest risk and its effects on prey constitute a complex, multi-dimensional process with expressions varying by spatiotemporal scale. Our survey suggests this multi-scale complexity is reflected in the literature as a whole but often underappreciated in any given study, which complicates comparability among studies and leads to an overemphasis on documenting the presence of risk effects rather than their mechanisms or scale of influence. We suggest risk metrics be placed in a more concrete conceptual framework to clarify inference surrounding risk effects and their cascading effects throughout ecosystems. We recommend studies (i) take a multi-scale approach to characterizing risk; (ii) explicitly consider 'true' predation risk (probability of predation per unit time); and (iii) use risk metrics that facilitate comparison among studies and the evaluation of multiple competing hypotheses. Addressing the pressing questions in risk effects research, including how, to what extent and on what scale they occur, requires leveraging the advantages of the many methods available to characterize risk while minimizing the confusion caused by variability in their application.


Relationship of sleep abnormalities to patient genotypes in Prader-Willi syndrome.
To assess whether sleep abnormalities are related to the genetic abnormalities in Prader-Willi Syndrome (PWS), we performed polysomnographic studies (nighttime and daytime) and determined the chromosome 15 genotypes in eight patients with PWS. Four patients demonstrated sleep onset REM periods (SOREM), and five met the objective polysomnographic criteria for severe or moderate excessive daytime sleepiness (EDS). Three of the four patients with SOREM displayed a paternally derived deletion of chromosome 15q11-q13, whereas the fourth exhibited maternal uniparental heterodisomy in this chromosomal region (UPD). Two of the four patients that did not display SOREM carried paternally derived deletions; the remaining two demonstrated UPD. Four of the five patients with EDS displayed paternal deletions, and the fifth exhibited UPD. One of three patients without evidence of EDS demonstrated paternal deletion; the remaining two showed UPD. Although neither EDS nor SOREM was not consistently associated with a specific genetic abnormality, these phenotypes may be more common in patients with paternal deletions than in those UPD. Sleep abnormalities in PWS cannot be explained by a single genetic model.


Did smokefree legislation in England reduce exposure to secondhand smoke among nonsmoking adults? Cotinine analysis from the Health Survey for England.
On 1 July 2007, smokefree legislation was implemented in England, which made virtually all enclosed public places and workplaces smokefree. We examined trends in and predictors of secondhand smoke exposure among nonsmoking adults to determine whether exposure changed after the introduction of smokefree legislation and whether these changes varied by socioeconomic status (SES) and by household smoking status. We analyzed salivary cotinine data from the Health Survey for England that were collected in 7 of 11 annual surveys undertaken between 1998 and 2008. We conducted multivariate regression analyses to examine secondhand smoke exposure as measured by the proportion of nonsmokers with undetectable levels of cotinine and by geometric mean cotinine. Secondhand smoke exposure was higher among those exposed at home and among lower-SES groups. Exposure declined markedly from 1998 to 2008 (the proportion of participants with undetectable cotinine was 2.9 times higher in the last 6 months of 2008 compared with the first 6 months of 1998 and geometric mean cotinine declined by 80%). We observed a significant fall in exposure after legislation was introduced--the odds of having undetectable cotinine were 1.5 times higher [95% confidence interval (CI): 1.3, 1.8] and geometric mean cotinine fell by 27% (95% CI: 17%, 36%) after adjusting for the prelegislative trend and potential confounders. Significant reductions were not, however, seen in those living in lower-social class households or homes where smoking occurs inside on most days. We found that the impact of England's smokefree legislation on secondhand smoke exposure was above and beyond the underlying long-term decline in secondhand smoke exposure and demonstrates the positive effect of the legislation. Nevertheless, some population subgroups appear not to have benefitted significantly from the legislation. This finding suggests that these groups should receive more support to reduce their exposure.