HGM-4: A new multi-cameras dataset for hand gesture recognition.
Gesture recognition technology is rapidly growing in the recent years due to the demands of many application such as computer game and sport, human robot interaction, assistant systems, sign language interpretation and e-commerce. One of the most important of gesture recognition is hand-gesture recognition. For example, it can be used to control all devices (television, radio, air-condition, and doors) by just hand gestures for smart home application. The HGM-4 dataset is built for hand gesture recognition (the full dataset is available from: https://data.mendeley.com/datasets/jzy8zngkbg/4) which contains total 4,160 color images (1280 × 700 pixels) of 26 hand gestures captured by four cameras at different position. The training and testing set are defined to create a benchmark framework for comparing the experimental results.


Liquid chromatography-thermospray tandem mass spectrometry for identification of a heptabarbital metabolite and sample work-up artefacts.
An unknown heptabarbital metabolite, observed in the liquid chromatogram of rat plasma and urine samples after administration of heptabarbital, was identified by liquid chromatography-thermospray tandem mass spectrometry. By applying the parent scan mode for screening and the daughter scan mode for structure elucidation, the metabolite was determined to be 5-ethyl-5-(1'-, 3'- or 6'-cycloheptadienyl)barbituric acid. It was demonstrated that artefact formation occurred when hydrochloric acid was used for conjugate hydrolysis in the sample clean-up. Identification of the artefacts was achieved by the same method. Confirmation of the structures of the metabolite and the artefacts was obtained by gas chromatography-electron impact mass spectrometry.


Effects of free fatty acids on glucose transport and IRS-1-associated phosphatidylinositol 3-kinase activity.
To examine the mechanism by which free fatty acids (FFA) induce insulin resistance in human skeletal muscle, glycogen, glucose-6-phosphate, and intracellular glucose concentrations were measured using carbon-13 and phosphorous-31 nuclear magnetic resonance spectroscopy in seven healthy subjects before and after a hyperinsulinemic-euglycemic clamp following a five-hour infusion of either lipid/heparin or glycerol/heparin. IRS-1-associated phosphatidylinositol 3-kinase (PI 3-kinase) activity was also measured in muscle biopsy samples obtained from seven additional subjects before and after an identical protocol. Rates of insulin stimulated whole-body glucose uptake. Glucose oxidation and muscle glycogen synthesis were 50%-60% lower following the lipid infusion compared with the glycerol infusion and were associated with a approximately 90% decrease in the increment in intramuscular glucose-6-phosphate concentration, implying diminished glucose transport or phosphorylation activity. To distinguish between these two possibilities, intracellular glucose concentration was measured and found to be significantly lower in the lipid infusion studies, implying that glucose transport is the rate-controlling step. Insulin stimulation, during the glycerol infusion, resulted in a fourfold increase in PI 3-kinase activity over basal that was abolished during the lipid infusion. Taken together, these data suggest that increased concentrations of plasma FFA induce insulin resistance in humans through inhibition of glucose transport activity; this may be a consequence of decreased IRS-1-associated PI 3-kinase activity.


Impact of cultural background on fundamental movement skill and its correlates.
Children's fundamental movement skill levels (FMS) predict moderate-to-vigorous physical activity (MVPA). Asian children have been reported as less active than English-Europeans, possibly due to poorer skills. This study compared the FMS of children from Culturally and Linguistically Diverse (CALD) backgrounds and examined FMS correlates. A total of 261 children (122 males) aged 9-to-11 years were divided based on language spoken at home: English-European (n = 105) and Asian (n = 156). Height, mass, FMS (Test of Gross Motor Development-2), MVPA (accelerometer) and cardio-respiratory fitness (20m multistage shuttle run) were directly measured. Sex, age, language and perceived sport competence (CY-PSPP) were self-reported. Independent sample t-tests assessed age, BMI, FMS and perception by CALD group. Linear mixed models examined FMS correlates. Asian-speaking children had lower object control skill (35.5 v 37.2; CI [0.17, 3.18]; p < 0.03) compared to English-European- children, but no between-group differences in locomotor skills were observed. Fitness, physical activity and sport competence perception were positively associated with object control, yet adjusting for these variables (and age and BMI) did not remove the CALD effect (B = -2.02, SE = 0.69, p = 0.004). Cultural factors may affect object control competence in Asian-Australian children.


DNA polymerase I of Mycobacterium tuberculosis: functional role of a conserved aspartate in the hinge joining the M and N helices.
The highly conserved GXD sequence present in the Mycobacterium tuberculosis DNA polymerase I corresponds to a hinge region in the finger subdomain connecting M and N helices of Escherichia coli pol I. An examination of the crystal structures of pol I family polymerases reveals that the invariant aspartate of the hinge forms a salt bridge with the conserved arginine of the O-helix and an H-bond with Gln-708. To clarify the role of this region, we generated and characterized conserved and nonconserved mutant derivatives of this aspartate, the preceding glutamate and the Gln in TB pol I. For comparison, D732A mutein of pol I was also included. The muteins representing conserved aspartate (Asp-707 of TB pol I or Asp-732 of pol I) showed a strong K(m)((dNTP)) effect and minor alteration in K(d)((DNA)), with about 10-20-fold decrease in overall catalytic efficiency. The TB muteins, E706A and Q683A, have less pronounced deviations from the wild-type enzyme. Further examination of D707A of TB pol I showed no alteration in the processivity or the dideoxynucleotide sensitivity patterns. However, both TB pol D707A and homologous E. coli D732A failed to form a stable E.DNA.dNTP ternary complex. These results suggest that the aspartate in the hinge region is catalytically important and is required for dNTP binding and in the formation of a prepolymerase ternary complex.


Patients' attitudes to general practice registrars: a review of the literature.
With the population ageing, it is imperative for training practices to provide general practice registrars (GPRs) with sound experience in managing the health problems of older persons, especially chronic conditions. However, it is reported that a significant proportion of these patients will be resistant to consulting registrars, with concerns regarding disruption of continuity of care being a significant factor. The challenge for training practices is to identify approaches to engage registrars in the management of older patients whilst maintaining patient satisfaction. This paper presents a review of the literature on patient attitudes to GPRs to better understand the nature and magnitude of the challenge, and to identify important research gaps. Major electronic medical literature databases were searched for relevant articles using search terms including general practice, registrar, doctor-patient relationship, patient attitudes and elderly, for the period from January 1980 to March 2009. The studies were analysed by methodology, content and theme. A total of 15 studies were identified that directly addressed patients' attitudes to GPRs. Whilst there appeared to be an overall high acceptance of registrars by patients, increasing patient age was associated with more negative attitudes towards registrars, reduced trust and decreased satisfaction with communication. Presentations for chronic or emotional problems were associated with reduced willingness to consult registrars. Patients generally appreciated an ongoing involvement with their usual GP. These findings have implications for training practices and research directions. Demonstrating continuity of care through shared chronic disease management between supervisors and registrars is a possible model that meets registrars' training and patients' continuity needs. There is a need for quality research on the type and magnitude of problems affecting GPR encounters with older patients and, based on results from these studies, to create and assess models of registrar training involving older patients, that meet patients' needs for continuity of care.


Patient Presentations in Outpatient Settings: Epidemiology of Adult Head Trauma Treated Outside of Hospital Emergency Departments.
While deaths, hospitalizations, and emergency department visits for head trauma are well understood, little is known about presentations in outpatient settings. Our objective was to examine the epidemiology and extent of healthcare-seeking adult (18-64 years) head trauma patients presenting in outpatient settings compared with patients receiving nonhospitalized emergency department care. We used 2004-2013 MarketScan Medicaid/commercial claims to identify head trauma patients managed in outpatient settings (primary care provider, urgent care) and the emergency department. We examined differences in demographic and injury-specific factors, Centers for Disease Control and Prevention-defined head trauma diagnoses, and extent of and reasons for postindex visit ambulatory care use within 30/90/180 days by index visit location, as well as annual and monthly variations in head trauma trends. We used outpatient incidence rates to estimate the US nationwide outpatient burden. A total of 1.19 million index outpatient visits were included (emergency department: 348,659). Nationwide, they represented a weighted annual burden of 1.16 million index outpatient cases. These encompassed 46% of all known healthcare-seeking head trauma in 2013 (outpatient/emergency department/inpatient/fatalities) and increased in magnitude (+31%) from 2004 to 2013. One fourth (27%) of office/clinic visits led to diagnosis with concussion on index presentation (urgent care: 32%). Distributions of demographic factors varied with index visit location while injury-specific factors were largely comparable. Subsequent visits reflected high demand for follow-up treatment, increased concussive diagnoses, and sequelae-associated care. Adult outpatient presentations of head trauma remain poorly understood. The results of this study demonstrate the extensive magnitude of their occurrence and close association with need for follow-up care.


Prognostic significance of antithrombin activity in patients with crimean-congo hemorrhagic Fever.
Crimean-Congo hemorrhagic fever (CCHF) is a tick-borne viral hemorrhagic fever. Disseminated intravascular coagulation (DIC) is an important complication of this disease, especially in severe and fatal cases. Antithrombin (AT) acts as an anticoagulant by inactivating thrombin, Factor IX, Factor X and Factor XI. We conducted this study to investigate the AT levels and their prognostic value in CCHF. Twenty-eight confirmed CCHF patients were included in this study. Diagnosis of the disease was made by CCHF IgM and/or PCR positivity. Patients were grouped based on the severity criteria described previously. The patients with platelet counts <20 000×10(6) cell/L, white blood counts >10×10(9) cell/L, prothrombin times >60 seconds, aspartate aminotransferase levels >700 IU/L or alanine aminotransferase levels >900 IU/L were accepted as severe cases. Patients whose illnesses were self-limited and who did not require blood component replacement were accepted as mild cases, and patients who improved but required blood component replacement were accepted as moderate cases. Blood samples were obtained on the day that the patient had the lowest platelet count and before any thrombocyte replacement. The antithrombin activity was measured using a chromogenic substrate test (Diagnostica Stago STA Compact) at a research laboratory. Twenty-two (78.6%) of the cases were mild, 3 (10.7%) were moderate, and 3 were (10.7%) severe. The mean AT value was 101% for mild cases, 116.6 % for moderate cases, and 88% for severe cases (p>0.05). Although there were no statistically significant differences between the AT values, the mean AT activity was lower in severe CCHF cases. The AT activity may have been decreased in severe CCHF cases. Further studies with greater numbers of patients are required to determine the level of AT activity and its correlation with disease severity and the prognosis of CCHF.


Recent advances in electronic tongues.
This minireview describes the main developments of electronic tongues (e-tongues) and taste sensors in recent years, with a summary of the principles of detection and materials used in the sensing units. E-tongues are sensor arrays capable of distinguishing very similar liquids employing the concept of global selectivity, where the difference in the electrical response of different materials serves as a fingerprint for the analysed sample. They have been widely used for the analysis of wines, fruit juices, coffee, milk and beverages, in addition to the detection of trace amounts of impurities or pollutants in waters. Among the various principles of detection, electrochemical measurements and impedance spectroscopy are the most prominent. With regard to the materials for the sensing units, in most cases use is made of ultrathin films produced in a layer-by-layer fashion to yield higher sensitivity with the advantage of control of the film molecular architecture. The concept of e-tongues has been extended to biosensing by using sensing units capable of molecular recognition, as in films with immobilized antigens or enzymes with specific recognition for clinical diagnosis. Because the identification of samples is basically a classification task, there has been a trend to use artificial intelligence and information visualization methods to enhance the performance of e-tongues.


Intracellular acid-base heterogeneity in nucleated avian erythrocytes.
1. Intracellular hydrogen ion activity, [H+]i, was extimated in human erythrocytes and in nucleated avian erythrocytes from measurements of the distribution of ammonia and 5,5'-dimethyloxazolidine-2,4'-dione (DMO) between intracellular and extracellular fluid. 2. In human erythrocytes there was no difference between values for [H+]i derived from measurements of either DMO or ammonia. 3. In avian erythrocytes, [H+]i(ammonia) was consistently greater than [H+]i(DMO), indicating significant acid-base heterogeneity of the intracellular water. The degree of heterogeneity was assessed by reference to a theoretical model of two compartments of equal size. 4. Experiments with nuclei isolated from avian erythrocytes suggested that DMO is not bound to nucleoproteins, and that the nucleus may be more acidic than the cytoplasm.


Is trauma a causal agent of psychopathologic symptoms in posttraumatic stress disorder? Findings from identical twins discordant for combat exposure.
The diagnosis of posttraumatic stress disorder (PTSD) is unique in that its criteria are embedded with a presumed causal agent, viz, a traumatic event. This assumption has come under scrutiny as a number of recent studies have suggested that many symptoms of PTSD may not necessarily be the result of trauma and may merely represent general psychiatric symptoms that would have existed even in the absence of a trauma event but are subsequently misattributed to it. The current study tests this hypothesis. A case-control twin study conducted between 1996-2001 examined psychopathologic symptoms in a national convenience sample of 104 identical twin pairs discordant for combat exposure in Vietnam, with (n = 50) or without (n = 54) combat-related PTSD (DSM-IV-diagnosed) in the exposed twin. Psychometric measures used were the Symptom Checklist-90-Revised, the Clinician-Administered PTSD Scale, and the Mississippi Scale for Combat-Related PTSD. If a psychopathologic feature represents a factor that would have existed even without traumatic exposure, then there is a high chance that it would also be found at elevated rates in the non-trauma-exposed, identical cotwins of trauma-exposed twins with PTSD. In contrast, if a psychopathologic feature is acquired as a result of an environmental factor unique to the exposed twin, eg, the traumatic event, their cotwins should not have an increased incidence of the feature. Combat veterans with PTSD demonstrated significantly higher scores (P < .0001) on the Symptom Checklist-90-Revised and other psychometric measures of psychopathology than their own combat-unexposed cotwins (and than combat veterans without PTSD and their cotwins). These results support the conclusion that the majority of psychiatric symptoms reported by combat veterans with PTSD would not have been present were it not for their exposure to traumatic events.


Transient homologous chromosome pairing marks the onset of X inactivation.
Mammalian X inactivation turns off one female X chromosome to enact dosage compensation between XX and XY individuals. X inactivation is known to be regulated in cis by Xite, Tsix, and Xist, but in principle the two Xs must also be regulated in trans to ensure mutually exclusive silencing. Here, we demonstrate that interchromosomal pairing mediates this communication. Pairing occurs transiently at the onset of X inactivation and is specific to the X-inactivation center. Deleting Xite and Tsix perturbs pairing and counting/choice, whereas their autosomal insertion induces de novo X-autosome pairing. Ectopic X-autosome interactions inhibit endogenous X-X pairing and block the initiation of X-chromosome inactivation. Thus, Tsix and Xite function both in cis and in trans. We propose that Tsix and Xite regulate counting and mutually exclusive choice through X-X pairing.


Two amphibian diseases, chytridiomycosis and ranaviral disease, are now globally notifiable to the World Organization for Animal Health (OIE): an assessment.
The global trade in amphibians entails the transport of tens of millions of live animals each year. In addition to the impact harvesting wild animals can have on amphibian populations, there is mounting evidence that the emerging pathogens Batrachochytrium dendrobatidis and ranaviruses, the aetiological agents of chytridiomycosis and ranaviral disease, respectively, are spread through this trade. The link between these pathogens and amphibian declines and extinctions suggests that the epidemiological impact of the trade is significant and may negatively affect conservation and trade economics. Here we present a brief assessment of the volume of the global trade in live amphibians, the risk of individuals harboring infection, and information on the recent listing by the World Organization for Animal Health (OIE) of chytridiomycosis and ranaviral disease in the OIE Aquatic Animal Health Code. This listing made chytridiomycosis and ranaviral disease internationally notifiable diseases and thus subject to OIE standards, which aim to assure the sanitary safety of international trade in live amphibians and their products.


Host-pathogen interactions during coronavirus infection of primary alveolar epithelial cells.
Viruses that infect the lung are a significant cause of morbidity and mortality in animals and humans worldwide. Coronaviruses are being associated increasingly with severe diseases in the lower respiratory tract. Alveolar epithelial cells are an important target for coronavirus infection in the lung, and infected cells can initiate innate immune responses to viral infection. In this overview, we describe in vitro models of highly differentiated alveolar epithelial cells that are currently being used to study the innate immune response to coronavirus infection. We have shown that rat coronavirus infection of rat alveolar type I epithelial cells in vitro induces expression of CXC chemokines, which may recruit and activate neutrophils. Although neutrophils are recruited early in infection in several coronavirus models including rat coronavirus. However, their role in viral clearance and/or immune-mediated tissue damage is not understood. Primary cultures of differentiated alveolar epithelial cells will be useful for identifying the interactions between coronaviruses and alveolar epithelial cells that influence the innate immune responses to infection in the lung. Understanding the molecular details of these interactions will be critical for the design of effective strategies to prevent and treat coronavirus infections in the lung.


The structural characterization of a prophage-encoded extracellular DNase from Streptococcus pyogenes.
The pathogenic bacterium Group A Streptococcus pyogenes produces several extracellular DNases that have been shown to facilitate invasive infection by evading the human host immune system. DNases degrade the chromatin in neutrophil extracellular traps, enabling the bacterium to evade neutrophil capture. Spd1 is a type I, nonspecific ββα/metal-dependent nuclease from Streptococcus pyogenes, which is encoded by the SF370.1 prophage and is likely to be expressed as a result of prophage induction. We present here the X-ray structure of this DNase in the wild-type and Asn145Ala mutant form. Through structural and sequence alignments as well as mutagenesis studies, we have identified the key residues His121, Asn145 and Glu164, which are crucial for Spd1 nucleolytic activity and shown the active site constellation. Our wild-type structure alludes to the possibility of a catalytically blocked dimeric form of the protein. We have investigated the multimeric nature of Spd1 using size-exclusion chromatography with multi-angle light scattering (SEC-MALLS) in the presence and absence of the divalent metal ion Mg(2+), which suggests that Spd1 exists in a monomeric form in solution.


Socioeconomic disadvantage, social participation and networks and the self-rated health of English men and women with mild and moderate intellectual disabilities: cross sectional survey.
Extremely high rates of mortality and morbidity have been reported among people with intellectual disabilities. Virtually no research has addressed the potential social determinants of health status within this very vulnerable population. Cross-sectional survey of self-reported health status and indicators of socioeconomic disadvantage and social connectedness in 1273 English adults with mild or moderate intellectual disabilities. Indicators of socioeconomic disadvantage accounted for a statistically significant proportion of variation in health status, over and above any variation attributable to the personal characteristics and living circumstances of participants. Indicators of social participation and networks did not add to the explanatory power of the model. Among the indicators of socioeconomic disadvantage, hardship was more strongly associated with variation in health status than either employment status or area-level deprivation. As in the general population, self-reported health was associated with indicators of socioeconomic disadvantage, especially hardship. In contrast, there was no evidence of any association between health status and social participation and networks.


The Effect of Previous Wingate Performance Using one Body Region on Subsequent Wingate Performance Using a Different Body Region.
The 30 second Wingate Anaerobic Test (WAnT) is the gold standard measure of anaerobic performance. The present investigation aimed to determine if a previous WAnT using one body region significantly affected a subsequent WAnT using a different body region. Twelve male university students (n = 12, 23 ± 2 years, 84 ± 16.1 kg, 178.5 ± 7.4 cm) volunteered to complete two repeated WAnT protocols (either lower body WAnT followed by an upper body WAnT or vice versa) on two separate testing occasions. The upper body WAnT was conducted on a modified electromagnetically braked cycle ergometer using a flywheel braking force corresponding to 5% bodyweight. The lower body WAnT was conducted on an electronically braked cycle ergometer using a flywheel braking force corresponding to 7.5% bodyweight. Participants had a 1 minute rest period for transition between WAnTs. Data are reported as mean ± standard deviation. No significant differences were identified in power indices for the lower body between 30 s WAnTs. When the upper body WAnT was performed 2nd, absolute peak power (p < 0.01), mean power (p < 0.001) and relative mean power (p < 0.001) were significantly lower compared to when the upper body WAnT was performed 1st. The value of maximum revolutions per minute was significantly lower (p < 0.001) when the upper body WAnT was performed after the lower body WAnT, compared to when it was performed 1st (193.3 ± 11.4 1st vs 179.8 ± 14.4 2nd). Previous upper body sprint exercise does not significantly affect lower body sprint exercise; however, previous lower body sprint exercise severely compromises subsequent upper body sprint performance.


Regulatory T cells expanded from HIV-1-infected individuals maintain phenotype, TCR repertoire and suppressive capacity.
While modulation of regulatory T cell (Treg) function and adoptive Treg transfer are being explored as therapeutic modalities in the context of autoimmune diseases, transplantation and cancer, their role in HIV-1 pathogenesis remains less well defined. Controversy persists regarding their beneficial or detrimental effects in HIV-1 disease, which warrants further detailed exploration. Our objectives were to investigate if functional CD4(+) Tregs can be isolated and expanded from HIV-1-infected individuals for experimental or potential future therapeutic use and to determine phenotype and suppressive capacity of expanded Tregs from HIV-1 positive blood and tissue. Tregs and conventional T cell controls were isolated from blood and gut-associated lymphoid tissue of individuals with HIV-1 infection and healthy donors using flow-based cell-sorting. The phenotype of expanded Tregs was assessed by flow-cytometry and quantitative PCR. T-cell receptor ß-chain (TCR-β) repertoire diversity was investigated by deep sequencing. Flow-based T-cell proliferation and chromium release cytotoxicity assays were used to determine Treg suppressive function. Tregs from HIV-1 positive individuals, including infants, were successfully expanded from PBMC and GALT. Expanded Tregs expressed high levels of FOXP3, CTLA4, CD39 and HELIOS and exhibited a highly demethylated TSDR (Treg-specific demethylated region), characteristic of Treg lineage. The TCRß repertoire was maintained following Treg expansion and expanded Tregs remained highly suppressive in vitro. Our data demonstrate that Tregs can be expanded from blood and tissue compartments of HIV-1+ donors with preservation of Treg phenotype, function and TCR repertoire. These results are highly relevant for the investigation of potential future therapeutic use, as currently investigated for other disease states and hold great promise for detailed studies on the role of Tregs in HIV-1 infection.


Sensorimotor coupling in music and the psychology of the groove.
The urge to move in response to music, combined with the positive affect associated with the coupling of sensory and motor processes while engaging with music (referred to as sensorimotor coupling) in a seemingly effortless way, is commonly described as the feeling of being in the groove. Here, we systematically explore this compelling phenomenon in a population of young adults. We utilize multiple levels of analysis, comprising phenomenological, behavioral, and computational techniques. Specifically, we show (a) that the concept of the groove is widely appreciated and understood in terms of a pleasurable drive toward action, (b) that a broad range of musical excerpts can be appraised reliably for the degree of perceived groove, (c) that the degree of experienced groove is inversely related to experienced difficulty of bimanual sensorimotor coupling under tapping regimes with varying levels of expressive constraint, (d) that high-groove stimuli elicit spontaneous rhythmic movements, and (e) that quantifiable measures of the quality of sensorimotor coupling predict the degree of experienced groove. Our results complement traditional discourse regarding the groove, which has tended to take the psychological phenomenon for granted and has focused instead on the musical and especially the rhythmic qualities of particular genres of music that lead to the perception of groove. We conclude that groove can be treated as a psychological construct and model system that allows for experimental exploration of the relationship between sensorimotor coupling with music and emotion.


Hepatic perfusion changes in patients with liver metastases: comparison with those patients with cirrhosis.
Previous studies using dynamic scintigraphy have shown that the measurement of changes in hepatic perfusion may be exploited to detect liver metastases. Similar hepatic haemodynamic changes also occur in cirrhosis, however, thereby reducing the diagnostic power of the technique. The ability of duplex colour Doppler sonography (DCDS) to differentiate between the changes in liver perfusion in patients with cirrhosis and those with hepatic metastases was assessed. Hepatic arterial and portal venous blood flows were measured in 30 control subjects, 20 patients with cirrhosis, and 55 patients with overt liver metastases. The Doppler perfusion index (DPI) (the rate of hepatic arterial to total liver blood flow) and the congestive index (ratio of the cross sectional area of the vessel to time averaged velocity of blood flow in the vessel) of the hepatic artery (HCI) and portal vein (PCI) were calculated. The hepatic arterial blood flow of the cirrhotic and metastatic groups was significantly raised compared with that of controls, and the portal venous blood flow of the former groups were reduced (p < 0.0001). The DPIs of the cirrhotic and metastatic groups were therefore significantly raised compared with those of controls (p < 0.0001). No significant difference was noted in HCI values between the three groups. The PCI values of the cirrhotic group, however, were significantly raised compared with those of controls and patients with metastases (p < 0.0001). The data suggest that DCDS measurement of PCI may be of value in differentiating between the hepatic perfusion changes caused by cirrhosis and those resulting from hepatic metastases, thereby increasing the diagnostic power of this technique.


Further studies on single fibres of bovine muscles.
Young & Davey (1981) (Biochem. J. 195, 317-327) identified numbers of polymorphs of myofibrillar proteins by sodium dodecyl sulphate/polyacrylamide gel electrophoresis of single muscle fibres isolated from three bovine muscles. Fibres were classed according to the distribution of polymorphs. The study has now been extended to eight diverse bovine muscles. The previous distinction made between fast and slow fibres is valid without exception in the extended study. Within these classes, variations in myofibrillar expression are examined within and between fibres, muscles and animals. Two slow muscles are contrasted; masseter is homogeneous in fibre type, whereas diaphragm is subtly heterogeneous, possibly arising from greater physiological demands. Of the myofibrillar polymorphs, attention is concentrated on two variants of fast-muscle myosin heavy chain. Both are present in all fast and mixed muscles examined, except sternomandibularis, and each is respectively associated with certain unidentified proteins. Within a muscle the fast-muscle myosin light-chain expression is the same irrespective of the heavy-chain variant. Histochemical techniques demonstrated that the variants are respectively associated with types IIA and IIB as defined by other investigators.


The burden of traumatic brain injury from low-energy falls among patients from 18 countries in the CENTER-TBI Registry: A comparative cohort study.
Traumatic brain injury (TBI) is an important global public health burden, where those injured by high-energy transfer (e.g., road traffic collisions) are assumed to have more severe injury and are prioritised by emergency medical service trauma triage tools. However recent studies suggest an increasing TBI disease burden in older people injured through low-energy falls. We aimed to assess the prevalence of low-energy falls among patients presenting to hospital with TBI, and to compare their characteristics, care pathways, and outcomes to TBI caused by high-energy trauma. We conducted a comparative cohort study utilising the CENTER-TBI (Collaborative European NeuroTrauma Effectiveness Research in TBI) Registry, which recorded patient demographics, injury, care pathway, and acute care outcome data in 56 acute trauma receiving hospitals across 18 countries (17 countries in Europe and Israel). Patients presenting with TBI and indications for computed tomography (CT) brain scan between 2014 to 2018 were purposively sampled. The main study outcomes were (i) the prevalence of low-energy falls causing TBI within the overall cohort and (ii) comparisons of TBI patients injured by low-energy falls to TBI patients injured by high-energy transfer-in terms of demographic and injury characteristics, care pathways, and hospital mortality. In total, 22,782 eligible patients were enrolled, and study outcomes were analysed for 21,681 TBI patients with known injury mechanism; 40% (95% CI 39% to 41%) (8,622/21,681) of patients with TBI were injured by low-energy falls. Compared to 13,059 patients injured by high-energy transfer (HE cohort), the those injured through low-energy falls (LE cohort) were older (LE cohort, median 74 [IQR 56 to 84] years, versus HE cohort, median 42 [IQR 25 to 60] years; p < 0.001), more often female (LE cohort, 50% [95% CI 48% to 51%], versus HE cohort, 32% [95% CI 31% to 34%]; p < 0.001), more frequently taking pre-injury anticoagulants or/and platelet aggregation inhibitors (LE cohort, 44% [95% CI 42% to 45%], versus HE cohort, 13% [95% CI 11% to 14%]; p < 0.001), and less often presenting with moderately or severely impaired conscious level (LE cohort, 7.8% [95% CI 5.6% to 9.8%], versus HE cohort, 10% [95% CI 8.7% to 12%]; p < 0.001), but had similar in-hospital mortality (LE cohort, 6.3% [95% CI 4.2% to 8.3%], versus HE cohort, 7.0% [95% CI 5.3% to 8.6%]; p = 0.83). The CT brain scan traumatic abnormality rate was 3% lower in the LE cohort (LE cohort, 29% [95% CI 27% to 31%], versus HE cohort, 32% [95% CI 31% to 34%]; p < 0.001); individuals in the LE cohort were 50% less likely to receive critical care (LE cohort, 12% [95% CI 9.5% to 13%], versus HE cohort, 24% [95% CI 23% to 26%]; p < 0.001) or emergency interventions (LE cohort, 7.5% [95% CI 5.4% to 9.5%], versus HE cohort, 13% [95% CI 12% to 15%]; p < 0.001) than patients injured by high-energy transfer. The purposive sampling strategy and censorship of patient outcomes beyond hospital discharge are the main study limitations. We observed that patients sustaining TBI from low-energy falls are an important component of the TBI disease burden and a distinct demographic cohort; further, our findings suggest that energy transfer may not predict intracranial injury or acute care mortality in patients with TBI presenting to hospital. This suggests that factors beyond energy transfer level may be more relevant to prehospital and emergency department TBI triage in older people. A specific focus to improve prevention and care for patients sustaining TBI from low-energy falls is required.


Childhood trauma and adulthood physical health in Mexico.
The present study examined the effect of childhood trauma on adulthood physical health among a randomly selected sample of adults (N = 2,177) in urban Mexico. Adults were interviewed about their experiences of trauma, post-traumatic stress disorder, depression, and physical health symptoms using Module K of the Composite International Diagnostic Interview, the Center for Epidemiologic Studies Depression Scale, and the Physical Symptoms Checklist. Trauma was prevalent, with 35% reporting a traumatic event in childhood. In general, men reported more childhood trauma than women, with the exception of childhood sexual violence where women reported more exposure. For men, childhood sexual violence was related to total and all physical health symptom subscales. For women, childhood sexual violence was related to total, muscular-skeletal, and gastrointestinal-urinary symptoms; hazards/accidents in childhood were related to total, muscular-skeletal, cardio-pulmonary, and nose-throat symptom subscales. Depression mediated the relationship between childhood sexual violence and physical health symptoms for men and women. Among women only, PTSD mediated the relationship between childhood sexual violence and total, muscular-skeletal, and gastrointestinal-urinary symptoms. PTSD also mediated the relationship between hazards/accidents in childhood and total, muscular-skeletal, cardio-pulmonary, and nose-throat symptoms. These findings can be used to increase awareness among general practitioners, as well as community stakeholders, about the prevalence of childhood trauma in Mexican communities and its impact on subsequent physical health outcomes. With this awareness, screening practices could be developed to identify those with trauma histories in order to increase positive health outcomes among trauma survivors.


The effect of pulsed 900-MHz GSM mobile phone radiation on the acrosome reaction, head morphometry and zona binding of human spermatozoa.
Several recent studies have indicated that radiofrequency electromagnetic fields (RF-EMF) have an adverse effect on human sperm quality, which could translate into an effect on fertilization potential. This study evaluated the effect of RF-EMF on sperm-specific characteristics to assess the fertilizing competence of sperm. Highly motile human spermatozoa were exposed for 1 h to 900-MHz mobile phone radiation at a specific absorption rate of 2.0 W/kg and examined at various times after exposure. The acrosome reaction was evaluated using flow cytometry. The radiation did not affect sperm propensity for the acrosome reaction. Morphometric parameters were assessed using computer-assisted sperm analysis. Significant reduction in sperm head area (9.2 ± 0.7 μm² vs. 18.8 ± 1.4 μm²) and acrosome percentage of the head area (21.5 ± 4% vs. 35.5 ± 11.4%) was reported among exposed sperm compared with unexposed controls. Sperm-zona binding was assessed directly after exposure using the hemizona assay. The mean number of zona-bound sperm of the test hemizona and controls was 22.8 ± 12.4 and 31.8 ± 12.8 (p < 0.05), respectively. This study concludes that although RF-EMF exposure did not adversely affect the acrosome reaction, it had a significant effect on sperm morphometry. In addition, a significant decrease in sperm binding to the hemizona was observed. These results could indicate a significant effect of RF-EMF on sperm fertilization potential.


MOVE-HF: an internet-based pilot study to improve adherence to exercise in patients with heart failure.
The use of the internet and newer activity monitors such as the Fitbit Charge HR to improve exercise adherence is limited. The primary aim of the Move on Virtual Engagement (MOVE-HF) was to investigate the effects of group social support by internet-based synchronized face-to-face video and objective physical activity feedback on adherence to recommended exercise guidelines. Thirty stable heart failure patients (New York Heart Association class I-III), aged 64.7±11.5 years, were randomly assigned to an experimental or comparison group. Participants were provided a handout on self-care in heart failure, an exercise routine, a Fitbit Charge HR and were asked to wear the Fitbit Charge HR daily, and record their exercise sessions using both the Fitbit Charge HR and exercise diaries. In addition, participants in the experimental group connected to Vidyo software, once a week, for 8 weeks, for a 45-minute face-to-face online group discussion/education session. Overall Vidyo session attendance was 68%, with 73% of participants attending five or more sessions. Adherence to exercise was 58.8% in the experimental group and 57.3% in the comparison group. The experimental group perceived receiving social support through the internet-based synchronized face-to-face video meetings but due to a small sample size and lack of adequate power, no significant impact on exercise adherence was observed. Participants commented that feedback regarding physical activity from the Fitbit Charge HR was helpful and motivational. Delivering social support by internet-based synchronized face-to-face video is feasible with heart failure patients. However, more investigations are needed to understand its impact on exercise adherence.


Three Months Monitored Metabolic Fitness Modulates Cardiovascular Risk Factors in Diabetic Patients.
Cardiovascular diseases represent the leading cause of death and moderate physical exercise is associated with a reduction in cardiovascular risk. The aim of the study was to evaluate the correlation between the amount of exercise recorded daily by a wearable gravitometer for 3 months and selected biochemical and clinical parameters. Nineteen sedentary type 2 diabetics were recruited and distributed into three homogenous groups, low, medium, and high exercise, according to the level of physical exercise monitored and expressed as MOVEs. Data showed an inverse correlation between MOVEs and oxidative stress indexes and a significant improvement in paraoxonase-1 activities and endothelial functionality. Decrease of visceral/total adipose tissue ratio, systolic blood pressure and a down-regulation of the inflammatory microRNA-146a in high exercise group were observed. Finally, a decrease of glycosylated hemoglobin and an up-regulation of the angiogenic microRNA-130a in medium exercise one was obtained. In this study, precise daily monitoring permitted to underline the importance of the amount of physical activity to counteract some cardiovascular risk factors persisting in diabetes. Finally, it identifies new microRNA biomarkers for future investigation on the same topic.


Laparoscopic transdiaphragmatic access to the apex of the left ventricle of the heart.
: Delivery of a collapsable aortic valve prosthesis via the left ventricular (LV) apex has proven problematic clinically. We describe our experience with a novel technique for a laparoscopic transdiaphragmatic approach to the LV outflow tract (LVOT). : Laparoscopic transabdominal access to the left ventricle was achieved in four live swine and one human cadaver using three abdominal laparoscopic trocars. Pericardioscopy and cardioscopy were performed. A hemostatic purse-string suture was placed laparoscopically at the apex of the left ventricle in one pig, and an instrument passed through the purse-string and into the LVOT. After the procedure, a thoracotomy was performed and the heart explanted for gross examination. : Transdiaphragmatic exposure of the LV apex was accomplished at a mean of 23 minutes. Hemodynamic stability was maintained in all animals and the pleural cavities were not violated. Pericardioscopy allowed visualization of both right and left pulmonary veins along with the left atrial appendage. In situ cardioscopy confirmed that access to the LVOT and the aortic annulus was possible from the LV apex entry site. : Laparoscopic transdiaphragmatic approach to the LVOT is a possible route for minimally invasive beating heart aortic valve implantation. This strategy permits a straight transapical line of access to the aortic valve; avoiding the potential for cardiac torsion via a thoracotomy.


Characterization of a minus end-directed kinesin-like motor protein from cultured mammalian cells.
Using the CHO2 monoclonal antibody raised against CHO spindles (Sellitto, C., M. Kimble, and R. Kuriyama. 1992. Cell Motil. Cytoskeleton. 22:7-24) we identified a 66-kD protein located at the interphase centrosome and mitotic spindle. Isolated cDNAs for the antigen encode a 622-amino acid polypeptide. Sequence analysis revealed the presence of 340-amino acid residues in the COOH terminus, which is homologous to the motor domain conserved among other members of the kinesin superfamily. The protein is composed of a central alpha-helical portion with globular domains at both NH2 and COOH termini, and the epitope to the monoclonal antibody resides in the central alpha-helical stalk. A series of deletion constructs were created for in vitro analysis of microtubule interactions. While the microtubule binding and bundling activities require both the presence of the COOH terminus and the alpha-helical domain, the NH2-terminal half of the antigen lacked the ability to interact with microtubules. The full-length as well as deleted proteins consisting of the COOH-terminal motor and the central alpha-helical stalk supported microtubule gliding, with velocity ranging from 1.0 to 8.4 microns/minute. The speed of microtubule movement decreased with decreasing lengths of the central stalk attached to the COOH-terminal motor. The microtubules moved with their plus end leading, indicating that the antigen is a minus end-directed motor. The CHO2 sequence shows 86% identify to HSET, a gene located at the centromeric end of the human MHC region in chromosome 6 (Ando, A., Y. Y. Kikuti, H. Kawata, N. Okamoto, T. Imai, T. Eki, K. Yokoyama, E. Soeda, T. Ikemura, K. Abe, and H. Inoko. 1994. Immunogenetics. 39:194-200), indicating that HSET might represent a human homologue of the CHO2 antigen.


High performance relaxor-based ferroelectric single crystals for ultrasonic transducer applications.
Relaxor-based ferroelectric single crystals Pb(Mg1/3Nb2/3)O3-PbTiO3 (PMN-PT) have drawn much attention in the ferroelectric field because of their excellent piezoelectric properties and high electromechanical coupling coefficients (d33~2000 pC/N, kt~60%) near the morphotropic phase boundary (MPB). Ternary Pb(In1/2Nb1/2)O3-Pb(Mg1/3Nb2/3)O3-PbTiO3 (PIN-PMN-PT) single crystals also possess outstanding performance comparable with PMN-PT single crystals, but have higher phase transition temperatures (rhombohedral to tetragonal Trt, and tetragonal to cubic Tc) and larger coercive field Ec. Therefore, these relaxor-based single crystals have been extensively employed for ultrasonic transducer applications. In this paper, an overview of our work and perspectives on using PMN-PT and PIN-PMN-PT single crystals for ultrasonic transducer applications is presented. Various types of single-element ultrasonic transducers, including endoscopic transducers, intravascular transducers, high-frequency and high-temperature transducers fabricated using the PMN-PT and PIN-PMN-PT crystals and their 2-2 and 1-3 composites are reported. Besides, the fabrication and characterization of the array transducers, such as phased array, cylindrical shaped linear array, high-temperature linear array, radial endoscopic array, and annular array, are also addressed.


Analysis of economic evaluations of pharmacological cancer treatments in Spain between 1990 and 2010.
Economic evaluation of pharmacological cancer treatment is a critical clinical problem currently under consideration worldwide. We have analysed their main characteristics in Spain between 1990 and 2010 following a systematic review of the 29 complete economic analyses published. The pathology most frequently evaluated was non-small cell lung cancer (31 %). Cost-effectiveness analyses (69 %) were the most frequent analyses. A wide range of incremental cost-effectiveness values (295-160,667 € /QALY) has been reported, and mostly are developed from the perspective of the National Health System (65.5 %). However, none of the studies estimated the indirect costs. The major conclusion is that the absence of regulations concerning the application of the efficiency criterion in decision-making on the subject of price and financing and, most importantly, the fact that these are not included in Spanish hospitals forms make it difficult to analyse the real impact of economic evaluations of cancer treatments on such decisions.


Exploring Factors Associated With Morbidity and Mortality in Patients With Do-Not-Resuscitate Orders: A National Surgical Quality Improvement Program Database Analysis Within Surgical Groups.
Anesthesiologists caring for patients with do-not-resuscitate (DNR) orders may have ethical concerns because of their resuscitative wishes and may have clinical concerns because of their known increased risk of morbidity/mortality. Patient heterogeneity and/or emphasis on mortality outcomes make previous studies among patients with DNR orders difficult to interpret. We sought to explore factors associated with morbidity and mortality among patients with DNR orders, which were stratified by surgical subgroups. Exploratory retrospective cohort study in adult patients undergoing prespecified colorectal, vascular, and orthopedic surgeries was performed using the American College of Surgeons National Surgical Quality Improvement Program Participant Use File data from 2010 to 2013. Among patients with preoperative DNR orders (ie, active DNR order written in the patient's chart before surgery), factors associated with 30-day mortality, increased length of stay, and inpatient death were determined via penalized regression. Unadjusted and adjusted estimates for selected variables are presented. After selection as above, 211,420 patients underwent prespecified procedures, and of those, 2755 (1.3%) had pre-existing DNR orders and met above selection to address morbidity/mortality aims. By specialty, of these patients with a preoperative DNR, 1149 underwent colorectal, 870 vascular, and 736 orthopedic surgery. Across groups, 36.2% were male and had a mean age 79.9 years (range 21-90). The 30-day mortality was 15.4%-27.2% and median length of stay was 6-12 days. Death at discharge was 7.0%, 13.1%, and 23.0% in orthopedics, vascular, and colorectal patients with a DNR, respectively. The strongest factors associated with increased odds of 30-day mortality were preoperative septic shock in colorectal patients, preoperative ascites in vascular patients, and any requirement of mechanical ventilation at admission in orthopedic patients. In patients with DNR orders undergoing common surgical procedures, the association of characteristics with morbidity and mortality varies in both direction and magnitude. The DNR order itself should not be the defining measure of risk.


Understanding the persistence of plague foci in Madagascar.
Plague, a zoonosis caused by Yersinia pestis, is still found in Africa, Asia, and the Americas. Madagascar reports almost one third of the cases worldwide. Y. pestis can be encountered in three very different types of foci: urban, rural, and sylvatic. Flea vector and wild rodent host population dynamics are tightly correlated with modulation of climatic conditions, an association that could be crucial for both the maintenance of foci and human plague epidemics. The black rat Rattus rattus, the main host of Y. pestis in Madagascar, is found to exhibit high resistance to plague in endemic areas, opposing the concept of high mortality rates among rats exposed to the infection. Also, endemic fleas could play an essential role in maintenance of the foci. This review discusses recent advances in the understanding of the role of these factors as well as human behavior in the persistence of plague in Madagascar.


A two-year program of aerobics and weight training enhances bone mineral density of young women.
Previous research suggests that physical activity may have a beneficial effect on bone mineral density (BMD) in women. This relationship was explored in a 2-year, randomized, intervention trial investigating the efficacy of exercise and calcium supplementation on increasing peak bone mass in young women. One hundred and twenty-seven subjects (ages of 20-35 years) were randomly assigned either to an exercise program that contained both aerobics and weight training components or to a stretching program. Calcium supplementation (up to 1500 mg/day including dietary intake) or placebo was given in a double-blinded design to all subjects. Spinal trabecular BMD was determined using quantitative computed tomography (QCT). Spinal integral, femoral neck, and trochanteric BMD were measured by dual X-ray absorptiometry (DXA) and calcaneal BMD by single photon absorptiometry (SPA). Fitness variables included maximal aerobic capacity (VO2max), and isokinetic muscle performance of the trunk and thigh. Measurements were made at baseline, 1 year, and 2 years. Sixty-three subjects (32 exercise, 31 stretching) completed the study, and all the measured bone parameters indicated a positive influence of the exercise intervention. There were significant positive differences in BMD between the exercise and stretching groups for spinal trabecular (2.5%), femoral neck (2.4%), femoral trochanteric (2.3%), and calcaneal (6.4%) measurements. The exercise group demonstrated a significant gain in BMD for spinal integral (1.3 +/- 2.8%, p < 0.02), femoral trochanteric (2.6 +/- 6.1%, p < 0.05), and calcaneal (5.6 +/- 5.1, p < 0.01) measurements. In contrast to exercise, the calcium intervention had no positive effect on any of the bone parameters. In regard to fitness parameters, the exercise group completed the study with significant gains in VO2max and isokinetic (peak torque) values for the knee flexion and extension and trunk extension. This study indicates that over a 2-year period, a combined regimen of aerobics and weight training has beneficial effects on BMD and fitness parameters in young women. However, the addition of daily calcium supplementation does not add significant benefit to the intervention.


Unraveling the temporal pattern of diet-induced insulin resistance in individual organs and cardiac dysfunction in C57BL/6 mice.
Type 2 diabetes is a heterogeneous disease characterized by insulin resistance and altered glucose and lipid metabolism in multiple organs. To understand the complex series of events that occur during the development of obesity-associated diabetes, we examined the temporal pattern of changes in insulin action and glucose metabolism in individual organs during chronic high-fat feeding in C57BL/6 mice. Insulin-stimulated cardiac glucose metabolism was significantly reduced after 1.5 weeks of high-fat feeding, and cardiac insulin resistance was associated with blunted Akt-mediated insulin signaling and GLUT4 levels. Insulin resistance in skeletal muscle, adipose tissue, and liver developed in parallel after 3 weeks of high-fat feeding. Diet-induced whole-body insulin resistance was associated with increased circulating levels of resistin and leptin but unaltered adiponectin levels. High-fat feeding caused insulin resistance in skeletal muscle that was associated with significantly elevated intramuscular fat content. In contrast, diet-induced hepatic insulin resistance developed before a marked increase in intrahepatic triglyceride levels. Cardiac function gradually declined over the course of high-fat feeding, and after 20 weeks of high-fat diet, cardiac dysfunction was associated with mild hyperglycemia, hyperleptinemia, and reduced circulating adiponectin levels. Our findings demonstrate that cardiac insulin resistance is an early adaptive event in response to obesity and develops before changes in whole-body glucose homeostasis. This suggests that obesity-associated defects in cardiac function may not be due to insulin resistance per se but may be attributable to chronic alteration in cardiac glucose and lipid metabolism and circulating adipokines.


Peripheral nerve stimulation in intractable neuropathic pain.
Peripheral nerve stimulation (PNS) is a neurostimulation analgesic technique. PNS is utilized to treat peripheral neuropathic pain. It is highly sophisticated and a specialized technique used where other forms of treatment have failed. This paper describes the PNS procedure, its therapeutic principles, indications, and the comprehensive care for patients after the PNS implant. First, we summarize our experience using this type of invasive treatment. In the second part, a case of intractable neuropathic pain following repeated surgery to the ulnar nerve is reported. Prior to PNS, the patient underwent multiple types of antineuralgic treatment with no significant result. Only after the PNS application, was a significant analgesic effect achieved.


Forward-directed bremsstrahlung of 10- to 30-MeV electrons incident on thick targets of Al and Pb.
Bremsstrahlung spectra from thick targets of Al and Pb have been measured absolutely (photons per incident electron) along the beam axis for electrons of 10-, 15-, 20-, 25-, and 30-MeV incident energy. The spectra have a 220-keV low-energy cutoff. The targets were cylinders with nominal thicknesses of 110% of the electron CSDA range. A thin transmission detector, calibrated against a toroidal current monitor, was placed upstream of the target to measure the beam current. The spectrometer was a 20-cm diameter by 25-cm-long cylindrical NaI detector. Measured spectra were corrected for pile-up, background, detector response, detector efficiency, attenuation in materials between the target and detector and the collimator effect. Spectra were calculated using the EGS4 Monte Carlo system for simulating the radiation transport. The simulation model included the small amount of material upstream of the target. This material contributed about 40% of the spectrum, but its presence or absence had little effect on the calculated bremsstrahlung yield. The shapes of the measured and calculated spectra were in excellent agreement. The ratio of the total number of photons in each measured spectrum to those in the corresponding calculated spectrum varied from 0.97 +/- 0.06 to 1.12 +/- 0.06, depending largely on the atomic number of the target. Absolute spectral measurements in the literature agreed with our calculations of spectral shape but showed a range of +/- 30% in the number of photons per incident electron relative to the calculated values, which is contrary to our result.


A novel 3D constellation-masked method for physical security in hierarchical OFDMA system.
This paper proposes a novel 3D constellation-masked method to ensure the physical security in hierarchical optical orthogonal frequency division multiplexing access (OFDMA) system. The 3D constellation masking is executed on the two levels of hierarchical modulation and among different OFDM subcarriers, which is realized by the masking vectors. The Lorenz chaotic model is adopted for the generation of masking vectors in the proposed scheme. A 9.85 Gb/s encrypted hierarchical QAM OFDM signal is successfully demonstrated in the experiment. The performance of illegal optical network unit (ONU) with different masking vectors is also investigated. The proposed method is demonstrated to be secure and efficient against the commonly known attacks in the experiment.


Nuclear accumulation of histone deacetylase 4 (HDAC4) coincides with the loss of androgen sensitivity in hormone refractory cancer of the prostate.
To examine the effect of androgen treatment upon histone deacetylase 4 (HDAC4) localisation and, thus, enzymatic function in androgen sensitive prostate cancer (CaP) models. To study HDAC4 expression in benign prostatic hyperplasia, primary and hormone refractory (HR) CaP and to investigate the involvement of histone deacetylase activity in the development of the androgen insensitive phenotype. Immunohistochemical staining of prostate sections of both benign tissue and primary and hormone relapsed prostate cancer, as well as of the CWR22 mouse xenograft model, and indirect quantitative immunofluorescence staining of endogenous HDAC4 in LNCaP cells. HDAC4 is recruited to the nuclei of HR cancer cells, where it may exert an inhibitory effect on differentiation and contribute to the development of the aggressive phenotype of late stage CaP. The above may result from the loss of androgen responsiveness characterising HR CaP, since HDAC4 nuclear localisation is regulated by androgens in androgen responsive systems (i.e. LNCaP, CWR22) reflecting earlier phase disease. HDAC4 may contribute to the development of HR CaP and, therefore, constitute a potential therapeutic target, particularly in the most lethal phase of androgen independence.


Exploring resistance to implementation of welfare technology in municipal healthcare services - a longitudinal case study.
Industrialized and welfare societies are faced with vast challenges in the field of healthcare in the years to come. New technological opportunities and implementation of welfare technology through co-creation are considered part of the solution to this challenge. Resistance to new technology and resistance to change is, however, assumed to rise from employees, care receivers and next of kin. The purpose of this article is to identify and describe forms of resistance that emerged in five municipalities during a technology implementation project as part of the care for older people. This is a longitudinal, single-embedded case study with elements of action research, following an implementation of welfare technology in the municipal healthcare services. Participants included staff from the municipalities, a network of technology developers and a group of researchers. Data from interviews, focus groups and participatory observation were analysed. Resistance to co-creation and implementation was found in all groups of stakeholders, mirroring the complexity of the municipal context. Four main forms of resistance were identified: 1) organizational resistance, 2) cultural resistance, 3) technological resistance and 4) ethical resistance, each including several subforms. The resistance emerges from a variety of perceived threats, partly parallel to, partly across the four main forms of resistance, such as a) threats to stability and predictability (fear of change), b) threats to role and group identity (fear of losing power or control) and c) threats to basic healthcare values (fear of losing moral or professional integrity). The study refines the categorization of resistance to the implementation of welfare technology in healthcare settings. It identifies resistance categories, how resistance changes over time and suggests that resistance may play a productive role when the implementation is organized as a co-creation process. This indicates that the importance of organizational translation between professional cultures should not be underestimated, and supports research indicating that focus on co-initiation in the initial phase of implementation projects may help prevent different forms of resistance in complex co-creation processes.


Thiamine plays a critical role in the acid tolerance of Listeria monocytogenes.
Understanding the molecular basis of acid tolerance in the food-borne pathogen Listeria monocytogenes is important as this property contributes to survival in the food-chain and enhances survival within infected hosts. The aim of this study was to identify genes contributing to acid tolerance in L. monocytogenes using transposon mutagenesis and subsequently to elucidate the physiological role of these genes in acid tolerance. One mutant harboring a Tn917 insertion in the thiT gene (formerly lmo1429), which encodes a thiamine (vitamin B1) uptake system, was found to be highly sensitive to acid. The acid-sensitive phenotype associated with loss of this gene was confirmed with an independently isolated mutant, from which the thiT gene was deleted (∆thiT). Cells of both wild-type and ∆thiT mutant that were thiamine depleted were found to be significantly more acid sensitive than control cultures. Thiamine-depleted cultures failed to produce significant concentrations of acetoin, consistent with the known thiamine dependence of acetolactate synthase, an enzyme required for acetoin synthesis from pyruvate. As acetoin synthesis is a proton-consuming process, we suggest that the acid sensitivity observed in thiamine-depleted cultures may be owing to an inability to produce acetoin.


Protamine reversal of heparin affects platelet aggregation and activated clotting time after cardiopulmonary bypass.
Bleeding after cardiopulmonary bypass (CPB) is related to multiple factors. Excess protamine weakens clot structure and decreases platelet function; therefore, an increased activated clotting time (ACT) after protamine reversal of heparin may be misinterpreted as residual heparin anticoagulation. We evaluated the effects of protamine, recombinant platelet factor 4 (rPF4), and hexadimethrine on ACT in blood obtained after CPB. In addition, we examined the effect of protamine on in vitro platelet aggregation. Incremental doses of protamine, rPF4, and hexadimethrine were added to heparinized blood from CPB, and ACTs were performed. Incremental concentrations of protamine were added to heparinized platelet-rich plasma, and aggregometry was induced by adenosine diphosphate (ADP) and collagen. The mean heparin concentration at the end of CPB was 3.3 U/mL. Protamine to heparin ratios >1.3:1 produced a significant prolongation of the ACT that was not seen with rPF4 and was observed only with 5:1 hexadimethrine to heparin ratios. ADP-induced platelet aggregation was reduced with protamine administration > or =1.3:1. Excessive protamine reversal of heparin prolongs ACT and alters ADP-induced platelet aggregation in a dose-dependent manner in vitro. Additional protamine administered to treat a prolonged ACT may further increase clotting time, reduce platelet aggregation, and potentially contribute to excess bleeding after CPB. We found that excess protamine prolonged the activated clotting time and altered platelet function after cardiopulmonary bypass, whereas heparin antagonists, such as recombinant platelet factor 4 and hexadimethrine, exhibited a wider therapeutic range without adversely affecting the activated clotting time. Approaches to avoid excess protamine or use of alternative heparin antagonists after cardiopulmonary bypass may be beneficial.


Matching shape sequences in video with applications in human movement analysis.
We present an approach for comparing two sequences of deforming shapes using both parametric models and nonparametric methods. In our approach, Kendall's definition of shape is used for feature extraction. Since the shape feature rests on a non-Euclidean manifold, we propose parametric models like the autoregressive model and autoregressive moving average model on the tangent space and demonstrate the ability of these models to capture the nature of shape deformations using experiments on gait-based human recognition. The nonparametric model is based on Dynamic Time-Warping. We suggest a modification of the Dynamic time-warping algorithm to include the nature of the non-Euclidean space in which the shape deformations take place. We also show the efficacy of this algorithm by its application to gait-based human recognition. We exploit the shape deformations of a person's silhouette as a discriminating feature and provide recognition results using the nonparametric model. Our analysis leads to some interesting observations on the role of shape and kinematics in automated gait-based person authentication.


Clinical indications for the albumin use: still a controversial issue.
Human serum albumin (HSA) is the most abundant circulating protein and accounts for about 70% of the plasma colloid osmotic pressure. Beside the well known capacity to act as plasma-expander, HSA is provided of many other properties which are unrelated to the regulation of fluid compartmentalization, including binding and transport of many endogenous and exogenous substances, antioxidant function, immuno-modulation, anti-inflammatory activity, and endothelial stabilization. Treatment (hepatorenal syndrome) or prevention (renal failure after spontaneous bacterial peritonitis and post-paracentesis circulatory dysfunction after large volume paracentesis) of severe clinical complications in patients with cirrhosis and fluid resuscitation in critically ill patients, when crystalloids and non-proteic colloids are not effective or contra-indicated, represents the major evidence-based clinical indications for HSA administration. However, a large proportion of HSA prescription is inappropriate. Despite the existence of solid data against a real benefit, HSA is still given for nutritional interventions or for correcting hypoalbuminemia per se (without hypovolemia). Other clinical uses for HSA administration not supported by definitive scientific evidence are long-term treatment of ascites, nephrotic syndrome, pancreatitis, abdominal surgery, acute distress respiratory syndrome, cerebral ischemia, and enteric diseases. HSA prescription should be not uncritically restricted. Enforcement of clinical practice recommendations has been shown to allow a more liberal use for indications supported by strong scientific data and to avoid the futile administration in settings where there is a lack of clinical evidence of efficacy. As a result, a more appropriate HSA use can be achieved maintaining the health care expenditure under control.


Physical examination tests of the shoulder: a systematic review and meta-analysis of diagnostic test performance.
Physical examination tests of the shoulder (PETS) are clinical examination maneuvers designed to aid the assessment of shoulder complaints. Despite more than 180 PETS described in the literature, evidence of their validity and usefulness in diagnosing the shoulder is questioned. This meta-analysis aims to use diagnostic odds ratio (DOR) to evaluate how much PETS shift overall probability and to rank the test performance of single PETS in order to aid the clinician's choice of which tests to use. This study adheres to the principles outlined in the Cochrane guidelines and the PRISMA statement. A fixed effect model was used to assess the overall diagnostic validity of PETS by pooling DOR for different PETS with similar biomechanical rationale when possible. Single PETS were assessed and ranked by DOR. Clinical performance was assessed by sensitivity, specificity, accuracy and likelihood ratio. Six thousand nine-hundred abstracts and 202 full-text articles were assessed for eligibility; 20 articles were eligible and data from 11 articles could be included in the meta-analysis. All PETS for SLAP (superior labral anterior posterior) lesions pooled gave a DOR of 1.38 [1.13, 1.69]. The Supraspinatus test for any full thickness rotator cuff tear obtained the highest DOR of 9.24 (sensitivity was 0.74, specificity 0.77). Compression-Rotation test obtained the highest DOR (6.36) among single PETS for SLAP lesions (sensitivity 0.43, specificity 0.89) and Hawkins test obtained the highest DOR (2.86) for impingement syndrome (sensitivity 0.58, specificity 0.67). No single PETS showed superior clinical test performance. The clinical performance of single PETS is limited. However, when the different PETS for SLAP lesions were pooled, we found a statistical significant change in post-test probability indicating an overall statistical validity. We suggest that clinicians choose their PETS among those with the highest pooled DOR and to assess validity to their own specific clinical settings, review the inclusion criteria of the included primary studies. We further propose that future studies on the validity of PETS use randomized research designs rather than the accuracy design relying less on well-established gold standard reference tests and efficient treatment options.


Microwave field distribution in a magic angle spinning dynamic nuclear polarization NMR probe.
We present a calculation of the microwave field distribution in a magic angle spinning (MAS) probe utilized in dynamic nuclear polarization (DNP) experiments. The microwave magnetic field (B(1S)) profile was obtained from simulations performed with the High Frequency Structure Simulator (HFSS) software suite, using a model that includes the launching antenna, the outer Kel-F stator housing coated with Ag, the RF coil, and the 4mm diameter sapphire rotor containing the sample. The predicted average B(1S) field is 13μT/W(1/2), where S denotes the electron spin. For a routinely achievable input power of 5W the corresponding value is γ(S)B(1S)=0.84MHz. The calculations provide insights into the coupling of the microwave power to the sample, including reflections from the RF coil and diffraction of the power transmitted through the coil. The variation of enhancement with rotor wall thickness was also successfully simulated. A second, simplified calculation was performed using a single pass model based on Gaussian beam propagation and Fresnel diffraction. This model provided additional physical insight and was in good agreement with the full HFSS simulation. These calculations indicate approaches to increasing the coupling of the microwave power to the sample, including the use of a converging lens and fine adjustment of the spacing of the windings of the RF coil. The present results should prove useful in optimizing the coupling of microwave power to the sample in future DNP experiments. Finally, the results of the simulation were used to predict the cross effect DNP enhancement (ϵ) vs. ω(1S)/(2π) for a sample of (13)C-urea dissolved in a 60:40 glycerol/water mixture containing the polarizing agent TOTAPOL; very good agreement was obtained between theory and experiment.


MDR1-mediated interaction of digoxin with antiarrhythmic or antianginal drugs.
The multidrug transporter, MDR1-mediated interaction of digoxin with antiarrhythmic or antianginal drugs was examined in vitro by using the MDR1-overexpressing LLC-GA5-COL150 cells, which were established by transfection with human MDR1 cDNA into porcine kidney epithelial LLC-PK(1) cells. Amiodarone, its active metabolite monodesethyl-amiodarone (DEA), and quinidine markedly inhibited the basal-to-apical transport (renal secretion) of [(3)H]digoxin and increased the apical-to-basal transport (reabsorption), but cibenzoline and lidocaine showed slight inhibition of the transport, and disopyramide and mexiletin had no such effects. The IC(50) values for amiodarone, DEA and quinidine on [(3)H]digoxin transport in LLC-GA5-COL150 cells were 5.48 microM, 1.27 microM and 9.52 microM, respectively. These were comparable to, or only several times the achievable concentration in clinical use, suggesting that MDR1 could be responsible for the drug interaction between digoxin and amiodarone found in clinical reports and that DEA contributes the elevation of digoxin serum concentration. Similarly, dipyridamole altered the transport, but isosorbide showed only slight modification of the transport. The IC(50) value for dipyridamole was 40.0 microM, also only several times the achievable concentration in clinical use, indicating a risk of interaction.


Aqueous extract of Glycyrrhiza inflata inhibits aggregation by upregulating PPARGC1A and NFE2L2-ARE pathways in cell models of spinocerebellar ataxia 3.
Spinocerebellar ataxia (SCA) types 1, 2, 3, 6, 7, and 17 and dentatorubropallidoluysian atrophy, as well as Huntington disease, are a group of neurodegenerative disorders caused by a CAG triplet-repeat expansion encoding a long polyglutamine (polyQ) tract in the respective mutant proteins. The cytoplasmic and nuclear aggregate formation, a pathological hallmark of polyQ diseases, is probably the initial process triggering the subsequent pathological events. Compromised oxidative stress defense capacity and mitochondrial dysfunction have emerged as contributing factors to the pathogenesis of polyQ diseases. The roots of licorice (Glycyrrhiza species) have long been used as an herbal medicine. In this study, we demonstrate the aggregate-inhibitory effect of Glycyrrhiza inflata herb extract and its constituents licochalcone A and ammonium glycyrrhizinate (AMGZ) in both 293 and SH-SY5Y ATXN3/Q75 cells, SCA3 cell models. The reporter assay showed that G. inflata herb extract, licochalcone A, and AMGZ could enhance the promoter activity of peroxisome proliferator-activated receptor γ, coactivator 1α (PPARGC1A), a known regulator of mitochondrial biogenesis and antioxidative response genes. G. inflata extract, licochalcone A, and AMGZ upregulated PPARGC1A expression and its downstream target genes, SOD2 and CYCS, in the 293 ATXN3/Q75 cell model. The expression of nuclear factor erythroid 2-related factor 2 (NFE2L2), the principal transcription factor that binds to antioxidant-responsive elements (AREs) to promote ARE-dependent gene expression when the cells respond to oxidative stress, and its downstream genes, HMOX1, NQO1, GCLC, and GSTP1, was also increased by G. inflata herb extract, licochalcone A, and AMGZ. Knockdown of PPARGC1A increased aggregates in ATXN3/Q75 cells and also attenuated the aggregate-inhibiting effect of the tested compounds. G. inflata extract and its constituents significantly elevated GSH/GSSG ratio and reduced reactive oxidative species in ATXN3/Q75 cells. The study results suggest that the tested agents activate PPARGC1A activity and NFE2L2-ARE signaling to increase mitochondrial biogenesis, decrease oxidative stress, and reduce aggregate formation in SCA3 cellular models.


Far-field interference from a sphere and its applications.
A theoretical model of far-field interference from a sphere has been established, and its applications have been investigated. When two coherent parallel laser beams shine on a smooth sphere surface from opposite directions, the reflected lights form interference fringes at far field. The fringes have hyperbolic shapes and are not uniformly distributed. This paper derives a method for calculating the path-length difference between two parallel reflected lights, analyzes the interference field, and discusses reasons that cause the fringe density variations. A formula for calculating the highest orders of interference fringes is also provided. A method for using a spectrometer, CCD camera, and computer to measure the sphere diameter is demonstrated. The results agree with those from an Abbe comparator. The theory and methods are also suitable for measuring diameters of smooth cylinders.


Controlled cortical impact traumatic brain injury in 3xTg-AD mice causes acute intra-axonal amyloid-β accumulation and independently accelerates the development of tau abnormalities.
Alzheimer's disease (AD) is a neurodegenerative disorder characterized pathologically by progressive neuronal loss, extracellular plaques containing the amyloid-β (Aβ) peptides, and neurofibrillary tangles composed of hyperphosphorylated tau proteins. Aβ is thought to act upstream of tau, affecting its phosphorylation and therefore aggregation state. One of the major risk factors for AD is traumatic brain injury (TBI). Acute intra-axonal Aβ and diffuse extracellular plaques occur in ∼30% of human subjects after severe TBI. Intra-axonal accumulations of tau but not tangle-like pathologies have also been found in these patients. Whether and how these acute accumulations contribute to subsequent AD development is not known, and the interaction between Aβ and tau in the setting of TBI has not been investigated. Here, we report that controlled cortical impact TBI in 3xTg-AD mice resulted in intra-axonal Aβ accumulations and increased phospho-tau immunoreactivity at 24 h and up to 7 d after TBI. Given these findings, we investigated the relationship between Aβ and tau pathologies after trauma in this model by systemic treatment of Compound E to inhibit γ-secretase activity, a proteolytic process required for Aβ production. Compound E treatment successfully blocked posttraumatic Aβ accumulation in these injured mice at both time points. However, tau pathology was not affected. Our data support a causal role for TBI in acceleration of AD-related pathologies and suggest that TBI may independently affect Aβ and tau abnormalities. Future studies will be required to assess the behavioral and long-term neurodegenerative consequences of these pathologies.


The Aminoalkylindole BML-190 Negatively Regulates Chitosan Synthesis via the Cyclic AMP/Protein Kinase A1 Pathway in Cryptococcus neoformans.
Cryptococcus neoformans can cause fatal meningoencephalitis in patients with AIDS or other immunocompromising conditions. Current antifungals are suboptimal to treat this disease; therefore, novel targets and new therapies are needed. Previously, we have shown that chitosan is a critical component of the cryptococcal cell wall and is required for survival in the mammalian host and that chitosan deficiency results in rapid clearance from the mammalian host. We had also identified several specific proteins that were required for chitosan biosynthesis, and we hypothesize that screening for compounds that inhibit chitosan biosynthesis would identify additional genes/proteins that influence chitosan biosynthesis. To identify these compounds, we developed a robust and novel cell-based flow cytometry screening method to identify small-molecule inhibitors of chitosan production. We screened the ICCB Known Bioactives library and identified 8 compounds that reduced chitosan in C. neoformans We used flow cytometry-based counterscreens and confirmatory screens, followed by a biochemical secondary screen to refine our primary screening hits to 2 confirmed hits. One of the confirmed hits that reduced chitosan content was the aminoalkylindole BML-190, a known inverse agonist of mammalian cannabinoid receptors. We demonstrated that BML-190 likely targets the C. neoformans G-protein-coupled receptor Gpr4 and, via the cyclic AMP (cAMP)/protein kinase A (PKA) signaling pathway, contributes to an intracellular accumulation of cAMP that results in decreased chitosan. Our discovery suggests that this approach could be used to identify additional compounds and pathways that reduce chitosan biosynthesis and could lead to potential novel therapeutics against C. neoformansIMPORTANCECryptococcus neoformans is a fungal pathogen that kills ∼200,000 people every year. The cell wall is an essential organelle that protects fungi from the environment. Chitosan, the deacetylated form of chitin, has been shown to be an essential component of the cryptococcal cell wall during infection of a mammalian host. In this study, we screened a set of 480 compounds, which are known to have defined biological activities, for activity that reduced chitosan production in C. neoformans Two of these compounds were confirmed using an alternative method of measuring chitosan, and one of these was demonstrated to impact the cAMP signal transduction pathway. This work demonstrates that the cAMP pathway regulates chitosan biosynthesis in C. neoformans and validates that this screening approach could be used to find potential antifungal agents.


Evolution of bioconvective patterns in variable gravity.
Measurements are reported of the evolution of bioconvective patterns in shallow, dense cultures of microorganisms subjected to varying gravity. Various statistical properties of this random, quasi-two-dimensional structure have been found: Aboav's law is obeyed, the average vertex angles follow predictions for regular polygons, and the area of a pattern varies linearly with its number of sides. As gravity varies between 1 g and 1.8g (g = 9.8 m s-1), these statistical properties continue to hold despite a tripling of the number of polygons and a reduced average polygon dimension by a third. This work compares with experiments on soap foams, Langmuir monolayer foams, metal grains, and simulations.


State-to-state quantum dynamics of the N(4S) + CH(X2Π) → CN(X2Σ+,A2Π) + H(2S) reactions.
The reactions between N((4)S) and CH(X(2)Π) lead to H((2)S) plus CN in its two lowest electronic states (X(2)Σ(+) and A(2)Π), which are responsible for the interstellar CN formation. Accurate quantum dynamics of these reactions are investigated on new global potential energy surfaces of the two lowest-lying triplet states of HCN (1(3)A' and 1(3)A") fitted to more than 37,000 points at the internally contracted multi-reference configuration interaction level with the Davidson correction. The pathways for these highly exothermic and barrierless reactions feature both the HCN and HNC wells. Long-lived resonances supported by these wells manifest in reaction probabilities as numerous oscillations, particularly for low J partial waves. The 1(3)A" state is found to be more reactive than the 1(3)A' state, due apparently to its more attractive nature in the entrance channel. The CN products in both electronic states are highly excited in both vibrational and rotational degrees of freedom. The near forward-backward symmetric differential cross sections are consistent with a complex-forming mechanism.


Reproductive toxicity and toxicokinetics of lindane in the male offspring of rats exposed during lactation.
1. Reproductive toxicity and toxicokinetics of lindane during lactation were studied. For the reproductive toxicity study the dams were treated with a single dose of 6 mg/kg on day 9 or 14 of lactation, or with 1 mg/kg on days 9 to 14 of lactation. The male offspring were investigated at puberty and adulthood. For the toxicokinetic study, two groups of dams were treated with 6 mg/kg on day 9 or 14 of lactation. The concentration of lindane was measured in maternal plasma and milk, as well as in male offspring organs. 2. At adulthood, testicular weight and the number of sperm and spermatids were significantly reduced in all treated groups. 3. The testosterone level of the groups treated with 6 mg/ kg was significantly reduced to approximately 50% at puberty as well as in adulthood. In the group treated with 1 mg/kg, the testosterone level was in both age periods reduced, however, only at puberty was the reduction statistically significant. 4. The concentration of lindane in the testis was similar to that found in brain and was half the concentration found in the liver. 5. Histologically some areas of the testis exhibited distinct alterations ranging from small changes to a pronounced effect. 6. Exposure to lindane during lactation induces reproductive hazards to male offspring rats which are detectable at adulthood.


Reengineering vital registration and statistics systems for the United States.
For more than a hundred years, the United States has operated a decentralized vital statistics system as an essential component of public health. Statistics based on births and deaths registered in the United States are a primary source of data used to track health status, to plan, implement, and evaluate health and social services, and to set health policy. The national vital statistics system provides nearly complete, continuous, and comparable federal, state, and local data. The system, however, is based on outmoded vital registration practices and structures, which raises concerns about data quality, timeliness, and the lack of real-time linkage capabilities. While many organizations are working together to address these issues and have made notable achievements, questions remain to be answered. Efforts to rejuvenate the nation's vital statistics system will need to expand dramatically to provide public health with a timely, high-quality, and flexible system to monitor vital health outcomes at the local, state, and national levels.


Combined intensive blood pressure and glycemic control does not produce an additive benefit on microvascular outcomes in type 2 diabetic patients.
A reduction of either blood pressure or glycemia decreases some microvascular complications of type 2 diabetes, and we studied here their combined effects. In total, 4733 older adults with established type 2 diabetes and hypertension were randomly assigned to intensive (systolic blood pressure less than 120 mm Hg) or standard (systolic blood pressure less than 140 mm Hg) blood pressure control, and separately to intensive (HbA1c less than 0.060) or standard (HbA1c 0.070-0.079) glycemic control. Prespecified microvascular outcomes were a composite of renal failure and retinopathy and nine single outcomes. Proportional hazard regression models were used without correction for type I error due to multiple tests. During a mean follow-up of 4.7 years, the primary outcome occurred in 11.4% of intensive and 10.9% of standard blood pressure patients (hazard ratio 1.08), and in 11.1% of intensive and 11.2% of standard glycemia control patients. Intensive blood pressure control only reduced the incidence of microalbuminuria (hazard ratio 0.84), and intensive glycemic control reduced the incidence of macroalbuminuria and a few other microvascular outcomes. There was no interaction between blood pressure and glycemic control, and neither treatment prevented renal failure. Thus, in older patients with established type 2 diabetes and hypertension, intensive blood pressure control improved only 1 of 10 prespecified microvascular outcomes. None of the outcomes were significantly reduced by simultaneous intensive treatment of glycemia and blood pressure, signifying the lack of an additional beneficial effect from combined treatment.


The chemical dynamics of NO and reactive nitrogen oxides: a practical guide.
Nitric oxide has emerged as one of the most important and diverse players in physiology. This small diatomic radical stunned researchers because of its existence and unique biological properties in human physiology. Over the last two decades it was found that NO often has fickle behavior in pathophysiological mechanisms. Where benefiting the host in one case yet inducing and augmenting injury in another. This has lead to confusion in is NO good or bad? Much of the answers to this dichotomy lies in the chemistry of NO and its related nitrogen oxide species. To help understand the complex chemistry with perspective to biology, a discussion on the chemical biology of NO is useful. The chemical biology defines the relevant chemical reaction of NO and nitrogen monoxide in the context of the biological conditions. We discuss in this article the chemistry of nitrogen oxide with different types of biological motifs. Reaction of NO with metal complexes and radicals require low concentration, where formation of reactive nitrogen oxide species require considerably higher amounts and generally are isolated to specific microenvironments in vivo. Though many reactive nitrogen oxide species are formed from chemical reactions with NO, there are several which appear to not require NO to be present, HNO and NO(2). These two species have unique physiological effects and represent additional complexity to this biological picture. From this discussion, a picture can be formed concerning the possible chemical dynamics, which can be plausible in different biological mechanisms.


Postintensive Care Syndrome in Pediatric Critical Care Survivors: Therapeutic Options to Improve Outcomes After Acquired Brain Injury.
Children surviving the pediatric intensive care unit (PICU) with neurologic illness or injury have long-term morbidities in physical, cognitive, emotional, and social functioning termed postintensive care syndrome (PICS). In this article, we review acute and longitudinal management strategies available to combat PICS in children with acquired brain injury. Few intervention studies in this vulnerable population target PICS morbidities. Small studies show promise for both inpatient- and outpatient-initiated therapies, mainly focusing on a single domain of PICS and evaluating heterogeneous populations. While evaluating the effects of interventions on longitudinal PICS outcomes is in its infancy, longitudinal clinical programs targeting PICS are increasing. A multidisciplinary team with inpatient and outpatient presence is necessary to deliver the holistic integrated care required to address all domains of PICS in patients and families. While PICS is increasingly recognized as a chronic problem in PICU survivors with acquired brain injury, few interventions have targeted PICS morbidities. Research is needed to improve physical, cognitive, emotional, and social outcomes in survivors and their families.


Plasma Cell Myeloma with an Aggressive Clinical Course and Anaplastic Morphology in a 22-Year-Old Patient: A Case Report and Review of Literature.
BACKGROUND Plasma cell myeloma is a neoplastic plasma cell disorder that usually presents after the fifth decade of life; it is rarely described in younger population especially under 30 years of age. However, there are conflicting reports in the literature about the clinical behavior and overall survival in younger age groups. In approximately 2% of plasma cell myeloma, the morphology of the neoplastic cells is highly pleomorphic, quite anaplastic, and may resemble metastatic tumor cells. While this poses a challenge for morphological interpretation during diagnosis, it has been demonstrated that bone marrow morphologic features (including diffuse sheet growth pattern, immature cell morphology and high mitotic index) significantly correlates with high risk disease. Moreover, there is limited description available about the morphology of the neoplastic cells when correlating the age at presentation with the clinical outcome/biological behavior; hence, the need to report and collect such cases. CASE REPORT We report a case of plasma cell myeloma in a 22-year-old male who presented with non-specific clinical features and posed a diagnostic challenge during clinical, radiological, and laboratory examination. The pathology specimens showed anaplastic morphology. Unfortunately, after diagnosis, despite treatment with brotezomib, his disease had an aggressive clinical course and he passed away 4 months after diagnosis. CONCLUSIONS Although plasma cell myeloma is rare in patients younger than 30 years, it must be considered in the differential diagnosis and investigated properly especially in patients with clinical suspicion of a metastatic non-hematological tumor. The anaplastic variant in a young patient is a diagnostic challenge and is associated with bizarre morphology, aggressive presentation, adverse cytogenetics, resistance to chemotherapy, and poor, short-term, survival.


Cadaver brains and excesses in Baccho and Venere: dementia paralytica in Dutch psychiatry (1870-1920).
This article explores the approach of dementia paralytica by psychiatrists in the Netherlands between 1870 and 1920 against the background of international developments. The psychiatric interpretation of this mental and neurological disorder varied depending on the institutional and social context in which it was examined, treated, and discussed by physicians. Psychiatric diagnoses and understandings of this disease had in part a social-cultural basis and can be best explained against the backdrop of the establishment of psychiatry as a medical specialty and the specific efforts of Dutch psychiatrists to expand their professional domain. After addressing dementia paralytica as a disease and why it drew so much attention in the late nineteenth and early twentieth century, this essay discusses how psychiatrists understood dementia paralytica in asylum practice in terms of diagnosis, care, and treatment. Next we consider their pathological-anatomical study of the physical causes of the disease and the public debate on its prevalence and causes.


Prevalence of antibodies to Trypanosoma cruzi, Leishmania infantum, Encephalitozoon cuniculi, Sarcocystis neurona, and Neospora caninum in Capybara, Hydrochoerus hydrochaeris, from São Paulo State, Brazil.
Little is known about the importance of capybara, Hydrochoerus hydrochaeris, as reservoirs for parasites of zoonotic or veterinary importance. Sera from 63 capybaras, from 6 counties in the state of São Paulo, Brazil, were examined for antibodies to Trypanosoma cruzi, Leishmania infantum, Encephalitozoon cuniculi, Sarcocystis neurona, and Neospora caninum using an indirect immunofluorescent antibody test. Five (8%) of the 63 capybaras had antibodies to T. cruzi epimastigotes. None of the samples from capybara reacted positively with L. infantum promastigotes or with spores of E. cuniculi . Two (3%) of the serum samples were positive for antibodies to S. neurona merozoites, and 2 (3%) of the serum samples were positive for antibodies to N. caninum tachyzoites. A serum sample from 1 capybara was positive for antibodies to both T. cruzi and N. caninum. None of the remaining 62 samples reacted with more than 1 parasite.