Reduced antibody reactivity to hepatitis C virus antigens in hemodialysis patients coinfected with hepatitis B virus.
Antibody reactivities to hepatitis C virus (HCV) antigens and to synthetic peptides derived from different parts of the HCV genome (core, NS4, and NS5) were evaluated in HCV-infected hemodialysis patients. In the RIBA 3 assay, NS5 was significantly less recognizable by sera of hemodialysis patients compared to other HCV-infected subjects. Among hemodialysis patients, those coinfected with hepatitis B virus (HBV) (positive for hepatitis B surface antigen [HBsAg+]) showed a reduction in reactivity to C33 and C100. Sera of only 23% of the hemodialysis patients (37 of 161) reacted with more than three of eight peptides tested, significantly fewer than the 60% (12 of 20) of the sera of other HCV-infected patients tested (P = 0.001). This immunosuppression was also manifested by a reduced frequency of recognition of additional peptides on follow-up. An even more reduced reactivity was observed among the HBV-coinfected patients (HBsAg+). The low-responder hemodialysis patients were not infected with any particular genotype of HCV, and the same HCV genotypes observed in the whole group of hemodialysis patients (1a, 1b, 2a, and 3a) were found circulating in the low-responder group. Even in this low-responder population, the good performance of two peptides (peptide 716, corresponding to a portion of the core, and peptide 59, corresponding to a portion of NS4) corroborates the immunodominance of the conserved epitopes within these peptides.


The Capital of Race Capitals: Toward a Connective Cartography of Black Internationalisms.
A great deal of ink has been spilled reflecting upon the historically contingent nature of race as a category, and as a lived experience. Bringing together the case studies of the interwar sites of Harlem, Paris, and London and, in the post-World War Two period of decolonization, the cities of Algiers and Dakar, this article is a contribution to ongoing conversations about how we might develop a critical conceptual apparatus for understanding the relationship between historical examples of black internationalism and the racial assumptions that underpin it by linking it to notions of place.


Acute care surgery in heart transplant recipients.
Orthotopic heart transplantation (OHT) is the optimal treatment for end-stage heart failure. We reviewed our institutional experience between 2008 and 2012 with acute care surgery (ACS) consultations and procedures within 1 year of OHT in recipients bridged to transplantation with medical therapy (MT, n = 169), including intravenous inotropes, and ventricular assist devices (VADs, n = 74). In total, 28 consultations were required in 21 patients (9%) and 16 procedures were performed in 11 patients (5%). The interval from transplantation to consultation was shorter for the MT group (50 vs 82 days; P = 0.015), whereas the interval from consultation to operation was longer (5 vs 1 day; P = 0.03). Patients undergoing MT were more likely to require consultation for abdominal problems (88 vs 27%; P = 0.004). All but one of the seven ischemic/inflammatory abdominal problems occurred in the MT group. Complications occurred after five ACS procedures (31%) in two patients undergoing MT and three patients undergoing VAD. Mortality was 24 per cent with five deaths occurring within 30 days of ACS consultation and/or operation. In summary, this is one of the largest series of ACS problems in patients undergoing OHT bridged to transplant with MT or VAD. With similar incidence in MT and VAD groups, ACS consultations and operations are infrequent with high mortality and morbidity.


Enhanced stability of Bacillus licheniformis L-arabinose isomerase by immobilization with alginate.
Recombinant Escherichia coli whole cells harboring Bacillus licheniformis L-arabinose isomerase (BLAI) were harvested to prepare alginate-immobilized biocatalysts. The operational conditions for immobilization were optimized according to relative activity and the cell leakage of the immobilized cell. The optimal conditions are as follows: alginate concentration, Ca(2+) concentration, cell mass loading, and curing time were 2% (w/v), 0.1 M, 50 g l(-1), and 4 hours, respectively. After immobilization, cross-linking with 0.1% glutaraldehyde significantly reduced cell leakage. The immobilized whole cells harboring BLAI were very stable with 89% residual activity remaining after 33 days of incubation at 50 degrees C and were much more stable than the free enzyme and cells. The results showed that immobilizing whole cells harboring BLAI is suitable for use as a biocatalyst in the production of L-ribulose, largely due to its high stability and low cost.


Exploratory Health Disparities Research: The Need to Provide a Tangible Benefit to Vulnerable Respondents.
This article examines the responsibilities of researchers who conduct exploratory research to provide a service to vulnerable respondents. The term "service" is used to denote the provision of a tangible benefit in relation to the research question that is apart from the altruistic research benefits. This article explores what this "service" could look like, who might be responsible for providing it, and the challenges associated with such a service. The article argues that not providing a tangible benefit to vulnerable research participants is inconsistent with the principle of social justice that undergirds much of the rationale for conducting health disparities research.


Biological properties of crosslinked salmon collagen fibrillar gel as a scaffold for human umbilical vein endothelial cells.
Collagen derived from chum salmon (Oncorhynchus keta) was crosslinked with 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide (EDC) during collagen fibrillogenesis and applied to an in vitro cell culture to evaluate its potential use as a scaffold for vascular tissue engineering. Human umbilical vein endothelial cells (HUVEC) were cultured on the crosslinked salmon collagen fibrillar gel (EDC-SC gel), and their growth rates and production levels of cytokines, including platelet-derived growth factor-BB and von Willebrand factor, were measured. Comparison was also made with bovine collagen gel crosslinked with EDC (EDC-BC gel). The growth and cytokine production of the HUVEC cultured on the EDC-SC gel were higher than those on the EDC-BC gel. In addition, HUVEC were found to attach to the EDC-BC gel through alpha2beta1 integrin for native collagen, whereas they attached to the EDC-SC gel through alphavbeta3 integrin for denatured collagen as well as the alpha2beta1 integrin, indicating that HUVEC recognized denatured domains in the EDC-SC gel. In conclusion, the EDC-SC gel can be used as a scaffold to support HUVEC growth, although the integrin-mediated attachment manner differs between the two gels.


Engineering human cell-based, functionally integrated osteochondral grafts by biological bonding of engineered cartilage tissues to bony scaffolds.
In this study, we aimed at developing and validating a technique for the engineering of osteochondral grafts based on the biological bonding of a chondral layer with a bony scaffold by cell-laid extracellular matrix. Osteochondral composites were generated by combining collagen-based matrices (Chondro-Gide) containing human chondrocytes with devitalized spongiosa cylinders (Tutobone) using a fibrin gel (Tisseel). We demonstrate that separate pre-culture of the chondral layer for 3 days prior to the generation of the composite allows for (i) more efficient cartilaginous matrix accumulation than no pre-culture, as assessed histologically and biochemically, and (ii) superior biological bonding to the bony scaffold than 14 days of pre-culture, as assessed using a peel-off mechanical test, developed to measure integration of bilayered materials. The presence of the bony scaffold induced an upregulation in the infiltrated cells of the osteoblast-related gene bone sialoprotein, indicative of the establishment of a gradient of cell phenotypes, but did not affect per se the quality of the cartilaginous matrix in the chondral layer. The described strategy to generate osteochondral plugs is simple to be implemented and--since it is based on clinically compliant cells and materials--is amenable to be readily tested in the clinic.


Does Cell Polarization Matter in Single-Ion Conducting Electrolytes?
Single-ion conducting polymer electrolytes (SIPE) are particularly promising electrolyte materials in lithium metal-based batteries since theoretical considerations suggest that the immobilization of anions avoids polarization phenomena at electrode|electrolyte interfaces. SIPE in principle could allow for fast charging while preventing cell failure induced by short circuits arising from the growth of inhomogeneous Li depositions provided that SIPE membranes possess sufficient mechanical stability. To date, different chemical structures are developed for SIPE, where new compounds are often reported through electrochemical characterization at low current rates. Experimental counterparts to model-based assumptions and determination of system limitations by correlating both models and experiments are rare in the literature. Herein, Chazalviel's model, which is derived from ion concentration gradients, is applied to theoretically determine the limiting current density (JLim) of a SIPE. Comparison with the experimentally obtained JLim reveals a large deviation between the theoretical and practical values. Beyond that, charge-discharge profiles show a distinct arcing behavior at moderate current densities (0.5 to 1 mA cm-2), indicating polarization of the cell, which is not so far reported for SIPE. In this context, by application of various electrochemical and physiochemical methods, the details of cell polarization and the role of the solid electrolyte interphase in producing arcing behavior in the voltage profiles in stripping/plating experiments are revealed, which eventually also elucidate the inconsistency of JLim.


The herpes simplex virus type 1 latency associated transcript locus is required for the maintenance of reactivation competent latent infections.
Herpes simplex virus (HSV) establishes latent infections in sensory neurons from which it can periodically reactivate and cause recurrent disease and transmission to new hosts. Little is known about the virally encoded mechanisms that influence the maintenance of HSV latent infectious and modulate the frequency of virus reactivation from the latent state. Here, we report that the latency associated transcript locus of HSV-1 is required for long-term maintenance of reactivation competent latent infections.


Air pollution, deprivation and health: understanding relationships to add value to local air quality management policy and practice in Wales, UK.
Air pollution exposure reduces life expectancy. Air pollution, deprivation and poor-health status combinations can create increased and disproportionate disease burdens. Problems and solutions are rarely considered in a broad public health context, but doing so can add value to air quality management efforts by reducing air pollution risks, impacts and inequalities. An ecological study assessed small-area associations between air pollution (nitrogen dioxide and particulate matter), deprivation status and health outcomes in Wales, UK. Air pollution concentrations were highest in 'most' deprived areas. When considered separately, deprivation-health associations were stronger than air pollution-health associations. Considered simultaneously, air pollution added to deprivation-health associations; interactions between air pollution and deprivation modified and strengthened associations with all-cause and respiratory disease mortality, especially in 'most' deprived areas where most-vulnerable people lived and where health needs were greatest. There is a need to reduce air pollution-related risks for all. However, it is also the case that greater health gains can result from considering local air pollution problems and solutions in the context of wider health-determinants and acting on a better understanding of relationships. Informed and co-ordinated air pollution mitigation and public health action in high deprivation and pollution areas can reduce risks and inequalities. To achieve this, greater public health integration and collaboration in local air quality management policy and practice is needed.


Rural oral health workforce issues in NSW and the Charles Sturt University Dentistry Program.
Adequate numbers of dental, medical and allied health professionals in rural and regional areas of NSW are vital for the health of these populations and supporting local community structures and economies. Well-documented shortages of health professionals are a major social and political issue in rural and regional communities and this workforce shortfall is recognised by both the NSW Government State Plan and the State Health Plan. This paper outlines rural and regional dental workforce shortages in NSW and describes current rural oral health workforce initiatives, including the new Charles Sturt University Dentistry Program.


Temperature-Dependent Water and Ion Transport Properties of Barley and Sorghum Roots : II. Effects of Abscisic Acid.
Water flux through excised roots (J(v)) is determined by root hydraulic conductance (L(p)) and the ion flux to the xylem (J(i)) that generates an osmotic gradient to drive water movement. These properties of roots are strongly temperature dependent. Abscisic acid (ABA) can influence J(v) by altering L(p), J(i), or both. The effects of root temperature on responses to ABA were determined in two species differing in their temperature tolerances. In excised barley (Hordeum vulgare L.) roots, J(v) was maximum at 25 degrees C; 10 micromolar ABA enhanced J(v), primarily by increasing L(p), at all temperatures tested (15-40 degrees C). In sorghum (Sorghum bicolor L.) roots, J(v) peaked at 35 degrees C; ABA reduced this optimum temperature for J(v) to 25 degrees C by increasing L(p) at low temperatures and severely inhibiting J(i) (dominated by fluxes of K(+) and NO(3) (-)) at warm temperatures. The inhibition of K(+) flux by ABA at high temperature was mostly independent of external K(+) availability, implying an effect of ABA on ion release into the xylem. In sorghum, ABA enhanced water flux through roots at nonchilling low temperatures but at the expense of tolerance of warm temperatures. These effects imply that ABA may shift the thermal tolerance range of roots of this heat-tolerant species toward cooler temperatures.


Neural correlates of set-shifting: decomposing executive functions in schizophrenia.
Although there is considerable evidence that patients with schizophrenia have impaired executive functions, the neural mechanisms underlying these deficits are unclear. Generation and selection is one of the basic mechanisms of executive functioning. We investigated the neural correlates of this mechanism by means of functional magnetic resonance imaging (fMRI) in patients with schizophrenia and healthy controls. We used the Wisconsin Card Sorting Test (WCST) in an event-related fMRI study to analyze neural activation patterns during the distinct components of the WCST in 36 patients with schizophrenia and 28 controls. We focused our analyses on the process of set-shifting. After participants received negative feedback, they had to generate and decide on a new sorting rule. A widespread activation pattern encompassing the inferior and middle frontal gyrus, parietal, temporal and occipital cortices, anterior cingulate cortex (ACC), supplementary motor area, insula, caudate, thalamus and brainstem was observed in patients with schizophrenia after negative versus positive feedback, whereas in healthy controls, significant activation clusters were more confined to the cortical areas. Significantly increased activation in the rostral ACC after negative feedback and in the dorsal ACC during matching after negative feedback were observed in schizophrenia patients compared with controls. Controls showed activation in the bilateral dorsolateral prefrontal cortex (Brodmann area 46), whereas schizophrenia patients showed activation in the right dorsolateral prefrontal cortex only. All patients were taking neuroleptic medication, which has an impact on cognitive function as well as on dopaminergic and serotonergic prefrontal metabolism. Our data suggest that, in patients with schizophrenia, set-shifting is associated with increased activation in the rostral and dorsal ACC, reflecting higher emotional and cognitive demands, respectively.


Histological and biochemical alterations in early-stage lobar ischemia-reperfusion in rat liver.
To investigate the structural and biochemical changes in the early stage of reperfusion in the rat livers exposed to lobar ischemia-reperfusion (IR). The median and left lobes of the liver were subjected to 60 min ischemia followed by 5, 10, 30, 45, 60 and 120 min reperfusion. Blood samples were taken at different time intervals to test enzyme activities and biochemical alterations induced by reperfusion. At the end of each reperfusion period, the animals were killed by euthanasia and tissue samples were taken for histological examination and immunohistochemistry. Cell vacuolation, bleb formation and focal hepatitis were the most important changes occur during ischemia. While some changes including bleb formation were removed during reperfusion, other alterations including portal hepatitis, inflammation and the induction of apoptosis were seen during this stage. The occurrence of apoptosis, as demonstrated by apoptotic cells and bodies, was the most important histological change during reperfusion. The severity of apoptosis was dependent on the time of reperfusion, and by increasing the time of reperfusion, the numbers of apoptotic bodies was significantly enhanced. The amounts of lactate dehydrogenase, alanine aminotransferase, aspartate aminotransferase, creatinine and urea were significantly increased in serum obtained from animals exposed to hepatic IR. Inflammation and subsequent apoptotic cell death were the most important changes in early-stage hepatic reperfusion injury, and the number of apoptotic bodies increased with time of reperfusion.


[Impaired cognitive function in hepatitis C virus infection].
Impaired cognitive function is commonly seen in patients with hepatitis C-virus (HCV). This might be due to a toxic effect of the virus itself or to neuroinflammatory processes with a direct damaging cerebral effect. The symptoms appear in the pre-cirrhotic stage and impair the patient's level of functioning. Therefore, doctors in contact with HCV patients should be up to date on the existing knowledge in the field to be able to inform patients about their cognitive deficits and take them into consideration. It is unknown if the cognitive deficits decline when the virus is eradicated.


Lutein-Loaded, Biotin-Decorated Polymeric Nanoparticles Enhance Lutein Uptake in Retinal Cells.
Age related macular degeneration (AMD) is one of the leading causes of visual loss and is responsible for approximately 9% of global blindness. It is a progressive eye disorder seen in elderly people (>65 years) mainly affecting the macula. Lutein, a carotenoid, is an antioxidant, and has shown neuroprotective properties in the retina. However, lutein has poor bioavailability owing to poor aqueous solubility. Drug delivery to the posterior segment of the eye is challenging due to the blood-retina barrier. Retinal pigment epithelium (RPE) expresses the sodium-dependent multivitamin transporter (SMVT) transport system which selectively uptakes biotin by active transport. In this study, we aimed to enhance lutein uptake into retinal cells using PLGA-PEG-biotin nanoparticles. Lutein loaded polymeric nanoparticles were prepared using O/W solvent-evaporation method. Particle size and zeta potential (ZP) were determined using Malvern Zetasizer. Other characterizations included differential scanning calorimetry, FTIR, and in-vitro release studies. In-vitro uptake and cytotoxicity studies were conducted in ARPE-19 cells using flow cytometry and confocal microscopy. Lutein was successfully encapsulated into PLGA and PLGA-PEG-biotin nanoparticles (<250 nm) with uniform size distribution and high ZP. The entrapment efficiency of lutein was ≈56% and ≈75% for lutein-loaded PLGA and PLGA-PEG-biotin nanoparticles, respectively. FTIR and DSC confirmed encapsulation of lutein into nanoparticles. Cellular uptake studies in ARPE-19 cells confirmed a higher uptake of lutein with PLGA-PEG-biotin nanoparticles compared to PLGA nanoparticles and lutein alone. In vitro cytotoxicity results confirmed that the nanoparticles were safe, effective, and non-toxic. Findings from this study suggest that lutein-loaded PLGA-PEG-biotin nanoparticles can be potentially used for treatment of AMD for higher lutein uptake.


Optical realization of a Clos nonblocking broadcast switching network with constant time network control algorithm.
The Clos interconnection network is one of the earliest multistage interconnection networks. Recently, a necessary condition on the number of middle-stage switches required to achieve broadcast capability was presented [Tech. Rep. JHU 90/04 (Computer Science Department, Johns Hopkins University, Baltimore, Md, 1990)]. A linear time control algorithm that determines whether a new input request is feasible or not was also provided. Here, the special characteristics of optics are used to provide a constant time parallel realization of the network control setup. This permits a reconfigurable Clos broadcast network.


Utilization of anion-exchange chromatography and monoclonal antibodies to characterize multiple pilus types on a uropathogenic Escherichia coli O6 isolate.
Multiple pilus types from a uropathogenic strain of Escherichia coli O6, strain 6260, were characterized by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), high-pressure liquid chromatography, binding assays, and erythrocyte adsorption. In addition, monoclonal antibodies were raised against purified pili of E. coli 6260 and used for immunological characterization. SDS-PAGE analysis of the purified pili showed at least three different subunits with molecular weights of 15,700, 17,800, and 19,300. SDS-PAGE analysis of four protein peaks from anion-exchange chromatography of intact pili showed polypeptides with molecular weights of 19,300 (fraction 1), 15,700 (fraction 2), and 17,800 and 15,700 (both fractions 3 and 4). Erythrocyte adsorption of the whole-pilus preparation removed the 17,800-molecular-weight subunit (17.8K subunit) and reduced the 15.7K subunit. Pili from an isogenic hemagglutination-negative variant of E. coli 6260, showing only the 15.7K and 19.3K subunits by SDS-PAGE, lacked the 17.8K subunit of fractions 3 and 4 present in the parent high-pressure liquid chromatography profile. Our data suggest that two of the pilus subunits, the 15.7K and 17.8K subunits, mediate mannose-resistant agglutination of human erythrocytes. Pili in fractions 1 and 2 from the parent strain bound specifically to mannose residues, while pili in fraction 4 bound to P-coated horse erythrocytes; no receptor specificity was identified for pili in fraction 3. Immunological analysis by the immunoblot technique showed that monoclonal antibody 11-2 reacted with the 19.3K subunit, monoclonal antibodies 34-3 and 73-3 reacted with the 15.7K subunit, and monoclonal antibodies 81-1, 82-1, and 91-1 reacted with polymers of subunits retained in the stacking gel. Intact pili precipitated by any of the six monoclonal antibodies showed two polypeptides by SDS-PAGE: 15.7K and 19.3K polypeptides for monoclonal antibody 11-2, and 15.7K and 17.8K polypeptides for monoclonal antibodies 34-3, 73-3, 81-1, 82-1, and 91-1. The cross-reactivity of the monoclonal antibodies with purified pili from other E. coli strains was determined by enzyme-linked immunosorbent assay. Monoclonal antibody 11-2 showed no significant cross-reactivity with heterogeneous pili. In contrast, the other monoclonal antibodies showed equivalent or greater reactivity with P pili from heterologous strains as compared with reactivity with E. coli 6260 pili.(ABSTRACT TRUNCATED AT 400 WORDS)


Experimental Evidence of the Existence of Interleaflet Coupled Nanodomains: An MC-FRET Study.
Plasma membranes of living cells are compartmentalized into small submicroscopic structures (nanodomains) having potentially relevant biological functions. Despite this, structural features of these nanodomains remain elusive, primarily due to the difficulties in characterizing such small dynamic entities. It is unclear whether nanodomains found in the upper bilayer leaflet are transversally registered with those found in the lower leaflet. Experiments performed on larger microscopic domains indicate that the coupling between the leaflets is strong, forcing the domains to be in perfect registration, but can the same thing be said about the biologically more relevant nanodomains? This work provides experimental evidence that even small nanodomains of variable sizes between 10 and 160 nm are interleaflet coupled. Importantly, the alternative scenarios of partially registered, independent, or antiregistered nanodomains could be excluded.


Effects of cellular iron deficiency on the formation of vascular endothelial growth factor and angiogenesis. Iron deficiency and angiogenesis.
Young women diagnosed with breast cancer are known to have a higher mortality rate from the disease than older patients. Specific risk factors leading to this poorer outcome have not been identified. In the present study, we hypothesized that iron deficiency, a common ailment in young women, contributes to the poor outcome by promoting the hypoxia inducible factor-1α (HIF-1α and vascular endothelial growth factor (VEGF) formation. This hypothesis was tested in an in vitro cell culture model system. Human breast cancer MDA-MB-231 cells were transfected with transferrin receptor-1 (TfR1) shRNA to constitutively impair iron uptake. Cellular iron status was determined by a set of iron proteins and angiogenesis was evaluated by levels of VEGF in cells as well as by a mouse xenograft model. Significant decreases in ferritin with concomitant increases in VEGF were observed in TfR1 knockdown MDA-MB-231 cells when compared to the parental cells. TfR1 shRNA transfectants also evoked a stronger angiogenic response after the cells were injected subcutaneously into nude mice. The molecular mechanism appears that cellular iron deficiency elevates VEGF formation by stabilizing HIF-1α. This mechanism is also true in human breast cancer MCF-7 and liver cancer HepG2 cells. Cellular iron deficiency increased HIF-1α, VEGF, and angiogenesis, suggesting that systemic iron deficiency might play an important part in the tumor angiogenesis and recurrence in this young age group of breast cancer patients.


[Serum prolactin during oral metoclopramide in normal nulliparous women].
As a first step in an extensive project planned to determine serum PRL levels in response to oral metoclopramide in women with a diverse gyneco-obstetric history, it was decided to study 51 clinically healthy nulliparous women, aged 15.8 to 48.2 years, with history of regular menses at least one year before the study (except the three postmenopausal women), with no regular drug ingestion during the last six months. Women were studied on days 18 to 22 of menstrual period, after a 30 minute rest on basal conditions (3 samples) at 60, 90, and 120 minutes after a single 10 mg. oral dose of metoclopramide. Duplicate PRL determinations were performed in all samples and progesterone(P) only in a pool of the three basal samples by radioimmunoanalysis. All women had serum P levels > or = 4.0 ng/ml. A significant linear positive correlation (r > or = 0.6795, p < 0.001) was observed between chronologic age (CA) and serum PRL levels, regardless the way they were expressed. Considering the individual responses it was decided to divide the group according to CA and it was observed that serum PRL levels--expressed in any form were always significantly greater in women aged > 25 years (Group 2) in contrast with women aged < or = 25 years (Group 1). Since differences were evident, percentiles 3, 50 and 97 for serum PRL levels were calculated during each test time for both groups.(ABSTRACT TRUNCATED AT 250 WORDS)


Dabska tumor developing within a preexisting vascular malformation.
Malignant endovascular papillary angioendothelioma, first described by Dabska in 1969, is a rare vascular tumor that primarily affects children and is characterized by papillary proliferations of endothelial cells into vessel lumens. We report a case of this rare neoplasm in a boy with angiomatosis who developed Kasabach-Merritt syndrome. The tumor evolved as an ulcerated lesion superficially within a previous vascular malformation on his buttock. A review of the literature is presented.


Bone position estimation from skin marker co-ordinates using global optimisation with joint constraints.
Widespread use of gait or motion analysis in the diagnosis of patients with locomotor pathology and the subsequent planning and assessment of treatment has been limited because of its reliability, particularly in evaluating frontal and transverse plane components. This is because spatial reconstruction of the musculoskeletal system and calculation of its kinematics and kinetics via a skin marker-based multi-link model are subject to marker skin movement artefacts. Traditional methods treat each body segment separately without imposing joint constraints, resulting in apparent dislocations at joints predominantly because of skin movement artefacts. An optimisation method for the determination of the positions and orientations of multi-link musculoskeletal models from marker co-ordinates is presented. It is based on the minimisation of the weighted sum of squared distances between measured and model-determined marker positions. The model imposes joint constraints. Numerical experiments were performed to show that the new method is capable of eliminating joint dislocations and giving more accurate model position and orientation estimations. It is suggested that, with joint constraints and a global error compensation scheme, the effects of measurement errors on the reconstruction of the musculoskeletal system and subsequent mechanical analyses can be reduced globally. The proposed method minimises errors in axial rotation and ab/adduction at the joints and may extend the applicability of gait analysis to clinical problems.


A global perspective on vaccine safety and public health: the Global Advisory Committee on Vaccine Safety.
Established in 1999, the Global Advisory Committee on Vaccine Safety advises the World Health Organization (WHO) on vaccine-related safety issues and enables WHO to respond promptly, efficiently, and with scientific rigor to issues of vaccine safety with potential global importance. The committee also assesses the implications of vaccine safety for practice worldwide and for WHO policies. We describe the principles on which the committee was established, its modus operandi, and the scope of the work undertaken, both present and future. We highlight its recent recommendations on major issues, including the purported link between the measles-mumps-rubella vaccine and autism and the safety of the mumps, influenza, yellow fever, BCG, and smallpox vaccines as well as that of thiomersal-containing vaccines.


Flexible micro-sensors with self-assembled graphene on a polyolefin substrate for dopamine detection.
The electrochemical sensing of dopamine is of great significance for studying and treating neurochemical diseases due to its potential feasibility for in vivo diagnostics. The commonly used sensors suffer from low sensitivity, the interference of ascorbic acid, and poor flexibility. In this paper, the function of electrode substrates including polyolefin, polystyrene, and polyethylene terephthalate films were investigated for their ability to improve electrochemical performances and provide favorable flexibility. The interference from ascorbic acid was cut down to a minimum by reducing the electrochemical resistance and the ascorbic acid diffusion current. The results demonstrate that gold electrodes prepared on polyolefin films exhibit a low charge transfer resistance of about 20 Ω, high sensitivity of dopamine detection (7.8 μA/μM), which is about 312 folds that of silicon electrode (0.025 μA/μM) and excellent flexibility. Having regulated the fabrication process of graphene by altering self-assembly layers and modification area, the sensor shows a dopamine detection limit of 0.11 μM in the presence of 500 μM ascorbic acid, and a sensitivity of 0.33 μA/μM. This work is valuable for the further improvement of the sensitivity and selectivity of the electrochemical sensor.


Pregnancy Loss in Women with HIV is not Associated with HIV Markers: Data from a National Study in Italy, 2001-2018.
There is limited information on pregnancy loss in women with HIV, and it is still debated whether HIV-related markers may play a role.Objectives: To explore potential risk factors for pregnancy loss in women with HIV, with particular reference to modifiable risk factors and markers of HIV disease. Multicenter observational study of HIV-positive pregnant women. The main outcome measure was pregnancy loss, including both miscarriage (<22 weeks) and stillbirth (≥22 weeks). Possible associations of pregnancy loss were evaluated in univariate and multivariate analyses. Among 2696 eligible pregnancies reported between 2001 and 2018, 226 (8.4%) ended in pregnancy loss (miscarriage 198, 7.3%; stillbirth 28, 1.0%). In multivariate analyses, only older age (adjusted odds ratio [AOR] per additional year of age: 1.079, 95% confidence interval [CI] 1.046-1.113), HIV diagnosis before pregnancy (AOR: 2.533, 95%CI 1.407-4.561) and history of pregnancy loss (AOR: 1.625, 95%CI 1.178-2.243) were significantly associated with pregnancy loss. No significant association with pregnancy loss was found for parity, coinfections, sexually transmitted diseases, hypertension, smoking, alcohol and substance use, CD4 cell count, HIV-RNA viral load, and CDC HIV stage. Older women and those with a previous history of pregnancy loss should be considered at higher risk of pregnancy loss. The severity of HIV disease and potentially modifiable risk factors did not increase the risk of pregnancy loss.


Protein kinase CK2 in health and disease: Structural bases of protein kinase CK2 inhibition.
Protein kinase CK2 is involved in many fundamental aspects of normal cell life, but it is also able to establish favourable conditions for tumorigenesis. CK2 is elevated in various cancers, it is a potent suppressor of apoptosis, it strongly promotes cell survival, it strengthens the multi-drug resistant phenotype and can be considered a valuable drug target for cancer therapy. In this review, the structural bases of CK2 inhibition deduced from the analysis of crystal structures of CK2alpha-inhibitor complexes are presented and discussed. The best ATP-competitive inhibitors show an adequate hydrophobic character, an excellent shape complementarity with the unique active site of CK2, and the ability to establish polar interactions with both the hinge region and the positive electrostatic area near the conserved water W1 and the Lys68-Glu81 salt bridge. The state of the art of non-ATP-competitive inhibitors is also presented.


Prolonged, continuous treatment of hairy cell leukemia patients with recombinant interferon-alpha 2a.
Interferons are not curative in hairy cell leukemia (HCL), and retreatment is necessary in most patients whose therapy is stopped. In an attempt to maintain or improve responses, we administered recombinant interferon-alpha 2a (rIFN-alpha 2a) continuously to patients with HCL who initially responded to this therapy. Of 53 evaluable patients enrolled in this study, 32 have received rIFN-alpha 2a continuously for a median of 5 years. Patients received 3 million units of rIFN-alpha 2a subcutaneously (SC) daily for 6 months, followed, in responding patients, by the same dose three times weekly. Twenty-one patients (40%) discontinued IFN after a median of 29 months, seven of whom developed resistant disease in association with anti-IFN antibodies. Treatment produced high response rates: complete response plus partial response (CR + PR) = 40 of 53 (76%), CR + PR + minor response (MR) = 43 of 53 (82%), with no differences in response rates between patients with and without splenectomy. Sixteen patients who had MR at 18 months had PR with prolonged treatment, nine of whom had a significant further reduction in the hairy cell infiltrate in the bone marrow (BM). The median granulocyte and platelet counts have continued to increase and the median serum soluble interleukin-2 receptor (sIL-2R) level has continued to decrease with prolonged treatment. Two patients developed erythrocytosis that may be treatment related, but no other new toxicities were noted with prolonged treatment. We conclude that prolonged, continuous rIFN-alpha 2a treatment has acceptable toxicity, is not associated with late development of IFN resistance, and results in continued hematologic improvement with time on treatment.


Nonadditive Transport in Multi-Channel Single-Molecule Circuits.
As stated in the classic Kirchhoff's circuit laws, the total conductance of two parallel channels in an electronic circuit is the sum of the individual conductance. However, in molecular circuits, the quantum interference (QI) between the individual channels may lead to apparent invalidity of Kirchhoff's laws. Such an effect can be very significant in single-molecule circuits consisting of partially overlapped multiple transport channels. Herein, an investigation on how the molecular circuit conductance correlates to the individual channels is conducted in the presence of QI. It is found that the conductance of multi-channel circuit consisting of both constructive and destructive QI is significantly smaller than the addition of individual ones due to the interference between channels. In contrast, the circuit consisting of destructive QI channels exhibits an additive transport. These investigations provide a new cognition of transport mechanism and manipulation of transport in multi-channel molecular circuits.


The relationship between pressure and volume when using Rapid Rhino(r) packs in the management of epistaxis.
Despite the popularity of Rapid Rhino packs, there are no clear guidelines regarding the volume of air to be inflated when used in the management of epistaxis. The manufacturers suggest that subjective assessment by pilot cuff palpation is used to guide inflation. However, studies have clearly demonstrated that clinicians are poor at judging balloon pressure by pilot cuff palpation when used in other settings. Our objective was to investigate the relationship between the volume of air inflated and the resultant intra-nasal pressure generated by nasal balloon packing. Twelve healthy subjects were packed with 5.5 cm Rapid Rhino packs, which were connected to a manometer and 20 ml syringe via a 3-way tap in a closed circuit. Increments of 2.5 mls of air were inflated and the resultant intra-nasal pack pressure was measured. There appeared to be a linear relationship between increasing volume and pack pressure. However, between individuals, there was a large variation in the intra-nasal pack pressure produced for a given fixed volume of air inflated. This is presumably due to variations in nasal anatomy. It may be that a manometer-measured, pressure guided nasal pack inflation technique would represent best practice, especially for less experienced staff.


Phase transition of fibrillarin LC domain regulates localization and protein interaction of fibrillarin.
A key nucleolar protein, fibrillarin, has emerged as an important pharmacological target as its aberrant expression and localization are related to tumorigenesis, chemoresistance and poor survival in breast cancer patients. Fibrillarin contains a N-terminal low complexity sequence (LC) domain with a skewed amino acid distribution, which is known to undergo a phase transition to liquid-like droplets. However, the underlying mechanism of the phase transition of the fibrillarin LC domain and its physiological function are still elusive. In this study, we show that the localization of fibrillarin and its association with RNA binding proteins is regulated by this phase transition. Phenylalanine-to-serine substitutions of the phenylalanine:glycine repeats in the fibrillarin LC domain impede its phase transition into liquid-like droplets, as well as the hydrogel-like state composed of polymers, and also its incorporation into hydrogel or liquid-like droplets composed of wild-type LC domains. When expressed in cultured cells, fibrillarin containing the mutant LC domain fails to localize to the dense fibrillar component of nucleoli in the same way as intact fibrillarin. Moreover, the phase transition of the fibrillarin LC domain is required for the interaction of fibrillarin with other RNA binding proteins, such as FUS, TAF15, DDX5 and DHX9. Taken together, the results suggest that the phenylalanine residues in the LC domain are critical for the phase transition of fibrillarin, which in turn regulates the sub-nucleolar localization of fibrillarin and its interaction with RNA binding proteins, providing a useful framework for regulating the function of fibrillarin.


[Radiotherapy treatment of subfoveal retinal neovascularization: results after two years].
The treatment by radiotherapy (10 Grays) of subfoveal choroidal neovascular membranes is disappointing. Although after one year, 22% of cases had a positive result, after a mean follow up of 2.5 years only 14% of cases had a favourable outcome. The final visual acuity 30 months after treatment was the same as the one observed after 21 months of natural evolution. The well-defined nature of the subretinal new vessels, the presence of a pigment epithelial detachment and the occurrence of a vast hemorrhage were of bad prognosis.


Efficacy and safety of HSK3486 for the induction and maintenance of general anesthesia in elective surgical patients: a multicenter, randomized, open-label, propofol-controlled phase 2 clinical trial.
To evaluate the efficacy and safety of HSK3486 for the induction and maintenance of general anesthesia in elective surgical patients, but excluding emergency, cardiothoracic, cerebral and endoscopic sinus cases. A total of 40 eligible patients were randomly assigned to HSK3486 (n = 30) or propofol (n = 10) dosage groups in a ratio of 3:1. Drugs were administered as a bolus injection of 0.4 mg/kg (HSK3486) or 2.0 mg/kg (propofol) for induction, followed by maintenance infusion with the same anesthetic. An additional 6 non-randomized patients received propofol (2.0 mg/kg) for induction and were given HSK3486 for maintenance. The primary efficacy endpoint - the success rate of anesthesia maintenance - was 100% in the 3 arms. The secondary efficacy endpoints included times from discontinuation of HSK3486 or propofol maintenance to full alertness, respiratory recovery, extubation and reaching the goal of the Aldrete score. Also, the proportion of patients who constantly maintained BIS40-60 or those with a period of BIS40-60 during maintenance anesthesia showed no significant difference in the HSK3486 and propofol groups (all p > 0.05). Patients who received HSK3486 exhibited a higher satisfaction score from anesthesiologists during the induction period (p = 0.024). The occurrence and types of treatment-emergent adverse events were similar among the 3 arms, both with a severity of grade 1 or 2. Drug-related hypotension occurred in 14 (46.7%) and 7 (70.0%) patients treated with HSK3486 and propofol, respectively. HSK3486 exhibited good efficacy for the induction and maintenance of general anesthesia and was well tolerated by patients who underwent elective surgery.


Curcumin Encapsulated into Biocompatible Co-Polymer PLGA Nanoparticle Enhanced Anti-Gastric Cancer and Anti-Helicobacter Pylori Effect.
The current disadvantages (high cost, toxicity, resistance) of chemotherapy for gastric cancer opted people for alternative therapy from natural source. Curcumin (natural product) possess multiple biological activities but low bio-availability limits their uses as therapeutic. The Nano-formulation of curcumin increased the bioavailability and productivity of anti-cancer and anti-bacterial properties. The present study was initiated to determine the anti-cancer and anti-bacterial effect of Nano curcumin against gastric cancer and H. pylori. Curcumin loaded PLGA nanoparticles (CUR-NPs) was prepared by single emulsion solvent evaporation method. The MIC were determined using agar dilution method to find the anti-H. Pylori activity of Nano curcumin. The cytotoxicity of Nano curcumin was evaluated by MTT assay and the apoptotic effect (cell cycle arrest and morphology change) was shown by PI staining and microscopy. The MIC of nanocurcumin and curcumin for all four H. pylori strains were 8 µg/ml and 16 µg/ml respectively. The inhibition rate of gastric cancer cells after treatment with curcumin was increased from 6% to 67% for 24h, from 8% to 75% for 48h, from 10% to 83% for 72h. In case of nanocurcumin, the inhibition rate increased from 7% to 69% for 24h, 11% to 87% for 48h and 16% to 97% for 72h. The IC50 of curcumin and Nano-curcumin were 24.20 µM and 18.78 µM respectively for 72 h. The population of cells in sub-G0 population increased from 4.1% in the control group to 24.5% and 57.8% when treated with curcumin and nanocurcumin respectively. After 72h of treatment with nanocurcumin, the apoptotic cells population increased as compared to native curcumin treated cells. The Nano curcumin might be used as a potential therapeutics against gastric cancer and H. Pylori. There is need of further in vivo study in order to validate CUR-NPs activity.


Liquid chromatography tandem mass spectrometry in the clinical laboratory.
Clinical laboratory medicine has seen the introduction and evolution of liquid chromatography tandem mass spectrometry in routine clinical laboratories over the last 10-15 years. There still exists a wide diversity of assays from very esoteric and highly specialist manual assays to more simplified kit-based assays. The technology is not static as manufacturers are continually making improvements. Mass spectrometry is now commonly used in several areas of diagnostics including therapeutic drug monitoring, toxicology, endocrinology, paediatrics and microbiology. Some of the most high throughput analyses or common analytes include vitamin D, immunosuppressant monitoring, androgen measurement and newborn screening. It also offers flexibility for the measurement of analytes in a variety of different matrices which would prove difficult with immunoassays. Unlike immunoassays or high-pressure liquid chromatography assays using ultraviolet or fluorescence detection, mass spectrometry offers better specificity and reduced interferences if attention is paid to potential isobaric compounds. Furthermore, multiplexing, which enables multiple analytes to be measured with the same volume of serum is advantageous, and the requirement for large sample volumes is decreasing as instrument sensitivity increases. There are many emerging applications in the literature. Using mass spectrometry to identify novel isoforms or modified peptides is possible as is quantification of proteins and peptides, with or without protein digests. Future developments by the manufacturers may also include mechanisms to improve the throughput of samples and strategies to decrease the level of skill required by the operators.


Differentiation of qacA and qacB using high-resolution melt curve analysis, and both qacA and qacB but not qacC or norA types increase chlorhexidine minimal inhibitory concentrations in Staphylococcus aureus isolates.
Chlorhexidine is one of the most essential ingredients in infection control applications. Except qacA, the effects of other various efflux-medicated biocide genes (including qacB, qacC, qacEΔ1, qacH or norA) on biguanides resistance are still controversial. In addition, most of the studies have discussed the effect of qacA/B on clinical S. aureus isolates but not that qacA or qacB individually. In total, 254 methicillin-resistant Staphylococcus aureus (MRSA), selected 30 methicillin-susceptible S. aureus (MSSA) clinical isolates from different patients during 2014-2015 and 15 S. aureus quality control strains (including Mu3 and Mu50) were included in the study. Various biocide genes, including qacA/B, qacC, qacH, qacEΔ1, and different types of norA, were determined through conventional PCR. S. aureus isolates with qacA/B (+) were analyzed using high-resolution melting curve (HRM) to differentiate qacA from qacB. The chlorhexidine MIC was determined using the agar dilution method. Univariate and multivariate statistics were analyzed to see which biocide resistant genes had effects on chlorhexidine MIC. Results of all HRM analyses (n = 22) were consistent with those of Sanger sequencing for differentiation of qacA from qacB. None of the isolates harbored qacH and only one MRSA harbored qacEΔ1. The harboring rate of qacA, qacB, and qacC among MRSA/MSSA isolates was 7.1% (n = 18)/0%, 38.2% (n = 97)/0%, and 7.5% (n = 19)/3.3% (n = 1), respectively. The most type of norA was norAI (n = 158), followed by norAIII (n = 87) and norAII (n = 9) among MRSA isolates. Based on the results of multivariate logistic regression analyses, only qacA and qacB would increase chlorhexidine MIC from ≤ 1 ug/ml to ≥ 2 ug/ml in MRSA isolates (P < 0.001) but not qacC or norA types (P=0.976 and 0.633 or 0.933, respectively). In addition, only qacA but not qacB was contributed to elevate chlorhexidine from ≤ 1 ug/ml to 4 ug/ml in MRSA isolates (P < 0.001 and 0.017, respectively). HRM analysis can be a great method to differentiate qacA from qacB. The biocide gene with the most effect on chlorhexidine MIC in S. aureus isolates was qacA, followed by qacB, but qacC and different types of norA did not have any effect on chlorhexidine susceptibility. Further investigation on the influence of qacB, qacC and types of norA on chlorhexidine susceptibility is necessary.


Kraepelin's concept of psychiatric illness.
Emil Kraepelin fundamentally shaped our current psychiatric nosology. Although much has been written about his diagnostic formulations, less is known about his views on the fundamental nature of psychiatric illness and the goals of psychiatric nosology. We focus on his writings from 1896 to 1903 but also review his inaugural lecture in Dorpat in 1887 and his last two papers, published in 1919–1920. Kraepelin hoped for a ' natural ' classification of psychiatric illness but realized that the level of etiologic knowledge required to undergird this effort was not feasible in his own lifetime. This did not stop him, however, from developing a pragmatic approach based on his clinical method of careful description with detailed follow-up, coupled with the available fallible tools of pathological anatomy and, by 1919, genetics and biochemistry. Kraepelin saw psychiatric disorders as multifactorial, arising from the difficult to untangle action and interaction of internal and external causes. He was aware of the problem of defining the boundaries of illness and health but knew this was not unique to psychiatry. Contrary to his stereotype, he was sensitive to the importance of personality factors in psychiatric illness and advocated for their investigation. He also recognized the limitations of his ' clinical method' and was especially critical of classifications based on single prominent symptoms. Ultimately, Kraepelin was a skeptical realist when it came to psychiatric nosology. His goal of developing a consistent ' natural ' classification of the major mental disorders has yet to be attained, but his ' research agenda' remains central to psychiatry to the present day.


Medical aspect and minimal invasive treatment of urinary stones in children.
Despite its relatively uncommon incidence, management of the urinary stones in children poses a specific technical challenge to the urologist. Aims of the management should be complete clearance of stones, preservation of renal function and prevention of stone recurrence. In pediatric patients with urinary stones metabolic conditions have been demonstrated in up to 50% of cases whereas a variety of anatomic anomalies have been found in about 30% of children with urolithiasis. For this reason in addition to stone removal procedures, treatment of pediatric urolithiasis requires a thorough metabolic and urological evaluation on an individual basis. Obstructive pathologies along with the established metabolic abnormalities should be treated on time. Urine volume should be increased encouraging adequate fluid intake evenly distributed to the whole day and medical therapeutic agents which increase urine citrate levels may be considered in the medical management of hypocitraturia. In order to select the most appropriate surgical treatment, location, composition, and size of the stone(s), the anatomy of the collecting system, and the presence of obstruction along with the presence of infection of the urinary tract should be considered. Improvements in technology and growing experience have resulted in greater acceptance of minimally invasive techniques for the management of pediatric stones and currently urologists can benefit from the whole spectrum of stone management alternatives also in children. SWL is the first choice treatment for upper tract calculi while other minimally invasive methods have more specific indications. Although SWL is safe and efficient in the treatment of both renal and ureteral stones, ureteroscopy and PCNL in expert hands, can be successfully applied in appropriate cases. In fact due to the technically demanding nature of these procedures prior experience in the adult population is mandatory. With judicious application of these treatment modalities, excellent stone free rates with minimal morbidity could be obtained in this specific patient population. In patients with anatomical abnormalities open surgery will continue to be the preferred treatment alternative.


[Prevention and management of pseudoaneurysm after radical gastrectomy for gastric cancer].
With the promotion of standard radical resection of gastric cancer, the incidence of postoperative pseudoaneurysm is significantly increasing. Both the patient's own factors and iatrogenic factors are accoutable. Surgeons should clarify the causes of pseudoaneurysm, pay attention to the clinical symptoms and signs, and treat the patients appropriately. In order to avoid the occurrence of postoperative pseudoaneurysm, surgeons should carefully evaluate the preoperative conditions, perform precision operation and reduce the morbidity of postoperative infection and fistula.


An approach to increase the success rate of cultivation of soil bacteria based on fluorescence-activated cell sorting.
Soil microbiota are considered a source of undiscovered bioactive compounds, yet cultivation of most bacteria within a sample remains generally unsuccessful. Two main reasons behind the unculturability of bacteria are the presence of cells in a viable but not culturable state (such as dormant cells) and the failure to provide the necessary growth requirements in vitro (leading to the classification of some bacterial taxa as yet-to-be-cultured). The present work focuses on the development of a single procedure that helps distinguish between both phenomena of unculturability based on viability staining coupled with flow cytometry and fluorescence-activated cell sorting. In the selected soil sample, the success rate of cultured bacteria was doubled by selecting viable and metabolically active bacteria. It was determined that most of the uncultured fraction was not dormant or dead but likely required different growth conditions. It was also determined that the staining process introduced changes in the taxonomic composition of the outgrown bacterial biomass, which should be considered for further developments. This research shows the potential of flow cytometry and fluorescence-activated cell sorting applied to soil samples to improve the success rate of bacterial cultivation by estimating the proportion of dormant and yet-to-be-cultured bacteria and by directly excluding dormant cells from being inoculated into growth media.


Routes of cytochrome a3 reduction. The neoclassical model revisited.
A model for cytochrome oxidase is presented in which cytochrome a, cytochrome a3, and CuB are mutally interacting centers. Cytochrome a3, at equilibrium, is always reduced after CuB. The redox potential of cytochrome a declines progressively as the a3 CuB center is reduced. Dithionite reduction involves up to five steps: (i) reduction of cytochrome a and CuA; (ii) reduction of CuB; (iii) dissociation of ligands (exogenous and endogenous) from cytochrome a3; (iv) spin state changes (high to low) in cyt. a3 and (v) reduction of cytochrome a3. Any of (ii), (iii), and (iv) may be implicated as part of the slow step in this process, which is seen in the resting enzyme.


Evaluation of graphene-derived bone scaffold exposure to the calvarial bone_in-vitro and in-vivo studies.
Graphene is a novel material which has recently been gaining great interest in the biomedical fields. Our previous study observed that graphene-derived particles help induce bone formation in a murine calvarial model. Here, we further developed a blended graphene-contained polycaprolactone (PCL/G) filament for application in a 3D-printed bone scaffold. Since implants are expected to be for long-term usage, in vitro cell culture and in vivo scaffold implants were evaluated in a critical-size bone defect calvarial model for over 60 weeks. Graphene greatly improved the mechanical strength by 30.2% compared to pure PCL. The fabricated PCL/G scaffolds also showed fine cell viability. In animal model, an abnormal electroencephalogram power spectrum and early signs of aging, such as hair graying and hair loss, were found in the group with a PCL/G scaffold compared to pure PCL scaffold. Neither of the abnormal symptoms caused death of all animals in both groups. The long-term use of graphene-derived biomaterials for in-vivo implants seems to be safe. But the comprehensive biosafety still needs further evaluation.


Zinc potentiation of androgen receptor binding to nuclei in vitro.
Zn2+ potentiates binding of the 4.5S [3H]dihydrotestosterone-receptor complex to isolated rat prostate Dunning tumor nuclei in vitro when assayed in the presence of 300 microM ZnCl2, 3 mM MgCl2, 0.25 M sucrose, 5 mM mercaptoethanol, 0.15 M KCl, and 50 mM tris(hydroxymethyl)aminomethane, pH 7.5. In the presence of 5 mM mercaptoethanol, the concentration of 50 microM total Zn2+ required to promote half-maximal receptor binding to nuclei corresponds to a free Zn2+ concentration of 50 nM. The receptor-nuclear interaction appears to be selective for Zn2+; other divalent cations when added at a concentration of 1 mM to a buffer containing 5 mM mercaptoethanol are less effective (Ni2+) or have essentially no effect (Ca2+, Mg2+, Mn2+, Co2+, Cu2+, and Cd2+). Zn2+ does not alter the sedimentation rate of the 4.5S [3H]dihydrotestosterone receptor in the presence of mercaptoethanol; however, in the absence of mercaptoethanol, Zn2+ causes the receptor to aggregate. Zn2+-dependent nuclear binding of the 4.5S [3H]dihydrotestosterone receptor is saturable at 1.4 X 10(-13) mol of receptor sites/mg of DNA, corresponding to approximately 1150 sites/nucleus. In the presence of excess nuclei, up to 60% of added receptor is nuclear bound. An apparent binding constant for the receptor-nuclear interaction of 10(13) M-1 was approximated. Pyridoxal 5'-phosphate (less than or equal to 10 mM), but not 0.4 M KCl, inhibits Zn2+-dependent nuclear binding of the [3H]dihydrotestosterone receptor. Up to 66% of nuclear-bound receptor can be extracted in buffer containing 3 mM ethylenediaminetetraacetic acid plus either 0.4 M KCl or 10 mM pyridoxal 5'-phosphate.(ABSTRACT TRUNCATED AT 250 WORDS)


Severe hyperlipemia-induced pseudoerythrocytosis - Implication for misdiagnosis and blood transfusion: A case report and literature review.
Severe hyperlipemia (SHLE) has an impact on the results of many kinds of laboratory tests. Complete blood count (CBC) examination by automated blood cell counter (ABCC) is a quick and convenient measurement for screening abnormalities of blood cells that are triggered by various pathogenic insults in disease diagnosis and for monitoring changes in the treatment of existing hematological conditions. However, CBC results are frequently affected by many intrinsic and extrinsic factors from blood samples, such as in the setting of hypergammaglobulinemia and certain anticoagulants. SHLE could also affect CBC results. A 33-year-old Chinese male presented with painful foot numbness and abdominal pain. He was initially misdiagnosed as having a myeloproliferative neoplasm (MPN) because of the marked abnormalities in CBC examination by the ABCC. Morphological evaluation of the bone marrow smears and biopsy showed no evidence of MPN. Gene mutations in Breakpoint cluster regions-Abelson murine leukemia viral oncogene homologue 1 (BCR-ABL1), Janus kinase 2 (JAK2), calreticulin (CALR), myeloproliferative leukemia virus (MPL), and colony-stimulating factor 3 receptor (CSF3R) were negative. Having noticed the thick chylomicron layer on blood samples and the dramatically fluctuating CBC results, we speculated that the fat droplets formed by shaking the blood samples in the setting of SHLE were mistakenly identified as blood cells due to the limited parameters of ABCC. Therefore, we removed a large part of the chylomicron layer and then reexamined the CBC, and the CBC results, as we expected, differed significantly from that of the sample before the chylomicron layer was removed. These significant differences had been validated by the subsequently repeated laboratory tests by measuring dual blood samples that the chylomicron layer was removed in one sample and was not in another, and comparing the CBC results. Computerized tomography reexamination of the upper abdomen revealed an exudative lesion surrounding his pancreas. After intensive consultation, definitive diagnosis was made as recurrent pancreatitis, hyperlipemia and pseudoerythrocytosis. SHLE may become a potential cause of misdiagnosis of hyperlipemia-related diseases as MPNs and the resultant mistreatment. It may also lead to the misinterpretation of transfusion indications in patients with hematological disorders who critically need blood transfusion for supportive treatment.


350-μm side-view optical probe for imaging the murine brain in vivo from the cortex to the hypothalamus.
Miniature endoscopic probes offer a solution for deep brain imaging by overcoming the limited depth of intravital microscopy. We describe a small-diameter (350 μm) graded-index optical probe with a side-view design for in vivo cellular imaging of the mammalian brain. The side-view probe provides a unique view of the vertical network of neurons and penetrating blood vessels. At a given insertion site, the translational and rotational scanning of the probe provides access to a large tissue area (>1 mm(2)) across the cortex, hippocampus, thalamus, and hypothalamus.


[Long-term effects of PUVA therapy on Israeli patients with vitiligo].
Long-term treatment of psoriasis patients with PUVA (psoralen and ultraviolet A) is associated with an increased risk of photoaging and non-melanomic skin cancer, and perhaps of melanoma as well. Very little information is available on the long-term effects of PUVA treatment on vitiligo patients in general, and specifically on the risk of developing skin tumors. Among vitiligo patients treated with PUVA or heliotherapy, only a few cases of squamous cell carcinoma (SCC) have been described. The objective of this research is to examine the long-term effects of PUVA treatment among vitiligo patients and the incidence of long-term side effects, including various types of skin cancers. The medical files of all patients treated with PUVA at the Rabin Medical Center and the Emek Medical Center between 1982 and 1996 were surveyed. Each patient was interviewed by telephone and then invited to come in for a medical examination. A total of 28 out of 31 patients completed the questionnaire, and 12 of them were also examined. The average age of the patients was 47 years (range 25-84). The average amount of radiation to which each patient was exposed was 546.8 J/cm2 (range 26.5-1561), with a median of 336.8 J/cm2. The average number of treatments per patient was 84.2 (median 77). The average time that elapsed since beginning the treatment was 11 years (range 7-20), and the average time since treatment ended was 9.4 years (range 2-23). Partial or total repigmentation was experienced by 60% of the patients. In 18% of the patients, total or almost total repigmentation was seen, which lasted an average of 46 months. No skin cancer of any kind was seen in any of the patients. A recurrence of the illness was seen in all the vitiligo patients who had responded to PUVA treatment. Long-term treatment with PUVA for vitiligo patients does not entail photoaging damages or increased risk of skin cancer.


Otariodibacter oris gen. nov., sp. nov., a member of the family Pasteurellaceae isolated from the oral cavity of pinnipeds.
A total of 27 bacterial isolates from California sea lions and a walrus tentatively classified within the family Pasteurellaceae was further characterized by genotypic and phenotypic tests. Phylogenetic analysis of partial 16S rRNA and rpoB gene sequences showed that the isolates investigated formed a monophyletic group, tentatively designated Bisgaard taxon 57. According to 16S rRNA gene sequences, the most closely related species with a validly published name was Bisgaardia hudsonensis and the most closely related species based on rpoB sequence comparison was Pasteurella multocida subsp. multocida; highest similarities between the isolates and the type strains of B. hudsonensis and P. multocida subsp. multocida were 95.0 and 88.2%. respectively. All isolates of Bisgaard taxon 57 exhibit the phenotypic characters of the family Pasteurellaceae. Members of Bisgaard taxon 57 can be separated from existing genera of the Pasteurellaceae by the following tests: positive reactions for catalase, oxidase, Voges-Proskauer and indole; no X- or V-factor dependency; and acid production from L-arabinose (slow), L-fucose, maltose and trehalose, but not from dulcitol, D-mannitol, D-mannose or sucrose. The main fatty acids of Bisgaard taxon 57 (CCUG 59994(T)) are C(14:0), C(16:0), C(16:1)ω7c and the summed feature C(14:0) 3-OH/iso-C(16:1) I. This fatty acid profile is characteristic of members of the Pasteurellaceae. The quinone profile of Bisgaard taxon 57 (DSM 23800(T)) was similar to that of other genera in the Pasteurellaceae. The DNA G+C content of strain Baika1(T) is 36.2 mol%, which is at the lower end of the range for members of the family Pasteurellaceae. On the basis of both phylogenetic and phenotypic evidence, it is proposed that members of Bisgaard taxon 57 should be classified as representatives of a novel species in a new genus, Otariodibacter oris gen. nov., sp. nov. The type strain of Otariodibacter oris is Baika1(T) (=CCUG 59994(T)=DSM 23800(T)), which was isolated from the oral cavity of a healthy California sea lion in Copenhagen Zoo, Denmark, in 2007.


Keratosis punctata palmoplantaris controlled with topical retinoids: a case report and review of the literature.
Keratosis punctata palmoplantaris (KPPP) is a rare genodermatosis with an autosomal-dominant pattern of inheritance. We report the case of a 61-year-old woman who presented with a long history of multiple symptomatic hyperkeratotic papules on the palms and soles. In addition, we review the literature and present the current classification of the heterogeneous group of punctate palmoplantar keratoses, the cutaneous and histologic findings, the differential diagnosis, the possible association with various anomalies including malignancies, and the various treatment options.


Cognitive-behavior therapy, sertraline, and their combination for children and adolescents with obsessive-compulsive disorder: the Pediatric OCD Treatment Study (POTS) randomized controlled trial.
The empirical literature on treatment of obsessive-compulsive disorder (OCD) in children and adolescents supports the efficacy of short-term OCD-specific cognitive-behavior therapy (CBT) or medical management with selective serotonin reuptake inhibitors. However, little is known about their relative and combined efficacy. To evaluate the efficacy of CBT alone and medical management with the selective serotonin reuptake inhibitor sertraline alone, or CBT and sertraline combined, as initial treatment for children and adolescents with OCD. The Pediatric OCD Treatment Study, a balanced, masked randomized controlled trial conducted in 3 academic centers in the United States and enrolling a volunteer outpatient sample of 112 patients aged 7 through 17 years with a primary Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition diagnosis of OCD and a Children's Yale-Brown Obsessive-Compulsive Scale (CY-BOCS) score of 16 or higher. Patients were recruited between September 1997 and December 2002. Participants were randomly assigned to receive CBT alone, sertraline alone, combined CBT and sertraline, or pill placebo for 12 weeks. Change in CY-BOCS score over 12 weeks as rated by an independent evaluator masked to treatment status; rate of clinical remission defined as a CY-BOCS score less than or equal to 10. Ninety-seven of 112 patients (87%) completed the full 12 weeks of treatment. Intent-to-treat random regression analyses indicated a statistically significant advantage for CBT alone (P = .003), sertraline alone (P = .007), and combined treatment (P = .001) compared with placebo. Combined treatment also proved superior to CBT alone (P = .008) and to sertraline alone (P = .006), which did not differ from each other. Site differences emerged for CBT and sertraline but not for combined treatment, suggesting that combined treatment is less susceptible to setting-specific variations. The rate of clinical remission for combined treatment was 53.6% (95% confidence interval [CI], 36%-70%); for CBT alone, 39.3% (95% CI, 24%-58%); for sertraline alone, 21.4% (95% CI, 10%-40%); and for placebo, 3.6% (95% CI, 0%-19%). The remission rate for combined treatment did not differ from that for CBT alone (P = .42) but did differ from sertraline alone (P = .03) and from placebo (P<.001). CBT alone did not differ from sertraline alone (P = .24) but did differ from placebo (P = .002), whereas sertraline alone did not (P = .10). The 3 active treatments proved acceptable and well tolerated, with no evidence of treatment-emergent harm to self or to others. Children and adolescents with OCD should begin treatment with the combination of CBT plus a selective serotonin reuptake inhibitor or CBT alone.


Trends and variation in the management of oesophagogastric cancer patients: a population-based survey.
Previous evidence indicates potential variation in the quality of care of cancer patients. We aimed to examine whether recent changes in the treatment of oesophagogastric cancers have been distributed equally among different patient subgroups. We analysed population-based cancer registry data about the treatment patterning of oesophagogastric cancer (other than oesophageal squamous cell carcinoma) during 1995-2006. There were 14,077 patients aged > or =40 years (69% men). There was only limited information on stage, and no information on co-morbidity status. During successive triennia, curative surgery use decreased from 28% to 20% (p < 0.001) whilst chemotherapy use increased from 9% to 30% (p < 0.001). Use of palliative surgery and of radiotherapy increased significantly but modestly (7% to 10%, and 9% to 11%, respectively). In multivariable logistic regression adjusting for age group, gender, diagnosis period and tumour type, curative surgery and chemotherapy were used less frequently in more deprived patients [per increasing deprivation group Odds Ratio (OR) = 0.96, 95% Confidence Interval (CI) 0.93-0.99, and OR = 0.90, 95%CI 0.87-0.93, respectively, p < 0.001 for both)]. Chemotherapy was also used less frequently in women (OR = 0.76, p < 0.001). During the study period, curative surgery decreased by a third and chemotherapy use increased by more than three-fold, reflecting improvements in the appropriateness and quality of management, but chemotherapy use, in particular, was unequal, both by socioeconomic status and gender.


Evaluation of an alternative skeletal muscle index for skeletal muscle mass assessment in a group of Australian women.
Sarcopenia is assessed by several methods, including dual energy X-ray absorptiometry (DEXA), which provide a height-adjusted skeletal muscle index (H-SMI). A SMI 2 standard deviation below the young adult reference [1] combined with low muscle strength or performance is used to identify sarcopenia. As height declines with age, H-SMI may underestimate low skeletal muscle mass in the older population. Our study aims to evaluate an alternative SMI and to examine its relationship to grip strength in a group of Australian women. Women from two cohorts were analysed. 2041 women had body composition data (112 had calf circumference, 137 had leg length measurements) without grip strength, and 49 women had grip strength measured (40 had body composition data).The relationship between leg length-adjusted SMI (LL-SMI) to grip strength and anthropometric variables to skeletal muscle mass by DEXA were examined by linear regression analysis. Cohort 1: Older women were compared to younger women. Older women were shorter but leg length did not differ between different age groups. H-SMI was not different between groups (P = 0.528). LL-SMI was lower in older women (P = 0.002). Cohort 2: LL-SMI was significantly associated with grip strength (P = 0.048) after adjustment for age. Older women were shorter, while leg length did not differ from the younger group. H-SMI may obscure and may underestimate low muscle mass in older individuals. LL-SMI may be a better measure of skeletal muscle mass in older individuals. These alternate SMI would benefit from further exploration in older individuals.


Enhanced conflict monitoring via a short-duration, video-assisted deep breathing in healthy young adults: an event-related potential approach through the Go/NoGo paradigm.
Practitioners of mindfulness are reported to have greater cognitive control especially in conflict monitoring, response inhibition and sustained attention. However, due to the various existing methods in each mindfulness practices and also, the high commitment factor, a barrier still exists for an individual to pick up the practices. Therefore, the effect of short duration deep breathing on the cognitive control is investigated here. Short duration guided deep breathing videos consisting of 5, 7 and 9 min respectively were created and used on subjects training. The effect on cognitive control was assessed using a Go/NoGo task along with event-related potential (ERP) measurements at Fz, Cz, and Pz. From the study, the significant outcome showed at the follow-up session in which participants engaged for 5 min deep breathing group showed a profound NoGo N2 amplitude increment as compared to the control group, indicating an enhanced conflict monitoring ability. An inverse relationship between the NoGo N2 amplitude and the breathing duration is observed as well at the follow-up session. These results indicated the possibility of performing short duration deep breathing guided by a video to achieve an enhanced conflict monitoring as an alternative to other mindfulness practices and 5 min is found to be the optimum practice duration. This study is the first to establish a relationship between deep breathing and conflict monitoring through ERP. The study population of young adults taken from the same environment reduces the variance in ERP results due to age and environment. A larger sample size would provide a greater statistical power. A longer duration of deep breathing should be investigated to further clarify the relationship between the practice duration and the NoGo N2 amplitude. The result can be split by gender and analyzed separately due to the different brain structure of males and females.


Cardiorenal syndrome: a cardiologist's perspective of pathophysiology.
The cardiorenal syndrome has recently been defined as "disorders of the heart and kidney whereby acute or chronic dysfunction in one organ may induce acute or chronic dysfunction of the other." The syndrome is extremely common and independently associated with poor clinical outcomes. However, no pharmacological therapy has been shown to improve its outcomes. Unfortunately, the mechanisms that initiate the development of renal dysfunction in heart failure are still debated. This review tries to clarify some of the misunderstanding regarding the principle hemodynamic factors that drive the kidneys to retain salt and water.


Parental Decision-Making in the Pediatric Intensive Care Unit: An Integrative Review.
Parents are commonly responsible for making health care decisions for their seriously ill children in the pediatric intensive care unit (PICU); however, the factors influencing their decisions may vary. This integrative review examined the empirical literature between 2013 and 2018 to understand factors pertaining to parents' decision-making about serious illness care of their children in the PICU. Seventeen studies met the inclusion criteria with three key findings. First, parent-clinician communication in the PICU is critical; second, most parents want to be the final decision-maker for their critically ill child; and third, parents' emotions, support systems, and the child's clinical status impact decision-making. Parental perspectives are important to consider when discussing serious illness care decisions for critically ill children. Further inquiry is needed into how the parent-clinician encounter impacts the decision-making process and subsequent outcomes in this population.


Risk factors associated with language development problems in childhood--a literature review.
Children with language problems are found to have a higher risk for future academic difficulties and learning disabilities. Conclusions from related literature were in many ways inconsistent. To identify systematically, the existing literature, and factors that influence language development in children. Databases of scientific literature were screened through the internet for publications that involved factors effecting language development in childhood. Hard copies of related scientific journals were also sought for relevant topics by the authors, making use of reference lists of publications, and citation search. Studies were included if they were published since 1984 and investigated factors that affect language development in children. They were excluded if they were not original research articles. Fifteen studies were included for this review--a case-control study, a cross-sectional study, and thirteen longitudinal studies. Most studies demonstrated that the following factors affect language development--antenatal care, Apgar scores, birth weight, premature delivery, birth order, parental education, environmental factors, gender of the children, and family history with specific language impairment. Perinatal/postnatal and environmental factors influence language development. Such factors should be taken into account as confounding factors in further language development studies.


Complete genome sequence of Methanothermobacter marburgensis, a methanoarchaeon model organism.
The circular genome sequence of the chemolithoautotrophic euryarchaeon Methanothermobacter marburgensis, with 1,639,135 bp, was determined and compared with that of Methanothermobacter thermautotrophicus. The genomes of the two model methanogens differ substantially in protein coding sequences, in insertion sequence (IS)-like elements, and in clustered regularly interspaced short palindromic repeats (CRISPR) loci.


Tongue protrusion strength and fatiguability: relationship to apnoea/hypopnoea index and age.
The sleep apnoea/hypopnoea syndrome (SAHS) is characterized by retroglossal or retropalatal narrowing. The site of obstruction, and the fact that negative pressure in the upper airway increases retroglossal airway size, suggests that tongue muscles may play a role in the maintenance of upper airway patency. We therefore hypothesized that tongue protrusion strength and fatiguability may be predictors of apnoea/hypopnoea index, vary with age and may be different in SAHS patients and normal subjects. Maximal strength (Fmax) and fatiguability (measured as the total time subjects were able to maintain 50% Fmax on three consecutive occasions separated by 30 s) were assessed using a force transducer in 98 consecutive apnoeic/hypopnoeic male patients referred to our laboratory for sleep studies [apnoea/hypopnoea index (AHI) range 3-130/h, age range 30-74 y]. Fmax and fatiguability were also compared in 15 male SAHS patients (mean AHI 20/h) and 15 nonsnoring male subjects matched for age, body mass index and fat free mass. A further 26 SAHS patients had tongue protrusion strength/fatiguability measured before, during and after a night's sleep. Log AHI was only weakly correlated with Fmax (r=- 0.21; P=0.03) and age (r=0.23; P=0.025), but not to fatiguability (P > 0.05). Comparison between SAHS and nonsnoring subjects did not demonstrate significant differences in Fmax (P=0.1) or fatiguability (P=0.1). There was no evidence of a change in muscle strength (P > 0.05) or fatigue (P > 0.05) during the course of a night's sleep. We conclude that tongue protrusion strength and fatiguability are unlikely to be important factors in the pathogenesis of SAHS.


Philanthropies croisées: a joint venture in public health at Lyon (1917-1940).
Since the end of the First World War the Rockefeller Foundation has spearheaded a large-scale programme in the field of education for the health professions (doctors and nurses). In several countries throughout the world, but with its efforts concentrated on Europe, it has financed schools, constructed information networks, granted research scholarships and awarded training bursaries. In so doing it has not, however, been in the business of propagating an irresistible "American model," nor has it pursued a huge undertaking in disinterested aid. Through an attempt to contextualize these programmes, to bring to light the existence of common reference points, to retrace the work with local participants and to appraise cleavages within the philanthropic apparatus, this article proposes a fine-grained reading of the role of the Rockefeller Foundation at the Faculté de Médecine (Faculty of Medicine) and the Ecole d'Infirmières et d'assistantes sociales (Training School for Nurses and Social Workers) in Lyon between 1917- and 1940. It analyses these institutions in terms of the transactions, negotiations and appropriations that highlight their joint-venture character and it identifies their varied impact.


BSS and ICA in neuroinformatics: from current practices to open challenges.
We give a general overview of the use and possible misuse of blind source separation (BSS) and independent component analysis (ICA) in the context of neuroinformatics data processing. A clear emphasis is given to the analysis of electrophysiological recordings, as well as to functional magnetic resonance images (fMRI). Two illustrative examples include the identification and removal of artefacts in both kinds of data, and the analysis of a simple fMRI. A second part of the paper addresses a set of currently open challenges in signal processing. These include the identification and analysis of independent subspaces, the study of networks of functional brain activity, and the analysis of single-trial event-related data.


Post-differentiation Replating of Human Pluripotent Stem Cell-derived Neurons for High-content Screening of Neuritogenesis and Synapse Maturation.
Neurons differentiated in two-dimensional culture from human pluripotent stem-cell-derived neural progenitor cells (NPCs) represent a powerful model system to explore disease mechanisms and carry out high content screening (HCS) to interrogate compound libraries or identify gene mutation phenotypes. However, with human cells the transition from NPC to functional, mature neuron requires several weeks. Synapses typically start to form after 3 weeks of differentiation in monolayer culture, and several neuron-specific proteins, for example the later expressing pan-neuronal marker NeuN, or the layer 5/6 cerebral cortical neuron marker CTIP2, begin to express around 4-5 weeks post-differentiation. This lengthy differentiation time can be incompatible with optimal culture conditions used for small volume, multi-well HCS platforms. Among the many challenges are the need for well-adhered, uniformly distributed cells with minimal cell clustering, and culture procedures that foster long-term viability and functional synapse maturation. One approach is to differentiate neurons in a large volume format, then replate them at a later time point in HCS-compatible multi-wells. Some main challenges when using this replating approach concern reproducibility and cell viability, due to the stressful disruption of the dendritic and axonal network. Here we demonstrate a detailed and reliable procedure for enzymatically resuspending human induced pluripotent stem cell (hiPSC)-derived neurons after their differentiation for 4-8 weeks in a large-volume format, transferring them to 384-well microtiter plates, and culturing them for a further 1-3 weeks with excellent cell survival. This replating of human neurons not only allows the study of synapse assembly and maturation within two weeks from replating, but also enables studies of neurite regeneration and growth cone characteristics. We provide examples of scalable assays for neuritogenesis and synaptogenesis using a 384-well platform.


Machine learning: A modern approach to pediatric asthma.
Among modern methods of statistical and computational analysis, the application of machine learning (ML) to healthcare data has been gaining recognition in helping us understand the heterogeneity of asthma and predicting its progression. In pediatric research, ML approaches may provide rapid advances in uncovering asthma phenotypes with potential translational impact in clinical practice. Also, several accurate models to predict asthma and its progression have been developed using ML. Here, we provide a brief overview of ML approaches recently proposed to characterize pediatric asthma.


Spinal Reactive Oxygen Species and Oxidative Damage Mediate Chronic Pain in Lame Dairy Cows.
Lameness in dairy cows is a worldwide prevalent disease with a negative impact on animal welfare and herd economy. Oxidative damage and antioxidant system dysfunction are common features of many CNS diseases, including chronic pain. The aim of this study was to evaluate the levels of reactive oxygen species (ROS) and oxidative damage markers in the spinal cord of dairy cows with chronic inflammatory lameness. Locomotion score was performed in order to select cows with chronic lameness. Dorsal horn spinal cord samples were obtained post mortem from lumbar segments (L2-L5), and ROS, malondialdehyde (MDA), and carbonyl groups were measured along with the activity of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and total antioxidant response (TAR). Lame cows had increased levels of ROS, MDA, and carbonyl groups, while no differences were observed between lame and non-lame cows in SOD, GPx, CAT, and TAR activity. We conclude that painful chronic inflammatory lameness in dairy cows is associated with an increase in ROS, MDA, and carbonyl groups. Nonetheless, an association between ROS generation and dysfunction of the antioxidant system, as previously proposed, could not be established.


Schwannoma base tongue: Case report and review of literature.
Schwannomas are benign peripheral nerve sheath tumors. These are rare in the oral cavity (1%). The most common site of involvement in oral cavity is the tongue. Posterior third of tongue is not frequently involved. The aim of this paper is to present a case report of base tongue schwannoma and review literature of this rare tumor. Data from literature were analyzed for age, gender, presenting symptom, size at presentation, and surgical approach. We report a case of 26 year-old male who presented with swelling posterior 1/3rd tongue and change in quality of voice. He was evaluated for the same with MR and incision biopsy and was planned for surgery. Surgery was abandoned at a district hospital due to difficulty in intubation. At our center he underwent fibro optic bronchoscopy guided intubation followed by general anesthesia. He underwent excision of mass using left paramedian lip spitting approach with mandibulotomy and mandibular swing. Tumor was excised in toto. His postoperative recovery was uneventful. Literature review between 2001 and 2012 was done. 15 cases of base tongue schwannoma were identified. The most common age group involved was between 30-40 years. There was a slightly higher incidence in females. All patients were symptomatic at presentation. Most common complaints were related to swallowing and throat pain. Most patients underwent transoral excision of the tumor.


A new 180-kDa dermal endothelial cell activation antigen: in vitro and in situ characteristics.
PN-E2 is a monoclonal antibody generated against recombinant tumor necrosis factor-alpha (TNF-alpha)-treated human umbilical vein endothelial cells (EC). PN-E2 recognized a molecule with expression levels in vitro that could be downregulated by TNF, and in situ PN-E2 showed only weak reactivity with vascular EC in normal skin, as assessed by immunohistochemical staining. The expression of PN-E2 was considerably increased on EC in various pathologic skin lesions, including psoriasis, granulation tissue, and inflamed skin. PN-E2 antigen expression was analyzed in more detail in vitro on cultured EC and fibroblasts by use of enzyme-linked immunosorbent assay and fluorescence-activated cell sorter techniques. The expression level on human umbilical vein endothelial cells and capillary EC was, in contrast to the in situ immunohistologic findings, invariably high. On fibroblasts, a low expression was found. Incubation of the EC with recombinant TNF-alpha decreased expression by a factor of 2. Incubation of EC with recombinant interferon-gamma resulted in a twofold increase in PN-E2 antigen expression, whereas other cytokines [recombinant interleukin (rIL)-1 alpha, rIL-1 beta, rIL-4, rIL-6], lipopolysaccharide, or recombinant basic fibroblast growth factor had no effect. Immunoelectron microscopy of tissue specimens and EC preparations localized the antigen on the luminal membrane of the endothelium. Immunoprecipitation followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis revealed a major band at 90 kDa and a minor band at 80 kDa under reducing conditions and bands of 180 and 400 kDa under non-reducing conditions. Molecular weight and expression patterns in vitro on EC after incubation with cytokines excluded most of the known endothelium-specific molecules, with the possible exception of endoglin (the 44G4 antigen). We conclude from our findings that this new antigen could be useful as a marker for endothelial activation in skin biopsy material.


Retooling social work practice for high volume, short stay.
The re-engineered acute care environment that emphasizes managed care, reduced costs per case and shorter lengths of stay also demands innovative approaches to the delivery of social work service. As departments disappear and other professions compete for roles in counselling, discharge planning and community liaison, there is a real threat to the viability of the acute hospital as a setting for social work. This paper focuses on the adaptive skills needed for the restructured acute care context, including (1) the creation of key roles for social work on the multidisciplinary team, (2) pre-admission high-risk screening and discharge planning, (3) high volume recording, (4) solution-focused brief interventions, and (5) the development of community partnerships. These conceptual strategies are implemented differently in examples drawn from three distinct high-volume patient groups: reconstructive orthopaedics, high-risk fetal assessment and thoracic oncology.


Human umbilical cord mesenchymal stem cells contribute to the reconstruction of bladder function after acute spinal cord injury via p38 mitogen-activated protein kinase/nuclear factor-kappa B pathway.
The association between spinal cord injury (SCI) and bladder symptoms has been intensively described. Human umbilical cord mesenchymal stem cell (hUC-MSC) treatment is beneficial to the recovery of bladder function after SCI, but its mechanism is unclear. We established an SCI model, and prepared hUC-MSCs in advance, followed by verification using flow cytometry. The Basso, Beattie and Bresnahan (BBB) score and urodynamic index were employed to evaluate motor function and bladder functions, respectively. Hematoxylin-eosin staining, luxol fast blue staining, and Masson's trichrome staining were utilized to assess pathological changes. Real-time quantitative PCR and Western blot were used to determine the mRNA and protein expressions in bladder tissues. The immunophenotypes of the HUC-MSCs were CD90+ and CD105+, but CD34-, CD45- and HLA-DR-. Rats appeared severe motor dysfunction after SCI, but the BBB score was increased in hUC-MSCs after the second week. Pathologically, the improvement of the lesion area on the dorsal spinal cord, augmented anterior gray horn neuron cells of the spinal cord and lessened bladder tissue remodeling (fibrosis, collagen deposition) as well as modulated inflammation could be observed. Besides, SCI increased bladder weight, bladder capacity, urine volume and residual urine volume, and decreased urination efficiency. HUC-MSCs ameliorated SCI-induced pathological changes and bladder functions, the expressions of Collagen I, Collagen III, fibroblast growth factor 2 (FGF2), phospho-p38, transient receptor potential vanilloid 1, Toll-like receptor 4 and phospho-nuclear factor-kappa B (p-NF-κB). To sum up, HUC-MSCs contribute to the reconstruction of bladder function after SCI by repressing p38 MAPK/NF-κB pathway.


Keratitis-ichthyosis-deafness syndrome: Phenotypic heterogeneity and treatment perspective of patients with p.Asp50Asn GJB2 mutation.
Keratitis-ichthyosis-deafness (KID) syndrome is caused by mutations in the GJB2 gene encoding connexin 26, a component of transmembrane hemichannels which form gap junction channels, critical for cell-cell communication. Here, we report two patients from two distinct families with KID syndrome with the same GJB2 mutation (p.Asp50Asn); in both cases the mutation was de novo, as the parents depicted the wild-type allele only. The patients' cutaneous manifestations were strikingly different illustrating the wide spectrum of phenotype of these patients, even with the same GJB2 mutation. One of the patients was treated with acitretin with dramatic improvement in his skin findings, illustrating the role of oral acitretin in treatment of patients with KID syndrome. Collectively, these patients attest to the phenotypic spectrum of KID syndrome, with therapeutic perspective.


Influence of heat stress on genome of grass pea (Lathyrus sativus L.).
Meiosis is an event of high evolutionary stability that culminates in a reduction of chromosome number. Several abiotic environmental factors such as heat may cause anomalies at genetic level that ultimately impair fertility of the plant. In the present study, the effect of heat stress on various morphological and cytological parameters has been studied in Lathyrus sativus. The most interesting anomaly recorded during the study was the formation of synezetic knot in prophase-l instead of leptotene and zygotene stages. Furthermore, a large number of interesting karyological and cytoplasmic irregularities viz. multivalents, transmigration of chromosomes, bridges, tripolarity, etc. were found among the heat treated population of 48 hr duration in M2 generation.


Healthcare information technology and medical-surgical nurses: the emergence of a new care partnership.
Healthcare information technology in US hospitals and ambulatory care centers continues to expand, and nurses are expected to effectively and efficiently utilize this technology. Researchers suggest that clinical information systems have expanded the realm of nursing to integrate technology as an element as important in nursing practice as the patient or population being served. This study sought to explore how medical surgical nurses make use of healthcare information technology in their current clinical practice and to examine the influence of healthcare information technology on nurses' clinical decision making. A total of eight medical surgical nurses participated in the study, four novice and four experienced. A conventional content analysis was utilized that allowed for a thematic interpretation of participant data. Five themes emerged: (1) healthcare information technology as a care coordination partner, (2) healthcare information technology as a change agent in the care delivery environment, (3) healthcare information technology-unable to meet all the needs, of all the people, all the time, (4) curiosity about healthcare information technology-what other bells and whistles exist, and (5) Big Brother is watching. The results of this study indicate that a new care partnership has emerged as the provision of nursing care is no longer supplied by a single practitioner but rather by a paired team, consisting of nurses and technology, working collaboratively in an interdependent relationship to achieve established goals.