Demographic predictors of treatments and surgical complications of lumbar degenerative diseases: An analysis of over 250,000 patients from the National Inpatient Sample.
This was a national database study.To examine the role of comorbidities and demographics on inpatient complications in patients with lumbar degenerative conditions.Degenerative conditions of the lumbar spine account for the most common indication for spine surgery in the elderly population in the United States. Significant studies investigating demographic as predictors of surgical rates and health outcomes for degenerative lumbar conditions are lacking.Data were obtained from the National Inpatient Sample from 2010 to 2014 and International Classification of Diseases, 9th revision, Clinical Modification codes were used to identify patients with a primary diagnosis of degenerative lumbar condition. Patients were stratified based on demographic variables and comorbidity status. Multivariate regression analyses were used to determine whether any individual demographic variables, such as race, sex, insurance, and hospital status predicted postoperative complications.A total of 256,859 patients were identified for analysis. The rate of overall complications was found to be 16.1% with a mortality rate of 0.10%. Female, Black, Hispanic, and Asian/Pacific Islander patients had lower odds of receiving surgical treatment compared to White patients (P<.001). Medicare and Medicaid patients were less likely to be surgically managed than patients with private insurance (OR = 0.75, 0.37; P<.001, respectively). Urban hospitals were more likely to provide surgery when compared to rural hospitals (P < .001). Patients undergoing fusion had more complications than decompression alone (P < .001). Females, Medicare insurance status, Medicaid insurance status, urban hospital locations, and certain geographical locations were found to predict postoperative complications (P < .001).There were substantial differences in surgical management and postoperative complications among individuals of different sex, races, and insurance status. Further investigation evaluating the effect of demographics in spine surgery is warranted to fully understand their influence on patient complications.


[Intervention of glypican-3 genetic transcription on anti-proliferative effect of hepatoma cells with high metastatic potentiality].
To explore the silencing glypican-3 (GPC-3) gene transcription by specific small hairpin RNA (shRNA) on the inhibition of hepatoma cells with high metastatic potentiality and hepatoma growth. After MHCC-97H cells were transfected with higher effective GPC-3-shRNA, GPC-3 mRNA was analyzed by multiple FG-RT-PCR or protein by Western blot. Cell proliferation was detected by 5-ethynyl-2'-deoxyuridine and sulforhodamine B assay, its migratory metastasis and invasiveness by wound healing or transwell chamber system and cell apoptosis was detected by Caspase-Glo(®) 3/7 Luminescence assay. Nude mice were subcutaneously injected with stable MHCC-97H cells for observing the forming time or volume of xenograft tumors. And the expressions of GPC-3, β-catenin, p-GSK3β and CyclinD1 were analyzed by immunohistochemistry. After shRNA1 transfection with high efficiency (>80%), the expression of GPC-3 was down-regulated to 75.6% (t = 15.473, P < 0.001) at mRNA level in accordance with its protein, inhibiting cell proliferation (71.1%, t = 10.468, P < 0.001) notably, decreasing its migration (80.1%, t = 32.697, P < 0.001) and invasiveness (69.1%, t = 39.647, P < 0.001). β-catenin was down-regulated (67.7%, t = 18.4, P < 0.001) and Gli1 increased (53.5%, t = -4.824, P = 0.008) with its protein. The average forming time of subcutaneous tumors was 11.2 days (d) in the shRNA group and it was significantly longer (P < 0.01) than that in the control (5.3 d) or shRNA-neg (5.5 d) group. And the average volume (65.5 mm(3)) of tumors with decreased GPC-3, β-catenin, p-GSK3β, and cyclinD1 expressions in the shRNA group was significantly smaller (P < 0.01) than that in the shRNA-neg (365.7 mm(3)) or control (404.8 mm(3)) group, respectively. Specific shRNA might intervene effectively the GPC-3 gene transcription and inhibit invasion and tumor growth. Thus GPC-3 may become a potential molecular target for hepatoma gene therapy.


A clinical and polysomnographic comparison of neuroleptic-induced akathisia and the idiopathic restless legs syndrome.
Neuroleptic-induced akathisia (NIA) is motor restlessness caused by dopamine receptor blocking antipsychotic agents. Nine patients with NIA and 11 patients with idiopathic restless legs syndrome (RLS) were studied polysomnographically. The sleep disturbances were milder in NIA than idiopathic RLS but increased numbers of awakenings and decreased sleep efficiencies were common to both groups. In addition, RLS patients demonstrated prolonged sleep latencies. Periodic movements in sleep (PMS) were present in only 5 of 9 patients with NIA but in all 11 patients with idiopathic RLS. In no NIA patient did we see the multiple, large amplitude, violent, resting myoclonic jerks of the legs that we saw during wakefulness in some of our more severe cases of idiopathic RLS. NIA patients tended to experience inner restlessness and idiopathic RLS patients tended to experience leg paresthesias as an antecedent to motor restlessness. Idiopathic RLS patients had symptoms that were worse at night and in repose far more frequently than patients with NIA. NIA and idiopathic RLS have similarities and differences. Because both NIA and idiopathic RLS are characterized by motor restlessness and sleep disturbances, the pharmacodynamics of antipsychotic medications may give clues as to both the cause and treatment of idiopathic RLS.


Mechanism of antihypertensive effect of potassium depletion in renovascular hypertension.
K depletion (KD) prevents the development of hypertension in two-kidney, one-clip renovascular, hypertension [mean arterial pressure: 110 +/- 5 (KD) vs. 142 +/- 3 mmHg in potassium replete (KR); P less than 0.001]. The protective effect of KD is associated with a 60% decrease in angiotensin II (ANG II) pressor responsiveness and a 40% decrease in ANG II binding to mesenteric artery particles from rats with renovascular hypertension (receptor number 117 +/- 16 in KD vs. 165 +/- 14 fmol/mg protein in KR, P less than 0.05). To determine whether decreases in binding could account for decreases in ANG II pressor responsivity, we measured ANG II binding after bilateral nephrectomy or sustained administration of converting-enzyme inhibitor. Both maneuvers resulted in increases in binding, such that total binding and receptor number were greater than in comparably treated KR rats; e.g., after nephrectomy, receptor number was 215 +/- 26 in KD vs. 98 +/- 12 fmol/mg protein in KR, (P less than 0.01). Despite increased binding, the pressor response to ANG II in KD rats, which were nephrectomized or treated with converting-enzyme inhibitor, was still reduced by 50% compared with comparably treated KR rats. To determine whether the decreased ANG II pressor responsivity of KD was caused by cellular K depletion or to increases in ANG H induced by KD, we administered K to KD, ANG II-deficient rats. ANG II pressor responsivity increased, and total binding and receptor number decreased (KD, ANG II- deficient 246 +/ 22 fmol/mg protein; KD, ANG II-deficient + K 91 +/ 16 fmol/mg protein; P less than 0.005) with K.(ABSTRACT TRUNCATED AT 250 WORDS)


A pilot study of an interactive web site in the workplace for reducing alcohol consumption.
An interactive web-site-based intervention for reducing alcohol consumption was pilot tested. Participants were 145 employees of a work site in the Silicon Valley region of California, categorized as low or moderate risk for alcohol problems. All participants were given access to a web site that provided feedback on their levels of stress and use of coping strategies. Participants randomized to the full individualized feedback condition also received individualized feedback about their risk for alcohol-related problems. Some evidence was found for greater alcohol reduction among participants who received full individualized feedback, although due to difficulties in recruiting participants, the sample size was inadequate for evaluating treatment effects on drinking. The results provide preliminary support for using an interactive web site to provide individualized feedback for persons at risk for alcohol problems. However, the low participation rate (2.7%) suggests that such an intervention must address the challenges of recruiting employees through their work site.


Early Childhood Psychopathology Prospectively Predicts Social Functioning in Early Adolescence.
Psychopathology in school-age children predicts impairment later in development. However, the long-term psychosocial consequences of early childhood psychopathology are less well known. The current study is the first to prospectively examine how a range of diagnoses and symptoms in early childhood predict psychosocial functioning across specific domains during early adolescence 6-9 years later. A community sample (N = 595; 44.9% female; 88.7% White, 12.6% Hispanic) was assessed for psychopathology at ages 3 and 6 using the Preschool Age Psychiatric Assessment. Diagnoses and dimensional scores for depressive, anxiety, attention-deficit/hyperactivity (ADHD), and oppositional defiant disorders (ODD) were examined. When children were 12 years old, children and parents completed the UCLA Life Stress Interview for Children, a semistructured interview assessing functioning in multiple domains (academic, behavior, close friends, broader peers, maternal relationship, paternal relationship). Having a diagnosis in early childhood predicted greater impairment in all domains in early adolescence, except paternal relationship. Externalizing disorders predicted impairment in more domains than internalizing disorders. Most of the associations between early childhood psychopathology and poorer functioning in adolescence persisted after taking into account adolescent psychopathology. Moreover, the majority of bivariate associations with depressive, ODD, and ADHD symptoms, but not anxiety symptoms, persisted in a subsample of children who did not meet criteria for a diagnosis in early childhood. Early childhood psychopathology has long-lasting deleterious effects on several domains of psychosocial functioning, often beyond the effects of continuing or recurring adolescent psychopathology. Findings thereby highlight the validity and clinical significance of early psychopathology.


Slipped DNA structures within the enhancer region of the Moloney murine leukemia virus.
We have examined the S1 nuclease sensitivity of supercoiled plasmids harboring the Moloney Murine Leukemia Virus (MoMuLV) long terminal repeat (LTR). S1 sensitivity was found within the LTR enhancer direct repeats. Transformation of E. coli DH5 cells with a construct containing most of the MoMuLV LTR yielded the precise deletion of one direct repeat and loss of S1 sensitivity. The dependence of S1 sensitivity on the presence of both direct repeats, together with the exact excision of one direct repeat by E. coli, suggests the presence of slipped DNA within the enhancer. Such structures may represent targets for effector proteins which mediate vital functions during viral propagation.


Is Cerazette the minipill of choice?
Around 5% of women aged 16-49 years in Great Britain use a progestogen-only pill (POP; 'minipill') as contraception. These pills are used as alternatives to combined oral contraceptives (COCs), compared to which they are less reliable at preventing pregnancy: the estimated contraceptive failure rate of POPs is 0.5 pregnancies per 100 woman-years when used consistently and correctly, compared with 0.1 per 100 woman-years for COCs. Cerazette (Organon), a new POP, is being promoted by the company as "the first oestrogen free pill to consistently inhibit ovulation", as having "the efficacy of a combined pill, with the reassurance of an oestrogen free pill" and offering "reliable contraception for women of any reproductive age". Here, we consider whether Cerazette offers advantages over established POPs.


Hybrid combinations of parametric and empirical likelihoods.
This paper develops a hybrid likelihood (HL) method based on a compromise between parametric and nonparametric likelihoods. Consider the setting of a parametric model for the distribution of an observation Y with parameter θ. Suppose there is also an estimating function m(·, μ) identifying another parameter μ via Em(Y, μ) = 0, at the outset defined independently of the parametric model. To borrow strength from the parametric model while obtaining a degree of robustness from the empirical likelihood method, we formulate inference about θ in terms of the hybrid likelihood function Hn (θ) = Ln (θ)1-a Rn (μ(θ)) a . Here a ∈ [0,1) represents the extent of the compromise, Ln is the ordinary parametric likelihood for θ, Rn is the empirical likelihood function, and μ is considered through the lens of the parametric model. We establish asymptotic normality of the corresponding HL estimator and a version of the Wilks theorem. We also examine extensions of these results under misspecification of the parametric model, and propose methods for selecting the balance parameter a.


Antioxidant chemistry of green tea catechins. Identification of products of the reaction of (-)-epigallocatechin gallate with peroxyl radicals.
(-)-Epigallocatechin gallate (EGCG), isolated from green tea, displays antioxidant properties and is thought to act as an antioxidant in biological systems. However, the specific mechanisms of its antioxidant actions remain unclear. In this study, we have isolated and identified for the first time two reaction products of EGCG derived from its reaction with peroxyl radicals generated by thermolysis of the initiator 2,2'-azobis(2,4-dimethylvaleronitrile) (AMVN). The products include a seven-membered B-ring anhydride and a novel dimer. The identification of these products provides the first unambiguous proof that the principal site of antioxidant reactions on the EGCG molecule is the trihydroxyphenyl B ring, rather than the 3-galloyl moiety. In contrast to phenoxyl radicals from simple phenolic antioxidants, an initially formed EGCG phenoxyl radical apparently does not form stable addition products with AMVN-derived peroxyl radicals. Characteristic reaction products may provide novel markers for EGCG antioxidant reactions in living systems.


Primary malignant fibrous histiocytoma of the pleura. A case report.
An uncommon primary malignant fibrous histiocytoma (MFH) of the pleura is described. At light microscopy the tumor was characterized by a 'storiform' pattern of growth, with numerous multinucleated giant cells. Immunohistochemistry showed an intense, diffuse immunostaining for alpha-1-antitrypsin, focal for lysozyme. Ultrastructurally, histiocyte- and fibroblast-like cells and cells with intermediate features were present; moreover, it was possible to demonstrate the presence of mesenchymal 'stem' cells. Findings are discussed, also with respect to histogenesis of MFH.


Perceived Need for and Perceived Sufficiency of Mental Health Care in the Canadian Armed Forces: Changes in the Past Decade and Comparisons to the General Population.
Failure to perceive need for care (PNC) is the leading barrier to accessing mental health care. After accessing care, many individuals perceive that their needs were unmet or only partially met, an additional problem related to perceived sufficiency of care (PSC). The Canadian Armed Forces (CAF) invested heavily in workplace mental health in the past decade to improve PNC/PSC; yet, the impact of these investments remains unknown. To assess the impact of these investments, this study 1) captures changes in PNC/PSC over the past decade in the CAF and 2) compares current PNC/PSC between the CAF and civilians. Data were drawn from the 2013 and 2002 CAF surveys and the 2012 civilian mental health survey (total N = ∼40 000), conducted by Statistics Canada using similar methodology. Exclusions were applied to the civilian sample to make them comparable to the military sample. Prevalence rates for No need, Need met, Need partially met, and Need unmet categories across service types (Information, Medication, Counselling and therapy, Any services) were calculated and compared between 1) the 2 CAF surveys and 2) the 2013 CAF and 2012 civilian surveys after sample matching. Reports of Any need and Need met were higher in the CAF in 2013 than in 2002 by approximately 6% to 8% and 2% to 8%, respectively, and higher in the CAF than in civilians by 3% to 10% and 2% to 8%, respectively. These results suggest that investments in workplace mental health, such as those implemented in the CAF, can lead to improvements in recognizing the need for care (PNC) and subsequently getting those needs met (PSC).


Roles of NTE protein and encoding gene in development and neurodevelopmental toxicity.
Neuropathy Target Esterase (NTE) is a membrane protein codified by gene PNPLA6. NTE was initially discovered as a target of the so-called organophosphorus-induced delayed polyneuropathy triggered by the inhibition of the NTE-associated esterase center by neuropathic organophosphorus compounds (OPs). The physiological role of NTE might be related to membrane lipid homeostasis and seems to be involved in adult organisms in maintaining nervous system integrity. However, NTE is also involved in cell differentiation and embryonic development. NTE is expressed in embryonic and adult stem cells, and the silencing of Pnpla6 by interference RNA in D3 mouse cells causes significant alterations in several genetic pathways related to respiratory tube and nervous system formation, and in vasculogenesis and angiogenesis. The silencing of gene PNPLA6 in human NT2 cells at the beginning of neurodifferentiation causes severe phenotypic alterations in neuron-like differentiated cells; e.g. reduced electrical activity and the virtual disappearance of markers of neural tissue, synapsis and glia. These phenotypic effects were not reproduced when NTE esterase activity was inhibited by neuropathic OP mipafox instead of being silenced at the genetic level. Neuropathic OP chlorpyrifos seems able to induce neurodevelopmental alterations in animals. However, the effects of chlorpyrifos in the expression of biomarker genes of differentiation in D3 cells differ considerably from the effects induced by Pnpla6 silencing. In conclusion, available information suggests that PNPLA6 and/or the NTE protein play a role in early neurodifferentiation stages, although this role is not dependent upon the esterase NTE center. Therefore, impairments caused by OPs, such as chlorpyrifos, on neurodevelopment are not due to inhibition of NTE esterase enzymatic activity.


FcγRIIb expression on B cells is associated with treatment efficacy for acute rejection after kidney transplantation.
Fcγ receptors (FcγR) play a role in the acute rejection (AR) of organ transplants. FcγRIIB is an inhibitory FcγR expressed on B cells. Intravenous IgG (IVIG) and CD28 monoclonal antibody (mAb) have been shown to have immunomodulatory properties against AR. To examine the association between FcγRIIB expression on B cell subpopulations and AR treatment efficacy. Male F344 rats were used as kidney donors and Lewis rats as recipients to establish models of renal transplantation. Rats were divided into five groups: sham, AR-PBS, AR-IVIG, AR-PNGase F-IVIG, and AR-CD28. Serum creatinine (Scr), blood urea nitrogen (BUN), and urine protein content were determined. Inflammatory markers were measured by ELISA, FcγR by western blotting, and spleen B cell activation by flow cytometry. Scr, BUN, urinary protein content, levels of CRP, IL-10, TNF-α, IL-6, IL-8, and IgG were all increased in the AR-PBS group compared with the sham group (all P<0.01); these increases were partly reversed in the AR-IVIG, AR-PNGase F IVIG, and AR-CD28 groups (all P<0.01), with IVIG showing the better efficacy than PNGase F IVIG. Furthermore, blood and spleen FcγRIA and FcγRIIIA were increased by AR, while FcγRIIB expressions in splenic activated B cells and regulatory B cells were decreased; these changes were partly alleviated by all three treatments, with IVIG having the better effect than PNGase F IVIG. We observed an association between B cell FcγRIIB expression and treatment efficacy for AR after kidney transplantation in rats.


Lymphocyte chromosome studies in humans exposed to chemical mutagens. The validity of the method in 67 patients under cytostatic therapy.
Eighty-three lymphocyte cultures from 67 patients exposed to high therapeutic doses of chemical mutagens and from 10 healthy controls were examined for structural aberrations of the chromatid type (gaps, breaks and exchanges) and chromosome type (rings, dicentrics, acentric fragments and abnormal chromosomes) in order to evaluate the reliability of this testing system. Most of the patients had received several drugs; a few had radiotherapy as well. Owing to insufficient yields of mitoses at shorter incubation periods a culture time of 72 h had to be chosen. Whenever possible, 100 mitoses were analyzed. Because evaluation is highly subjective, gaps (i.e. interruptions of the chromatid structure not clearly exceeding a chromatid's width) were not included in the results. The incidence of chromatid breaks was 0--2% in the controls and 0--4% in most of the patients. In 6 cases containing 5--15% mitoses with chromatid breaks and exchanges, these values did not correlate with increased incidences of chromosome type aberrations. The incidence of chromosome type aberrations was 0--1% in the controls as well as in 19/20 patients who had received anti-metabolites and spindle poisons only and in 22/53 patients who had received therapeutic irradiation and/or well-known clastogenic agents. From these findings it is concluded that an increased incidence of chromatid breaks and exchanges is not a typical finding in lymphocyte cultures of persons exposed in vivo to chromosome breaking agents, and that a normal incidence of chromosome type aberrations does not exclude exposure to massive doses of clastogens. This testing system is therefore judged to be inadequate for monitoring weak or questionable mutagens in exposed populations.


Poly[bis-(acetonitrile-κN)bis-[μ(3)-bis(tri-fluoro-methane-sulfonyl)-imido-κO,O':O'':O''']dilithium].
In the title compound, [Li(2)(CF(3)SO(2)NSO(2)CF(3))(2)(CH(3)CN)(2)](n), two Li(+) cations reside on crystallographic inversion centers, each coordinated by six O atoms from bis(trifluoromethanesulfonyl)imide (TFSI(-)) anions. The third Li(+) cation on a general position is four-coordinated by two anion O atoms and two N atoms from acetonitrile mol-ecules in a tetra-hedral geometry.


Antibody-Drug Conjugates for Cancer Therapy.
Antibody-drug conjugates (ADCs) take advantage of the specificity of a monoclonal antibody to deliver a linked cytotoxic agent directly into a tumour cell. The development of these compounds provides exciting opportunities for improvements in patient care. Here, we review the key issues impacting on the clinical success of ADCs in cancer therapy. Like many other developing therapeutic classes, there remain challenges in the design and optimisation of these compounds. As the clinical applications for ADCs continue to expand, key strategies to improve patient outcomes include better patient selection for treatment and the identification of mechanisms of therapy resistance.


Investigating the validity of the environmental framework underlying the original and modified Dynamic Gait Index.
The modified Dynamic Gait Index (mDGI), developed from a person-environment model of mobility disability, measures mobility function relative to specific environmental demands. The framework for interpreting mDGI scores relative to specific environmental dimensions has not been investigated. The aim of this study was to examine the person-environmental model underlying the development and interpretation of mDGI scores. This was a cross-sectional, descriptive study. There were 794 participants in the study, including 140 controls. Out of the total study population, 239 had sustained a stroke, 140 had vestibular dysfunction, 100 had sustained a traumatic brain injury, 91 had gait abnormality, and 84 had Parkinson disease. Exploratory factor analysis was used to investigate whether mDGI scores supported the 4 environmental dimensions. Factor analysis showed that, with some exceptions, tasks loaded on 4 underlying factors, partially supporting the underlying environmental model. Limitations of this study included the uneven sample sizes in the 6 groups. Support for the environmental framework underlying the mDGI extends its usefulness as a clinical measure of functional mobility by providing a rationale for interpretation of scores that can be used to direct treatment and infer change in mobility function.


Traumatic lung and paramediastinal pneumatoceles.
Traumatic pulmonary and paramediastinal pneumatoceles are definite, acutely formed, primary structural manifestations incident to nonpenetrating chest trauma. They are not secondary lesions, i.e., cavities or pneumatoceles resulting from the resolution of a pulmonary hematoma. Awareness of this fact will explain the not uncommon finding of a cavitary lesion, often containing an air-fluid level, on initial emergency room radiographs of patients who have sustained closed chest trauma. This will avoid unnecessary and unpleasant diagnostic procedures, including thoracotomy, for traumatic pneumatoceles are self-limiting, benign abnormalities which usually require no therapy other than observation.


Class III antiarrhythmic drug action in experimental atrial fibrillation. Differences in reverse use dependence and effectiveness between d-sotalol and the new antiarrhythmic drug ambasilide.
Drug therapy to maintain sinus rhythm in patients with atrial fibrillation (AF) is limited by adverse effects and inadequate efficacy. There has been an increased interest in the use of class III drugs to treat AF, and several new agents have been developed, but there is little information available about mechanisms of class III drug action in AF. The present study was designed to compare the effects of two class III agents, d-sotalol and ambasilide, in dog models of experimental AF. A previously developed dog model of sustained vagotonic AF was used to assess the ability of equal loading doses of d-sotalol and ambasilide (2 mg/kg, followed by maintenance infusions), to terminate AF and prevent its induction. At this dose, ambasilide terminated AF in 12 of 12 dogs and prevented AF induction in 10 of 12 dogs; d-sotalol terminated AF in 1 of 8 dogs (P = .001 versus ambasilide) and prevented AF induction in none of 8 dogs (P = .002). An additional dose of d-sotalol (cumulative load, 8 mg/kg) terminated AF in 7 of 8 dogs and prevented induction in 5 of 8 dogs. In an additional 6 dogs with sterile pericarditis and inducible AF, ambasilide prevented AF induction in all 6. An equal dose of d-sotalol (2 mg/kg) failed to suppress AF induction in any dog, but 8 mg/kg of d-sotalol suppressed AF induction in all. Atrial effective refractory period (AERP) was increased by both drugs. However, the effects of d-sotalol on AERP showed strong reverse use dependence, whereas those of ambasilide did not. Neither ambasilide nor d-sotalol significantly altered conduction velocity, and both increased ventricular refractoriness, with d-sotalol once again showing more reverse use dependence. Effective doses of both agents increased AERP and the wavelength for atrial reentry at rapid rates, slowing atrial activation and terminating the arrhythmia. The class III drugs d-sotalol and ambasilide terminate AF by increasing AERP and the wavelength for reentry. Ambasilide, which has been reported to block both the rapid and slow components of the delayed rectifier (IKr and IKs), shows less reverse use dependence of effects on refractoriness than the pure IKr blocker d-sotalol, possibly explaining the greater effectiveness of ambasilide at an equal dose level. These results indicate that class III drugs can exhibit different profiles of rate-dependent action on AERP and suggest that it may be possible to develop agents that have more desirable rate-dependent profiles than pure blockers of Ikr.


Clonidine in the central nervous system: site and mechanism of hypotensive action.
The data presented in this paper must be considered in conjunction with the fact that clonidine is both a partial alpha-adrenergic agonist and a partial alpha-adrenergic antagonist. In the anterior hypothalamus, clonidine, acting as an alpha-agonist, excites a pathway that inhibits excitatory cardiovascular neurons. Thus, the effect of neurons from the nucleus tractus solitarii (NTS) in inhibiting sympathetic outflow from the vasomotor center is effectively increased. In the posterior hypothalmus, clonidine, acting as an alpha-antagonist, decreases excitation of excitatory cardiovascular neurons, or acting as an alpha-presynaptic agonist to decrease norepinephrine release, decreases excitation of excitatory cardiovascular neurons. Again the effect of neurons from the NTS in inhibiting sympathetic outflow from the vasomotor center is effectively increased. In the medulla, clonidine, acting as an alpha-antagonist, inhibits excitatory input to the sympathetic nervous system and thereby appears to enhance the excitatory vagal cardiac reflex and the inhibitory baroreceptor reflex. All of these actions produce the same final response: diminished sympathetic outflow from the CNS, which translates clinically into decreased arterial blood pressure. In addition, these sites and mechanisms of action provide a rational basis for the lack of orthostatic hypotension seen following clonidine and offer a possible mechanism of the post-treatment syndrome.


Evaluation of Medetomidine-Ketamine for Immobilization of Feral Horses in Romania.
Feral horses are immobilized for a variety of reasons including population control via contraceptives. Although opioid combinations have been successfully used for immobilization of feral horses, there is a need for combinations using drugs that are more readily available and present less of a human health hazard. We evaluated the chemical immobilization with physiological measurements and blood gas analyses of 91 free-ranging feral horses (Equus ferus caballus) remotely immobilized with a combination of 30 mg medetomidine and 775 mg ketamine in a single disposable 6 ml dart. During immobilization, heart rate, respiratory rate, rectal temperature, capillary refill time and peripheral oxygen hemoglobin saturation (SpO2) were evaluated. In eight horses, arterial blood samples were analyzed to evaluate the blood gases, acid-base status and hematologic variables. Targeted horses presented a wide range of age, size and body condition. Eighty-one horses had an uneventful mean induction of 7.2 min. Eighty-nine horses were immobilized in lateral recumbency with good muscle relaxation and a median recumbency time of 67 min. Ten horses required supplemental ketamine intravenously (x̄ = 434 mg) due to incomplete immobilization. In 58 horses the effects of medetomidine were antagonized with atipamezole intravenously. Increased respiratory rate (>20 breaths/min), increased heart rate (>45 beats/min) and decreased SpO2 < 90% were noted in more than half of the individuals, while increased rectal temperature (>39.0°C) was recorded in six animals. Blood parameters showed hypoxemia (<90 mmHg, n = 8), hypercapnia (>45 mmHg, n = 5), high glucose levels (>134 mmol/L, n = 3), increased blood lactate (>1.5 mmol/L), total carbon dioxide, bicarbonate and base excess which further increased in the second sample, whereas SpO2 and calcium values decreased. Recoveries were smooth, with one (n = 86) or more (n = 5) attempts of standing. Eighty-nine recoveries were uneventful, besides one male that showed signs of monoparesis of the left front leg and one mare with signs consistent with exertional myopathy. In conclusion, medetomidine-ketamine provided a reliable immobilization in feral horses over a wide range of body mass and age. However, based on the observed hypoxemia during immobilization, oxygen supplementation is strongly recommended for this protocol.


Selective depletion of nonspecific T cells during the early stage of immune responses to infection.
Transient T cell depletion occurs before the development of an effective immune response to infection. In this study we show that most T cells, regardless of specificity, are induced to express early activation markers soon after infection with Listeria monocytogenes or lymphocytic choriomeningitis virus. Ag-specific T cells are further activated to display late activation markers and undergo extensive proliferation. As Ag-specific T cells begin to expand, nonspecific T cells are depleted en masse and exhibit no sign of further activation or proliferation before their depletion. This selective depletion of nonspecific T cells is due to in situ death via apoptosis, as visualized by confocal microscopy. Thus, early activation and subsequent depletion of nonspecific T cells are integral parts of the immune response to proinflammatory infections. These results have important implications for our understanding of early events in the development of a robust T cell response.


Hyperbolic crystallography of two-periodic surfaces and associated structures.
This paper describes the families of the simplest, two-periodic constant mean curvature surfaces, the genus-two HCB and SQL surfaces, and their isometries. All the discrete groups that contain the translations of the genus-two surfaces embedded in Euclidean three-space modulo the translation lattice are derived and enumerated. Using this information, the subgroup lattice graphs are constructed, which contain all of the group-subgroup relations of the aforementioned quotient groups. The resulting groups represent the two-dimensional representations of subperiodic layer groups with square and hexagonal supergroups, allowing exhaustive enumeration of tilings and associated patterns on these surfaces. Two examples are given: a two-periodic [3,7]-tiling with hyperbolic orbifold symbol {\sf {2223}} and a {\sf {22222}} surface decoration.


Evaluation of the gamma-H2AX assay for radiation biodosimetry in a swine model.
There is a paucity of large animal models to study both the extent and the health risk of ionizing radiation exposure in humans. One promising candidate for such a model is the minipig. Here, we evaluate the minipig for its potential in γ-H2AX-based biodosimetry after exposure to ionizing radiation using both Cs137 and Co60 sources. γ-H2AX foci were enumerated in blood lymphocytes and normal fibroblasts of human and porcine origin after ex vivo γ-ray irradiation. DNA double-strand break repair kinetics in minipig blood lymphocytes and fibroblasts, based on the γ-H2AX assay, were similar to those observed in their human counterparts. To substantiate the similarity observed between the human and minipig we show that minipig fibroblast radiosensitivity was similar to that observed with human fibroblasts. Finally, a strong γ-H2AX induction was observed in blood lymphocytes following minipig total body irradiation. Significant responses were detected 3 days after 1.8 Gy and 1 week after 3.8 and 5 Gy with residual γ-H2AX foci proportional to the initial radiation doses. These findings show that the Gottingen minipig provides a useful in vivo model for validation of γ-H2AX biodosimetry for dose assessment in humans.


The fetal sheep: a unique model system for assessing the full differentiative potential of human stem cells.
The naturally occurring stem cell migratory patterns, the availability of expanding homing and engraftment sites, and the presence of tissue/organ-specific signals in the developing mammalian fetus provide the ideal setting for stem cells to exhibit their full biological potential. These characteristics combined with the relative immunological naivete of the early gestational age fetus that permits the engraftment and long-term persistence of allogeneic and xenogeneic donor stem cells make it possible to use the developing fetus to assess the in vivo potential of a variety of stem cells. We have taken advantage of these permissive characteristics of the fetus to develop a large animal model of human hematopoiesis in sheep that permits not only the long-term engraftment of human hematopoietic stem cell/progenitor cells and their differentiation into the full range of lymphohematopoietic elements, but also the relatively robust expression of their potential to contribute to the formation of non-hematopoietic tissues.


QSAR study and rustic ligand-based virtual screening in a search for aminooxadiazole derivatives as PIM1 inhibitors.
Quantitative structure-activity relationship (QSAR) was carried out to study a series of aminooxadiazoles as PIM1 inhibitors having pki ranging from 5.59 to 9.62 (k i in nM). The present study was performed using Genetic Algorithm method of variable selection (GFA), multiple linear regression analysis (MLR) and non-linear multiple regression analysis (MNLR) to build unambiguous QSAR models of 34 substituted aminooxadiazoles toward PIM1 inhibitory activity based on topological descriptors. Results showed that the MLR and MNLR predict activity in a satisfactory manner. We concluded that both models provide a high agreement between the predicted and observed values of PIM1 inhibitory activity. Also, they exhibit good stability towards data variations for the validation methods. Furthermore, based on the similarity principle we performed a database screening to identify putative PIM1 candidates inhibitors, and predict their inhibitory activities using the proposed MLR model. This approach can be easily handled by chemists, to distinguish, which ones among the future designed aminooxadiazoles structures could be lead-like and those that couldn't be, thus, they can be eliminated in the early stages of drug discovery process.


Primary Adult Renal Ewing's Sarcoma: A Rare Entity.
Ewing's sarcoma/primitive neuroectodermal tumors are high-grade small round blue cell tumors traditionally found in children and adolescents.These tumors primarily affect the bone and soft tissue, with extraskeletal sites rarely being affected. The clinical presentation and imaging findings are non-specific and are not characteristic. The diagnosis is essentially based on the histopathologic findings assisted by immunohistochemistry and/or cytogenetic molecular studies. Proper diagnoses and timely management of this tumor are essential owing to the aggressive nature and poor prognosis of the disease.


Effects of black cohosh and estrogen on the hypothalamic nuclei of ovariectomized rats at different temperatures.
Cimicifuga racemosa (L.) Nutt. (CR), known as black cohosh, has been used in Europe as a medicinal plant for more than a century and its roots have been widely used for the treatment of menopausal symptoms. Remifemin, the main ingredient in liquid or tablet medications prepared from isopropyl alcohol extracts of black cohosh rhizome, has also been evaluated in clinical studies. To observe changes in the expression of the c-Fos protein in the hypothalamic nuclei of four groups of rats-sham-operated group (SHAM), ovariectomized (OVX) group, ovariectomized group treated with estrogen(OVX+E), and ovariectomized group treated with the isopropanol extract of Cimicifuga racemosa (OVX+ICR)-and to investigate the mechanisms of black cohosh and estrogen that take place in the hypothalamic nuclei of ovariectomized rats. Fifty rats were assigned to each of the four groups and placed in incubators at 4 °C, 10 °C, 25 °C, 33 °C, or 38 °C for 2 h. They were then anesthetized, and their brains were removed after heart perfusion. c-Fos expression in the hypothalamic nuclei was evaluated using immunohistochemical methods. In the median preoptic nucleus (MnPO), ventromedial preoptic nucleus (VMPO), and suprachiasmatic nucleus (SCh) of the SHAM group, in the anterior hypothalamic area (AH) and supraoptic nucleus (SO) of all four groups, and in the paraventricular nucleus (PVN) of the SHAM, OVX and OVX+E groups, the c-Fos-positive cell densities all changed in a similar manner: the cell density decreased when the temperature was less than 25 °C and the density increased when the temperature was greater than 25 °C, demonstrating a V-type curve. The c-Fos density was lowest at 25°C. The other nuclei demonstrated irregular changes. The positive cell densities in the MnPO, AH, and PVN of the SHAM, OVX+E, and OVX+ICR groups were greater than the densities measured in the OVX group at all temperatures, except 25 °C. Positive cell densities in the SHAM, OVX+E, and OVX+ICR groups were greater than the densities measured in the OVX groups in the MPA at 25 °C, in the VMPO at 4 °C, 33 °C, and 38 °C, in the SO at 4 °C, 10 °C, and 38 °C, and in the SCh at 33 °C. Regardless of the temperature, positive cell densities were lower in the MnPO, MPA, VMPO, AH, SCh, SO, and PVN of the OVX groups in comparison with the densities measured in the same sites in the SHAM group. Following the administration of black cohosh and estrogen, the positive cell densities in the OVX groups increased and became closer to, or exceeded, those measured in the SHAM group, suggesting that both drugs may act on the hypothalamic nuclei and have therapeutic effects on menopausal symptoms.


RNA N6-methyladenosine reader IGF2BP3 promotes acute myeloid leukemia progression by controlling stabilization of EPOR mRNA.
N6-methyladenosine (m6A) methylation epigenetically regulates normal hematopoiesis and plays a role in the pathogenesis of acute myeloid leukemia (AML). However, its potential value for prognosis remains elusive. Analysis of the datasets downloaded from The Cancer Genome Atlas and Genotype Tissue Expression databases revealed that the expression level of 20 regulators related to m6A RNA methylation differ between patients with AML and normal individuals. A prognostic risk model with three genes (YTHDF3, IGF2BP3, and HNRNPA2B1) was developed using univariate Cox regression and the least absolute shrinkage and selection operator Cox regression methods. This established signature demonstrated good predictive efficacy with an area under the curve of 0.892 and 0.731 in the training cohort and the validation cohort, respectively. Patients with AML and an increased level of Insulin growth factor 2 mRNA binding protein 3 (IGF2BP3) expression exhibited a poor prognosis. IGF2BP3 knockdown significantly induced G0/G1 phase arrest and inhibited cell proliferation, apoptosis, and/or differentiation. Further, the JAK/STAT pathway may be involved in the regulation of EPOR expression by IGF2BP3-mediated m6A RNA methylation. These findings indicate that IGF2BP3 plays a carcinogenic role in AML, implying that it can predict patient survival and could be an effective strategy for AML therapy.


Tension pneumocephalus after CSF shunting procedures.
We report a case of tension pneumocephalus following the insertion of a ventriculoperitoneal shunt for hydrocephalus secondary to aqueduct stenosis and discuss the possible genesis of the complication, diagnosis and treatment.


The PERK-EIF2α-ATF4 signaling branch regulates osteoblast differentiation and proliferation by PTH.
Parathyroid hormone (PTH) and its related peptide (PTH-related peptide 1-34) are two of the Food and Drug Administration-approved bone-promoting drugs for age-related osteoporosis. Treatment with PTH stimulates bone formation. However, the molecular mechanisms of PTH-mediated osteoblast differentiation and cell proliferation are still not completely understood. In this study, we showed that PTH induced endoplasmic reticulum (ER) stress in osteoblasts through the PKR-like endoplasmic reticulum kinase (PERK)-eukaryotic initiation factor 2α (EIF2α)-activating transcription factor 4 (ATF4)-signaling pathway. After separately blocking PERK-EIF2α-ATF4 signaling with two different inhibitors [AMG'44 and integrated stress response inhibitor (ISRIB)] or specific small interfering RNA for PERK and ATF4, the following targets were all downregulated: expression of osteoblast differentiation markers [runt-related transcription factor 2 (Runx2), alkaline phosphatase (Alp), type I collagen (Col1a1), and osteocalcin (Ocn)], cell proliferation markers (CyclinE, CyclinD, and CDC2), amino acid import (Glyt1), and metabolism-related genes (Asns). Additionally, Alp-positive staining cells, Alp activity, matrix mineralization, Ocn secretion, and cell proliferation indexes were inhibited. Interestingly, we found that salubrinal enhanced PTH-induced osteoblast differentiation and proliferation by maintenance of phosphorylation of EIF2α. Furthermore, we observed that PTH increased the association between heat shock protein 90 (HSP90) and PERK and maintained PERK protein stabilization in the early stages of PTH-induced ER stress. Treatment of MC3T3-E1 cells with geldanamycin, an HSP90 inhibitor, decreased PERK protein expression and inhibited osteoblast differentiation and cell proliferation upon PTH treatment. Taken together, our data demonstrate that PTH regulates osteoblast differentiation and cell proliferation, partly by activating the HSP90-dependent PERK-EIF2α-ATF4 signaling pathway.


Investigations into the haemorheological significance of postprandial and fasting hypertriglyceridaemia.
Two study designs were conceived to evaluate the rheological significance of hypertriglyceridaemia. We first investigated the course of serum- (SV) and plasma viscosity (PV) and erythrocyte aggregation in serum (SEA) and plasma (PEA) of healthy normolipidaemic individuals over 4 h after a fatty rich meal, in native material and after removal of triglyceride rich lipoproteins by centrifugation. Secondly, blood from patients with untreated hypertriglyceridaemia was investigated under fasting conditions. PEA and SEA increased in parallel with postprandial triglycerides (+135 mg dl-1), but the effect on PEA was more pronounced (+0.8 abs% increase; 2 h after the meal) as compared to SEA (+0.4 abs% increase). PV and SV increased in parallel to the same extent (+0.05 mPas). In the triglyceride poor infranatant no significant changes occurred. In fasting plasma PEA and PV were significantly lower (1.1 abs% and PV 0.04 mPas respectively) in infranatant than in native plasma, while only small differences in triglyceride (mostly VLDL) were observed. This phenomenon was barely detectable in serum samples. We conclude that triglyceride rich lipoproteins have a profound influence on haemorheological parameters, and that fibrinogen in particular, potentiates the effect of large fasting VLDL on plasma viscosity and erythrocyte aggregation.


Preventive Treatment with Astaxanthin Microencapsulated with Spirulina Powder, Administered in a Dose Range Equivalent to Human Consumption, Prevents LPS-Induced Cognitive Impairment in Rats.
Cognitive alterations are a common feature associated with many neurodegenerative diseases and are considered a major health concern worldwide. Cognitive alterations are triggered by microglia activation and oxidative/inflammatory processes in specific areas of the central nervous system. Consumption of bioactive compounds with antioxidative and anti-inflammatory effects, such as astaxanthin and spirulina, can help in preventing the development of these pathologies. In this study, we have investigated the potential beneficial neuroprotective effects of a low dose of astaxanthin (ASX) microencapsulated within spirulina (ASXSP) in female rats to prevent the cognitive deficits associated with the administration of LPS. Alterations in memory processing were evaluated in the Y-Maze and Morris Water Maze (MWM) paradigms. Changes in microglia activation and in gut microbiota content were also investigated. Our results demonstrate that LPS modified long-term memory in the MWM and increased microglia activation in the hippocampus and prefrontal cortex. Preventive treatment with ASXSP ameliorated LPS-cognitive alterations and microglia activation in both brain regions. Moreover, ASXSP was able to partially revert LPS-induced gut dysbiosis. Our results demonstrate the neuroprotective benefits of ASX when microencapsulated with spirulina acting through different mechanisms, including antioxidant, anti-inflammatory and, probably, prebiotic actions.


Terms of the specialized nursing language for the care of ostomates.
to identify terms of the specialized nursing language for the care of ostomates from the literature of the area, and to map the identified terms with terms of the International Classification for Nursing Practice (ICNP®). descriptive study of quantitative approach guided by the guidelines for the elaboration of terminology subsets of the ICNP®. The terms were collected in 49 scientific articles, extracted using a computational tool, selected according to the relevance for the theme, and normalized and mapped with the ICNP®. 20,668 terms were extracted. The standardization process resulted in 425 relevant terms (151 were constant in ICNP® and 274 were not contained in ICNP®), of which 154 were similar, 19 were more comprehensive, 50 were more restricted, and 51 were not in concordance. the use of standardized language can minimize the ambiguities and redundancies identified in the mapping. The existence of terms not in concordance with the ICNP® reinforces the need for constant updating of this classification.


Structural analysis of the human inter-alpha-trypsin inhibitor light-chain gene.
The human inter-alpha-trypsin inhibitor (ITI) light-chain gene, which codes for the two proteins alpha 1-microglobulin (protein HC) and ITI-derived human inhibitor of 30 kDa (HI-30), was isolated from a human genomic library. This gene, present as a single copy in the human genome, is composed of 10 exons and 9 introns distributed over 20 kbp. A single transcriptional initiation site was identified in the 5'-flanking region which contained promoter elements, but no typical TATA box. However a sequence equivalent to the TATA box is present on both sense and anti-sense strands in the 5'-flanking region of the first exon coding for HI-30. The exon-intron organization suggests that the regions coding for protein HC and other members of the lipocalin superfamily evolved from a common ancestral gene that is probably different from that coding for HI-30. These data suggest that two distinct ancestral genes could have existed and fused during evolution. Several direct and one inverted repeats are also found within this gene, as well as potential glucocorticoid-receptor binding sites.


Differences in smoking cessation strategies between men and women.
This descriptive research was designed to identify differences in smoking cessation strategies between men and women in a cross-sectional population sample of current smokers in the upper Midwest. Data on the number of previous quit attempts, the success and persistence in quit attempts, future intentions to change smoking habits, and strategies planned for cessation were obtained from 1669 smokers. Log-linear analyses controlling for age and the number of cigarettes smoked revealed significant gender differences. Men and women appear to approach smoking cessation differently. Women were more tentative and less committed to quitting smoking entirely. Women were also less successful in sustaining smoking cessation attempts for longer than one week. Efficacy expectations and differential attributions for failure were suggested as possible explanations for the results, however further research will be necessary to confirm or disconfirm these hypotheses.


Thermal biology of the deep-sea vent annelid Paralvinella grasslei: in vivo studies.
The annelid Paralvinella grasslei is a deep-sea vent endemic species that colonizes the wall of active chimneys. We report here the first data on its thermal biology based on in vivo experiments in pressurized aquaria. Our results demonstrate that P. grasslei survives a 30 min exposure at 30 degrees C, and suggest that the upper thermal limit of this species is slightly above this temperature. The first signs of stress were noticed at 30 degrees C, such as a significant increase in the animal's activity and the expression of HSP70 stress proteins. A preliminary investigation of the kinetics of stress protein expression surprisingly showed high levels of HSP70 proteins as late as 3.5 h after the heat shock. Finally, we provide here the first sequences for vent annelid hsp70 (P. grasslei, Hesiolyra bergi and Alvinella pompejana). These constitute valuable tools for future studies on the thermal biology of these annelids.


HIPAA...one size does not necessarily fit all.
HIPPA is an important piece of legislation that will affect agency operations, clinical practice, regulatory compliance, and patient care. This article gives you the foundation needed to understand how HIPPA will affect you!


Hepatitis C virus related cryoglobulinemic glomerulonephritis.
A 46 years male presented with skin rash and acute nephritic syndrome. He had history of jaundice four months back. Rheumatoid factor and cryoglobulins were present in the serum. Although anti-HCV antibodies were negative, HCV RNA was detected by polymerase chain reaction. Kidney biopsy showed membranoproliferative glomerulonephritis and thrombi in the lumen of the glomerular capillary loops. His renal functions improved with steroids.


Dynamics and Functional Interplay of Nonhistone Lysine Crotonylome and Ubiquitylome in Vascular Smooth Muscle Cell Phenotypic Remodeling.
The crotonylation of histones is discovered of late as one of the post-translational modifications (PTMs) that can regulate gene expression. However, the function of crotonylation on nonhistone proteins in vascular smooth muscle cells (VSMCs) is unclear. Here, we aim to find the cellular characteristics of crotonylated nonhistone proteins and the cross talk with ubiquitinated proteins in VSMC phenotypic remodeling using the modified omics and proteomic analysis. We performed the modified omics and proteomic analysis of VSMCs before and after the stimulation with platelet-derived growth factor-BB (PDGF-BB). The crotonylated and ubiquitinated pan-antibody was used to enrich proteins and then subjected to a high-throughput mass spectrometry analysis. The enrichment analysis was performed within differentially modified proteins in regard to GO terms, KEGG, and protein domains. As a result, there were 2,138 crotonylation sites in 534 proteins and 1,359 ubiquitination sites corresponding to 657 proteins. These crotonylated proteins detected after PDGF-BB stimulation might be involved in various vital cellular pathways and carry out important functions in VSMCs. Some of them closely took part in significant physiological processes of VSMC phenotypic remodeling, including glycolysis/gluconeogenesis, vascular smooth muscle contraction, and the PI3K-Akt signaling pathway. Furthermore, the KEGG pathway enrichment analysis showed the involvement of ubiquitinated proteins in the physiological processes of VSMC phenotypic remodeling, including glycolysis/gluconeogenesis, vascular smooth muscle contraction, RAS signaling pathway, or the PI3K-Akt signaling pathway. A cross talk analysis showed that there were 199 sites within the 177 proteins modified by crotonylation and ubiquitination simultaneously. Protein-protein interaction (PPI) network analysis indicated that crotonylated and ubiquitinated proteins play an important role in cellular bioprocess commonly and possibly have a synergistic effect. In summary, our bioinformatics analysis shows that the crotonylation and ubiquitination of nonhistone proteins play an essential role in VSMC phenotypic transformation induced by PDGF-BB stimulation. The cross talk between crotonylation and ubiquitination in glycolysis is possibly a novel mechanism during VSMC phenotypic remodeling.


Evaluation of platelet surface antigens: localization of the PlA1 alloantigen.
An approach is described for localizing antigenic determinants to specific platelet proteins. Platelets are solubilized, electrophoresed and transferred to nitrocellulose paper where they are immobilized. After incubation with radiolabelled specific antibody, the antigenic determinants are localized by radioautography. Purified proteins ranging in size from 50000 to 540000 could be studied in this manner and still retain their antigenicity. Solubilized immobilized platelet proteins were reacted with serum IgG from two patients with post-transfusion purpura known to have anti-PlA1 antibodies. The radioactivity was associated with a major protein band with an apparent molecular weight of 100000 daltons. However, when purified anti-PlA1 antibody eluted from PlA1 (+) platelets was used, at least six additional minor bands were noted with molecular weights ranging from about 86000 to 175000. No radioactive bands were noted using PlA1 negative platelets or reduced PlA1 (+) platelet proteins. Reaction of the antibody from one patient wih proteins from thrombasthenic platelets resulted in a marked reduction in the intensity of all radioactive bands. In addition, a new high molecular weight band was noted which was not present in reactions containing PlA1 (+) platelets. These data suggest that the PlA1 antigen is primarily but not entirely localized to glycoprotein IIIa. This approach is relatively simple, requires only minimal amounts of antibody and should be generally useful in the study of cellular antigens and other complex mixtures of proteins.


Effective Content-Aware Chroma Reconstruction Method for Screen Content Images.
In this paper, we propose an effective novel content-aware chroma reconstruction (CACR) method for screen content images (SCIs). After receiving the decoded downsampled YUV image on the client side, our fast chroma-copy approach reconstructs the missing chroma pixels in the flat regions of SCI. Then, for non-flat regions, a non-flat region-based winner-first voting (NRWV) strategy is proposed to identify the chroma subsampling scheme used on the server side prior to compression. Further, an effective adaptive hybrid approach is proposed to reconstruct each missing chroma pixel in the non-flat region by fusing the two reconstructed results, one from our modified NRWV-based chroma subsampling-binding and luma-guided chroma reconstruction scheme, which favors the sharp edges in SCI, as well as the other from the bicubic interpolation scheme, which favors blurred and continuous-tone textures. Further, based on the identified chroma subsampling scheme, a geometry alignment-based error compensation approach is proposed to enhance the reconstructed chroma image. Based on typical test SCIs and JCT-VC screen content videos, comprehensive experiments are carried out in HEVC-16.17 to demonstrate that in terms of quality, visual effect, and quality-bitrate tradeoff of the reconstructed SCIs, our CACR method significantly outperforms the existing state-of-the-art methods.


Lithium: contributor to movement disorder sensitivity after anoxic brain injury?
Although lithium-induced dystonia has been well documented in the literature, conflicting evidence discusses whether a patient may be susceptible to adverse effects from the drug after an anoxic brain injury. More recent literature discusses that lithium may, in fact, be neuroprotective. This case report presents a 35-year-old male who, after an anoxic brain injury after a suicide attempt, developed lithium-induced dystonia with characteristic symptoms of sustained muscle contractions, repetitive movements, and postures, which was not markedly improved with benztropine or benzodiazepines. It is postulated that because this patient received a depot neuroleptic with a subsequent anoxic brain injury, he may have become more sensitive to lithium and its rare complications.


[Maternal risks for newborn macrosomia, incidence of a shoulder dystocia and of damages of the plexus brachialis].
PATIENTS RESPECTIVELY AND METHODS: In the HEPE 619 242 births have been analysed (1990 - 2000) to calculate the incidence of a birthweight between 4000 and 4499 g and of a weight > or = 4500 g in relationship to maternal obesity, high maternal weight gain and of a duration of pregnancy more than 298 days. The risk of a macrosomia > or = 4500 g is in cases of obesity 3.4 times higher, in cases of obesity and prolongation of pregnancy 6.6 times higher and in the presence of all 3 risk factors 10 times higher. Data of the Frauenklinik Wiesbaden (HSK) (n = 6075 births) complete the results, because a correlation between macrosomia, shoulder dystocia and a damage to the plexus brachialis has been found. The incidence of a damage to the plexus brachialis is in case of a shoulder dystocia and a birth weight of < or = 4000 g 6.3%, at a birth weight between 4000-4499 g 25% and in newborns with a weight > or = 4500 g 40%. Because of the low sensitivity (60%) of the ultrasonic weight measurement the 3 maternal risk factors--if they exist--of a shoulder dystocia and of a damage of the plexus brachialis should be discussed with the pregnant woman to help her about the decision of an alternative cesarean section. Still one third of the newborns weigh more than 4000 g if all 3 maternal risk factors exist.


Altered interplay between endoplasmic reticulum and mitochondria in Charcot-Marie-Tooth type 2A neuropathy.
Mutations in the MFN2 gene encoding Mitofusin 2 lead to the development of Charcot-Marie-Tooth type 2A (CMT2A), a dominant axonal form of peripheral neuropathy. Mitofusin 2 is localized at both the outer membrane of mitochondria and the endoplasmic reticulum and is particularly enriched at specialized contact regions known as mitochondria-associated membranes (MAM). We observed that expression of MFN2R94Q induces distal axonal degeneration in the absence of overt neuronal death. The presence of mutant protein leads to reduction in endoplasmic reticulum and mitochondria contacts in CMT2A patient-derived fibroblasts, in primary neurons and in vivo, in motoneurons of a mouse model of CMT2A. These changes are concomitant with endoplasmic reticulum stress, calcium handling defects, and changes in the geometry and axonal transport of mitochondria. Importantly, pharmacological treatments reinforcing endoplasmic reticulum-mitochondria cross-talk, or reducing endoplasmic reticulum stress, restore the mitochondria morphology and prevent axonal degeneration. These results highlight defects in MAM as a cellular mechanism contributing to CMT2A pathology mediated by mutated MFN2.


[Tissue repositories for research at Sheba Medical Center(SMC].
Cancer is the number one cause of death in both genders. Breakthroughs in the understanding of cancer biology, the identification of prognostic factors, and the development of new treatments are increasingly dependent on access to human cancer tissues with linked clinicopathological data. Access to human tumor samples and a large investment in translational research are needed to advance this research. The SMC tissue repositories provide researchers with biological materials, which are essential tools for cancer research. SMC tissue repositories for research aim to collect, document and preserve human biospecimens from patients with cancerous diseases. This is in order to provide the highest quality and well annotated biological biospecimens, used as essential tools to achieve the growing demands of scientific research needs. Such repositories are partners in acceLerating biomedical research and medical product development through clinical resources, in order to apply best options to the patients. Following Institutional Review Board approval and signing an Informed Consent Form, the tumor and tumor-free specimens are coLLected by a designated pathologist at the operating room only when there is a sufficient amount of the tumor, in excess of the routine needs. Blood samples are collected prior to the procedure. Other types of specimens collected include ascites fluid, pleural effusion, tissues for Optimal Cutting Temperature [OCT] and primary culture etc. Demographic, clinical, pathologicaL, and follow-up data are collected in a designated database. SMC has already established several organ or disease-specific tissue repositories within different departments. The foundation of tissue repositories requires the concentrated effort of a multidisciplinary team composed of paramedical, medical and scientific professionals. Research projects using these specimens facilitate the development of 'targeted therapy', accelerate basic research aimed at clarifying molecular mechanisms involved in cancer, and support the development of novel diagnostic tools.


Altered diaphragm contractile properties with controlled mechanical ventilation.
This study shows that, over time, diaphragm inactivity with controlled mechanical ventilation (CMV) decreases diaphragm force and produces myofibril damage contributing to the reduced force. We measured in vivo and in vitro diaphragm contractile and morphological properties in 30 sedated rabbits grouped (n = 6) as follows: 1 or 3 days of CMV, 1 or 3 days of 0 cmH(2)O continuous positive airway pressure, and control. The CMV rate was set sufficient to suppress diaphragm electrical activity. Compared with the control group, phrenic-stimulated maximum transdiaphragmatic pressure did not decrease with continuous positive airway pressure but decreased to 63% after 1 day of CMV and to 49% after 3 days of CMV. The in vitro tetanic force decreased to 86% after 1 day of CMV and to 44% after 3 days of CMV. After 3 days of CMV, significant myofibril damage occurred in the diaphragm but not in the soleus. The decrease in tetanic force correlated with the volume density of abnormal myofibrils. We conclude that CMV had a detrimental effect on diaphragm contractile properties.


Socioeconomic variation in discretionary and mandatory hospitalization of infants: an ecologic analysis.
To examine geographic variation in rates of infant hospitalization for diagnoses classified by type of hospitalization decision in Monroe County (Rochester), New York. Study design was cross-sectional and ecologic. International Classification of Diseases (ICD) codes were used to categorize all 7883 hospitalizations for infants (age, <24 months) beyond the newborn period between 1985 and 1991. Postal zip codes defined socioeconomic areas as inner-city, other urban, and suburban for the population at risk. In 1990, inner-city infants included 62% black and 65% Medicaid-covered infants, whereas suburban infants included 3% black and 6% covered by Medicaid. Hospitalization rates were compared among the three socioeconomic areas. Overall hospitalization rate was 50.3 per 1000 child years. Admissions classified as discretionary accounted for 59% of these, followed by those classified as mandatory, 18%; sometime (congenital heart disease, cleft palate), 15%; discretionary surgery (inguinal hernia, tonsillectomy/adenoidectomy), 6%; and unlikely to need admission, 2%. A stepwise, socioeconomic gradient in hospitalization was found, with rates of 38.1, 51.3, and 82.9 per 1000 child-years, respectively, for suburban, other urban, and inner-city areas. Rates for discretionary, unlikely, and mandatory admissions followed this gradient. Using the odds for hospitalization of suburban infants as the base odds, the odds ratio for discretionary hospitalization for inner-city infants was 2.88 (95% confidence interval [CI], 2.69 to 3. 08) and that for mandatory hospitalization was 2.20 (95% CI, 1.94 to 2.49). In multiple regression analysis, low education level of mothers explained 81% of the variance in discretionary hospitalization rate. Although the per capita rate of hospital care of inner-city infants was more than twofold greater than that for suburban infants, potential for reducing this difference is suggested by the fact that discretionary admissions accounted for 78. 9% of this difference, whereas mandatory admissions accounted for 17. 7% of the difference. The hospitalization rate for inner-city infants is much greater than that for suburban infants. A substantial portion of the difference, namely that attributable to mandatory admissions, reflected higher rates of serious illness. Differences attributable to discretionary admissions may reflect higher rates of serious illness to some extent, but also appear to reflect less effective health services to a substantial degree.


Acute coronary syndrome in the Asia-Pacific region.
More than 4.2 billion inhabitants populate the Asia-Pacific region. Acute coronary syndrome (ACS) is now a major cause of death and disability in this region with in-hospital mortality typically exceeding 5%. Yet, the region still lacks consensus on the best approach to overcoming its specific challenges in reducing mortality from ACS. The Asia-Pacific Real world evIdenCe on Outcome and Treatment of ACS (APRICOT) project reviewed current published and unpublished registry data, unmet needs in ACS management and possible approaches towards improving ACS-related mortality in the region. There was striking heterogeneity in the use of invasive procedures, pharmacologic practice (hospitalization/post-discharge), and in short- and long-term clinical outcomes across healthcare systems; this heterogeneity was perceived to be far greater than in Western Europe or the United States. 'Benchmark' short-term clinical outcomes are preferred over long-term outcomes due to difficulties in follow-up, recording and maintenance of medication adherence in a geographically large and culturally diverse region. Key 'barriers' towards improving outcomes include patient education (pain awareness, consequences of missing medication and secondary prevention), geographical landscape (urban vs. metropolitan), limited long-term adherence to guideline-based management and widespread adoption of cost-based rather than value-based healthcare systems. Initiatives to overcome these barriers should include implementation of pre-hospital management strategies, toolkits to aid in-hospital treatment, greater community outreach with online patient/physician education and telemedicine, sustainable economic models to improve accessibility to effective pharmacotherapies and the acquisition of high-quality 'real-world' regional data to tailor secondary prevention initiatives that meet the unique needs of countries in this region.


Enzian classification: does it correlate with clinical symptoms and the rASRM score?
To assess the extent to which the Enzian classification correlates with the revised American Society for Reproductive Medicine (rASRM) score and clinical symptoms in women with deeply infiltrating endometriosis. Retrospective cohort study (Canadian Task Force classification II-2). Endometriosis competence center specializing in minimally invasive surgery. Between 1 January 2009 and 31 December 2011, a total of 194 women underwent surgery due to deeply infiltrating endometriosis. After histological confirmation, they were classified using the rASRM and Enzian systems. Clinical symptoms were recorded preoperatively. Operative laparoscopy to treat endometriosis. A clear correlation was seen between grades of severity in the rASRM score and the Enzian classification (p < 0.001). In addition, the rASRM severity grade and clinical symptoms correlated with the locations in the Enzian classification in relation to deeply infiltrating endometriosis. Pain and dysmenorrhea correlated strongly (p = 0.002, p < 0.001) with the severity grade in the Enzian classification. Deeply infiltrating endometriosis is well characterized using the Enzian classification as a supplement to the rASRM score. There is also a clear correlation between the rASRM and Enzian classifications, because of the way in which the disease crosses morphological boundaries. The locations in the Enzian classification correlate partially with clinical symptoms, and the classification's severity grades correlate substantially with pain and dysmenorrhea. In view of these clinical results, use of the Enzian classification can be recommended as a supplement to the rASRM score for detailed description of endometriosis.


Potential Role of VHL, PTEN, and BAP1 Mutations in Renal Tumors.
The genetic profiling of renal tumors has revealed genomic regions commonly affected by structural changes and a general genetic heterogeneity. The VHL, PTEN, and BAP1 genes are often mutated in renal tumors. The frequency and clinical relevance of these mutations in renal tumors are still being researched. In our study, we investigated VHL, PTEN, and BAP1 genes and the sequencing of 24 samples of patients with renal tumors, revealing that VHL was mutated at a noticeable frequency (25%). Six of the investigated samples showed mutations, and one genetic polymorphism (rs779805) was detected in both heterozygote and homozygote forms. PTEN gene mutation was observed in only one sample, and one specimen showed genetic polymorphism. In the case of the BAP1 gene, all of the samples were wild types. Interestingly, VHL mutation was detected in two female patients diagnosed with AML and in one with oncocytoma. We assume that VHL or PTEN mutations may contribute to the development of human renal cancer. However, the overall mutation rate was low in all specimens investigated, and the development and prognosis of the disease were not exclusively associated with these types of genetic alterations.


Enhanced resistance to blast (Magnaporthe grisea) in transgenic Japonica rice by constitutive expression of rice chitinase.
Rice blast is the most devastating plant disease in Japan. Our goal is to create new rice varieties which show enhanced resistance against blast, regardless of the race of blast. By an Agrobacterium-mediated transformation method, we reintroduced a rice class-I chitinase gene, Cht-2 or Cht-3, under the control of the enhanced CaMV 35S promoter and a hygromycin phosphotransferase gene, as a selection marker into the Japonica rice varieties Nipponbare and Koshihikari, which have retained the best popularity over a long period in Japan. In regenerated plants (R(0)), the Cht-2 product was found to accumulate intracellularly whereas the Cht-3 product was found to be targeted extracellularly. The transgenic rice plants which constitutively expressed either chitinase gene showed significantly higher resistance against the rice blast pathogen Magnaporthe grisea races 007.0 and 333. Both high-level expression of the chitinase and blast-resistance were stably inherited by the next generation in several lines.


Butein inhibits NF-κB, AP-1 and Akt activation in adult T-cell leukemia/lymphoma.
Human T-cell leukemia virus type 1 (HTLV-1) is the causative agent of adult T-cell leukemia/lymphoma (ATLL) but there is no effective treatment for HTLV-1-associated diseases. Herein, we determined the effect of butein, a bioactive plant polyphenol, on cell growth, apoptosis and signaling pathways in HTLV-1-infected T-cell lines and on tumor growth in SCID mice. Treatment with butein caused a decrease in viability of HTLV-1-infected T-cell lines. T cells cultured with butein showed obvious apoptosis morphology, and cleavage of poly(ADP-ribose) polymerase with activation of caspase-3, -8 and -9. Pretreatment of cells with caspase inhibitor partially blocked butein-induced inhibition of cell viability. Butein also resulted in cell cycle arrest at G1 phase. Butein markedly downregulated the protein expression levels of CDK4, CDK6, cyclin D1, cyclin D2, cyclin E, survivin, XIAP, c-IAP2 and phospho-pRb. Butein also inhibited i) total and phospho-protein levels of IκB kinase (IKK)α and IKKβ, ii) degradation and phosphorylation of IκBα, iii) JunB and JunD, iv) total and phospho-protein levels of Akt, v) phosphorylation of RelA, vi) heat shock protein 90, and vii) DNA-binding activity of NF-κB and AP-1. In mice harboring ATLL xenograft tumors, butein caused a significant inhibition of tumor growth and reduced serum levels of soluble interleukin-2 receptor α chain and soluble cluster of differentiation 30. Considered together, the results indicated that butein has antiproliferative and proapoptotic properties through the suppression of NF-κB, AP-1 and Akt signaling in HTLV-1-infected T cells, both in vitro and in vivo, suggesting its therapeutic potential against HTLV-1-associated diseases including ATLL.


Cycloaddition Reactions of Azomethine Ylides and 1,3-Dienes on the C2v-Symmetrical Pentakisadduct of C60.
The reactivity of the C2v-symmetric pentakisadduct of C60 with azomethine ylides and conjugated dienes was studied experimentally and computationally. This derivative possesses four [6,6] double bonds, each with unique electrophilicity. The Diels-Alder reaction studied is a regiospecific, kinetically and thermodynamically guided [4 + 2] process producing [5:1]-hexaadducts with an octahedral addition pattern. The kinetically controlled Prato reaction gives a mixture of regioisomeric [5:1]-hexaadducts. The synthesis of geometrically well-defined supramolecular architectures may benefit from these new types of highly functionalized [5:1]-hexaadducts.


Use of small RNA as antiaging cosmeceuticals.
Over the past two decades, RNA interference (RNAi) has achieved great improvements in medicine, which has benefited the development of innovative cosmeceutical products, particular, to antiaging cosmeceuticals. A variety of ongoing research has tried to employ small RNAs-small interference RNA and microRNA as new cosmeceutical ingredients. Furthermore, several skin care companies have released new small RNA products in cosmetic market. In this review, we will describe the latest and most advanced approaches and strategies of using small RNA as antiaging cosmetics, including investigations on aging-related genes that small RNA target, method of delivering them, and challenges in the development of RNAi-based therapeutics for skin care cosmeceuticals. It is certain that advancement in this direction will evolve a new landscape for innovative antiaging cosmeceuticals.


Thymic development in human CD4 transgenic mice. Positive selection occurs after commitment to the CD8 lineage.
Developing T cells are positively selected on the basis of their recognition of polymorphic MHCs (major histocompatibility molecules). The CD4 and CD8 co-receptors, together with a compatible TCR-alpha beta, bind class II and class I MHC, respectively, delivering a signal that allows T cell maturation to proceed along the appropriate co-receptor lineage. During development, thymocytes first co-express CD4 and CD8 and subsequently commit to a single co-receptor phenotype. Debate exists over the stage at which positive selection occurs. Positive selection may precede or accompany co-receptor lineage commitment or occur subsequent to the acquisition of a single co-receptor phenotype. We developed transgenic (TG) mice expressing human CD4 (huCD4) on T cells. To study differentiation of CD8+ cells, huCD4 TG mice were bred with mice lacking class I MHC (class I-). This enabled us to assess maturation of mCD8+mCD4+huCD4+ thymocytes to mCD8+mCD4-huCD4+ cells after interaction between huCD4 and mclass II MHC. In the absence of huCD4, class I- mice failed to produce mCD8+ cells. However, expression of huCD4 allowed development of mCD8+mCD4-huCD4+ T cells, suggesting that selection of cells precommitted to the mCD8+mCD4- lineage occurred. Importantly, CD8+ T cells were increased in both the thymus and the periphery of huCD4 TG x class I- animals, indicating their intrathymic origin. V beta 14+ CD8+ T cells were also increased, as predicted for positive selection of CD8+ cells bearing class II-reactive TCRs. These data provide evidence that positive selection occurs at a late stage of thymocyte differentiation, after commitment to the CD8 lineage.


The INO80 chromatin remodeling complex promotes thermomorphogenesis by connecting H2A.Z eviction and active transcription in Arabidopsis.
Global warming poses a major threat to plant growth and crop production. In some plants, including Arabidopsis thaliana, elevated temperatures induce a series of morphological and developmental adjustments termed thermomorphogenesis, which facilitates plant cooling under high-temperature conditions. Plant thermal response is suppressed by histone variant H2A.Z. At warm temperatures, H2A.Z is evicted from nucleosomes at thermoresponsive genes, resulting in changes in their expression. However, the mechanisms that regulate H2A.Z eviction and subsequent transcriptional changes are largely unknown. Here, we show that the INO80 chromatin remodeling complex (INO80-C) promotes thermomorphogenesis and activates the expression of thermoresponsive and auxin-related genes. INO80-C associates with PHYTOCHROME-INTERACTING FACTOR 4 (PIF4), a potent regulator of thermomorphogenesis, and mediates temperature-induced H2A.Z eviction at PIF4 targets. Moreover, INO80-C directly interacts with COMPASS-like and transcription elongation factors to promote active histone modification, histone H3 lysine 4 trimethylation, and RNA polymerase II elongation, leading to the thermal induction of transcription. Notably, the transcription elongation factors SPT4 and SPT5 are required for H2A.Z eviction at PIF4 targets, suggesting the cooperation of INO80-C and transcription elongation in H2A.Z removal. Taken together, these results suggest that the (PIF4)-(INO80-C)-(COMPASS-like)-(transcription elongator) module controls plant thermal response, thereby establishing a link between H2A.Z eviction and active transcription.


Calcitriol and genistein actions to inhibit the prostaglandin pathway: potential combination therapy to treat prostate cancer.
We present an overview of the prostaglandin (PG) pathway as a novel target for the treatment of prostate cancer (PCa) using a combination of calcitriol and genistein, both of which have known antiproliferative properties. Calcitriol inhibits the PG pathway in PCa cells in 3 separate ways: by decreasing cyclooxygenase-2 (COX-2) expression, stimulating 15-hydroxyprostaglandin dehydrogenase (15-PGDH) expression, and decreasing EP (PGE2) and FP (PGF(2alpha)) receptors. These actions of calcitriol result in reduced levels of biologically active PGE2, leading ultimately to growth inhibition of the PCa cells. We also demonstrate the advantages of using calcitriol in combination with genistein for the treatment of PCa. Genistein, a major component of soy, is a potent inhibitor of the activity of CYP24, the enzyme that initiates the degradation of calcitriol. This leads to increased half-life of bioactive calcitriol, thereby enhancing all of calcitriol's actions including those on the PG pathway. In addition to inhibiting CYP24 enzyme activity, genistein has its own independent actions on the PG pathway in PCa cells. Like calcitriol it inhibits COX-2 expression and activity, leading to decreased synthesis of PGE2. It also inhibits the EP and FP receptors, thereby reducing the biological function of PGE2. Thus, the combination of calcitriol and genistein acts additively to inhibit the PG pathway. Both calcitriol and genistein are relatively safe and have little toxicity associated with their intake. We postulate that the combination of calcitriol and genistein is an attractive therapeutic option for the treatment of PCa.


[Fractionation of ciguatoxic lipid extracts in alkaline medium].
A modification of the extraction procedure for obtaining ciguatoxic substances from the tissues of various poisonous reef fish has been developed. Rapid alkali treatment of the residue obtained at an early stage is efficient in separating the ciguatoxic fraction from toxic impurities which interfere with pharmacological tests. It is thus possibles to carry out a more precise dosage of the material separated in this way. Alkali treatment does not affect either the physiological activity in cats and mice of the ciguatoxic substances nor their behaviour in a preparative thin layer chromatography in a benzene-butanol system.


Effect of different chilling rates on the quality parameters of mule duck fatty liver.
The aim of this experiment was to study the effect of chilling rates on the quality features of fatty livers. Three different chilling rates were applied: ultra-fast (UF), fast (FA), and slow (SL). Technological and proteomic results were compared at time T1 when the internal temperature of livers reached 10°C and at time T2=24 h post mortem. Samples from the UF group reached the T1 temperature at 50 min post mortem and had the least hard livers and the lowest cooking loss percentage (25±9%) at time T2=24 h post mortem (P-value of <0.01). The FA and SL groups reached the T1 temperature after 120 and 210 min post mortem and presented higher melting (36±9 and 41±9%, respectively, at time T2) and harder livers compared to the UF group. In parallel, we conducted semi-quantifications of proteins by electrophoresis and proteolytic activities by mono-dimensional zymography for three families of proteases: Matrix metalloproteases (MMP), Cathepsins, and Calpains. The proteomic assays revealed less modified proteolytic activities in samples from the UF group, and less associated proteins degradations than in samples from the FA and the SL groups. Effects of the different chilling rates were mainly significant at time T2 (24 h post mortem). As a conclusion we were able to highlight an indirect positive relation between proteolysis and melting yield in ducks' fatty liver.


Reduced expression of PSA-NCAM in the hippocampus and piriform cortex of the R6/1 and R6/2 mouse models of Huntington's disease.
Cognitive deficits and impaired olfactory function are observed in early stages of Huntington's disease (HD). The polysialylated form of the neural cell adhesion molecule (PSA-NCAM) is strongly associated with plastic events in the brain. During adulthood, it is most abundantly expressed in the hippocampus and the piriform cortex, which are involved in cognition and olfaction, respectively. We show that the numbers of PSA-NCAM-positive cells in the hippocampus and piriform cortex are dramatically reduced in the R6/1 and the R6/2 mouse models of HD. We hypothesize that the decrease in NCAM polysialylation reflects an impaired plasticity and might underlie some of the early symptoms in HD.


Development of anxiety symptoms during a deep diving experiment.
Six commercial divers were investigated for anxiety responses during a 29-day, open-sea world record dive at 500 meters of depth. Three of six (50%) divers developed anxiety. The authors emphasize the importance of research on personality traits as possible predictors for the development of anxiety during deep dives of exceptional depth and duration of confinement.


Efficient transition path sampling for systems with multiple reaction pathways.
A new algorithm is developed for sampling transition paths and computing reaction rates. To illustrate the use of this method, we study a two-dimensional system that has two reaction pathways: one pathway is straight with a relatively high barrier and the other is roundabout with a lower barrier. The transition rate and the ratio between the numbers of the straight and roundabout transition paths are computed for a wide range of temperatures. Our study shows that the harmonic approximation for fluctuations about the steepest-descent paths is not valid even at relatively low temperatures and, furthermore, that factors related to entropy have to be determined by the global geometry of the potential-energy surface (rather than just the local curvatures alone) for complex reaction systems. It is reasonable to expect that this algorithm is also applicable to higher dimensional systems.


Relationship between Helicobacter pylori infection and nonalcoholic fatty liver disease: What should we expect from a meta-analysis?
The relationship between Helicobacter pylori (H. pylori) infection and nonalcoholic fatty liver disease (NAFLD) is a matter of debate. Although it has been studied in many observational studies, the results remain controversial. Therefore, we performed a meta-analysis to assess the association between H pylori infection and risk of NAFLD. We searched Pubmed, EMBASE, and Web of Science databases, from inception to September 10, 2020. Odds ratio (OR) and 95% confidence interval (CI) were pooled by random-effects model. The statistical heterogeneity among studies (I2-index), subgroup analyses, regression analyses, sensitivity analysis and the possibility of publication bias were assessed. A total of seventeen studies involving 91,958 individuals were included in our meta-analysis. Meta-analysis of data from cross-sectional and case-control studies showed that H pylori infection was associated with increased risk of prevalent NAFLD (n = 15; involving 74,561 middle-aged individuals; OR1.38, 95% CI 1.23-1.55, I2 = 86.8%, P < .001). The results of meta-regression implicated that the study type and the case-control ratio impacted the total effect size. Funnel plot did not show significant publication bias. Meta-analysis of data from longitudinal studies showed that H pylori infection was also associated with increased NAFLD incidence (n = 2; involving 17397 individuals; OR 1.21, 95% CI 1.01-1.44, I2 = 6.5%, P = .301). The results indicated that a positive association between H pylori infection and the risk of NAFLD. Further studies are required to strengthen the association and clarify the mechanism.


Ataxia-telangiectasia: flow cytometric cell-cycle analysis of lymphoblastoid cell lines in G2/M before and after gamma-irradiation.
It has been estimated that 1 to 3% of the general population may be ataxia-telangiectasia (A-T) heterozygotes and hypersensitive to conventional doses of radiation. We attempted to identify heterozygotes by evaluating the proportion of cells in various phases of the cell cycle in response to irradiation. This was accomplished by using flow cytometry to study lymphoblastoid cell lines (LCLs) from 14 A-T homozygotes, 17 genotypic A-T heterozygotes, and 18 normal individuals, including 10 genotypic normals. The LCLs were exposed to 2-gRay radiation and were analyzed after 24 hr along with nonirradiated controls. The difference between the percentage of cells in G2/M with and without irradiation after 24 hr ranged, respectively, from: 12.0 to 31.5% (mean = 18.7 +/- 5.5) for A-T homozygotes; 6.7 to 19.3% (mean = 12.5 +/- 3.8) for A-T heterozygotes; and -1.5 to 12.4% (mean = 6.4 +/- 3.2) for normals. A cut-off region of 9.6 to 13.2% defined by one standard deviation above the mean for normals and one standard deviation below the mean for A-T homozygotes served as the grey zone between normals and A-T heterozygotes or homozygotes. Two of the 18 normals overlapped with the grey zone. Four of 17 heterozygotes were within the normal range; seven fell within the grey zone. This may reflect nongenetic variables, such as the status of the LCLs at the time of testing. Flow cytometry cell-cycle analysis on irradiated LCLs is a useful adjunctive test for establishing a diagnosis of A-T in questionable cases.(ABSTRACT TRUNCATED AT 250 WORDS)


Digital anaesthesia: one injection or two?
Digital nerve blocks (DNB) are performed frequently in the Emergency Department (ED). The aim of this study was to establish whether single injection subcutaneous digital nerve block (SDNB) is as effective as the traditional (two injection) digital nerve block (TDNB) for digital anaesthesia. Single blinded, prospective, randomised-controlled multicentre trial within Hampshire EDs. Patients > or = 16 years attending the ED with fingertip injuries/infections (distal to the distal-interphalangeal joint) requiring a DNB were randomised to SDNB/TDNB groups. Outcome measures were: primary - successful anaesthesia; secondary - patient distress, clinician satisfaction (CS), complications. 76 patients were randomised. (37 received SDNB). At 5 min, more patients in the SDNB group (28/37, 76%) were adequately anaesthetised than in the TDNB group, (22/34, 65%). At 10 min, 33/37 (89%) of the SDNB group compared to 28/34 (82%) of the TDNB group were adequately anaesthetised. The mean (SD) of self-reported distress scores for the SDNB group were lower than those reported for the TDNB group, whereas the mean (SD) of CS scores for SDNB were higher than those reported for TDNB. Neither group reported complications from anaesthesia. SDNB is as effective as TDNB. Outcome measures favoured SDNB, but only CS scores achieved statistical significance. Trial recruitment is much slower than anticipated. However, clinical practice has demonstrated that SDNB works and practice is already changing within the Hampshire region, with some departments adopting SDNB as standard practice. Therefore, the results are being presented now to allow clinicians to make an informed choice. Our results may also contribute to future metanalyses.


Type 2 diabetes mellitus complicated with smoldering myeloma and non-alcoholic steatohepatitis.
We report a 59-year-old woman with type 2 diabetes mellitus (DM) complicated with smoldering myeloma and non-alcoholic steatohepatitis. A diagnosis of smoldering myeloma was made on the basis of elevation of IgA, M-protein (type:IgA-lambda) and histological findings of bone marrow without bone lesion. As to liver dysfunction, anti-HBV, anti-HCV and a series of auto-immune antibody were negative. She had no alcohol drinking habit and histological findings showed pericellular fibrosis without fatty degeneration, suggesting liver cirrhosis due to non-alcoholic steatohepatitis (NASH). To date, there are no reports of cases with DM, NASH and myeloma. Particular attention may be necessary for these complications.


Dynamic sorting of lipids and proteins in membrane tubes with a moving phase boundary.
Cellular organelle membranes maintain their integrity, global shape, and composition despite vigorous exchange among compartments of lipids and proteins during trafficking and signaling. Organelle homeostasis involves dynamic molecular sorting mechanisms that are far from being understood. In contrast, equilibrium thermodynamics of membrane mixing and sorting, particularly the phase behavior of binary and ternary model membrane mixtures and its coupling to membrane mechanics, is relatively well characterized. Elucidating the continuous turnover of live cell membranes, however, calls for experimental and theoretical membrane models enabling manipulation and investigation of directional mass transport. Here we introduce the phenomenon of curvature-induced domain nucleation and growth in membrane mixtures with fluid phase coexistence. Membrane domains were consistently observed to nucleate precisely at the junction between a strongly curved cylindrical (tube) membrane and a pipette-aspirated giant unilamellar vesicle. This experimental geometry mimics intracellular sorting compartments, because they often show tubular-vesicular membrane regions. Nucleated domains at tube necks were observed to present diffusion barriers to the transport of lipids and proteins. We find that curvature-nucleated domains grow with characteristic parabolic time dependence that is strongly curvature-dependent. We derive an analytical model that reflects the observed growth dynamics. Numerically calculated membrane shapes furthermore allow us to elucidate mechanical details underlying curvature-dependent directed lipid transport. Our observations suggest a novel dynamic membrane sorting principle that may contribute to intracellular protein and lipid sorting and trafficking.


Genetics of vasculitis.
We aim to give an overview of the recent progress in the knowledge of the genetic component of vasculitides. Using a state-of-the-art imputation method to analyse the major histocompatibility complex (MHC) region, Ombrello and colleagues narrowed down the association between human leukocyte antigen (HLA)-B51 and Behçet's disease to a model of five amino acids of the HLA-B molecule involved in the binding of the antigen, the interactions with receptors on CD8 T cells and natural killer cells, and the signal peptide of HLA-B, suggesting a crucial role of the cellular cytotoxicity on this disease. Other recent genetic studies have identified several loci with strong effects on vasculitis predisposition, most of them representing important players in the immune and inflammatory response. These associations include ERAP1, CCR1-CCR3, STAT4, KLRC4, GIMAP4, and TNFAIP3 in Behçet's disease; BLK and CD40 in Kawasaki disease; SERPINA1 and SEMA6A in antineutrophil cytoplasmic antibody associated vasculitides; IL12B and FCGR2A/ FCGR2A in Takayasu arteritis; and CECR1 in a newly defined vascular inflammatory syndrome associated with adenosine deaminase (ADA2) deficiency. Although other vasculitides, such as giant cell arteritis (GCA) or immunoglobulin A vasculitis, have not benefitted by the great advantage of the large-scale genetic analyses yet, some interesting associations have been recently suggested, such as the classical functional PTPN22 allele rs2476601 (R620W) with GCA. The analysis of high-throughput genotyping and exome-sequencing data has produced a considerable advance in the identification of consistent genetic risk factors in vasculitides during the last 3 years. Further collaborative efforts, which will increase the sample size, and the use of custom arrays like the immunochip, will definitively help to better understand the genetic basis of vasculitides and to identify the common and specific molecular pathways underlying their pathophysiology.