Autistic patients' experiences of the hospital setting: A scoping review.
To explore the factors that affect the experiences of autistic patients in the hospital setting. A scoping review. A systematic literature search using the databases CINAHL, Medline and Google Scholar was undertaken in September 2021 and updated in January 2023. This review is based on the methodological framework of Arksey and O'Malley (International Journal of Social Research Methodology, 8(1):19-32, 2005), which was further refined by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews. Autistic patients, as well as their families and healthcare staff, face several barriers that can impact their healthcare experiences within hospital settings. Of 211 articles screened, 30 were eligible and included. Through our review, we identified two main themes. The first theme, 'challenges to hospital experiences', includes four sub-themes: (1) communication, (2) a mismatch between the needs for autistic patients and the hospital environment, (3) challenges related to parents' experiences and (4) challenges related to hospital systems. The second theme, 'facilitators that improve hospital experiences', includes three sub-themes: (1) provision of care pathways, (2) partnership between parents and experts and (3) facilitators to improve hospital systems. By understanding these themes, we can work to address the barriers that autistic patients and their families face, while leveraging the facilitators to improve their hospital experiences. It is critical to understand the experiences of autistic patients in the hospital setting because they present a substantial risk of hospital admission due to their associated acute to chronic health conditions. Additionally, nurses and other medical staff must understand the unique hospital experiences and challenges of autistic patients to improve care and facilitate better hospital experiences. This review further highlights the crucial need to adopt a collaborative and inclusive approach between autistic patients, their families and healthcare staff. To achieve this, co-design initiatives that incorporate the perspectives and lived experiences of the autistic community are necessary. By placing autistic voices at the forefront of these initiatives, it is hoped that changes are meaningful, relevant and can be sustained. Understanding the unique hospital experiences and challenges of autistic patients can improve their quality of life and well-being by reducing stress and anxiety during hospitalization, leading to better health outcomes and potentially shorter hospital stays. It can also promote a more positive view of healthcare among autistic individuals, encouraging them to seek medical care when needed and have broader societal impacts such as reducing healthcare costs and improving the overall health and well-being of the population. Autistic patients present a substantial risk of hospital admission due to their associated acute to chronic conditions. Nurses and other medical staff must understand the unique hospital experiences and challenges of autistic patients to improve care and facilitate better hospital experiences. No patient or public contribution.


Effects of task language and second-language proficiency on the neural correlates of phonemic fluency in native Japanese speakers: a functional near-infrared spectroscopy study.
Data collected during a phonemic fluency task (or 'FAS test'), a standard component of neuropsychological batteries for assessment of cognitive deficits, may be language-dependent and may differ depending on second-language proficiency. The unique orthographic/phonological system of the task language, and the reported cognitive advantages inherent to bilinguals, may each influence the task's neural correlates. However, language background is not currently assessed in most studies testing phonemic fluency. Here, we used 52-channel functional near-infrared spectroscopy in college-aged native-Japanese subjects to examine functional changes in oxygenated hemoglobin elicited during a phonemic fluency task performed in Japanese and in English. We found activity differences that were related to task language and second-language proficiency. Besides loci activated in the Japanese test, bilateral precentral channels were specifically recruited in the English test. Furthermore, the higher-proficiency group showed almost no increase in oxygenated hemoglobin in either language context, whereas participants with lower proficiency showed widespread increases for both contexts. We interpret precentral increases as the consequence of additional articulatory resource recruitment in a second-language context. As for the lack of such variation in the higher-proficiency group, it may reflect an advantage in nonverbal executive control in this group. Together, our results point to language background and proficiency as confounding variables in neuroimaging studies of phonemic fluency and that the adequacy of such measures in populations with varying language backgrounds needs to be considered in future studies.


Management and care of the dying patient.
The recent widespread interest in the problems of the dying patient is reviewed, and the dynamics of the psychological process involved in dying are discussed. Recommendations for the management of the dying patient are presented, with special attention to the issues of 1) truth telling, 2) the essential features patients request themselves in their own care and management, and 3) the unique and individualized goals of treatment.


Foliar concentrations of volunteer willows growing on polluted sediment-derived sites versus sites with baseline contamination levels.
Many alluvial soils along navigable waterways are affected by disposal of dredged sediments or overbank sedimentation and contain metal concentrations that are elevated compared to baseline levels. Uptake patterns for metals and other elements by several volunteer Salix species growing on these sites were determined during a growing season in field plots and compared with the same species growing on soils with baseline contamination levels. For Cd and Zn, foliar concentrations were clearly higher on dredged sediment landfills. Uptake patterns differed significantly between species. A high uptake of Mn and low uptake of Cu, K and S in S. cinerea was attributed to wetland soil chemistry. Site effects on metal uptake were evaluated in more detail for Salix cinerea and S. alba growing on different sediment-derived sites under field conditions. Foliar Cd concentrations were higher in S. cinerea than in S. alba. This appeared to be a genetic feature not influenced by soil chemical properties, as it was observed both on clean sites and polluted sediment-derived sites. For S. cinerea, soil chemistry was reflected in foliar concentrations, while foliar Cd concentrations and bioavailability were found to be independent of the thickness of the polluted horizon. Dredged sediment landfills and freshwater tidal marshes with comparable Cd soil pollution had significantly different foliar Cd concentrations.


[Effectiveness of neuro-electric therapy in drug resistant endogenous psychoses].
A retrospective chart review of 50 pharmacotherapeutically resistant patients was performed after treatment with NET in 1986-1988. 28 patients suffered from schizophrenia and 22 from affective psychosis. In contrast to literature where NET as therapy of first choice has favourable results in depression in this study 60.7% of the treatment resistant acute schizophrenics responded well to NET. 3 months after discharge from hospital 9 schizophrenics (32.1%) but only 3 patients with affective psychosis (13.6%) presented a 'good' outcome (full remission). A longer duration of schizophrenia (more than 5 years since first manifestation) and a good response to neuroleptics in history was predictive for a good actual NET response (14 of 17 patients), whereas 7 of 11 patients suffering from schizophrenia less than 3 years without any period of full remission on neuroleptics were also non-responders to NET.


[Anatomical relations in innominate artery compression syndrome: retrospective case-control study].
To compare the anatomical relations between brachiocephalic trunk (BT), trachea, spine and sternum in patients with Innominate Artery Compressing Syndrome (IACS) and control patients. Retrospective case-control study of patients diagnosed with IACS in our center, in whom vascular computerized tomography (CT) was performed. The CT were compared with those of control patients free of obstructive respiratory pathology, without congenital heart disease and free of deforming thoracic mass, in whom CT was performed due to other reason. Each case was paired with three controls per case, in similar age groups. The significance value was set as p<0,05. Nine cases were included (7 boys and 2 girls) with their 27 respective controls (20 boys and 7 girls). The BT origin position with respect to the trachea, thought as a clock face, was 01:30 (00:30- 03:00) in cases and 01:30 (00:30-02:30) in controls. No differences were observed (p=0.72). The relation between anteroposterior/transversal tracheal diameters was 0.44 (0.184-0.6) in cases, 0.885 (0.64-1.16) in controls. The sternum-trachea/sternum-vertebra relation was 0.685 (0.6-0.76) in cases, 0.67 (0.49-0.79) in controls. No differences were observed (p=0.75). The angle of thoracic kyphosis was 29º (9º-34º) in cases, 24º (4º-33º) in controls. There were no statistically significant differences (p=0.45). We found no differences between the two groups in the BT origin in relation to the trachea. In all cases, the origin was on the left side of the body. Therefore, we question the premise that IACS is due to a more left origin of BT.


Chronic renal failure: oxidative stress, endothelial dysfunction and wine.
Atherosclerosis development is accelerated in chronic renal failure (CRF) and is the major cause of death in this clinical condition. An increased oxidative stress and an endothelial dysfunction, with their complex interrelationships, are relevant aspects of atherogenesis in CRF patients and might be targets for treatment. Many studies have underlined the cardiovascular protection provided by a moderate wine consumption. This beneficial effect is due to both alcohol and nonalcoholic components of wine including several phenolic molecules such as quercetin and resveratrol. Wine polyphenols have antioxidant properties and favorably influence endothelial function, in particular by stimulating nitric oxide-mediated vasodilation and inhibiting the endothelin-1 pathway. The possible advantage of a moderate wine consumption in CRF patients can be hypothesized and deserves clinical investigation.


Results from the Mars Global Surveyor Thermal Emission Spectrometer.
The Thermal Emission Spectrometer spectra of low albedo surface materials suggests that a four to one mixture of pyroxene to plagioclase, together with about a 35 percent dust component provides the best fit to the spectrum. Qualitative upper limits can be placed on the concentration of carbonates (<10 percent), olivine (<10 percent), clay minerals (<20 percent), and quartz (<5 percent) in the limited regions observed. Limb observations in the northern hemisphere reveal low-lying dust hazes and detached water-ice clouds at altitudes up to 55 kilometers. At an aerocentric longitude of 224 degrees a major dust storm developed in the Noachis Terra region. The south polar cap retreat was similar to that observed by Viking.


Multicenter phase I/II trial of the safety of allogeneic endothelial cell implants after the creation of arteriovenous access for hemodialysis use: the V-HEALTH study.
Vascular access dysfunction is the major cause of morbidity in patients on hemodialysis to treat end stage renal disease. Preclinical studies have demonstrated that the perivascular placement of implants containing allogeneic aortic endothelial cells (Vascugel) reduces thrombosis, inflammation, stenosis and increases lumen diameter in porcine models of arteriovenous fistulae (AVF) and arteriovenous grafts (AVG). We conducted a phase I/II clinical study to investigate the safety of Vascugel placement around the surgical anastomotic sites of newly constructed dialysis accesses. From July 2006 to August 2006, eight patients (4 AVG, 4 AVF) were treated with two Vascugel sponges at the venous anastomosis in the open-label phase I trial. From January 2007 to August 2007 57 patients (30 AVG and 27 AVF) were randomized in a 2:1 fashion to receive either Vascugel or control matrices (placebo) at surgery. The phase II AVG patients had sponges placed at both the venous and arterial anastomoses. All patients were followed for 24 weeks. The primary objective of the study was to demonstrate the safety (incidence of infection, intervention, and thrombosis) of Vascugel compared with placebo within 30 days post-surgery. Secondary endpoints included assessments of patency, lumen diameter, and immunologic sensitization to human leukocyte antigens (HLA) determined by measurement of panel reactive antibodies (PRA). There was no difference in early complication rates between the Vascugel and placebo groups at 4 weeks (10.9% vs 21.1%, respectively). There were no statistically significant differences in primary or assisted primary patency between the intent to treat groups at 24 weeks. Vascugel treated AVG had a primary patency rate of 38% and an assisted primary patency rate of 72% (vs 23% and 58%, respectively, for placebo). Vascugel treated AVF had a primary patency rate of 60% at 24 weeks and an assisted primary patency rate of 96% (vs 62% and 88%, respectively, for placebo). A greater than 30% increase in PRA was detected in 9 of the 46 (19.5%) Vascugel treated patients and one of the 19 (5.2%) placebo patients (P = .26) and was not associated with any evidence of local or systemic complications. Targeted local therapy with perivascular, allogeneic endothelial cells is a safe and novel therapeutic approach that may be ideally suited to control the response to injury at surgical anastomoses. Larger randomized trials are needed to determine if Vascugel can prolong AVG or AVF patency.


Metabolism of cholesterol and progesterone is differentially regulated in primary trophoblastic subtypes and might be disturbed in recurrent miscarriages.
During pregnancy, extravillous trophoblasts (EVTs) invade the maternal decidua and remodel the local vasculature to establish blood supply for the growing fetus. Compromised EVT function has been linked to aberrant pregnancy associated with maternal and fetal morbidity and mortality. However, metabolic features of this invasive trophoblast subtype are largely unknown. Using primary human trophoblasts isolated from first trimester placental tissues, we show that cellular cholesterol homeostasis is differentially regulated in EVTs compared with villous cytotrophoblasts. Utilizing RNA-sequencing, gene set-enrichment analysis, and functional validation, we provide evidence that EVTs display increased levels of free and esterified cholesterol. Accordingly, EVTs are characterized by increased expression of the HDL-receptor, scavenger receptor class B type I, and reduced expression of the LXR and its target genes. We further reveal that EVTs express elevated levels of hydroxy-delta-5-steroid dehydrogenase 3 beta- and steroid delta-isomerase 1 (HSD3B1) (a rate-limiting enzyme in progesterone synthesis) and are capable of secreting progesterone. Increasing cholesterol export by LXR activation reduced progesterone secretion in an ABCA1-dependent manner. Importantly, HSD3B1 expression was decreased in EVTs of idiopathic recurrent spontaneous abortions, pointing toward compromised progesterone metabolism in EVTs of early miscarriages. Here, we provide insights into the regulation of cholesterol and progesterone metabolism in trophoblastic subtypes and its putative relevance in human miscarriage.


Reevaluating Cue Exposure and Response Prevention in a Pilot Study: An Updated Treatment for Binge Eating Disorder.
Approximately half of individuals with binge eating disorder (BED) fail to improve when treated with cognitive behavioral therapy; thus, better treatments are needed. Cue exposure and response prevention (CERP) may be one option, but its full potential for reducing binge eating remains unknown because prior applications for binge eating have not utilized the broad range of strategies believed to optimize exposure therapy. The current single-subject AB design investigated the acceptability and effectiveness of a comprehensive CERP treatment among 8 women who met DSM-5 criteria for binge eating disorder. Changes in the number of binges were measured from baseline to the end of treatment, and desire to eat, salivation, and idiographic expectancies of aversive outcomes to food-cue exposure (idiographic CS-US expectancies), including expectancies about ability to tolerate distress when exposed to food cues were measured across the course of treatment. Statistical analysis revealed a significant reduction in the number of binges from baseline to the end of treatment. Across the course of treatment, desire to eat and idiographic CS-US expectancies reduced, and distress tolerance expectancies increased. No participants dropped out and all reported being maximally satisfied with the treatment. Based on these findings, future randomized-control trials with larger samples should examine the efficacy of CERP and mechanisms underlying change with the aim of establishing a more effective treatment for binge eating disorder.


Using control to shape stochastic escape and switching dynamics.
We present a strategy to control the mean stochastic switching times of general dynamical systems with multiple equilibrium states subject to Gaussian white noise. The control can either enhance or abate the probability of escape from the deterministic region of attraction of a stable equilibrium in the presence of external noise. We synthesize a feedback control strategy that actively changes the system's mean stochastic switching behavior based on the system's distance to the boundary of the attracting region. With the proposed controller, we are able to achieve a desired mean switching time, even when the strength of noise in the system is not known. The control method is analytically validated using a one-dimensional system, and its effectiveness is numerically demonstrated for a set of dynamical systems of practical importance.


[The behavioral development of rats with prenatal hypoinsulinemia].
Influence of the prenatal hypoinsulinaemia (streptozocin diabetes) on the behaviour of the offsprings of Wistar rats was studied from 1 to 20 postnatal days. In experimental pups there were slower weight increment, later eye opening, later development of elementary behavioural acts (grooming elements, rearing, sniffing), and later formation of complex behavioural patterns (investigation of an environment) than in the control offsprings of healthy females.


Few-shot image generation with reverse contrastive learning.
Generative models, such as Generative Adversarial Networks (GANs), have recently shown remarkable capabilities in various generation tasks. However, the success of these models heavily depends on the availability of a large-scale training dataset. When the size of the training dataset is limited, the quality and diversity of the generated results suffer from severe degradation. In this paper, we propose a novel approach, Reverse Contrastive Learning (RCL), to address the problem of high-quality and diverse image generation under few-shot settings. The success of RCL benefits from a two-sided, powerful regularization. Our proposed regularization is designed based on the correlation between generated samples, which can effectively utilize the latent feature information between different levels of samples. It does not require any auxiliary information or augmentation techniques. A series of qualitative and quantitative results show that our proposed method is superior to the existing State-Of-The-Art (SOTA) methods under the few-shot setting and is still competitive under the low-shot setting, showcasing the effectiveness of RCL. Code will be released upon acceptance at https://github.com/gouayao/RCL.


Single-Molecule Förster Resonance Energy Transfer Methods for Real-Time Investigation of the Holliday Junction Resolution by GEN1.
Bulk methods measure the ensemble behavior of molecules, in which individual reaction rates of the underlying steps are averaged throughout the population. Single-molecule Förster resonance energy transfer (smFRET) provides a recording of the conformational changes taking place by individual molecules in real-time. Therefore, smFRET is powerful in measuring structural changes in the enzyme or substrate during binding and catalysis. This work presents a protocol for single-molecule imaging of the interaction of a four-way Holliday junction (HJ) and gap endonuclease I (GEN1), a cytosolic homologous recombination enzyme. Also presented are single-color and two-color alternating excitation (ALEX) smFRET experimental protocols to follow the resolution of the HJ by GEN1 in real-time. The kinetics of GEN1 dimerization are determined at the HJ, which has been suggested to play a key role in the resolution of the HJ and has remained elusive until now. The techniques described here can be widely applied to obtain valuable mechanistic insights of many enzyme-DNA systems.


Suppression of 5'-nucleotidase enzymes promotes AMP-activated protein kinase (AMPK) phosphorylation and metabolism in human and mouse skeletal muscle.
The 5'-nucleotidase (NT5) family of enzyme dephosphorylates non-cyclic nucleoside monophosphates to produce nucleosides and inorganic phosphates. We hypothesized that gene silencing of NT5 enzymes to increase the intracellular availability of AMP would increase AMP-activated protein kinase (AMPK) activity and metabolism. We determined the role of cytosolic NT5 in metabolic responses linked to the development of insulin resistance in obesity and type 2 diabetes. Using siRNA to silence NT5C2 expression in cultured human myotubes, we observed a 2-fold increase in the AMP/ATP ratio, a 2.4-fold increase in AMPK phosphorylation (Thr(172)), and a 2.8-fold increase in acetyl-CoA carboxylase phosphorylation (Ser(79)) (p < 0.05). siRNA silencing of NT5C2 expression increased palmitate oxidation by 2-fold in the absence and by 8-fold in the presence of 5-aminoimidazole-4-carboxamide 1-β-d-ribofuranoside. This was paralleled by an increase in glucose transport and a decrease in glucose oxidation, incorporation into glycogen, and lactate release from NT5C2-depleted myotubes. Gene silencing of NT5C1A by shRNA injection and electroporation in mouse tibialis anterior muscle reduced protein content (60%; p < 0.05) and increased phosphorylation of AMPK (60%; p < 0.05) and acetyl-CoA carboxylase (50%; p < 0.05) and glucose uptake (20%; p < 0.05). Endogenous expression of NT5C enzymes inhibited basal lipid oxidation and glucose transport in skeletal muscle. Reduction of 5'-nucleotidase expression or activity may promote metabolic flexibility in type 2 diabetes.


Cell Therapy in Veterinary Medicine as a Proof-of-Concept for Human Therapies: Perspectives From the North American Veterinary Regenerative Medicine Association.
In the past decade, the potential to translate scientific discoveries in the area of regenerative therapeutics in veterinary species to novel, effective human therapies has gained interest from the scientific and public domains. Translational research using a One Health approach provides a fundamental link between basic biomedical research and medical clinical practice, with the goal of developing strategies for curing or preventing disease and ameliorating pain and suffering in companion animals and humans alike. Veterinary clinical trials in client-owned companion animals affected with naturally occurring, spontaneous disease can inform human clinical trials and significantly improve their outcomes. Innovative cell therapies are an area of rapid development that can benefit from non-traditional and clinically relevant animal models of disease. This manuscript outlines cell types and therapeutic applications that are currently being investigated in companion animals that are affected by naturally occurring diseases. We further discuss how such investigations impact translational efforts into the human medical field, including a critical evaluation of their benefits and shortcomings. Here, leaders in the field of veterinary regenerative medicine argue that experience gained through the use of cell therapies in companion animals with naturally occurring diseases represent a unique and under-utilized resource that could serve as a critical bridge between laboratory/preclinical models and successful human clinical trials through a One-Health approach.


[Changes of neurocytes in CNS under general exposure to UHF field with local protection applied].
Experiments on white rats were performed to study influence of UHF field on cortical sensomotor area under general exposure or with the head shielded. The changes in CNS caused by UHF field were not prevented completely by means of the shield. That is probably due to pathologic reflex impulses from the body receptors.


Surgical masks for protection of health care personnel against pandemic novel swine-origin influenza A (H1N1)-2009: results from an observational study.
There is ongoing debate about the efficacy of surgical masks versus N95 respirators for protection against pandemic novel swine-origin influenza A (H1N1)-2009. Our hospital, which is designated to manage outbreaks of emerging infection, has robust surveillance systems to detect infection in staff. The incidence of pandemic H1N1-2009 remained low in staff with use of surgical masks.


Involving consumers in health research: what do consumers say?
To ensure that the contribution of patients and consumers in health research is better understood, respected and fully utilised. Type of program or service: Consumer representative networks that form part of a broader quality improvement program in local health services. Consultations were held with members of health consumer networks in Sydney, Northern Sydney and Western Sydney Local Health Districts, and the Sydney Children's Hospitals Network (at Westmead) about how to better involve consumers in health research. Feedback from 20 volunteers suggested that consumer involvement in research would be improved if: consumers understood more about research; communications clearly explained the research, why it was relevant to consumers and what might be involved; consumers' contributions were heard and respected; and being involved in research was made an easy and positive experience. People want to be involved in health research, and have valuable contributions to make. We must ensure that the potential contribution of patients and consumers is fully utilised, and get a great deal better at communicating benefits and risks.


Mechanism-based selection of a potent kallikrein-related peptidase 7 inhibitor from a versatile library based on the sunflower trypsin inhibitor SFTI-1.
Potent and specific enzyme inhibition is a key goal in development of therapeutic inhibitors targeting proteolytic activity. The backbone-cyclised peptide, Sunflower Trypsin Inhibitor (SFTI-1) affords a scaffold that can be engineered to achieve both these aims. SFTI-1's mechanism of inhibition is unusual in that it shows fast-on/slow-off kinetics driven by cleavage and religation of a scissile bond. This phenomenon was used to select a nanomolar inhibitor of kallikrein related peptidase 7 (KLK7) from a versatile library of SFTI variants with diversity tailored to exploit distinctive surfaces present in the active site of serine proteases. Inhibitor selection was achieved through use of size exclusion chromatography to separate protease/inhibitor complexes from unbound inhibitors followed by inhibitor identification according to molecular mass ascertained by mass spectrometry. This approach identified a single dominant inhibitor species with molecular weight of 1562.4 Da, which is consistent with the SFTI variant SFTI-WCTF. Once synthesised individually this inhibitor showed an IC50 of 173.9±7.6 nM against chromogenic substrates and could block protein proteolysis. Molecular modelling analysis suggested that selection of SFTI-WCTF was driven by specific aromatic interactions and stabilised by an enhanced internal hydrogen bonding network. This approach provides a robust and rapid route to inhibitor selection and design. © 2013 Wiley Periodicals, Inc. Biopolymers, 2013.


Genomic Prediction for Grain Yield and Yield-Related Traits in Chinese Winter Wheat.
Genomic selection (GS) is a strategy to predict the genetic merits of individuals using genome-wide markers. However, GS prediction accuracy is affected by many factors, including missing rate and minor allele frequency (MAF) of genotypic data, GS models, trait features, etc. In this study, we used one wheat population to investigate prediction accuracies of various GS models on yield and yield-related traits from various quality control (QC) scenarios, missing genotype imputation, and genome-wide association studies (GWAS)-derived markers. Missing rate and MAF of single nucleotide polymorphism (SNP) markers were two major factors in QC. Five missing rate levels (0%, 20%, 40%, 60%, and 80%) and three MAF levels (0%, 5%, and 10%) were considered and the five-fold cross validation was used to estimate the prediction accuracy. The results indicated that a moderate missing rate level (20% to 40%) and MAF (5%) threshold provided better prediction accuracy. Under this QC scenario, prediction accuracies were further calculated for imputed and GWAS-derived markers. It was observed that the accuracies of the six traits were related to their heritability and genetic architecture, as well as the GS prediction model. Moore-Penrose generalized inverse (GenInv), ridge regression (RidgeReg), and random forest (RForest) resulted in higher prediction accuracies than other GS models across traits. Imputation of missing genotypic data had marginal effect on prediction accuracy, while GWAS-derived markers improved the prediction accuracy in most cases. These results demonstrate that QC on missing rate and MAF had positive impact on the predictability of GS models. We failed to identify one single combination of QC scenarios that could outperform the others for all traits and GS models. However, the balance between marker number and marker quality is important for the deployment of GS in wheat breeding. GWAS is able to select markers which are mostly related to traits, and therefore can be used to improve the prediction accuracy of GS.


Urban vs Rural Residence and the Prevalence of Depression and Mood Disorder Among African American Women and Non-Hispanic White Women.
There is a paucity of research among African Americans and rural residents. Little is known about the association between urbanicity and depression or about the interaction of urbanicity, race/ethnicity, and sex on depression and mood disorder prevalence. To examine the interaction of urbanicity and race/ethnicity on lifetime and 12-month major depressive disorder (MDD) and mood disorder prevalence for African American women and non-Hispanic white women. The US National Survey of American Life data were used to examine the interaction of urbanicity and race/ethnicity on lifetime and 12-month diagnoses of DSM-IV MDD and mood disorder among female respondents, who included noninstitutionalized African American, Caribbean black, and non-Hispanic white women in the United States between February 2001 and June 2003. Participants included 1462 African American women and 341 non-Hispanic white women recruited from the South because all suburban and rural National Survey of American Life respondents resided in this region. Bivariate multiple logistic regression and adjusted prevalence analyses were performed. Urban, suburban, or rural location (assessed via Rural-Urban Continuum Codes), self-reported race/ethnicity, and sociodemographic factors (age, education, household income, and marital status) were included in the analysis. Lifetime and 12-month MDD and mood disorder assessed via the World Mental Health Composite International Diagnostic Interview. Compared with urban African American women, rural African American women had a significantly lower odds of meeting criteria for lifetime (odds ratio [OR], 0.39; 95% CI, 0.23-0.65) and 12-month (OR, 0.29; 95% CI, 0.18-0.46) MDD and for lifetime (F = 0.46; 95% CI, 0.29-0.73) and 12-month (F = 0.42; 95% CI, 0.26-0.66) mood disorder. However, the interaction of urbanicity and race/ethnicity suggested that rural non-Hispanic white women had a significantly higher odds of meeting criteria for lifetime (OR, 2.76; 95% CI, 1.22-6.24) and 12-month (OR, 9.48; 95% CI, 4.65-19.34) MDD and for lifetime (OR, 2.27; 95% CI, 1.06-4.87) and 12-month (OR, 5.99; 95% CI, 3.01-11.94) mood disorder than rural African American women. Adjusted prevalence analyses revealed significantly lower rates of lifetime (4.2%) and 12-month (1.5%) MDD among rural African American women than their urban counterparts (10.4% vs 5.3%; P ≤ .01). The same pattern was found for mood disorder, with rural African American women experiencing significantly lower rates of lifetime (6.7%) and 12-month (3.3%) mood disorder when compared to urban African American women (13.9% vs 7.6%; P ≤ .01) Conversely, rural non-Hispanic white women had significantly higher rates of 12-month MDD (10.3%) and mood disorder (10.3%) than their urban counterparts (3.7% vs 3.8%; P ≤ .01). Rural residence differentially influences MDD and mood disorder prevalence among African American women and non-Hispanic white women. These findings offer a first step toward understanding the cumulative effect of rural residence and race/ethnicity on women's depression prevalence, suggesting the need for further research in this area.


[ Fungal extracellular ribonucleases (Review)].
Results of studies of certain fungal extracellular ribonucleases mainly isolated from representatives of the genera Aspergillus and Penicillium are summarized. The isolation of these enzymes in highly purified states in the 1970-1980s strongly stimulated further studies of their structure, functions, and mechanisms of action. This also promoted the use of ribonucleases as catalysts in oligoribonucleotide syntheses and as objects of comparative and evolutionary biochemistry and other research works. Results of studies of the primary, secondary, and spatial structures of guanyl-specific fungal ribonucleases are reviewed. These studies revealed a high homology within the subfamilies of fungal, bacterial, and actinomycete RNases. Characteristics of the nonspecific Pb2 RNase are considered.


X inactivation as a source of behavioural differences in monozygotic female twins.
Although members of monozygotic twin pairs are identical in genome sequence, they may differ in patterns of gene expression. One early and irreversible process affecting gene expression, which can create differences within pairs of female monozygotic twins, is X inactivation - one twin can express mainly paternally-received genes on the X chromosome while the other twin expresses mainly maternally-received genes. It follows that non-identical X chromosome expression may cause female monozygotic twins to correlate less strongly than male monozygotic twins on complex behavioural traits affected by X-linked loci. We tested this hypothesis using data from around 4000 same-sex twin pairs on 9 social, behavioural and cognitive measures at ages 2, 3 and 4. Consistent with our hypothesis, monozygotic males were generally more similar than monozygotic females. Three of four significant differences were in traits showing higher correlations in males than females, and these traits - prosocial behaviour, peer problems, and verbal ability - have all been proposed previously in the literature as being influenced by genes on the X chromosome. Interestingly, dizygotic twins showed the reverse pattern of correlations for similar variables, which is also consistent with the X inactivation hypothesis; taken together, then, our monozygotic and dizygotic results suggest the presence of quantitative trait loci on the X chromosome.


Hypothermia attenuates delayed cortical cell death and ROS generation following CO inhalation.
Carbon monoxide (CO) is the most popular cause of poisoning. The bilateral basal ganglia lesion characterizes the delayed neuronal cell death (DCD). We demonstrated there were both apoptosis and necrosis in the cortex, basal ganglia and hippocampus in a case of human CO accident. To elucidate the mechanism of DCD after CO inhalation, histological studies on the rat brain were conducted. Rats were ventilated with nitrous oxide (sham group), 10% O(2) (hypoxia group) or 1005 ppm CO (CO group) for 90 min, while the pericranial temperature was controlled at either 32, 37, or 39 degrees C during CO inhalation. After reoxygenation for 30 min, the rats were allowed to recover for 48 h. The ratio of eosinophilic and HNE-positive neurons in the cortex were higher in the CO group than in the hypoxia group at 37 degrees C, while the PaO(2) was much lower in the hypoxia than in the CO group. The damage was alleviated in the hypothermia (32 degrees C) as compared with normothermia, while the hyperthermia (39 degrees C) did not significantly increased it. CO inhalation injures neuron by reactive oxygen species (ROS), independent of hypoxia, as can be concluded from the histological comparison of DCD with HNE immunoreactivity.


Two-step curing reaction of epoxy resin studied by thermal analysis and infrared spectroscopy.
A curing reaction of bisphenol A diglycidyl ether epoxy resin with 4,4'-diaminodicyclohexyl methane hardener was investigated by means of modulated differential scanning calorimetry (MDSC) and infrared (IR) spectroscopy. MDSC observation revealed that the curing process of the resin occurred in two steps. Mid-infrared and near-infrared spectra of the resin were measured as a function of temperature. The obtained spectra were analyzed by perturbation-correlation moving-window two-dimensional correlation spectroscopy (PCMW2D-COS). The first step was revealed as a polymerization reaction among the oxirane group and primary and secondary amine groups, followed by etherification; the second step of the curing process occurred in the vicinity of the gelation point and was characterized by the growth of a three-dimensional cross-linking structure with tertiary amine and etherification of the hydroxyl group.


Western blotting as a tool for the serodiagnosis of farmer's lung disease: validation with Lichtheimia corymbifera protein extracts.
Electrosyneresis and double diffusion are immunoprecipitation techniques commonly used in the serological diagnosis of Farmer's lung disease (FLD). These techniques are reliable but lack standardization. The aim of this study was to evaluate Western blotting for the serodiagnosis of FLD. We carried out Western blotting with an antigenic extract of Lichtheimia corymbifera, an important aetiological agent of the disease. The membranes were probed with sera from 21 patients with FLD and 21 healthy exposed controls to examine the IgG antibody responses against purified somatic antigens. Given the low prevalence of the disease, 21 patients could be considered as a relevant series. Four bands were significantly more frequently represented in membranes probed with FLD sera (bands at 27.7, 40.5, 44.0 and 50.5 kDa) than those probed with control sera. We assessed the diagnostic value of different criteria alone or in combination. The diagnostic accuracy of the test was highest with the inclusion of at least two of the following criteria: at least five bands on the strip and the presence of one band at 40.5 or 44.0 kDa. Sensitivity, specificity and positive and negative predictive values were all 81%, and the odds ratio was 18.06. Inclusion of bands of high intensity diminished rather than improved the diagnostic value of the test. We concluded that Western blotting is a valuable technique for the serodiagnosis of FLD. The industrial production of ready-to-use membranes would enable the routine use of this technique in laboratories, and provide reliable and standardized diagnostic results within a few hours.


High-flow nasal oxygen reduces endotracheal intubation: a randomized clinical trial.
The benefits of high-flow nasal cannula (HFNC) as primary intervention in patients with acute hypoxemic respiratory failure (AHRF) are still a matter in debate. Our objective was to compare HFNC therapy versus conventional oxygen therapy (COT) in the prevention of endotracheal intubation in this group of patients. An open-label, controlled and single-centre clinical trial was conducted in patients with severe AHRF, defined by a PaO2/FIO2 ratio ⩽200, to compare HFNC with a control group (CG) treated by COT delivered through a face mask, with the need to perform intubation as the primary outcome. The secondary outcomes included tolerance of the HFNC device and to look for the predictive factors for intubation in these patients. A total of 46 patients were included (22 in the COT group and 24 in the HFNC group) 48% of whom needed intubation: 63% in the COT group and 33% in the HFNC group, with significant differences both in intention to treat [χ2 = 4.2; p = 0.04, relative risk (RR) = 0.5; confidence interval (CI) 95%: 0.3-1.0] and also in treatment analysis (χ2 = 4.7; p = 0.03; RR = 0.5; IC 95%: 0.3-0.9) We obtained a number needed to treat (NNT) = 3 patients treated to avoid an intubation. Intubation occurred significantly later in the HFNC group. Estimated PaO2/FIO2, respiratory rate and dyspnea were significantly better in the HFNC group. Patients treated with HFNC who required intubation presented significant worsening after the first 8 h, as compared with non-intubated HFNC group patients. Mortality was 22% with no differences. The HFNC group patients were hospitalized for almost half of the time in the intensive care unit (ICU) and in the ward, with significantly less hospital length of stay. A total of 14 patients in the HFNC group (58%) complained of excessive heat and 17% of noise; 3 patients did not tolerate HFNC. Patients with severe acute hypoxemic respiratory failure who tolerate HFNC present a significantly lower need for endotracheal intubation compared with conventional oxygen therapy. EUDRA CT number: 2012-001671-36The reviews of this paper are available via the supplemental material section.


Orf: a case report.
Ecthyma contagiosum (orf), a viral disease endemic to sheep and goats, can be zoonotically transmitted to humans through contact with infected animals. While the disease is common among sheep and goat herders worldwide, it comes to medical attention infrequently since it is generally a mild self-limited illness. We recently treated a healthy 36-year-old female who presented with bullous lesions on her fingers and a diffuse macular rash which had developed after antibiotic therapy for her bullae. She had been caring for her neighbor's goats which had recently been ill with "sore mouth." We discuss this case of orf and review the medical literature on this self-limited illness uncommon to the midwestern United States.


Composites of kaolin and polydimethylsiloxane.
Kaolin particles were surface-treated with isobutyltrimethoxysilane (IBTMS), hydrogenated tallow (HT), and a polyisobutyl chain-based stabilizer (SAP) to make composites with polydimethylsiloxane (PDMS). IBTMS did not cover the strong acid sites on the kaolin surface and as a result a cross-linking reaction occurred for silanol-terminated PDMS. The polyisobutyl chain of SAP was found to be incompatible with PDMS and this caused aggregation of the kaolin particles. HT was the most effective at dispersing the particles into silanol-terminated PDMS. The aggregation state of the composites was characterized using rheology and microscopy. Both showed the HT-treated particles were well-dispersed in low molecular weight silanol-terminated PDMS, and they were weakly flocculated in higher molecular weight silanol-terminated PDMS. However, the same particles aggregated when dispersed in methyl-terminated PDMS. It appears the silanol-terminated PDMS acted as costabilizer through interaction with the kaolin surface. Transverse relaxation NMR was used to probe mobility of the PDMS chains in the composites. This showed little dependence on surface treatment, aggregation state, or polymer end groups. For all samples, chain mobility decreased with increasing kaolin concentration.


[High prevalence of group B Streptococcus colonization in Mexican pregnant women].
To determine the prevalence of group B Streptococcus (GBS) colonization in two anatomical sites in Mexican women of childbearing age, as well as the associated risk factors. A retrospective cohort analysis was made with two groups of women between 14 and 44 years old. We formed two groups of 72 women; one had a recent positive group B Streptococcus culture and the other, paired by age and culture date, had a negative culture of the same bacterium. All of them answered a validated questionnaire and two rectal swabs were obtained and cultured for isolation of group B Streptococcus. Prevalence of GBS colonization was 18% for two anatomical sites (heavy colonization), and 37% for one anatomical site; the overall prevalence was 54.9%. Three or more sexual partners increased by 4-fold the risk of heavy GBS colonization (p < 0.01). In this study 49 (34%) women were pregnant, 26 (53%) of them were colonized by GBS and 7 (14.3%) were heavy colonized. Prevalence of GBS during pregnancy in Mexican women was higher than the reported previously, even in developed countries. Risk of colonization increased by 4-fold with a history of three or more sexual partners.


Cohabitation Expectations among Young Adults in the United States: Do They Match Behavior?
Cohabitation continues to rise, but there is a lack of knowledge about expectations to cohabit and the linkage between expectations and subsequent cohabitation. We capitalize on a new opportunity to study cohabitation expectations by drawing on the National Longitudinal Study of Youth (NLSY79) main youth and two waves (2008 and 2010) of the NLSY young adult (YA) surveys (n=1,105). We find considerable variation in cohabitation expectations: 39.9% have no expectation of cohabiting in the future and 16.6% report high odds of cohabiting in the next two years. Cohabitation expectations are associated with higher odds of entering a cohabiting relationship, but are not perfectly associated. Only 38% of young adults with certain cohabitation expectations in 2008 entered a cohabiting union by 2010. Further investigation of the mismatch between expectations and behaviors indicates that a substantial minority (30%) who entered a cohabiting union had previously reported no or low expectations, instances of what we term "unplanned cohabitation." Our findings underscore the importance of considering not just behavior, but also individuals' expectations for understanding union formation, and more broadly, family change.


Non-invasive Brain Stimulation in Pediatric Migraine: A Perspective From Evidence in Adult Migraine.
Pediatric migraine remains still a challenge for the headache specialists as concerns both diagnostic and therapeutic aspects. The less ability of children to describe the exact features of their migraines and the lack of reliable biomarker for migraine contribute to complicate the diagnostic process. Therefore, there's need for new effective tools for supporting diagnostic and therapeutic approach in children with migraine. Recently, promising results have been obtained in adult headache by means of application of neurostimulation techniques both for investigating pathophysiological mechanisms and also for therapeutical applications. Non-invasive brain stimulation (NIBS) techniques like transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) indeed proved to be generally safe and showing also some evidence of efficacy particularly for the symptomatic treatment. On such basis, in the last years increasing interest is rising in scientific pediatric community to evaluate the potential of such approaches for treatment pediatric headaches, particularly in migraine, even if the evidence provided is still very poor. Here we present a perspective for application of TMS and tDCS technique in children migraine principally based on evidence coming by studies in adults.


Mental disorder, imprisonment and reduced life expectancy--A nationwide psychiatric inpatient cohort study.
There is a strong correlation between severe mental illness and criminality, but little is known about how these two problem areas together may affect health outcomes. The objective of this paper is to compare survival rates of male psychiatric inpatients over a 25-year period who have and have not been subject to imprisonment, allowing for nature of psychiatric morbidity. A nationwide cohort of men who had ever been psychiatric inpatients was identified from Icelandic data-registers, and their diagnoses after first discharge, cumulative incidence of imprisonment, and mortality established from records. Using a nested case-control design, survival differences were determined between those ever imprisoned and those never imprisoned. Between January 1983 and March 2008, 7665 men were admitted to psychiatric wards in Iceland, of whom 812 (10.6%) had served a prison sentence during that time. Cumulative incidence of imprisonment was highest in the youngest age group (21%). Substance use and personality disorders were more common amongst those imprisoned. All-cause mortality, adjusted for diagnosis, age, and year of admission, was twice as high amongst those imprisoned as those not imprisoned (Hazard ratio = 2.0, 95% CI 1.5-2.6, p < 0.001). Our findings indicate that psychiatric inpatients with criminal records should receive special attention with respect to all aspects of their health, not only within psychiatric services but also through more collaboration between the healthcare and judicial systems.


MicroRNAs can generate thresholds in target gene expression.
MicroRNAs (miRNAs) are short, highly conserved noncoding RNA molecules that repress gene expression in a sequence-dependent manner. We performed single-cell measurements using quantitative fluorescence microscopy and flow cytometry to monitor a target gene's protein expression in the presence and absence of regulation by miRNA. We find that although the average level of repression is modest, in agreement with previous population-based measurements, the repression among individual cells varies dramatically. In particular, we show that regulation by miRNAs establishes a threshold level of target mRNA below which protein production is highly repressed. Near this threshold, protein expression responds sensitively to target mRNA input, consistent with a mathematical model of molecular titration. These results show that miRNAs can act both as a switch and as a fine-tuner of gene expression.


The Outcome of Patients With Localized Undifferentiated Pleomorphic Sarcoma of the Lower Extremity Treated at Stanford University.
As a diagnosis of exclusion, Undifferentiated Pleomorphic Sarcoma (UPS) has unclear clinical characteristics. The objective of this retrospective cohort study is to investigate which clinical and prognostic factors of primary lower-extremity UPS will determine failure. We retrospectively reviewed 55 primary lower-extremity UPS cases treated at Stanford between 1998 and 2015. Overall Survival (OS) and Disease-Free Survival (DFS) curves were calculated. Univariate Fisher's Exact Tests were used to examine relationships between disease recurrence, treatment, patient factors, tumor characteristics, and surgical margins. 5-year DFS and OS rates were 60% (95% CI, 45%-72%) and 68% (95% CI, 53%-79%), respectively. The 5-year DFS rate for patients with positive margins was 33.3% (95% CI, 5%-68%) compared with 63% (95% CI, 47%-76%) for patients with negative margins. (Log-rank, P=0.03). The OS rate for those with disease recurrence was 42% % (95% CI, 16%-67%) compared with 76% (95% CI, 59%-87%) for patients who did not have disease recurrence (log-rank, P=0.021). Local failure occurred more frequently with omission of radiation therapy (Fisher's exact test, P=0.009). Positive surgical margins are an important prognostic factor for predicting relapse in UPS. Relapse of any kind led to worse OS. Radiation therapy improved local control of disease but had no statistically significant effect on DFS, highlighting the need for improved diagnostics to identify those at highest risk for hematogenous metastasis and for selection of patients for adjuvant systemic treatment.


Single-Cell Transcriptomics Links Loss of Human Pancreatic β-Cell Identity to ER Stress.
The maintenance of pancreatic islet architecture is crucial for proper β-cell function. We previously reported that disruption of human islet integrity could result in altered β-cell identity. Here we combine β-cell lineage tracing and single-cell transcriptomics to investigate the mechanisms underlying this process in primary human islet cells. Using drug-induced ER stress and cytoskeleton modification models, we demonstrate that altering the islet structure triggers an unfolding protein response that causes the downregulation of β-cell maturity genes. Collectively, our findings illustrate the close relationship between endoplasmic reticulum homeostasis and β-cell phenotype, and strengthen the concept of altered β-cell identity as a mechanism underlying the loss of functional β-cell mass.


Aberration of porphyrin metabolism in iron-deficient anaemic rats.
Iron-deficient rats excreted greater amounts of 5-aminolaevulinate in urine but the output of porphobilinogen was decreased considerably. In addition, activity of the enzyme 5-aminolaevulinate dehydratase was diminished in bone marrow and liver. The results suggest that in iron deficiency a defect occurs in porphyrin synthesis at the level of porphobilinogen formation.


Phase 2 study of the JAK kinase inhibitor ruxolitinib in patients with refractory leukemias, including postmyeloproliferative neoplasm acute myeloid leukemia.
We conducted a phase 2 study of ruxolitinib in patients with relapsed/refractory leukemias. Patients with acceptable performance status (0-2), adequate organ function, and no active infection, received ruxolitinib 25 mg orally twice a day for 4 weeks (1 cycle). Response was assessed after every 2 cycles of treatment, and patients who completed 2 cycles were allowed to continue treatment until disease progression. Dose escalation to 50 mg twice daily was permitted in patients demonstrating a benefit. Thirty-eight patients, with a median age of 69 years (range, 45-88), were treated. The median number of prior therapies was 2 (range, 1-6). Twelve patients had JAK2V617F mutation. Patients received a median of 2 cycles of therapy (range, 1-22). Three of 18 patients with postmyeloproliferative neoplasm (MPN) acute myeloid leukemia (AML) showed a significant response; 2 achieved complete remission (CR) and one achieved a CR with insufficient recovery of blood counts (CRi). The responding patients with palpable spleens also had significant reductions in spleen size. Overall, ruxolitinib was very well tolerated with only 4 patients having grade 3 or higher toxicity. Ruxolitinib has modest antileukemic activity as a single agent, particularly in patients with post-MPN AML. The study was registered at www.clinicaltrials.gov as NCT00674479.


The effects of calf muscle self-massage on ankle joint range of motion and tendon-muscle morphology.
Self-massage using a foam roller (foam rolling) has been used to improve joint range of motion (ROM). However, the effect of foam rolling on the morphology of a targeted muscle, tendon, and muscle-tendon unit (MTU) has not been fully clarified. This study aimed to investigate extensibility changes in the gastrocnemius muscle (GM), MTU, and the Achilles tendon (AT) in terms of maximum ankle dorsiflexion (max-DF) following a foam rolling intervention. This was an interventional study with no controls. Study participants comprised 10 male and female students (mean [standard deviation]: 22.7 [2.5] years; height, 164.2 [6.7] cm; weight, 57.9 [7.9] kg). The foam rolling intervention was performed on the right leg plantar flexor muscles for 3 min. The outcomes were max-DF with specified resistance values (ROM-SR) and non-specified resistance values (ROM-NSR) and GM, MTU, and AT extensibility. An ultrasound device was used to determine the rate of change by subtracting the value in a neutral ankle joint position (0°) from the ankle max-DF to identify GM, MTU, and AT extensibility. All outcomes were measured pre- and post-intervention. The range of ankle joint dorsiflexion increased significantly following the foam rolling intervention (Δ: ROM-SR, +4.35 [5.79]; ROM-NSR, +4.18 [4.43]), whereas GM extensibility increased 4.0 mm, although no significant difference was observed pre- and post-intervention. Foam rolling was effective in increasing ankle joint dorsiflexion ROM. Moreover, it was suggested that the GM morphology might be affected by the intervention.


Hepatic cyclooxygenase-2 overexpression induced spontaneous hepatocellular carcinoma formation in mice.
Cyclooxygenase (COX)-2 is upregulated in hepatocellular carcinoma (HCC). However, the direct causative effect of COX-2 in spontaneous HCC formation remains unknown. We thus investigate the role and molecular pathogenesis of COX-2 in HCC by using liver-specific COX-2 transgenic (TG) mice. We found spontaneous HCC formation with elevated inflammatory infiltrates and neovessels in male TG mice (3/21, 14.3%), but not in any of male WT mice (0/19). Reduced representation bisulfite sequencing (RRBS) and gene expression microarrays were performed in the HCC tumor and non-HCC liver tissues to investigate the molecular mechanisms of COX-2-driven HCC. By RRBS, DNA promoter hypermethylation was identified in HCC from TG mice. Induction of promoter hypermethylation was associated with reduced tet methylcytosine dioxygenase 1 (TET1) expression by COX-2. TET1 could catalyze the conversion of 5-methylcytosine into 5-hydroxymethylcytosine (5hmC) and prevents DNA hypermethylation. In keeping with this, loss of 5hmC was demonstrated in COX-2-induced HCC. Consistently, COX-2 overexpression in human HCC cell lines could reduce both TET1 expression and 5hmc levels. Integrative analyses of DNA methylation and gene expression profiles further identified significantly downregulated genes including LTBP1, ADCY5 and PRKCZ by promoter methylation in COX-2-induced HCC. Reduced expression of LTBP1, ADCY5 and PRKCZ by promoter hypermethylation was further validated in human HCCs. Bio-functional investigation revealed that LTBP1 inhibited cell proliferation in HCC cell lines, suggesting its potential role as a tumor suppressor in HCC. Gene expression microarrays revealed that signaling cascades (AKT (protein kinase B), STK33 (Serine/Threonine kinase 33) and MTOR (mechanistic target of rapamycin) pathways) were enriched in COX-2-induced HCC. In conclusion, this study demonstrated for the first time that enhanced COX-2 expression in hepatocytes is sufficient to induce HCC through inducing promoter hypermethylation by reducing TET1, silencing tumor-suppressive genes and activating key oncogenic pathways. Inhibition of COX-2 represents a mechanism-based target for HCC prevention.


Derivation and genome-wide association study of a principal component-based measure of heat tolerance in dairy cattle.
Heat stress represents a key factor that negatively affects the productive and reproductive performance of farm animals. In the present work, a new measure of tolerance to heat stress for dairy cattle was developed using principal component analysis. Data were from 590,174 test-day records for milk yield, fat and protein percentages, and somatic cell score of 39,261 Italian Holstein cows. Test-day records adjusted for main systematic factors were grouped into 11 temperature-humidity index (THI) classes. Daughter trait deviations (DTD) were calculated for 1,540 bulls as means of the adjusted test-day records for each THI class. Principal component analysis was performed on the DTD for each bull. The first 2 principal components (PC) explained 42 to 51% of the total variance of the system across the 4 traits. The first PC, a measure of the level at which the curve is located, was interpreted as a measure of the level at which the DTD curve was located. The second PC, which shows the slope of increasing or decreases DTD curves, synthesized the behavior of the DTD pattern. Heritability of the 2 component scores was moderate to high for level across all traits (range = 0.23-0.82) and low to moderate for slope (range = 0.16-0.28). For each trait, phenotypic and genetic correlations between level and slope were equal to zero. A genome-wide association analysis was carried out on a subsample of 423 bulls genotyped with the Illumina 50K bovine bead chip (Illumina, San Diego, CA). Two single nucleotide polymorphisms were significantly associated with slope for milk yield, 4 with level for fat percentage, and 2 with level and slope of protein percentage, respectively. The gene discovery was carried out considering windows of 0.5 Mb surrounding the significant markers and highlighted some interesting candidate genes. Some of them have been already associated with the mechanism of heat tolerance as the heat shock transcription factor (HSF1) and the malonyl-CoA-acyl carrier protein transacylase (MCAT). The 2 PC were able to describe the overall level and the slope of response of milk production traits across increasing levels of THI index. Moreover, they exhibited genetic variability and were genetically uncorrelated. These features suggest their use as measures of thermotolerance in dairy cattle breeding schemes.


High-frequency Bekesy audiometry: III. Reliability and validity revisited.
Normal-hearing young adults (N: 30) produced 3 fixed-frequency monaural audiograms by Bekesy tracking on a Grason-Stadler E-800 audiometer (modified for high frequencies) for pulsed pure tones in 2-kc/s steps progressively from 7-19 kc/s. The earphone was not moved between one pair of audiograms but was removed and replaced between another pair. After 1 mo, 16 Ss returned for retest on the HF E-800 audiometer and on a similar audiometer using the conventional Method of Limits. Maximum group mean retest HTL differences approximated 5 db. Statistical analysis indicated that the arrays of HTLs within and across sessions were equivalent. Reliability and validity coefficients were high and significantly different from zero. It was concluded that the HF E-800 could with such Ss be used with some confidence to assess high-frequency sensitivity.


Reliving lifelong episodic autobiographical memories via the hippocampus: a correlative resting PET study in healthy middle-aged subjects.
We aimed at identifying the cerebral structures whose synaptic function subserves the recollection of lifetime's episodic autobiographical memory (AM) via autonoetic consciousness. Twelve healthy middle-aged subjects (mean age: 59 years +/- 2.5) underwent a specially designed cognitive test to assess the ability to relive richly detailed episodic autobiographical memories from five time periods using the Remember/Know procedure. We computed an index of episodicity (number of Remember responses justified by the recall of specific events and details) and an index of retrieval spontaneity, and additionally an index of semanticized memories (number of Know responses). The regional cerebral blood flow (rCBF) was measured in the resting state, with H(2)O(15) as part of an activation PET study. The indexes were correlated with blood flow using volumes of interest in frontotemporal regions, including hippocampus and voxel-wise analyses in SPM. With both analyses, significant correlations were mainly found between the index of episodicity and rCBF in the medial temporal lobe, including hippocampus, across the five time periods (unlike the index of semanticized memories) and between the spontaneity index and rCBF in the prefrontal areas. These results highlight, in healthy subjects, the distinct role of these two structures in AM retrieval and support the view that the hippocampus is needed for reexperiencing detailed episodic memories no matter how old they are.


Study of basic electrostatic radiation shield characteristics on board the Cosmos 605 satellite.
Direct measurement of conduction currents in the electrostatic radiation shield model carried out on board the Cosmos 605 satellite yielded additional information on the dose, weight and size characteristics and helped to evaluate the power requirements for a real electrostatic radiation shield. It was found that the electrostatic shield power requirements (at an electric field strength of 10(7)V m-1 and total shielded surface of 10(2) m2) did not exceed 10 watts, i.e. it was at least one order of magnitude lower than had been assumed from data obtained in ground-based studies. These results show the feasibility of protective electric fields of the required strength, with the space vacuum around the vehicle being used as an insulating medium.


[Comparative characteristics of septal "burst" neurons after elimination of afferent effects of the reticular formation in the rabbit].
Comparative analysis of characteristics of rhythmic theta-activity in the neurones of the medial septal nucleus and nucleus of diagonal band was performed in intact rabbits after. i. v. injection of pentobarbital, and in rabbits with chronic lesion of the ascending brain-stem afferent fibers. In both conditions theta-bursts disappeared in some cells with unstable periodic rhythmic modulation; substantial population of the septal units preserved regular burst activity. Main characteristics of theta-bursts were almost identical in both states, their mean frequency decreased to 3.5 Hz. The theta-rhythm in hippocampal EEG was usually absent; but low-frequency rhythmic activity could be evoked by electrical or sensory stimulation as well as by injection of bemegrid or physostigmine. The data show that the ascending brain-stem afferents control: the frequency of the bursts in a population of septal units regarded as bursting pace-maker cells; the total number of the septal cells secondarily (synaptically) involved into rhythmic activity. The effect of pentobarbital upon theta-rhythm results from elimination of these influences upon the septal cells.


Iatrogenic aortic dissection during right coronary artery stenting.
Aortic dissection limited to one sinus of Valsalva has been observed as an iatrogenic complication during coronary intervention. We report on a 65-year-old female patient who had a diagnosis of acute inferior myocardial infarction and experienced type A aortic dissection during stenting of the right coronary artery (RCA). Dissection was seen during aortic injection. There were no associated diseases in the sinuses of Valsalva or the aortic valve. An opening was seen intraoperatively in the right sinus of Valsalva. The opening was immediately and successfully sutured. The RCA was bypassed.


Assembly of cellulose nanocrystals in a levitating drop probed by time-resolved small angle X-ray scattering.
Assembly of bio-based nano-sized particles into complex architectures and morphologies is an area of fundamental interest and technical importance. We have investigated the assembly of sulfonated cellulose nanocrystals (CNC) dispersed in a shrinking levitating aqueous drop using time-resolved small angle X-ray scattering (SAXS). Analysis of the scaling of the particle separation distance (d) with particle concentration (c) was used to follow the transition of CNC dispersions from an isotropic state at 1-2 vol% to a compressed nematic state at particle concentrations above 30 vol%. Comparison with SAXS measurements on CNC dispersions at near equilibrium conditions shows that evaporation-induced assembly of CNC in large levitating drops is comparable to bulk systems. Colloidal states with d vs. c scalings intermediate between isotropic dispersions and unidirectional compression of the nematic structure could be related to the biphasic region and gelation of CNC. Nanoscale structural information of CNC assembly up to very high particle concentrations can help to fabricate nanocellulose-based materials by evaporative methods.


Phase I/II study of biweekly paclitaxel and radiation in androgen-ablated locally advanced prostate cancer.
To determine the maximum-tolerated dose (MTD) of concurrent paclitaxel and radiation therapy (RT) in patients with locally advanced prostate cancer. Eligible patients had T2-4 tumors with Gleason scores greater than 7 and/or PSA levels greater than 10 ng/mL and/or had tumors with pathologic stage TxN1. Hormonal ablation was initiated 3 months before RT and was given for 9 months. RT was delivered daily (1.8 Gy) with concurrent twice-weekly paclitaxel (30 mg/m(2)). The whole pelvis was irradiated to 39.6 Gy. The radiation dose was escalated as follows: 63 Gy, 66.6 Gy, 70.2 Gy, and 73.8 Gy. The last RT dose level was fixed at 73.8 Gy. Between January 2000 and October 2006, 22 patients were enrolled. The median age was 59 years (range, 48 to 72 years); the median PSA level was 22.4 ng/mL (range, 2.8 to 113 ng/mL). The number of patients per stage was as follows: three with T1, eight with T2, 11 with T3, and five with pN1 = 5. No grade 3 toxicities occurred at 63 Gy. Grade 3 diarrhea occurred in three patients at 66.6 Gy. The protocol then was amended to treat the prostate volume first followed by the whole pelvis. No grade 3 toxicities were observed at 70.2 Gy. One patient experienced grade 3 diarrhea at 73.8 Gy. Five additional patients were treated to 73.8 Gy without grade 3 toxicity, which established the MTD for combined paclitaxel and RT at 73.8 Gy. At 38 months median follow-up (range, 9 to 87 months), 21 (95%) of 22 patients are alive. Six (27%) of 22 experienced recurrence. Concurrent biweekly paclitaxel with RT is feasible, with an MTD of 73.8 Gy. Recovery of gonadal function occurs in the majority of patients. These results encourage testing in a phase III setting.


Head injury in multiple trauma.
Head injury is a major contemporary health problem. Obviously, the best solution is the avoidance and prevention of accidents. The physician who treats patients with multiple injuries must be prepared to make an intelligent assessment of the neurologic injuries, to undertake the initial resuscitation and, when necessary, to do the definitive surgery.


cGMP-independent inotropic effects of nitric oxide and peroxynitrite donors: potential role for nitrosylation.
Nitric oxide (NO) has concentration-dependent biphasic myocardial contractile effects. We tested the hypothesis, in isolated rat hearts, that NO cardiostimulation is primarily non-cGMP dependent. Infusion of 3-morpholinosydnonimine (SIN-1, 10(-5) M), which may participate in S-nitrosylation (S-NO) via peroxynitrite formation, increased the rate of left ventricular pressure rise (+dP/dt; 19 +/- 4%, P < 0.001, n = 11) without increasing effluent cGMP or cAMP. Superoxide dismutase (SOD; 150 U/ml) blocked SIN-1 cardiostimulation and led to cGMP elaboration. Sodium nitroprusside (10(-10)-10(-7) M), an iron nitrosyl compound, did not augment +dP/dt but increased cGMP approximately eightfold (P < 0.001), whereas diethylamine/NO (DEA/NO; 10(-7) M), a spontaneous NO. donor, increased +dP/dt (5 +/- 2%, P < 0.05, n = 6) without augmenting cGMP. SIN-1 and DEA/NO +dP/dt increase persisted despite guanylyl cyclase inhibition with 1H-(1,2,4)oxadiazolo-(4,3,-a)quinoxalin-1-one (10(-5) M, P < 0.05 for both donors), suggesting a cGMP-independent mechanism. Glutathione (5 x 10(-4) M, n = 15) prevented SIN-1 cardiostimulation, suggesting S-NO formation. SIN-1 also produced SOD-inhibitable cardiostimulation in vivo in mice. Thus peroxynitrite and NO donors can stimulate myocardial contractility independently of guanylyl cyclase activation, suggesting a role for S-NO reactions in NO/peroxynitrite-positive inotropic effects in intact hearts.


Microfracture mechanisms of composite resins containing prepolymerized particle fillers.
The effect of prepolymerized particle fillers on fracture toughness of four commercial composite resins was studied. The ground surface morphology was examined with a field emission scanning electron microscope. Fracture toughness was determined by using single edge notched specimens. Acoustic Emission (AE), which is the elastic wave due to the release of energy from the localized sources of material, was detected by sensors of a high-sensitivity and low-noise resonance type during the fracture toughness test. Acoustic Emission signals detected were analyzed for parameters such as amplitude and energy. Fracture surfaces were examined with a scanning electron microscope. The fracture toughness values, AE releasing patterns during fracture toughness test, and the fracture surface findings were analyzed to understand the fracture behavior of composite resins containing prepolymerized particle fillers. A microfracture model and fracture mechanisms to increase the fracture toughness of this type of composite resins are proposed.


Tailoring the LCST of thermosensitive hydrogel thin films deposited by iCVD.
Using the iCVD (initiated chemical vapor deposition) polymerization technique, we generated a library of thermosensitive thin film hydrogels in the physiological temperature range. The library shows how a specific hydrogel with a desired temperature response can be synthesized via the copolymerization of three main components: (a) the main thermosensitive monomer, which determines the temperature range of the LCST; (b) the comonomer, which modulates the temperature according to its hydrophilic/hydrophobic behavior; and (c) the cross-linker, which determines the swelling degree and the polymer chain mobility of the resulting hydrogel. The thermosensitive thin films included in the library have been characterized by the water contact angle (WCA), revealing a switchable hydrophobic/hydrophilic behavior depending on the temperature and a decrease in the WCA with the incorporation of hydrophilic moieties. Moreover, a more accurate characterization by quartz crystal microbalance (QCM) is performed. With temperature and flow control, the switchable swelling properties of the thermosensitive thin films (due to the polymer mixture transition) can be recorded and analyzed in order to study the effects of the comonomer moieties on the lower critical solution temperature (LCST). Thus, the LCST tailoring method has been successfully used in this paper, and thermoresponsive thin films (50 nm in thickness) have been deposited by iCVD, exhibiting LCSTs in the 32-49 °C range. Due to the presented method's ability to tailor the LCST in the physiological temperature range, the developed thermoresponsive films present potential biosensing and drug delivery applications in the biomedical field.


Single-centre Experience of Patients with Metastatic Urothelial Cancer Treated with Chemotherapy Following Immune Checkpoint Inhibition.
There are few data on outcomes for patients with metastatic urothelial carcinoma (MUC) who receive chemotherapy (CT) after progression on immune checkpoint inhibitors (ICIs). We carried out a retrospective single-centre analysis of MUC patients who progressed after ICI and then received CT. Patients fell into two groups: CT-naive (no prior-CT) and CT-pretreated (platinum-based CT followed by ICI on progression). The response rate (RR), progression-free survival (PFS), and duration of response (DOR) were assessed. A total of 29 patients received CT following progression on ICI. The median follow-up was 17.0mo (interquartile range 9.1-20.5mo). In the CT-naive group (n=17), 53% had a partial response, 18% had stable disease, and 29% had progressive disease. In the CT-pretreated group (n=12) 17% had a partial response, 67% had stable disease, and 16% had progressive disease. The median PFS was 6.4mo (95% confidence interval [CI] 3.8-9.1) in the CT-naive and 4.4mo (95% CI 1.5-7.3) in the CT-pretreated group. The median DOR was 8.1mo (range 5.1-11.1) among the ten patients with a response to CT after ICI in both groups. Some 38% of patients in the CT-naive and 17% in the CT-pretreated group had dose reductions on post-ICI CT. CT and ICI can be sequenced after previous chemotherapy exposure, although this does not induce long-term durable remissions in most patients. PATIENT SUMMARY: We looked at outcomes for patients with metastatic bladder cancer who received chemotherapy after the cancer got worse while on immunotherapy. We found that patients can be safely treated with further chemotherapy. However, the positive effects of chemotherapy will not be durable in the majority of patients.


Chronic In Vivo Evaluation of PEDOT/CNT for Stable Neural Recordings.
Subcellular-sized chronically implanted recording electrodes have demonstrated significant improvement in single unit (SU) yield over larger recording probes. Additional work expands on this initial success by combining the subcellular fiber-like lattice structures with the design space versatility of silicon microfabrication to further improve the signal-to-noise ratio, density of electrodes, and stability of recorded units over months to years. However, ultrasmall microelectrodes present very high impedance, which must be lowered for SU recordings. While poly(3,4-ethylenedioxythiophene) (PEDOT) doped with polystyrene sulfonate (PSS) coating have demonstrated great success in acute to early-chronic studies for lowering the electrode impedance, concern exists over long-term stability. Here, we demonstrate a new blend of PEDOT doped with carboxyl functionalized multiwalled carbon nanotubes (CNTs), which shows dramatic improvement over the traditional PEDOT/PSS formula. Lattice style subcellular electrode arrays were fabricated using previously established method. PEDOT was polymerized with carboxylic acid functionalized carbon nanotubes onto high-impedance (8.0 ± 0.1 MΩ: M ± S.E.) 250-μm(2) gold recording sites. PEDOT/CNT-coated subcellular electrodes demonstrated significant improvement in chronic spike recording stability over four months compared to PEDOT/PSS recording sites. These results demonstrate great promise for subcellular-sized recording and stimulation electrodes and long-term stability. This project uses leading-edge biomaterials to develop chronic neural probes that are small (subcellular) with excellent electrical properties for stable long-term recordings. High-density ultrasmall electrodes combined with advanced electrode surface modification are likely to make significant contributions to the development of long-term (permanent), high quality, and selective neural interfaces.


Myotoxic and cytolytic activities of dimeric Lys49 phospholipase A2 homologues are reduced, but not abolished, by a pH-induced dissociation.
Lys49 phospholipase A2 (PLA2) homologues are myotoxic proteins devoid of catalytic activity. Their toxic determinants map to the C-terminal region 115-129, which plays an effector role in membrane damage. The dimeric state was reported to be essential for a Lys49 PLA2 which lost its liposome-disrupting activity after dissociating into monomers at pH 5.0. This study, evaluated the effects of a pH-induced dissociation on the toxicity of four Lys49 PLA2s, using biological targets instead. Both their cytolytic and myotoxic activities were lower at pH 5.0 than at pH 7.2. However, in contrast with experiments using artificial bilayers, toxic effects upon biological targets were not abolished at pH 5.0. Importantly, C-terminal synthetic peptides of two Lys49 PLA2s also showed lower cytolytic action at pH 5.0 than at pH 7.2, indicating that factors other than the dimeric/monomeric state of the proteins may also be involved in these differences of toxicity. Results support the view that the dimeric state of Lys49 PLA2s could play an enhancing, although not essential role, in their C-terminal region-mediated mechanism of myotoxicity.


Fractal and Wada escape basins in the chaotic particle drift motion in tokamaks with electrostatic fluctuations.
The E×B drift motion of particles in tokamaks provides valuable information on the turbulence-driven anomalous transport. One of the characteristic features of the drift motion dynamics is the presence of chaotic orbits for which the guiding center can experience large-scale drifts. If one or more exits are placed so that they intercept chaotic orbits, the corresponding escape basins structure is complicated and, indeed, exhibits fractal structures. We investigate those structures through a number of numerical diagnostics, tailored to quantify the final-state uncertainty related to the fractal escape basins. We estimate the escape basin boundary dimension through the uncertainty exponent method and quantify final-state uncertainty by the basin entropy and the basin boundary entropy. Finally, we recall the Wada property for the case of three or more escape basins. This property is verified both qualitatively and quantitatively using a grid approach.


Identification of hitherto unrecognized arboviruses from Ecuador: members of serogroups B, C, Bunyamwera, Patois, and Minatitlan.
Three hundred seventy-nine virus isolates were obtained from mosquitoes collected and sentinel hamsters exposed in coastal Ecuador from 1974 to 1978. These included four alphaviruses [Venezuelan equine encephalitis 1B (1), Venezuelan equine encephalitis 1D (35), western equine encephalitis (1) and eastern equine encephalitis (4)]; two flaviviruses [St. Louis encephalitis (3) and Naranjal (6)]; 11 bunyaviruses [Maguari (243), Playas (3), Vinces (33), Turlock (2), Abras (5), Babahoyo (3), Acara (2), Guajara (3), San Juan (6), Pueblo Viejo (3), 18 unspecified Gamboa serogroup viruses, Palestina (7)]; and one vesiculovirus (vesicular stomatitis New Jersey). All but Venezuelan equine encephalitis virus were new to Ecuador, and Naranjal (serogroup B), Playas (Bunyamwera serogroup), Vinces (serogroup C), Abras and Babahoyo (Patois serogroup), San Juan and Pueblo Viejo (Gamboa serogroup) and Palestina (Minatitlan serogroup) are newly recognized viruses. These isolates have enabled us to 1) expand our knowledge of the geographic distribution of recognized viruses, 2) expand our knowledge of the members of certain serogroups and 3) establish two new serogroups (Gamboa and Minatitlan).


The labyrinth of interactions of Epstein-Barr virus-encoded small RNAs.
Epstein-Barr Virus (EBV) is an oncogenic herpesvirus implicated in the pathogenesis of a number of human malignancies. However, the mechanism by which EBV leads to malignant transformation is not clear. A number of viral latent gene products, including non-protein coding small RNAs, are believed to be involved. Epstein-Barr virus-encoded RNA 1 (EBER1) and EBER2 are two such RNA molecules that are abundantly expressed (up to 10(7) copies) in all EBV-infected cells, but their function remains poorly understood. These polymerase III transcripts have extensive secondary structure and exist as ribonucleoproteins. An accumulating body of evidence suggests that EBERs play an important role, directly or indirectly, in EBV-induced oncogenesis. Here, we summarize the current understanding of the complex interactions of EBERs with various cellular factors and the potential pathways by which these small RNAs are able to influence EBV-infected cells to proliferate and to induce tumorigenesis. The exosome pathway is probably involved in the cellular excretion of EBERs and facilitating some of their biological effects.


Confined helium on Lagrange meshes.
The Lagrange-mesh method has the simplicity of a calculation on a mesh and can have the accuracy of a variational method. It is applied to the study of a confined helium atom. Two types of confinement are considered. Soft confinements by potentials are studied in perimetric coordinates. Hard confinement in impenetrable spherical cavities is studied in a system of rescaled perimetric coordinates varying in [0,1] intervals. Energies and mean values of the distances between electrons and between an electron and the helium nucleus are calculated. A high accuracy of 11 to 15 significant figures is obtained with small computing times. Pressures acting on the confined atom are also computed. For sphere radii smaller than 1, their relative accuracies are better than 10(-10). For larger radii up to 10, they progressively decrease to 10(-3), still improving the best literature results.


Measurement of peak inspiratory flow with in-check dial device to simulate low-resistance (Diskus) and high-resistance (Turbohaler) dry powder inhalers in children with asthma.
Drug delivery and lung deposition from a dry powder inhaler (DPI) are dependent on the peak inspiratory flow (PIF) through the DPI. Therefore, when prescribing a DPI, it is important to know whether a child is able to generate sufficient PIF through a particular device. Using a PIF meter (In-Check Dial) that mimics the internal resistance of DPIs, two commonly used devices (high-resistance Turbohaler (TH) and low-resistance Diskus (DK)) determined the PIF generated by asthmatic children through each of them. Two hundred and twenty-three children were studied, of whom 100 (mean age, 9.1 +/- 3.0 years; range, 3-15 years) were experienced with the use of a DPI (>1 month of regular DPI use), and 123 (mean, 5.5 +/- 1.9 years; range, 3-9 years) were inexperienced (no previous DPI use). All of the experienced patients generated more than 30 l/min through both devices, but a PIF of 60 l/min through the TH was obtained by only 68 (68%) of them. The age above which a minimal PIF of 30 l/min (for DK) or 60 l/min (for TH) could be achieved in new DPI users (inexperienced) was 4 years and 9 years, respectively. Even among experienced patients, many young children may not generate optimal PIFs through high-resistance DPIs. When DPI treatment is considered for young children, some devices may be successfully introduced at a younger age. It may thus be important to measure PIF in children who use a DPI or in whom DPI use is contemplated. This evaluation can be easily undertaken in the clinic with the In-Check Dial device.


Recognising and managing migraine.
Migraine is a common neurological disorder characterised by a severe, pulsating headache, sometimes accompanied with photophobia or phonophobia and nausea and/or vomiting. The symptoms of migraine can have a significant adverse effect on a person's ability to undertake normal activities. Nurses have an important role in assisting patients in identifying migraine triggers and in supporting them to manage the symptoms of migraines through lifestyle changes and pharmacological treatments. This article describes different types of migraines and some differential diagnoses and 'red flag' symptoms that could indicate a more serious condition. The author also discusses non-pharmacological and pharmacological management strategies and treatments.


Binding, unbinding and aggregation of crescent-shaped nanoparticles on nanoscale tubular membranes.
Using molecular dynamics simulations of a coarse-grained implicit solvent model, we investigate the binding of crescent-shaped nanoparticles (NPs) on tubular lipid membranes. The NPs adhere to the membrane through their concave side. We found that the binding/unbinding transition is first-order, with the threshold binding energy being higher than the unbinding threshold, and the energy barrier between the bound and unbound states at the transition that increases with increasing the NP's arclength Lnp or curvature mismatch μ = Rc/Rnp, where Rc and Rnp are the radii of curvature of the tubular membrane and the NP, respectively. Furthermore, we found that the threshold binding energy increases with increasing either Lnp or μ. NPs with curvature larger than that of the tubule (μ > 1) lie perpendicularly to the tubule's axis. However, for μ smaller than a specific arclength-dependent mismatch μ*, the NPs are tilted with respect to the tubule's axis, with the tilt angle that increases with decreasing μ. We also investigated the self-assembly of the NPs on the tubule at relatively weak adhesion strength and found that for μ > 1 and high values of Lnp, the NPs self-assemble into linear chains, and lie side-by-side. For μ < μ* and high Lnp, the NPs also self-assemble into chains, while being tilted with respect to the tubule's axis.


On neighbourhood degree sequences of complex networks.
Network topology is a fundamental aspect of network science that allows us to gather insights into the complicated relational architectures of the world we inhabit. We provide a first specific study of neighbourhood degree sequences in complex networks. We consider how to explicitly characterise important physical concepts such as similarity, heterogeneity and organization in these sequences, as well as updating the notion of hierarchical complexity to reflect previously unnoticed organizational principles. We also point out that neighbourhood degree sequences are related to a powerful subtree kernel for unlabeled graph classification. We study these newly defined sequence properties in a comprehensive array of graph models and over 200 real-world networks. We find that these indices are neither highly correlated with each other nor with classical network indices. Importantly, the sequences of a wide variety of real world networks are found to have greater similarity and organisation than is expected for networks of their given degree distributions. Notably, while biological, social and technological networks all showed consistently large neighbourhood similarity and organisation, hierarchical complexity was not a consistent feature of real world networks. Neighbourhood degree sequences are an interesting tool for describing unique and important characteristics of complex networks.


Lorazepam strongly prolongs visual information processing.
Lorazepam is a drug that has been widely used for over 30 years. Whereas its therapeutic and amnestic effects are fairly well known, the visuo-perceptual impairments induced by this drug have been studied to a much lesser degree and only little is known about the influence of lorazepam on the time course of visual information processing. To gain a better insight specifically on these temporal characteristics, we used the recently discovered backward masking technique, 'shine-through', in which a vernier target precedes a grating. We tested subjects, treated with lorazepam, diazepam, or a placebo, with masking gratings of various spatial layouts. Our experiments reveal surprising results. First, for the unmasked vernier target, lorazepam induced a strong deterioration of performance compared to both diazepam and placebo. Performance deteriorated even more significantly if a masking grating was presented following the vernier. We observed that vernier discrimination could be completely abolished even if the grating appeared 400 ms after the vernier presentation. Such long time intervals are beyond usual visual masking effects. When performing the task under placebo, the participants perceived the vernier target and the masking grating as two independent time events rather than as a single event. It appears that lorazepam prolongs dramatically the processing of visual targets. The masking effects revealed here are specific to the type of grating and are much stronger under lorazepam than under diazepam.


Physician-laboratory interface in X-chromosome mapping.
At the world's largest DNA diagnostic laboratory, roughly half of family studies to date have involved X-linked diseases. With the recent characterization of the fragile X gene, that percentage may increase. No matter what the genetic disease, patient studies can be readily combined with physician education, and heightened physician awareness increases the number of referrals.


Severity of ASD symptoms and their correlation with the presence of copy number variations and exposure to first trimester ultrasound.
Current research suggests that incidence and heterogeneity of autism spectrum disorder (ASD) symptoms may arise through a variety of exogenous and/or endogenous factors. While subject to routine clinical practice and generally considered safe, there exists speculation, though no human data, that diagnostic ultrasound may also contribute to ASD severity, supported by experimental evidence that exposure to ultrasound early in gestation could perturb brain development and alter behavior. Here we explored a modified triple hit hypothesis [Williams & Casanova, ] to assay for a possible relationship between the severity of ASD symptoms and (1) ultrasound exposure (2) during the first trimester of pregnancy in fetuses with a (3) genetic predisposition to ASD. We did so using retrospective analysis of data from the SSC (Simon's Simplex Collection) autism genetic repository funded by the Simons Foundation Autism Research Initiative. We found that male children with ASD, copy number variations (CNVs), and exposure to first trimester ultrasound had significantly decreased non-verbal IQ and increased repetitive behaviors relative to male children with ASD, with CNVs, and no ultrasound. These data suggest that heterogeneity in ASD symptoms may result, at least in part, from exposure to diagnostic ultrasound during early prenatal development of children with specific genetic vulnerabilities. These results also add weight to on-going concerns expressed by the FDA about non-medical use of diagnostic ultrasound during pregnancy. Autism Res 2017, 10: 472-484. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.


Adenosine inhibits beta-adrenoceptor but not DBcAMP-induced renin release.
The purpose of these studies was to assess the direct effect of adenosine on the renin release response to beta-adrenoceptor activation in vivo in the canine kidney. In an initial study, innervated, intrarenal beta-adrenoceptors were activated selectively via renal nerve stimulation in kidneys in which the alpha-adrenoceptor response to renal nerve stimulation had been blocked with phentolamine. Adenosine, infused directly into the renal artery (10 and 30 micrograms/min), significantly blunted the renin release response to renal nerve stimulation. However, adenosine also caused significant reductions in base-line glomerular filtration rate, sodium excretion rate, and filtration fraction. To eliminate these confounding effects of adenosine on renal function and to prevent changes in norepinephrine release due to prejunctional inhibition by adenosine, we also studied the effect of intrarenal infusions of adenosine on norepinephrine-induced renin release in the nonfiltering, alpha-adrenoceptor-blocked, canine kidney. In this model of beta-adrenoceptor activation, adenosine abolished the renin release response to intrarenal infusions of norepinephrine. In a final series of experiments, the effect of adenosine on the renin response to dibutyryl-adenosine 3',5'-cyclic monophosphate (cAMP) was examined in the nonfiltering, beta-adrenoceptor-blocked, canine kidney. In this model of cAMP-induced renin release, adenosine was ineffective in attenuating the renin release response. These data demonstrate that in vivo adenosine directly inhibits beta-adrenoceptor-mediated renin release by a mechanism that does not involve a reduction in the ability of cAMP to activate intracellular mechanisms leading to renin release.


Anaesthetic management of acute laryngeal trauma.
Three patients suffering acute laryngeal trauma illustrate problems of missed diagnosis and airway management confronting anaesthetists. A 55-year-old man suffered multiple injuries, including a supraglottic laryngeal fracture which was not diagnosed during administration of a subsequent general anaesthetic. The diagnostic delay compromised any reconstructive surgery. Two 26-year-old males suffered laryngeal fractures, but tracheal intubation for reconstruction and tracheostomy was successful. Guidelines for management are suggested.


Clinicopathological significance of insulin-like growth factor-1 receptor expression in breast cancer.
Insulin-like growth factor 1 receptor (IGF1R) is a receptor protein tyrosine kinase that is claimed to be related with tumor development and progression of breast cancer with some conflicting results in the literature. The aims of the study are to investigate expression of IGF1R, and correlate with clinicopathological parameters to clarify the significance of IGF1R on breast cancer. IGF1R and Ki67 were applied immunohistochemically to the tissue microarray sections of 370 female breast cancer patients. The results were correlated with clinical, prognostic, histopathological features, and other immunohistochemical findings [ER, PR, HER2, CK5/6, and CK14] statistically. IGF1R overexpression showed direct correlation with Ki67 index (P=0.028), HER2 positivity (P=0.001), mitotic count (P=0.004), tumor grade (P=0.015), and geographic necrosis (P=0.023); and negative correlation with ER positivity (P=0.003). There was statistically significant difference between IGF1R expression and the molecular subtypes (P<0.001), mostly HER2+ phenotype. IGF1R expression was found to be higher in invasive ductal carcinoma (IDC) than invasive lobular carcinoma (ILC) (P=0.036). Both IGF1R and Ki67 expression were negatively correlated with disease-free survival (DFS) (P=0.020, P=0.023, respectively) and overall survival (OS) [P<0.001, each] rates. The inverse association between IGF1R overexpression and OS rate was also supported by multivariate analyses (P=0.025). Overexpression of IGF1R was found to be directly correlated with shorter DFS and OS as well as some clinicopathological features associated with adverse prognosis such as higher Ki67 index, mitotic count, tumor grade, presence of geographic necrosis, HER2 positivity, ER negativity, HER2+ molecular subtype, histological tumor type of IDC rather than ILC. Thus, IGF1R might be considered as an useful target for comprehensive future anti-tumor therapy investigations. Additionally, using IGF1R as well as Ki67 as a part of routine pathology practice might be fruitful in breast cancer therapy and prediction of prognosis. Breast carcinoma, IGF1R, Insulin-like growth factor-1 receptor, Immunohistochemistry, Prognosis.