Behind the Organic Veil: Assessing the Impact of Chemical Deflocculation on Organic Content Reduction and Lacustrine Arcellinida (Testate Amoebae) Analysis.
Arcellinida (testate lobose amoebae) are widely used as bio-indicators of lacustrine environmental change. Too much obscuring organic material in a gridded wet Petri dish preparation makes it difficult to observe all specimens present and slows quantification as the organic material has to be carefully worked through with a dissection probe. Chemical deflocculation using soda ash (Na2CO3·H2O), potassium hydroxide (KOH), or sodium hexametaphosphate ((NaPO3)6) has previously been shown to disaggregate and reduce organic content in lake sediments, but to date, no attempt has been made to comparatively evaluate the efficiency of these deflocculants in disaggregating organic content and their impact on Arcellinida analysis in lacustrine sediments. Here, we assess the effectiveness of soda ash, potassium hydroxide, and sodium hexametaphosphate treatments on removing organic content and the impact of those digestions on Arcellinida preservation in 126 sample aliquots subdivided from three sediment samples (YK-20, YK-25, and YK-57) collected from three lakes near Yellowknife, Northwest Territories, Canada. Following treatment, cluster analysis and Bray-Curtis dissimilarity matrix (BCDM) were utilized to determine whether treatments resulted in dissolution-driven changes in Arcellinida assemblage composition. Observed Arcellinida tests in aliquots increased drastically after treatment of organic-rich samples (47.5-452.7% in organic-rich aliquots and by 14.8% in aliquots with less organic matter). The BCDM results revealed that treatment with 5% KOH resulted in the highest reduction in observed organic content without significantly affecting Arcellinida assemblage structure, while soda ash and sodium hexametaphosphate treatments resulted in marginal organic matter reduction and caused severe damage to the arcellinidan tests.


RCIT: A Robust Catadioptric-based Instrument 3D Tracking Method For Microsurgical Instruments In a Single-Camera System.
The field of robotic microsurgery and micro-manipulation has undergone a profound evolution in recent years, particularly with regard to the accuracy, precision, versatility, and dexterity. These advancements have the potential to revolutionize high-precision biomedical procedures, such as neurosurgery, vitreoretinal surgery, and cell micro-manipulation. However, a critical challenge in developing micron-precision robotic systems is accurately verifying the end-effector motion in 3D. Such verification is complicated due to environmental vibrations, inaccuracy of mechanical assembly, and other physical uncertainties. To overcome these challenges, this paper proposes a novel single-camera framework that utilizes mirrors with known geometric parameters to estimate the 3D position of the microsurgical instrument. Euclidean distance between reconstructed points by the algorithm and the robot movement recorded by the highly accurate encoders is considered an error. Our method exhibits an accurate estimation with the mean absolute error of 0.044 mm when tested on a 23G surgical cannula with a diameter of 0.640 mm and operates at a resolution of 4024 × 3036 at 30 frames per second.


RNA in extracellular vesicles.
Cells release a range of membrane-enclosed extracellular vesicles (EVs) into the environment. Among them, exosomes and microvesicles (collectively measuring 40-1000 nm in diameter) carry proteins, signaling lipids, and nucleic acids from donor cells to recipient cells, and thus have been proposed to serve as intercellular mediators of communication. EVs transport cellular materials in many physiologic processes, including differentiation, stem cell homeostasis, immune responses, and neuronal signaling. EVs are also increasingly recognized as having a direct role in pathologies such as cancer and neurodegeneration. Accordingly, EVs have been the focus of intense investigation as biomarkers of disease, prognostic indicators, and even therapeutic tools. Here, we review the classes of RNAs present in EVs, both coding RNAs (messenger RNAs) and noncoding RNAs (long noncoding RNAs, microRNAs, and circular RNAs). The rising attention to EV-resident RNAs as biomarkers stems from the fact that RNAs can be detected at extremely low quantities using a number of methods. To illustrate the interest in EV biology, we discuss EV RNAs in cancer and neurodegeneration, two major age-associated disease processes. WIREs RNA 2017, 8:e1413. doi: 10.1002/wrna.1413 For further resources related to this article, please visit the WIREs website.


Inhibition of NF-kappaB signaling reduces virus load and gammaherpesvirus-induced pulmonary fibrosis.
Idiopathic pulmonary fibrosis (IPF) is a chronic progressive lung disorder of unknown etiology. Several studies have demonstrated an association between pulmonary infection with a herpesvirus and IPF. Based on those observations, we have developed a mouse model in which interferon (IFN)gammaR(-/-) mice infected intranasally with murine gammaherpesvirus 68 (MHV68) develop lung fibrosis. We hypothesize that viral load was a critical factor for the development of fibrosis. Because nuclear factor (NF)-kappaB signaling is required to efficiently establish gammaherpesvirus, latency we infected IFNgammaR(-/-) mice with a MHV68 virus that expresses a mutant dominant inhibitor of the NF-kappaB signaling pathway, called IkappaBalphaM. Striking differences were observed at the onset of the chronic infection, which correlated with a decreased virus load in mice infected with MHV68-IkappaBalphaM compared with mice infected with control MHV68 (MHV68-MR). IFNgammaR(-/-) mice infected with MHV68-IkappaBalphaM lacked vasculitis and fibrosis 15 to 120 days post infection. Inhibition of NF-kappaB in MHV68-infected cells of the lungs diminished the expression of the fibrocyte recruiting chemokines monocyte chemoattractant protein 1 (MCP-1) and CXCL12, ameliorated macrophage expression of markers of alternative activation, and failed to increase expression of the integrin alphavbeta6, which is implicated in the activation of the profibrotic factor TGF-beta. Thus, the inhibition of NF-kappaB signaling in the infected lung cells of IFNgammaR(-/-) mice reduces virus persistence and ameliorates profibrotic events. Host determinants of latency might therefore represent new therapeutic targets for gammaherpesvirus-associated pulmonary fibrosis.


Terahertz pulsed imaging of skin cancer in the time and frequency domain.
Terahertz Pulsed Imaging(TPI) is a new medical imaging modality forthe detection of epithelial cancers. Overthe last two years this technique has beenapplied to the study of in vitrobasal cell carcinoma (BCC). Usingtime-domain analysis the contrast betweendiseased and normal tissue has been shownto be statistically significant, andregions of increased terahertz (THz)absorption correlated well with thelocation of the tumour sites in histology.Understanding the source of this contrastthrough frequency-domain analysis mayfacilitate the diagnosis of skin cancer andrelated skin conditions using TPI. Wepresent the first frequency-domain analysisof basal cell carcinoma in vitro,with the raw power spectrum giving aninsight into the surface features of theskin. Further data manipulation is requiredto determine whether spectral informationcan be extrapolated at depth. These resultshighlight the complexity of working inreflection geometry.


Ibogaine signals addiction genes and methamphetamine alteration of long-term potentiation.
The mapping of the human genetic code will enable us to identify potential gene products involved in human addictions and diseases that have hereditary components. Thus, large-scale, parallel gene-expression studies, made possible by advances in microarray technologies, have shown insights into the connection between specific genes, or sets of genes, and human diseases. The compulsive use of addictive substances despite adverse consequences continues to affect society, and the science underlying these addictions in general is intensively studied. Pharmacological treatment of drug and alcohol addiction has largely been disappointing, and new therapeutic targets and hypotheses are needed. As the usefulness of the pharmacotherapy of addiction has been limited, an emerging potential, yet controversial, therapeutic agent is the natural alkaloid ibogaine. We have continued to investigate programs of gene expression and the putative signaling molecules used by psychostimulants such as amphetamine in in vivo and in vitro models. Our work and that of others reveal that complex but defined signal transduction pathways are associated with psychostimulant administration and that there is broad-spectrum regulation of these signals by ibogaine. We report that the actions of methamphetamine were similar to those of cocaine, including the propensity to alter long-term potentiation (LTP) in the hippocampus of the rat brain. This action suggests that there may be a "threshold" beyond which the excessive brain stimulation that probably occurs with compulsive psychostimulant use results in the occlusion of LTP. The influence of ibogaine on immediate early genes (IEGs) and other candidate genes possibly regulated by psychostimulants and other abused substances requires further evaluation in compulsive use, reward, relapse, tolerance, craving and withdrawal reactions. It is therefore tempting to suggest that ibogaine signals addiction gene products.


Effect of acupressure in treating urodynamic stress incontinence: a randomized controlled trial.
The efficacy of acupressure therapy in managing urodynamic stress incontinence has not been fully investigated. This study evaluates the effects of a validated acupressure protocol for treating women with urodynamic stress incontinence. A randomized, single-blinded, placebo-controlled trial with a before-and-after study design was conducted. Eighty-one women aged between 18 and 60 were recruited at a urogynecology clinic in an acute hospital in Hong Kong. Participants were randomly assigned to an intervention (acupressure) group, a sham group, or a usual care (control) group. A validated acupressure protocol was employed in the intervention group. The intervention comprised three weekly sessions of 30 minutes each for a total of thirty sessions. Outcome measures included pelvic floor muscle strength, number of episodes of urine leakage over four days, self-reported severity of urine leakage, and responses on the Chinese version of the King's Health Questionnaire. No adverse effects were reported. Five percent of the participants dropped out of the study. Intention-to-treat analysis was conducted, the results indicated significant differences in pelvic floor muscle strength across the three groups (H =7.05, p =0.03) and in self-reported severity of urine leakage between the intervention and control groups (Z = -2.48, p = 0.01). Significant improvement in all domains of the Chinese version of the King's Health Questionnaire was evident in the intervention group. Acupressure is a simple and non-invasive intervention that appears to have positive physiological and psychological effects on women with urodynamic stress incontinence. The findings support acupressure as an intervention option for managing urodynamic stress incontinence in women.


Long-term morbidity of respiratory viral infections during chemotherapy in children with leukaemia.
Respiratory viruses are a common cause of infection in immunosuppressed children undergoing cancer therapy. Pulmonary sequelae have been documented following respiratory viral infections (RVIs) in hematopoietic stem cell transplant (HSCT) recipients; however potential late effects in children undergoing nonmyeloablative chemotherapy have not been investigated. To evaluate the long-term pulmonary morbidity of respiratory viral infections during chemotherapy in children with acute lymphoblastic leukemia (ALL). Childhood ALL survivors, aged 7 to 18 years, greater than 6 months posttreatment were recruited. Exclusion criteria included HSCT or proven bacterial/fungal respiratory infection during treatment. Subjects were classified into "viral" or "control" groups according to retrospective medical records that documented the presence of laboratory-proven RVIs during chemotherapy. Symptom questionnaires (Liverpool, ISAAC) and lung function testing (spirometry, plethysmography, diffusing capacity, forced oscillation technique to ATS/ERS standards) were then performed cross-sectionally at the time of recruitment. Fifty-four patients (31 viral, 23 control) were recruited: median (range) age 11.2 (7.2-18.1) years, and at 4.9 (0.5-13) years posttherapy. Abnormalities were detected in 17 (31%) individuals (8 viral, 9 control), with the most common being DLCO impairment (3 viral, 4 control) and reduced respiratory reactance at 5 Hz (5 viral, 6 control). Children with RVIs during chemotherapy reported more current respiratory symptoms, particularly wheeze (odds ratio [OR], 3.0; 95% confidence interval [CI]: 0.9-10.0; P = .09) and cough (OR, 2.7; 95% CI: 0.8-9.5; P = .11). No differences in lung function tests were observed between the two groups. Our study found children with RVIs during chemotherapy developed more long-term respiratory symptoms than controls; however, differences did not reach statistical significance. No differences in static lung function were found between the two groups. Overall, pulmonary abnormalities and/or significant ongoing respiratory symptoms were detected in nearly a third of ALL survivors treated without HSCT. Larger, prospective studies are warranted to evaluate the etiology and clinical significance of these findings.


[Standardization and evaluation of the modified vibriocidal assay].
The vibriocidal antibody test is a reliable and well-documented method to determine bacterial antibodies to Vibrio cholerae 01 antigens. It consists of mixing serum dilutions and a steady quantity of bacteria and supplement to cause cell lysis. Titer is determined by visual observation. In this paper, we implemented a change in the presented method where a pH and glucose indicator was added to the culture medium used to stop the reaction, which allowed a quicker reading by any person who are not very familiar with the carrying out of this test since the colour change in the plaque is quite evident.


The combination of milatuzumab, a humanized anti-CD74 antibody, and veltuzumab, a humanized anti-CD20 antibody, demonstrates activity in patients with relapsed and refractory B-cell non-Hodgkin lymphoma.
As a result of the anti-tumour activity observed in vitro and in vivo with combined anti-CD20 and anti-CD74 antibodies, we initiated a phase I/II trial of veltuzumab and milatuzumab in patients with relapsed or refractory B-cell non-Hodgkin lymphoma (NHL). Patients received an induction of veltuzumab 200 mg/m(2) weekly combined with escalating doses of milatuzumab at 8, 16 and 20 mg/kg weekly for 4 weeks. Patients without disease progression could receive an extended induction with treatment on weeks 12, 20, 28 and 36. A total of 35 patients enrolled on the study. Median age was 63 years, median number of prior therapies was 3, and 63% of patients were rituximab refractory. No dose-limiting toxicities were observed in the phase I study. Related grade 3-4 toxicities included lymphopenia, leucopenia, neutropenia, anaemia, infusion reactions, hyperglycaemia, fatigue and atrial tachycardia. Median weeks of therapy was 12 and 29% of patients completed all 36 weeks of therapy. The overall response rate was 24%, median duration of response was 12 months, and responses were observed at all dose levels and in 50% of patients refractory to rituximab. Combination therapy with veltuzumab and milatuzumab demonstrated activity in a population of heavily pre-treated patients with relapsed or refractory indolent NHL.


Increased expression of SLAM receptors SLAMF3 and SLAMF6 in systemic lupus erythematosus T lymphocytes promotes Th17 differentiation.
Altered T cell function in systemic lupus erythematosus (SLE) is determined by various molecular and cellular abnormalities, including increased IL-17 production. Recent evidence suggests a crucial role for signaling lymphocyte activation molecules (SLAMs) in the expression of autoimmunity. In this study, we demonstrate that SLAMF3 and SLAMF6 expression is increased on the surface of SLE T cells compared with normal cells. SLAM coengagement with CD3 under Th17 polarizing conditions results in increased IL-17 production. SLAMF3 and SLAMF6 T cell surface expression and IL-17 levels significantly correlate with disease activity in SLE patients. Both naive and memory CD4(+) T cells produce more IL-17 in response to SLAM costimulation as compared with CD28 costimulation. In naive CD4(+) cells, IL-17 production after CD28 costimulation peaks on day 3, whereas costimulation with anti-SLAMF3 and anti-SLAMF6 Abs results in a prolonged and yet increasing production during 6 d. Unlike costimulation with anti-CD28, SLAM costimulation requires the presence of the adaptor molecule SLAM-associated protein. Thus, engagement of SLAMF3 and SLAMF6 along with Ag-mediated CD3/TCR stimulation represents an important source of IL-17 production, and disruption of this interaction with decoy receptors or blocking Abs should mitigate disease expression in SLE and other autoimmune conditions.


Resistance to vasopressin action on the kidney in patients with Cushing's disease.
To assess the plasma levels and action of arginine vasopressin (AVP) in patients with Cushing's disease. There are many reports that patients with Addison's disease have increased AVP levels associated with hyponatraemia and hypoosmolality, but none on the dynamics of secretion of this neurohormone during osmolality-based stimulation in patients with chronic hypercortisolism. The plasma AVP concentration and the urinary and plasma osmolality after a 7.5-h water deprivation test (WDT) were evaluated in 13 patients with Cushing's disease and 15 normal (control) individuals. In patients with Cushing's disease we also assessed the urinary osmolality in response to 10 micrograms i.v. desmopressin (DDAVP) administered at the end of the WDT. At the end of the WDT, urinary osmolality was significantly lower in patients with Cushing's disease (511.5 +/- 148.5 mOsm/l) than in the normal subjects (981.1 +/- 107.1 mOsm/l, P < 0.001), whereas plasma osmolality did not differ between the two groups. Consequently, the urine/plasma osmolality ratio (Uosm/Posm) was lower in patients with Cushing's disease than in normal individuals (1.8 +/- 0.5 compared with 3.4 +/- 0.4, P < 0.001). The AVP concentration also was greater (7.3 +/- 3.1 pmol/l) in those with Cushing's disease than in the controls (3.9 +/- 2.3 pmol/l, P < 0.005). After administration of DDAVP to the hypercortisolaemic patients, the urinary osmolality attained (718.0 +/- 200.0 mOsm/l) was still lower than that in the normal group at the end of WDT (P < 0.005). Patients with Cushing's disease presented higher AVP levels and smaller Uosm/Posm ratios than normal subjects. After DDAVP, the patients with Cushing's disease were unable to concentrate the urine adequately. These data suggest that the kidney shows resistance to the action of both endogenous and exogenous AVP in patients with Cushing's disease.


[Functional organization of the kinesthetic projections of the 1st somatosensory region of the cat cortex].
Electrophysiological studies were performed on adult cats under ethaminal anesthesia. Kinesthetic potentials were evoked by passive extension of the ulnar joint and recorded in contralateral primary somatosensory cortical area. Natural (nonelectrical) stimulation of peripheral kinesthetic receptors was performed according to the author's original method. The results obtained show significantly shorter latent period of contralateral kinesthetic potentials in comparison with somatosensory potentials in response to electrical stimulation of the skin. These data demonstrate the possibility of super-rapid conduction of modal-specific volleys to the cortical projection centres in the kinesthetic system of cats.


Spatial distribution of venous gas emboli in the lungs.
The distribution of gaseous pulmonary emboli is presumed to be determined by their buoyancy. We hypothesized that regional pulmonary blood flow may also influence their distribution. Therefore, pulmonary blood flow was measured in supine, anesthetized dogs with use of 15-microm fluorescent microspheres at baseline and during N(2) embolism. The animals were killed, and the lungs were excised, air-dried, and diced into approximately 2-cm(3) pieces with weights and spatial coordinates recorded. Embolism was defined as a >10% flow decrease relative to baseline. Vertically, the incidence of embolism increased substantially by 6 +/- 1% per additional centimeter in height compared with baseline (P = 0.0003). Embolism also increased radially by 3 +/- 1%/cm from the hilum (P = 0.002). There was a weaker but statistically significant increase in embolism to pieces with greater baseline flow, 9 +/- 2% for every 1. 0 increase in relative baseline flow (P = 0.008). We conclude that the distribution of gaseous emboli is influenced by buoyancy and flow dynamics within the pulmonary vasculature.


Molecular and biochemical mechanisms of diabetic encephalopathy.
Diabetes mellitus is one of the important independent risk factors for the development of neurological disorders such as ischemic stroke, transient ischemic attacks, vascular dementia and neurodegenerative processes. Hyperglycemia plays a crucial role as a trigger in the pathogenesis of these disorders. In this review, we summarize the existing data on the molecular mechanisms of diabetic encephalopathy development, consider the features of oxidative and nitrosative stresses, changes in the thiol-disulfide system, as well as mitochondrial and endothelial dysfunction in diabetes. We focus on the role of HSP 70 in cellular responses in diabetic encephalopathy. HSP70 protein is an important component of the endogenous system of neuroprotection. It acts as an intracellular chaperone, providing the folding, retention, and transport of synthesized proteins, as well as their degradation under both normoxic and stress-induced denaturation conditions. HSP70 can be considered a molecular marker and a promising therapeutic target in the treatment of diabetes mellitus.


Application of Mycorrhiza and Soil from a Permaculture System Improved Phosphorus Acquisition in Naranjilla.
Naranjilla (Solanum quitoense) is a perennial shrub plant mainly cultivated in Ecuador, Colombia, and Central America where it represents an important cash crop. Current cultivation practices not only cause deforestation and large-scale soil degradation but also make plants highly susceptible to pests and diseases. The use of arbuscular mycorrhizal fungi (AMF) can offer a possibility to overcome these problems. AMF can act beneficially in various ways, for example by improving plant nutrition and growth, water relations, soil structure and stability and protection against biotic and abiotic stresses. In this study, the impact of AMF inoculation on growth and nutrition parameters of naranjilla has been assessed. For inoculation three European reference AMF strains (Rhizoglomus irregulare, Claroideoglomus claroideum, and Cetraspora helvetica) and soils originating from three differently managed naranjilla plantations in Ecuador (conventional, organic, and permaculture) have been used. This allowed for a comparison of the performance of exotic AMF strains (reference strains) versus native consortia contained in the three soils used as inocula. To study fungal communities present in the three soils, trap cultures have been established using naranjilla as host plant. The community structures of AMF and other fungi inhabiting the roots of trap cultured naranjilla were assessed using next generation sequencing (NGS) methods. The growth response experiment has shown that two of the three reference AMF strains, a mixture of the three and soil from a permaculture site led to significantly better acquisition of phosphorus (up to 104%) compared to uninoculated controls. These results suggest that the use of AMF strains and local soils as inoculants represent a valid approach to improve nutrient uptake efficiency of naranjilla and consequently to reduce inputs of mineral fertilizers in the cultivation process. Improved phosphorus acquisition after inoculation with permaculture soil might have been caused by a higher abundance of AMF and the presence of Piriformospora indica as revealed by NGS. A higher frequency of AMF and enhanced root colonization rates in the trap cultures supplemented with permaculture soil highlight the importance of diverse agricultural systems for soil quality and crop production.


Infection by gram-negative organisms via the biliary route results in greater mortality than portal venous infection.
Cholangitis requires bile duct obstruction and infection. Patients with cholangitis are often more affected than those with infections that reach the liver through the portal vein. We will attempt to study the influences of (i) route of entry and (ii) presence of bile duct obstruction on hepatic infection. C57BL/6 mice received injections of Escherichia coli or lipopolysaccharide into the obstructed bile duct or portal vein and were monitored for survival. Livers were assayed for bacteria, and cytokine mRNA was measured. In order to examine the effect of biliary obstruction on hepatic infection, animals were subjected to bile duct ligation 1 day prior to portal vein injection and were monitored for survival. The 50% lethal dose (LD(50)) for E. coli injected into the bile duct was 50 CFU/animal; the LD(50) for E. coli injected into the portal vein was 5 x 10(7) CFU/animal. Initial hepatic delivery of bacteria was equivalent 1 h after injection into the bile duct or portal vein. However, by 24 h, a significantly greater amount of bacteria was recovered from the livers of the bile duct-injected group. Interleukin 10 (IL-10) and IL-1RA mRNA was expressed at greater levels in the bile duct-injected group. Prior bile duct ligation followed by portal vein injection resulted in a higher incidence of death than when sham operation was performed prior to portal vein injection. Our data suggest that the increased mortality from cholangitis, compared with that from other hepatic infections, is related to the different route of delivery of pathogen and the maladaptive response (possibly involving IL-10 and IL-1RA) to biliary obstruction itself.


Sarcoidosis.
Sarcoidosis is a systemic disease of unknown cause that is characterised by the formation of immune granulomas in various organs, mainly the lungs and the lymphatic system. Studies show that sarcoidosis might be the result of an exaggerated granulomatous reaction after exposure to unidentified antigens in individuals who are genetically susceptible. Several new insights have been made, particularly with regards to the diagnosis and care of some important manifestations of sarcoidosis. The indications for endobronchial ultrasound in diagnosis and for PET in the assessment of inflammatory activity are now better specified. Recognition of unexplained persistent disabling symptoms, fatigue, small-fibre neurological impairment, cognitive failure, and changes to health state and quality of life, has improved. Mortality in patients with sarcoidosis is higher than that of the general population, mainly due to pulmonary fibrosis. Predicted advances for the future are finding the cause of sarcoidosis, and the elucidation of relevant biomarkers, reliable endpoints, and new efficient treatments, particularly in patients with refractory sarcoidosis, lung fibrosis, and those with persistent disabling symptoms.


Genetic Variation Related to High Elevation Adaptation Revealed by Common Garden Experiments in Pinus yunnanensis.
Local adaptation, adaptation to specialized niches and environmental clines have been extensively reported for forest trees. Investigation of the adaptive genetic variation is crucial for forest resource management and breeding, especially in the context of global climate change. Here, we utilized a Pinus yunnanensis common garden experiments established at high and low elevation sites to assess the differences in growth and survival among populations and between the two common garden sites. The studied traits showed significant variation between the two test sites and among populations, suggesting adaptive divergence. To detect genetic variation related to environment, we captured 103,608 high quality SNPs based on RNA sequencing, and used them to assess the genetic diversity and population structure. We identified 321 outlier SNPs from 131 genes showing significant divergence in allelic frequency between survival populations of two sites. Functional categories associated with adaptation to high elevation were found to be related to flavonoid biosynthesis, response to UV, DNA repair, response to reactive oxygen species, and membrane lipid metabolic process. Further investigation of the outlier genes showed overrepresentation of the flavonoid biosynthesis pathway, suggesting that this pathway may play a key role in P. yunnanensis adaptation to high elevation environments. The outlier genes identified, and their variants, provide a basic reference for advanced investigations.


Adenosine-5'-O-phosphorylated and adenosine-5'-O-phosphorothioylated polyols as strong inhibitors of (symmetrical) and (asymmetrical) dinucleoside tetraphosphatases.
Dinucleoside 5',5"'- P (1), P ( n )-polyphosphates, and particularly the diadenosine compounds, have been implicated in extracellular purinergic signalling and in various intracellular processes, including DNA metabolism, tumour suppression and stress responses. If permitted to accumulate, they may also be toxic. One approach to understanding their function is through the various specific degradative enzymes that regulate their levels. Eight adenosine-5'- O -phosphorylated polyols (derivatives of glycerol, erythritol and pentaerythritol) and 11 adenosine-5'- O -phosphorothioylated polyols (derivatives of glycerol, erythritol, pentaerythritol, butanediol and pentanediol) have been tested as inhibitors of specific diadenosine tetraphosphate (Ap(4)A) hydrolases. Of these two groups of novel nucleotides, the adenosine-5'- O -phosphorothioylated polyols were generally stronger inhibitors than their adenosine-5'- O -phosphorylated counterparts. 1,4-Di(adenosine-5'- O -phosphorothio) erythritol appeared to be the strongest inhibitor of ( asymmetrical ) Ap(4)A hydrolases (EC 22.214.171.124) from both lupin and human, with K (i) values of 0.15 microM and 1.5 microM respectively. Of eight adenosine-5'- O -phosphorylated polyols, 1,4-di(adenosine-5'- O -phospho) erythritol was the only compound that inhibited the lupin enzyme. Two derivatives of pentaerythritol, di(adenosine-5'- O -phosphorothio)-di(phosphorothio) pentaerythritol and tri(adenosine-5'- O -phosphorothio)-phosphorothio-pentaerythritol, proved to be the strongest inhibitors of the prokaryotic ( symmetrical ) Ap(4)A hydrolase (EC 126.96.36.199) so far reported. The estimated K (i) values were 0.04 microM and 0.08 microM respectively. All of these inhibitors were competitive with respect to Ap(4)A. These new selectively acting Ap(4)A analogues should prove to be valuable tools for further studies of Ap(4)A function and of the enzymes involved in its metabolism.


Magnitude of extended-spectrum β-lactamase and carbapenemase producing Enterobacteriaceae among commonly vended street foods in Arba Minch town, southern Ethiopia.
The rising prevalence of extended-spectrum beta-lactamase and carbapenemase-producing Enterobacteriaceae (ESβL-PE) in street foods poses a significant risk to human health due to its epidemiological significance. Thus, the aim of this study was to determine the magnitude of foodborne Enterobacteriaceae that produce carbapenemase and ESβL, as well as their patterns of antibiotic resistance, in the studied area. A community-based cross-sectional study was carried out from January 1st, 2023, to February 30th, 2023. One hundred randomly chosen street-vended food items (one hundred grams of each food item) were aseptically collected, and aliquots of 0.1 ml from the homogenized (25 g of samples into 225 ml of buffered peptone water (BPW)) were inoculated on MacConkey agar and Xylose Lysine Deoxycholate Agar (XLD). Enterobacteriaceae isolates were identified using various biochemical tests. ESβL and carbapenemase were first screened by indicator cephalosporins and carbapenem antibiotics, respectively. ESβL and carbapenemase were confirmed by a double-disc synergy test and modified carbapenem inactivation methods, respectively. Kirby-Bauer disc diffusion method was used for the antimicrobial-resistant test. A total of 112 Enterobacteriaceae belonging to six different genera were isolated. E. coli was attributed 39 (34.8%), followed by Citrobacter spp. 22 (19.6%) and K. pneumoniae 18 (16.1%), with only 8 (7.1%) isolated Salmonella spp. About 15.2% (n = 17) and 8.9% (n = 10) of Enterobacteriaceae were phenotypically confirmed to be extended-spectrum beta-lactamase (ESβL) and carbapenemase producers, respectively. The highest percentage of ESβL-producing isolates was attributed to K. pneumoniae (n = 5), E. coli (n = 4), and Enterobacter spp. (n = 3). Proteus spp. and Salmonella spp. isolates were carbapenemase-negative. All carbapenemase-positive isolates were found to be ESβL-producers. 70.6% (12/17) of ESβL-producing Enterobacteriaceae were found to be multidrug-resistant (MDR). A considerable number of multidrug-resistant ESβL and carbapenemase-producing Enterobacteriaceae were identified, suggesting that street foods may be a potential source of MDR foodborne infections. Consequently, it is important to conduct routine examinations of street food items and track trends in medication resistance.


Temperamental characteristics in adults with attention-deficit hyperactivity disorder: a comparison with bipolar disorder and healthy control groups.
To date, the affective temperamental characteristics of adults with attention-deficit hyperactivity disorder (ADHD) have not been studied. The aim of this study is to explore those temperamental characteristics for adults diagnosed with ADHD as measured by the TEMPS-A and then to compare those results with results for individuals diagnosed with bipolar disorder (BD) and with healthy controls. Forty adults with ADHD, 40 patients with BD, and 40 healthy controls were enrolled in this study. The groups were matched by age and gender. All patients were assessed using the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID I), the Hamilton Depression Rating Scale, the Hamilton Anxiety Rating Scale, the Young Mania Rating Scale and the Wender Utah Rating Scale. Subjects' temperamental characteristics were examined using the Turkish version of the Temperament Evaluation of Memphis, Pisa, Paris and San Diego-auto questionnaire (TEMPS-A). Ten subjects (25%) in the ADHD group and 15 subjects (30%) in the bipolar group had at least one dominant temperament. There was no identifiable dominant temperament in the control group. Compared to the control group, the ADHD group scored higher than other groups on all domains of the TEMPS-A: depressive cyclothymic, irritable and anxious. However, the hyperthymic domain was not higher for this group. Adults with ADHD scored higher on the irritable temperament scale as compared to the BD group. The ADHD and BD groups had similar mean scores for each of the other four temperaments. The adults diagnosed with ADHD in this study had different temperamental characteristics from the control group, and these temperamental characteristics were similar to those of the bipolar patients. Recognizing the role of temperamental characteristics in adults with ADHD may increase our understanding of ADHD.


CREST (Carotid Revascularization Endarterectomy versus Stent Trial): background, design, and current status.
The Carotid Revascularization Endarterectomy versus Stent Trial (CREST) contrasts the relative efficacy of carotid endarterectomy (CEA) and carotid angioplasty-stent (CAS) in preventing primary outcomes of stroke, myocardial infarction, or death during a 30-day periprocedural period, or ipsilateral stroke over the follow-up period extending up to 4 years. Stroke events will be verified by an Adjudication Committee masked to the assigned treatment. The primary eligibility criterion is a significant (> or =50%) stenosis of the carotid artery in patients with transient ischemic attack or ipsilateral nondisabling stroke within the prior 180 days. Men and women will be eligible for the trial, but patients with medical conditions likely to limit their participation during the follow-up or to interfere with outcome evaluation will be excluded. After a credentialing and training phase, 2,500 patients will be randomized to the treatments. Statistical analysis of the primary outcome will employ standard survival techniques and will result in 90% power to detect annual differences between groups of 1.2% or higher in event rates of the primary outcomes.


How do men and women define sexual desire and sexual arousal?
The purpose of this study was to understand how men and women define sexual desire and sexual arousal and how they distinguish between the two. The authors conducted 32 semi-structured interviews with individuals in South East England, using a purposive sampling strategy to maximize the variation in experience of sexual function across the group. The authors identified three criteria that participants used to define and distinguish between desire and arousal: the sequence in which they occurred; whether the mind or the body (or both) were engaged; and the extent to which feelings of desire or arousal were responsive (in response to person or stimulus) and motivational (oriented toward a goal). Most participants attempted to distinguish between desire and arousal when prompted, but often with difficulty. Participants commonly felt that desire preceded arousal; some felt that desire was "mind" and arousal "body"; and many felt that both desire and arousal were responsive and motivational. However, the authors identified numerous times when these distinctions were reversed or the differences between terms were blurred. The results support recent proposals to merge the two diagnostic categories of female sexual arousal disorder and hyposexual desire disorder into a single diagnostic category.


Dimensions of anxiety in Major depressive disorder and their use in predicting antidepressant treatment outcome: an iSPOT-D report.
Major depressive disorder (MDD) commonly co-occurs with clinically significant levels of anxiety. However, anxiety symptoms are varied and have been inconsistently associated with clinical, functional, and antidepressant treatment outcomes. We aimed to identify and characterise dimensions of anxiety in people with MDD and their use in predicting antidepressant treatment outcome. 1008 adults with a current diagnosis of single-episode or recurrent, nonpsychotic, MDD were assessed at baseline on clinical features and cognitive/physiological functioning. Participants were then randomised to one of three commonly prescribed antidepressants and reassessed at 8 weeks regarding symptom change, as well as remission and response, on the 17-item Hamilton Rating Scale Depression (HRSD17) and the 16-item Quick Inventory of Depressive Symptomatology (QIDS-SR16). Exploratory factor analysis was used on items from scales assessing anxiety symptoms, and resulting factors were assessed against clinical features and cognitive/physiological functioning. Factors were also assessed on their ability to predict treatment outcome. Three factors emerged relating to stress, cognitive anxiety, and somatic anxiety. All factors showed high internal consistency, minimal cross-loadings, and unique clinical and functional profiles. Furthermore, only higher somatic anxiety was associated with poorer QIDS-SR16 remission, even after adjusting for covariates and multiple comparisons. Anxiety symptoms in people with MDD can be separated onto distinct factors that differentially respond to treatment outcome. Furthermore, these factors do not align with subscales of established measures of anxiety. Future research should consider cognitive and somatic symptoms of anxiety separately when assessing anxiety in MDD and their use in predicting treatment outcome.


Early symptoms of ovarian cancer: a case-control study without recall bias.
Ovarian cancer is usually diagnosed after it has spread and is difficult to cure. Previous attempts to identify early symptoms have either lacked a control group or have been based on interviews of cases, with possible recall bias. The purpose of this study was to identify early symptoms of ovarian cancer by reviewing prediagnostic medical records, free of recall bias, and comparing women with and without ovarian cancer. In an integrated health care delivery system, symptoms recorded in medical records of 102 women with ovarian cancer during the two years before diagnosis were compared with those of 102 matched control women. More cases than controls complained of several symptoms up to one year before diagnosis. Most of these symptoms were abdominal or gastrointestinal in nature and were more prevalent in the advanced stage cases. Other symptom sites included pelvic, urinary, back, and systemic. Because case-control differences were not large and prevalence is low, positive predictive values were generally quite low. Previous reports of early symptoms of ovarian cancer were confirmed in a study with a control group and free of recall bias. It is not clear that these symptoms occurred while the disease was still localized. Because hundreds of women would have to be investigated to detect one case of ovarian cancer, the clinical utility of these symptoms is uncertain. Nevertheless, health care providers should keep ovarian cancer in mind, when women present with symptoms such as abdominal pain and bloating.


Task-Based Mirror Therapy Augmenting Motor Recovery in Poststroke Hemiparesis: A Randomized Controlled Trial.
To establish the effect of the task-based mirror therapy (TBMT) on the upper limb recovery in stroke. A pilot, randomized, controlled, assessor-blinded trial was conducted in a rehabilitation institute. A convenience sample of 33 poststroke (mean duration, 12.5 months) hemiparetic subjects was randomized into 2 groups (experimental, 17; control, 16). The subjects were allocated to receive either TBMT or standard motor rehabilitation-40 sessions (5/week) for a period of 8 weeks. The TBMT group received movements using various goal-directed tasks and a mirror box. The movements were performed by the less-affected side superimposed on the affected side. The main outcome measures were Brunnstrom recovery stage (BRS) and Fugl-Meyer assessment (FMA)-FMA of upper extremity (FMA-UE), including upper arm (FMA-UA) and wrist-hand (FMA-WH). The TBMT group exhibited highly significant improvement on mean scores of FMA-WH (P < .001) and FMA-UE (P < .001) at postassessment in comparison to the control group. Furthermore, there was a 12% increase in the number of subjects at BRS stage 5 (out of synergy movement) in the experimental group as compared to a 0% rise at the same stage in the control group. This pilot trial confirmed the role of TBMT in improving the wrist-hand motor recovery in poststroke hemiparesis. MT using tasks may be used as an adjunct in stroke rehabilitation.


A fast magnetic bead-based colorimetric immunoassay for the detection of tetrodotoxins in shellfish.
Tetrodotoxin (TTX) is a potent neurotoxin responsible for many food poisoning incidents and some fatalities. Although mainly associated with the consumption of pufferfish, in recent years, TTX has been found in shellfish, particularly in Europe. In this work, a magnetic bead (MB)-based colorimetric immunoassay was applied to the detection of TTX in Pacific oysters (Crassostrea gigas), razor clams (Solen marginatus) and mussels (Mytilus galloprovincialis). Effective LODs (eLODs) for TTX of 1 μg/kg in oysters and razor clams and 3.3 μg/kg in mussels, significantly below the EFSA guidance threshold (44 μg/kg), were obtained. The strategy was applied to the analysis of naturally-contaminated Pacific oysters (Crassostrea gigas) and mussels (Mytilus edulis) from the Netherlands, and TTX was detected in all samples. The approach, which takes less than 1.5 h, proved to be useful as a rapid and simple method to detect TTX, support shellfish safety and protect consumers.


Synaptic integration at a sensory-motor reflex in the leech.
1. In the medicinal leech the distribution of synapses from the pressure sensory (P) neurone to the annulus erector (AE) motoneurone and the site of impulse initiation in the AE cell were determined to understand better the integration of sensory inputs by the motoneurone. 2. The axon of the AE cell bifurcates before leaving the ganglion. Laser photoablation experiments indicated that the axon proximal to the bifurcation is inexcitable. Two techniques, laser photoablation and measurement of impulse timing, each located the site of impulse initiation at the bifurcation. 3. The medial P cell makes a monosynaptic connection with the AE cell, eliciting an excitatory postsynaptic potential (EPSP) of 1-3 mV amplitude recorded in the AE cell soma. 4. Intracellular injection of dyes into separate cells showed that P cell branches appear to contact AE cell branches both ipsilaterally and contralaterally. Laser photoablation of selected portions of the P and AE cells' axons revealed functional contacts on both sides. 5. The primary axon bifurcation of the AE cell is the site of integration of synaptic potentials that spread passively from both sides of the ganglion. These summed synaptic potentials account for the concerted activity of the two AE cells in each ganglion.


Developmental programming of natural killer and innate lymphoid cells.
In recent years we have witnessed a blooming interest in innate lymphoid cell (ILC) biology thanks to the discovery of novel lineages of ILC that are phenotypically and functionally distinct from NK cells. While the importance of these novel ILC subsets as essential functional components of the early immune responses are now clearly established, many questions remain as to how early ILC developmental fates are determined and how specific effector functions associated with individual ILC subsets are achieved. As the founding member of the ILC family, properties of NK cells have defining attributes that characterize this group of innate effectors. Analysing their developmental rules may provide clues to principles that guide ILC development in general.


Genome-enabled prediction of indicator traits of resistance to gastrointestinal nematodes in sheep using parametric models and artificial neural networks.
This study aimed to assess the predictive ability of parametric models and artificial neural network method for genomic prediction of the following indicator traits of resistance to gastrointestinal nematodes in Santa Inês sheep: packed cell volume (PCV), fecal egg count (FEC), and Famacha© method (FAM). After quality control, the number of genotyped animals was 551 (PCV), 548 (FEC), and 565 (FAM), and 41,676 SNP. The average prediction accuracy (ACC) calculated by Pearson correlation between observed and predicted values and mean squared errors (MSE) were obtained using genomic best unbiased linear predictor (GBLUP), BayesA, BayesB, Bayesian least absolute shrinkage and selection operator (BLASSO), and Bayesian regularized artificial neural network (three and four hidden neurons, BRANN_3 and BRANN_4, respectively) in a 5-fold cross-validation technique. The average ACC varied from moderate to high according to the trait and models, ranging between 0.418 and 0.546 (PCV), between 0.646 and 0.793 (FEC), and between 0.414 and 0.519 (FAM). Parametric models presented nearly the same ACC and MSE for the studied traits and provided better accuracies than BRANN. The GBLUP, BayesA, BayesB and BLASSO models provided better accuracies than the BRANN_3 method, increasing by around 23% for PCV, and 18.5% for FEC. In conclusion, parametric models are suitable for genome-enabled prediction of indicator traits of resistance to gastrointestinal nematodes in sheep. Due to the small differences in accuracy found between them, the use of the GBLUP model is recommended due to its lower computational costs.


Influences of Climate Change and Variability on Estuarine Ecosystems: An Impact Study in Selected European, South American and Asian Countries.
It is well-known that climate change significantly impacts ecosystems (at the macro-level) and individual species (at the micro-level). Among the former, estuaries are the most vulnerable and affected ecosystems. However, despite the strong relations between climate change and estuaries, there is a gap in the literature regarding international studies across different regions investigating the impacts of climate change and variability on estuaries in different geographical zones. This paper addresses this need and reviews the impacts of climate change, variability and extreme weather on estuaries. It emphasises the following: (i) a set of climate parameters governing estuarine hydrology and processes; and (ii) a sample of countries in Asia (Bangladesh), Europe (Portugal) and South America (Uruguay). We reviewed the influences of the climatic drivers of the estuarine hydrology, ecological processes and specific species in estuarine communities across the selected geographical regions, along with an analysis of their long-term implications. The key results from the three estuaries are as following: (i) Hilsa fish, of which the catches contribute to 10% of the total earnings of the fishery sector (1% of GDP), are affected by climate-forced hydrological and productivity changes in the Meghna; (ii) extreme droughts and short-term severe precipitation have driven the long-term abundance and spatial distribution of both fish larvae and juveniles/adults in the Mondego; and (iii) the river inflow and fluctuations increases since the early 1970s have contributed to variations in the salinity, the stratification, the oxygen, nutrient and trophic levels and the spatial pattern for the life stages of planktonic species, fish biomass and captures in the Rio de la Plata. The results suggested that immediate action is needed to reduce the vulnerability of estuaries to climate stressors, mainly the changing river flows, storms and sea-level rise. As a contribution to addressing current problems, we described a set of adaptation strategies to foster climate resilience and adaptive capacity (e.g., early-warning systems, dam management to prevent overflows and adaptive fisheries management). The implications of this paper are two-fold. Firstly, it showcases a variety of problems that estuaries face from changing climate conditions. Secondly, the paper outlines the need for suitable adaptive management strategies to safeguard the integrity of such vital ecosystems.


The development of co-representation effects in a joint task: do children represent a co-actor?
When two adults jointly perform a task, they often show interference effects whereby the other's task interferes with their own performance (Sebanz, Knoblich, & Prinz, 2003). The current study investigated whether these co-representation effects can be observed in young children. This phenomenon can be used as a criterion for adult-like joint action in children, which has been under debate in existing literature due to the difficulty in identifying what mechanisms underlie the behaviours observed (Brownell, 2011). In Experiment 1, two children performed an adapted Bear Dragon task (Kochanska, Murray, Jacques, Koenig, & Vandegeest, 1996), where children were required to point to a picture when instructed to do so by one puppet and to inhibit pointing when instructed to by the other. In the Same Task condition, both children in a pair were asked to respond to the same puppet, whereas in the Different Task condition, they were asked to respond to different puppets. Children made more errors in the Different Task condition than the Same Task, suggesting that they were experiencing interference from their partner's task rule. In Experiment 2 children in Different and Same task conditions began with the same task as in Experiment 1 and then switched which puppet to respond to. Switch costs were lower in the Different task condition, consistent with children having already represented the alternative task rule on behalf of their partner during the pre-switch phase. Experiment 3 replicated the effect of Task in a novel computer-based paradigm with children between 4 and 5years, but not younger. These data provide the first direct evidence that children as young as 4years co-represent a partner's task during a joint activity, and that younger children may not be capable of co-representation.


Exercise training in solid organ transplant recipients: a systematic review and meta-analysis.
Exercise training is effective in improving the cardiovascular risk profiles of nontransplanted patients, but the health benefits and potential harms of routine exercise training after solid organ transplantation are unclear. This study aims to assess the health benefits and harms of supervised exercise training programs in solid organ recipients. We systematically reviewed all randomized controlled trials (RCTs) comparing the outcomes of exercise training programs in solid organ recipients against standard care. MEDLINE, EMBASE, the Transplant Library from the Centre for Evidence in Transplantation, and the Cochrane Central Register of Controlled Trials were searched to June 2012. In total, 15 eligible RCTs involving 643 patients (9 cardiac transplants [n=250 patients], 2 kidney transplants [n=164 patients], 3 lung transplants [n=110 patients], and 1 liver transplant [n=119 patients]) were included. Cardiac transplant recipients who engaged in an exercise program after transplantation showed significant improvement in maximal oxygen uptake (standardized mean difference, 0.77; 95% confidence interval, 0.10-1.45) but no improvement in the overall serum lipid profile, blood pressure, and glycemic control compared with standard care. Among other solid organ transplant recipients, no significant improvements in exercise capacity or cardiovascular risk factors such as incidence of new-onset diabetes after transplantation were observed, but all effect estimates were very imprecise. Exercise training is a promising but unproven intervention for improving the cardiovascular outcomes of solid organ transplant recipients. Existing trials are small, of relatively short duration, and focused on surrogate outcomes. Large-scale RCTs are urgently required if resources are to be directed toward exercise programs.


Screening and case finding tools for the detection of dementia. Part I: evidence-based meta-analysis of multidomain tests.
To evaluate the diagnostic accuracy of all brief multidomain alternatives to the Mini-Mental State Examination (MMSE) in the detection of dementia. A literature search, critical appraisal, and meta-analysis were conducted of robust diagnostic validity studies involving cognitive batteries. Twenty-nine distinct brief batteries were tested in 44 large-scale analyses. Twenty studies took place in specialist settings (11 in memory clinics and 9 in secondary care), ten studies were conducted in primary care, and 14 in the community. In community settings with a low prevalence of dementia, short screening methods of no more than 10 minutes had an overall sensitivity of 72.0% (95% confidence interval [CI] = 60.4%-82.3%) and a specificity of 88.2% (95% CI = 83.0%-92.5%). The optimal individual tests were the Telephonic interview based on MSQ, Category fluency/Memory impairment screen-Telephonic interview and 6 item Cognitive Impairment Test (6-CIT), but data were limited by the absence of multiple independent confirmation for any individual test. In primary care where the prevalence of dementia is usually modest, the optimal individual tools were the Abbreviated mental test score/Mental status questionnaire (MSQ), and Prueba cognitive de leganes (PCL). Furthermore, the Abbreviated mental test score (AMTS) was superior to the MMSE for case finding, but for screening the MMSE was optimal. If length is not a major consideration, the MMSE may remain the best tool for primary care clinicians who want to rule in and rule out a diagnosis. In specialist settings where the prevalence of dementia is often high, the optimal individual tools were the DEMTECT, Montreal cognitive assessment (MOCA), Memory Alteration test, and MINI-COG. Two tools were potentially superior to the MMSE for rule in and rule out, namely the 6-CIT and MINI-COG. Only four analyses looked specifically at accuracy in early-stage dementia, and each showed at least equivalent diagnostic accuracy, suggesting these methods might be applicable to early identification. A large number of alternatives to the MMSE have now been validated in large samples with favorable rule-in and rule-out accuracy. Evidence to date suggests for those wishing to use brief battery tests then the original MMSE or the AMTS should be considered in primary care and either the 6-CIT or the MINI-COG should be considered in specialist settings.


Rural-Urban Differences: Using Finer Geographic Classifications to Reevaluate Distance and Choice of Health Services in Malawi.
There is no universal understanding of what defines urban or rural areas nor criteria for differentiating within these. When assessing access to health services, traditional urban-rural dichotomies may mask substantial variation. We use geospatial methods to link household data from the 2015-2016 Malawi Demographic Health Survey to health facility data from the Malawi Service Provision Assessment and apply a new proposed four-category classification of geographic area (urban major metropolitan area, urban township, rural, and remote) to evaluate households' distance to, and choice of, primary, secondary, and tertiary health care in Malawi. Applying this new four-category definition, approximately 3.8 million rural- and urban-defined individuals would be reclassified into new groups, nearly a quarter of Malawi's 2015 population. There were substantial differences in distance to the nearest facility using this new categorization: remote households are (on average) an additional 5 km away from secondary and tertiary care services versus rural households. Health service choice differs also, particularly in urban areas, a distinction that is lost when using a simple binary classification: those living in major metropolitan households have a choice of five facilities offering comprehensive primary care services within a 10-km zone, whereas urban township households have no choice, with only one such facility within 10 km. Future research should explore how such expanded classifications can be standardized and used to strengthen public health and demographic research.


Harnessing the power of radionuclides for optical imaging: Cerenkov luminescence imaging.
Over the past several years, nuclear imaging modalities such as PET and SPECT have received much attention because they have been instrumental not only in preclinical cancer research but also in nuclear medicine. Yet nuclear imaging is limited by high instrumentation cost and subsequently low availability to basic researchers. Cerenkov radiation, a relativistic physical phenomenon that was discovered 70 years ago, has recently become an intriguing subject of study in molecular imaging because of its potential in augmenting nuclear imaging, particularly in preclinical small-animal studies. The intrinsic capability of radionuclides emitting luminescent light from decay is promising because of the possibility of bridging nuclear imaging with optical imaging-a modality that is much less expensive, is easier to use, and has higher throughput than its nuclear counterpart. Thus, with the maturation of this novel imaging technology using Cerenkov radiation, which is termed Cerenkov luminescence imaging, it is foreseeable that advances in both nuclear imaging and preclinical research involving radioisotopes will be significantly accelerated in the near future.


Tryptophan depletion impairs memory consolidation but improves focussed attention in healthy young volunteers.
Animal and human studies have provided evidence for serotonergic modulation of cognitive processes. However, the exact nature of this relationship is not clear. We used the acute tryptophan depletion (ATD) method to investigate the effects of lowered serotonin synthesis on cognitive functions in 17 healthy young volunteers. The study was conducted according to a placebo-controlled, double-blind, crossover design. Cognitive performance and mood were assessed at baseline and 5 and 9 h after administration of ATD. A specific impairment of word recognition, without effects on short-term memory, occurred during ATD. No memory deficits were seen if ATD was induced after acquisition of new words. The Stroop Test and dichotic listening task demonstrated a modality independent improvement of focussed attention after ATD. Fluency was also improved after ATD. ATD did not alter speed of information processing, divided attention or planning functions. These results indicate that serotonin is essential in the process of long-term memory consolidation, primarily in the first 30 min after acquisition. Improvement of specific cognitive processes by lowered 5-HT function may be linked to the removal of inhibitory actions of 5-HT in the cortex.


Assessment of an innovative seat belt with independent control of the shoulder and lap portions using THOR tests, the THUMS model, and PMHS tests.
The objective of this study was to determine the potential chest injury benefits and influence on occupant kinematics of a belt system with independent control of the shoulder and lap portions. This article investigates the kinematics and dynamics of human surrogates in 35 km/h impacts with 2 different restraints: a pretensioning (PT), force-limiting (FL) seat belt, a reference belt system, and a concept design with a split buckle consisting (SB) of 2 separate shoulder and lap belt bands. The study combines mathematical simulations with the THOR dummy and THUMS human body model, and mechanical tests with the THOR dummy and 2 postmortem human surrogate (PMHS) tests of similar age (39 and 42 years) and anthropometry (62 kg, 181 cm vs. 60 kg, 171.5 cm). The test setup consisted of a rigid metallic frame representing a standard seating position of a right front passenger. The THOR dummy model predictions were compared to the mechanical THOR dummy test results. The THUMS-predicted number of fractured ribs were compared to the number of fractured ribs in the PMHS. THOR sled tests showed that the SB seat belt system decreased chest deflection significantly without increasing the forward displacement of the head. The THOR model and the THOR physical dummy predicted a 13- and 7-mm reduction in peak chest deflection, respectively. Peak diagonal belt force in the mechanical test with the reference belt was 5,582 N and the predicted force was 4,770 N. The THOR model also predicted lower belt forces with the SB system than observed in the tests (5,606 vs. 6,085 N). THUMS predicted somewhat increased head displacement for the SB system compared to the reference system. Peak diagonal force with the reference belt was 4,000 N and for the SB system it was 5,200 N. The PMHS test with the SB belt resulted in improved kinematics and a smaller number of rib fractures (2 vs. 5 fractures) compared to the reference belt. Concepts for a belt system that can reduce the load on the chest of the occupant in a crash and thereby reduce the number of injured occupants, in particular the elderly, was proposed.


Consistency of handwriting in early elementary students.
The purpose of this longitudinal study was to examine the consistency of handwriting in children from the beginning of kindergarten to the middle of the first-grade year. Consistency was defined as retaining the same qualitative performance and relative ranking over time. Ninety-three children were tested at the beginning of the kindergarten year and again in the middle of the first-grade year on the Scale of Children's Readiness In PrinTing (SCRIPT). Data were analyzed with a repeated measures analysis of variance (ANOVA) (3 performance groups [lower, middle, upper] x 2 grades) followed by a Tukey's HSD post hoc analysis. An analysis of the change in performance of individual children also was conducted. The main effects and the interaction in the ANOVA were significant. Post hoc analysis for grade demonstrated that both the middle and the lower performing groups showed a significant improvement from kindergarten to first grade, whereas the upper performing group remained unchanged. Post hoc analysis found significant differences among all three performance groups in kindergarten. In first grade, the lower performing group continued to score significantly lower than the middle and upper performing groups, whereas the middle and upper performing groups were not significantly different. Analysis of individual data revealed that 60% of the students were consistent in their performance from kindergarten to first grade. The correlation between kindergarten SCRIPT scores and first-grade SCRIPT scores provides initial evidence that a moderately consistent pattern of handwriting performance exists. Students with low- and middle-ranked handwriting skills show relatively similar improvement over time, whereas change for students ranked high is limited.


Can healthcare providers obtain judicial intervention against surrogates who demand "medically inappropriate" life support for incompetent patients?
This article analyzes, from a legal perspective, a recent phenomenon involving a clash between the values of attending medical personnel and the instructions of surrogate decision-makers acting on behalf of incompetent patients. Some hospitals have gone to court to challenge decisions by surrogates to continue life support for permanently unconscious or other gravely debilitated patients. Their claim has been that continuation of life support would be medically inappropriate and that the surrogates' decisions ought to be overridden. These petitions have thus far been rejected. The objective here is to explain those decisions and to predict the outcome of future, similar litigation. The primary data are the judicial decisions and legislation accumulated since the Quinlan case in 1976, regarding the medical handling of dying medical patients. Judicial rejection of healthcare providers' claims in the decided cases is explainable under traditional guardianship principles. The explanation lies in surrogates' authority to make decisions in the best interests of incompetent patients, and in judicial reluctance to brand life preservation of nonsuffering patients as abusive or contrary to patient interests. At the same time, the author anticipates a change in judicial posture, as courts acknowledge the widespread antipathy of people toward being indefinitely preserved in a noncognitive status. Because the judicial approach to the handling of dying persons often seeks to replicate what the patient would have wanted, there is room to consider consensus preferences where the particular patients has never indicated any deviation from those preferences. Courts will eventually override surrogate decisions that do not conform to widely shared preferences for avoiding the indignity of permanent unconsciousness or other gravely debilitated states.


Association of breakfast, total diet quality, and mental health in adolescents: a cross-sectional study of HBSC in Greece.
The emerging field of nutritional psychiatry offers proof that diet quality can be changed to reduce one's risk of developing mental illness. What you eat has a big impact on teenage mental health, and the quality and frequency of breakfast, as well as the different food groups, can affect adolescent mental health. In this study, regression models were employed to analyze four indicators (self-rated health, body satisfaction, life satisfaction, and eight symptoms) of mental health problems as well as demographic factors (gender, age, body mass index, affluence class, physical activity), with forest plots displaying the regression connections. This study, a descriptive cross-sectional survey of 3480 adolescents aged 11 to 15 years, chosen data from the 2018 Greek Health Behaviour in School-aged Children (HBSC) International Study for secondary analysis. The data revealed that high levels of four indicators of mental health (self-rated health, body satisfaction, life satisfaction, and eight symptoms) were significantly related to breakfast quality, total dietary patterns. Students reporting poor total food quality, for example, were more predictive of self-assessment when unhealthy (2.286 95% CI 1.851-2.824), and the largest connections with eating a "bad" breakfast were discovered when the eight symptoms of mental status were the worst (- 0.869 95% CI: - 1.300, - 0.439); physical activity may enhance the positive relationship of diet quality on mental health, while obesity weakens this positive relationship; and age patterns varied by gender, with girls and older individuals showing a higher risk of diet quality and mental health. Conclusions: The findings revealed that each of the four indices of general mental health was correlated with teenage breakfast and overall diet quality. Physical activity and weight were shown to be moderating factors, and obesity had the biggest impact on psychological risk. Gender, age, and family economic inequality were potential explanations for the rise in psychological symptoms. Researchers are urged to focus more on nutritional psychiatry research and look into psychological perception disparities in the future. What is Known: • There is a potential correlation between adolescent dietary patterns or quality and mental health. • Factors such as age, gender, socio-economic status, body weight and physical activity all have an impact on diet and mental health outcomes. What is New: • There have been no studies of the ability to simultaneously predict breakfast quality and overall diet quality for broadly defined mental health complaints [positive (life satisfaction), neutral (body satisfaction, self-rated health) and negative (eight symptoms: depressed mood, irritability, nervousness, difficulty sleeping, dizziness, headache, stomachache and backache)]. • Differences in overall diet quality trends between demographic subgroups remain unclear.


Does Implicit Racial Bias Affect Auditory-Perceptual Evaluations of Dysphonic Voices?
The purpose of this study was to understand the role of implicit racial bias in auditory-perceptual evaluations of dysphonic voices by determining if a biasing effect exists for novice listeners in their auditory-perceptual ratings of Black and White speakers. Thirty speech-language pathology graduate students at Boston University listened to audio files of 20 Black speakers and 20 White speakers of General American English with voice disorders. Listeners rated the overall severity of dysphonia of each voice heard using a 100-unit visual analog scale and completed the Harvard Implicit Association Test (IAT) to measure their implicit racial bias. Both Black and White speakers were rated as less severely dysphonic when their race was labeled as Black. No significant relationship was found between Harvard IAT scores and differences in severity ratings by race labeling condition. These findings suggest a minimizing bias in the evaluation of dysphonia for Black patients with voice disorders. These results contribute to the understanding of how a patient's race may impact their visit with a clinician. Further research is needed to determine the most effective interventions for implicit bias retraining and the additional ways that implicit racial bias impacts comprehensive voice evaluations.


SMT19969 for Clostridium difficile infection (CDI): in vivo efficacy compared with fidaxomicin and vancomycin in the hamster model of CDI.
SMT19969 is a novel narrow-spectrum antimicrobial under development for the treatment of Clostridium difficile infection (CDI). The objectives were to assess the relative efficacies of SMT19969, vancomycin and fidaxomicin in the hamster model of CDI. Hamsters were infected with either C. difficile BI1 (ribotype 027) or C. difficile 630 (ribotype 012) prior to treatment with vehicle, SMT19969, fidaxomicin or vancomycin for 5 days. Animals were further monitored through to day 28 and survival recorded. Plasma and gastrointestinal concentrations of SMT19969 following single and repeat administration in infected hamsters were determined. Following infection with C. difficile BI1, treatment with SMT19969, vancomycin and fidaxomicin resulted in 100% survival during the 5 day dosing period, with 90%-100% of animals receiving SMT19969 and fidaxomicin surviving during the post-dosing follow-up period. Whilst protective during treatment, onset of mortality was observed on day 11 in animals treated with vancomycin, with a 10% survival recorded by day 28. Similar results were observed for SMT19969 and vancomycin following infection with C. difficile 630, with day 28 survival rates of 80%-100% and 0%, respectively. Fidaxomicin protected animals infected with C. difficile 630 from mortality during dosing, although day 28 survival rates varied from 0% to 40% depending on dose. Plasma levels of SMT19969 were typically below the limit of quantification, but levels in the gastrointestinal tract remained far in excess of the MIC. These data show that SMT19969 is highly effective at treating both acute infection and preventing recurrent disease and support continued investigation of SMT19969 as a potential therapy for CDI.


Genetic testing in motor neuron disease and frontotemporal dementia: a 5-year multicentre evaluation.
Motor neuron disease (MND) and frontotemporal dementia (FTD) comprise a neurodegenerative disease spectrum. Genetic testing and counselling is complex in MND/FTD owing to incomplete penetrance, variable phenotype and variants of uncertain significance. Affected patients and unaffected relatives are commonly referred to clinical genetics to consider genetic testing. However, no consensus exists regarding how such genetic testing should best be undertaken and on which patients. We sought to ascertain UK clinical genetics testing practice in MND/FTD referrals, with the aim of helping inform guideline development. MND/FTD clinical genetics referrals comprising both affected patients and unaffected relatives between 2012 and 2016 were identified and a standardised proforma used to collate data from clinical records. 301 referrals (70 affected, 231 unaffected) were reviewed across 10 genetics centres. Previously identified familial variants were known in 107 cases and 58% subsequently underwent testing (8 of 8 diagnostic and 54 of 99 predictive). The median number of genetic counselling appointments was 2 for diagnostic and 4 for predictive testing. Importantly, application of current UK Genomic Test Directory eligibility criteria would not have resulted in detection of all pathogenic variants observed in this cohort. We propose pragmatic MND/FTD genetic testing guidelines based on appropriate genetic counselling.


Electronic Circular Dichroism Imaging (ECDi) Casts a New Light on the Origin of Solid-State Chiroptical Properties.
Solid-state ECD (ss-ECD) spectra of a model microcrystalline solid, finasteride, dispersed into a KCl pellet were recorded by using the synchrotron radiation source at the Diamond B23 beamline. Scanning a surface of 36 mm2 with a step of 0.5 mm, we measured a set of ECD imaging (ECDi) spectra very different from each other and from the ss-ECD recorded with a bench-top instrument (1 cm2 area). This is due to the anisotropic part of the ECD (ACD), which averages to zero in solution or on a large number of randomly oriented crystallites, but can otherwise be extremely large. Two-way singular value decomposition (SVD) analysis, through experimental and simulated TDDFT spectra, disclosed that the measured and theoretical principal components are in line with each other. This finding demonstrates that the observed isotropic ss-ECD spectrum is governed by the anisotropy of locally oriented crystals. It also introduces a new quality for ss-ECD measurements and opens a new future for probing and mapping chiral materials in the solid state such as active pharmaceutical ingredients (APIs).


Incidence of Omicron Variant Reinfection and Reduction of Reinfection Risk After Coronavirus Disease 2019 Vaccination in Children.
Data are limited on the incidence of coronavirus disease 2019 (COVID-19) reinfection in children. This population-based cohort study in Niigata, Japan from January to November 2022 demonstrated the incidence of reinfection was 1337/48 099 (2.8%), and the hazard ratio for reinfection in vaccinated children was 0.29 (95% confidence interval, 0.20-0.40).


Comparing the influence of big data resources on medical knowledge recall for staff with and without medical collaboration platform.
This study aims to examine how big data resources affect the recall of prior medical knowledge by healthcare professionals, and how this differs in environments with and without remote consultation platforms. This study investigated two distinct categories of medical institutions, namely 132 medical institutions with platforms, and 176 medical institutions without the platforms. Big data resources are categorized into two levels-medical institutional level and public level-and three types, namely data, technology, and services. The data are analyzed using SmartPLS2. (1) In both scenarios, shared big data resources at the public level have a significant direct impact on the recall of prior medical knowledge. However, there is a significant difference in the direct impact of big data resources at the institutional level in both scenarios. (2) In institutions with platforms, for the three big data resources (the medical big data assets and big data deployment technical capacity at the medical institutional level, and policies of medical big data at the public level) without direct impacts, there exist three indirect pathways. (3) In institutions without platforms, for the two big data resources (the service capability and big data technical capacity at the medical institutional level) without direct impacts, there exist three indirect pathways. The different interactions between big data, technology, and services, as well as between different levels of big data resources, affect the way clinical doctors recall relevant medical knowledge. These interaction patterns vary between institutions with and without platforms. This study provides a reference for governments and institutions to design big data environments for improving clinical capabilities.


Effects of recombinant granulocyte colony-stimulating factor treatment on hematopoietic cycles and cellular defects associated with canine cyclic hematopoiesis.
Canine cyclic hematopoiesis (CH) is an autosomal recessive disease of gray collie dogs that is characterized by 14-day cycles of neutropenia, monocytosis, thrombocytosis, and reticulocytosis. Platelets from CH dogs have decreased dense-granule serotonin pools and decreased aggregation responses to collagen, platelet-activating factor (PAF), and thrombin. Recombinant granulocyte colony-stimulating factor (rG-CSF) was administered (5 micrograms/kg, b.i.d.) to four CH and six normal dogs to determine if G-CSF therapy corrected qualitative platelet defects in CH dogs. Neutrophil counts increase to greater than 25,000 cells/microliters within 24 h after starting treatment in all dogs. Treatment with G-CSF blocked neutropenic episodes in the CH dogs. Platelet aggregation, and serotonin content and secretion were significantly (p less than 0.05) decreased in the CH dogs both before and during recombinant human (rh) G-CSF treatment compared to normal dogs. Neutrophil myeloperoxidase, a primary granule enzyme, was significantly (p less than 0.05) decreased in CH dogs and was not corrected by rhG-CSF treatment. Administration of rG-CSF to CH dogs eliminated cell cycles but apparently did not correct cellular defects in CH dogs. Identification of primary biochemical defects in cells from CH dogs may be crucial to investigating the biochemical basis for cyclic hematopoiesis.


Leukotriene synthesis inhibition and receptor blockade do not inhibit hypoxic pulmonary vasoconstriction in sheep.
Several lines of evidence suggest that leukotrienes may be mediators of hypoxic pulmonary vasoconstriction (HPV). However, the effect of leukotriene inhibition on HPV remains controversial. The present study investigated the effect of leukotriene synthesis inhibition and receptor blockade on HPV in the halothane-anesthetized sheep. After initial baseline measurements, the pulmonary pressor response to 15 min of global hypoxia (FIO2 = 0.13) was measured. A second set of baseline measurements was obtained and the sheep then received the combined cyclooxygenase/lipoxygenase inhibitor BW755C, the selective lipoxygenase inhibitor U60257, or the leukotriene receptor antagonist LY171883. Hemodynamic measurements were obtained after drug administration and during a subsequent hypoxic challenge (FIO2 = 0.13). Initial hypoxic challenge increased pulmonary artery pressure 68% and increased pulmonary vascular resistance 104%. Pulmonary hemodynamics after recovery from hypoxia were similar to initial baseline values. Drug administration had no significant hemodynamic effect. Hypoxic challenge after drug administration resulted in a pulmonary pressor response identical to the initial hypoxic challenge. Because leukotriene synthesis inhibition and receptor blockade did not alter the response to hypoxia, we conclude that leukotrienes are not obligatory mediators of HPV. A critical review of the literature supports a modulatory rather than an obligatory role for leukotrienes in HPV.


The safe use of automated external defibrillators in a wet environment.
There has been concern regarding potential shock hazards for rescuers or bystanders when a defibrillator is used in a wet environment and the recommended safety procedure, moving the patient to a dry area, is not followed. To measure the electrical potentials associated with the use of an automated external defibrillator (AED) in a realistically modeled wet environment. A raw processed turkey was used as a patient surrogate. The turkey was placed on a cement floor while pool water was applied to the surrounding area. To simulate a rescuer or bystander in the vicinity of a patient, a custom sense probe was constructed. Defibrillation shocks were delivered to the turkey and the probe was used to measure the voltage an operator/bystander would receive at different points surrounding the surrogate. The test was repeated with salt water. The maximum voltage occurred approximately 15 cm from the simulated patient and measured 14 V peak (current 14 mA peak) in the case of pool water, and 30 V peak (current 30 mA peak) in the case of salt water. Thirty volts may result in some minor sensation by the operator or bystander, but is considered unlikely to be hazardous under these circumstances. The maximum currents were lower than allowed by safety standards. Although defibrillation in a wet environment is not recommended practice, our simulation of a patient and a rescuer/bystander in a wet environment did not show significant risk should circumstances demand it.


Inhaled ketotifen in exercise-induced asthma--a negative report.
The effects of 2 concentrations of inhaled ketotifen (0.25 g/l and 0.5 g/l) were compared with saline in 7 extrinsic asthmatics with exercise induced asthma (EIA). Inhaled ketotifen produced bronchodilatation with a significant increase of 15.4% on mean baseline FEV1 at the higher concentration (p less than 0.05). After exercise the mean percentage fall in FEV1 was 38.4% in the saline group, with no significant difference in the ketotifen pretreated groups, although 2 patients did not have EIA after inhalation of either ketotifen concentrations.


Predictive performance of urine neutrophil gelatinase-associated lipocalin for dialysis requirement and death following cardiac surgery in neonates and infants.
Urine neutrophil gelatinase-associated lipocalin (uNGAL) has been shown to accurately predict and allow early detection of AKI, as assessed by an increase in serum creatinine in children and adults. The present study explores the accuracy of uNGAL for the prediction of severe AKI-related outcomes in neonates and infants undergoing cardiac surgery: dialysis requirement and/or death within 30 days. Prospective, observational cohort study conducted in a tertiary referral pediatric cardiac intensive care unit, including 75 neonates and 125 infants undergoing surgery with cardiopulmonary bypass between August 1, 2010, and May 31, 2011. Urine samples were collected before surgery and at median of five time points within 48 hours of bypass. Urine NGAL was quantified as absolute concentration, creatinine-normalized concentration, and absolute excretion rate, and a clusterization algorithm was applied to the individual uNGAL kinetics. The accuracy for the prediction of the outcome was assessed using receiver-operating characteristic areas, likelihood ratios, diagnostic odds ratios, net reclassification index, integrated reclassification improvement, and number needed to screen. A total of 1176 urine samples were collected. Of all patients, 8% required dialysis and 4% died. Three clusters of uNGAL kinetics were identified, including patients with significantly different outcomes. The uNGAL level peaked between 1 and 3 hours of bypass and remained high in half of all patients who required dialysis or died. The uNGAL levels measured within 24 hours of bypass accurately predicted the outcome and performed best after normalization to creatinine, with varying cutoffs according to the time elapsed since bypass. The number needed to screen to correctly identify the risk of dialysis or death in one patient varied between 1.5 and 2.6 within 12 hours of bypass. uNGAL is a valuable predictive tool of dialysis requirement and death in neonates and infants with AKI after cardiac surgery.


Growth rate and behaviour in separated, partially separated or non-separated kids and the corresponding milk production of their mothers.
We address the hypothesis that keeping kids and mothers together would have positive effects on the milk composition of the mother and the behaviour of the kids. Kids were either permanently separated (SEP), daily separated between 7.30 and 15 h (DAY-SEP) or kept with mothers 24 h/d (NON-SEP). The NON-SEP kids were only allowed to suckle one teat. All kids had similar growth rate throughout the study (lactation days 5-70). DAY-SEP kids spent 24% of their time with their mother at both ages. NON-SEP spent only 15% of the time with their mothers at 2 weeks of age and this increased to 28% at 2 months of age. NON-SEP kids showed more hiding behaviour at 2 weeks and SEP were more active alone, at both 2 weeks and 2 months, compared to the other treatments. The mean available milk yield and fat concentration were higher in DAY-SEP goats (2420 g ± 119 g and 4.9 ± 0.1%) compared with NON-SEP goats (2149 ± 79 g and 4.4 ± 0.1%). There were no differences between DAY-SEP and NON-SEP goats in total protein, lactose, or casein concentrations. Based on these data it was estimated that 7.1 kg milk was needed to produce 1 kg semi-hard cheese in DAY-SEP goats and 7.5 kg in NON-SEP goats, respectively. When comparing milk yield and composition between udder halves, the milk yield was, as expected, higher from the machine milked teat than from the suckled one in the NON-SEP goats but there was no difference between right and left udder halves in DAY-SEP goats. Milk fat concentration varied between teats at morning and afternoon milkings in NON-SEP goats, but there was no difference in milk fat between udder-halves in DAY-SEP goats. In conclusion, the kid growth rate was similar in all treatments, however, an altered behaviour was seen in permanently separated kids (SEP). The results show that it is possible to have a high milk yield and fat concentration with one kid together with the dam.


Colonization with Enterobacteriaceae producing ESBLs in children attending pre-school childcare facilities in the Lao People's Democratic Republic.
Intestinal carriage constitutes an important reservoir of antimicrobial-resistant bacteria, with some of the highest rates reported from Asia. Antibiotic resistance has been little studied in Laos, where some antibiotics are available without restriction, but others such as carbapenems are not available. We collected stools from 397 healthy children in 12 randomly selected pre-school childcare facilities in and around Vientiane. Colonization with ESBL-producing Enterobacteriaceae (ESBLE) and carbapenemase-producing Enterobacteriaceae (CPE) was detected using a disc diffusion screening test and ESBLE were characterized using WGS. Risk factor data were collected by questionnaire. Ninety-two children (23%) were colonized with ESBLE, mainly Escherichia coli carrying blaCTX-M and Klebsiella pneumoniae carrying blaSHV or blaCTX-M, which were frequently resistant to multiple antibiotic classes. Although residence in Vientiane Capital, foreign travel, higher maternal level of education, antibiotic use in the preceding 3 months and attending a childcare facility with a 'good' level of hygiene were all associated with ESBLE colonization on univariable analysis, a significant association remained only for antibiotic use when a stepwise approach was used with a multivariate random-effects model. WGS analysis suggested transmission in both childcare facilities and community settings. The high prevalence of paediatric colonization with ESBLE in Laos, one of the highest reported in Asia, is probably the result of inappropriate antibiotic use. Paediatric colonization with CPE was not identified in this study, but it is important to continue to monitor the spread of antibiotic-resistant Enterobacteriaceae in Laos.


Naked oats: metabolisable energy yield from a range of varieties in broilers, cockerels and turkeys.
1. Naked oats belong to the same species as 'common oats', Avena sativa, but have a non-lignified husk which readily becomes detached during harvesting. The absence of the indigestible husk can be predicted to give an increased metabolisable energy (ME) content for poultry. 2. Measurements of true metabolisable energy (TME(N)) were performed on 3-week-old broiler chicks (Cobb males), adult cockerels (ISA Brown, greater than one year old) and 7-week-old turkeys (BUT T8 males). The measurements were repeated in 2000, 2001 and 2002, with some measurements on a subset of varieties in 2004. 3. High-oil naked oat lines yielded 12% more energy (TME(N)) than wheat. Naked oats, excluding the experimental high-oil lines, yielded 8.5% more energy than simultaneously assayed wheat samples. 4. In samples from the 2004 harvest, conventional oats gave TME(N) values about 13% lower than those of wheat. 5. The addition of beta-glucanase produced an increase of about 4% in the apparent metabolisable energy (AME) of oats for broiler chickens. This effect was associated with a 70% decrease in the jejunal viscosity of broilers receiving a 500 g/kg naked-oat diet. 6. The oil content of naked oats was about 5 times greater than that of wheat, with the high-oil lines rising to more than 6 times greater. Naked oats had a lower starch content than wheat but not sufficiently lower to negate the energy benefits of the higher oil content. The crude protein (CP) contents of naked oats were similar to those of wheat, with the high-oil varieties tending to be higher in CP also.


Black-white differences in the economic value of improving health.
This article examines how differences in longevity over time and across groups add to the typical measures of economic progress and intergroup differentials. We focus on gains for and differences between groups defined both by race (black and white) and by gender, relying on willingness to pay as our measure of the economic value of gains in longevity. Measured at birth, the gains for white males between 1968 and 1998 were about 245,000 dollars per person, while the gains for black males were far larger, about 390,000 dollars per person. The gains for women were somewhat smaller, with white females gaining about 150,000 dollars per person and black females gaining about 305,000 dollars per person. Our estimates suggest that differences in income explain about 1/3 to 1/2 of the current black-white gap in longevity.


Evidence that the bed nucleus of the stria terminalis contributes to the modulation of hypophysiotropic corticotropin-releasing factor cell responses to systemic interleukin-1beta.
Systemic infection activates the hypothalamic-pituitary-adrenal (HPA) axis, and brainstem catecholamine cells have been shown to contribute to this response. However, recent work also suggests an important role for the central amygdala (CeA). Because direct connections between the CeA and the hypothalamic apex of the HPA axis are minimal, the present study investigated whether the bed nucleus of the stria terminalis (BNST) might act as a relay between them. This was done by using an animal model of acute systemic infection involving intravascular delivery of the proinflammatory cytokine interleukin-1beta (IL-1beta, 1 microg/kg). Unilateral ibotenic acid lesions encompassing the ventral BNST significantly reduced both IL-1beta-induced increases in Fos immunoreactivity in corticotropin-releasing factor (CRF) cells of the hypothalamic paraventricular nucleus (PVN) and corresponding increases in adrenocorticotropic hormone (ACTH) secretion. Similar lesions had no effect on CRF cell responses to physical restraint, suggesting that the effects of BNST lesions were not due to a nonspecific effect on stress responses. In further studies, we examined the functional connections between PVN, BNST, and CeA by combining retrograde tracing with mapping of IL-1beta-induced increases in Fos in BNST and CeA cells. In the case of the BNST, these studies showed that systemic IL-1beta administration recruits ventral BNST cells that project directly to the PVN. In the case of the CeA, the results obtained were consistent with an arrangement whereby lateral CeA cells recruited by systemic IL-1beta could regulate the activity of medial CeA cells projecting directly to the BNST. In conclusion, the present findings are consistent with the hypothesis that the BNST acts as a relay between the CeA and PVN, thereby contributing to CeA modulation of hypophysiotropic CRF cell responses to systemic administration of IL-1beta.


Safety and immunogenicity of human rotavirus vaccine strain M37 in adults, children, and infants.
Rotavirus vaccine strain M37 (serotype 1), recovered from the stool of an asymptomatic newborn infant and serially passaged in cell culture, was given orally to adults, children, and infants. Serologic responses were detected by neutralization assay or EIA in 59% of 17 adults (10(5)-pfu dose), 55%-60% of 21 infants and children (10(4)-pfu dose), and 70% of 10 infants (10(5)-pfu dose), vaccine virus was shed by 24%, 20%-36%, and 70%, respectively. In adults, neutralizing antibody rises to strain M37 and the related serotype 1 strain Wa occurred with equal frequency (41% vs. 47%). In pediatric subjects, the former were more frequent (36%-40%) than the latter (10%-18%). This was also true of 8 infants who received two doses of vaccine. Mild gastrointestinal illnesses occurred with equal frequency in pediatric subjects who received vaccine or placebo. Thus, strain M37 was well tolerated and immunogenic in young infants, but elicited primarily vaccine-strain-specific rather than serotype-specific neutralizing antibody responses.


Thyroid Cancer Patients' View of Clinician Professionalism and Multidisciplinary Approach to Their Management.
The objective of this study was to query thyroid cancer patients about 1) both the characteristics of the healthcare facilities where they were treated and the healthcare professionals that provided that treatment, as well as 2) the multidisciplinary approach used in the treatment process. Using a web-based survey, patients were asked to give their opinion of the healthcare centers, the professionalism of their team of specialists, and the thyroid cancer multidisciplinary teams (MDT). For the 485 patients that responded, the most highly rated aspect of healthcare centers was the reduced waiting time between diagnosis and surgical intervention, an opinion expressed by 62.7% of patients. The most appreciated aspect of professionalism was the kindness shown toward patients by healthcare staff (66.6%). About 44.3% of patients were aware of the existence of thyroid cancer MDT. Most of respondents (82.7%) agreed that patients' opinions should be considered by their physicians when making treatment decisions. We conclude that most patients with thyroid cancer appreciate therapeutic efficacy and kindness, and almost all are clearly in favor of using a multidisciplinary approach to their disease. Since such patients often demand to participate in the decision-making process, multidisciplinary teams should make every effort to share information with, and to integrate the opinion of, patients in the management of their thyroid disease.