Protective Effects of Black Hoof Medicinal Mushroom from Korea, Phellinus linteus (Higher Basidiomycetes), on Osteoporosis In Vitro and In Vivo.
The protective effect of Phellinus linteus (ethanol extract) against osteoporosis was investigated using the Saos-2 human osteoblast-like cell line and osteoclasts. A nontoxic concentration of Ph. linteus (10-2 to 10-8 mg mL-1) increased alkaline phosphatase (ALP) (EC 22.214.171.124) activity to a larger extent than soy did. Ph. linteus also attenuated the number and the activity of tartrate-resistant acid phosphatase-positive multinucleated osteoclasts. These results indicate that Ph. linteus likely regulated both osteoblasts and osteoclasts, contributing to the protection against osteoporosis. The protective effect of Ph. linteus was examined in ovariectomized (OVX) rats. Histological analysis indicates that Ph. linteus improved trabecular bone mass and reduced osteoclast frequency without affecting lipid droplet accumulation in the femur of OVX rats. A Ph. linteus supplementation for 12 weeks also significantly increased serum ALP activity and reduced urinary deoxypyridinoline level in OVX rats. Ultimately, we found that 12-week Ph. linteus supplementation increased the bone accumulation of minerals, including calcium, magnesium, and phosphorus. Collectively, Ph. linteus protected against osteoporosis by balancing the number of osteoblasts and osteoclasts, which was particularly associated with increased ALP activity in vitro and in vivo and mineral accumulation in bone.


Hypertensive female Sprague-Dawley rats require an intact nitric oxide synthase system for compensatory increases in renal regulatory T cells.
We have previously shown that hypertensive female rats have more regulatory T cells (Tregs), which contribute more to blood pressure (BP) control in female versus male rats. Based on known protective properties of Tregs, the goal of the present study was to investigate the mechanisms by which female rats maintain Tregs. The present study was designed to 1) compare the impact of three hypertension models on the percentage of renal Tregs and 2) test the hypothesis that nitric oxide synthase (NOS) inhibition prevents increases in renal Tregs and exacerbates renal damage in female Sprague-Dawley rats. Rats (11-14 wk old) were randomized to one of the following four groups: control, norepinephrine (NE) infusion, angiotensin II infusion, or the NOS inhibitor Nω-nitro-l-arginine methyl ester (l-NAME) in drinking water. BP was measured via tail cuff. After 2 wk of treatment, kidneys were isolated and processed to measure Tregs via flow cytometric analysis and renal injury via urinary albumin excretion, plasma creatinine, and histological analyses. Hypertensive treatments increased BP in all experimental animals. Increases in BP in norepinephrine-and angiotensin II-treated rats were associated with increases in renal Tregs versus control. In contrast, l-NAME treatment decreased Tregs compared with all groups. l-NAME treatment modestly increased albumin excretion. However, plasma creatinine was comparable among the groups, and there was no histological evidence of glomerular or tubular injury. This study provides insights into the mechanisms regulating renal Tregs and supports that an intact NOS system is crucial for female rats to have BP-related increases in renal Tregs.


Home parenteral nutrition in neuroendocrine tumour intestinal failure: improved quality of life and longevity.
Neuroendocrine tumours (NETs) are neoplastic yet behave differently to typical cancers. Despite often being slow growing, they can lead to significant gastrointestinal complications including intestinal failure (IF). The use of home parenteral nutrition (HPN) in neoplastic conditions is rising, primarily for palliation and bridging through treatments for cancer, but remains a challenging decision with a paucity of high-grade evidence-based guidance. A retrospective analysis of patients with NET on HPN was performed. Data collected included the cause of IF, complications encountered with HPN and changes in nutritional assessments. Eight patients were identified, all with metastatic NET. Median weight improved following HPN commencement and line sepsis was the sole complication. All patients had stabilisation and optimisation of nutritional and hydration status. HPN is commenced to improve or maintain patients' nutritional status during often lifelong treatment. The principle aim in providing HPN was to improve survival and quality of life. While NETs are cancers, our case series demonstrates the potential of HPN to actively support longer term survival in the subgroup of patients who develop IF.


Single-layer carbon-coated FeCo alloy nanoparticles embedded in single-walled carbon nanotubes for high oxygen electrocatalysis.
Herein, novel and durable single-layer carbon-coated FeCo alloy nanoparticles embedded in single-walled carbon nanotubes (FeCo/SWCNTs) are rationally synthesized using a facile one-step route by aerosol-assisted floating catalyst chemical vapor deposition (CCVD). The as-synthesized unique FeCo/SWCNT catalyst exhibits remarkable oxygen electrocatalysis performance, especially oxygen evolution reaction activity and superior stability owing to the efficient synergistic effect between FeCo alloy and single-layer carbon regarding the electronic interaction and surface protection, achieving an overpotential (η) of 253 mV at 10 mA cm-2 and a Tafel slope of 44 mV dec-1 in 1.0 M KOH solution while presenting outstanding stability after being tested for 50 hours. Such high oxygen electrocatalysis performance advances realistic renewable zinc-air batteries with high efficiency as well.


Optical refractometer based on a birefringent Bragg grating written in an H-shaped fiber.
An optical refractometer based on a birefringent (Hi-Bi) fiber Bragg grating (FBG) written in a new H-shaped fiber structure is proposed. This structure is formed by opening the two holes of a side-hole fiber using chemical etching. When the Hi-Bi FBG is immersed in different liquids, different responses of the slow and fast wavelengths are obtained. The refractometer is also capable of simultaneous measurement of refractive index and temperature.


Effects of pretreatment hypothermia during resuscitated porcine hemorrhagic shock.
Accidental hypothermia increases mortality and morbidity after hemorrhage, but controversial data are available on the effects of therapeutic hypothermia. Therefore, we tested the hypothesis whether moderate pretreatment hypothermia would beneficially influence organ dysfunction during long-term, porcine hemorrhage and resuscitation. Prospective, controlled, randomized study. University animal research laboratory. Twenty domestic pigs of either gender. Using an extracorporeal heat exchanger, anesthetized and instrumented animals were maintained at 38°C, 35°C, or 32°C core temperature and underwent 4 hours of hemorrhage (removal of 40% of the blood volume and subsequent blood removal/retransfusion to maintain mean arterial pressure at 30 mm Hg). Resuscitation comprised of hydroxyethyl starch and norepinephrine infusion titrated to maintain mean arterial pressure at preshock values. Before, immediately at the end of, and 12 and 22 hours after hemorrhage, we measured systemic and regional hemodynamics (portal vein, hepatic and right kidney artery ultrasound flow probes) and oxygen transport, and nitric oxide and cytokine production. Hemostasis was assessed by rotation thromboelastometry. Postmortem biopsies were analyzed for histomorphology (hematoxylin and eosin staining) and markers of apoptosis (kidney Bcl-xL and caspase-3 expression). Hypothermia at 32°C attenuated the shock-related lactic acidosis but caused metabolic acidosis, most likely resulting from reduced carbohydrate oxidation. Although hypothermia did not further aggravate shock-related coagulopathy, it caused a transitory attenuation of kidney and liver dysfunction, which was ultimately associated with reduced histological damage and more pronounced apoptosis. During long-term porcine hemorrhage and resuscitation, moderate pretreatment hypothermia was associated with a transitory attenuation of organ dysfunction and less severe histological tissue damage despite more pronounced metabolic acidosis. This effect is possibly due to a switch from necrotic to apoptotic cell death, ultimately resulting from reduced tissue energy deprivation during the shock phase.


Radiobiological characterization of human tumor cell multilayers after conventional and particle irradiation.
The goal of this study was to establish planar multilayers from human tumor cells (WiDr and SiHa) as a model for irradiation of solid tumors. In addition to using conventional X rays (250 kV) as a reference standard, multilayers were tested for their suitability in cell survival studies with heavy-ion irradiation ((12)C(6+)) in the plateau and the extended Bragg peak with a scanned ion beam. Multilayers of both cell lines showed decreased survival compared to the corresponding monolayers after both X and heavy-ion irradiation. This multicellular sensitization effect is in contrast to the multicellular resistance or contact effect commonly described in the literature. Flow cytometry measurements showed an arrest of irradiated SiHa cells in G(2)/M phase. In contrast to the transient arrest of the monolayers, the multilayers stayed in a prolonged arrest. After Bragg-peak irradiation of monolayers, the arrest time was increased by 12-24 h, and more cells were arrested than with X rays. For multilayers, there were no differences between G(2) arrest after X rays and heavy ions for the entire observation period.


Neuroanatomical Comparison of the "Word" and "Picture" Versions of the Free and Cued Selective Reminding Test in Alzheimer's Disease.
Episodic memory tests with cued recall, such as the Free and Cued Selective Reminding Test (FCSRT), allow for the delineation of hippocampal and prefrontal atrophy contributions to memory performance in Alzheimer's disease (AD). Both Word and Picture versions of the test exist but show different profiles, with the Picture version usually scoring higher across different cohorts. One possible explanation for this divergent performance between the different modality versions of the test might be that they rely on different sets of neural correlates. The current study explores this by contrasting the neural correlates of the Word and Picture versions of the FCSRT with voxel-based morphometry (VBM) in AD and healthy subjects. We predicted that the Picture version would be associated with different cortical regions than the Word version, which might be more hippocampal-centric. When comparing 35 AD patients and 34 controls, AD patients exhibited impairments on both versions of the FCSRT and both groups performed higher in the Picture version. A region of interest analysis based on prior work revealed significant correlations between free recall of either version with atrophy of the temporal pole and hippocampal regions. Thus, contrary to expectations, performance on both the Word and the Picture version of the FCSRT is associated with largely overlapping networks. Free recall is associated with hippocampal volume and might be properly considered as an indicator of hippocampal structural integrity.


Health policy and the underserved.
Historically, the provision of health benefits and health services has been wedded to the needs of an industrial society to maintain a productive labor force. The casual observer will note that since the late 19th century the role of government as a participant either in the provision for health services or the delivery of health services has been strongly tied to the labor movement in Western Europe. Overtime benefits, initially procured for the worker, were expanded to include the dependents of the worker and, finally, to include the former worker who was no longer able to work due to age or infirmity. The provision of health care to the poor was considered an act of charity and was never liberal enough to reward poverty nor was it essentially humane, for poverty was a condition to be punished. The rise of "alms houses" and public hospitals for the poor provided constant physical reassurance to the worker that he was, indeed, successful. Such institutions were also warnings to the worker lest he slip into the numbers of the poor.


Classification of Various Marijuana Varieties by Raman Microscopy and Chemometrics.
The Raman analysis of marijuana is challenging because of the sample's easy photo-degradation caused by the laser intensity. In this study, optimization of collection parameters and laser focusing on marijuana trichome heads allowed collecting Raman spectra without damaging the samples. The Raman spectra of Δ9-tetrahydrocannabinol (THC), cannabidiol (CBD), and cannabinol (CBN) standard cannabinoids were compared with Raman spectra of five different types of marijuana: four Sativa varieties (Amnesia Haze, Amnesia Hy-Pro, Original Amnesia, and Y Griega) and one Indica variety (Black Domina). The results verified the presence of several common spectral bands that are useful for marijuana characterization. Results were corroborated by the quantum chemical simulated Raman spectra of their acid-form (tetrahydrocannabinol acid (THCA), cannabidiol acid (CBDA)) and decarboxylated cannabinoids (THC, CBD, and CBN). A chemometrics-assisted method based on Raman microscopy and OPLS-DA offered good classification among the different marijuana varieties allowing identification of the most significant spectral bands.


Neuropeptide Y gene polymorphisms confer risk of early-onset atherosclerosis.
Neuropeptide Y (NPY) is a strong candidate gene for coronary artery disease (CAD). We have previously identified genetic linkage to familial CAD in the genomic region of NPY. We performed follow-up genetic, biostatistical, and functional analysis of NPY in early-onset CAD. In familial CAD (GENECARD, N = 420 families), we found increased microsatellite linkage to chromosome 7p14 (OSA LOD = 4.2, p = 0.004) in 97 earliest age-of-onset families. Tagged NPY SNPs demonstrated linkage to CAD of a 6-SNP block (LOD = 1.58-2.72), family-based association of this block with CAD (p = 0.02), and stronger linkage to CAD in the earliest age-of-onset families. Association of this 6-SNP block with CAD was validated in: (a) 556 non-familial early-onset CAD cases and 256 controls (OR 1.46-1.65, p = 0.01-0.05), showing stronger association in youngest cases (OR 1.84-2.20, p = 0.0004-0.09); and (b) GENECARD probands versus non-familial controls (OR 1.79-2.06, p = 0.003-0.02). A promoter SNP (rs16147) within this 6-SNP block was associated with higher plasma NPY levels (p = 0.04). To assess a causal role of NPY in atherosclerosis, we applied the NPY1-receptor-antagonist BIBP-3226 adventitially to endothelium-denuded carotid arteries of apolipoprotein E-deficient mice; treatment reduced atherosclerotic neointimal area by 50% (p = 0.03). Thus, NPY variants associate with atherosclerosis in two independent datasets (with strong age-of-onset effects) and show allele-specific expression with NPY levels, while NPY receptor antagonism reduces atherosclerosis in mice. We conclude that NPY contributes to atherosclerosis pathogenesis.


Phototherapy with narrowband vs broadband UVB.
Phototherapy with ultraviolet (UV) radiation of wavelengths between 280 and 320 nm (UVB) is a safe and effective treatment for a variety of diseases. In addition to standard broadband UVB (bUVB), narrowband phototherapy with fluorescent bulbs emitting near monochromatic UV around 311 nm (nUVB) has become an important treatment for diseases such as psoriasis, atopic dermatitis and vitiligo. In addition to these indications, the number of diseases for which nUVB phototherapy is reported to be effective is continuously growing. The differential effects of nUVB phototherapy in comparison to other UV wavelengths as well as established and new indications for this treatment modality are reviewed.


Towards Imaging Pt Chemoresistance Using Gd(III)-Pt(II) Theranostic MR Contrast Agents.
Cisplatin and related Pt(II) chemotherapeutics are indispensable tools for the treatment of various solid tumors. Despite their widespread clinical use in approximately 50 % of chemotherapy regimens, they are hindered by issues with off-target toxicity and chemoresistance, both innate and acquired. To date, there is no effective way to predict the outcome of Pt(II) chemotherapy because the genes associated with resistance are not completely known or understood. Instead, patients undergo weeks to months of potentially harmful therapy before knowing if it is effective. Here we report two Gd(III)-Pt(II) theranostic MR contrast agents that contain cisplatin and carboplatin-based moieties respectively. We used these agents to demonstrate that accumulation differences in Pt(II) sensitive and resistant cells, a dominant factor in chemoresistance, can be imaged by MR. Both theranostic agents bind to DNA, are cytotoxic, and enhance the intracellular T1 -weighted MR contrast of multiple cell lines. Most importantly, the cisplatin-based agent accumulates less in Pt(II) resistant cells in vitro and in vivo, resulting in decreased MR contrast enhancement compared to the parent Pt(II) sensitive cell line. This straightforward method to image a key factor of Pt(II) resistance using MRI is an important first step towards the ultimate goals of predicting response to Pt(II) chemotherapy and monitoring for the onset of chemoresistance - a critical unmet need in medicine that could significantly improve patient outcomes.


Firearm Violence, Access to Care, and Gentrification: A Moving Target for American Trauma Systems.
We aimed to determine whether gentrification predicts the movement of shooting victims over time and if this process has decreased access to care. Trauma centers remain fixed in space, but the populations they serve do not. Nationally, gentrification has displaced disadvantaged communities most at risk for violent injury, potentially decreasing access to care. This process has not been studied, but an increase of only 1 mile from a trauma center increases shooting mortality up to 22%. We performed a cross-sectional study utilizing Philadelphia Police Department (PPD) and Pennsylvania trauma systems outcome (PTOS) data 2006-2018. Shootings were mapped and grouped into census tracts. They were then cross-mapped with gentrification data and hospital location. PPD and PTOS shooting data were compared to ensure patients requiring trauma care were captured. Census tracts with ≥500 residents with income and median home values in the bottom 40th percentile of the metropolitan area were eligible to gentrify. Tracts were gentrified if residents ≥25 with a bachelor's degree increased and home price increased to the top third in the metropolitan area. Change in distribution of shootings and its relation to gentrification was our primary outcome while proximity of shootings to a trauma center was our secondary outcome. Thirty-two percent (123/379) of eligible tracts gentrified and 31,165 shootings were captured in the PPD database. 9090 (29.2%) patients meeting trauma criteria were captured in PTOS with an increasing proportion over time. The proportion of shootings within gentrifying tracts significantly dropped 2006-2018 (40%-35%, P < 0.001) and increased in non-gentrifying tracts (52%-57%, P < 0.001). In evaluation of shooting densities, a predictable redistribution occurred 2006-2018 with incident density decreasing in gentrified areas and increasing in non-gentrified areas. Shootings within 1 mile of a trauma center increased overall, but proportional access decreased in gentrified areas. Shootings in Philadelphia predictably moved out of gentrified areas and concentrated in non-gentrified ones. In this case study of a national crisis, the pattern of change paradoxically resulted in an increased clustering of shootings around trauma centers in non-gentrified areas. Repetition of this work in other cities can guide future resource allocation and be used to improve access to trauma care.


Diffusion in networks and the virtue of burstiness.
Whether an idea, information, or infection diffuses throughout a society depends not only on the structure of the network of interactions, but also on the timing of those interactions. People are not always available to interact with others, and people differ in the timing of when they are active. Some people are active for long periods and then inactive for long periods, while others switch more frequently from being active to inactive and back. We show that maximizing diffusion in classic contagion processes requires heterogeneous activity patterns across agents. In particular, maximizing diffusion comes from mixing two extreme types of people: those who are stationary for long periods of time, changing from active to inactive or back only infrequently, and others who alternate frequently between being active and inactive.


A national and state profile of leading health problems and health care quality for US children: key insurance disparities and across-state variations.
Parent/consumer-reported data is valuable and necessary for population-based assessment of many key child health and health care quality measures relevant to both the Children's Health Insurance Program Reauthorization Act (CHIPRA) of 2009 and the Patient Protection and Affordable Care Act of 2010 (ACA). The aim of this study was to evaluate national and state prevalence of health problems and special health care needs in US children; to estimate health care quality related to adequacy and consistency of insurance coverage, access to specialist, mental health and preventive medical and dental care, developmental screening, and whether children meet criteria for having a medical home, including care coordination and family centeredness; and to assess differences in health and health care quality for children by insurance type, special health care needs status, race/ethnicity, and/or state of residence. National and state level estimates were derived from the 2007 National Survey of Children's Health (N = 91,642; children aged 0-17 years). Variations between children with public versus private sector health insurance, special health care needs, specific conditions, race/ethnicity, and across states were evaluated using multivariate logistic regression and/or standardized statistical tests. An estimated 43% of US children (32 million) currently have at least 1 of 20 chronic health conditions assessed, increasing to 54.1% when overweight, obesity, or being at risk for developmental delays are included; 19.2% (14.2 million) have conditions resulting in a special health care need, a 1.6 point increase since 2003. Compared with privately insured children, the prevalence, complexity, and severity of health problems were systematically greater for the 29.1% of all children who are publicly insured children after adjusting for variations in demographic and socioeconomic factors. Forty-five percent of all children in the United States scored positively on a minimal quality composite measure: 1) adequate insurance, 2) preventive care visit, and 3) medical home. A 22.2 point difference existed across states and there were wide variations by health condition (autism, 22.8, to asthma, 39.4). After adjustment for demographic and health status differences, quality of care varied between children with public versus private health insurance on all but the following 3 measures: not receiving needed mental health services, care coordination, and performance on the minimal quality composite. A 4.60 fold (gaps in insurance) to 1.27 fold (preventive dental and medical care visits) difference in quality scores was observed across states. Notable disparities were observed among publicly insured children according to race/ethnicity and across all children by special needs status and household income. Findings emphasize the importance of health care insurance duration and adequacy, health care access, chronic condition management, and other quality of care goals reflected in the 2009 CHIPRA legislation and the ACA. Despite disparities, similarities for public and privately insured children speak to the pervasive nature of availability, coverage, and access issues for mental health services in the United States, as well as the system-wide problem of care coordination and accessing specialist care for all children. Variations across states in key areas amenable to state policy and program management support cross-state learning and improvement efforts.


Evaluation of P-POSSUM Risk Scoring System in Prediction of Morbidity and Mortality after Pancreaticoduodenectomy.
Background: POSSUM and P-POSSUM are risk scores recommended by ERAS Society for the preoperative evaluation of patients undergoing major surgery. Methods: This study includes 113 consecutive pancreaticoduodenectomy performed in a single centre between July 2013-December 2015. Patients data were prospectively collected using Excel 2009 and retrospectively analysed with R v3.2.4 software. Biological status score, surgical severity score and risk scores for complications and death were calculated using: http://www.riskprediction. org.uk/index-pp.php. Results: Morbidity rate was 61,95%: 19,47% general complications, 14,16% wound infections and 28,32% PD specific complications (11,5% POPF; 8,85% DGE and 6,19% PPH). Comparing the observed and estimated morbidity and mortality, we obtained statistical significant results (p=0,05 and p=0,03, respectivelly). When we considered only specific PD complications and subsequent mortality, there was no longer significant difference between observed and estimated values (p=0,8 and p=0,86).The under ROC curve aria was 0,61 for morbidity and 0,64 for specific PD morbidity, respectively 0,61 for mortality and 0,68 for specific PD complications related mortality. P-POSSUM represents a useful tool for appreciating the complication and death risk after PD, but better results could be obtain by considering also specific PD risk factors.


Multifunctional polyelectrolyte multilayers as nanofiltration membranes and as sacrificial layers for easy membrane cleaning.
This manuscript investigates the modification of an ultra-filtration (UF) membrane support with polyelectrolyte multilayers (PEMs) consisting of the weak polyelectrolytes poly(allyl amine) hydrochloride (PAH) and poly(acrylic acid) (PAA). These prepared polyelectrolyte multilayer membranes have a dual function: They act as nanofiltration (NF) membranes and as sacrificial layers to allow easy cleaning of the membranes. In order to optimize the conditions for PEM coating and removal, adsorption and desorption of these layers on a model surface (silica) was first studied via optical reflectometry. Subsequently, a charged UF membrane support was coated with a PEM and after each deposited layer, a clear increase in membrane resistance against pure water permeation and a switch of the zeta potential were observed. Moreover these polyelectrolyte multilayer membranes, exhibited rejection of solutes in a range typical for NF membranes. Monovalent ions (NaCl) were hardly rejected (<24%), while rejections of >60% were observed for a neutral organic molecule sulfamethoxazole (SMX) and for the divalent ion SO3(2-). The rejection mechanism of these membranes seems to be dominated by size-exclusion. To investigate the role of these PEMs as sacrificial layers for the cleaning of fouled membranes, the prepared polyelectrolyte multilayers were fouled with silica nano particles. Subsequent removal of the coating using a rinse and a low pressure backwash with pH 3, 3M NaNO3 allowed for a drop in membrane resistance from 1.7⋅10(14)m(-1) (fouled membrane) to 9.9⋅10(12)m(-1) (clean membrane), which is nearly equal to that of the pristine membrane (9.7⋅10(12)m(-1)). Recoating of the support membrane with the same PEMs resulted in a resistance equal to the resistance of the original polyelectrolyte multilayer membrane. Interestingly, less layers were needed to obtain complete foulant removal from the membrane surface, than was the case for the model surface. The possibility for backwashing allows for an even more successful use of the sacrificial layer approach in membrane technology than on model surfaces. Moreover, these PEMs can be used to provide a dual function, as NF membranes and as a Sacrificial coating to allow easy membrane cleaning.


Warming Up Before a 20-Minute Endurance Effort: Is It Really Worth It?
To analyze the effects of different warm-up protocols on endurance-cycling performance from an integrative perspective (by assessing perceptual, neuromuscular, physiological, and metabolic variables). Following a randomized crossover design, 15 male cyclists (35 [9] y; peak oxygen uptake [VO2peak] 66.4 [6.8] mL·kg-1·min-1) performed a 20-minute cycling time trial (TT) preceded by no warm-up, a standard warm-up (10 min at 60% of VO2peak), or a warm-up that was intended to induce potentiation postactivation (PAP warm-up; 5 min at 60% of VO2peak followed by three 10-s all-out sprints). Study outcomes were jumping ability and heart-rate variability (both assessed at baseline and before the TT), TT performance (mean power output), and perceptual (rating of perceived exertion) and physiological (oxygen uptake, muscle oxygenation, heart-rate variability, blood lactate, and thigh skin temperature) responses during and after the TT. Both standard and PAP warm-up (9.7% [4.7%] and 12.9% [6.5%], respectively, P < .001), but not no warm-up (-0.9% [4.8%], P = .074), increased jumping ability and decreased heart-rate variability (-7.9% [14.2%], P = .027; -20.3% [24.7%], P = .006; and -1.7% [10.5%], P = .366). Participants started the TT (minutes 0-3) at a higher power output and oxygen uptake after PAP warm-up compared with the other 2 protocols (P < .05), but no between-conditions differences were found overall for the remainder of outcomes (P > .05). Compared with no warm-up, warming up enhanced jumping performance and sympathetic modulation before the TT, and the inclusion of brief sprints resulted in a higher initial power output during the TT. However, no warm-up benefits were found for overall TT performance or for perceptual or physiological responses during the TT.


Ion channels involved in stroke.
Ion channels are membrane proteins that flicker open and shut to regulate the flow of ions down their electrochemical gradient across the membrane and consequently regulate cellular excitability. Every living cell expresses ion channels, as they are critical life-sustaining proteins. Ion channels are generally either activated by voltage or by ligand interaction. For each group of ion channels the channels' molecular biology and biophysics will be introduced and the pharmacology of that group of channels will be reviewed. The in vitro and in vivo literature will be reviewed and, for ion channel groups in which clinical trials have been conducted, the efficacy and therapeutic potential of the neuroprotective compounds will be reviewed. A large part of this article will deal with glutamate receptors, focusing specifically on N-methyl-D-aspartate (NMDA) receptors. Although the outcome of clinical trials for NMDA receptor antagonists as therapeutics for acute stroke is disappointing, the culmination of these failed trials was preceded by a decade of efforts to develop these agents. Sodium and calcium channel antagonists will be reviewed and the newly emerging efforts to develop therapeutics targeting potassium channels will be discussed. The future development of stroke therapeutics targeting ion channels will be discussed in the context of the failures of the last decade in hopes that this decade will yield successful stroke therapeutics.


Biochemical markers as additional measurements in dietary validity studies: application of the method of triads with examples from the European Prospective Investigation into Cancer and Nutrition.
The validity coefficient of dietary questionnaire measurements can be estimated from a triangular comparison between questionnaire, reference, and biochemical marker measurements with the method of triads. The method assumes that the measurements are linearly related to true intake and have independent random errors. We applied the method of triads to examples from the European Prospective Investigation into Cancer and Nutrition. In some examples, Heywood cases occurred, ie, the estimated validity coefficients were > 1 or the validity coefficients were not estimable. Such results are caused by random sampling fluctuations or violation of the model assumptions. One possible violation is a positive correlation between the random errors of questionnaire and reference measurements. We used a bootstrap method to estimate CIs for the validity coefficients. Validity studies with several hundred subjects, more accurate biochemical indicators of dietary intake, or both, are needed to estimate validity coefficients precisely and avoid complications with the bootstrap method.


Predictors for successful bacteriological culture from milk samples.
A total of 757 milk samples were taken from 57 farms throughout Wales as part of a mastitis investigation. Problem cows were selected using the most recent milk recording or, if these data were unavailable, the whole herd was assessed using the California mastitis test (CMT) and scored on a scale of 0 to 3. The affected quarter was identified using CMT. The results of the bacteriology were grouped into negative and positive culture. All contaminated samples were excluded. The CMT recording at the time of sampling, the infection status of the cow (new, first, chronic or repeat) as defined by national milk records and the number of quarters infected at the time of sampling were identified for negative and positive samples. Selecting quarters with a higher CMT score increased the likelihood of positive culture. Culturing from a sample with a CMT score of 3 was over three times more likely to yield a positive culture than a score of 1 (odds ratio [OR] 3.74, 95 per cent confidence interval [CI] 1.41 to 9.97) and 1.7 times more likely to yield a positive culture than a score of 2 (OR 1.70, 95 per cent CI 1.16 to 2.50). Culturing from a score of 2 was not statistically different from a score of 1 in terms of the likelihood that a positive culture would be identified (OR 2.20, 95 per cent CI 0.83 to 5.93). There was no statistically significant difference in the proportion of negative samples when comparing chronic, repeat, new and first infections or number of quarters infected.


Comprehensive landscape of the renin-angiotensin system in Pan-cancer: a potential downstream mediated mechanism of SARS-CoV-2.
Background: SARS-CoV-2, the cause of the worldwide COVID-19 pandemic, utilizes the mechanism of binding to ACE2 (a crucial component of the renin-angiotensin system [RAS]), subsequently mediating a secondary imbalance of the RAS family and leading to severe injury to the host. However, very few studies have been conducted to reveal the mechanism behind the effect of SARS-CoV-2 on tumors. Methods: Demographic data extracted from 33 cancer types and over 10,000 samples were employed to determine the comprehensive landscape of the RAS. Expression distribution, pretranscriptional and posttranscriptional regulation and posttranslational modifications (PTMs) as well as genomic alterations, DNA methylation and m6A modification were analyzed in both tissue and cell lines. The clinical phenotype, prognostic value and significance of the RAS during immune infiltration were identified. Results: Low expression of AGTR1 was common in tumors compared to normal tissues, while very low expression of AGTR2 and MAS1 was detected in both tissues and cell lines. Differential expression patterns of ACE in ovarian serous cystadenocarcinoma (OV) and kidney renal clear cell carcinoma (KIRC) were correlated with ubiquitin modification involving E3 ligases. Genomic alterations of the RAS family were infrequent across TCGA pan-cancer program, and ACE had the highest alteration frequency compared with other members. Low expression of AGTR1 may result from hypermethylation in the promoter. Downregulation of RAS family was linked to higher clinical stage and worse survival (as measured by disease-specific survival [DSS], overall survival [OS] or progression-free interval [PFI]), especially for ACE2 and AGTR1 in KIRC. ACE-AGTR1, a classical axis of the RAS family related to immune infiltration, was positively correlated with M2-type macrophages, cancer-associated fibroblasts (CAFs) and immune checkpoint genes in most cancers. Conclusion: ACE, ACE2, AGT and AGTR1 were differentially expressed in 33 types of cancers. PTM of RAS family was found to rely on ubiquitination. ACE2 and AGTR1 might serve as independent prognostic factors for LGG and KIRC. SARS-CoV-2 might modify the tumor microenvironment by regulating the RAS family, thus affecting the biological processes of cancer.


Phenotypic and genotypic diversity of fluorescent pseudomonads isolated from field-grown sugar beet.
A sample of 30 fluorescent pseudomonads isolated from the phyllosphere of sugar beet throughout a single growing season and shown to be closely related on the basis of fatty acid methyl ester (FAME) analysis was subjected to detailed phenotypic and genotypic characterization. Phenotypic traits were assessed on the basis of biochemical properties, assimilation of sole carbon sources, FAME analysis, organic pyrolysate content (MS-pyrolysis), and total cellular protein profiles. With the exception of total cellular protein profiles, numerical analysis of the data revealed two main clusters, each of which was divided into several subclusters. Numerical analysis of total cellular protein data failed to differentiate isolates into two main clusters, but nevertheless grouped isolates into six subclusters. On the basis of biochemical and carbon source assimilation profiles, 19 isolates were identified as Pseudomonas fluorescens biovar V, eight isolates as P. fluorescens biovar III and three isolates as P. syringae pathovar syringae. In general, all methods of phenotypic analysis grouped isolates according to time of sampling and leaf type. Genome analysis was undertaken by pulsed-field gel electrophoresis (PFGE) of PacI, SpeI, SwaI and XbaI macrorestriction fragments and revealed the presence of eight distinct genomic (clonal) groups. These groups correlated closely with the clusters generated by numerical analysis of phenotypic data, but there was no correlation between macrorestriction fragment profile and isolate identification; in fact the variation in macrorestriction fragment patterns within P. fluorescens biovars was as great as the variation detected between biovars, and between P. fluorescens and P. syringae. Statistical evaluation of macrorestriction fragment patterns revealed two examples of recent strain divergence: one was due to the presence of a 400 kbp plasmid within one isolate of a collection of nine otherwise genomically identical isolates, and the other was observed between two phenotypically similar isolates sampled 220 d apart. Genetic variation was expressed in terms of nucleotide diversity (pi) and pairwise comparisons yielded values ranging from 0.0029 to 0.1517. The mean intrapopulation genetic variation was high (0.0993), but limited genetic variation was detected among isolates sampled on each occasion. Taken together this suggests a population comprised of a variety of apparently distantly related clones (genomic groups), each adapted to local conditions. Genome sizes were estimated from the sum of SpeI restriction fragments and ranged from 4.2 to 5.5 Mbp. Examination of the distribution of XbaI, SpeI, SwaI and PacI restriction endonuclease sites showed that the distribution of SpeI sites differed significantly from the expected (random) distribution.


Negative clinical trials in cystic fibrosis research.
The statistical power of 61 negative clinical trials of therapeutic regimens in patients with cystic fibrosis published from 1977 through 1988 was reviewed and the ability of the investigations to detect small, medium, and large standardized differences was calculated. Small, medium, and large standardized differences were defined as ratios of 0.2, 0.5, and 0.8, respectively, of the observed difference compared with the standard deviation. The average numbers (+/- SD) of patients in the treatment and control groups were 14.3 +/- 6.9 and 14.5 +/- 7.9, respectively. None of the studies had 80% power to detect a small or medium standardized difference and only 4 of the reports had 80% statistical power to detect a large standardized difference. The variability of cystic fibrosis causes a decrease in the standardized difference, making it more difficult to demonstrate statistical significance. Statistical power of negative clinical trials reported in the literature deserves more attention from investigators as well as physicians who treat patients with cystic fibrosis.


Tetracyclines of various hydrophobicities as a probe for permeability of Escherichia coli outer membranes.
The outer membrane of gram-negative cells excludes hydrophobic molecules and is responsible for the resistance of these cells to a number of dyes, detergents, and antibiotics. We describe a test for hydrophobic permeability in which a series of tetracyclines with various hydrophobicities are used. Normal Escherichia coli cells became more resistant as hydrophobicity was increased in this series, but mutants altered in outer membrane permeability remained susceptible. A mutant lacking all polysaccharide except 2-keto-3- deoxyoctonic acid in its lipopolysaccharide is virtually as susceptible to the hydrophobic drug 13- phenylmercapto -alpha-6- deoxytetracycline as to oxytetracycline (MIC 100 times lower than that of the wild type), and a mutant with another, as yet undefined outer membrane defect, acrA , also shows increased, although somewhat lesser, susceptibility (MIC 20 times lower than that of the wild type). Increased susceptibility to this tetracycline derivative is associated with greater fluorescence of the derivative when added to the cells, which we interpret as increased interaction of the derivative with hydrophobic domains, such as membranes, in the mutants. This series of tetracyclines may provide an assay for measuring the permeability of gram-negative organisms and their mutants to hydrophobic molecules.


[Ganglioside composition of normal and leukemic bovine lymphocytes].
The ganglioside composition of bovine peripheral lymphocytes was shown to change sharply under lymphoid leukemia. In normal lymph, lymph nodes, spleen and blood lymphocytes the major ganglioside is N-glycolylhematoside, whereas in calf thymus lymphocytes appreciable amounts of more polar components (GM1- and GD1a-like gangliosides) were found. In leukemic lymphocytes isolated from the same tissues the hematoside content is decreased, while the amount of more polar gangliosides is increased. Possible causes of the altered ganglioside pattern in leukemic lymphocytes are discussed.


Efficacy of a school-based education intervention on the consumption of fruits, vegetables and carbonated soft drinks among adolescents.
To evaluate the efficacy of a school-based education intervention on the consumption of fruit, vegetables and carbonated soft drinks among adolescents. Cluster-randomised controlled trial. Eight secondary schools from Dhaka, Bangladesh, participated in this trial and were randomly allocated to intervention (n 160) and control groups (n 160). A total of 320 students from 8th to 9th grades participated and completed the self-reported questionnaires at baseline, and at 8 and 12 weeks. The intervention included weekly classroom-based nutrition education sessions for students and healthy eating materials for students and parents. Repeated measures ANCOVA was used to assess the effects of the intervention. Daily fresh fruit intake was more frequent in the intervention (26 %) compared to the control group (3 %) at 12 weeks (p = 0·006). Participants from the intervention group also reported a significantly (P < 0·001) higher (49 %) proportion of fresh vegetable intake compared to the control group (2 %) at 12 weeks. Frequency of daily carbonated soft drinks intake decreased (25 %) in the intervention group at 12 weeks compared to baseline, while it remained unchanged in the control group; the interaction effect was observed significant (P = 0·002). Our school-based education intervention increased the daily frequency of fresh vegetables and fruit intake and decreased carbonated soft drink consumption among adolescents in the intervention group. There is a need for scaling up the intervention to engage students and empower them to develop healthy dietary habits.


Managing the harmful effects of unsupportive organizations during pregnancy.
Unfortunately, not all organizations are supportive of employees' family lives. Family unsupportive workplaces can be stressful for all employees and particularly for pregnant women, who carry a physical reminder of their family life. In the present study, we draw on conservation of resources (COR) theory (Hobfoll, 1989, 2001) to investigate how women manage family unsupportive organizational perceptions during pregnancy via social identity-based impression management behaviors as well as how these strategies relate to changes in stress and changes in conflict between work and family. Specifically, we find that image maintenance strategies-impression management strategies aimed at maintaining one's prepregnancy image-are associated with decreases in work stress and work-family conflict over the course of pregnancy, while decategorization-impression management strategies aimed at avoiding negative outcomes by hiding the pregnancy or dodging the issue-are related to increases in work-family conflict. These results suggest strategies for both organizations and pregnant workers to decrease stress during a time when health is vital for both mother and baby. (PsycINFO Database Record


Tumour-associated eosinophilia in the bladder.
Tumour eosinophilia is an uncommon but striking phenomenon which has been found in many tumours, mostly of large cell type or squamous differentiation. The incidence, appearance and importance of tumour eosinophilia in the bladder are described. Eosinophilia is commoner in deeply invasive tumours and in tumours showing squamous metaplasia. Transitional cell carcinomas with eosinophilia have a better prognosis than those without, but this improvement is not seen in squamous cell carcinomas of the bladder. When eosinophilia is found on superficial biopsies of a bladder tumour, the possibility of muscle invasion should be considered.


Caffeine consumption and sleep in a submarine environment: An observational study.
Submariners face many environmental and operational challenges to maintaining good sleep, including suboptimal lighting, shift work, and frequent interruptions. Anecdotally, many Sailors consume caffeine to alleviate the effects of poor sleep on alertness, mood, and performance; however, caffeine itself may also degrade sleep quantity and/or quality. This study provides the first exploration of the potential relationship between caffeine use and sleep onboard submarines. Objective measures (wrist actigraphy, available from 45 participants), self-report sleep metrics, and self-reported caffeine consumption were collected from 58 US Navy Sailors before and during a routine submarine underway at sea lasting 30 days. Contrary to expectations, less caffeine was reportedly consumed at sea (232.8 ± 241.1 mg) than on land prior to the underway (M = 284.4 ± 251.7 mg; X2 (1) = 7.43, p = 0.006), positive rather than negative relationships were observed between caffeine consumption and sleep efficiency (F = 6.11, p = 0.02), and negative relationships were observed between caffeine consumption and wake after sleep onset (F = 9.36, p = 0.004) and sleep fragmentation (F = 24.73, p < 0.0001). However, in contrast, higher caffeine consumption was also negatively related to self-reported sleep duration while at sea (F = 4.73, p = 0.03). This observational study is the first to measure relationships between caffeine consumption and sleep quantity and/or quality in a submarine environment. We propose that the unique submarine environment and the unique caffeine consumption patterns of submariners should be considered in the development of potential countermeasures for sleepiness.


Augmentation strategy with olanzapine in resistant obsessive compulsive disorder: an Italian long-term open-label study.
The present study reports the results of an open-label trial on the use of the combination of olanzapine (an atypical antipsychotic) serotonin reuptake inhibitors (SRIs) in 26 resistant outpatients affected by resistant obsessive-compulsive disorder (OCD). All patients had been suffering from OCD, according to DSM IV criteria, for at least 2 years and had different comorbid disorders; they had been treated with an SRI at adequate dosages for at least 6 months, or had tried different augmentation strategies with no or poor response. As a result, olanzapine was added and continued for 1 year. After 12 weeks of this regimen, most of the patients (17) had shown a reduction in OC symptoms, as assessed by a decrease in the Yale-Brown Obsessive Compulsive Scale total score, which continued throughout subsequent months. Only mild side-effects were recorded and no patient halted the treatment. The addition of olanzapine would appear to be a useful short- and long-term strategy for augmenting SRI effectiveness in resistant OCD patients, especially in those presenting comorbidity with bipolar disorders.


Using the Gensini score to estimate severity of STEMI, NSTEMI, unstable angina, and anginal syndrome.
Gensini score (GS) provides valuable information on severity and prognosis of coronary artery disease (CAD).To evaluate the relationship between the severity of CAD determined by the GS and relation to ST-elevation myocardial infarction, non-ST segment elevation myocardial infarction (NSTEMI), unstable angina pectoris, chest pain (suspected angina syndrome on admission) and risk-factors for CAD and predictors of severity.Observational cross-sectional study.Consecutive patients who underwent clinically-indicated coronary angiography for ST-elevation myocardial infarction, NSTEMI, unstable angina pectoris or chest pain were enrolled.Among 600 patients, 417 (average age 67.8 ± 12.2 years) had CAD-related symptoms. Mean GS was 66.7 ± 63.8. Patients presenting with NSTEMI had the highest GS (81.3 ± 42.3; P < .001) Regression analysis of risk-factors showed the best association of GS with multivessel disease and coronary artery bypass graft. Regression analysis of medications showed that clopidogrel, had the best association with low GS.GS correlated with the severity of CAD, multivessel disease, coronary artery bypass graft, and troponin. GS was related to the cardiovascular risk-factors of diabetes, hypertension, and high-density cholesterol.


Biodiversity showed positive effects on resistance but mixed effects on resilience to climatic extremes in a long-term grassland experiment.
Understanding the role of biodiversity in maintaining ecosystem functioning and stability under increasing frequency and magnitude of climatic extremes has fascinated ecologists for decades. Although growing evidence suggests that biodiversity affects ecosystem productivity and buffers ecosystem against climatic extremes, it remains unclear whether the stability of an ecosystem is caused by its resistance against disturbances or resilience towards perturbations or both. In attempting to explore how species richness affects resistance and resilience of above-ground net primary productivity (ANPP) against climatic extremes, we analyzed the grassland ANPP of the long-running (1997-2020) Bayreuth Biodiversity experiment in Germany. We used the Standardized Precipitation Evapotranspiration Index to identify climatic conditions based on 5- and 7-class classifications of climatic conditions. Mixed-effects models and post-hoc test show that ANPP varied significantly among different intensities (e.g. moderate or extreme) and directions (e.g. dry or wet) of climatic conditions, with the highest ANPP in extreme wet and the lowest in extreme dry conditions. Resistance and resilience of ANPP to climatic extremes in different intensities were examined by linear-mixed effects models and we found that species richness increased ecosystem resistance against all dry and wet climatic extremes, but decreased ecosystem resilience towards all dry climatic extremes. Species richness had no effects on ecosystem resilience towards wet climatic extremes. When the five level of species richness treatment (i.e., 1, 2, 4, 8, and 16 species) were considered, the relationships between species richness and resistance and resilience of ANPP under extreme wet and dry conditions remained similar. Our study emphasizes that plant communities with greater species richness need to be maintained to stabilize ecosystem productivity and increase resistance against different climatic extremes.


Greater tuberosity medial malposition: does it affect shoulder abductor moment?
The detrimental effect of greater tuberosity malposition on functional scores is well known. Superior or posterior malpositions exceeding five mm lead to excessive loading on the deltoid strength. However, the significance of situations where greater tuberosity becomes medialized due to the compressive effect of the locking plate fixation, especially in fractures with metaphyseal dead space, has not been emphasized. It is hypothesized that this condition may cause shortening of the rotator cuff moment arm and consequently impact functional scores. Between 2012 and 2018, 52 patients, aged 65,28 (ranging 40-85) proximal humerus fractures treated with locking plate fixation were included in the study. Cephalodiaphyseal angle, greater tuberosity displacement , patients reported outcome and Constant-Murley scores were evaluated. The mean Constant Murley score was determined to be 78.76 (ranging from 38 to 100). According to the patients reported outcome 39 excellent , five good , two fair, six poor results were observed. Avascular necrosis with screw migration was detected in five cases, while one patient experienced implant insufficiency along with varus deformity. Greater tuberosity was found to be positioned between 6 mm posterior-superior and -13 mm medial. Significant medial malposition was observed in three patients, with -9, -12, and -13 mm of medialization, respectively. Cephalodiaphysial angle was determined as 139.30 degrees (ranging from 120 to 150 degrees) and showed weak correlation with the functional score. Greater tuberosity medialization also showed weak correlation with the Constant-Murley score. The values exhibiting deviation were associated with low patient-reported outcome results and functional scores. In the examination of greater tuberosity displacement values, it was observed that Neer type 3 and 4 fractures differed significantly from Neer type 2 fractures regarding to Kruskal-Wallis test. Medial impaction of greater tuberosity may be the reason of decreased functional scores, similar to superior or posterior malposition. The medialization of greater tuberosity should be considered as a potential factor leading to the shortening of the rotator cuff's abductor moment.


Cryogen spray cooling during laser tissue welding.
Cryogen cooling during laser tissue welding was explored as a means of reducing lateral thermal damage near the tissue surface and shortening operative time. Two centimetre long full-thickness incisions were made on the epilated backs of guinea pigs, in vivo. India ink was applied to the incision edges then clamps were used to appose the edges. A 4 mm diameter beam of 16 W, continuous-wave, 1.06 microm, Nd:YAG laser radiation was scanned over the incisions, producing approximately 100 ms pulses. There was a delay of 2 s between scans. The total irradiation time was varied from 1-2 min. Cryogen was delivered to the weld site through a solenoid valve in spurt durations of 20, 60 and 100 ms. The time between spurts was either 2 or 4 s, corresponding to one spurt every one or two laser scans. Histology and tensile strength measurements were used to evaluate laser welds. Total irradiation times were reduced from 10 min without surface cooling to under 1 min with surface cooling. The thermal denaturation profile showed less denaturation in the papillary dermis than in the mid-dermis. Welds created using optimized irradiation and cooling parameters had significantly higher tensile strengths (1.7 +/- 0.4 kg cm(-2)) than measured in the control studies without cryogen cooling (1.0 +/- 0.2 kg cm(-2)) (p < 0.05). Cryogen cooling of the tissue surface during laser welding results in increased weld strengths while reducing thermal damage and operative times. Long-term studies will be necessary to determine weld strengths and the amount of scarring during wound healing.


[Tandem mass spectrometry as screening for inborn errors of metabolism].
The use of tandem mass spectrometry for the diagnosis of inborn errors of metabolism has the potential to expand the newborn screening panel to include a vast number of diseases. This technology allows the detection, in the same spot of dried blood on filter paper and during one single analytical run, of different metabolic diseases. Tandem mass spectrometry is rapidly replacing the classical screening techniques approach of one-metabolite detected per analysis per disease by its ability of simultaneous quantification of several metabolites as markers of many diseases, such as acylcarnitines and amino acids. It is clear that a single metabolite can be a biomarker for several diseases, so the multiplex approach of using tandem mass spectrometry enhances, on average, the sensitivity and specificity of the screening. However, there are differences for particular metabolites and the diseases they detect within the same method. Disorders such as the tyrosinemias and among the organic acidemias, the methylmalonic acidemias, have a substantially higher false-positive rate than other more common metabolic diseases such as medium-chain acyl-CoA dehydrogenase deficiency and phenylketonuria. Before introducing this technology into routine newborn screening programs it is necessary to consider the frequency of each disease, as well as the response to early treatment or variables related to the collection of the sample.


Targeted disruption of the type 2 selenodeiodinase gene (DIO2) results in a phenotype of pituitary resistance to T4.
The type 2 deiodinase (D2), a selenoenzyme that catalyzes the conversion of T4 to T3 via 5'-deiodination, is expressed in the pituitary, brain, brown adipose tissue (BAT), and the reproductive tract. To examine the physiological role of this enzyme, a mouse strain lacking D2 activity was developed using homologous recombination. The targeting vector contained the Neo gene in place of a 2.6-kb segment of the Dio2 gene. This segment comprises 72% of the coding region and includes the TGA codon that codes for the selenocysteine located at the active site of the enzyme. Mice homologous for the targeted deletion [D2 knockout (D2KO)] had no gross phenotypic abnormalities, and development and reproductive function appeared normal, except for mild growth retardation (9%) in males. No D2 activity was observed in any tissue in D2KO mice under basal conditions, or under those that normally induce this enzyme such as cold-exposure (BAT) or hypothyroidism (brain, BAT, and pituitary gland). Furthermore, no D2 activity was present in cultured astrocytes, nor could it be induced by treatment of the cells with forskolin. Although D2 mRNA transcripts were detected in BAT RNA obtained from cold-exposed wild-type (WT) mice, none was detected in BAT RNA from comparably-treated D2KO mice. Levels of D1 in the liver, thyroid, and pituitary were the same in WT and D2KO animals, whereas D3 activity in D2KO cerebrum was twice that in WT cerebrum. Serum T3 levels were comparable in adult WT and D2KO mice. However, serum T4 and TSH levels were both elevated significantly (40% and 100%, respectively) in the D2KO mice, suggesting that the pituitary gland of the D2KO mouse is resistant to the feedback effect of plasma T4. This view was substantiated by the finding that serum TSH levels in hypothyroid WT mice were suppressed by administration of either T4 or T3, but only T3 was effective in the D2KO mouse. The data also suggest that the clearance of T4 from plasma was reduced in the D2KO mouse. In summary, targeted inactivation of the selenodeiodinase Dio2 gene results in the complete loss of D2 activity in all tissues examined. The increased serum levels of T4 and TSH observed in D2KO animals demonstrate that the D2 is of critical importance in the feedback regulation of TSH secretion.


[Carcinoma of the colon with bladder invasion; what is the role of preoperative chemotherapy?]
Preoperative chemotherapy followed by surgery was applied in three patients, aged 68 years (male), 48 years (female), and 80 years (male) with locally advanced cancer of the colon with bladder invasion. Achieving a resection with free margins (R0) is essential in colon-cancer surgery, but the role of preoperative chemotherapy in colon cancer remains unknown. When a tumour is presumed to be unresectable, guidelines recommend discussing the case and possibly referring the patient to an oncological expertise centre, where each patient will be individually assessed for the most suitable preoperative treatment and surgery during a multidisciplinary tumour board meeting. All three patients showed that preoperative chemotherapy led to down-staging and reduction of the tumour size, although removal of the bladder was still necessary in one patient. All patients underwent a complete resection, which resulted in long-term disease-free and overall survival.


Training parents to help their children read: a randomized control trial.
Low levels of literacy and high levels of behaviour problems in middle childhood often co-occur. These persistent difficulties pose a risk to academic and social development, leading to social exclusion in adulthood. Although parent-training programmes have been shown to be effective in enabling parents to support their children's development, very few parent interventions offer a combination of behavioural and literacy training. This paper (1) reports on a prevention programme which aimed to tackle behaviour and literacy problems in children at the beginning of school, and (2) presents the effects of the intervention on children's literacy. One hundred and four 5- and 6-year-old children selected from eight schools in an inner city disadvantaged community in London participated in the intervention. This is a randomized control trial with pre- and post-measurements designed to evaluate the effectiveness of an intervention. The behavioural intervention consisted of the 'Incredible Years' group parenting programme combined with a new programme designed to train parents to support their children's reading at home. Analyses demonstrated a significant effect of the intervention on children's word reading and writing skills, as well as parents' use of reading strategies with their children. A structured multicomponent preventive package delivered with attention to fidelity can enable parents to support their children's reading at home and increase their literacy skills. Together with the improvement in child behaviour, these changes could improve the life chances of children in disadvantaged communities.


Infection control and HIV-related discrimination and anxiety. Glove use during venipuncture.
Reports into HIV-related discrimination reveal continuing concerns about the behaviour of health care workers, particularly with reference to practices such as excessive or selective infection control. This study examines whether the selective adoption of an infection control procedure (using gloves during venipuncture) is related to discriminatory attitudes, anxiety about HIV/AIDS and the degree of contact with HIV-infected patients. In 1993 and 1994, 451 general practitioners (GPs) were surveyed in six of the 12 New South Wales Health Areas and Regions. The sample included 49 anti-retroviral prescribers. GPs were presented with six patient scenarios and asked with whom they would use gloves during venipuncture. 41.9% of GPs reported that they would selectively use gloves, and generally targeted the homosexual patient only, or combinations of patients that included the homosexual man. GPs revealed poor compliance with universal precautions, as only 37.5% reported that they would use gloves with all of the six patients. Intended glove use was significantly related to HIV-related discrimination (p < 0.0001) and anxiety about HIV/AIDS (p < 0.0001). GPs who selectively chose to use gloves had the highest discrimination and anxiety scores; GPs who chose not to use gloves with any of the patients had the lowest discrimination and anxiety scores, and were more likely to work in HIV medicine. Except for differences in Health Area, this study did not identify any factors that helped to explain which GPs consistently followed universal precautions. This study demonstrates that selective infection control is related to discriminatory attitudes and anxiety about HIV/AIDS. GPs can avoid a discriminatory practice by consistently following universal precautions. More research is needed to identify the factors that promote good infection control practices.


Scintigraphy of sacroiliac pyarthrosis in children.
Eight children with low back, hip, or lower limb pain who were subsequently shown to have pyogenic infections of their sacroiliac joints were examined by a combination of plain roentgenography and radionuclide bone scintigraphy. In all cases, the scintigraphic examination was diagnostic, while the roentgenograms were initially abnormal in only two cases. In the other six cases, one to six weeks passed before changes compatible with sacroiliac pyarthrosis were seen on roentgenographic examination. Radionuclide scintigraphy is recommended as part of the initial workup of children with appropriate symptoms.


Correlates of attachment at school age: maternal reported stress, mother-child interaction, and behavior problems.
The contribution of attachment, maternal reported stress, and mother-child interaction to the prediction of teacher-reported behavior problems was examined for a French-Canadian sample of 121 school-age children. Attachment classifications were assigned on the basis of reunion behavior with mother when the children were between 5 and 7 years of age. Maternal reported stress and mother-child interaction patterns were assessed concurrent to the attachment measure, whereas behavior problems were evaluated both at ages 5 to 7 and 7 to 9 years. Security of attachment significantly predicted the likelihood of school-age behavior problems: Controlling/other children were most at risk for both externalizing and internalizing problems across both age periods. Younger ambivalent children presented clinical cut-off levels of externalizing problems, and older avoidant boys had higher internalizing scores. Patterns of maternal-reported stress and mother-child interaction differed across attachment groups and contributed to prediction of school-age behavior problems, partially mediating the relation between attachment and adaptation. Results support the importance of attachment in explaining school-age adaptation and validity of attachment coding for children of this age.


The transforming growth factor beta type II receptor can replace the activin type II receptor in inducing mesoderm.
The type II receptors for the polypeptide growth factors transforming growth factor beta (TGF-beta) and activin belong to a new family of predicted serine/threonine protein kinases. In Xenopus embryos, the biological effects of activin and TGF-beta 1 are strikingly different; activin induces a full range of mesodermal cell types in the animal cap assay, while TGF-beta 1 has no effects, presumably because of the lack of functional TGF-beta receptors. In order to assess the biological activities of exogenously added TGF-beta 1, RNA encoding the TGF-beta type II receptor was introduced into Xenopus embryos. In animal caps from these embryos, TGF-beta 1 and activin show similar potencies for induction of mesoderm-specific mRNAs, and both elicit the same types of mesodermal tissues. In addition, the response of animal caps to TGF-beta 1, as well as to activin, is blocked by a dominant inhibitory ras mutant, p21(Asn-17)Ha-ras. These results indicate that the activin and TGF-beta type II receptors can couple to similar signalling pathways and that the biological specificities of these growth factors lie in their different ligand-binding domains and in different competences of the responding cells.


Face Validity of Observed Meal Patterns Reported with 7-Day Diet Diaries in a Large Population-Based Cohort Using Diurnal Variation in Concentration Biomarkers of Dietary Intake.
In a cross-sectional analysis of a population-based cohort (United Kingdom, N = 21,318, 1993-1998), we studied how associations between meal patterns and non-fasting triglyceride and glucose concentrations were influenced by the hour of day at which the blood sample was collected to ascertain face validity of reported meal patterns, as well as the influence of reporting bias (assessed using formula of energy expenditure) on this association. Meal size (i.e., reported energy content), mealtime and meal frequency were reported using pre-structured 7-day diet diaries. In ANCOVA, sex-specific means of biomarker concentrations were calculated by hour of blood sample collection for quartiles of reported energy intake at breakfast, lunch and dinner (meal size). Significant interactions were observed between breakfast size, sampling time and triglyceride concentrations and between lunch size, sampling time and triglyceride, as well as glucose concentrations. Those skipping breakfast had the lowest triglyceride concentrations in the morning and those skipping lunch had the lowest triglyceride and glucose concentrations in the afternoon, especially among acceptable energy reporters. Eating and drinking occasion frequency was weakly associated with glucose concentrations in women and positively associated with triglyceride concentrations in both sexes; stronger associations were observed for larger vs. smaller meals and among acceptable energy reporters. Associations between meal patterns and concentration biomarkers can be observed when accounting for diurnal variation and underreporting. These findings support the use of 7-day diet diaries for studying associations between meal patterns and health.


[Isolation, identification and serotyping of yeasts obtained from the vaginal fluid in patients with clinical vaginitis].
A study was carried out to determine the presence of Candida in 105 patients with clinical vaginitis who consulted in the Infectious Disease Unit of the Vargas Hospital after referral from Gynecology Service. Yeasts were detected in 23 cases (24%), and identified as C. albicans (12), C. tropicalis (5), C. guilliermondii (3), C. glabrata (2) and C. parapsilosis (1). The presence of hyphae was observed in 50% of the direct examinations, in which the isolated species was C. albicans. These structures were not observed in infections with other species of Candida. In this study, there was relatively little difference between the percentages of serotypes A and B, 58 % and 42, respectively. This is in contrast with previous studies reported in clinical material from Venezuela and other countries, in which serotype A presented a greater incidence than serotype B. Our observations suggest an increase in serotype B C. albicans in vaginal candidiasis.


Pulmonary function after exposure to the World Trade Center collapse in the New York City Fire Department.
On September 11, 2001, the World Trade Center collapse created an enormous urban disaster site with high levels of airborne pollutants. First responders, rescue and recovery workers, and residents have since reported respiratory symptoms and developed pulmonary function abnormalities. To quantify respiratory health effects of World Trade Center exposure in the New York City Fire Department. Longitudinal study of pulmonary function in 12,079 New York City Fire Department rescue workers employed on or before 09/11/2001. Between 01/01/1997 and 09/11/2002, 31,994 spirometries were obtained and the FEV(1) and FVC were analyzed for differences according to estimated World Trade Center exposure intensity. Adjusted average FEV(1) during the first year after 09/11/2001 was compared with the 5 yr before 09/11/2001. Median time between 09/11/2001 and a worker's first spirometry afterwards was 3 mo; 90% were assessed within 5 mo. World Trade Center-exposed workers experienced a substantial reduction in adjusted average FEV(1) during the year after 09/11/2001 (372 ml; 95% confidence interval, 364-381 ml; p < 0.001) This exposure-related FEV(1) decrement equaled 12 yr of aging-related FEV(1) decline. Moreover, exposure intensity assessed by initial arrival time at the World Trade Center site correlated linearly with FEV(1) reduction in an exposure intensity-response gradient (p = 0.048). Respiratory symptoms also predicted a further FEV(1) decrease (p < 0.001). Similar findings were observed for adjusted average FVC. World Trade Center exposure produced a substantial reduction in pulmonary function in New York City Fire Department rescue workers during the first year after 09/11/2001.


Copy number variation in familial Parkinson disease.
Copy number variants (CNVs) are known to cause Mendelian forms of Parkinson disease (PD), most notably in SNCA and PARK2. PARK2 has a recessive mode of inheritance; however, recent evidence demonstrates that a single CNV in PARK2 (but not a single missense mutation) may increase risk for PD. We recently performed a genome-wide association study for PD that excluded individuals known to have either a LRRK2 mutation or two PARK2 mutations. Data from the Illumina370Duo arrays were re-clustered using only white individuals with high quality intensity data, and CNV calls were made using two algorithms, PennCNV and QuantiSNP. After quality assessment, the final sample included 816 cases and 856 controls. Results varied between the two CNV calling algorithms for many regions, including the PARK2 locus (genome-wide p = 0.04 for PennCNV and p = 0.13 for QuantiSNP). However, there was consistent evidence with both algorithms for two novel genes, USP32 and DOCK5 (empirical, genome-wide p-values<0.001). PARK2 CNVs tended to be larger, and all instances that were molecularly tested were validated. In contrast, the CNVs in both novel loci were smaller and failed to replicate using real-time PCR, MLPA, and gel electrophoresis. The DOCK5 variation is more akin to a VNTR than a typical CNV and the association is likely caused by artifact due to DNA source. DNA for all the cases was derived from whole blood, while the DNA for all controls was derived from lymphoblast cell lines. The USP32 locus contains many SNPs with low minor allele frequency leading to a loss of heterozygosity that may have been spuriously interpreted by the CNV calling algorithms as support for a deletion. Thus, only the CNVs within the PARK2 locus could be molecularly validated and associated with PD susceptibility.


Residues of the beta-agonist clenbuterol in tissues of medicated farm animals.
Reports of the illegal use of clenbuterol as a growth promotant prompted the development of a competitive enzyme immunoassay for this drug. This procedure was utilized to study the elimination of clenbuterol from tissues in sheep medicated with both therapeutic and growth-promoting doses of the drug. The results indicated that prior to removal of medication clenbuterol was widely distributed throughout the animal tissues. However as the withdrawal periods increased fluid targets such as urine and bile became less effective at detecting clenbuterol usage. At both therapeutic and growth-enhancing concentrations of clenbuterol liver samples remained positive up to the maximum withdrawal time given in this experiment (15 days). Concentrations of clenbuterol likely to cause food poisoning (> 100 ng/g) were only detected in liver samples taken prior to the removal of medication. The highest recorded concentration of clenbuterol in muscle was 22.5 ng/g.


The effects of music on time perception and performance of a driving game.
There is an established and growing body of evidence highlighting that music can influence behavior across a range of diverse domains (Miell, MacDonald, & Hargreaves 2005). One area of interest is the monitoring of "internal timing mechanisms", with features such as tempo, liking, perceived affective nature and everyday listening contexts implicated as important (North & Hargreaves, 2008). The current study addresses these issues by comparing the effects of self-selected and experimenter-selected music (fast and slow) on actual and perceived performance of a driving game activity. Seventy participants completed three laps of a driving game in seven sound conditions: (1) silence; (2) car sounds; (3) car sounds with self-selected music, and car sounds with experimenter-selected music; (4) high-arousal (70 bpm); (5) high-arousal (130 bpm); (6) low-arousal (70 bpm); and (7) low-arousal (130 bpm) music. Six performance measures (time, accuracy, speed, and retrospective perception of these), and four experience measures (perceived distraction, liking, appropriateness and enjoyment) were taken. Exposure to self-selected music resulted in overestimation of elapsed time and inaccuracy, while benefiting accuracy and experience. In contrast, exposure to experimenter-selected music resulted in poorest performance and experience. Increasing the tempo of experimenter-selected music resulted in faster performance and increased inaccuracy for high-arousal music, but did not impact experience. It is suggested that personal meaning and subjective associations connected to self-selected music promoted increased engagement with the activity, overriding detrimental effects attributed to unfamiliar, less liked and less appropriate experimenter-selected music.


The stressed bird in the hand: Influence of sampling design on the physiological stress response in a free-living songbird.
Despite the widely used application of standardized capture-handling protocols to collect blood and assess the physiological stress response, the actual sampling design (e.g., timing and the number of blood samples) often differs between studies, and the potential implications for the measured physiological endpoints remain understudied. We, therefore experimentally tested the effects of repeated handling and multiple blood sampling on the stress response in wintering free-living great tits (Parus major). We modified a well-established sampling protocol of avian studies by adding either an additional blood sample or a "sham-manipulation" (i.e., handling associated with the blood sampling procedure without venepuncture), to disentangle the effects of handling stress and blood loss. We combined three different stress metrics along the endocrine-immune interface to investigate the acute short-term stress response: total corticosterone concentrations (Cort), the heterophil/lymphocyte ratio (H:L), and the Leucocyte Coping Capacity (LCC). Our study provided three key results: i) no relationship between Cort levels, LCC and H:L, confirming that these three parameters represent different physiological endpoints within the stress response; ii) contrasting dynamics in response to stress by the measured parameters and iii) no difference in physiological stress levels 30 min after capture due to one additional blood sampling or handling event. By optimising the sampling design, our results provide implications for animal welfare and planning experimental procedures on stress physiology in passerine species.


Comparison of montelukast and cabergoline for prevention of ovarian hyperstimulation syndrome: in an experimental rat model.
Ovarian hyperstimulation syndrome (OHSS) is a serious iatrogenic complication that can occur during assisted reproductive techniques. The aim of this study is to investigate the effects of the leukotriene receptor antagonist (montelukast) treatment in prevention of OHSS and compare to cabergoline treatment. Twenty-four immature female Wistar rats were assigned to four groups. Group 1 was the control group. In the remaining three groups, OHSS was induced through ovarian stimulation with gonadotropins. No treatment was given to Group 2. Group 3 was administered a low-dose 100 mg/kg cabergoline treatment and Group 4 was received 20 mg/kg montelukast. Body weight, ovarian weight, vasculary permability (VP), peritoneal fluid vascular endothelial growth factor (VEGF) values and VEGF immune-expression were compared between the groups. Both cabergoline and montelukast prevented progression of OHSS compared to the OHSS group. Body weight, ovarian weight, VP, peritoneal fluid VEGF values and VEGF expression were significantly lower in both cabergoline- and montelukast-treated rats than in those not treated OHSS group. In conclusion, montelukast is an effective option for prevention of OHSS, as well as cabergoline. Montelukast may be a new treatment option to prevent and control the OHSS.


Lrs14 transcriptional regulators influence biofilm formation and cell motility of Crenarchaea.
Like bacteria, archaea predominately exist as biofilms in nature. However, the environmental cues and the molecular mechanisms driving archaeal biofilm development are not characterized. Here we provide data suggesting that the transcriptional regulators belonging to the Lrs14-like protein family constitute a key regulatory factor during Sulfolobus biofilm development. Among the six lrs14-like genes encoded by Sulfolobus acidocaldarius, the deletion of three led to markedly altered biofilm phenotypes. Although Δsaci1223 and Δsaci1242 deletion mutants were impaired in biofilm formation, the Δsaci0446 deletion strain exhibited a highly increased extracellular polymeric substance (EPS) production, leading to a robust biofilm structure. Moreover, although the expression of the adhesive pili (aap) genes was upregulated, the genes of the motility structure, the archaellum (fla), were downregulated rendering the Δsaci0446 strain non-motile. Gel shift assays confirmed that Saci0446 bound to the promoter regions of fla and aap thus controlling the expression of both cell surface structures. In addition, genetic epistasis analysis using Δsaci0446 as background strain identified a gene cluster involved in the EPS biosynthetic pathway of S. acidocaldarius. These results provide insights into both the molecular mechanisms that govern biofilm formation in Crenarchaea and the functionality of the Lrs14-like proteins, an archaea-specific class of transcriptional regulators.


The Relevance of Sexual Dysfunction Related to Groin Pain After Inguinal Hernia Repair - The SexIHQ Short Form Questionnaire Assessment.
Chronic postoperative pain after inguinal hernia surgery can affect sexual function. A new short form questionnaire for inguinal hernia pain related sexual dysfunction (SexIHQ) was introduced and applied to a register based cohort of total extra-peritoneal hernioplasty (TEP) operated patients. Sexually active men, 30-60 years old, recorded in the Swedish Hernia Register for a primary inguinal hernia TEP operation were included. Two initial questions of the SexIHQ identify patients with pain at sexual activity. Only these patients proceeded to answer the specific questions on pain-induced impairment of sexual activity, pain frequency and intensity, physical functions (erection and ejaculation), and symptoms of depression. SexIHQ, the Short Form-36 (SF-36), the Inguinal Pain Questionnaire (IPQ) were mailed to participants for long term follow up. In 538 included patients, 44 (8.2%) reported pain during sexual activity at mean 33 months after surgery. Sexual dysfunction was seen in 33 of these patients. A postoperative complication was a risk factor for pain during sexual activity; OR 4.89 (95% CI 1.92-12.43; p < 0.001). Quality-of-life was reduced in almost all SF-36 domains in patients with pain during sexual activity. A short form questionnaire, suitable for large cohorts, was developed to assess sexual dysfunction due to groin pain after inguinal hernia repair in male patients. Sexual dysfunction due to groin pain after hernia surgery by TEP is surprisingly common. Patients should preoperatively be informed of the risk of having pain during sexual activity following groin hernia surgery.


Dyadic invariance of the Adult Self-Report and Adult Behavior Checklist: Evidence from young adult romantic couples.
The current paper investigated the invariance of the behavior problem scales of two measures from the Achenbach System of Empirically Based Assessment, the Adult Self Report (ASR) and the Adult Behavior Checklist (ABCL), across members of young adult romantic couples. Data were derived from three studies examining romantic relationships in young adulthood (total N = 672). Using a series of confirmatory factor analysis models, we tested levels of invariance of the behavior problem subscales of the ASR/ABCL across self- and partner-reports. All behavior problem subscales demonstrated invariant factor structures across self- and partner-reports. However, only the attention problems, aggressive behavior, and rule-breaking subscales achieved full metric invariance for both men and women. The intrusiveness (for men) and somatic complaints (for women) subscales also met full metric invariance. The remaining subscales only met partial metric invariance for both men (withdrawn, anxious/depressed, somatic complaints) and women (withdrawn, anxious/depressed, intrusiveness). All subscales only met partial scalar invariance. The current study extends the literature on cross-informant assessments by moving beyond studies of mean differences or correlations between informant reports. Moreover, our findings indicate that understanding agreement between informants should include multiple levels of measurement, such as factor structure, factor loadings, and item means. We recommend careful consideration of these issues when using the ASR/ABCL in a cross-informant framework. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


Chain Assembly and Disassembly Processes Differently Affect the Conformational Space of Ubiquitin Chains.
Ubiquitination is the most versatile posttranslational modification. The information is encoded by linkage type as well as chain length, which are translated by ubiquitin binding domains into specific signaling events. Chain topology determines the conformational space of a ubiquitin chain and adds an additional regulatory layer to this ubiquitin code. In particular, processes that modify chain length will be affected by chain conformations as they require access to the elongation or cleavage sites. We investigated conformational distributions in the context of chain elongation and disassembly using pulsed electron-electron double resonance spectroscopy in combination with molecular modeling. Analysis of the conformational space of diubiquitin revealed conformational selection or remodeling as mechanisms for chain recognition during elongation or hydrolysis, respectively. Chain elongation to tetraubiquitin increases the sampled conformational space, suggesting that a high intrinsic flexibility of K48-linked chains may contribute to efficient proteasomal degradation.


Snowmobile injuries in northern Newfoundland and Labrador: an 18-year review.
The charts of 310 consecutive patients with snowmobile injuries admitted to Charles S. Curtis Memorial Hospital, St. Anthony, Newfoundland, during the years 1969 through 1986 were reviewed in order to determine the causes and possible ways of prevention of these injuries. There were 237 males and 73 females. Most patients were less than 30 years of age (73%). Drivers represented 57% of the injured. Falling off the machine and collisions were responsible for 60% of the injuries; 3.0% were due to mechanical failure of the snowmobile. The lower limbs and head and neck regions were most commonly affected (42.6 and 27.6%, respectively); less than 10% of the patients were wearing helmets at the time of the accident. We conclude that the human factor was responsible for the majority of the injuries. We recommend enforcement of legislation, intensification of public education about the hazards of driving snowmobiles, and modifications in the design of the engine, especially to provide increased protection for the lower limbs.


Early clonality and high-frequency proviral integration into the c-myc locus in AKR leukemias.
Blot hybridization of thymocyte DNA from AKR/J mice was used to detect new proviral junction fragments as markers of clonality at different stages of viral leukemogenesis and to detect DNA rearrangements at the c-myc locus due to proviral insertion. Clonal populations of thymocytes were observed in mink cell focus-forming virus-injected mice as early as 35 days postinjection, at a stage distinguishable from frank leukemia by flow cytometric analysis and transplantation bioassay. Specific proviral integrations in the c-myc locus were detected in 15% of these early clones and in up to 65% of late-developing thymomas and frank leukemias. Thus, in this system c-myc activation appears to be a common mechanism in T-cell leukemogenesis.


Performance assessment of an opto-fluidic phantom mimicking porcine liver parenchyma.
An implantable, optical oxygenation and perfusion sensor to monitor liver transplants during the two-week period following the transplant procedure is currently being developed. In order to minimize the number of animal experiments required for this research, a phantom that mimics the optical, anatomical, and physiologic flow properties of liver parenchyma is being developed as well. In this work, the suitability of this phantom for liver parenchyma perfusion research was evaluated by direct comparison of phantom perfusion data with data collected from in vivo porcine studies, both using the same prototype perfusion sensor. In vitro perfusion and occlusion experiments were performed on a single-layer and on a three-layer phantom perfused with a dye solution possessing the absorption properties of oxygenated hemoglobin. While both phantoms exhibited response patterns similar to the liver parenchyma, the signal measured from the multilayer phantom was three times higher than the single layer phantom and approximately 21 percent more sensitive to in vitro changes in perfusion. Although the multilayer phantom replicated the in vivo flow patterns more closely, the data suggests that both phantoms can be used in vitro to facilitate sensor design.


Electroactive Scaffolds to Improve Neural Stem Cell Therapy for Spinal Cord Injury.
Spinal cord injury (SCI) is a serious condition caused by damage to the spinal cord through trauma or disease, often with permanent debilitating effects. Globally, the prevalence of SCI is estimated between 40 to 80 cases per million people per year. Patients with SCI can experience devastating health and socioeconomic consequences from paralysis, which is a loss of motor, sensory and autonomic nerve function below the level of the injury that often accompanies SCI. SCI carries a high mortality and increased risk of premature death due to secondary complications. The health, social and economic consequences of SCI are significant, and therefore elucidation of the complex molecular processes that occur in SCI and development of novel effective treatments is critical. Despite advances in medicine for the SCI patient such as surgery and anaesthesiology, imaging, rehabilitation and drug discovery, there have been no definitive findings toward complete functional neurologic recovery. However, the advent of neural stem cell therapy and the engineering of functionalized biomaterials to facilitate cell transplantation and promote regeneration of damaged spinal cord tissue presents a potential avenue to advance SCI research. This review will explore this emerging field and identify new lines of research.


The role of rifaximin therapy in patients with irritable bowel syndrome without constipation.
Alterations in gut flora may play an important role in the pathophysiology of bowel symptoms, especially in patients with irritable bowel syndrome (IBS). If so, antibiotics that affect gut flora may offer a novel approach for the management of patients with IBS. Here, we discuss the results of two identically designed, double-blind, placebo-controlled trials (TARGET 1 and TARGET 2) of a poorly absorbed antibiotic, rifaximin, in patients with IBS. In these studies, 1260 patients (females 76.1 and 72.1%, respectively) who had IBS without constipation were randomized to receive either rifaximin 550 mg or placebo, three-times daily for 2 weeks. Subsequently, daily symptoms were assessed and patients were followed up for 10 weeks. The primary outcome measure - adequate relief of global IBS symptoms during the first 4 weeks after treatment - was met in significantly more patients who received rifaximin than placebo (p < 0.001). In addition, more patients in the rifaximin group than in the placebo group (p < 0.001) reported an adequate relief of bloating, and an improvement in abdominal pain and stool consistency - secondary outcome measures. The incidence of adverse events with rifaximin was similar to placebo, and the drug was well tolerated. In summary, a 2-week course of rifaximin provided significant relief of IBS symptoms, as well as bloating and abdominal pain.


Using Maslow's pyramid and the national database of nursing quality indicators(R) to attain a healthier work environment.
The strongest predictor of nurse job dissatisfaction and intent to leave is that of stress in the practice environment. Good communication, control over practice, decision making at the bedside, teamwork, and nurse empowerment have been found to increase nurse satisfaction and decrease turnover. In this article we share our experience of developing a rapid-design process to change the approach to performance improvement so as to increase engagement, empowerment, effectiveness, and the quality of the professional practice environment. Meal and non-meal breaks were identified as the target area for improvement. Qualitative and quantitative data support the success of this project. We begin this article with a review of literature related to work environment and retention and a presentation of the frameworks used to improve the work environment, specifically Maslow's theory of the Hierarchy of Inborn Needs and the National Database of Nursing Quality Indicators Survey. We then describe our performance improvement project and share our conclusion and recommendations.


Attitudes, current behaviours and barriers to public health measures that reduce COVID-19 transmission: A qualitative study to inform public health messaging.
Public health measures to reduce COVID-19 transmission include masking in public places, physical distancing, staying home when ill, avoiding high-risk locations, using a contact tracing app, and being willing to take a COVID-19 vaccine. However, adoption of these measures varies greatly. We aimed to improve health messaging to increase adherence to public health behaviours to reduce COVID-19 transmission by: 1) determining attitudes towards public health measures and current behaviours; 2) identifying barriers to following public health measures; and, 3) identifying public health communication strategies. We recruited participants from a random panel of 3000 phone numbers across Alberta to fill a predetermined quota: age (18-29; 30-59; 60+ years), geographic location (urban; rural), and whether they had school-age children. Two researchers coded and themed all transcripts. We performed content analysis and in-depth thematic analysis. Nine focus groups were conducted with 2-8 participants/group in August-September, 2020. Several themes were identified: 1) importance of public health measures; 2) compliance with public health measures; 3) critiques of public health messaging; and 4) suggestions for improving public health messaging. Physical distancing and masking were seen as more important than using a contact tracing app. There were mixed views around willingness to take COVID-19 vaccine. Current public health messaging was perceived as conflicting. Participants felt that consistent messaging and using social media to reach younger people would be helpful. In conclusion, these findings provide insights that can be used to inform targeted (e.g., by age, current behaviour) public health communications to encourage behaviors that reduce COVID-19 transmission.


Preoptic leptin signaling modulates energy balance independent of body temperature regulation.
The adipokine leptin acts on the brain to regulate energy balance but specific functions in many brain areas remain poorly understood. Among these, the preoptic area (POA) is well known to regulate core body temperature by controlling brown fat thermogenesis, and we have previously shown that glutamatergic, long-form leptin receptor (Lepr)-expressing neurons in the POA are stimulated by warm ambient temperature and suppress energy expenditure and food intake. Here we further investigate the role of POA leptin signaling in body weight regulation and its relationship to body temperature regulation in mice. We show that POA Lepr signaling modulates energy expenditure in response to internal energy state, and thus contributes to body weight homeostasis. However, POA leptin signaling is not involved in ambient temperature-dependent metabolic adaptations. Our study reveals a novel cell population through which leptin regulates body weight.