The effect of psychopathy on cooperative strategies in an iterated Prisoner's Dilemma experiment with emotional feedback.
As decision-making research becomes more popular, the inclusion of personality traits has emerged as a focal point for an exhaustive analysis of human behaviour. In this study, we investigate the impact of psychopathic traits on cooperation in an iterated Prisoner's Dilemma game with emotional facial feedback. Firstly, we observed how receiving a facial feedback after each decision affected players with different psychopathic trait scores, and how being informed about the opponent's identity influenced cooperative behaviour. Secondly, we analysed the strategies adopted by each player, and how these choices were correlated with their psychopathic traits. Although our results showed no effect of different emotional content in the feedback on cooperation, we observed more cooperative behaviours in those players who were told their opponent was another fellow human, compared to those who were told it was a computer. Moreover, fearless dominance had a very small but consistent negative effect on overall cooperation and on the tendency to maintain cooperative behaviours. We also found that players' personality scores affected the strategies they chose to play throughout the game. Hence, our experiment adds complexity to the body of work investigating psychopathic traits and social interactions, considering not only the environment of facial feedback but also the role of deception in experimental games.


Polycythemia vera in a cat with cardiac hypertrophy.
Polycythemia vera, a rare and poorly documented disease in cats, was diagnosed in a 4-year-old domestic shorthair cat admitted because of seizures. The diagnosis was made on the basis of high PCV, normal serum erythropoietin concentration (as determined by bioassay, using rabbit bone marrow cells), and elimination of secondary polycythemia as a diagnosis. Cardiac hypertrophy, which might have been secondary to blood hyperviscosity, also was diagnosed. The cat has been treated by periodic phlebotomy and has been without clinical signs of disease for more than 20 months.


Wound irrigation with tap water.
The study hypothesis was that irrigation with tap water is as efficacious as irrigation with sterile saline in removing bacteria from simple lacerations in preparation for wound closure. The study was conducted in a laboratory rat model previously described in the literature for evaluating wound irrigation techniques. The study used a randomized, blinded crossover design using 10 animals. Two full-thickness skin lacerations were made on each animal and each wound was inoculated with standardized concentrations of a Staphylococcus aureus broth. Wounds were irrigated for 4 minutes with normal saline from a syringe or 4 minutes with tap water from a faucet. Tissue specimens were sampled from each laceration prior to and following irrigation. Bacterial counts per gram of tissue were determined for each specimen and compared pre- and postirrigation. Preirrigation bacterial counts were not significantly different for saline vs tap water specimens. The wounds irrigated with saline had a mean reduction in bacterial count of 54.7% (SD=+/-28%), while the wounds irrigated with tap water had a mean reduction in bacterial count of 80.6% (SD=+/-20%) (p < 0.05, 2-tailed, paired t-test). In this animal model, bacterial decontamination of simple lacerations was not compromised, and was actually improved using tap water irrigation. This is most likely due to the mechanical differences in the types of irrigation. In certain instances, such as with upper-extremity lacerations, tap water irrigation would likely be cheaper and less labor-intensive than irrigation with normal saline from a syringe.


Cancer and the coroner.
There exist few reports concerning cancer presenting in forensic autopsies. This study of 1,300 consecutive forensic autopsies yielded 22 cases of single cancers (1.7%) of multiple primary sites and histologic types. The forensic autopsy affords unique opportunity to study not only diagnosed and treated trauma, disease, and cancer, but the natural evolution of untreated cancer as well. Clinically occult cancer is not uncommon and may eventually present clinically or at autopsy in unusual fashion. Advanced cancer may, sometimes on initial presentation, be responsible for sudden unexpected death. Persons with cancer, even in an advanced state, uncommonly commit suicide. Conversely, those committing suicide ostensibly because of known cancer infrequently prove to have cancer at autopsy. Through these autopsy studies, the forensic pathologist gains information invaluable for statistical, clinical, and medicolegal purposes, truly fulfilling his role of "community pathologist".


Ethnography and family medicine: issues and overview.
Ethnography is a qualitative research model generally associated with anthropology. Ethnographic methods include inductively oriented strategies such as participant observation, structured interviews, and open-ended interviews. Issues in family medicine such as patient compliance, doctor-patient relationships, and patients' subjective experience of illness may be optimally studied with ethnography. Because it is inductive, ethnography is cognitively similar to clinical reasoning. Making use of ethnography provides family physicians with a greater array of research methods compatible with clinical practice.


Characterisation of non-transferrin-bound iron (ferric citrate) uptake by rat hepatocytes in culture.
Under conditions of iron overload plasma transferrin can be fully saturated and the plasma can transport non-transferrin-bound Fe which is rapidly cleared by the liver. Much of this Fe is complexed by citrate. The aim of the present work was to characterise the mechanisms by which Fe-citrate is taken up by hepatocytes using a rat hepatocyte cell culture model. The cells, after one day in culture, were incubated with 59Fe-labelled Fe-citrate for varying time periods, then washed and Fe uptake to the membrane and intracellular compartments of the cell was determined by radioactivity measurements. Maximal rates of internalisation of Fe occurred at a Fe:citrate molar ratio of 1:100 or greater, a pH of approximately 7.4 and an extracellular Ca2+ concentration of 1.0 mM. Fe uptake showed Michaelis-Menten kinetics and was a temperature-dependent process. The K(m) and Vmax for Fe internalisation by the cells at 37 degrees C were approximately 7 microM and 2 nmol/mg DNA/min (25 x 10(6) atoms/cell/min), respectively; and the Arrhenius activation energy was 35 kJ/mol. The transition metals, Zn2+, Co2+ and Ni2+, inhibited Fe uptake when used at 10 and 100 times the concentration of Fe. The rate of Fe internalisation from Fe-citrate was found to be approximately 20 times as great as that from Fe-transferrin with Fe concentrations of 1 and 2.5 microM for both forms of Fe. The rate of Fe uptake by iron-loaded hepatocytes obtained from rats which had been fed carbonyl Fe was not significantly different from that by normal hepatocytes. These experiments show that rat hepatocytes in primary culture have a high capacity to take up non-transferrin-bound Fe in the form of Fe-citrate and that uptake occurs by facilitated diffusion. The iron transport process does not appear to be regulated by cellular Fe levels.


Premigratory expectations and postmigratory mental health symptoms in Vietnamese Amerasians.
To determine the relationship between premigratory expectations for one's future life in the United States and postmigratory symptoms of anxiety and depression in a group of Vietnamese Amerasians. A cohort of 161 Vietnamese Amerasian migrants was assessed prior to departure from Vietnam using the Hopkins Symptom Checklist-25 (HSCL-25), the Vietnamese Depression Scale, and an Expectations Questionnaire. After migration to the United States, subjects were reassessed using the HSCL-25 and the Vietnamese Depression Scale. Premigratory expectations for support from the Vietnamese community in the United States were associated with significantly higher scores on the HSCL-25 Depression scale. Of subjects reassessed in the United States, 20% scored in the clinical range for depression. Like-ethnic community support is critically important in preventing depressive symptoms among Vietnamese Amerasian migrants. Clinicians working with Amerasians should target those with unrealistically high expectations for preventive intervention and should approach Vietnamese community leaders to mobilize support for recently arrived Amerasians.


The Cellular Prion Protein Prevents Copper-Induced Inhibition of P2X(4) Receptors.
Although the physiological function of the cellular prion protein (PrP(C)) remains unknown, several evidences support the notion of its role in copper homeostasis. PrP(C) binds Cu(2+) through a domain composed by four to five repeats of eight amino acids. Previously, we have shown that the perfusion of this domain prevents and reverses the inhibition by Cu(2+) of the adenosine triphosphate (ATP)-evoked currents in the P2X(4) receptor subtype, highlighting a modulatory role for PrP(C) in synaptic transmission through regulation of Cu(2+) levels. Here, we study the effect of full-length PrP(C) in Cu(2+) inhibition of P2X(4) receptor when both are coexpressed. PrP(C) expression does not significantly change the ATP concentration-response curve in oocytes expressing P2X(4) receptors. However, the presence of PrP(C) reduces the inhibition by Cu(2+) of the ATP-elicited currents in these oocytes, confirming our previous observations with the Cu(2+) binding domain. Thus, our observations suggest a role for PrP(C) in modulating synaptic activity through binding of extracellular Cu(2+).


Statins and stroke prevention.
Four randomized trials with a statin and one trial with a fibrate showed a modest but significant absolute reduction in the incidence of stroke in patients with a previous myocardial infarction. The reasons for the positive effect of statins on stroke end-point are unclear since, paradoxically, the link between serum cholesterol level and stroke has never been fully established. Furthermore, the positive results of statins trials were mainly obtained in patients with an average or a low serum cholesterol level. This suggests nonhypolipidemic effects of these drugs, so-called pleiotropic effects, acting on the biologic promoters of plaque instability. Statins have a good overall safety profile with no increase of hemorrhagic stroke and no increase in cancer. They have positive effects in primary prevention of cardiovascular disease in high-risk young as well as elderly populations. Statins reduced stroke incidence in high-risk (mainly CHD, diabetics and hypertensives) population even with a normal baseline blood cholesterol level, which argues for a global cardiovascular risk-based treatment strategy. In patients with prior strokes, statins likely reduce the incidence of cononary events, but it is not yet proven that statins actually reduce the incidence of recurrent strokes in secondary prevention. If current hypotheses are verified by ongoing trials, we may expect between 20 to 30 more stroke events avoided per 1,000 patients treated during 2 years with a lipid-lowering agent, which adds to the 28 stroke events prevented with an antiplatelet agent over the same time period. This would be one of the most significant advances in stroke and vascular dementia prevention since the era of aspirin therapy.


[The awareness of farmers with regard to bovine fascioliasis].
The owners of 54 cattle herds with bovine fasciolosis, as a livestock problem in Switzerland, were surveyed on their farm, on their education and knowledge on Fasciola hepatica. The aim of the survey was to assess the awareness of the farmers concerning this economically important parasitosis. The analysis of the questionnaires revealed that 72.2% of the farmers were unaware of the fasciolosis in their animals. The knowledge of 51 out of 54 (94.4%) respondents was classified as low to moderate, only four farmers (7.4%) had knowledge of control strategies in addition to the parasite cycle. The knowledge on fasciolosis did not correlate with farm data or year of graduation from school for agriculture. Furthermore, the results were compared to the answers of 33 farmers whose animals were not infected with Fasciola hepatica. Of this group of respondents 12.1% believed that their cattle suffered from fasciolosis.


Skin advanced glycation end products glucosepane and methylglyoxal hydroimidazolone are independently associated with long-term microvascular complication progression of type 1 diabetes.
Six skin collagen advanced glycation end products (AGEs) originally measured near to the time of the Diabetes Control and Complications Trial (DCCT) closeout in 1993 may contribute to the "metabolic memory" phenomenon reported in the follow-up Epidemiology of Diabetes Interventions and Complications (EDIC) study. We have now investigated whether the addition of four originally unavailable AGEs (i.e., glucosepane [GSPNE], hydroimidazolones of methylglyoxal [MG-H1] and glyoxal, and carboxyethyl-lysine) improves associations with incident retinopathy, nephropathy, and neuropathy events during 13-17 years after DCCT. The complete 10-AGE panel is associated with three-step Early Treatment of Diabetic Retinopathy Study scale worsening of retinopathy (P ≤ 0.002), independent of either mean DCCT or EDIC study A1C level. GSPNE and fructose-lysine (furosine [FUR]) correlate with retinopathy progression, independently of A1C level. The complete panel also correlates with microalbuminuria (P = 0.008) and FUR with nephropathy independently of A1C level (P ≤ 0.02). Neuropathy correlates with the complete panel despite adjustment for A1C level (P ≤ 0.005). MG-H1 and FUR are dominant, independent of A1C level (P < 0.0001), whereas A1C loses significance after adjustment for the AGEs. Overall, the added set of four AGEs enhances the association of the original panel with progression risk of retinopathy and neuropathy (P < 0.04) but not nephropathy, while GSPNE and MG-H1 emerge as the principal new risk factors. Skin AGEs are robust long-term markers of microvascular disease progression, emphasizing the importance of early and sustained implementation of intensive therapy.


High virologic response rate after second-line boosted protease inhibitor-based antiretroviral therapy regimens in children from a resource limited setting.
Limited data exist for the efficacy of second-line antiretroviral therapy among children in resource limited settings. We assessed the virologic response to protease inhibitor-based ART after failing first-line non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimens. A retrospective chart review was conducted at 8 Thai sites of children who switched to PI -based regimens due to failure of NNRTI -based regimens. Primary endpoints were HIV RNA < 400 copies/ml and CD4 change over 48 weeks. Data from 241 children with median baseline values before starting PI-based regimens of 9.1 years for age, 10% for CD4%, and 4.8 log10 copies/ml for HIV RNA were included; 104 (41%) received a single ritonavir-boosted PI (sbPI) with 2 NRTIs and 137 (59%) received double-boosted PI (dbPI) with/without NRTIs based on physician discretion. SbPI children had higher baseline CD4 (17% vs. 6%, p < 0.001), lower HIV RNA (4.5 vs. 4.9 log10 copies/ml, p < 0.001), and less frequent high grade multi-NRTI resistance (12.4% vs 60.5%, p < 0.001) than the dbPI children. At week 48, 81% had HIV RNA < 400 copies/ml (sbPI 83.1% vs. dbPI 79.8%, p = 0.61) with a median CD4 rise of 9% (+7%vs. + 10%, p < 0.005). However, only 63% had HIV RNA < 50 copies/ml, with better viral suppression seen in sbPI (76.6% vs. 51.4%, p 0.002). Second-line PI therapy was effective for children failing first line NNRTI in a resource-limited setting. DbPI were used in patients with extensive drug resistance due to limited treatment options. Better access to antiretroviral drugs is needed.


Development of Clinical Pharmacy in Switzerland: Involvement of Community Pharmacists in Care for Older Patients.
The role of the community pharmacist in primary care has been undergoing change in Switzerland in parallel to international developments: it has become more clinically and patient oriented. Special services of community pharmacists to older patients taking long-term or multiple medications, discharged from hospitals or experiencing cognitive impairment or disability have been developed. These services require more clinical knowledge and skills from community pharmacists and are based on, for example, 'simple or intermediate medication reviews' focused primarily to improve medication adherence and rational drug use by a patient. Reflecting the new role of community pharmacies, this article describes the current services provided by community pharmacies in Switzerland, e.g., 'polymedication check', 'weekly pill organizer', and 'services for chronic patients', as well as new Swiss educational and reimbursement systems supporting development of these services. In the international context, involvement of community pharmacists in patient-oriented care is growing. This review summarizes positive and negative experiences from implementation of community pharmacy services in Switzerland and provides examples for the development of such services in other countries.


Mediating the effects of drug abuse: the role of Narp in synaptic plasticity.
There has been remarkable progress in deciphering the molecular mechanisms that mediate synaptic plasticity. Advances have stimulated interest in determining whether these plasticity mechanisms also mediate the long-lasting behavioral effects induced by drugs of abuse. The observation that drugs of abuse, such as cocaine or morphine, can elicit robust immediate early gene (IEG) responses similar to those induced by long-term potentiation stimulation has provided important support for this hypothesis. Evidence that repeated administration of cocaine produces alterations in expression and trafficking of AMPA receptors, processes that play a central role in synaptic plasticity, has also bolstered this view. Neuronal activity-regulated pentraxin (Narp), an IEG, has emerged as an attractive candidate to mediate long-term effects of drugs of abuse because it encodes a secreted protein that binds to the extracellular surface of AMPA receptors and regulates their trafficking. In this review we provide background information on Narp and closely related proteins, the neuronal pentraxins, and summarize studies of Narp knockout mice demonstrating that this IEG modulates long-term behavioral responses to drugs of abuse.


Brugada syndrome: insights of ST elevation, arrhythmogenicity, and risk stratification from experimental observations.
Brugada syndrome (BrS), caused by ion channel abnormalities, is characterized by ST segment elevation and negative T waves in the right precordial electrocardiographic (ECG) leads recorded over the right ventricular outflow tract (RVOT). BrS is sensitive to body temperature and can lead to T-wave alternans (TWA), ventricular tachycardia, and sudden death. Recent studies in an isolated canine RVOT model of BrS demonstrated that reversal of the transmural gradient of repolarization caused the ECG characteristics and that major intraepicardial and transmural dispersion of action potentials (APs) initiated phase 2 reentry, premature ventricular activations, and tachyarrhythmias. Hypothermia enhanced the heterogeneity of the AP and promoted the origination of phase 2 reentry in the epicardium of the RVOT, but the prolonged AP duration frequently blocked reentry. Hyperthermia abbreviated the AP and facilitated the maintenance of reentry and tachyarrhythmias. Bradycardia promoted alternans in the phase 2 dome of the AP within the epicardium of the RVOT, resulting in TWA. The above phenomena were localized in the epicardium of the RVOT. Blockade of the transient outward current, I(to), reduced AP heterogeneity and prevented arrhythmias in the BrS model. In addition, epicardial activation delay led to fragmented QRS, a risk marker of prognosis in BrS. Body surface mapping in patients with BrS supported these experimental findings. In conclusion, the AP heterogeneity within the epicardium of the RVOT contributes to the ECG characteristics, temperature sensitivity, TWA, and arrhythmias in BrS, and body surface mapping and fragmented QRS can be effective predictors of risk in patients with BrS.


Polymer Surface Textured with Nanowire Bundles to Repel High-Speed Water Drops.
Water drops impacting windshields of high-speed trains and aircraft as well as blades in steam turbine power generators obliquely and at high speeds are difficult to repel. Impacting drops penetrate the void regions of nanotextured and microtextured superhydrophobic coatings, with this pinning resulting in the loss of drop mobility. In order to repel high-speed water drops, we nanotextured polymer surfaces with nanowire bundles separated from their neighbors by microscale void regions, with the nanowires in a bundle separated from their neighbors by nanoscale void regions. Water drops with speeds below a critical speed rebound completely. Water drops with speeds exceeding a critical speed rebound partially, but residual droplets that begin to be pinned undergo a spontaneous dewetting process and slide off. The natural oscillations of residual droplets drive this dewetting process in the interbundle void regions, resulting in a transition from the sticky Wenzel state to the slippery Cassie state without external stimuli.


A subset of hypersensitive response marker genes, including HSR203J, is the downstream target of a spermine signal transduction pathway in tobacco.
A cellular signal transduction pathway induced by the polyamine, spermine (Spm), and transmitted by mitochondrial dysfunction is proposed in tobacco. In this investigation, we further resolve the pathway by identifying a subset of hypersensitive response (HR) marker genes as downstream components. In a previous report, we identified harpin-induced 1 (HIN1) and two closely related genes as responsive to Spm. Other HR marker genes, HSR203J, HMGR, HSR201, and HSR515, are also Spm-responsive. Induction of these HR marker genes, including HIN1, by Spm was suppressed by pre-treatment with antioxidants, calcium channel blockers, inhibitor of mitochondrial permeability transition pore openings, and blockers of amine oxidase/polyamine oxidase. Such quenching is also observed for Spm-induced activation of two mitogen-activated protein kinases (MAPKs), salicylic acid-induced protein kinase (SIPK), and wound-induced protein kinase (WIPK), and upregulation of the WIPK gene, suggesting that all these components are part of the same signaling pathway. Furthermore, gain-of-function and loss-of-function studies on MAPK cascade members reveal that the expression of Spm-induced HR marker genes varies with respect to involvement of SIPK/WIPK activation.


In Situ Tensile Testing under High-Speed Optical Recording to Determine Hierarchical Damage Kinetics in Polymer Layers of Flax Fibre Elements.
This study aims at better understanding the damage and fracture kinetics in flax fibre elements at both the unitary and bundle scales, using an experimental setup allowing optical observation at high recording rate in the course of tensile loading. Defects and issues from flax unitary fibre extraction are quantitated using polarized light microscopy. Tensile loading is conducted according to a particular setup, adapted to fibres of 10 to 20 µm in diameter and 10 mm in length. Optical recording using a high-speed camera is performed during loading up to the failure at acquisition, with speed ranging from 108,000 to 270,000 frames per second. Crack initiation in polymer layers of fibre elements, propagation as well as damage mechanisms are captured. The results show different failure scenarios depending on the fibre element's nature. In particular, fractured fibres underline either a fully transverse failure propagation or a combination of transverse and longitudinal cracking with different balances. Image recordings with high time resolution of down to 3.7 μs suggest an unstable system and transverse crack speed higher than 4 m/s and a slower propagation for longitudinal crack deviation. Failure propagation monitoring and fracture mechanism studies in individual natural fibre or bundles, using tensile load with optical observation, showed contrasted behaviour and the importance of the structural scale exanimated. This study can help in tailoring the eco-design of flax-based composites, in terms of toughness and mechanical performances, for both replacement of synthetic fibre materials and innovative composites with advanced properties.


Peripheral neuropathy associated with weekly oral 5-fluorouracil, leucovorin and eniluracil.
5-Fluorouracil (5-FU)-associated neurotoxicity is uncommon; symptoms may occur abruptly or more gradually during the course of chemotherapy. Peripheral neuropathy with 5-FU therapy has only rarely been reported. Two patients treated in a phase I trial of oral 5-FU, leucovorin and eniluracil, an inhibitor of dihydropyrimidine dehydrogenase (DPD), developed delayed onset symptoms of unsteady gait and reduced sensation in the legs. Magnetic resonance imaging scans of the brain and neurologic examination did not support a CNS basis for the condition. Electromyograms and nerve conduction studies revealed sensorimotor polyneuropathy. Other common etiologies of peripheral neuropathy were excluded. The neurological condition of these patients stabilized after 5-FU dose reduction and partial resolution gradually occurred when protocol therapy was stopped. Although CNS symptoms may rarely complicate 5-FU therapy, peripheral neuropathy is unexpected. Patients with DPD deficiency treated with conventional doses of 5-FU typically develop acute CNS toxicity shortly after therapy, accompanied by extremely high systemic exposure to 5-FU. Patients with normal 5-FU clearance may also experience CNS toxicity, particularly with high-dose schedules, and both parent drug and its catabolites may be contributory. Since DPD was profoundly inhibited during eniluracil therapy in these two patients, it is likely that 5-FU or its active metabolites were contributing factors to the peripheral neuropathy.


[Effect of xylazine on acetylcholine content of the hippocampal CA1 region in urethane anesthetized rats].
By using acetylcholine selective microelectrode technique, a biphasic effect of xylazine on acetylcholine content of the hippocampal CA1 region in urethane anesthetized rats was observed as evidenced by the fact that small doses of xylazine (2.0 and 6.0 mg.kg-1) significantly increased, while higher dose (10.0 mg.kg-1) decreased the acetylcholine content. Though idazoxan (0.6 mg.kg-1) significantly antagonized the effect of xylazine when used in combination, the acetylcholine content in the hippocampal CA1 region of urethane anesthetized rats was still much lower than that of the control group. In rats whose nucleus locus coeruleus was chemically lesioned, xylazine (2.0 and 6.0 mg.kg-1) significantly decreased the acetylcholine content, and idazoxan (0.6 mg.kg-1), which increased the acetylcholine content in the hippocampal CA1 region when used alone, completely antagonized the effect of xylazine. These results suggest that the biphasic effect of xylazine and the lower than normal acetylcholine content observed when idazoxan was used to antagonize xylazine induced changes in acetylcholine content of the hippocampal CA1 region in urethane anesthetized rats might be related to the effects of xylazine and idazoxan on the central noradrenergic neurotransmitter system.


Improving the management of non-ST elevation acute coronary syndromes: systematic evaluation of a quality improvement programme European QUality Improvement Programme for Acute Coronary Syndrome: the EQUIP-ACS project protocol and design.
Acute coronary syndromes, including myocardial infarction and unstable angina, are important causes of premature mortality, morbidity and hospital admissions. Acute coronary syndromes consume large amounts of health care resources, and have a major negative economic and social impact through days lost at work, support for disability, and coping with the psychological consequences of illness. Several registries have shown that evidence based treatments are under-utilised in this patient population, particularly in high-risk patients. There is evidence that systematic educational programmes can lead to improvement in the management of these patients. Since application of the results of important clinical trials and expert clinical guidelines into clinical practice leads to improved patient care and outcomes, we propose to test a quality improvement programme in a general group of hospitals in Europe. This will be a multi-centre cluster-randomised study in 5 European countries: France, Spain, Poland, Italy and the UK. Thirty eight hospitals will be randomised to receive a quality improvement programme or no quality improvement programme. Centres will enter data for all eligible non-ST segment elevation acute coronary syndrome patients admitted to their hospital for a period of approximately 10 months onto the study database and the sample size is estimated at 2,000-4,000 patients. The primary outcome is a composite of eight measures to assess aggregate potential for improvement in the management and treatment of this patient population (risk stratification, early coronary angiography, anticoagulation, beta-blockers, statins, ACE-inhibitors, clopidogrel as a loading dose and at discharge). After the quality improvement programme, each of the eight measures will be compared between the two groups, correcting for cluster effect. If we can demonstrate important improvements in the quality of patient care as a result of a quality improvement programme, this could lead to a greater acceptance that such programmes should be incorporated into routine health training for health professionals and hospital managers. Clinicaltrials.gov NCT00716430.


First-time parents' experiences of home-based postnatal care in Sweden.
To gain a deeper understanding of first-time parents' experiences of early discharge from hospital after delivery and home-based postnatal care. The study was comprised of focus group interviews, interviews with couples and with fathers. Twenty-one parents participated. healthy women who have given birth to their first child after a normal pregnancy and delivery, the women's partners, healthy and full term babies, Swedish-speaking, discharge from the delivery ward within 24 hours, resident in the Uppsala community, the parents cohabited at the time of the delivery. The material was analysed by qualitative content analysis. Three themes emerged: The family's strategy, which describes the family's expectations of postnatal care and their experiences of the real situation. Some are flexible concerning going home early, and others have decided in advance. Self-reliance and strength, which explores the parents' feelings of security and uncertainty, freedom and independence, and shared responsibility. Breast-feeding is described as the 'main thing', an interactive learning process. Professional support in the home summarizes the parents' experience of the midwife's support at home. While conflicting feelings may be revealed during the first days, the midwife confirms their new roles as parents. The midwife is seen as a support and adviser to the parents. This study shows that parents welcome home-based postnatal care with professional support from midwives. We conclude that this care suits healthy families. We think it will be more important in the future to discriminate between healthy families and those in need of hospital care, than to focus on the moment when they leave the hospital, early or late.


In silico insights into potential gut microbial modulation of NAD+ metabolism and longevity.
Recent evidence has prompted the notion of gut-microbial signatures as an indirect marker of aging and aging-associated decline in humans. However, the underlying host-symbiont molecular interactions contributing to these signatures remain poorly understood. In this study, we address this gap using cheminformatic analyses to elucidate potential gut microbial metabolites that may perturb the longevity-associated NAD+ metabolic network. In silico ADMET, KEGG interaction analysis, molecular docking, molecular dynamics simulation, and molecular mechanics calculation predict a large number of safe and bioavailable microbial metabolites to be direct and/or indirect activators of NAD+-dependent sirtuin proteins. Our simulation results suggest dihydropteroate, phenylpyruvic acid, indole-3-propionic acid, phenyllactic acid, all-trans-retinoic acid, and multiple deoxy-, methyl-, and cyclic nucleotides from intestinal microbiota as the best-performing regulators of NAD+ metabolism. Retracing these molecules to their source microorganisms also suggest commensal Escherichia, Bacteroides, Bifidobacteria, and Lactobacilli to be associated with the highest number of pro-longevity metabolites. These findings from our early-stage study, therefore, provide an informatics-based context for previous evidence in the area and grant novel insights for future clinical investigation intersecting anti-aging drug discovery, probiotics, and gut microbial signatures.


Generation of activated killer (AK) cells by recombinant interleukin 2 (rIL 2) in collaboration with interferon-gamma (IFN-gamma).
Activation of human peripheral blood mononuclear cells (PBMC) by interleukin 2 (IL 2) and the role of interferon-gamma (IFN-gamma) in the IL 2-induced activation were investigated. Activated killer (AK) cells against NK-resistant tumor cell lines were induced in the medium containing recombinant IL 2 (rIL 2) and autologous serum without any other stimulating agents. AK activity was induced by doses of rIL 2 as low as 3 U/ml, and reached a maximum at 10(3) U/ml. Incubation of PBMC with rIL 2 resulted in IFN-gamma production and augmented NK activity after 1 day of culture, and in induction of AK cells and proliferative response after 2 days of culture. These results suggested that endogenous IFN-gamma was required for rIL 2-induction of AK cells and proliferative response. To prove this, PBMC were cultured with rIL 2 and rIFN-gamma or were pretreated with rIFN-gamma before culture with rIL 2. Both rIFN-gamma treatments of PBMC augmented rIL 2-induced AK activity and proliferative response. rIL 2-induced IFN-gamma production was also enhanced by the rIFN-gamma pretreatment of PBMC. The addition of anti-IFN-gamma antibody to rIL 2 cultures abrogated the rIL 2-induced NK augmentation, AK generation, and proliferative response in proportion to the decreased amounts of endogenous IFN-gamma detectable in culture. rIFN-gamma and/or rIL 2 cultures of PBMC increased Tac antigen expression on cell surfaces as measured by flow cytometry. Enhanced Tac expression by rIL 2 was abrogated by adding anti-IFN-gamma antibody. These data indicate that: 1) AK generation and IFN-gamma production are mediated by IL 2, and 2) IFN-gamma production may be required for IL 2 induction of AK cells and proliferative response. These finding are consistent with the hypothesis that AK generation involves a collaboration between IL 2 and IFN-gamma, in which IL 2 stimulates PBMC to produce IFN-gamma, which in turn acts as a differentiation signal that may be involved in the IL 2-initiated AK generation and proliferative response.


CLC Estimator: A Tool for Latent Construct Estimation via Congeneric Approaches in Survey Research.
This article proposes the Shiny app 'CLC Estimator' -Congeneric Latent Construct Estimator- to address the problem of estimating latent unidimensional constructs via congeneric approaches. While congeneric approaches provide more rigorous results than suboptimal parallel-based scoring methods, most statistical packages do not provide easy access to congeneric approaches. To address this issue, the CLC Estimator allows social scientists to use congeneric approaches to estimate latent unidimensional constructs smoothly. The present app provides a novel solution to the challenge of limited access to congeneric estimation methods in survey research.


Cognitive functioning in the acute phase poststroke: a predictor of discharge destination?
Cognitive dysfunction occurs in more than half of stroke survivors and can have far-reaching consequences for functioning in daily life. Assessment of cognitive function can play a major role in determining the appropriate discharge destination after a hospital stay. The present study aimed to determine the feasibility of cognitive screening in the acute phase poststroke and to investigate whether this cognitive screening can accurately predict discharge destination to either a dependent or an independent living situation. A total of 287 patients with a first-ever cerebral stroke consecutively admitted to a stroke unit of a general hospital were eligible for the study. All patients underwent neuropsychological screening, consisting of the Mini-Mental State Examination (MMSE), Cognitive Screening Test (CST), and Clock-Drawing Test, within 7 days poststroke. Screening was feasible in 73.2% of the patients. Logistic regression analysis showed that the Barthel Index (BI) score (ie, ability to perform activities of daily living) could predict the discharge destination with 47% explained variance when age and BI score were taken into account. Adding the 3 cognitive tests to the model with age and BI improved the explained variance substantially (53%), with a significant contribution of BI and CST. Cognitive screening in the acute phase poststroke appeared to be feasible and capable of supporting the decision of whether to discharge a patient to home or to a dependent living situation. Functional status improved the predictive value of the model; the MMSE was not suitable for prediction. A comprehensive set of various predictors, including cognition, is recommended to support discharge planning.


Genome-wide association identifies genetic variants associated with lentiform nucleus volume in N = 1345 young and elderly subjects.
Deficits in lentiform nucleus volume and morphometry are implicated in a number of genetically influenced disorders, including Parkinson's disease, schizophrenia, and ADHD. Here we performed genome-wide searches to discover common genetic variants associated with differences in lentiform nucleus volume in human populations. We assessed structural MRI scans of the brain in two large genotyped samples: the Alzheimer's Disease Neuroimaging Initiative (ADNI; N = 706) and the Queensland Twin Imaging Study (QTIM; N = 639). Statistics of association from each cohort were combined meta-analytically using a fixed-effects model to boost power and to reduce the prevalence of false positive findings. We identified a number of associations in and around the flavin-containing monooxygenase (FMO) gene cluster. The most highly associated SNP, rs1795240, was located in the FMO3 gene; after meta-analysis, it showed genome-wide significant evidence of association with lentiform nucleus volume (P MA = 4.79 × 10(-8)). This commonly-carried genetic variant accounted for 2.68 % and 0.84 % of the trait variability in the ADNI and QTIM samples, respectively, even though the QTIM sample was on average 50 years younger. Pathway enrichment analysis revealed significant contributions of this gene to the cytochrome P450 pathway, which is involved in metabolizing numerous therapeutic drugs for pain, seizures, mania, depression, anxiety, and psychosis. The genetic variants we identified provide replicated, genome-wide significant evidence for the FMO gene cluster's involvement in lentiform nucleus volume differences in human populations.


Effect of recombinant human erythropoietin on platelet production in dialysis patients.
Two hundred forty-four anemic hemodialysis patients were randomized into recombinant erythropoietin and placebo-treated groups during a 12-wk double-blind phase, followed by a 24-wk open-label period. Mean platelet count rose from the baseline value of 242 x 10(9)/L to 264 x 10(9)/L on day 5 of epoetin therapy (P < 0.001, paired t test). Mean platelet count peaked at 290 x 10(9)/L on day 40 and remained at a significantly elevated level below the peak thereafter. The peak platelet count did not exceed the normal range in a majority of cases. Platelet count was unaffected by placebo. Patients without an erythropoietic response during the first few weeks of therapy exhibited a rise in platelet count comparable to that in patients with a satisfactory erythropoiesis. Patients with low initial serum ferritin concentrations had baseline platelet counts comparable to those with normal or high ferritin values and showed a similar rise in platelet count during therapy. As a group, patients with baseline platelet counts above 400 x 10(9)/L showed no rise in platelet count, whereas those with normal or reduced platelet counts showed a marked thrombopoietic response to epoetin. Erythropoietin therapy did not significantly alter the incidence of blood access thrombosis when compared with placebo treatment.


Zebrafish as an Animal Model for Drug Discovery in Parkinson's Disease and Other Movement Disorders: A Systematic Review.
Movement disorders can be primarily divided into hypokinetic and hyperkinetic. Most of the hypokinetic syndromes are associated with the neurodegenerative disorder Parkinson's disease (PD). By contrast, hyperkinetic syndromes encompass a broader array of diseases, including dystonia, essential tremor, or Huntington's disease. The discovery of effective therapies for these disorders has been challenging and has also involved the development and characterization of accurate animal models for the screening of new drugs. Zebrafish constitutes an alternative vertebrate model for the study of movement disorders. The neuronal circuitries involved in movement in zebrafish are well characterized, and most of the associated molecular mechanisms are highly conserved. Particularly, zebrafish models of PD have contributed to a better understanding of the role of several genes implicated in the disease. Furthermore, zebrafish is a vertebrate model particularly suited for large-scale drug screenings. The relatively small size of zebrafish, optical transparency, and lifecycle, are key characteristics that facilitate the study of multiple compounds at the same time. Several transgenic, knockdown, and mutant zebrafish lines have been generated and characterized. Therefore, it is central to critically analyze these zebrafish lines and understand their suitability as models of movement disorders. Here, we revise the pathogenic mechanisms, phenotypes, and responsiveness to pharmacotherapies of zebrafish lines of the most common movement disorders. A systematic review of the literature was conducted by including all studies reporting the characterization of zebrafish models of the movement disorders selected from five bibliographic databases. A total of 63 studies were analyzed, and the most relevant data within the scope of this review were gathered. The majority (62%) of the studies were focused in the characterization of zebrafish models of PD. Overall, the zebrafish models included display conserved biochemical and neurobehavioral features of the phenomenology in humans. Nevertheless, in light of what is known for all animal models available, the use of zebrafish as a model for drug discovery requires further optimization. Future technological developments alongside with a deeper understanding of the molecular bases of these disorders should enable the development of novel zebrafish lines that can prove useful for drug discovery for movement disorders.


A Human Pluripotent Stem Cell-based Platform to Study SARS-CoV-2 Tropism and Model Virus Infection in Human Cells and Organoids.
SARS-CoV-2 has caused the COVID-19 pandemic. There is an urgent need for physiological models to study SARS-CoV-2 infection using human disease-relevant cells. COVID-19 pathophysiology includes respiratory failure but involves other organ systems including gut, liver, heart, and pancreas. We present an experimental platform comprised of cell and organoid derivatives from human pluripotent stem cells (hPSCs). A Spike-enabled pseudo-entry virus infects pancreatic endocrine cells, liver organoids, cardiomyocytes, and dopaminergic neurons. Recent clinical studies show a strong association with COVID-19 and diabetes. We find that human pancreatic beta cells and liver organoids are highly permissive to SARS-CoV-2 infection, further validated using adult primary human islets and adult hepatocyte and cholangiocyte organoids. SARS-CoV-2 infection caused striking expression of chemokines, as also seen in primary human COVID-19 pulmonary autopsy samples. hPSC-derived cells/organoids provide valuable models for understanding the cellular responses of human tissues to SARS-CoV-2 infection and for disease modeling of COVID-19.


COMPARATIVE VIRULENCE OF ST. LOUIS ENCEPHALITIS VIRUS CULTURED WITH BRAIN TISSUE FROM INNATELY SUSCEPTIBLE AND INNATELY RESISTANT MICE.
We find that St. Louis encephalitis virus cultured in 10 per cent serum-Tyrode solution plus brain tissue from 1-day-old innately susceptible mice attains a higher titre than when cultured in a similar solution plus brain tissue from 1-day-old closely related, yet innately resistant mice. This difference in titre persists regardless of whether the serum comes from innately susceptible or resistant mice. The relatively high titre of virus in the susceptible media is not affected by the addition of an extract (not cell-free) from the resistant brain; the relatively low titre of the virus in the resistant media may possibly be slightly enhanced by the addition of an extract from the susceptible brain. The findings as a whole show that the marked difference in the increase of St. Louis encephalitis virus in the brain tissue of innately susceptible and resistant mice, on culture in vitro, is due to some difference in the brain tissue itself.


Identifying Noise Sources governing cell-to-cell variability.
Phenotypic differences often occur even in clonal cell populations. Many potential sources of such variation have been identified, from biophysical rate variance intrinsic to all chemical processes to asymmetric division of molecular components extrinsic to any particular signaling pathway. Identifying the sources of phenotypic variation and quantifying their contributions to cell fate variation is not possible without accurate single cell data. By combining such data with mathematical models of potential noise sources it is possible to characterize the impact of varying levels of each noise source and identify which sources of variation best explain the experimental observations. The mathematical framework of information theory provides metrics of the impact of noise on the reliability of a cell to sense its environment. While the presence of noise in a single cellular system reduces the reliability of signal transduction its impact on a population of varied single cells remains unclear.


Automatic deconvolution in 4Pi-microscopy with variable phase.
4Pi-microscopy doubles the aperture of the imaging system by coherent addition of the wavefronts for illumination and/or detection through opposing objective lenses. This improves the axial resolution 3-7 fold, but the raw data usually features ghost images which have to be removed by image reconstruction. This straightforward procedure is sometimes precluded by imperfect alignment of the instrument or a specimen with strong variations of its refractive index, because the image formation process now depends on the space-variant phase difference between the counter-propagating wavefronts. Here we present a computationally fast method of parametric blind deconvolution that allows for automatic and robust simultaneous estimation of both the object and the phase function in such cases. We verify the performance of our approach on both synthetic and real data. Because the method does not require a-priori knowledge of the phase function it is major step towards reliable 4Pi-imaging and automatic image restoration by non-expert users.


Use of knowledge based DVH predictions to enhance automated re-planning strategies in head and neck adaptive radiotherapy.
This study aimed to investigate if a commercial, knowledge-based tool for radiotherapy planning could be used to estimate the amount of sparing in organs at risk (OARs) in the re-planning strategy for adaptive radiotherapy (ART). Eighty head and neck (HN) VMAT Pareto plans from our institute's database were used to train a knowledge-based planning (KBP) model. An evaluation set of another 20 HN patients was randomly selected. For each patient in the evaluation set, the planning computed tomography (CT) and 2 sets of on-board cone-beam CT, corresponding to the middle and second half of the radiotherapy treatment course, were extracted. The original plan was re-calculated on a daily deformed CT (delivered dose-volume histogram (DVH)) and compared with the KBP DVH predictions and with the final KBP DVH after optimisation of the plan, which was performed on the same image sets. To evaluate the feasibility of this method, the range of KBP DVH uncertainties was compared with the gains obtained from re-planning. DVH differences and receiver operating characteristic (ROC) curve analysis were used for this purpose. On average, final KBP uncertainties were smaller than the gain in re-planning. Statistical tests confirmed significant differences between the two groups. ROC analysis showed KBP performance in terms of area under the curve values higher than 0.7, which confirmed a good accuracy in predicted values. Overall, for 48% of cases, KBP predicted a desirable outcome from re-planning, and the final dose confirmed an effective gain in 47% of cases. We have established a systematic workflow to identify effective OAR sparing in re-planning based on KBP predictions that can be implemented in an on-line, ART process.


Binge drinking--a predictor for or a consequence of unemployment?
Research on the association between alcohol use and unemployment has been conducted in various settings and subgroups. While most studies confirm that problem use is related to subsequent unemployment, results are inconclusive regarding the reverse association. Few studies have analyzed binge drinking as either a predictor or an outcome. This study investigates 13,031 residents in Stockholm county, who participated in a 2002 survey with a follow-up in 2007, aged 20 to 59, and currently employed or on leave at T1. Associations between frequency of binge drinking and total unemployment duration in 2003 to 2006 were assessed using logistic regression, taking previous binge drinking and previous unemployment experience into account. After full adjustment, high frequency of binge drinking (1 per week or more) had a nonsignificant association with any subsequent unemployment for men and women and a significant association with long-term unemployment (>6 months) for women (OR 1.87). For men, both short-term unemployment and long-term unemployment were unrelated to later binge drinking after adjustment for previous binge drinking. Associations were stronger for women, but not significant in the full model. Frequent binge drinking among women was associated with long-term unemployment. There was little support for the social causation hypothesis.


Access to a health facility and care-seeking for danger signs in children: before and after a community-based intervention in Lusaka, Zambia.
To assess the association of accessibility to a health facility with caregivers' care-seeking practices for children with danger signs before and after community-based intervention in Lusaka, Zambia. Health education on childhood danger signs was started in September 2003 at the monthly Growth Monitoring Program Plus (GMP+) service through various channels of health talk and one-on-one communication in a peri-urban area of Lusaka. Two repeated surveys were conducted: in 2003 to collect baseline data before the intervention and in 2006 for 3-year follow-up data. Caregivers who had perceived one or more danger signs in their children within 2 months of the surveys were eligible for the analysis. The association between appropriate and timely care-seeking practices and socio-demographic and socio-economic factors, attendance at community-based intervention and the distance to a health facility was examined with logistic regression analysis. The percentage of caregivers immediately seeking care from health professionals increased from 56.1% (106/189) at baseline to 65.8% (148/225) at follow-up 3 years later (OR = 1.51, P < 0.05). Long distance to the health facility and low-household income negatively influenced caregivers' appropriate and timely care-seeking practices at baseline, but 3 years later, after the implementation of a community-based intervention, distance and household income were not significantly related to caregivers' care-seeking practices. Poor accessibility to health facilities was a significant barrier to care-seeking in a peri-urban area. However, when caregivers are properly educated about danger signs and appropriate responses through community-based intervention, this barrier can be overcome through behavioural change in caregivers.


[Effect of exogenous DNA on convulsive activity].
On the corazole model of the experimental epilepsy and epileptiform activity evoked by penicillin application to the cerebral cortex with electroencephalographic registration, it has been shown that exogenous DNAs in the most cases completely or partially inhibit convulsive activity. DNA inhibited also the pacemaker activity of the Helix RPa-1 neurons.


Improving Ribosomal RNA Integrity in Surgically Resected Human Brain Tumor Biopsies.
Biopsies extracted from brain cancer patients often display degraded ribosomal RNA, which makes them unusable in transcriptomic experiments. This has not been properly documented in previous works aimed at refining the molecular classification of brain cancer. To determine RNA integrity in a large cohort of human brain cancer biopsies and to evaluate different factors that may influence RNA integrity in both a murine model of glioblastoma and in additional subsets of patient biopsies. Total RNA was isolated from 255 biopsies of various human brain tumors (HBTs) and processed on a Bioanalyzer. Correct RNA integrity was considered for samples showing either the ribosomal 28S/18S peak ratio ≥ 1.2 or RNA integrity number ≥ 6. The time-dependent effect of ex vivo ischemia was evaluated in a murine model, whose results were tested in a new collection of 27 human biopsies. Multiple biopsy sampling was considered in a further set comprising 32 biopsies. The 255 human biopsies revealed a substantial percentage of samples displaying degraded RNA (27.5%). The murine model confirmed the known relevance of ex vivo ischemia time in increased RNA degradation. Human biopsies extracted immediately after cauterization showed a trend toward less RNA degradation. Combining snap freezing and multiple sampling of biopsies, the percentage of patients with degraded RNA was reduced by twofold (15.6%). We provide a first concise study of factors influencing RNA degradation in HBT biopsies. Immediate biopsy removal after cauterization of the tumor area, snap freezing, and multiple sampling improve RNA quality.


Intrinsic and acquired resistance to CDK4/6 inhibitors and potential overcoming strategies.
Abnormal activation of the cyclin-dependent kinases (CDKs), which result in aberrant cell proliferation, is one of the inherent characteristics of tumor. Thus targeting the activity of CDKs represents a promising tumor therapeutic strategy. Currently, the specific inhibitors that target CDK4 and CDK6 have been approved for the treatment of estrogen receptor positive, human epidermal growth factor receptor 2 negative (ER+ HER2-) breast cancer in combination with endocrine therapy; other combination strategies are being tested in a number of clinical trials. However, the acquired resistance to CDK4/6 inhibitors has emerged. As the cell cycle is orchestrated by a series of biological events, the alterations of other molecular events that regulate the cell cycle progression may be involved in intrinsic resistance to CDK4/6 inhibitors. In this review we mainly discuss the mechanisms underlying intrinsic resistance and acquired resistance to CDK4/6 inhibitors as well as combination strategies with other signal pathway inhibitors being tested in clinical and pre-clinical studies, to extend the use of CDK4/6 inhibitors in tumor treatment.


A Novel High-Throughput FLIPR Tetra-Based Method for Capturing Highly Confluent Kinetic Data for Structure-Kinetic Relationship Guided Early Drug Discovery.
Target engagement by small molecules is necessary for producing a physiological outcome. In the past, a lot of emphasis was placed on understanding the thermodynamics of such interactions to guide structure-activity relationships. It is becoming clearer, however, that understanding the kinetics of the interaction between a small-molecule inhibitor and the biological target [structure-kinetic relationship (SKR)] is critical for selection of the optimum candidate drug molecule for clinical trial. However, the acquisition of kinetic data in a high-throughput manner using traditional methods can be labor intensive, limiting the number of molecules that can be tested. As a result, in-depth kinetic studies are often carried out on only a small number of compounds, and usually at a later stage in the drug discovery process. Fundamentally, kinetic data should be used to drive key decisions much earlier in the drug discovery process, but the throughput limitations of traditional methods preclude this. A major limitation that hampers acquisition of high-throughput kinetic data is the technical challenge in collecting substantially confluent data points for accurate parameter estimation from time course analysis. Here, we describe the use of the fluorescent imaging plate reader (FLIPR), a charge-coupled device (CCD) camera technology, as a potential high-throughput tool for generating biochemical kinetic data with smaller time intervals. Subsequent to the design and optimization of the assay, we demonstrate the collection of highly confluent time-course data for various kinase protein targets with reasonable throughput to enable SKR-guided medicinal chemistry. We select kinase target 1 as a special case study with covalent inhibition, and demonstrate methods for rapid and detailed analysis of the resultant kinetic data for parameter estimation. In conclusion, this approach has the potential to enable rapid kinetic studies to be carried out on hundreds of compounds per week and drive project decisions with kinetic data at an early stage in drug discovery.


Incidence of anaphylactic self-treatment in an outpatient population.
Insect-allergic and food-allergic patients with a history of previous anaphylactic reactions were retrospectively and prospectively evaluated for incidence of self-administration of epinephrine or antihistamines. Participants were prescribed either Ana-KitR or Epi-PenR dosage forms. In 33 patients, 82 incidents were noted during 1,252 patient-months, an average of 0.78 incidents per patient-year (PPY). A mean of 0.38 epinephrine uses PPY was recorded, ranging from 0 to 2.82 doses PPY. Antihistamine uses averaged 0.69 PPY, ranging from 0 to 4.47 doses PPY. Antihistamines alone quelled reactions in 13 of 17 incidents involving Ana-Kits. Food-allergic patients were more likely to self-medicate, with 1.93 anti-allergic drug uses PPY, compared with 0.49 uses PPY for insect-allergic patients. Six of 22 insect-related epinephrine uses occurred during winter months. No statistically significant difference was noted between drug administration rates determined retrospectively and prospectively.


Structure-activity relationships among mycotoxins.
Relationships between structural features and biological effects of mycotoxins are reviewed. Structure-activity relationships are characterized at the molecular, subcellular, cellular, or supracellular level. Major chemical and physicochemical factors responsible for bioactivity of mycotoxins are stressed. A variety of chemical families of mycotoxins are then discussed from the point of view of structure-activity relationships. The structurally related families comprise small lactones, macrocyclic lactones, isocoumarin derivatives, aflatoxins and related compounds trichothecenes, anthraquinones, indole-derived tremorgens and selected amino acid-derived mycotoxins such as sporidesmins and cyclosporines. Biological effects of mycotoxins include acute and chronic toxicity, antimicrobial activity, mutagenicity and genotoxicity, carcinogenicity and biochemical modes of action.


Impact of the HIV integrase genetic context on the phenotypic expression and in vivo emergence of raltegravir resistance mutations.
HIV resistance to the integrase inhibitor raltegravir in treated patients is characterized by distinct resistance pathways. We hypothesize that differences in the in vivo dynamics of HIV resistance to raltegravir are due to the genetic context of the integrase present at baseline. We studied four patients whose viruses evolved towards different resistance pathways. The integrase baseline sequences were inserted into a reference clone. Primary resistance mutations were then introduced and their impact on viral replication capacity (RC) and resistance was measured. Patients A and B experienced emergence and persistence of mutation N155H under raltegravir therapy. In the integrase sequence from Patient A, N155H conferred potent resistance coupled with a lower impact on RC than Q148H. In Patient B, instead, selection of N155H could be explained by the dramatic loss of RC induced by the alternative Q148H mutation. In Patient C, N155H initially emerged and was later replaced by Q148H. In this integrase context, N155H resulted in higher RC but lower resistance than Q148H. In Patient D, Q148H rapidly emerged without appearance of N155H. This was the only patient for whom Q148H conferred higher RC and resistance than N155H. The emergence of different resistance mutations in patients was in full agreement with the impact of mutations in different baseline integrase contexts. Evolution towards different resistance genotypes is thus largely determined by the capacity of different integrase sequences present at baseline to minimize the effect of mutations on virus RC while allowing expression of resistance.


29Si NMR study of structural ordering in aluminosilicate geopolymer gels.
A systematic series of aluminosilicate geopolymer gels was synthesized and then analyzed using 29Si magic-angle spinning nuclear magnetic resonance (MAS NMR) in combination with Gaussian peak deconvolution to characterize the short-range ordering in terms of T-O-T bonds (where T is Al or Si). The effect of nominal Na2O/(Na2O + K2O) and Si/Al ratios on short-range network ordering was quantified by deconvolution of the 29Si MAS NMR spectra into individual Gaussian peaks representing different Q4(mAl) silicon centers. The deconvolution procedure developed in this work is applicable to other aluminosilicate gel systems. The short-range ordering observed here indicates that Loewenstein's Rule of perfect aluminum avoidance may not apply strictly to geopolymeric gels, although further analyses are required to quantify the degree of aluminum avoidance. Potassium geopolymers appeared to exhibit a more random Si/Al distribution compared to that of mixed-alkali and sodium systems. This work provides a quantitative account of the silicon and aluminum ordering in geopolymers, which is essential for extending our understanding of the mechanical strength, chemical and thermal stability, and fundamental structure of these systems.


[Cancer of the mobile tongue. Therapeutic development and results].
The authors analyse the results of treatment of 84 squamous cell carcinomas of the mobile portion of the tongue treated between 1961 and 1982. 64% of the patients treated were Stage I or II. The local recurrence rate was 13% at 5 years (6/43) for T1, T2. Recurrences were more frequent after interstitial radium therapy (17% at 5 years: 5/28) than after partial glossectomy performed at the outset (6.6% : 1.15). The treatment of stage NO remains controversial. The frequency of lymph node recurrences remains proportional to lymph node involvement by histology (NO, N-: no recurrences; NO, N+: 18.1%: 6/33) but seemed to be independent of the initial treatment of the regional nodes: no treatment, neck dissection with or without subsequent external radiotherapy. It is important to emphasize that lymph node recurrences contralateral to the tumour always occurred in the presence of initial homolateral lymphadenopathy with capsular rupture. Other oncological failures were frequent (35% : 20/56) at 5 years, grouping together visceral metastases (14.3% : 8/56) and second primary cancers in the upper respiratory/digestive tract (21.4% : 12/56).


Spatio-temporal modelling of foot-and-mouth disease outbreaks.
We present and analyse data collected during a severe epidemic of foot-and-mouth disease (FMD) that occurred between July and September 2000 in a region of northeastern Greece with strategic importance since it represents the southeastern border of Europe and Asia. We implement generic Bayesian methodology, which offers flexibility in the ability to fit several realistically complex models that simultaneously capture the presence of 'excess' zeros, the spatio-temporal dependence of the cases, assesses the impact of environmental noise and controls for multicollinearity issues. Our findings suggest that the epidemic was mostly driven by the size and the animal type of each farm as well as the distance between farms while environmental and other endemic factors were not important during this outbreak. Analyses of this kind may prove useful to informing decisions related to optimal control measures for potential future FMD outbreaks as well as other acute epidemics such as FMD.


Left Atrial Late Gadolinium Enhancement is Associated With Incident Atrial Fibrillation as Detected by Continuous Monitoring With Implantable Loop Recorders.
The authors hypothesized that left atrial (LA) fibrosis was associated with incident atrial fibrillation (AF) as detected by continuous long-term monitoring in an at-risk population. LA late gadolinium enhancement (LGE) measured with cardiac magnetic resonance is emerging as a marker of atrial fibrosis and has been associated with worse outcomes in AF ablation procedures; however, the prognostic value of LA LGE for incident AF remains unknown. Cardiac magnetic resonance, including measurement of left ventricular and LA volumes and function, as well as left ventricular extracellular volume fraction and LA LGE, was acquired in 68 patients aged at least 70 years with risk factors for stroke. All included patients received an implantable loop recorder and were continuously monitored for previously unknown AF. Incident AF was adjudicated by senior cardiologists. Patients were monitored for AF with an implantable loop recorder during a median of 41 (interquartile range: 7) months. AF episodes lasting ≥6 min were detected in 32 patients (47%), and 16 patients (24%) experienced AF episodes lasting ≥5.5 h. In Cox regression analyses adjusted for sex, age, and comorbidities, we found that LA volumes and function and LA LGE were independently associated with incident AF. For LA LGE, the hazard ratios for time to AF episodes lasting ≥6 min and ≥5.5 h were 1.40 (95% CI: 1.03 to 1.89) per 10 cm2 increase (p = 0.03) and 1.63 (95% CI: 1.11 to 2.40) per 10 cm2 increase (p = 0.01), respectively. LA LGE was significantly associated with high burden of AF. The addition of LA LGE to a multivariable risk prediction model for incident AF significantly increased the predictive value. Extent of LA fibrosis measured by LA LGE was significantly associated with incident AF detected by implantable loop recorder. (Atrial Fibrillation Detected by Continuous ECG Monitoring [LOOP]; NCT02036450).


The Molecular Basis of Gender Variations in Mortality Rates Associated With the Novel Coronavirus (COVID-19) Outbreak.
Since the outbreak of the novel coronavirus disease (COVID-19) at the end of 2019, the clinical presentation of the disease showed a great heterogeneity with a diverse impact among different subpopulations. Emerging evidence from different parts of the world showed that male patients usually had a longer disease course as well as worse outcome compared to female patients. A better understanding of the molecular mechanisms behind this difference might be a fundamental step for more effective and personalized response to this disease outbreak. For that reason, here we investigate the molecular basis of gender variations in mortality rates related to COVID-19 infection. To achieve this, we used publicly available lung transcriptomic data from 141 females and compare it to 286 male lung tissues. After excluding Y specific genes, our results showed a shortlist of 73 genes that are differentially expressed between the two groups. Further analysis using pathway enrichment analysis revealed downregulation of a group of genes that are involved in the regulation of hydrolase activity including (CHM, DDX3X, FGFR3, SFRP2, and NLRP2) in males lungs compared to females. This pathway is believed to be essential for immune response and antimicrobial activity in the lung tissues. In contrast, our results showed an increased upregulation of angiotensin II receptor type 1 (AGTR1), a member of the renin-angiotensin system (RAS) that plays a role in angiotensin-converting enzyme 2 (ACE2) activity modulation in male lungs compared to females. Finally, our results showed a differential expression of genes involved in the immune response including the NLRP2 and PTGDR2 in lung tissues of both genders, further supporting the notion of the sex-based immunological differences. Taken together, our results provide an initial evidence of the molecular mechanisms that might be involved in the differential outcomes observed in both genders during the COVID-19 outbreak. This maybe essential for the discovery of new targets and more precise therapeutic options to treat COVID-19 patients from different clinical and epidemiological characteristics with the aim of improving their outcome.


Methodological characteristics of the national dietary surveys carried out in the European Union as included in the European Food Safety Authority (EFSA) Comprehensive European Food Consumption Database.
In 2009 competent organisations in the European Union provided the European Food Safety Authority (EFSA) with data from the most recent national dietary survey at the level of individuals' consumption. Twenty different Member States provided EFSA with data from 22 different national dietary surveys, with consumption figures for adults and, when available, for children. Member States' dietary data were assembled into the EFSA Comprehensive European Food Consumption Database. In this paper an overview of the methodologies and protocols employed in the different national dietary surveys is provided. Specifically, details about dietary assessment methods, interview administration, sampling design, portion size estimation, dietary software, evaluation of under-reporting and non-dietary information collected are described. This information is crucial to evaluate the level of accuracy of food consumption data and to anticipate and acknowledge the utmost important sources of heterogeneity of national databases included in the Comprehensive Database. The Comprehensive Database constitutes a unique resource for the estimation of consumption figures across the European Union and represents a useful tool to assess dietary exposure to hazardous substances and nutrient intake in Europe. Nevertheless, the many substantial methodological differences that characterise the Comprehensive Database are acknowledged and critically discussed.


Neospora caninum associated with septic peritonitis in an adult dog.
A 7-year-old, male neutered Rhodesian Ridgeback dog was referred to the University of California-Davis Veterinary Medical Teaching Hospital with a 4-month history of peritonitis and episodic abdominal discomfort, lethargy, and weakness. Marked abdominal distension with a prominent fluid wave was noted on physical examination. Cytologic analysis of the abdominal fluid indicated a septic exudate with mixed bacteria and many protozoal zoites. Differentials for the identity of the protozoal zoites included Toxoplasma gondii, Sarcocystis neurona, and Neospora caninum. Indirect latex agglutination antigen testing, standard indirect fluorescent antibody testing, and PCR analysis were performed to identify the zoites. The dog's serum antibody titer for N caninum tachyzoites was 1:20,480, known polysera to N caninum reacted against zoites in the abdominal fluid, and PCR analysis of the abdominal fluid was positive for the presence of a known gene of N caninum. Based on the morphologic, immunologic, and molecular findings, the zoites were identified as N caninum. It remains unclear how the tachyzoites gained access to the peritoneal cavity. To the authors' knowledge, there are no reports of free N caninum in abdominal fluid of any species.


Preferred female body proportions among child-free men.
Based on conceptual extrapolations from sociobiological models concerning the significance of secondary sex characteristics as markers of a female's capacity to produce and nurture offspring, we reasoned that men's greater unwillingness to reproduce would be linked to preference for a female body type characterized by the relative absence of such markers. Heterosexual undergraduate men (N = 67) indicated their ideal (most arousing) female body type on-line by means of an adjustable female figure. As expected, the desire to remain childfree was linked to erotic preference for a combination of smaller breasts and larger waist-to-hip ratio. Additional research into individual factors that map onto variations in the preferred body proportions of erotic targets is thus encouraged.


Microsomal antiestrogen-binding site ligands induce growth control and differentiation of human breast cancer cells through the modulation of cholesterol metabolism.
The microsomal antiestrogen-binding site (AEBS) is a high-affinity membranous binding site for the antitumor drug tamoxifen that selectively binds diphenylmethane derivatives of tamoxifen such as PBPE and mediates their antiproliferative properties. The AEBS is a hetero-oligomeric complex consisting of 3beta-hydroxysterol-Delta8-Delta7-isomerase and 3beta-hydroxysterol-Delta7-reductase. High-affinity AEBS ligands inhibit these enzymes leading to the massive intracellular accumulation of zymostenol or 7-dehydrocholesterol (DHC), thus linking AEBS binding to the modulation of cholesterol metabolism and growth control. The aim of the present study was to gain more insight into the control of breast cancer cell growth by AEBS ligands. We report that PBPE and tamoxifen treatment induced differentiation in human breast adenocarcinoma cells MCF-7 as indicated by the arrest of cells in the G0-G1 phase of the cell cycle, the increase in the cell volume, the accumulation and secretion of lipids, and a milk fat globule protein found in milk. These effects were observed with other AEBS ligands and with zymostenol and DHC. Vitamin E abrogates the induction of differentiation and reverses the control of cell growth produced by AEBS ligands, zymostenol, and DHC, showing the importance of the oxidative processes in this effect. AEBS ligands induced differentiation in estrogen receptor-negative mammary tumor cell lines SKBr-3 and MDA-MB-468 but with a lower efficiency than observed with MCF-7. Together, these data show that AEBS ligands exert an antiproliferative effect on mammary cancer cells by inducing cell differentiation and growth arrest and highlight the importance of cholesterol metabolism in these effects.


Immunohistochemical detection of metallothionein in liver, duodenum and kidney after dietary copper-overload in rats.
Metallothionein (MT) has been used in immunohistochemical techniques to indicate presence and distribution of heavy metals within biological tissues. This study describes a comparison of the pattern of MT-immunostaining in the liver, duodenum and kidney during dietary copper overload in rats. Sixteen male 10-week-old Wistar rats were randomly allocated into groups of four. Two groups were fed a pelleted diet containing 1,500 mg/kg copper and two control groups received a rodent diet containing 10 mg/kg copper. After 6 weeks samples of liver, kidney and duodenum were collected for immunohistochemistry and histology. An indirect immunoperoxidase technique, using monoclonal antibody E9 against horse MT and polyclonal sera against rabbit MT, was employed. Copper-loaded rats had marked MT-immunoreactivity within the nucleus and cytoplasm of many periportal hepatocytes, renal proximal convoluted tubule epithelial cells, intestinal columnar epithelial cells and Paneth cells. Immunohistochemical staining was similar using either mouse anti-MT polyclonal serum, or monoclonal antibody E9. Hepatocytes surrounding inflammatory foci were positive for MT, supporting the proposed role of this protein in free radical scavenging. The presence of MT in the kidney appears to be associated with renal excretion of copper-metallothionein (Cu-MT) in copper-loaded rats. Paneth cells were easily detected using MT-immunostaining. MT may play a part in absorption of copper from intestinal contents and possible storage as Cu-MT in Paneth cells. The function of Paneth cells remains unknown but the presence of marked MT-immunoreactivity in these cells, observed in copper-loaded rats, suggests their involvement in homeostasis and metabolism of copper.


A PK2/Bv8/PROK2 antagonist suppresses tumorigenic processes by inhibiting angiogenesis in glioma and blocking myeloid cell infiltration in pancreatic cancer.
Infiltration of myeloid cells in the tumor microenvironment is often associated with enhanced angiogenesis and tumor progression, resulting in poor prognosis in many types of cancer. The polypeptide chemokine PK2 (Bv8, PROK2) has been shown to regulate myeloid cell mobilization from the bone marrow, leading to activation of the angiogenic process, as well as accumulation of macrophages and neutrophils in the tumor site. Neutralizing antibodies against PK2 were shown to display potent anti-tumor efficacy, illustrating the potential of PK2-antagonists as therapeutic agents for the treatment of cancer. In this study we demonstrate the anti-tumor activity of a small molecule PK2 antagonist, PKRA7, in the context of glioblastoma and pancreatic cancer xenograft tumor models. For the highly vascularized glioblastoma, PKRA7 was associated with decreased blood vessel density and increased necrotic areas in the tumor mass. Consistent with the anti-angiogenic activity of PKRA7 in vivo, this compound effectively reduced PK2-induced microvascular endothelial cell branching in vitro. For the poorly vascularized pancreatic cancer, the primary anti-tumor effect of PKRA7 appears to be mediated by the blockage of myeloid cell migration/infiltration. At the molecular level, PKRA7 inhibits PK2-induced expression of certain pro-migratory chemokines and chemokine receptors in macrophages. Combining PKRA7 treatment with standard chemotherapeutic agents resulted in enhanced effects in xenograft models for both types of tumor. Taken together, our results indicate that the anti-tumor activity of PKRA7 can be mediated by two distinct mechanisms that are relevant to the pathological features of the specific type of cancer. This small molecule PK2 antagonist holds the promise to be further developed as an effective agent for combinational cancer therapy.


Circulating steroid levels as correlates of adipose tissue phenotype in premenopausal women.
Background Obesity-related alterations in the circulating steroid hormone profile remain equivocal in women. Our objective was to identify circulating steroid levels that relate to increased adiposity and altered adipose phenotype in premenopausal women. Materials and methods In a sample of 42 premenopausal women [age 46 ± 3 years; body mass index (BMI) 27.1 ± 4.2 kg/m2], 19 plasma steroids were quantified by electrospray ionization-liquid chromatography-tandem mass spectroscopy (ESI-LC-MS/MS). Body composition and fat distribution were assessed by dual-energy X-ray absorptiometry (DXA) and computed tomography (CT), respectively. Markers of adipose tissue function including adipocyte size distributions, radiological attenuation and macrophage infiltration were also analyzed in surgically obtained visceral and subcutaneous fat samples. Results Many negative correlations were observed between adiposity measurements such as BMI, body fat percentage or total abdominal adipose tissue area and plasma levels of androstenedione (Δ4) (r = -0.33 to -0.39, p ≤ 0.04), androsterone (ADT) (r = -0.30 to -0.38, p ≤ 0.05) and steroid precursor pregnenolone (PREG) (r = -0.36 to -0.46, p ≤ 0.02). Visceral adipocyte hypertrophy was observed in patients with low PREG concentrations (p < 0.05). Visceral adipose tissue radiologic attenuation, a potential marker of adipocyte size, was also positively correlated with PREG levels (r = 0.33, p < 0.05). Low levels of PREG were related to increased number of macrophages infiltrating visceral and subcutaneous adipose tissue (p < 0.05). Conclusion Plasma levels of androgens and their precursors are lower in women with increased adiposity and visceral adipocyte hypertrophy. Low circulating PREG concentration may represent a marker of adipose tissue dysfunction.


The "decade of the environment" in the u.s.s.R.
The decade of the 1970's was for the U.S.S.R, as for the United States, a period of increased awareness of environmental deterioration. In response, new laws were passed, pollution control funding was increased, and natural resource conservation was heavily stressed. Despite such good intentions, the cumulative effects of new technologies, inadequate budgets and enforcement, the primacy of production goals, and various institutional impediments resulted in an uneven and in some places inadequate level of environmental enhancement.


Microbiome data reveal significant differences in the bacterial diversity in freshwater rohu (Labeo rohita) across the supply chain in Dhaka, Bangladesh.
The present study aimed to characterize and compare the skin and gut microbial communities of rohu at various post-harvest stages of consumption using quantitative real-time polymerase chain reaction and 16S rRNA-based amplicon sequencing. Real-time PCR amplification detected higher copy numbers for coliform bacteria-Escherichia coli, Salmonella enterica and Shigella spp. in the marketed fish-compared to fresh and frozen samples. The 16S rRNA data revealed higher alpha diversity measurements in the skin of fish from different retail markets of Dhaka city. Beta ordination revealed distinct clustering of bacterial OTUs for the skin and gut samples from three different groups. At the phylum level, Proteobacteria was most abundant in all groups except the Fusobacteria in the control fish gut. Although Aeromonas was found ubiquitous in all types of samples, diverse bacterial genera were identified in the marketed fish samples. Nonetheless, low species richness was observed for the frozen fish. Most of the differentially abundant bacteria in the skin samples of marketed fish are opportunistic human pathogens enriched at different stages of postharvest handling and processing. Therefore, considering the microbial contamination in the aquatic environment in Bangladesh, post-harvest handling should be performed with proper methods and care to minimize bacterial transmission into fish.


CHIP and BAP1 Act in Concert to Regulate INO80 Ubiquitination and Stability for DNA Replication.
The INO80 chromatin remodeling complex has roles in many essential cellular processes, including DNA replication. However, the mechanisms that regulate INO80 in these processes remain largely unknown. We previously reported that the stability of Ino80, the catalytic ATPase subunit of INO80, is regulated by the ubiquitin proteasome system and that BRCA1-associated protein-1 (BAP1), a nuclear deubiquitinase with tumor suppressor activity, stabilizes Ino80 via deubiquitination and promotes replication fork progression. However, the E3 ubiquitin ligase that targets Ino80 for proteasomal degradation was unknown. Here, we identified the C-terminus of Hsp70-interacting protein (CHIP), the E3 ubiquitin ligase that functions in cooperation with Hsp70, as an Ino80-interacting protein. CHIP polyubiquitinates Ino80 in a manner dependent on Hsp70. Contrary to our expectation that CHIP degrades Ino80, CHIP instead stabilizes Ino80 by extending its halflife. The data suggest that CHIP stabilizes Ino80 by inhibiting degradative ubiquitination. We also show that CHIP works together with BAP1 to enhance the stabilization of Ino80, leading to its chromatin binding. Interestingly, both depletion and overexpression of CHIP compromise replication fork progression with little effect on fork stalling, as similarly observed for BAP1 and Ino80, indicating that an optimal cellular level of Ino80 is important for replication fork speed but not for replication stress suppression. This work therefore idenitifes CHIP as an E3 ubiquitin ligase that stabilizes Ino80 via nondegradative ubiquitination and suggests that CHIP and BAP1 act in concert to regulate Ino80 ubiquitination to fine-tune its stability for efficient DNA replication.


Clearance of circulating IgA immune complexes is mediated by a specific receptor on Kupffer cells in mice.
To characterize the physiology of circulating IgA immune complexes (IgA-IC), the dynamics of IgA-IC removal by the liver were examined. After intravenous injection, covalently cross-linked IgA antibodies to the dinitrophenyl determinant were rapidly removed from the circulation by the liver. Immunofluorescence microscopy and light and electron microscope autoradiography showed that the IgA-IC were associated with Kupffer cells. With increasing doses of injected IgA-IC the clearance velocity approached a maximum, thus prolonging the circulation of IgA-IC. All these observations indicated a receptor-mediated process. Saturating doses of various potential receptor-blocking agents, heat-aggregated mouse IgG, microaggregated human serum albumin, and purified dimeric IgA did not influence the clearance pattern and hepatic uptake of radiolabeled IgA-IC. Mouse livers were also perfused via the portal vein with 1 microgram of IgA-IC. In the presence or absence of serum proteins, 43% of the perfused IgA-IC were removed in a single passage. This liver uptake was not reduced with simultaneous perfusion of large doses of aggregated mouse IgG, aggregated human serum albumin, or purified free dimeric mouse IgA. In contrast, the liver uptake of radiolabeled IgA-IC was decreased by 88% with the addition of 1 mg unlabeled IgA-IC. These observations support the conclusion that removal of IgA-IC from circulation is mediated by a specific IgA receptor on Kupffer cells.


Social consequences of pediatric conditions: fertile area for future investigation and intervention.
Very little systematic research has examined the peer relations and social functioning of youngsters with chronic illness. In order to stimulate empirical and clinical interest in this potentially important area of pediatric psychology, the present paper discusses several pertinent tissues. These include (a) the role of peers in disease adaptation and treatment management, (b) specific aspects of diseases or treatments that are likely to have implications for youngsters' social functioning, (c) guidelines for further investigation in this area, and (d) suggestions for incorporating peer/social issues into educational programs and intervention efforts for youngsters with chronic disease. Throughout the discussion, the complex interplay between peer relations and adaptation to chronic illness is highlighted.


H-SLAM: Rao-Blackwellized Particle Filter SLAM Using Hilbert Maps.
Occupancy Grid maps provide a probabilistic representation of space which is important for a variety of robotic applications like path planning and autonomous manipulation. In this paper, a SLAM (Simultaneous Localization and Mapping) framework capable of obtaining this representation online is presented. The H-SLAM (Hilbert Maps SLAM) is based on Hilbert Map representation and uses a Particle Filter to represent the robot state. Hilbert Maps offer a continuous probabilistic representation with a small memory footprint. We present a series of experimental results carried both in simulation and with real AUVs (Autonomous Underwater Vehicles). These results demonstrate that our approach is able to represent the environment more consistently while capable of running online.


Effect of Initial Conformation on the Starch Biopolymer Film Formation Studied by NMR.
The formation of a rigid porous biopolymer scaffold from aqueous samples of 1% w/v (suspension) and 5% w/v (gel) corn starch was studied using optical and nuclear magnetic resonance (NMR) techniques. The drying process of these systems was observed using a single-sided NMR scanner by application of the Carr-Purcell-Meiboom-Gill pulse sequence at different layer positions. The echo decays were analyzed and spin-spin relaxation times (T2) were obtained for each layer. From the depth dependent T2 relaxation time study, it was found that the molecular mobility of water within the forming porous matrix of these two samples varied notably at different stages of film formation. At an intermediate stage, a gradual decrease in mobility of the emulsion sample towards the air-sample interface was observed, while the gel sample remained homogeneous all along the sample height. At a later stage of drying, heterogeneity in the molecular dynamics was observed in both samples showing low mobility at the bottom part of the sample. A wide-angle X-ray diffraction study confirmed that the structural heterogeneity persisted in the final film obtained from the 5% corn starch aqueous sample, whereas the film obtained from the 1% corn starch in water was structurally homogeneous.


Highly Hydrophobic and Superoleophilic Nanofibrous Mats with Controllable Pore Sizes for Efficient Oil/Water Separation.
Both the wettability and pore size of filtration materials are of great importance in oil/water separation. However, conventional strategies have mainly focused on the fabrication of filtration materials with special wettability, regardless of the pore size. Herein, we demonstrated the design and construction of special wettable nanofibrous mats with tunable pore sizes as filtration materials for selective and efficient separation of oil from oil/water mixtures. The nanofibrous mats with different pore sizes were prepared by the electrospinning approach using a stainless steel wire mesh as the collector, and the results indicated that the pore size of the nanofibrous mats gradually increased with the decrease in the mesh number. The results of the wettability behavior demonstrated that all of the nanofibrous mats showed highly hydrophobic and superoleophilic properties. Owing to the special wettability and the porous structure, the nanofibrous mats were sequentially applied for oil/water separation, and they showed excellent ability to separate both layered oil/water mixture and water-in-oil emulsion; moreover, it was also found that the oil flux could be highly improved by controlling the pore size of the nanofibrous mat and that the oil flux of the nanofibrous mat with the largest pore size was about 10 times higher than that of the conventional nonwoven mat that had the smallest pore size. The nanofibrous mats developed with controllable pore sizes can therefore be practically used as highly efficient filtration materials in the management of oily water.


A prophylactic effect of local vibration on quadriceps muscle fatigue in non-athletic males: a randomized controlled trial study.
[Purpose] This study was conducted to investigate the immediate prophylactic effects of local vibration on quadriceps muscle fatigue in young non-athletic males. [Participants and Methods] Thirty healthy young males were randomly assigned to vibration and sham control groups. Participants in the local vibration group received a single session vibration (2 minutes, 30 Hz). They also in the control group received a 2-minute vibration, while the vibration system was off. MVC, RMS and median frequency of EMG findings and time to reach fatigue were measured. [Results] Time to reach fatigue and MVC in the local vibration group was significantly high than those in the sham control group. [Conclusion] It seems that the prior local muscle vibration may be useful to attenuate some signs and symptoms of muscle fatigue.


Regional Online Union Catalog of the Greater Midwest Regional Medical Library Network: development and operation.
The GMRMLN Online Catalog was developed as an easily accessible locator tool for monographs and audiovisuals held within the Greater Midwest Regional Medical Library Network. The catalog was generated from machine-readable records in MARC formats contributed by regional libraries. It was mounted by BRS as a private database and is fully free text searchable using BRS search. Each institutional file was merged and purged of duplicates to create a single entry for each title. The catalog features an online interlibrary loan system that automatically routes a request to the two nearest, smallest libraries that own the title. If the request is not filled within the region, the system automatically routes it to the National Library of Medicine without the need to rekeyboard data. The system collects management data on interlibrary loan processing. Funding for the catalog permitted a trial period of use with cost support. Data on system operation were gathered during this demonstration.


Effect of sildenafil (Viagra) on the genital reflexes of paradoxical sleep-deprived male rats.
Since there is evidence that paradoxical sleep deprivation (PSD) elicits penile erection (PE) and ejaculation (EJ), and that the erectile response of rats is mediated by nitric oxide, the present study sought to extend the latter finding by assessing the effects of sildenafil on the genital reflexes of male Wistar rats subjected to PSD. We also determined the influence of sildenafil on hormone concentrations. In the first experiment, sildenafil at doses ranging from 0.08 to 0.32 mg/kg was administered intraperitoneally to rats that had been deprived of sleep for 4 days and to home cage controls (N = 8-10/group). The frequency of PE and EJ was measured for 60 min. PSD alone induced PE in 50% of the animals; however, a single injection of sildenafil did not significantly increase the percentage of rats displaying PE compared to PSD-saline or to home cage groups. PSD alone also induced spontaneous EJ, but this response was not potentiated by sildenafil in the dose range tested. Testosterone concentrations were significantly lower in PSD rats (137 +/- 22 ng/dL) than in controls (365 +/- 38 ng/dL), whereas progesterone (0.9 +/- 0.1 vs 5.4 +/- 1 ng/mL) and plasma dopamine (103.4 +/- 30 vs 262.6 +/- 77 pg/mL) increased. These changes did not occur after sildenafil treatment. The data show that although sildenafil did not alter the frequency of genital reflexes, it antagonized hormonal (testosterone and progesterone) and plasma dopamine changes induced by PSD. The stimulation of the genital reflexes by sildenafil did not result in potentiating effects in PSD rats.


Calcium intake increases risk of prostate cancer among Singapore Chinese.
Consumption of dairy products, the primary source of calcium in Western diets, has been found to be positively associated with prostate cancer. In an Asian diet, nondairy foods are the major contributors of calcium. Thus, a study of dietary calcium and prostate cancer in Asians can better inform on whether calcium, as opposed to other dairy components, is responsible for the dairy foods-prostate cancer association. We examined calcium intake and prostate cancer risk among 27,293 men in the Singapore Chinese Health Study that was established between 1993 and 1998. As of December 31, 2007, 298 incident prostate cancer cases had been diagnosed among the cohort members. Diet was assessed at baseline with a validated 165-item food-frequency questionnaire. It is hypothesized that there is greater net absorption of calcium in smaller individuals. Therefore, the calcium-prostate cancer association was also assessed in stratified analyses by median body mass index. Vegetables were the largest contributor of daily calcium intake in the study population. Overall, we observed a modest, statistically nonsignificant 25% increase in prostate cancer risk for the 4th (median = 659 mg/d) versus 1st (median = 211 mg/d) quartiles of calcium intake after adjustment for potential confounders. The association became considerably stronger and achieved statistical significance (hazard ratio, 2.03; 95% confidence interval, 1.23-3.34; P for trend = 0.01) for men with a below median body mass index (22.9 kg/m(2)). Dietary calcium might be a risk factor for prostate cancer even at relatively low intake.