Functional coding variation in the presynaptic dopamine transporter associated with neuropsychiatric disorders drives enhanced motivation and context-dependent impulsivity in mice.
Recent genetic analyses have provided evidence that clinical commonalities associated with different psychiatric diagnoses often have shared mechanistic underpinnings. The development of animal models expressing functional genetic variation attributed to multiple disorders offers a salient opportunity to capture molecular, circuit and behavioral alterations underlying this hypothesis. In keeping with studies suggesting dopaminergic contributions to attention-deficit hyperactivity disorder (ADHD), bipolar disorder (BPD) and autism spectrum disorder (ASD), subjects with these diagnoses have been found to express a rare, functional coding substitution in the dopamine (DA) transporter (DAT), Ala559Val. We developed DAT Val559 knock-in mice as a construct valid model of dopaminergic alterations that drive multiple clinical phenotypes, and here evaluate the impact of lifelong expression of the variant on impulsivity and motivation utilizing the 5- choice serial reaction time task (5-CSRTT) and Go/NoGo as well as tests of time estimation (peak interval analysis), reward salience (sucrose preference), and motivation (progressive ratio test). Our findings indicate that the DAT Val559 variant induces impulsivity behaviors that are dependent upon the reward context, with increased impulsive action observed when mice are required to delay responding for a reward, whereas mice are able to withhold responding if there is a probability of reward for a correct rejection. Utilizing peak interval and progressive ratio tests, we provide evidence that impulsivity is likely driven by an enhanced motivational phenotype that also may drive faster task acquisition in operant tasks. These data provide critical validation that DAT, and more generally, DA signaling perturbations can drive impulsivity that can manifest in specific contexts and not others, and may rely on motivational alterations, which may also drive increased maladaptive reward seeking.


A Review on Platelet Activating Factor Inhibitors: Could a New Class of Potent Metal-Based Anti-Inflammatory Drugs Induce Anticancer Properties?
In this minireview, we refer to recent results as far as the Platelet Activating Factor (PAF) inhibitors are concerned. At first, results of organic compounds (natural and synthetic ones and specific and nonspecific) as inhibitors of PAF are reported. Emphasis is given on recent results about a new class of the so-called metal-based inhibitors of PAF. A small library of 30 metal complexes has been thus created; their anti-inflammatory activity has been further evaluated owing to their inhibitory effect against PAF in washed rabbit platelets (WRPs). In addition, emphasis has also been placed on the identification of preliminary structure-activity relationships for the different classes of metal-based inhibitors.


Plasma Citrate and Succinate Are Associated With Neurocognitive Impairment in Older People With HIV.
Neurocognitive impairment (NCI) is associated with monocyte activation in people with HIV (PWH). Activated monocytes increase glycolysis, reduce oxidative phosphorylation, and accumulate citrate and succinate, tricarboxylic acid (TCA) cycle metabolites that promote inflammation-this metabolic shift may contribute to NCI and slowed gait speed in PWH. Plasma citrate and succinate were assayed by liquid chromatography-mass spectrometry from 957 participants upon entry to a multicenter, prospective cohort of older PWH. Logistic, linear, and mixed-effects linear regression models were used to examine associations between entry/baseline TCA cycle metabolites and cross-sectional and longitudinal NCI, neuropsychological test scores (NPZ-4), and gait speed. Median age was 51 (range 40-78) years. Each 1 standard deviation (SD) citrate increment was associated with 1.18 higher odds of prevalent NCI at baseline (P = .03), 0.07 SD lower time-updated NPZ-4 score (P = .01), and 0.02 m/s slower time-updated gait speed (P < .0001). Age accentuated these effects. In the oldest age-quartile, higher citrate was associated with 1.64 higher odds of prevalent NCI, 0.17 SD lower NPZ-4, and 0.04 m/s slower gait speed (P ≤ .01 for each). Similar associations were apparent with succinate in the oldest age-quintile, but not with gait speed. In participants without NCI at entry, higher citrate predicted a faster rate of neurocognitive decline. Higher plasma citrate and succinate are associated with worse cross-sectional and longitudinal measures of neurocognitive function and gait speed that are age-dependent, supporting the importance of altered bioenergetic metabolism in the pathogenesis of NCI in older PWH.


[Anemia in the elderly].
Anaemia is a problem that affects almost 10% over 65 years and 20% over 85 years. There is no physiological anaemia in the elderly. Any anaemia expresses the existence of a pathological process, regardless of its severity. Anaemia in the elderly is always associated with a poor prognosis that is in terms of mortality, morbidity and risk of fragility. The diagnostic approach to anemia in the elderly is the same as in younger individual. There are many causes of anaemia; anaemia balance is a complex diagnostic process. Most anaemias are due to a deficiency, chronic inflammation or comorbidity. However, in the elderly, the etiology of anaemia is often multifactorial. In a number of cases remain unexplained anaemia. In a number of cases, anemia remain unexplained. Treatment of anaemia is the treatment of the cause, but specific therapeutic aspects to the elderly should be considered, as among other martial substitution or use of erythropoietin (EPO).


Water-assisted synthesis of stable and multicolored CsPbX3@SiO2 core-shell nanoparticles as fluorescent probes for biosensing.
Colloidal lead halide perovskite nanocrystals are highly luminescent materials with great promise as fluorescent probes in biosensing as long as their intrinsic instability in aqueous media is effectively addressed. In this study, we successfully prepared stable and multicolored CsPbX3@SiO2 (X = Cl/Br, Br and I) core-shell nanoparticles through a simple method based on the water-induced transformation of Cs4PbX6 into CsPbX3, combined with sol-gel procedures. We observed that the concentration of the Cs4PbX6 precursor plays a crucial role in the formation of isolated nanospheres with uniform silica coating and in controlling the number of core-free particles. Furthermore, our research expands this approach to other halide compositions, resulting in multicolored core-shell nanoparticles with emission wavelengths ranging from 490 to 700 nm, average sizes below 30 nm, and photoluminescence quantum yields close to 60%. Unlike in previous reports, the silica coating boosts the photoluminescence quantum yields compared to uncoated counterparts and provides increased structural stability for more than four days. Moreover, a controlled thermal treatment confers water stability to the as-synthesized nanoparticles. To establish the feasibility of the developed materials as fluorescent probes, we successfully demonstrated their specific recognition of a humanized antibody (omalizumab) used in treating patients with severe allergic asthma. This work paves the way to develop in vitro tests using CsPbX3@SiO2 core-shell nanoparticles as fluorogenic probes.


Lack of a relationship between circulating gamma-glutamyltransferase levels and carotid intima media thickness in hypertensive and diabetic patients.
By increasing the intracellular prooxidant burden, gamma-glutamyltransferase (GGT) may accelerate atherosclerotic vascular disease. That noxious influence may be reflected by circulating enzyme levels, a correlate of cardiovascular risk factors, and a predictor of incident events. To evaluate this hypothesis, we tested the association between circulating GGT and common carotid intima-media thickness (CIMT), a surrogate index of systemic atherosclerotic involvement, in a large and well-characterized group of patients at risk of cardiovascular disease (CVD). This study analyzed 548 patients with hypertension and/or diabetes and a widely prevalent history of CVD. Subjects with known hepatic disease and abnormal GGT values were excluded. CIMT (B-mode ultrasonography) values were the mean of four far-wall measurements at both common carotids. Metabolic syndrome (MetS) was diagnosed according to National Cholesterol Education Program-Adult Treatment Panel III criteria. Due to inherent sex-related differences in GGT levels, the data were analyzed separately in males and females in samples dichotomized by the median. The age-adjusted CIMT values did not differ by GGT levels in males or females. In contrast, the carotid wall was consistently thicker in patients with a history of CVD and MetS independent of age and concurrent GGT values. In both sexes, GGT was associated with key components of the MetS such as triglycerides, fasting plasma glucose, and body mass index. The data collected in this mixed group of hypertensive and/or diabetic patients with widely prevalent history of CVD do not support the concept of a direct pathophysiological link between GGT levels within reference limits and atherosclerotic involvement.


Gene copy number variation in male breast cancer by aCGH.
Male breast cancer (MBC) is a rare disease and little is known about its etiopathogenesis. Array comparative genomic hybridization (aCGH) provides a method to quantitatively measure the changes of DNA copy number and to map them directly onto the complete linear genome sequences. The aim of this study was to investigate DNA imbalances by aCGH and compare them with a female breast cancer dataset. We used Agilent Human Genome CGH Microarray Kit 44B and 44 K to compare genomic alterations in 25 male breast cancer tissues studied at NCC of Bari and 16 female breast cancer deposited with the Gene Expression Omnibus (GSE 12659). Data analysis was performed with Nexus Copy Number 5.0 software. All the 25 male and 16 female breast cancer samples displayed some chromosomal instability (110,93 alterations per patient in female, 69 in male). However, male samples presented a lower frequency of genetic alterations both in terms of loss and gains. aCGH is an effective tool for analysis of cytogenetic aberrations in MBC, which involves different biological processes than female. Male most significant altered regions contained genes involved in cell communication, cell division and immunological response, while female cell-cell junction maintenance, regulation of transcription and neuron development.


The pathophysiology of repetitive concussive traumatic brain injury in experimental models; new developments and open questions.
In recent years, there has been an increasing interest in the pathophysiology of repetitive concussive traumatic brain injury (rcTBI) in large part due to the association with dramatic cases of progressive neurological deterioration in professional athletes, military personnel, and others. However, our understanding of the pathophysiology of rcTBI is less advanced than for more severe brain injuries. Most prominently, the mechanisms underlying traumatic axonal injury, microglial activation, amyloid-beta accumulation, and progressive tau pathology are not yet known. In addition, the role of injury to dendritic spine cytoskeletal structures, vascular reactivity impairments, and microthrombi are intriguing and subjects of ongoing inquiry. Methods for quantitative analysis of axonal injury, dendritic injury, and synaptic loss need to be refined for the field to move forward in a rigorous fashion. We and others are attempting to develop translational approaches to assess these specific pathophysiological events in both animals and humans to facilitate clinically relevant pharmacodynamic assessments of candidate therapeutics. In this article, we review and discuss several of the recent experimental results from our lab and others. We include new initial data describing the difficulty in modeling progressive tau pathology in experimental rcTBI, and results demonstrating that sertraline can alleviate social interaction deficits and depressive-like behaviors following experimental rcTBI plus foot shock stress. Furthermore, we propose a discrete set of open, experimentally tractable questions that may serve as a framework for future investigations. In addition, we also raise several important questions that are less experimentally tractable at this time, in hopes that they may stimulate future methodological developments to address them. This article is part of a Special Issue entitled "Traumatic Brain Injury".


Simultaneous biological removal of sulphide and nitrate by autotrophic denitrification in an activated sludge system.
The feasibility of an autotrophic denitrification process in an activated sludge reactor, using sulphide as the electron donor, was tested for simultaneous denitrification and sulphide removal. The reactor was operated at nitrate (N) to sulphide (S) ratios between 0.5 and 0.9 to evaluate their effect on the N-removal efficiency, the S-removal efficiency and the product formation during anoxic oxidation of sulphide. One hundred per cent removal of both nitrate and sulphide was achieved at a NLR of 7.96 mmol N-L(-1) x d(-1) (111.44 mg NO3- -N x L(-1) x d(-1)) and at a N/S ratio of 0.89 with complete oxidation of sulphide to sulphate. The oxygen level in the reactor (10%) was found to influence the N-removal efficiency by inhibiting the denitrification process. Moreover, chemical (or biological) oxidation of sulphide with oxygen occurred, resulting in a loss of the electron donor. FISH analysis was carried out to study the microbial population in the system.


Continuous-wave mirrorless lasing at 2.21 μm in sodium vapors.
We demonstrate backward-directed continuous-wave (cw) emission at 2.21 μm generated on the 4P3/2-4S1/2 population-inverted transition in Na vapors that are two-photon excited with resonant laser light at 589 and 569 nm. Our study of power and atom-number-density threshold characteristics shows that lasing occurs at sub-10 mW total power of the applied laser light. The observed 6 mrad divergence is defined mainly by the aspect ratio of the gain region. We find that mirrorless lasing at 2.21 μm is magnetic field and polarization dependent and this may be useful for remote magnetometry. The presented results could help determine the requirements for obtaining directional return from sodium atoms in the mesosphere.


Glycaemic index and glycaemic load of selected popular foods consumed in Southeast Asia.
The objective of the present study was to determine the glycaemic index (GI) and glycaemic load (GL) values of standard portion sizes of Southeast Asian traditional foods. A total of fifteen popular Southeast Asian foods were evaluated. Of these foods, three were soft drinks, while the other twelve were solid foods commonly consumed in this region. In total, forty-seven healthy participants (eighteen males and twenty-nine females) volunteered to consume either glucose at least twice or one of the fifteen test foods after a 10-12 h overnight fast. Blood glucose concentrations were analysed before consumption of the test food, and 15, 30, 45, 60, 90 and 120 min after food consumption, using capillary blood samples. The GI value of each test food was calculated by expressing the incremental area under the blood glucose response curve (IAUC) value of the test food as a percentage of each participant's average IAUC value, with glucose as the reference food. Among the fifteen foods tested, six belonged to low-GI foods (Ice Green Tea, Beehoon, Pandan Waffle, Curry Puff, Youtiao and Kaya Butter Toast), three belonged to medium-GI foods (Barley Drink, Char Siew Pau and Nasi Lemak), and the other six belonged to high-GI foods (Ice Lemon Tea, Chinese Carrot Cake, Chinese Yam Cake, Chee Cheong Fun, Lo Mai Gai and Pink Rice Cake). The GI and GL values of these traditional foods provide valuable information to consumers, researchers and dietitians on the optimal food choice for glycaemic control. Moreover, our dataset provides GI values of fifteen foods that were not previously tested extensively, and it presents values of foods commonly consumed in Southeast Asia.


Breast papillomas in the United States: single institution data on underrepresented minorities with a multi-institutional update on incidence.
To assess the percentage of papillomas from all biopsies performed, comparing differences in patient age and race at a single institution. To assess trends in biopsied papillomas at institutions throughout the United States (US). This is a HIPPA-compliant IRB-approved single-institution (Southern1) retrospective review to assess race and age of all-modality-biopsied non-malignant papillomas as a percentage of all biopsies (percentage papillomas calculated as papilloma biopsies/all biopsies) from January 2012 to December 2019. To assess national variation, several academic or large referral centers were contacted to provide data regarding papilloma percentages, biopsy modalities, and trends in case numbers. Trends were estimated using the method of analysis of variance (ANOVA). Comparisons of differences in trends were assessed. Southern1 institution demonstrated a significant association between race and percentage of papillomas (p < 0.0001). After adjustment for multiple comparisons with Bonferroni correction at 5% type I family error, the percentage of biopsied papillomas in Black and Asian patients remained significantly higher than in White patients (p < 0.0001 and p = 0.0032, respectively) using a Chi-square test. The regional variation in percentage of papillomas was found to be 3-9%. Southern1 institution showed a 7-year significant trend of increase in percentage of papillomas. Other institutions showed a decreasing trend (p < 0.05). Black and Asian women had significantly higher papilloma percentages compared to white patients in our single institution review. This institution also showed a statistically significant trend of increasing percentage papillomas from 2012 to 2019. Multi-institutional survey found regional variation in percentage papillomas, ranging from 3% to 9%.


Childhood Abuse, Household Dysfunction, and Indicators of Impaired Adult Worker Performance.
We examined the relation between eight types of adverse childhood experience (ACE) and three indicators of impaired worker performance (serious job problems, financial problems, and absenteeism). We analyzed data collected for the Adverse Childhood Experiences Study from 9633 currently employed adult members of the Kaiser Foundation Health Plan in San Diego. Strong graded relations were found between the ACE Score (total number of ACE categories experienced) and each measure of impaired worker performance (p < .001). We found strong evidence that the relation between ACE Score and worker performance was mediated by interpersonal relationship problems, emotional distress, somatic symptoms, and substance abuse. The long-term effects of adverse childhood experiences on the workforce impose major human and economic costs that are preventable. These costs merit attention from the business community in conjunction with specialists in occupational medicine and public health.


[Hypermethylation of the CDH1, SEPT9, HLTF and ALX4 genes and their diagnostic significance in colorectal cancer].
Sequential treatment of bisulfate-converted DNA was used to study methylation of promoter areas of SEPT9, HLTF, ALX4 and CDH1 genes. Methylation profiles were evaluated by comparing bioptical findings on colorectal cancer (n=55) and morphologically intact areas of the large bowel (n=71). Significant differences between groups were established for SEPT9, HLTF and ALX4 genes (p < or = 10(-9)) in evaluating medium-rate methylation of CpG. Diagnostic sensitivity (Se) peaked for SEPT9 (78 +/- 7%); specificity--(86 +/- 4%) (Sp). On site CpG (position "+14"), similar findings were reported: Se=81 +/- 6%, Sp=77 +/- 5%. Therefore, CpG(14)SEPT9 may be used as a separate marker. As a result of the use of HLTF as marker on all 23 sites, Se was 67 +/- 6% and Sp--87 +/- 3%; ALX4 diagnostic sensitivity--59 +/- 6%. Specificity level was similar to those of the other genes (88 +/- 3%). Despite the role of CDH1 gene in colorectal cancer, the group-to-group differences in methylation rates were minimal. Such values of Se and Sp as 54 +/- 6% and 67 +/- 5%, respectively, could not support methylation of the CDH1 promoter area for diagnostic purposes. Therefore, combined evaluation of SEPT9, HLTF and ALX4 genes offered more advantage as far as diagnosis is concerned. Hypermethylation in two of the three genes was assumed as a criterion for diagnosis. Under such conditions, diagnostic sensitivity was 81 +/- 7% (Sp=93 +/- 3%). With such high values, the criterion has a potential of being instrumental in working out diagnostic tests for colorectal cancer.


Protracted effect of converting-enzyme inhibition on the rat's response to intraarterial bradykinin.
Intravenous infusion of the converting-enzyme (CE) inhibitor, MK422 (1 mg X kg-1 X hr-1 for 30 minutes) in normotensive controls and two-kidney, one clip (2K1C) rats in the acute phase of renovascular hypertension had a significant hypotensive effect that persisted after 24 hours. In contrast to that prolonged effect, inhibition of the pressor responses to intraarterial or intravenous angiotensin I, and the potentiation of the depressor responses to intravenous bradykinin (BK), were evident during the hour following the infusion of MK422, but not 24 hours later. Potentiation of intraarterially administered BK, however, persisted for 24 hours after infusion of the CE inhibitor. It is concluded that at least the prolonged (24-hour) effect of the treatment with MK422 was due to inhibition of the CE activity in tissues other than the lung, and that increased levels of endogenous BK may be responsible for the inhibitor's hypotensive effect.


Maternal residential pesticide use during pregnancy and risk of malignant childhood brain tumors: A pooled analysis of the ESCALE and ESTELLE studies (SFCE).
Some previous epidemiological studies have suggested that pesticide exposure during pregnancy may have a possible role in the development of childhood brain tumors (CBT). We pooled data from two French national population-based, case-control studies to investigate the association between maternal residential use of pesticides during pregnancy and the risk of CBT. The mothers of 437 CBT cases and 3,102 controls aged under 15 years who resided in France at diagnosis/interview, frequency-matched by age and gender, answered a structured telephone interview conducted by trained interviewers. Unconditional logistic regression was used to estimate pooled odds ratio (OR) and 95% confidence intervals (95% CI). CBT was significantly associated with the maternal home use of pesticides during pregnancy (OR 1.4, 95% CI 1.2-1.8) and, more specifically, with insecticide (OR 1.4, 1.2-1.8). We could not draw any conclusions about herbicides and/or fungicides because few women used them during pregnancy and most of these mothers also used insecticides. Although potential recall bias cannot be excluded, our findings of this pooled analysis support the hypothesis that residential maternal use of pesticides during pregnancy and particularly insecticides may increase the risk of CBT. Future investigations to verify these findings and to explore for CBT subtypes and dose-response are necessary to have a better understanding of the possible role of pesticides in etiology of CBT.


Conformation-selective inhibitors reveal differences in the activation and phosphate-binding loops of the tyrosine kinases Abl and Src.
Over the past decade, an increasingly diverse array of potent and selective inhibitors that target the ATP-binding sites of protein kinases have been developed. Many of these inhibitors, like the clinically approved drug imatinib (Gleevec), stabilize a specific catalytically inactive ATP-binding site conformation of their kinases targets. Imatinib is notable in that it is highly selective for its kinase target, Abl, over other closely related tyrosine kinases, such as Src. In addition, imatinib is highly sensitive to the phosphorylation state of Abl's activation loop, which is believed to be a general characteristic of all inhibitors that stabilize a similar inactive ATP-binding site conformation. In this report, we perform a systematic analysis of a diverse series of ATP-competitive inhibitors that stabilize a similar inactive ATP-binding site conformation as imatinib with the tyrosine kinases Src and Abl. In contrast to imatinib, many of these inhibitors have very similar potencies against Src and Abl. Furthermore, only a subset of this class of inhibitors is sensitive to the phosphorylation state of the activation loop of these kinases. In attempting to explain this observation, we have uncovered an unexpected correlation between Abl's activation loop and another flexible active site feature, called the phosphate-binding loop (p-loop). These studies shed light on how imatinib is able to obtain its high target selectivity and reveal how the conformational preference of flexible active site regions can vary between closely related kinases.


Neuroprotective electrical stimulation of cerebellar fastigial nucleus attenuates expression of periinfarction depolarizing waves (PIDs) and inhibits cortical spreading depression.
In rat, electrical stimulation of the cerebellar fastigial nucleus (FN) for 1 h reduces the volume of focal ischemic infarctions produced by occluding the middle cerebral artery (MCAO), even 10 days later. The mechanism by which this 'central neurogenic neuroprotection' salvages ischemic brain is not known but does not result from changes in cerebral perfusion. MCAO also triggers periodic periinfarction depolarizing waves (PIDs) in the ischemic penumbra, the territory of salvage. These may contribute to neuronal death and promote infarct expansion. Conceivably, FN stimulation, which can otherwise modify cortical excitability, may alter the development of PIDs. We investigated in anesthetized rats whether FN stimulation modifies PIDs expression and, if so, the threshold for evoking cortical spreading depression (CSD), a process sharing characteristics with PIDs and an index of cortical excitability. Stimulation of FN immediately or 72 h before MCAO decreased infarction volumes by approximately 45% (p<0.01), increased PID latency >10-fold, and decreased the number of PIDs by >50% (p<0.001). In normal rats, stimulation of FN increased the threshold current for eliciting CSD by 175% and slowed its propagation velocity by 35% (p<0.01 for each) immediately, but not 72 h, after FN stimulation. We conclude: FN stimulation elicits long-lasting suppression of PIDs in parallel with neuroprotection. However, PIDs suppression over time is unlikely to result from a major increase in cortical tolerance to depolarization and probably is not the principal mechanism of salvage.


Closing the gap between science and practice: the need for professional leadership.
Major opportunity exists to better align clinical science and clinical practice. To do so will require efforts not only to develop clinical practice guidelines, but to facilitate their application in practice. The American College of Cardiology operates a program to develop and assess the effectiveness of tools that facilitate the application of guidelines in practice. Here we review what we have learned about the process of guideline implementation, lay out the major research questions that need to be addressed, and argue that professional societies play a critical role in moving from guideline development to application.


[3H]5-methyl-urapidil labels 5-HT1A receptors and alpha 1-adrenoceptors in the rat CNS. In vitro binding and autoradiographic studies.
The tritiated derivative of the potent antihypertensive agent, 5-methyl-urapidil, was used as a radioligand in binding studies with rat brain membranes and tissue sections. Serotonin and prazosin inhibited [3H]5-methyl-urapidil binding to membranes from the rat hippocampus, cerebral cortex and brainstem biphasically, leading to the definition of serotonin high-affinity and prazosin high-affinity [3H]5-methyl-urapidil binding sites. Comparison of these serotonin-sensitive [3H]5-methyl-urapidil binding sites with the 5-HT1A sites labelled by [3H]8-hydroxy-2-(di-n-propylamino)tetralin ([3H]8-OH-DPAT) revealed striking similarities regarding pharmacological properties, respective densities and regional distribution. On the other hand, the prazosin-sensitive [3H]5-methyl-urapidil binding sites should correspond to the alpha 1A-subtype of adrenoceptors which has recently been defined. Detailed autoradiographic investigations allowed the detection of 5-HT1A sites labelled by both [3H]5-methyl-urapidil and [3H]8-OH-DPAT in the posterior raphe nuclei (pallidus and obscurus) which are possibly involved in the hypotensive action of 5-methyl-urapidil. These data demonstrate that [3H]5-methyl-urapidil is a useful radioligand for the visualization and quantification of both 5-HT1A serotonin receptors and alpha 1A-adrenoceptors in the central nervous system.


Multivalency in CXCR4 chemokine receptor targeted iron oxide nanoparticles.
The CXCR4 chemokine receptor is an important biomolecular target in cancer diagnostics and therapeutics. In a new multivalent approach, iron oxide nanoparticles were conjugated with multiple binding units of a low affinity azamacrocylic CXCR4 antagonist. The silica coated nanostructure has good suspension stability, a mode size of 72 nm and high affinity for CXCR4, showing >98% inhibition of anti-CXCR4 mAb binding in a receptor binding competition assay on Jurkat cells.


Down-regulation of Gal alpha(1,3)Gal expression by alpha1,2-fucosyltransferase: further characterization of alpha1,2-fucosyltransferase transgenic mice.
In pig-to-primate transplantation, antibody-mediated hyperacute rejection is the consequence of binding of natural antibodies to Gal alpha(1,3)Gal on pig endothelium. The elimination of the Gal alpha(1,3)Gal antigen from pig cells should prevent hyperacute rejection. Using in vitro techniques, we have previously reported that using the alpha1,2-fucosyltransferase gene induces the preferential expression of H substance with a concomitant reduction in the expression of Gal alpha(1,3)Gal. The aim of the present study was to examine the effect of expressing the alpha1,2-fucosyltransferase gene in vivo on Gal alpha(1,3)Gal. Three alpha1,2-fucosyltransferase transgenic lines of mice were produced and characterized serologically and histologically. Immunohistological studies showed heavy staining for H substance in liver, spleen, kidney, and heart, with a reduction in staining for Gal alpha(1,3)Gal. In addition, there was a reduction in the binding of human anti-Gal alpha(1,3)Gal antibody to lymphocytes from alpha1,2-fucosyltransferase transgenic mice and a substantial decrease in complement-mediated cytolysis of alpha1,2-fucosyltransferase transgenic lymphocytes when compared with that obtained with normal mice. The findings have important implications, in that alpha1,2-fucosyltransferase transgenic pigs could be produced as a source for humans. Such pigs should have a reduced expression of Gal alpha(1,3)Gal.


Silencing of transforming growth factor-beta1 in situ by RNA interference for breast cancer: implications for proliferation and migration in vitro and metastasis in vivo.
Overexpression of transforming growth factor (TGF)-beta has been implicated in promoting immune suppression, tumor angiogenesis, tumor cell migration, and invasion in many cancers, including carcinoma of the breast. Thus, targeted down-regulation of TGF-beta1 expression in breast cancer in situ and determination of its implications would provide new treatment approaches for disease management. Small interfering RNA constructs targeting TGF-beta1 were validated and used to develop clonal derivatives of the metastatic breast cancer cell line MDA-MB-435. The cells were used in several in vitro analyses, including migration, invasion, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, apoptosis, and signaling assays. A wound-healing assay was used to determine migration of the cells in culture and a Boyden chamber transwell assay was used for invasion. Further, the clones were used in an in vivo mouse model for the kinetics of tumor growth and gene expression in the primary site and in lungs upon metastasis. Inhibition of TGF-beta1 expression in MDA-MB-435 cells showed a 35% decrease in migration and a 55% decrease in invasion in vitro, with a 50% increase in proliferation and no effect on apoptosis. In vivo analysis indicated a 90% decrease in the number of mice bearing macroscopic lung metastases; however, the primary tumors did not show any difference in the growth kinetics when compared with the parental MDA-MB-435 cells. Analysis of TGF-beta signaling pathways in the clonal derivatives showed a decrease in Smad2 activation and an increase in AKT and extracellular signal-regulated kinase activation. Interestingly, analysis of TGF-beta receptor expression showed a decrease in both receptor I and II expression in TGF-beta1 silenced cells. These results suggest that inhibition of TGF-beta1 ligand may act as a negative feedback loop to disrupt the function of all TGF-beta isoforms. Therapies targeting the TGF-beta signaling pathway may be more effective in late-stage disease to prevent organ metastasis but not primary tumor formation and may be combined with other tumor-targeted therapies normally limited by increased circulating TGF-beta levels.


Smoking Cessation in Stroke Survivors in the United States: A Nationwide Analysis.
Continued smoking after stroke is associated with a high risk of stroke recurrence and other cardiovascular disease. We sought to comprehensively understand the epidemiology of smoking cessation in stroke survivors in the United States. Furthermore, we compared smoking cessation in stroke and cancer survivors because cancer is another smoking-related condition in which smoking cessation is prioritized. We performed a cross-sectional analysis of data from the Centers for Disease Control and Prevention Behavioral Risk Factor Surveillance System, an annual, nationally representative health survey. Using pooled data from 2013 to 2019, we identified stroke and cancer survivors with a history of smoking. We used survey procedures to estimate frequencies and summarize quit ratios with attention to demographic and geographic (state-wise and rural-urban) factors for stroke survivors. The quit ratio is conventionally defined as the proportion of ever smokers who have quit. Then, we used multivariable logistic regression to compare quit ratios in stroke and cancer survivors while adjusting for demographics and smoking-related comorbidities. Among 4 434 604 Americans with a history of stroke and smoking, the median age was 68 years (interquartile range, 59-76), and 45.4% were women. The overall quit ratio was 60.8% (95% CI, 60.1%-61.6%). Quit ratios varied by age group, sex, race and ethnicity, and several geographic factors. There was marked geographic variation in quit ratios, ranging from 48.3% in Kentucky to 71.5% in California. Furthermore, compared with cancer survivors, stroke survivors were less likely to have quit smoking (odds ratio, 0.72 [95% CI, 0.67-0.79]) after accounting for differences in demographics and smoking-related comorbidities. There were considerable demographic and geographic disparities in smoking quit ratios in stroke survivors, who were less likely to have quit smoking than cancer survivors. A targeted initiative is needed to improve smoking cessation for stroke survivors.


Reduced expression and altered subcellular localization of the cyclin-dependent kinase inhibitor p27(Kip1) in human colon cancer.
The p27(Kip1) protein is a negative regulator of the cell cycle and a potential tumor suppressor gene. Reduced expression of the p27(Kip1) protein has been reported in several human tumors and has been associated with higher tumor grade and increased mortality in breast, lung, colon, prostate, bladder, and gastric cancers. On the other hand, increased expression of the p27(Kip1) protein, in the absence of gene mutation, has been observed in primary colon and breast cancers. It was recently suggested that sequestration in the cytoplasm might be an alternative way to inactivate p27(Kip1)-associated inhibitory activity. This study was undertaken to further evaluate p27(Kip1) expression in primary colon tumors and to verify whether differences exist between normal and cancer tissues in terms of subcellular localization of this protein. Both normal and neoplastic tissues expressed variable amounts of the p27(Kip1) protein, as assessed by western blot analyses. Although the mean values were not different between tumor and normal mucosa samples, the expression of total p27(Kip1) was reduced in a subset of tumors. Decreased levels of total p27(Kip1) were associated with high tumor grade (P=0.03) and stage (P=0.04). Moreover, while there was no significant difference in nuclear p27(Kip1), the amount of p27(Kip1) in the cytoplasmic fraction was significantly higher in the tumor samples than in the normal mucosa samples (P=0.0001). These results suggest that p27(Kip1) expression is lost in a subset of colorectal tumors and that alterations in the subcellular localization of this protein might play a role in colon carcinogenesis.


Anesthesia on the rheumatoid patient.
In the orthopedic setting, the anesthesiologist often encounters the rheumatoid patient after the disease has run a resistant course. Despite optimal medical therapy, the patient at this point has intolerable levels of pain or limitation of function because of structural joint damage. Given the duration of the disease and severity of symptoms, a number of pharmacologic modalities already have been tried for which the patient has suffered some side effects. Now that the disease has spanned a significant period, the patient has become older with one or more coexisting illnesses. These comorbidities may occur independently or as part of the extra-articular manifestations of the underlying rheumatic disorder. Because of these reasons, rheumatoid patients today present major anesthetic challenges.


Evaluation and Quality Assessment of Prestripped, Preloaded Descemet Membrane Endothelial Keratoplasty Grafts.
To determine graft quality and feasibility of Descemet membrane endothelial keratoplasty (DMEK) grafts that are prestripped and preloaded into injectors by eye bank technicians before shipping to surgeons. DMEK grafts (n = 31) were prepared from donor corneas and preloaded into Straiko Modified Jones tubes and set inside viewing chambers filled with 20 mL of Optisol-GS. Preloaded grafts were evaluated using specular microscopy and slit-lamp biomicroscopy. Endothelial cell loss (ECL) was captured by vital dye staining and quantified using FIJI. A subset of preloaded tissues was subjected to a shipping validation and 5-day storage assay. Fourteen additional DMEK grafts (not preloaded) were examined to quantify damage resulting from prestripping alone. Specular microscopy was able to be performed for all preloaded tissues. Average ECL for preloaded tissues quantified by vital dye staining and FIJI after overnight storage was 16.8% ± 5.9%, and differed from slit-lamp ECL estimation by an average of 5.3% ± 3.6%. The average damage caused by prestripping alone was 9.3% ± 5.9%, and it was significantly less than that of preloaded tissues (P < 0.01). Average ECL for preloaded tissues subjected to round-trip shipping events was 18.5% ± 12.4%, and ECL for tissues stored at 4°C for 5 days after preloading was 13.1% ± 9.5%. It is possible to prepare, evaluate, and ship DMEK grafts loaded inside a glass carrier and viewing chamber. The ability to evaluate tissues after processing allows for adherence to the Eye Bank Association of America Medical Standards, and for surgeons to receive the most accurate tissue information.


Illegal drug use among rural adults: mental health consequences and treatment utilization.
This study uses the National Household Survey on Drug Abuse to examine mental health consequences and treatment utilization among nonmetropolitan and rural adults. The study employs an ecological system perspective, dividing the study population into three groups: nonmetropolitan-rural, nonmetropolitan-urban, and metropolitan-rural. Logistic regression analysis is used to examine four sets of factors related to self-report of mental health problems among drug-using adults, including community level features, family characteristics, personal characteristics, and stress factors. Perceived ease of purchasing cocaine, number of moves in last five years, employment in blue-collar occupations, number of jobs in last five years, and residence in neighborhoods with a low rate (< 10%) of minority households were significantly related to self-report problems. Results of the analysis are discussed in terms of barriers to utilization of treatment and rehabilitation services among nonmetropolitan and rural adults, such as availability and access to facilities and professional services, social stigma, ability to afford services, and the difficulty for rural communities to support inhospital and outpatient services.


Smoking Susceptibility in Canadian Adolescent Electronic-Cigarette Users.
Background: E-cigarette use is increasing among Canadian youth, with experimentation especially prevalent among never-smoking youth. Among this group, there is concern e-cigarette use contributes to future initiation of smoking through a gateway effect. However, e-cigarette use and smoking share many common risk factors; a postulated mechanism to explain the apparent causal pathway from e-cigarette use to smoking initiation in previously smoking-naïve youth. A better understanding of the relationships between smoking susceptibility and e-cigarette use among never-smoking youth is needed. Purpose/objectives: The primary aim of this study was to gain a deeper understanding of the risk factors associated with smoking susceptibility in youth who have recently used e-cigarettes. Methods: This study used data (n = 40,363) from the 2018/2019 Canadian Student Tobacco Alcohol and Drug Use Survey (CSTADS) to compare the risk factor profiles of susceptible and non-susceptible never-smoking e-cigarette users, as well as susceptible and non-susceptible never-smoking youth who have never used an e-cigarette. Results: E-cigarette use, independent of susceptibility status, was associated with a sociodemographic and behavioral risk factor profile likely to confer a higher risk of initiating smoking. Among e-cigarette users, smoking susceptibility was associated with more smoking risk factors. Conclusions/importance: Study findings support a common risk-factor model, rather than e-cigarette use itself, to explain differences in the likelihood of smoking initiation among e-cigarette users. E-cigarette use and smoking initiation may be interchangeable outcomes amongst those with smoking risk factors. The risks of e-cigarette use, and their regulatory status, need to be balanced with their potential as harm reduction tools.


An Integrated Database for Complex Protein Structure Modeling.
In homology modeling of protein structures, it is typical to find templates through a sequence search against a database of proteins with known structures. In more complicated modeling cases, such as modeling a protein structure in contact with a ligand, sequence information itself may not be enough and more biological information is required for a successful modeling process. SCOP and PFAM are two databases providing protein domain information which can be utilized in complex protein structure modeling. However, due to the manually-curated nature of both databases, they fail to provide timely coverage of protein sequences existing in the Protein Data Bank (PDB). In this paper, we introduce a new relational database, IDOPS, which integrates sequence and biological information extracted from remediated PDB files and protein domain information generated with HMM profiles of PFAM families. With a carefully designed protocol, this database is updated regularly and the coverage rate of PDB entries is guaranteed to be high.


Single-molecule DNA patterning and detection by padlock probing and rolling circle amplification in microchannels for analysis of small sample volumes.
The rolling circle amplification (RCA) is a versatile DNA amplification method in which a DNA molecule is amplified using a single DNA primer, allowing the product to be counted as a single dot. Circular templates for RCA can arise from padlock probes in highly specific DNA target-mediated ligation reactions. However, improvement of detection efficiency represents an important challenge. In homogeneous assays, the detection efficiency is generally only under 0.1%, mainly because the sample volume is too large compared with the detection volume. Here, we used microchannel surfaces in a glass microchip for DNA detection in small volume samples. First, DNA patterning on glass surfaces in microchannels was demonstrated using chemical surface patterning by UV light. By using a photochemical reaction, we realized DNA patterning in a closed space. Second, RCA was demonstrated using dilutions of target molecules, and a calibration curve was obtained. The highest detection efficiency was 22.5% by virtue of the reduced sample volumes from several hundred microliters to 5.0 nL. Accordingly, a countable number of DNA molecules was successfully detected. This method is suitable for analysis of very small volume samples such as single cells, especially by using extended-nanochannels with dimensions of 10-1000 nm.


Mechanistic issues of the interaction of the hairpin-forming domain of tBid with mitochondrial cardiolipin.
The pro-apoptotic effector Bid induces mitochondrial apoptosis in synergy with Bax and Bak. In response to death receptors activation, Bid is cleaved by caspase-8 into its active form, tBid (truncated Bid), which then translocates to the mitochondria to trigger cytochrome c release and subsequent apoptosis. Accumulating evidence now indicate that the binding of tBid initiates an ordered sequences of events that prime mitochondria from the action of Bax and Bak: (1) tBid interacts with mitochondria via a specific binding to cardiolipin (CL) and immediately disturbs mitochondrial structure and function idependently of its BH3 domain; (2) Then, tBid activates through its BH3 domain Bax and/or Bak and induces their subsequent oligomerization in mitochondrial membranes. To date, the underlying mechanism responsible for targeting tBid to mitochondria and disrupting mitochondrial bioenergetics has yet be elucidated. The present study investigates the mechanism by which tBid interacts with mitochondria issued from mouse hepatocytes and perturbs mitochondrial function. We show here that the helix alphaH6 is responsible for targeting tBid to mitochondrial CL and disrupting mitochondrial bioenergetics. In particular, alphaH6 interacts with mitochondria through electrostatic interactions involving the lysines 157 and 158 and induces an inhibition of state-3 respiration and an uncoupling of state-4 respiration. These changes may represent a key event that primes mitochondria for the action of Bax and Bak. In addition, we also demonstrate that tBid required its helix alphaH6 to efficiently induce cytochrome c release and apoptosis. Our findings provide new insights into the mechanism of action of tBid, and particularly emphasize the importance of the interaction of the helix alphaH6 with CL for both mitochondrial targeting and pro-apoptotic activity of tBid. These support the notion that tBid acts as a bifunctional molecule: first, it binds to mitochondrial CL via its helix alphaH6 and destabilizes mitochondrial structure and function, and then it promotes through its BH3 domain the activation and oligomerization of Bax and/or Bak, leading to cytochrome c release and execution of apoptosis. Our findings also imply an active role of the membrane in modulating the interactions between Bcl-2 proteins that has so far been underestimated.


Child psychiatry: what it is all about.
This paper discusses the history of child psychiatry, and outlines the role and training of a child psychiatrist. Case histories are introduced as illustrations of the factors with which both therapist and patient have to contend during the course of their relationship.


Mentoring experiences of psychiatric nurses: from acquaintance to affirmation.
Mentoring is regarded as involving a voluntary and mutually beneficial relationship in which one person is experienced and knowledgeable (mentor) who supports the maturation of a less-experienced person (mentee). While there have been studies on mentorship in a wide range of areas within nursing, so far studies on psychiatric nursing are scarce. The hallmark of psychiatric nursing is the use of interpersonal process as a means of bringing about positive health changes in the clients. If psychiatric nurses are involved in mentorship, they can, through experiential learning, be nurtured to use interpersonal process as therapeutic tools in their work more effectively. This study examines the mentorship experiences of psychiatric nurses. Personal accounts of 27 psychiatric nurses were analyzed using qualitative methodology. Results of the study shed light on the role of mentorship in facilitating the socialization of psychiatric nurses and revealed the main aspects involved in this process. Four themes experienced by mentees during the mentoring process are the key to its success. These are: becoming acquaintances, developing bond, feeling being included and obtaining affirmation. These themes were found to be progressive in terms of mentees' degree of connection with their mentors and their involvement in the nursing profession.


Mutational analysis of simian virus 40 T antigen: stimulation of cellular DNA synthesis and activation of rRNA genes by mutants with deletions in the T-antigen gene.
The biological activity of several deletion mutants of simian virus 40, cloned in pBR322, was determined. Three functions of the simian virus 40 A gene were studied: (i) the ability to express T antigen; (ii) the ability to induce cell DNA replication; and (iii) the ability to reactivate silent rRNA genes in hybrid cells. Recombinant plasmid DNA was introduced into cells by manual microinjection or by transfection. The results (together with previous reports) indicate that the critical sequences for these three functions are located separately on the simian virus 40 A gene, as follows: (i) the sequences necessary for the detection of the common antigenic determinant of T antigen extend from nucleotide 4147 to nucleotide 4001 (map units 0.45 to 0.42); (ii) the sequences critical for the stimulation of cell DNA synthesis extend from nucleotide 4327 to nucleotide 4001 (map units 0.49 to 0.42); and (iii) those critical for the reactivation of rRNA genes extend approximately from nucleotide 3827 to nucleotide 3526 (map units 0.39 to 0.33).


Chronic parotitis: not another SPINKosis.
Pancreatitis and parotitis share several etiological, pathohistological and functional similarities. It arose from recent pancreatitis research that some cases of chronic pancreatitis are associated with mutations of the serine protease inhibitor, Kazal type-1 (SPINK1). We tested the hypothesis that the pancreatitis-associated N34S mutation of SPINK1 is also a risk factor for chronic parotitis. Reverse-transcriptase polymerase chain reaction was used to investigate SPINK1 transcription in the parotid gland. Forty-five blocks of formalin-fixed, paraffin wax-embedded tissues with chronic parotitis of unknown cause were analyzed for the SPINK1-N34S mutation. The SPINK1 gene is transcribed in the parotid gland. Two of the 45 patients (4.4%) with chronic parotitis carried the N34S mutation heterozygously. Of 82 healthy blood donors, 3 subjects (3.7%) were identified as carrying this mutation heterozygously (p = 0.83). The SPINK1-N34S mutation is not associated with chronic parotitis.


Evaluating Adherence to Guideline-based Injury Grading in Pediatric Renal Trauma: How Are Patients Being Worked Up Prior to Transfer to a Level 1 Trauma Center?
To determine whether children with renal trauma who are transferred to a level I trauma center (TC) receive appropriate imaging studies before transfer and whether this impacts care. The American Urologic Association (AUA) Urotrauma guidelines state clinicians should perform IV contrast-enhanced CT with immediate and delayed images when renal trauma is suspected. Adherence to these guidelines in pediatric patients is unknown. Children treated for renal trauma at our TC between 2005 and 2019 were identified. Comparisons between patients with initial imaging at a transferring hospital (TH) and patients with initial imaging at our TC were performed using logistic regression. Of the included 293 children, 67% (197/293) were transferred into our TC and 61% (180/293) received initial imaging at the TH. Patients with initial imaging at the TH were more likely to have higher-grade renal injuries (P = .001) and were less likely to have guideline-recommended imaging (31% vs 82%, P < .001). Of patients who were imaged at the TH, 28% (50/180) underwent an additional CT imaging shortly after transfer. When imaging was incomplete at the TH, having an additional scan upon transfer was associated with emergent urologic surgery (P = .004). Adherence to the AUA Urotrauma guidelines is low, with most pediatric renal trauma patients not receiving complete staging with delayed-phase imaging before transfer to a TC. Furthermore, patients initially imaged at THs were more likely to receive more CT scans per admission and were exposed to higher amounts of radiation. There is a need to improve imaging protocols for complete staging of renal trauma in children before transfer.


Identification of new small molecule inhibitors of cystic fibrosis transmembrane conductance regulator protein: in vitro and in vivo studies.
Cystic fibrosis transmembrane conductance regulator (CFTR) protein is a cAMP-regulated chloride channel that has been proposed as a pharmacological target to reduce intestinal fluid loss in cholera. The aim of this study was to identify new CFTR inhibitors by high-throughput screening. Screening of 50,000 drug-like small molecules was performed using a cell-based assay of iodide influx in Fisher rat thyroid (FRT) cells co-expressing human CFTR and halide-sensitive yellow fluorescent protein (YFP-H148Q). Two new CFTR inhibitors, 2-[N-(3-hydroxy-4-carboxyphenyl) amino]-4-(4-methylphenyl)-thiazole (INH 1) and 1-acetyl-5-bromo-2,3-dihydro-N-(1,2,3,4-tetrahydro-1-naphthalenyl)-1H-Indole-7-sulfonamide (INH 2), were identified. They were then determined for potency, reversibility and specificity by electrophysiological methods, and for in vivo efficacy in mouse model of cholera toxin-induced intestinal fluid secretion. INH 1 and INH 2 reversibly inhibited cAMP-activated apical chloride current in FRT cells with Kis of 15 and 20 microM, respectively. Similarly, in short-circuit current analysis in human colonic epithelial cell lines (T84 cells), cAMP-activated chloride secretion was inhibited by INH 1 and INH 2 with Kis of 24.5 and 25.3 microM, respectively. Calcium-activated chloride secretion in the T84 cells was markedly inhibited by 100 microM of INH 1, but was unaffected by 100 microM of INH 2. In vivo studies in mice showed that a single intraperitoneal injection of INH 1 (3 mg/kg) reduced cholera toxin-induced intestinal fluid secretion by 40%, whereas INH 2 produced no effect. Our results indicate that INH 1 could be a new class candidate for a blocker of cholera toxin-induced intestinal fluid secretion as well as a CFTR inhibitor.


[Angiocardiography as an indicator dilution technic in the diagnosis of heart valve insufficiency].
On the basis of theoretical calculations and an analysis of data of angiocardiography and electrodilution the authors make a conclusion that it is possible to determine the degree of heart valve insufficiency by the intensity of contrast in the heart chambers and the time of elimination of the contrast substance.


Shifting the Current Clinical Perspective: Isolated Eccentric Exercise as an Effective Intervention to Promote the Recovery of Muscle After Injury.
Eccentric exercise is able to mechanically engage muscle, initiating strain-sensing molecules that promote muscle recovery by inducing beneficial adaptations in neural activity and muscle morphology, 2 critical components of muscle function that are negatively altered after injury. However, due to misinterpreted mathematic modeling and in situ and in vitro stretch protocols, a dogma that exposing muscle to eccentric exercise is associated with injury has been perpetuated in the literature. In response, clinicians have been biased toward using concentric exercise postinjury to improve the recovery of muscle function. Unfortunately, this conventional approach to rehabilitation does not restore muscle function, and reinjury rates remain high. Here, the authors present experimental evidence and theoretical support for the idea that isolated eccentric exercise is ideally suited to combat muscle inhibition and muscle strains and is an attractive alternative to concentric exercise.


Modifications of cell signalling in the cytotoxicity of metals.
Many metals act on biological systems at low concentrations and recent epidemiological and experimental research indicates that toxic effects of certain metals occur at levels only marginally higher than those found in healthy subjects. Despite a large number of studies describing metal cytotoxicity, the molecular mechanisms involved are still poorly understood. However, it now seems evident that several metals can interact with enzyme functional groups and that proteins involved in signal transduction, including Ca2+ channels and pumps, may be especially sensitive to this interaction. Impairment of the ability of cells to adequately respond to the stimulation by hormones and growth factors may result in the loss of important cell functions or activation of mechanisms that compromise cell survival. In the following sections we will briefly describe the effects of various metals on cell signalling and present our recent findings on the mechanism by which inorganic mercury affects signal transduction.


Multi-site evaluation of the BD Stem Cell Enumeration Kit for CD34(+) cell enumeration on the BD FACSCanto II and BD FACSCalibur flow cytometers.
Evaluation of the BD Stem Cell Enumeration Kit was conducted at four clinical sites with flow cytometry CD34(+) enumeration to assess agreement between two investigational methods: (i) the BD FACSCanto II and BD FACSCalibur systems and (ii) the predicate method (Beckman Coulter StemKit and StemTrol, Immunotech SAS, Beckman Coulter, Marseille Cedex 9, France). Leftover and delinked specimens (n = 1032) from clinical flow cytometry testing were analyzed on the BD FACSCanto II (n = 918) and BD FACSCalibur (n = 905) in normal and mobilized blood, frozen and thawed bone marrow and leucopheresis and cord blood anticoagulated with citrate phosphate dextrose, anticoagulant citrate dextrose-solution A, heparin and ethylenediaminetetraacetate, alone or in combination. Fresh leucopheresis analysis addressed site equivalency for sample preparation, testing and analysis. The mean relative bias showed agreement within predefined parameters for the BD FACSCanto II (-2.81 to 4.31 ±7.1) and BD FACSCalibur (-2.69 to 5.2 ±7.9). Results are reported as absolute and relative differences compared with the predicate for viable CD34(+), percentage of CD34(+) in CD45(+) and viable CD45(+) populations (or gates). Bias analyses of the distribution of the predicate low, mid and high bin values were done using BD FACSCanto II optimal gating and BD FACSCalibur manual gating for viable CD34(+), percentage of CD34(+) in CD45(+) and viable CD45(+). Bias results from both investigational methods show agreement. Deming regression analyses showed a linear relationship with R(2) > 0.92 for both investigational methods. In conclusion, the results from both investigational methods demonstrated agreement and equivalence with the predicate method for enumeration of absolute viable CD34(+), percentage of viable CD34(+) in CD45(+) and absolute viable CD45(+) populations.


Relationship between Use of Rehabilitation Resources and ICU Readmission and ER Visits in ICU Survivors: the Korean ICU National Data Study 2008-2015.
Despite the increasing importance of rehabilitation for critically ill patients, there is little information regarding how rehabilitation therapy is utilized in clinical practice. Our objectives were to evaluate the implementation rate of rehabilitation therapy in the intensive care unit (ICU) survivors and to investigate the effects of rehabilitation therapy on outcomes. A retrospective nationwide cohort study with including > 18 years of ages admitted to ICU between January 2008 and May 2015 (n = 1,465,776). The analyzed outcomes were readmission to ICU readmission and emergency room (ER) visit. During the study period, 249,918 (17.1%) patients received rehabilitation therapy. The percentage of patients receiving any rehabilitation therapy increased annually from 14% in 2008 to 20% in 2014, and the percentages for each type of therapy also increased over time. The most common type of rehabilitation was physical therapy (91.9%), followed by neuromuscular electrical stimulation (29.6%), occupational (28.6%), respiratory, (11.6%) and swallowing (10.3%) therapies. After adjusting for confounding variables, the risk of 30-day ICU readmission was lower in patients who received rehabilitation therapy than in those who did not (P < 0.001; hazard ratio [HR], 0.70; 95% confidence interval [CI], 0.65-0.75). And, the risk of 30-day ER visit was also lower in patients who received rehabilitation therapy (P < 0.001; HR, 0.83; 95% CI, 0.77-0.88). In this nationwide cohort study in Korea, only 17% of all ICU patients received rehabilitation therapy. However, rehabilitation is associated with a significant reduction in the risk of 30-day ICU readmission and ER visit.


How do H2 oxidation molecular catalysts assemble onto carbon nanotube electrodes? A crosstalk between electrochemical and multi-physical characterization techniques.
Molecular catalysts show powerful catalytic efficiency and unsurpassed selectivity in many reactions of interest. As their implementation in electrocatalytic devices requires their immobilization onto a conductive support, controlling the grafting chemistry and its impact on their distribution at the surface of this support within the catalytic layer is key to enhancing and stabilizing the current they produce. This study focuses on molecular bioinspired nickel catalysts for hydrogen oxidation, bound to carbon nanotubes, a conductive support with high specific area. We couple advanced analysis by transmission electron microscopy (TEM), for direct imaging of the catalyst layer on individual nanotubes, and small angle neutron scattering (SANS), for indirect observation of structural features in a relevant aqueous medium. Low-dose TEM imaging shows a homogeneous, mobile coverage of catalysts, likely as a monolayer coating the nanotubes, while SANS unveils a regular nanostructure in the catalyst distribution on the surface with agglomerates that could be imaged by TEM upon aging. Together, electrochemistry, TEM and SANS analyses allowed drawing an unprecedented and intriguing picture with molecular catalysts evenly distributed at the nanoscale in two different populations required for optimal catalytic performance.


Hostile attributions in bipolar disorder and schizophrenia contribute to poor social functioning.
To compare the profile of attributional style of a group of out-patients with bipolar disorder (BD) and schizophrenia (SZ), and a group of healthy controls - along with other social cognition domains - such as emotion recognition and theory of mind (ToM). A total of 46 out-patients diagnosed with BD, 49 with SZ, and 50 healthy controls were assessed in attributional style (Ambiguous Intentions Hostility Questionnaire), facial emotion recognition (FEIT, FEDT, ER-40), and ToM (Hinting Task). Symptomatology, clinical variables and global functioning were also collected. Both groups with SZ and BD showed hostile social cognitive biases, compared with the control group. Patients with BD also showed a capacity for emotional recognition similar to those with SZ and worse than control subjects. In contrast, patients with SZ showed poorer ToM. Subthreshold depressive symptoms and an attributional style toward hostility appeared as the factors with a strongest association to global functioning in BD. In SZ, PANSS score and a tendency to aggressiveness were the most relevant factors. Attributional style (along with other domains of social cognition) is altered in out-patients with BD and SZ. The presence of residual symptoms and a hostile social cognitive bias may contribute to the functional impairment of both groups.


Oxygen tension-mediated erythrocyte membrane interactions regulate cerebral capillary hyperemia.
The tight coupling between cerebral blood flow and neural activity is a key feature of normal brain function and forms the basis of functional hyperemia. The mechanisms coupling neural activity to vascular responses, however, remain elusive despite decades of research. Recent studies have shown that cerebral functional hyperemia begins in capillaries, and red blood cells (RBCs) act as autonomous regulators of brain capillary perfusion. RBCs then respond to local changes of oxygen tension (PO2) and regulate their capillary velocity. Using ex vivo microfluidics and in vivo two-photon microscopy, we examined RBC capillary velocity as a function of PO2 and showed that deoxygenated hemoglobin and band 3 interactions on RBC membrane are the molecular switch that responds to local PO2 changes and controls RBC capillary velocity. Capillary hyperemia can be controlled by manipulating RBC properties independent of the neurovascular unit, providing an effective strategy to treat or prevent impaired functional hyperemia.


Influence of early phase clinical trial enrollment on patterns of end-of-life care for children with advanced cancer.
We conducted a retrospective cohort study of 125 pediatric oncology patients who died in 2010-2014 to explore how healthcare utilization, pediatric palliative care (PPC) receipt, and end-of-life care (EOLC) differed between patients enrolled in early phase clinical trials (EP) and those not enrolled (NEP). Baseline characteristics and healthcare utilization did not significantly differ between groups. EP patients received PPC consultation closer to death than NEP patients (median days before death = 58 [interquartile range = 16-84] vs. 85 [32-173]; P = 0.04). Our findings suggest that early phase trial enrollment does not substantially alter EOLC for children with advanced cancer but may contribute to later PPC engagement. Future studies should definitively assess the relationship between trial enrollment and PPC timing.


Accessing perfluoroalkyl nickel(II), (III), and (IV) complexes bearing a readily attached [C4F8] ligand.
The [C4F8] ligand was shown to support well-defined terpyridyl nickel complexes in the +2 and +3 oxidation states. Notably, a cyclic voltammetry study of the nickel(iii) species indicates that an additional oxidation is accessible, providing a family of related fluoroalkyl nickel complexes spanning the +2 to +4 oxidation states.


Detection of renal anomalies by abdominal palpation in newborn infants.
In a new technique of palpation for renal anomalies in the newborn one hand supports the infant while the fingers of the other hand support the loin and the thumb explores the abdomen. In a series of 11 000 otherwise normal newborn children superficial palpation detected 11 renal anomalies, and deep palpation led to the discovery of another 42 anomalies. One of two other series in which palpation was performed bimanually gave a similar incidence of renal anomalies (0-5%). Early discovery of an asymptomatic anomaly enables early treatment of the complications that are often found in patients with congenital renal anomalies detected in later life.


Red blood cell invasion by Plasmodium vivax: structural basis for DBP engagement of DARC.
Plasmodium parasites use specialized ligands which bind to red blood cell (RBC) receptors during invasion. Defining the mechanism of receptor recognition is essential for the design of interventions against malaria. Here, we present the structural basis for Duffy antigen (DARC) engagement by P. vivax Duffy binding protein (DBP). We used NMR to map the core region of the DARC ectodomain contacted by the receptor binding domain of DBP (DBP-RII) and solved two distinct crystal structures of DBP-RII bound to this core region of DARC. Isothermal titration calorimetry studies show these structures are part of a multi-step binding pathway, and individual point mutations of residues contacting DARC result in a complete loss of RBC binding by DBP-RII. Two DBP-RII molecules sandwich either one or two DARC ectodomains, creating distinct heterotrimeric and heterotetrameric architectures. The DARC N-terminus forms an amphipathic helix upon DBP-RII binding. The studies reveal a receptor binding pocket in DBP and critical contacts in DARC, reveal novel targets for intervention, and suggest that targeting the critical DARC binding sites will lead to potent disruption of RBC engagement as complex assembly is dependent on DARC binding. These results allow for models to examine inter-species infection barriers, Plasmodium immune evasion mechanisms, P. knowlesi receptor-ligand specificity, and mechanisms of naturally acquired P. vivax immunity. The step-wise binding model identifies a possible mechanism by which signaling pathways could be activated during invasion. It is anticipated that the structural basis of DBP host-cell engagement will enable development of rational therapeutics targeting this interaction.


Quality of life, developmental milestones, and self-esteem of young adults with congenital hypothyroidism diagnosed by neonatal screening.
With advances in the treatment of congenital hypothyroidism (CH), the neuropsychological functioning of CH patients is considerably improved. Although much is written about cognitive and motor development, little is known about emotional and social consequences for patients growing up with CH, diagnosed by neonatal screening. The objectives of the study were to: 1) compare health-related quality of life (HRQoL), developmental milestones also called course of life (CoL), sociodemographical outcomes, and self-esteem of CH patients with the general population; and 2) explore whether severity of CH was related to these outcomes. A total of 69 young adults with CH, born in The Netherlands in 1981-1982, completed the "TNO-AZL Questionnaire for Adult's Health related Quality of Life" questionnaire, the CoL survey (developmental milestones and sociodemographical outcomes), and a self-esteem questionnaire. HRQoL, CoL, social demographical outcomes, and self-esteem in young adults with CH were determined. CH patients are more often at risk for HRQoL impairment and reported lower HRQoL on several domains (cognitive functioning, P < 0.0001; sleeping, P < 0.004; pain, P < 0.0001; daily activities, P < 0.004; vitality, P < 0.0001; aggressiveness, P < 0.0001; and depressive moods, P < 0.0001) compared with healthy adults. Patients reported a lower self-esteem (P < 0.005) and had a delayed CoL on the domain of social development (P < 0.016). There were no significant within-group differences between the severity groups for HRQoL, CoL, and self-esteem. Negative consequences in terms of HRQoL, development, and self-esteem are prevalent in young adults with CH. Health care physicians should be attentive to these consequences and provide additional support (emotional and educational guidance) if necessary.


Epidemiology of cardiovascular disease in patients with type 1 diabetes: European perspective.
The International Diabetes Federation estimated that 5.1 million people aged between 20 and 79 years died from diabetes in 2013, accounting for 8.4% of global all-cause mortality among people in this age group. Type 1 diabetes is associated with a 2- to 4-fold increased mortality risk compared with the general population. Before the onset of late complications, most of the excess mortality is from potentially preventable causes of death such as ketoacidosis, whereas the long-term excess mortality is largely due to cardiovascular disease. However, a wide geographic variation in mortality of type 1 diabetic patients has been evidenced and accurate estimates of mortality attributable to diabetes are difficult to obtain. The review provides an overview of currently available evidence and summarizes main problems in estimating early and long-term mortality by cause of death in type 1 diabetes, paying particular attention to European studies.


Comparison of the effects of extracorporeal shock wave therapy and a vacuum erectile device on penile erectile dysfunction: a randomized clinical trial.
This randomized clinical trial (October 2012-December 2013) compared extracorporeal shock wave therapy (ESWT) and a vacuum erectile device (VED) for management of erectile dysfunction (ED). Consecutive Chinese patients (20-55 years) with ED, abnormal nocturnal penile tumescence and rigidity (NPTR), and international index of erectile function-5 items (IIEF-5) score <22 were randomized to receive ESWT or VED (twice weekly, 4 weeks). Primary outcomes were treatment efficacy and success rate 4 weeks after completion of therapy. Secondary outcomes included changes in IIEF-5 score, sex encounter profile (SEP) score, erection hardness score (EHS) and NPTR assessments 4 weeks post-therapy. All enrolled patients (n = 30 per group) completed the study. At baseline, age, IIEF-5 score, SEP score, EHS, and NPTR assessments were similar between groups. Four weeks post-therapy, IIEF-5 score increased in the ESWT (15.03 ± 3.00 vs. 11.60 ± 2.28) and VED (15.10 ± 3.06 vs. 11.53 ± 2.27) groups, as did SEP score, EHS, and NPTR measures (all P < .05). Efficacy in the ESWT and VED groups was excellent in 10% and 13.3%, respectively, and moderate in 63.3% and 53.3%, respectively. Treatment success rate in the ESWT and VED groups was 73.3% and 67.7%, respectively. VED use and ESWT have comparable efficacies in the treatment of ED in Chinese patients.


Evaluation of Telephone Cardiopulmonary Resuscitation Performance in Current Practice in Saudi Arabia.
Out-of-hospital cardiac arrest (OHCA) is a global health problem with a low survival rate. Telephone cardiopulmonary resuscitation (T-CPR) guidance by emergency medical services (EMS) dispatchers can improve CPR performance and, consequently, survival rates. Accordingly, the American Heart Association (AHA) has released performance standards for T-CPR in current practice to improve its quality. However, no study has examined T-CPR performance in Saudi Arabia. Therefore, this study aims to evaluate T-CPR performance in the Saudi Arabian EMS system. A retrospective observation of OHCA calls in current practice was conducted in Riyadh, Saudi Arabia. OHCA calls were reviewed to identify those that met the selection criteria. Variables collected included return of spontaneous circulation (ROSC), OHCA recognition rate, time from EMS call receipt to location acquisition, to OHCA recognition and to commencement of CPR. A total of 308 OHCA cases were reviewed, and 100 calls were included. ROSC was identified in 10% of the included calls. OHCA was correctly recognized in 62% of the calls. The time to OHCA identification and CPR performance from EMS call receipt were found to be 303 s and 367 s, respectively. T-CPR performance in Saudi Arabia is below AHA standards. However, this is similar to what has been reported in the literature. Avoiding any unnecessary call transfer during OHCA calls and prompt identification of callers' locations could improve T-CPR performance.


Comparing task performance, visual comfort and alertness under different lighting sources: an experimental study.
The aim of this study is to compare the effects of different light sources - namely light-emitting diode (LED), compact fluorescent (FLcomp) and fluorescent with warm color temperature (FLwarm) and cool color temperature (FLcool) - on the performances, alertness, visual comfort level and preferences in a pilot study. A laboratory controlled experiment was conducted by focusing on 20 postgraduate students who volunteered to participate in a series of tests under four different light sources. "GO NO GO" task and Karolinska Sleepiness Scale (KSS) were employed to assess objective and subjective alertness, while modified OLS questionnaire was used to gauge comfort level and preferences. In addition, editing and typing tasks were carried out as a performance evaluation. Significant increase was observed in subjective and objective alertness level under FLcool condition and LED in comparison to FLwarm and FLcomp (p < 0.05). In terms of typing performances, respondents performed significantly better with regard to typing speed under FLcool than FLwarm and FLcomp. The lowest number of typing errors was made under FLcool, followed by LED, FLcomp and FLwarm. LED was the most preferred (p=0.001) and most comfortable (p=0.011) lighting condition. The study concludes that the FLcool and LED were more beneficial for alertness level and performance for both computer-based and paper-based activities.


Clonal and chronological genetic analysis of multifocal cancers of the bladder and upper urinary tract.
Recent molecular genetic studies have suggested that multifocal urothelial cancers are derived from an identical progenitor cell. However, the clonal origin of multifocal urothelial cancers of a low-grade superficial type has not been fully defined. Using microsatellite markers, we examined genetic alterations at 20 loci on eight chromosomal arms (2q, 4p, 4q, 8p, 9p, 9q, 11p, and 17p) in 87 metachronous and/or synchronous multifocal urothelial cancers, which included 84 low-grade superficial papillary tumors from 29 patients. Judging from the patterns of loss of heterozygosity, microsatellite shifts, and the subchromosomal partial deletion, multifocal tumors in at least 20 (80%) of the 25 evaluable patients were considered to be derived from a single progenitor cell, although the possibility remained that multifocal tumors in a small subset of patients might develop from distinct progenitor cells due to field cancerization. In 13 of the 20 patients, a chronological genetic analysis was available: genetic heterogeneity was detected in 3 (23%) patients, and an apparent accumulated pattern of genetic alterations was detected in only 1 (8%) patient. In the 20 patients with multifocal tumors of an identical clonal origin, discordant microsatellite alterations were observed, with significantly lower frequencies on chromosome 9 compared to those on the other chromosomes tested. The results indicate that most multifocal low-grade superficial urothelial cancers are genetically stable despite their incidence of frequent recurrence, and genetic divergence occurs in a subset of patients. This heterotopic spread and genetic divergence may occur long before the clinical manifestation of multiplicity from a single transformed cell. These data support the previous view that heterotopic spread of transformed progenitor cells and genetic divergence occur after chromosome 9 alterations in most of low-grade superficial urothelial cancers.


The effect of sodium hyaluronate treating knee osteoarthritis on synovial fluid interleukin -1β and clinical treatment mechanism.
In order to explore the influence of sodium hyaluronate on knee osteoarthritis (KOA) patients synovial fluid interleukin -1β (IL-1β) and analyze its clinical mechanism, this study analyzed 40 cases of KOA patients in our hospital's orthopaedic department, randomly divided them into two groups: Sodium hyaluronate group (group A) and normal saline group (group B), each consists 20 patients. Besides, we selected another 20 patients as normal control group. Group A treated knee joint cavity by injecting sodium hyaluronate, and group B injected knee joint cavity in equal amount of normal saline, once a week for five weeks. Collect respectively knee joint synovial fluid in patients of group A and group B before treatment and after five weeks of treatment, detect the content of knee joint synovial fluid IL-1βin of all the three groups by using enzyme linked immunosorbent assay (ELISA). We can conclude that (1) IL-1β content of knee joint synovial fluid in KOA patients before treatment was significantly higher than healthy people; (2) IL-1β content of group A knee joint synovial fluid after treatment was significantly reduced than before treatment, there was no significant difference for group BIL-1β content before and after treatment; (3) there was no significant difference between group A knee joint synovial fluid IL-1β content after treatment and healthy people. Thus it can be proved that content of IL-1β in knee joint synovial fluid KOA patients is higher than healthy people; sodium hyaluronate can reduce the content of IL-1β in synovial joints and can be effective in the treatment of knee osteoarthritis.


Arabidopsis thaliana and Plant Molecular Genetics.
Arabidopsis thaliana is a small flowering plant with various properties that make it an excellent organism for experiments in molecular genetics. These properties include having a small nuclear genome, a near absence of dispersed repetitive DNA, and a generation time of 4 to 5 weeks. In addition, mutations that affect hormone synthesis and response, many different enzyme activities, and numerous developmental processes have been identified and characterized.


Direct demonstration of persistent Epstein-Barr virus gene expression in peripheral blood of infected common marmosets and analysis of virus-infected tissues in vivo.
Epstein-Barr virus (EBV) infection in animal model systems has been studied previously in marmosets and tamarins using serology and PCR of saliva. Here we directly demonstrated long-term persistence of EBV in the peripheral blood of marmosets by assaying EBER RNA expression. A new reverse transcription-PCR assay, able to distinguish a naturally occurring strain polymorphism in EBER 2 that may be useful as a strain marker for monitoring persistence and interactions between multiple strains in the same animal or person, has been developed. In situ hybridization and immunohistochemistry have also been used to search for EBV-infected cells in the animals. The carrier state in the common marmoset is similar to that of humans in that it is asymptomatic, long-lived and displays a very low level of circulating virus-infected cells. It differs from the human in lacking the characteristic antibody response to EBNA 1.


PEGylation site-dependent structural heterogeneity study of monoPEGylated human parathyroid hormone fragment hPTH(1-34).
The structures of C- and N-terminally monoPEGylated human parathyroid hormone fragment hPTH(1-34) as well as their unmodified counterparts, poly(ethylene glycol) (PEG) and hPTH(1-34), have been studied by small-angle neutron scattering (SANS). The scattering results show that free hPTH(1-34) in 100 mM phosphate buffer (pH 7.4) aggregates into clusters. After conjugation with PEG, the PEG-peptide conjugates self-assemble into a supramolecular core-shell structure with a cylindrical shape. The PEG chains form a shell around the hPTH(1-34) core to shield hPTH(1-34) from the solvent. The detailed structural information on the self-assembled structures is extracted from SANS using a model of the cylindrical core with a shell of Gaussian chains attached to the core surface. On the basis of the data, because of the charge-dipole interactions between the conjugated PEG chain and the peptide, the conjugated PEG chain forms a more collapsed conformation compared to free PEG. Moreover, the size of the self-assembled structures formed by the C-terminally monoPEGylated hPTH(1-34) is about 3 times larger than that of the N-terminally monoPEGylated hPTH(1-34). The different aggregation numbers of the self-assembled structures, triggered by different PEGylation sites, are reported. These size discrepancies because of different PEGylation sites could potentially affect the pharmacokinetics of the hPTH(1-34) drug.


Functional composition drives ecosystem function through multiple mechanisms in a broadleaved subtropical forest.
Understanding the role of biodiversity (B) in maintaining ecosystem function (EF) is a foundational scientific goal with applications for resource management and conservation. Two main hypotheses have emerged that address B-EF relationships: niche complementarity (NC) and the mass-ratio (MR) effect. We tested the relative importance of these hypotheses in a subtropical old-growth forest on the island nation of Taiwan for two EFs: aboveground biomass (ABG) and coarse woody productivity (CWP). Functional dispersion (FDis) of eight plant functional traits was used to evaluate complementarity of resource use. Under the NC hypothesis, EF will be positively correlated with FDis. Under the MR hypothesis, EF will be negatively correlated with FDis and will be significantly influenced by community-weighted mean (CWM) trait values. We used path analysis to assess how these two processes (NC and MR) directly influence EF and may contribute indirectly to EF via their influence on canopy packing (stem density). Our results indicate that decreasing functional diversity and a significant influence of CWM traits were linked to increasing AGB for all eight traits in this forest supporting the MR hypothesis. Interestingly, CWP was primarily influenced by NC and MR indirectly via their influence on canopy packing. Maximum height explained more of the variation in both AGB and CWP than any of the other plant functional traits. Together, our results suggest that multiple mechanisms operate simultaneously to influence EF, and understanding their relative importance will help to elucidate the role of biodiversity in maintaining ecosystem function.


Muscle Metabolism and Fatigue during Simulated Ice Hockey Match-Play in Elite Players.
The present study investigated muscle metabolism and fatigue during simulated elite male ice hockey match-play. Thirty U20 male national team players completed an experimental game comprising three periods of 8 × 1-min shifts separated by 2-min recovery intervals. Two vastus lateralis biopsies were obtained either during the game (n = 7) or pregame and postgame (n = 6). Venous blood samples were drawn pregame and at the end of the first and last periods (n = 14). Activity pattern and physiological responses were continuously monitored using local positioning system and heart rate recordings. Further, repeated-sprint ability was tested pregame and after each period. Total distance covered was 5980 ± 199 m with almost half the distance covered at high skating speeds (>17 km·h). Average and peak on-ice heart rate was 84% ± 2% and 97% ± 2% of maximum heart rate, respectively. Muscle lactate increased (P ≤ 0.05) more than fivefold and threefold, whereas muscle pH decreased (P ≤ 0.05) from 7.31 ± 0.04 pregame to 6.99 ± 0.07 and 7.13 ± 0.11 during the first and last periods, respectively. Muscle glycogen decreased by 53% postgame (P ≤ 0.05) with ~65% of fast- and slow-twitch fibers depleted of glycogen. Blood lactate increased sixfold (P ≤ 0.05), whereas plasma free fatty acid levels increased 1.5-fold and threefold (P ≤ 0.05) after the first and last periods. Repeated-sprint ability was impaired (~3%; P ≤ 0.05) postgame concomitant with a ~10% decrease in the number of accelerations and decelerations during the second and last periods (P ≤ 0.05). Our findings demonstrate that a simulated ice hockey match-play scenario encompasses a high on-ice heart rate response and glycolytic loading resulting in a marked degradation of muscle glycogen, particularly in specific sub-groups of fibers. This may be of importance both for fatigue in the final stages of a game and for subsequent recovery.


Radiologist assistant: best fit for medical imaging.
The radiologist assistant (RA) is an emerging mid-level provider who can benefit radiologists, technologists, radiology departments, patients, and the healthcare system in the United States. A review of the peer-reviewed literature published from 2005-2013 revealed a moderate amount of research about these benefits, which was supplemented with research on collaborative relationships and advanced practice registered nurses (APRN). As an advanced practice radiologic technologist, the RA has a strong technically based, patient-centered background and is the ideal mid-level provider in an imaging-centered clinical environment.


Boundary Effects on Diffusiophoresis and Electrophoresis: Motion of a Colloidal Sphere Normal to a Plane Wall
A combined analytical-numerical study of the diffusiophoresis and electrophoresis of a rigid sphere in a uniform applied field perpendicular to a plane wall is presented. The range of the interaction between the solute species and the solid surfaces is assumed to be small relative to the particle's radius and to the spacing between the particle and the wall, but the polarization of the diffuse species in the thin particle-solute interaction layer is allowed. A slip velocity of fluid and normal fluxes of solute species at the outer edge of the thin diffuse layer are used as the boundary conditions for the fluid domain outside the diffuse layer. Through the use of a collocation method along with these boundary conditions, a set of conservative equations governing the system is solved in the quasisteady state situation and the effects of a plane wall on diffusiophoresis and electrophoresis are calculated for various cases. For the cases of diffusiophoresis in a nonelectrolyte gradient and of electrophoresis, the particle velocity decreases monotonically with the decrease of the distance of the particle center from the wall. For the case of diffusiophoresis in an electrolyte gradient, however, the boundary effect is a complicated function of the properties of the particle and ions, and it no longer varies monotonically with the separation distance for some situations.


Directed self-assembly of solvent-vapor-induced non-bulk block copolymer morphologies on nanopatterned substrates.
We report a study on directed self-assembly (DSA) with solvent annealing to induce the formation of non-bulk block copolymer microdomains on chemical patterns. Ultrathin films of symmetric polystyrene-block-poly(methyl methacrylate) (PS-b-PMMA) display morphologies of PMMA dots, stripes, and PS hexagons with increasing exposure time to acetone vapor, a PMMA-selective solvent. All three nanostructures form long-range-ordered and registered arrays on striped chemical patterns with periods (LS) commensurate to the solvated PS-b-PMMA microdomain period (L0,s). Solvent annealing is shown to facilitate DSA on non-regular chemical patterns, on which the local periods are incommensurate to L0,s. DSA with feature density multiplication, via solvent annealing, is also demonstrated.


Remote in situ analytical spectroscopy and its applications in the nuclear industry.
An experimental system based on Laser Induced Breakdown Spectroscopy (LIBS) has been used to analyze various ferrous samples. A fibre optic system has been used to transmit the incident laser pulse which produces the plasma plume at the surface of the analyte and to transmit back to a spectrometer the optical radiation emitted by the plasma. The measuring system may therefore be placed remote from the analyte which may be situated in a hostile environment such as an operating nuclear reactor. Results show that the system is capable of detecting chromium, nickel, manganese, molybdenum, silicon and vanadium at concentrations smaller than 5x10(-4) g/g


Prosthesis nonuse and discontinuation in United States veterans with major limb amputation: Results of a national survey.
Prosthesis use in persons with amputation can improve mobility and functional independence. Better understanding of the reasons for and outcomes associated with prosthesis nonuse is important to optimize function and long-term health in persons with amputation. Study objectives were to describe the rate, reasons for, and factors associated with never using or discontinuing prosthesis use in United States (US) veterans with amputation. Cross-sectional study design. The study used an online survey to assess prosthesis use and satisfaction in veterans with upper-limb and lower-limb amputation. Survey participation invitations were distributed by email, text message, and mail to 46,613 potential participants. The survey response rate was 11.4%. After exclusions, an analytic sample of 3,959 respondents with a major limb amputation was identified. The sample was 96.4% male; 78.3% White, with mean age of 66.9; and mean of 18.2 years since amputation. The rate of never using a prosthesis was 8.2%, and the rate of prosthesis discontinuation was 10.5%. Functionality (62.0%), undesirable prosthesis characteristics (56.9%), and comfort (53.4%) were the most common reasons for discontinuation. After controlling for the amputation subgroup, the odds of prosthesis discontinuation were higher for those with unilateral upper-limb amputation, female gender, White race (compared with Black race), diabetes, above-knee amputation, and lower prosthesis satisfaction. Prosthesis satisfaction and quality of life were highest for current prosthesis users. This study adds new understanding regarding the rate and reasons for prosthesis nonuse in veterans and highlights the important relationship between prosthesis discontinuation and prosthesis satisfaction, quality of life, and satisfaction with life.


Surgical rehabilitation of voice and swallowing after jugular foramen surgery.
We sought to determine the patient population that will benefit from surgical rehabilitation of voice and swallowing after jugular foramen tumor (JFT) resection. We performed a retrospective case study of patients with a history of JFT resection. The patients' files were reviewed for data on preoperative and postoperative function of cranial nerves VII and IX through XII, voice and swallowing function, and surgical procedures for voice and swallowing rehabilitation and their timing. Twenty-one patients underwent JFT resection. Thirty-eight percent presented with deficits of cranial nerves VII and IX through XII, and 61% developed new postoperative deficits. Three patients recovered glossopharyngeal nerve function, 2 recovered vagus nerve function, and 1 recovered facial nerve function. Surgical rehabilitation procedures were undertaken in 8 patients. Patients who eventually underwent surgical rehabilitation procedures for voice and swallowing tended to have larger tumors, tumors within the nerve bundle in the jugular foramen, and multiple nerve deficits. Most patients with multiple deficits of cranial nerves VII and IX through XII after JFT resection are unlikely to regain spontaneous nerve function, will experience long-term dysphonia and dysphagia, and will elect to undergo corrective surgery to improve voice and swallowing. Preoperative evaluation and close postoperative follow-up can identify patients who would benefit from early surgical rehabilitation.


Refined cigarette smoke as a method for reducing nicotine intake.
We developed a method of refining tobacco smoke to deliver sensory components of cigarette smoking while minimizing the delivery of nicotine and other toxic smoke constituents. In the first experiment, smokers rated puffs of their own brands of cigarette, a commercial low tar and nicotine cigarette, and refined smoke. The refined smoke was rated significantly stronger and more desirable than the low tar and nicotine cigarette despite a comparably low nicotine delivery; subjects' own brands were rated best, but in standardized smoking tests delivered over ten times more tar, nicotine and carbon monoxide. In the second experiment, subjects smoked five times on each of two mornings; one day they received refined smoke and the other day smoked a low tar and nicotine cigarette. The refined smoke produced significantly more satisfaction, yet delivered far less carbon monoxide and tar (assessed by mouth intake). Nicotine intake was comparable to that of the low tar and nicotine cigarette. Because refined smoke substantially reduced subjects' craving for cigarettes while reducing nicotine intake, it may prove to be a useful short-term adjunct to a smoking cessation program. Additionally, the method may be useful in research analyzing the relative contributions of pharmacologic actions of inhaled smoke and the sensory cues associated with nicotine intake as reinforcers maintaining smoking behavior.


Bacteriological contamination in wastewaters from slaughterhouses.
Eighty samples of wastewater from 4 slaugherhouses (A and B pig and cattle, C pig and D cattle slaughterhouse), were examined to determine the bacteriological contamination. At the same time, attention was given to the influence of the types of slaughterhouses and the presence of a guttery on the composition of the bacterial flora in the wastewater. The total viable bacteria at 37 degrees C and 22 degrees C varied from 10(6) to 10(8)/ml. The coliforms and E. coli in the samples of the same slaughterhouse varied widely. The slaughtering of pigs did increase the contamination of wastewater with Salmonella compared with that of the slaughtering of cattle. The cleaning and scraping of the gut increased considerably the number of coliforms, E. coli and Salmonellae. All samples examined were contaminated with Coagulase and/or DNase positive staphylococci of which the maximum number was 1.5 x 1.0(4)/ml. Strains coming from slaughterhouse C belonged to the species Staph, aureus and Staph. hyicus subsp. hyicus and those of slaughterhouse D only to the species Staph. hyicus subsp. hyicus.