Modulate Organic-Metal Oxide Heterojunction via [1,6] Azafulleroid for Highly Efficient Organic Solar Cells.
By creating an effective π-orbital hybridization between the fullerene cage and the aromatic anchor (addend), the azafulleroid interfacial modifiers exhibit enhanced electronic coupling to the underneath metal oxides. High power conversion efficiency of 10.3% can be achieved in organic solar cells using open-cage phenyl C61 butyric acid methyl ester (PCBM)-modified zinc oxide layer.


Progressive lupus glomerulonephritis. Treatment with prednisone and combined prednisone and cyclophosphamide.
We report a prospective randomized study of 39 patients with systemic lupus erythematosus and progressive glomerulonephritis who were assigned to treatment groups that received either prednisone alone or prednisone and cyclophosphamide combined. They received treatment for 6 months and were then followed up for an additional 18 months. No difference in outcome was seen in the two groups at the end of 6 months. Among patients followed up for an average of 24 months, fewer individuals showed later renal progression among those treated with cyclophosphamide and prednisone than among the group treated with prednisone alone.


How absorbed hydrogen affects the catalytic activity of transition metals.
Heterogeneous catalysis is commonly governed by surface active sites. Yet, areas just below the surface can also influence catalytic activity, for instance, when fragmentation products of catalytic feeds penetrate into catalysts. In particular, H absorbed below the surface is required for certain hydrogenation reactions on metals. Herein, we show that a sufficient concentration of subsurface hydrogen, H(sub) , may either significantly increase or decrease the bond energy and the reactivity of the adsorbed hydrogen, H(ad) , depending on the metal. We predict a representative reaction, ethyl hydrogenation, to speed up on Pd and Pt, but to slow down on Ni and Rh in the presence of H(sub) , especially on metal nanoparticles. The identified effects of subsurface H on surface reactivity are indispensable for an atomistic understanding of hydrogenation processes on transition metals and interactions of hydrogen with metals in general.


Molecular typing of Mycobacterium Abscessus isolated from cystic fibrosis patients.
The possibility of inter-human transmission of Mycobacterium abscessus in cystic fibrosis centres has been recently hypothesized suggesting the need for the molecular characterization of strains isolated from such patients. One hundred and forty one isolates of M. abscessus grown from sputum samples of 29 patients with cystic fibrosis were genotyped resorting to variable number of tandem repeats (VNTR) determination and whole genome sequencing (WGS). Out of 29 VNTR profiles, 15 were unique to the same number of patients while seven were shared by multiple patients. WGS showed that only two of the patients sharing common VNTR patterns were indeed infected by the same strain. The shared VNTR patterns were mostly present among the isolates of M. abscessus subsp. abscessus. As expected WGS showed a clearly higher discriminatory power in comparison with VNTR and appeared the only molecular epidemiology tool suitable to effectively discriminate the isolates of M. abscessus subsp. abscessus.


Pericentric inversion with partial 7(q35-->qter) duplication and 7pter deletion: diagnosis by cytogenetic and fish analysis in a 29-year-old male patient.
We report on a 29-year-old male patient with an inverted 7(q35-qter) duplication diagnosed by combining cytogenetic and FISH studies. Traditional G-banding detected an abnormally long chromosome 7 which was further demonstrated to be entirely of chromosome 7 origin by using fluorescent whole chromosome 7 painting. The presence within the additional segment of a signal for 7q36 region (Williams control probe) and the absence of signals for 7q33 (Y938G5 probe) and 7q34 (Y815G5 probe) regions indicated that the breakpoint for this rearrangement was distal to 7q34 and proximal to 7q36. A distal 7p22 deletion was confirmed by the absence of signal for the 7p subtelomeric probe. Apart from kyphosis, developmental/mental retardation and abnormal ears, the clinical features of the present patient, who is the oldest individual ever reported with this duplication/deletion, were not typical for partial 7q trisomy syndrome. A review of the cases reported with 7(q35-qter) duplication is made and shows important clinical variability but constantly normal pre- and postnatal growth, a feature which can therefore be confirmed as distinctive of distal 7q trisomy syndrome.


A consensus mechanism for Radical SAM-dependent dehydrogenation? BtrN contains two [4Fe-4S] clusters.
BtrN catalyzes the two-electron oxidation of the C3 secondary alcohol of 2-deoxy-scyllo-inosamine to the corresponding ketone and is a member of a subclass of radical S-adenosylmethionine (SAM) enzymes called radical SAM (RS) dehydrogenases. Like all RS enzymes, BtrN contains a [4Fe-4S] cluster that delivers an electron to SAM, inducing its cleavage to the common intermediate in RS reactions, the 5'-deoxyadenosyl 5'-radical. In this work, we show that BtrN contains an additional [4Fe-4S] cluster, thought to bind in contact with the substrate to facilitate loss of the second electron in the two-electron oxidation.


Preparation and characterization of intravenously injectable nimodipine nanosuspension.
The purpose of this study was to develop an alternative, improved and better tolerated injectable nimodipine nanosuspension compared with commercially available ethanol solution. In this study, nimodipine nanosuspension was prepared by high-pressure homogenization (HPH). The effects of the production parameters such as pressure, cycle numbers and crushing principles on the mean particle size, 99% diameter and polydispersity of the nanosuspension were investigated. Characterization of the product was performed by scanning electron microscope (SEM) and differential scanning calorimeter (DSC). The safety of the nimodipine nanosuspension was discussed with special attention to contamination by microparticles and the increase in saturation solubility C(s). Irritability study in rabbits showed that this formulation provided less local irritation and phlebitis risks than the commercial ethanol product, which represented a promising new drug formulation for intravenous therapy of subarachnoid hemorrhage (SAH)-related vasospasm.


Antifungal susceptibility testing: technical advances and potential clinical applications.
The clinical application of in vitro antifungal susceptibility testing has been limited by a lack of reproducibility and uncertain clinical relevance. As a result of several collaborative studies, the National Committee for Clinical Laboratory Standards (NCCLS) has proposed a standardized antifungal susceptibility test method, NCCLS M27-T. More convenient, user-friendly methods (microdilution broth and stable gradient technology) have been evaluated, and the potential for a similar process with a disk diffusion method is apparent. Adaptation of the standard method for susceptibility testing of filamentous fungi appears promising. The existence of a standardized method facilitates meaningful analysis of studies addressing the issue of clinical relevance of antifungal susceptibility testing. Correlation of MICs with clinical response to therapy is beginning to emerge, most notably in relation to fluconazole and itraconazole therapy for oropharyngeal candidiasis associated with infection with the human immunodeficiency virus. This accumulated experience with antifungal susceptibility testing allows us to provide several specific recommendations for antifungal susceptibility testing in the clinical laboratory. Application of this developing technology to new antifungal agents and other disease states will enhance our ability to effectively deal with the emerging problem of fungal infection.


Initial Experience with the Use of Thrombopoetin Receptor Agonists in Patients with Refractory HIV-Associated Immune Thrombocytopenic Purpura: A Case Series.
HIV-associated immune thrombocytopenic purpura (ITP) has decreased in incidence 10-fold since the advent of highly active antiretroviral therapy (HAART). For patients with detectable HIV viral loads, first-line treatment approaches involve optimizing HAART followed by standard ITP options used to treat those without HIV infection. In the general population, the thrombopoetin receptor agonists (TRAs), eltrombopag and romiplostim, are effective when used as salvage ITP therapy. In addition, eltrombopag has been used effectively in patients with thrombocytopenia secondary to hepatitis C--a virus seen commonly in HIV-infected patients, especially in those who also have a history of intravenous drug use. There are, however, few reports or studies of TRAs use in those with HIV infection. Herein, we describe 5 cases of refractory HIV-associated ITP managed with TRAs. Although platelet counts improved for all patients, 2 patients succumbed to thromboembolic complications. Our initial experience, as well as our findings from a Medline review, supports the potential utility of TRA as salvage therapy in the treatment of HIV-related ITP; however, we recommend caution in the use of these agents in those who are at highest risk of thrombosis. Additional studies are needed to determine the efficacy and, more importantly, the safety of TRAs in treatment of HIV-associated ITP.


Flow-induced agitations create a granular fluid.
We fluidize a granular medium through localized stirring and probe the mechanical response of quiescent regions far away from the main flow. In these regions the material behaves like a liquid: high-density probes sink, low-density probes float at the depth given by Archimedes' law, and drag forces on moving probes scale linearly with the velocity. The fluidlike character of the material is set by agitations generated in the stirred region, suggesting a nonlocal rheology: the relation between applied stress and observed strain rate in one location depends on the strain rate in another location.


"I look at my own forest and fields in a different way": the lived experience of nature-based therapy in a therapy garden when suffering from stress-related illness.
Evidence confirms that nature-based therapy (NBT) has a positive effect on people with mental illnesses. However, there is a lack of evidence on the meaning of NBT for specific patient groups. The Nacadia® Therapy Garden was designed according to an evidence-based design process, and an NBT programme was developed. The aim of the study was to illuminate the phenomenon of participants' lived experience of the NBT in Nacadia. Fourteen participants took part in semi-structured interviews (SSIs), and by way of reflective lifeworld research, the SSIs were analysed to identify and describe the meanings of the phenomenon. The essence of the phenomenon was found to be a process of adopting a searching approach to NBT and Nacadia to become familiar with the conditions. This familiarity stimulated the development of confidentiality and attachment to Nacadia. Feeling protected, safe, cared for, and not exposed was important, and motivated feelings of freedom, reduced demands, and increased the ability to access and try a spectrum of NBT activities. It encouraged participants to develop personal approaches and coping strategies to implement in their everyday lives for moving on.


Synaptic distinction of laminar-specific prefrontal-temporal pathways in primates.
Prefrontal pathways exert diverse effects in widespread cortical areas, issuing projections both to the middle layers and to layer I, which are anatomically and functionally distinct. Here we addressed the still unanswered question of whether cortical pathways that terminate in different layers are distinct at the synaptic level. We addressed this issue using as a model system the robust and functionally significant pathways from prefrontal areas 10 and 32 to superior temporal areas in rhesus monkeys. Boutons from prefrontal axons synapsing in the middle layers of superior temporal cortex were significantly larger than boutons synapsing in layer I. Most synapses were on spines in both layers, which are found on dendrites of excitatory neurons. The less prevalent synapses on smooth dendrites, characteristic of inhibitory interneurons, were more common in the middle cortical layers than in layer I. Bouton volume was linearly related to vesicular and mitochondrial content in both layers, though a subset of small boutons, found mostly in layer I, contained no mitochondria. The systematic laminar-specific presynaptic differences in stable cortical synapses in adult primates were independent of their origin in the functionally distinct prefrontal areas 10 and 32, or their destination in architectonically distinct superior temporal areas. This synaptic distinction suggests differences in efficacy of synaptic transmission and metabolic demands in laminar-specific pathways that may be selectively recruited in behavior.


Boeravinone B a natural rotenoid exerts anticancer activity via inducing internalization and degradation of inactivated EGFR and ErbB2 in human colon cancer cells.
Epidermal growth factor receptors (EGFR) are identified to be favorable targets for cancer treatment. In present work, we showed that Boeravinone B, a Rotenoid from natural origin has significant anticancer activity via internalization of ErbB2 and EGFR, and thereby resulting in destruction of the receptors. For cell viability and apoptosis were done by MTT assay. Annexin V-FITC staining was done for determining the extent of apoptosis. Immunoblotting for expression of proteins in HT-29 cell lysates after exposing them to Boeravinone G. Immunofluorescence and Confocal microscopic analysis was done for HT-29 cells incubated with anti-EGFR or anti-ErbB2 antibodies. Surface biotinylation assay was done followed by western blot analysis for expression of proteins using antibodies against transferrin receptor, ErbB2 and EGFR. Exposure of HT-29 cells with Boeravinone B suppressed constitutive as well as ligand mediated phosphorylation of ErbB2, ErbB3 and EGFR. The treatment also inhibited the activation of mitogen-activated protein kinase (MAPK), Akt and Erk1/2 which are downstream signaling molecules. The treatment also bought about internalization of ErbB2 and EGFR causing destruction of receptors, Boeravinone B also caused apoptosis in HT-29 cells. Boeravinone B mediated degradation was halted by Chloroquine (lysosomal inhibitor). Boeravinone B caused nuclear translocation of apoptosis-inducing factor (AIF) and caused proteolytic processing of PARP along with caspase-3, confirming Boeravinone B may induce caspase-independent apoptosis in HT-29 cells. The findings of present study provide first ever evidences for Boeravinone B suggesting anticancer activity via internalization and destruction of EGFR family receptors i.e. ErbB2 and EGFR in HT-29 cell lines.


High-resolution, reconfigurable printing of liquid metals with three-dimensional structures.
We report an unconventional approach for high-resolution, reconfigurable 3D printing using liquid metals for stretchable, 3D integrations. A minimum line width of 1.9 μm can be reliably formed using direct printing, and printed patterns can be reconfigured into diverse 3D structures with maintaining pristine resolutions. This reconfiguration can be performed multiple times, and it also generates a thin oxide interface that can be effective in preventing the spontaneous penetration of gallium atoms into different metal layers while preserving electrical properties under ambient conditions. Moreover, these free-standing features can be encapsulated with stretchable, conformal passivations. We demonstrate applications in the form of a reconfigurable antenna, which is tunable by changing geometeries, and reversibly movable interconnections used as mechanical switches. The free-standing 3D structure of electrodes is also advantageous for minimizing the number and space between interconnections, which is important for achieving higher integrations, as demonstrated in an array of microLEDs.


Factors Affecting the Dissolution of Indomethacin Solid Dispersions.
The aim of this study was to investigate the influence of factors such as carrier type, drug/carrier ratio, binary carriers, and preparation method on the dissolution of an insoluble drug, indomethacin (IM), under supersaturation conditions. Using a solvent evaporation (SE) method, poloxamer 188 and PVP K30 showed better dissolution among the selected carriers. Furthermore, as the ratio of carriers increased (drug/carrier ratio from 1:0.5 to 1:2), the dissolution rate increased especially in almost two times poloxamer 188 solid dispersions (SDs), while the reverse results were observed for PVP K30 SDs. For the binary carrier SD, a lower dissolution was found. Under hot melt extrusion (HME), the dissolution of poloxamer 188 SD and PVP K30 SD was 0.83- and 0.94-folds lower than that using SE, respectively, while the binary carrier SD showed the best dissolution. For poloxamer 188 SDs, the drug's crystal form changed when using SE, while no crystal form change was observed using HME. IM was amorphous in PVP K30 SDs prepared by both methods. For binary carrier systems, amorphous and crystalline drugs coexisted in SD using SE, and negligible amorphous IM was in SD using HME. This study indicated that a higher amorphous proportion in SD did not correlate with higher dissolution rate, and other factors, such as carrier type, particle size, and density, were also critical.


[Late potentials analysis in patients with malignant ventricular arrhythmia].
To assess the relationship between late potentials and spontaneous ventricular arrhythmias, organic heart disease, inducibility of arrhythmias at electrophysiological study and ejection fraction. The population is comprised by 52 patients (41 men, 11 women with mean age 50 +/- 16 years) with spontaneous clinically documented ventricular tachycardia or ventricular fibrillation. An electrophysiological study was performed with conventional programmed stimulation. Within a week of the test a study of late potentials was also performed. Late potentials were documented in 73% of the patients with ventricular tachycardia and only in 17% of the patients with ventricular fibrillation. Sixty-eight percent of the patients with ischemic cardiopathy presented late potentials and in these, ventricular tachycardia was inducible in 93%. Only one from a group of 7 patients with ventricular arrhythmias and no organic heart disease, presented late potentials. In patients with late potentials, 84% have inducible ventricular tachycardia, but only 26% of patients without late potentials have inducible ventricular tachycardia. The incidence of late potentials was inversely correlated with left ventricular ejection fraction. The presence of late potentials was more frequent in patients with ventricular tachycardia than in patients with ventricular fibrillation. The presence of late potentials has a sensibility of 81.5% and a specificity of 78% to detect patients with inducible ventricular tachycardia.


Impact of Spinous Process Integrity on Ten to Twelve-Year Outcomes After Posterior Decompression for Lumbar Spinal Stenosis: Study of Open-Door Laminoplasty Using a Spinous Process-Splitting Approach.
In posterior decompression for lumbar spinal stenosis, preservation of the posterior elements appears to provide patients with long-term favorable outcomes. To confirm this assumption, we evaluated the impact of spinous process integrity, i.e., osseous continuity between the spinous process and the lamina, on short to long-term outcomes. As a model for the study of spinous process integrity, we retrospectively reviewed the cases of forty-eight patients who underwent open-door laminoplasty using a spinous process-splitting approach without disrupting attachment sites of the multifidus muscle. In those patients, thirty-nine of the 103 spinous processes achieved spontaneous osseous union with the laminar flap, while the others did not achieve osseous union. The association between the number of ununited spinous processes, as well as baseline characteristics, and the outcomes were analyzed by primary and fully adjusted multivariate linear regression. Outcome measures were the Oswestry Disability Index (ODI) and a numeric rating scale (NRS) for symptoms at two, four, and ten to twelve years. The number of ununited spinous processes was significantly associated with ten to twelve-year scores for the ODI (β = 0.24, p = 0.030), low back pain NRS (β = 0.32, p = 0.030), and leg pain NRS (β = 0.50, p = 0.0012) in the fully adjusted models, but was not associated with two or four-year scores for each scale. The number of decompression levels was significantly associated with ten to twelve-year scores for low back pain and leg pain NRS in the primary models, but was not retained in the fully adjusted models. Osseous continuity between the spinous processes and the lamina after posterior decompression of the lumbar spine is important for maintaining the positive surgical benefit. Deleterious effects of osseous discontinuity on the outcomes were obvious at ten to twelve years, but not at two or four years.


[Epidemiology of venous thrombosis].
Venous thrombo-embolic disease (VTE) is a frequent pathology, responsible for around 10,000 deaths each year in France. Post-thrombotic sequellae is also a main problem related to the disease. The epidemiology of acquired and genetic risk factors of VTE is better understood and has allowed to show that in many cases it is a multifactorial disease. The association of several environmental or genetic and their analysis in the physiopathology of the disease and in the risk of recurrency is important in order to allow a better prevention of the disease and of its recurrencies.


Phenotype and natural history of variant late infantile ceroid-lipofuscinosis 5.
To characterize the phenotypic profile of a cohort of children affected with CLN5, a rare form of neuronal ceroid-lipofuscinosis (NCL), and to trace the features of the natural history of the disease. Records of 15 children (nine males, six females) were obtained from the data sets of the DEM-CHILD International NCL Registry. Disease progression was measured by rating six functional domains at different time points along the disease course. All patients underwent mutation analysis of the CLN5 gene and ultrastructural investigations of peripheral tissues. Expression of the gene product, pCLN5, was characterized in vitro in six patients. Disease onset was at 2 to 7 years 6 months of age: impaired learning and cognition were the most common early symptoms. Seizures occurred relatively late (median age 8y) and were the presenting symptoms in two children. Nine mutations were detected in 30 alleles, including six mutations predicting a truncated protein. Mixed cytosomes were observed by electron microscopy. Differences of disease progression were observed in two groups of patients and could be related to their genetic profile. Clinical features in a multicentre cohort of patients with CLN5 confirm that cognitive difficulties are early clinical markers of this condition. Severe mutations were associated with a more rapid decline of neurological function.


Differential skills of perception of frequency.
This study aimed to develop tests for differentiating auditory perception skills, e.g., to test drug effects. In Exp. 1 (N = 60), discrimination of succeeding frequencies, frequency identification assessed by a choice reaction task, and the perception of pitch contour assessed by frequency deviants in binaural melodies showed zero partial correlations. In Exp. 2 (N = 36), discrimination correlated with performance on a field dependence test; fast frequency identification correlated with verbal fluency. The auditory tests are likely suitable for assessing distinct skills, but correlations with general cognitive abilities require further investigations.


The value of combined elevation of D-dimer and neopterin as a predictive parameter for early stage acute mesenteric ischemia: An experimental study.
Background The diagnosis of acute mesenteric ischemia is variable. Early diagnosis is important for reducing the mortality and morbidity rates. Aim This experimental study aims to investigate the diagnostic utility of D-dimer and neopterin as a marker for the early stage of acute mesenteric ischemia caused by occlusion of superior mesenteric artery. Methods The levels of D-dimer and neopterin were measured using an animal acute mesenteric ischemia model in 21 male rabbits. Superior mesenteric artery occlusion (Group 1, n = 14) and control (Group 2, n = 7) groups were identified. Blood samples at different times are collected from each rabbits. Blood samples from superior mesenteric artery occlusion group were taken 30 min after anesthesia but before laparotomy, 1, 2, and 3 h after superior mesenteric artery ligation. Blood samples from control group were taken 1 h before, 1 and 3 h after anesthesia and laparotomy. The D-dimer and neopterin levels of each blood sample were measured. Results The probability of acute mesenteric ischemia was found to be 36 times higher when the D-dimer level was over 0.125 ng/L, whereas the probability was 19.2 times higher when the neopterin level was over 1.25 nmol/L. Conclusions In this experimental study, the combined elevation of two significant markers, D-dimer and neopterin, may be helpful for the early diagnosis of acute mesenteric ischemia.


Evaluating the Impact of Mediated Literature Searches at a Comprehensive Cancer Center.
Research informationists at a comprehensive cancer center sought to evaluate the impact and value of mediated literature searches in support of their users' work activities. An assessment tool was identified in the literature and modified by the investigators to solicit feedback from library users and identify the major reason(s) why scientists and health care professionals request literature searches, how they use the resulting information, and the impact that the results may or may not have on their research or patient care/decision-making activities. Survey results were qualitatively analyzed, and future avenues of outreach and promotion of mediated literature search services were identified.


Illegal drugs, anti-drug policy failure, and the need for institutional reforms in Colombia.
This paper is inspired by two anomalies encountered in the study of the illegal drugs industry. First, despite the very high profits of coca/cocaine and poppy/opium/heroin production, most countries that can produce do not. Why, for example, does Colombia face much greater competition in the international coffee, banana, and other legal product markets than in cocaine? And second, though illegal drugs are clearly associated with violence, why is it that illegal drug trafficking organizations have been so much more violent in Colombia and Mexico than in the rest of the world? The answers to these questions cannot be found in factors external to Colombia (and Mexico). They require identifying the societal weaknesses of each country. To do so, the history of the illegal drugs industry is surveyed, a simple model of human behavior that stresses the conflict between formal (legal) and informal (socially accepted) norms as a source of the weaknesses that make societies vulnerable is formulated. The reasons why there is a wide gap between formal and informal norms in Colombia are explored and the effectiveness of anti-drug policies is considered to explain why they fail to achieve their posited goals. The essay ends with reflections and conclusion on the need for institutional change.


Family-centered care: facing the new millennium. Interview by Elizabeth Ahmann.
In an interview with the column editor, Beverley Johnson, President and Chief Executive Officer of the Institute for Family-Centered Care, shares her views on the state of family-centered care (see Table 1). A notable achievement over the past several decades has been the acknowledgment of family-centered care as the standard of care for children with special health care needs. Today there is a growing momentum to more broadly apply the principles of family-centered care in both pediatric and adult care settings, and much work needs to be done to build on the strong foundation that has been laid. Changing attitudes and practice, changing how families are viewed and how care is provided, developing collaborative approaches, and emphasizing the importance of relationships--changing in these ways the very culture of health care--will be necessary to make family-centered care a full reality. Many of these changes need to begin during the process of educating medical and nursing students. Health care institutions can support these changes by incorporating principles of family-centered care into personnel policies and practices, ensuring the hiring and support of individuals with family-centered skills and attitudes, and rewarding family-centered practice. Many of these changes can also be supported by research on the relationships between family-centered care and health care utilization, lengths of stay, and health care outcomes. The interview concludes as follows: "What is good for families and patients is often good for the health care system as well. Family-centered care is a winning proposition for all concerned."


Associations between single nucleotide polymorphisms in RYBP and the prognosis of hepatocellular carcinoma in a Chinese population.
Down-regulated RINGl and YYl binding protein (RYBP) is reported to be an independent predictor of a poor prognosis in patients with hepatocellular carcinoma (HCC). However, the genetic association of RYBP polymorphisms with HCC risk and prognosis has not been investigated now. In this study, five RYBP SNPs, rs12956, rs2118593, rs17009699, rs4676875 and rs4532099, were studied from a hospital-based case-control study including 1100 cases (HCC patients) and 1100 controls (non-HCC patients) in Guangxi, China. All these SNPs interacted with environmental risk factors, such as HBV infection, alcohol intake and smoking in the pathogenesis of HCC. Compared to the CC genotype, patients with TT genotype of rs12956 had a decreased risk of HCC (OR = 0.587, 95% CI = 0.403~0.923) and an increased survival time (Co-dominant, HR = 0.745, 95% CI = 0.594~0.934), while those with TT genotype of rs2118593 had an increased risk of HCC (OR = 1.538, 95% CI = 1.093~2.735) and a decreased survival time (Co-dominant, HR = 1.447, 95% CI = 1.174~1.782). No significant difference was found between the other three RYBP polymorphisms with HCC risk and prognosis. Furthermore, we found that tumor number, tumor staging, metastasis and rs2118593 were associated with the overall survival of HCC patients by multivariate COX regression analysis. Our study suggests RYBP SNP, rs2118593 as a new predictor for poor prognosis of HCC patients.


Assessing primary care veterinarians' use of and confidence in performing point-of-care ultrasound.
Point-of-care ultrasound (POCUS) is gaining popularity in the veterinary field, but there is little information on operator confidence. A survey was distributed to primary care veterinarians (PCVs) via social media between May and July 2020. Details of participants' training in and use of POCUS were recorded. Participants' confidence in using thoracic and abdominal POCUS was also assessed using a five-point Likert scale. Two hundred and one PCVs used POCUS, of which 32% reported using a non-standardised protocol. Fifty percent of PCVs were self-taught and 17.4% had attended a specific practical course. The median confidence score was 4 out of 5 (interquartile range [IQR] 2-5) for identifying abdominal abnormalities, irrespective of the training method. The median confidence score for thoracic abnormalities was 3 out of 5 (IQR 1-4) for those taught by a colleague or who were self-taught using journal articles or videos. The survey-based nature of the study relies on self-reporting and is therefore liable to recall bias. PCVs' confidence in using POCUS is lacking, particularly with thoracic POCUS. Standardised practical training for PCVs, particularly in thoracic POCUS, would be beneficial. Future studies should explore how best to deliver this training.


Epidemiology and prophylaxis of viral hepatitis: a global perspective.
Viral hepatitis with various forms of acute and chronic liver disease as potential and ultimately fatal sequelae presents a public health problem worldwide. Recent published reports on the global epidemiology and prophylaxis of viral hepatitis were reviewed. With the advances in novel technologies, eight distinct types of hepatitis virus have been described: Hepatitis A, B, C, D, E, G, TT and SEN viruses. Hepatitis A and E viruses are transmitted by the fecal-oral route and do not induce a chronic carrier state. Due to major changes in epidemiology of hepatitis A virus their significance is more pronounced in areas of intermediate endemicity. Since the available hepatitis A vaccine is rather expensive, cost-benefit studies should be performed with emphasis on the area under consideration or specialized vulnerable groups. Parenterally transmitted hepatitis B and C viruses are major causes of chronic liver disease, including cirrhosis, hepatocellular carcinoma and end-stage liver failure. Hepatitis D virus is unable to replicate on its own, it requires an established hepatitis B virus infection to be able to replicate. Since its introduction, hepatitis B vaccine has been widely used leading to a significant decrease in HBV infection in countries with universal vaccination. Hepatitis G and TT viruses have been characterized within the latter part of the past decade but their significance as to the causation of human liver disease has yet to be elucidated. Likewise, the precise impact of the most recently described SEN virus isolated from patients with post-transfusion hepatitis awaits further studies. In the course of this review, we present the situation and focus on research activities emphasizing epidemiology and prevention of the various forms of viral hepatitis.


Gastrointestinal bleeding in critically ill immunocompromised patients.
Acute gastrointestinal bleeding (GIB) may be a severe condition in immunocompromised patients and may require intensive care unit (ICU) admission. We aimed to describe the clinical spectrum of critically ill immunocompromised patients with GIB and identify risk factors associated with mortality and severe GIB defined by hemorrhagic shock, hyperlactatemia and/or the transfusion of more than 5 red blood cells units. Finally, we compared this cohort with a control population of non-immunocompromised admitted in ICU for GIB. Retrospective study in 3 centers including immunocompromised patients with GIB admitted in ICU from January, 1st 2010 to December, 31rd 2019. Risk factors for mortality and severe GIB were assessed by logistic regression. Immunocompromised patients were matched with a control group of patients admitted in ICU with GIB. A total of 292 patients were analyzed in the study, including 141 immunocompromised patients (compared to a control group of 151 patients). Among immunocompromised patients, upper GIB was more frequent (73%) than lower GIB (27%). By multivariate analysis, severe GIB was associated with male gender (OR 4.48, CI95% 1.75-11.42, p = 0.00), upper GIB (OR 2.88, CI95% 1.11-7.46, p = 0.03) and digestive malignant infiltration (OR 5.85, CI95% 1.45-23.56, p = 0.01). Conversely, proton pump inhibitor treatment before hospitalization was significantly associated with decreased risk of severe GIB (OR 0.25, IC95% 0.10-0.65, p < 0.01). Fifty-four patients (38%) died within 90 days. By multivariate analysis, mortality was associated with hemorrhagic shock (OR 2.91, IC95% 1.33-6.38, p = 0 .01), upper GIB (OR 4.33, CI95% 1.50-12.47, p = 0.01), and long-term corticosteroid therapy before admission (OR 2.98, CI95% 1.32-6.71, p = 0.01). Albuminemia (per 5 g/l increase) was associated with lower mortality (OR 0.54, IC95% 0.35-0.84, p = 0.01). After matching with a control group of non-immunocompromised patients, severity of bleeding was increased in immunocompromised patients, but mortality was not different between the 2 groups. Mortality is high in immunocompromised patients with GIB in ICU, especially in patients receiving long term corticosteroids. Mortality of GIB is not different from mortality of non-immunocompromised patients in ICU. The prophylactic administration of proton pump inhibitors should be considered in this population.


Cocaine withdrawal reduces group I mGluR-mediated long-term potentiation via decreased GABAergic transmission in the amygdala.
Cocaine relapse can occur when cocaine-associated environmental cues induce craving. Conditioned place preference (CPP) is a behavioral paradigm modeling the association between cocaine exposure and environmental cues. The amygdala is involved in cocaine cue associations with the basolateral amygdala (BLA) and central amygdala (CeA) acting differentially in cue-induced relapse. Activation of metabotropic glutamate receptors induces synaptic plasticity, the mechanism of which is thought to underlie learning, memory and drug-cue associations. The goal of this study was to examine the neural alterations in responses to group I metabotropic glutamate receptor (mGluR) agonists in the BLA to lateral capsula of CeA (BLA-CeLc) pathway in slices from rats exposed to cocaine-CPP conditioning and withdrawn for 14 days. mGluR1, but not mGluR5, agonist-induced long-term potentiation (mGluR1-LTP) in the BLA-CeLc pathway was reduced in rats withdrawal from cocaine for 2 and 14 days, and exhibited an altered concentration response to picrotoxin. Cocaine withdrawal also reduced γ-aminobutyric acid (GABA)ergic synaptic inhibition in CeLc neurons. Blocking cannabinoid receptor 1 (CB(1) ) reduced mGluR1-LTP in the saline-treated but not cocaine-withdrawn group. Response to CB(1) but not CB(2) agonist was altered after cocaine. Additionally, increasing endocannabinoid (eCB) levels abolished mGluR1-LTP in the saline but not cocaine-withdrawn group. However, CB(1) and CB(2) protein levels were increased in the amygdala of cocaine-withdrawn rats while mGluR1 and mGluR5 remained unchanged. These data suggested that the mechanisms underlying the diminished mGluR1-LTP in cocaine-withdrawn rats involve an altered GABAergic synaptic inhibition mediated by modulation of downstream eCB signaling. These changes may ultimately result in potentiated responses to environmental cues that would bias behavior toward drug-seeking.


Alterations in the thymopoiesis in experimental autoimmune myasthenia gravis.
Experimental autoimmune myasthenia gravis (EAGM) was induced in female AO rats, by a single immunization with Torpedo acetylcholine receptor (AChR). Animals injected with saline served as controls. The study showed substantial changes in EAMG rats in the thymopoiesis, causing an increase in the relative proportion of mature CD8+ and, particularly, CD4+ (possibly autoreactive) single positive (SP) cells expressing TCRalphabeta at high level (TCRalphabeta(high)), as well as in that of mature double negative (DN) TCRalphabeta(high) cells, which are believed to be the immunoregulatory cells that augment autoantibody (autoAb) production. These results indicate that an augmented production of autoreactive CD4+ cells, on one side, and an increase of the immunoregulatory T cells that augment autoAb production, on the other side (reflecting, most likely, an increased entry of activated autoreactive CD4+ T cells from the periphery into the thymus), may have a significant role in the sustention of immune response in EAMG, and may suggest a putative mechanism underlying the sustention of autoimmune response in acquired MG.


Composition Wheels: Visualizing dissolved organic matter using common composition metrics across a variety of Canadian ecozones.
Dissolved organic matter (DOM) is a ubiquitous component of aquatic systems, impacting aquatic health and drinking water quality. These impacts depend on the mixture of organic molecules that comprise DOM. Changing climates are altering both the amount and character of DOM being transported from the terrestrial system into adjacent surface waters, yet DOM composition is not monitored as often as overall concentration. Many DOM characterization methods exist, confounding comparison of DOM composition across different studies. The objective of this research is to determine which parameters in a suite of relatively simple and common DOM characterization techniques explain the most variability in DOM composition from surface and groundwater sites. Further, we create a simple visualization tool to easily compare compositional differences in DOM. A large number of water samples (n = 250) was analyzed from six Canadian ecozones for DOM concentration, ultraviolet-visible light absorbance, molecular size, and elemental ratios. Principal component analyses was used to identify quasi-independent DOM compositional parameters that explained the highest variability in the dataset: spectral slope, specific-UV absorbance at 255nm, humic substances fraction, and dissolved organic carbon to dissolved organic nitrogen ratio. A 'Composition Wheel' was created by plotting these four parameters as a polygon. Our results find similarities in DOM composition irrespective of site differences in vegetation and climate. Further, two main end-member Composition Wheel shapes were revealed that correspond to DOM in organic-rich groundwaters and DOM influenced by photodegradation. The Composition Wheel approach uses easily visualized differences in polygon shape to quantify how DOM evolves by natural processes along the aquatic continuum and to track sources and degradation of DOM.


[Time-varying spectral analysis of cardiac murmurs].
In this paper, the cardiac murmurs (systolic murmurs, diastolic murmurs and machining murmurs) are classified by hemodynamics and studied by time-frequency analysis. We get the time-varying spectrum of the signals. The results, which are from the different kinds of murmurs in 28 patients with heart disease, show that the time-varying spectrum based on cone-shaped kernel distribution are capable to correctly represent the power density and dynamic course of the series in time-frequency domain. The method has high time-frequency resolution, and the time-varying spectrum of each murmur has its characteristics.


The role of lack of reciprocity, supervisory support, workload and work-family conflict on exhaustion: evidence from physicians.
Emotional exhaustion, argued to be burnout's core dimension, can manifest itself as decreased productivity and job dissatisfaction. This study aims to determine how lack of reciprocity, lack of supervisory support, high workload, and work-family conflict affect emotional exhaustion. Data were collected from 295 physicians working at private and public hospitals in Antalya and İstanbul, Turkey. The survey included lack of reciprocity, supervisory support, workload, WFC items, and exhaustion subscale of Maslach Burnout Inventrory: General Survey (MBI:GS). The proposed model was tested using AMOS 17, which enables assessment of hypothesized relations and degree of fit between data and model. Workload and lack reciprocity were found to increase emotional exhaustion, while supervisory support alleviated the exhaustion physicians experienced. As expected, workload increased work-family conflict. Quite unexpectedly, workload was associated with lack of reciprocity; meaning, physicians more likely perceive their efforts go unappreciated and their patient relationships are inequitable (i.e. investing more than receiving) when they perceive a high workload. In addition, supervisory support was also associated with lack of reciprocity. Physicians experiencing inadequate supervisory support tend to describe their patient relationships in negative terms and perceive inequitable relations. Physicians who do not receive either adequate supervisory support or patient appreciation tend to feel emotionally exhausted. Moreover, both workload and work-family conflict increase physicians' exhaustion. Suggestions to reduce workload and social problems in hospitals are offered to reduce exhaustion.


Effects of diethyldithiocarbamate and structural analogs in mice with systemic candidal infections.
Three different substituted dithiocarbamates: sodium diethyldithiocarbamate (DDTC), sodium dimethyldithiocarbamate (DmDTC), and sodium N-methyl-D-glucamine dithiocarbamate (NMG-DTC) were evaluated for their ability to combat the growth and development of three human pathogenic strains of Candida albicans, in vitro and in vivo, in mice. DDTC and DmDTC produced marked growth inhibition on agar plates, in vitro, of three different strains of Candida albicans, while NMG-DTC displayed little inhibitory effect. Low, nontoxic doses of each compound administered to immunosuppressed mice exhibited impressive therapeutic effects in treating candidiasis. NMG-DTC showed the best consistent therapeutic antifungal effect against Candida albicans in mice immunosuppressed with Solu-Medrol. Combinations of low doses of DDTC and Amphotericin-B appeared to be effective in treating systemic candidal infections, and the results suggested that these combinations may offer therapeutic advantages over those produced by the use of either agent alone.


Developmental and functional ultrastructure of Ornithodiplostomum ptychocheilus diplostomula (Trematoda: Strigeoidea) during invasion of the brain of the fish intermediate host, Pimephales promelas.
We examined tegumental development of the diplostomulum of Ornithodiplostomum ptychocheilus, with respect to structural transformations that have functional relevance to the invasion, migration, and site establishment processes in the brain of the fish second-intermediate host, Pimephales promelas. Using a combination of brightfield, scanning electron microscopy (SEM), transmission electron microscopy (TEM), and confocal microscopy (CM), we demonstrated that the diplostomula become established in the outer region of the optic lobes within 24-48 hr of penetration and continue to grow and transform over a period of 4-14 days. During this period, the J-shaped body consists of 2 distinct regions: (1) a highly motile prosoma with distinctive tegumental spines and (2) an opisthosoma, the tegument of which is elaborated into a dense uniform layer of long, thin microvilli. The prosoma is alternately invaginated into and everted from the opisthosoma, thus constituting a protrusible proboscis. By day 14 postinfection (PI), the body has lost this bipartite structure and has taken on the uniformly flattened form characteristic of metacercariae. The transitory complex structure of the diplostomula appears to be well suited to burrowing through host tissues (primarily by action of the prosoma), followed by rapid dissociation of host tissue and nutrient accumulation (primarily by action of the opisthosoma) in preparation for metacercaria encystment.


Urethroplasty Practices among Reconstructive Urologists in Nigeria.
To determine the national practice patterns in the management of male urethral stricture disease by the open urethroplasty technique. A questionnaire-based national survey of Nigerian urologists was performed during the 19(th) Annual General Meeting and Scientific Conference of the National Association of Urological Surgeons of Nigeria, held at Ibadan, Southwest Nigeria in 2013. A total of 55 respondents (67.1%) completed the questionnaire. About 43.6% were between the ages of 40 and 49 years. Almost 41.8% had between 5 and 9 years of experience as a reconstructive urologist, and 50.9% performed 1-9 urethroplasties/year. A total of 80 responders reported trauma as the most common etiology for their strictures. About 63.7% preferred to treat strictures after 3-6 months of diagnosis and 67.3% of respondents preferred the combination of retrograde urethrography and voiding cystourethrography for the diagnosis of urethral stricture. Stenting of the urethra was done after urethroplasty using size 16 Fr of 18 Fr silastic catheter; however, the duration of stenting varied among urologists. About 41.8% followed up their patients for a year, and uroflowmetry was used by 36.6% of the responders to follow-up their patients. Stricture recurrence was the most common reported complication by 36.4% of the respondents. In Nigeria, most urethral stricture diseases are treated by open urethroplasties. Very few of these surgeries are performed annually by young urologists. There is no uniformity in the method of diagnosis, stenting, and follow-up after treatment.


Humanoid Robot Cooperative Motion Control Based on Optimal Parameterization.
The implementation of low-energy cooperative movements is one of the key technologies for the complex control of the movements of humanoid robots. A control method based on optimal parameters is adopted to optimize the energy consumption of the cooperative movements of two humanoid robots. A dynamic model that satisfies the cooperative movements is established, and the motion trajectory of two humanoid robots in the process of cooperative manipulation of objects is planned. By adopting the control method with optimal parameters, the parameters optimization of the energy consumption index function is performed and the stability judgment index of the robot in the movement process is satisfied. Finally, the effectiveness of the method is verified by simulations and experimentations.


Allelic variation and differential expression of the mSIN3A histone deacetylase complex gene Arid4b promote mammary tumor growth and metastasis.
Accumulating evidence suggests that breast cancer metastatic progression is modified by germline polymorphism, although specific modifier genes have remained largely undefined. In the current study, we employ the MMTV-PyMT transgenic mouse model and the AKXD panel of recombinant inbred mice to identify AT-rich interactive domain 4B (Arid4b; NM_194262) as a breast cancer progression modifier gene. Ectopic expression of Arid4b promoted primary tumor growth in vivo as well as increased migration and invasion in vitro, and the phenotype was associated with polymorphisms identified between the AKR/J and DBA/2J alleles as predicted by our genetic analyses. Stable shRNA-mediated knockdown of Arid4b caused a significant reduction in pulmonary metastases, validating a role for Arid4b as a metastasis modifier gene. ARID4B physically interacts with the breast cancer metastasis suppressor BRMS1, and we detected differential binding of the Arid4b alleles to histone deacetylase complex members mSIN3A and mSDS3, suggesting that the mechanism of Arid4b action likely involves interactions with chromatin modifying complexes. Downregulation of the conserved Tpx2 gene network, which is comprised of many factors regulating cell cycle and mitotic spindle biology, was observed concomitant with loss of metastatic efficiency in Arid4b knockdown cells. Consistent with our genetic analysis and in vivo experiments in our mouse model system, ARID4B expression was also an independent predictor of distant metastasis-free survival in breast cancer patients with ER+ tumors. These studies support a causative role of ARID4B in metastatic progression of breast cancer.


Salt-inducible kinase 2 regulates energy metabolism in rats with cerebral ischemia-reperfusion.
To investigate the effects of salt-inducible kinase 2 (SIK2) on energy metabolism in rats with cerebral ischemia-reperfusion. Adult SD male rats were divided into 5 groups: sham group, ischemia group, reperfusion group, adenovirus no-load group, and SIK2 overexpression group with 5 animals in each group. The middle cerebral artery occlusion (MCAO) was induced with the modified Zea-Longa line thrombus method to establish the cerebral ischemia reperfusion model. Eight days before the MCAO, SIK2 overexpression was induced by injecting 7 μL adenovirus in the right ventricle, then MCAO was performed for followed by reperfusion HE staining was used to observe the pathological changes of cerebral tissue in rats; TTC staining was used to observe the volume of cerebral infarct. The levels of adenosine triphosphate (ATP) and adenosine diphosphate (ADP) in rat brain tissue were detected by ELISA; the levels of SIK2 and hypoxia-inducible factor 1α (HIF-1α) in the rat brain tissues were detected by RT-qPCR and Western blotting. Compared with the sham group, SIK2 level was decreased in the ischemia group, and it was further declined in the reperfusion group (<0.05). Compared with the sham group and ischemic group, the pathological injury in reperfusion group were more severe, and the infarct size was larger; compared with the reperfusion group and adenovirus no-load group, the pathological injury of the SIK2 overexpression group was milder, and the infarct size is less. Compared with the sharn group, HIF-1α was increased in both ischemia group and reperfusion group, especially in ischemia group (all <0.05); HIF-1α level in the SIK2 overexpression group was higher than that in the reperfusion group and adenovirus no-load group (all <0.05). ATP level in ischemia group and reperfusion group was lower than that in the sham group, and the reperfusion group decreased more significantly than the ischemia group (<0.05); ADP content was increased in the ischemia and reperfusion group, and the ADP content in reperfusion group was significantly higher than that in the ischemia group (<0.05). ATP level in the SIK2 overexpression group was higher than that in the reperfusion group and adenovirus no-load group (all <0.05), and ADP was decreased in the SIK2 overexpression group (all <0.05). SIK2 can up-regulate the ATP level and down-regulate the ADP level in rat brain tissue and alleviate cerebral ischemia-reperfusion injury by increase the level of HIF-1α.


An Anthropometric Study of Bimalleolar Breadth and its Relationship with Stature on Bangladeshi Garo People.
A cross sectional descriptive study was conducted at different areas of Mymensingh (Haluaghat, Vatikashor and Kachijhuly) from July 2015 to June 2016 on 101 Bangladeshi Garo people. Among them 60 were male and 41 were female. Sample collection was done by nonrandom purposive sampling technique. Mixed ethnicity and any kind of foot deformity resulting either from congenital or physical injury were excluded to construct standard measurement for Garo ethnicity. Bimalleolar breadth was measured using slide calipers. The subjects were asked to stand with weight distributed equally on both feet. The legs were perpendicular to the feet. The maximum right and left bimalleolar breadth for male was found 8.32cm and 8.34cm respectively; minimum was 5.42cm and 5.43cm respectively. In case of female maximum right and left bimalleolar breadth was 9.63cm and 9.64cm respectively and minimum was 5.41cm for both feet. In this study, difference of mean bimalleolar breadth of male and female were statistically analyzed by using students unpaired 't' test which was highly significant. Correlation was done with stature and found significant in case of male but non-significant in case of female.


Detection of electrophoretic heterogeneity of serum beta 2-microglobulin in chronic renal failure.
To determine the metabolic abnormality of serum beta 2-microglobulin (beta 2m) from patients with chronic renal failure, electrophoretic heterogeneity of beta 2m (novel beta 2m) was examined by analyzing 10 microliters or 50 microliters serum samples on immunoblotting using anti beta 2m serum after two dimensional electrophoresis or by chromatofocusing. Novel beta 2m had a lower molecular weight and a higher acidic isoelectric point. The serum levels of beta 2m might be dependent on the dialysis duration. Changes of conformation or amino acid composition in native beta 2m might occur in patients with chronic renal failure, and these changes may begin prior to the initiation of dialysis.


Comparison of the effect of lecture and blended teaching methods on students' learning and satisfaction.
Blended learning, a new approach in educational planning, is defined as an applying more than one method, strategy, technique or media in education. Todays, due to the development of infrastructure of Internet networks and the access of most of the students, the Internet can be utilized along with traditional and conventional methods of training. The aim of this study was to compare the students' learning and satisfaction in combination of lecture and e-learning with conventional lecture methods. This quasi-experimental study is conducted among the sophomore students of Public Health School, Tehran University of Medical Science in 2012-2013. Four classes of the school are randomly selected and are divided into two groups. Education in two classes (45 students) was in the form of lecture method and in the other two classes (48 students) was blended method with e-Learning and lecture methods. The students' knowledge about tuberculosis in two groups was collected and measured by using pre and post-test. This step has been done by sending self-reported electronic questionnaires to the students' email addresses through Google Document software. At the end of educational programs, students' satisfaction and comments about two methods were also collected by questionnaires. Statistical tests such as descriptive methods, paired t-test, independent t-test and ANOVA were done through the SPSS 14 software, and p≤0.05 was considered as significant difference. The mean scores of the lecture and blended groups were 13.18±1.37 and 13.35±1.36, respectively; the difference between the pre-test scores of the two groups was not statistically significant (p=0.535). Knowledge scores increased in both groups after training, and the mean and standard deviation of knowledge scores of the lectures and combined groups were 16.51±0.69 and 16.18±1.06, respectively. The difference between the post-test scores of the two groups was not statistically significant (p=0.112). Students' satisfaction in blended learning method was higher than lecture method. The results revealed that the blended method is effective in increasing the students' learning rate. E-learning can be used to teach some courses and might be considered as economic aspects. Since in universities of medical sciences in the country, the majority of students have access to the Internet and email address, using e-learning could be used as a supplement to traditional teaching methods or sometimes as educational alternative method because this method of teaching increases the students' knowledge, satisfaction and attention.


Noradrenergic activity is associated with response to pindolol in aggressive Alzheimer's disease patients.
Loss of noradrenergic (NE) neurones in the locus ceruleus and compensatory changes in NE activity have been described in Alzheimer's disease (AD), but have never been linked to treatment. The hypothesis of this study was that central NE responsivity would predict aggression response to treatment with a NE medication, pindolol. Fifteen institutionalized AD subjects [Mini-Mental State Examination (MMSE), mean 3.3 +/- 4.6] with significant behavioural disturbances (Neuropsychiatric Inventory Score, mean 30.6 +/- 14.6) were studied. Growth hormone (GH) response to clonidine challenge (5 microg/kg) was used as a measure of central NE responsivity. Subjects were then randomized to 7 weeks of treatment with pindolol, maximum dose 20 mg b.i.d., or an identical placebo capsule in a cross-over design. The primary outcome measure was change on the retrospective Overt Aggression Scale (r-OAS). Five of 11 completers (45%) had decreased total r-OAS scores. There was significant improvement noted on the r-OAS verbal aggression subscale (paired t = -2.5, p = 0.03) compared to placebo, but not r-OAS total. Higher baseline aggression, higher MMSE and lower GH response predicted improvement in aggression, accounting for 82% of the variance (r = 0.91, F = 10.5, p = 0.006). Changes in NE responsivity, as reflected by a blunted GH response to clonidine challenge and more severe aggression, were associated with better response to the NE agent pindolol. Individual patient characteristics, including underlying neurotransmitter changes, may be useful for predicting response to therapy.


Dynamic Lone Pairs and Fluoride-Ion Disorder in Cubic-BaSnF4.
Introducing compositional or structural disorder within crystalline solid electrolytes is a common strategy for increasing their ionic conductivity. (M,Sn)F2 fluorites have previously been proposed to exhibit two forms of disorder within their cationic host frameworks: occupational disorder from randomly distributed M and Sn cations and orientational disorder from Sn(II) stereoactive lone pairs. Here, we characterize the structure and fluoride-ion dynamics of cubic BaSnF4, using a combination of experimental and computational techniques. Rietveld refinement of the X-ray diffraction (XRD) data confirms an average fluorite structure with {Ba,Sn} cation disorder, and the 119Sn Mössbauer spectrum demonstrates the presence of stereoactive Sn(II) lone pairs. X-ray total-scattering PDF analysis and ab initio molecular dynamics simulations reveal a complex local structure with a high degree of intrinsic fluoride-ion disorder, where 1/3 of fluoride ions occupy octahedral "interstitial" sites: this fluoride-ion disorder is a consequence of repulsion between Sn lone pairs and fluoride ions that destabilizes Sn-coordinated tetrahedral fluoride-ion sites. Variable-temperature 19F NMR experiments and analysis of our molecular dynamics simulations reveal highly inhomogeneous fluoride-ion dynamics, with fluoride ions in Sn-rich local environments significantly more mobile than those in Ba-rich environments. Our simulations also reveal dynamical reorientation of the Sn lone pairs that is biased by the local cation configuration and coupled to the local fluoride-ion dynamics. We end by discussing the effect of host-framework disorder on long-range diffusion pathways in cubic BaSnF4.


A rapid increase in the level of binding protein (BiP) is accompanied by synthesis and degradation of storage proteins in pumpkin cotyledons.
The binding protein (BiP) has been implicated in cotranslational folding of nascent polypeptides, and in the recognition and disposal of aberrant polypeptides. To elucidate the involvement of BiP in the biosynthesis of vacuolar proteins, we have characterized the protein in pumpkin cotyledons during seed maturation and seedling growth. Isolated microsomes from maturing pumpkin cotyledons contained a significant amount of BiP, protein-disulfide isomerase and calreticulin. We have purified a 70-kDa protein; sequences of the N-terminus and internal fragments of this protein exhibited a high identity to the sequence of soybean. Immunoblot analysis with specific antibodies raised against the purified BiP showed that the amount of BiP in a cotyledon increased markedly at the middle stages and then decreased. The increase was accompanied by the synthesis of storage proteins and the development of the endoplasmic reticulum in the cotyledons at the middle stage of seed maturation. Most of these storage proteins degraded dramatically between 2 and 5 days after seed germination, and the degradation was also accompanied by a rapid increase in the level of BiP. Subcellular fractionation of the 4-day-old cotyledons showed a high accumulation of BiP in the endoplasmic reticulum. It is possible that BiP might be involved in the synthesis of seed storage proteins during maturation and in the synthesis of hydrolytic enzymes responsible for the degradation of the storage proteins during seed germination.


AIDS retrovirus antibodies in hemophiliacs treated with factor VIII or factor IX concentrates, cryoprecipitate, or fresh frozen plasma: prevalence, seroconversion rate, and clinical correlations.
Antibodies to the AIDS retrovirus, specifically to human T cell lymphotropic virus, type III, and AIDS-associated retrovirus, were detected with increasing prevalence in a population of 190 hemophiliacs from western Pennsylvania between 1981 and 1984: 7.7% in 1981, 20.0% in 1982, 45.5% in 1983, and 62.5% in 1984. The seropositive included approximately three fourths of those receiving factor VIII concentrate, nearly one third of those receiving factor IX concentrate, nearly one fifth of those receiving cryoprecipitate, and none of those receiving fresh frozen plasma. The seroconversion rate, determined on 43 seropositive hemophiliacs from this group who were serially sampled, was 0% in 1977, 4.7% in 1978, 4.9% in 1979, 2.6% in 1980, 10.5% in 1981, 52.9% in 1982, 87.5% in 1983, and 100% in 1984. Of 27 seropositive for three or more years (since 1982 or before), four (15%) have developed AIDS and seven (26%), diffuse lymphadenopathy (ARC); of 16 seropositive for less than three years, none has developed AIDS and three (19%) have developed ARC. The mean time from seroconversion to onset of ARC, 0.8 +/- 0.2 years (SEM), was shorter (P less than .001) than the time to onset of AIDS, 4.1 +/- 0.6 years. These findings confirm the widespread presence of AIDS retrovirus and support the association of these retroviruses with the acquired immunodeficiency syndrome and related conditions.


Circumferential fusion for cervical kyphotic deformity.
The treatment of cervical kyphotic deformity is challenging. Few prior reports have examined combined anterior/posterior correction methods, and fusion rates and standardized outcomes are rarely cited in literature examining these techniques. The authors present their midterm results with cervical kyphosis correction. The authors retrospectively reviewed the charts of 30 patients with cervical kyphotic deformity who underwent circumferential spine surgery between 2001 and 2007. The causes of the deformity included chronic fracture in 17 patients, degenerative disease in 10, and tumor in 3. Anterior procedures included discectomies and corpectomies/osteotomies at 1 or more levels with fusion. Posterior operations included decompression and/or osteotomies with lateral mass or pedicle fixation. Preoperative and postoperative Ishihara kyphosis indices, modified Japanese Orthopaedic Association (mJOA) scores, and Nurick grades were analyzed. Arthrodesis was assessed via dynamic radiographs, and CT scans were used to assess fusion in questionable cases. One patient was lost to follow-up. Two patients died within 1 month of surgery. The follow-up period in the remaining 27 patients ranged from 1 to 6.4 years (mean 2.6 years). Ishihara indices improved from a preoperative mean of -17.7 to a postoperative mean of +11.4. The mean Nurick grades improved from 3.2 preoperatively to 1.3 postoperatively. The mJOA scores improved from a preoperative mean of 10 to 15 postoperatively. All surviving patients who underwent follow-up showed postoperative fusion except 1 patient with renal failure and osteoporosis (95% fusion rate). The overall rate of complications (major and minor) was 33.3%. In cases of cervical kyphosis, management with decompression, osteotomy, and stabilization from both anterior and posterior approaches can restore cervical lordosis. Furthermore, such surgical techniques can produce measurable improvements in neurological function (as measured with Nurick grades and mJOA scores) and achieve high fusion rates. However, there is a significant rate of complications.


Wavelength Selection Method Based on Differential Evolution for Precise Quantitative Analysis Using Terahertz Time-Domain Spectroscopy.
Quantitative analysis of component mixtures is an important application of terahertz time-domain spectroscopy (THz-TDS) and has attracted broad interest in recent research. Although the accuracy of quantitative analysis using THz-TDS is affected by a host of factors, wavelength selection from the sample's THz absorption spectrum is the most crucial component. The raw spectrum consists of signals from the sample and scattering and other random disturbances that can critically influence the quantitative accuracy. For precise quantitative analysis using THz-TDS, the signal from the sample needs to be retained while the scattering and other noise sources are eliminated. In this paper, a novel wavelength selection method based on differential evolution (DE) is investigated. By performing quantitative experiments on a series of binary amino acid mixtures using THz-TDS, we demonstrate the efficacy of the DE-based wavelength selection method, which yields an error rate below 5%.


Therapeutic Effects of Breviscapine in Cardiovascular Diseases: A Review.
Breviscapine is a crude extract of several flavonoids of Erigeron breviscapus (Vant.) Hand.-Mazz., containing more than 85% of scutellarin, which has been traditionally used in China as an activating blood circulation medicine to improve cerebral blood supply. Accumulating evidence from various in vivo and in vitro studies has shown that breviscapine exerts a broad range of cardiovascular pharmacological effects, including vasodilation, protection against ischaemia/reperfusion (I/R), anti-inflammation, anticoagulation, antithrombosis, endothelial protection, myocardial protection, reduction of smooth muscle cell migration and proliferation, anticardiac remodeling, antiarrhythmia, blood lipid reduction, and improvement of erectile dysfunction. In addition, several clinical studies have reported that breviscapine could be used in conjunction with Western medicine for cardiovascular diseases (CVDs) including coronary heart disease, myocardial infarction, hypertension, atrial fibrillation, hyperlipidaemia, viral myocarditis, chronic heart failure, and pulmonary heart disease. However, the protective effects of breviscapine on CVDs based on experimental studies along with its underlying mechanisms have not been reviewed systematically. This paper reviewed the underlying pharmacological mechanisms in the cardioprotective effects of breviscapine and elucidated its clinical applications.


Diversity of Asian skin: A review on skin biophysical properties.
Asian is home to dozens of different ethnic groups that are characterised by fascinating social and cultural variations. Unfortunately, existing literature on the skin properties of Asians tends to group this diverse population solely based on skin colour, perpetuating the misconception and stereotype that all Asian skin is the same. While Asia is one of the largest continents in the world, the difference in the geographical location and climate have long shaped the population into various ethnic groups with significant differences in the collective and diverse customs, traditions, cultures and living habits. The diverse ethnic groups in this region hint us that their skin biophysical characteristics can be very different from each other. This review features the profiling of the distinctive skin biophysical properties of Asians. We learn more about the different ethnic groups in Asia and acknowledge the unique skin biophysical properties even from the same country.


Evidence for highly p-type doping and type II band alignment in large scale monolayer WSe2/Se-terminated GaAs heterojunction grown by molecular beam epitaxy.
Two-dimensional materials (2D) arranged in hybrid van der Waals (vdW) heterostructures provide a route toward the assembly of 2D and conventional III-V semiconductors. Here, we report the structural and electronic properties of single layer WSe2 grown by molecular beam epitaxy on Se-terminated GaAs(111)B. Reflection high-energy electron diffraction images exhibit sharp streaky features indicative of a high-quality WSe2 layer produced via vdW epitaxy. This is confirmed by in-plane X-ray diffraction. The single layer of WSe2 and the absence of interdiffusion at the interface are confirmed by high resolution X-ray photoemission spectroscopy and high-resolution transmission microscopy. Angle-resolved photoemission investigation revealed a well-defined WSe2 band dispersion and a high p-doping coming from the charge transfer between the WSe2 monolayer and the Se-terminated GaAs substrate. By comparing our results with local and hybrid functionals theoretical calculation, we find that the top of the valence band of the experimental heterostructure is close to the calculations for free standing single layer WSe2. Our experiments demonstrate that the proximity of the Se-terminated GaAs substrate can significantly tune the electronic properties of WSe2. The valence band maximum (VBM, located at the K point of the Brillouin zone) presents an upshift of about 0.56 eV toward the Fermi level with respect to the VBM of the WSe2 on graphene layer, which is indicative of high p-type doping and a key feature for applications in nanoelectronics and optoelectronics.


On pedagogy.
Humans are adapted to spontaneously transfer relevant cultural knowledge to conspecifics and to fast-learn the contents of such teaching through a human-specific social learning system called 'pedagogy' (Csibra & Gergely, 2006). Pedagogical knowledge transfer is triggered by specific communicative cues (such as eye-contact, contingent reactivity, the prosodic pattern of 'motherese', and being addressed by one's own name). Infants show special sensitivity to such 'ostensive' cues that signal the teacher's communicative intention to manifest new and relevant knowledge about a referent object. Pedagogy offers a novel functional perspective to interpret a variety of early emerging triadic communicative interactions between adults and infants about novel objects they are jointly attending to. The currently dominant interpretation of such triadic communications (mindreading) holds that infants interpret others' object-directed manifestations in terms of subjective mental states (such as emotions, dispositions, or intentions) that they attribute to the other person's mind. We contrast the pedagogical versus the mindreading account in a new study testing 14-month-olds' interpretation of others' object-directed emotion expressions observed in a communicative cueing context. We end by discussing the far-reaching implications of the pedagogical perspective for a wide range of early social-cognitive competences, and for providing new directions for future research on child development.


Reaping benefits from intellectual capital.
The wealth and value of organizations are increasingly based on intellectual capital. Although acquiring talented individuals and investing in employee learning adds value to the organization, reaping the benefits of intellectual capital involves translating the wisdom of employees into reusable and sustained actions. This requires a culture that creates employee commitment, encourages learning, fosters sharing, and involves employees in decision making. An infrastructure to recognize and embed promising and best practices through social networks, evidence-based practice, customization of innovations, and use of information technology results in increased productivity, stronger financial performance, better patient outcomes, and greater employee and customer satisfaction.


Treatment of psychiatric symptoms associated with neurosyphilis.
There is currently no consensus on how to manage the psychiatric manifestations of neurosyphilis, despite the resurgence of this condition. The authors present five cases of neurosyphilis in inpatient psychiatric settings that manifested with predominantly psychiatric symptoms and were appropriately diagnosed and successfully treated with psychotropic medication concurrent with antibiotic therapy. A review of available data reveals that presently there are no specific guidelines to address psychiatric symptomatology in neurosyphilis. The authors see merit in the prudent use of psychotropic medication to achieve symptom stabilization.


Directing Uphill Strand Displacement with an Engineered Superhelicase.
The ability to finely tune reaction rates and binding energies between components has made DNA strand displacement circuits promising candidates to replicate the complex regulatory functions of biological reaction networks. However, these circuits often lack crucial properties, such as signal turnover and the ability to transiently respond to successive input signals that require the continuous input of chemical energy. Here, we introduce a method for providing such energy to strand displacement networks in a controlled fashion: an engineered DNA helicase, Rep-X, that transiently dehybridizes specific DNA complexes, enabling the strands in the complex to participate in downstream hybridization or strand displacement reactions. We demonstrate how this process can direct the formation of specific metastable structures by design and that this dehybridization process can be controlled by DNA strand displacement reactions that effectively protect and deprotect a double-stranded complex from unwinding by Rep-X. These findings can guide the design of active DNA strand displacement regulatory networks, in which sustained dynamical behavior is fueled by helicase-regulated unwinding.


Histological Study of the Effect of Aqueous Extract of the Beetle Cocoon on Liver Tissue of Male Mice.
Traditional medicine has been long used to prevent and/or treat diseases worldwide based on a wealth of experiences, principles, and beliefs in different cultures. Among the extracts used in traditional medicine, we can refer to the aqueous beetle cocoon extract of Larinus maculates popularly known as Tihan in Iraq. To determine the histological effect of this extract on mice liver tissue, the animals were assigned to four groups (n=5) treated with (150,200,400) mg/kg of Cocoon aqueous extract of Larinus maculates for 14 days, respectively. Histology and immunohistochemistry test was performed to evaluate changes in liver tissue and tumor necrosis factor alpha (TNF-α) levels.The results showed various pathological dose-depended changes in the liver tissue, including infiltrations, congestion, and vacuolation, along with some dead cells; moreover, necrotic hepatocytes were observed in the liver of highly concentrated treatment group (400 mg kg-1). In addition, the TNF-α level in the liver tissue was elevated by the increased concentration of the extract. The immunohistochemistry result of positive reaction to TNF-α revealed high reaction in the liver tissue of mice treated with 200 mg kg-1 and 400 mg kg-1, as compared to the control group. Furthermore, as evidenced by the obtained results, changes in hepatocytes and the severity of pathological changes in the liver depends on the concentration of the extract of Larinus maculates.


Iron depletion with a novel apheresis system in patients with hemochromatosis.
Phlebotomy represents the standard treatment option for iron overload in hemochromatosis (HC). Recently, red blood cell (RBC) apheresis has increasingly been used to remove iron. In this study we evaluated the depletion program of the newly developed Spectra Optia device. Adult male patients (n = 11) with HC were RBC depleted with the Spectra Optia device (Terumo BCT). In total, 24 procedures were performed. A volume of 300 to 550 mL of RBCs was withdrawn per single treatment. No significant adverse events were recorded. A median blood volume of 857.3 ± 23.3 mL was processed. The median procedure time was 12.0 ± 0.4 minutes. The mean reduction of Hct value in each procedure was approximately 6% (Hct pre 42.6 ± 0.5% vs. Hct post 36.6 ± 0.6%) and iron removed per procedure was 405.2 ± 23.3 mg. The Spectra Optia device proved to be highly efficient in depleting RBCs in HC patients and allows for short procedure time. The Optia device can be safely used in this clinical setting. We recommend its use in case of severe iron overload if rapid iron depletion needs to be achieved and in case of cardiac compromise due to less blood volume removed.


A nonlinear l(2)-stability analysis for two-species population dynamics with dispersal.
The nonlinear L(2)-stability (instability) of the equilibrium states of two-species population dynamics with dispersal is studied. The obtained results are based on (i) the rigorous reduction of the L(2)-nonlinear stability to the stability of the zero solution of a linear binary system of ODEs and (ii) the introduction of a particular Liapunov functional V such that the sign ofdV/dt along the solutions is linked directly to the eigenvalues of the linear problem.


Analysis of vaginal delivery outcomes among pregnant women in Wuhan, China during the COVID-19 pandemic.
To study vaginal delivery outcomes and neonatal prognosis and summarize the management of vaginal delivery during the COVID-19 pandemic. A retrospective analysis of medical records and comparison of vaginal delivery outcomes between 10 pregnant women with clinical diagnosis of COVID-19 and 53 pregnant women without COVID-19 admitted to Zhongnan Hospital of Wuhan University between January 20 and March 2, 2020. Results of laboratory tests, imaging tests, and SARS-CoV-2 nucleic acid tests were also analyzed in neonates delivered by pregnant women with clinical diagnosis of COVID-19. There were no significant differences in gestational age, postpartum hemorrhage, and perineal resection rates between the two groups. There were no significant differences in birth weight of neonates and neonatal asphyxia rates between the two groups. Neonates delivered by pregnant women with clinical diagnosis of COVID-19 tested negative for SARS-CoV-2 infection. Under the premise of full evaluation of vaginal delivery conditions and strict protection measures, pregnant women with ordinary type COVID-19 can try vaginal delivery without exacerbation of COVID-19 and without increasing the risk of SARS-CoV-2 infection in neonates.


Xyloglucan, hibiscus and propolis for the prevention of urinary tract infections: results of in vitro studies.
To assess the properties of a medical device containing xyloglucan, propolis and hibiscus to create a bioprotective barrier to avoid the contact of uropathogenic Escherichia coli strains on cell walls in models of intestinal (CacoGoblet) and uroepithelial (RWPE-1) cells (derived from normal human prostate epithelium). Two uropathogenic E. coli strains (expressing type 1 fimbriae and P fimbriae) were used to assess, by electronic microscopy and ELISA, the barrier properties of the medical device. The antimicrobial activity was assessed in broth dilution assays. The three components (xyloglucan, propolis and hibiscus) did not alter E. coli cell integrity in intestinal and uroepithelial cell models and were devoid of antibacterial activity. The three components avoided bacterial contact in both cell monolayers. The nonpharmacological barrier properties of xyloglucan, propolis and hibiscus confirm the role of the medical device for the management of urinary tract infections.


Beryllium-Induced Conversion of Aldehydes.
Aldehydes play a key role in the human metabolism. Therefore, it is essential to know their reactivity with beryllium compounds in order to assess its effects in the body. The reactivity of simple aldehydes towards beryllium halides (F, Cl, Br, I) was studied through solution and solid-state techniques and revealed distinctively different reactivities of the beryllium halides, with BeF2 being the least and BeI2 the most reactive. Rearrangement and aldol condensation reactions were observed and monitored by in situ NMR spectroscopy. Crystal structures of various compounds obtained by Be2+ -catalyzed cyclization, rearrangement, and aldol addition reactions or ligation of beryllium halides have been determined, including unprecedented one-dimensional BeCl2 chains and the first structurally characterized example of an 1-iodo-alkoxide. Long-term studies showed that only aldehydes without a β-H can form stable beryllium complexes, whereas other aldehydes are oligo- and polymerized or decomposed by beryllium halides.


Serum interleukin-6 levels correlate with malnutrition and survival in patients with advanced non-small cell lung cancer.
To investigate the level of interleukin-6 in advanced non-small cell lung cancer and to analyze the relationship with malnutrition and survival. Seventy-one newly diagnosed advanced non-small cell lung cancer patients were enrolled in this prospective study. Malnutrition was defined by using subjective global assessment. Performance status was assessed by the Karnofsky scale. Serum levels of albumin, transferrin, C-reactive protein, lymphocytes/mm3, lactate dehydrogenase and growth hormone were determined before treatment. The patients were followed, and the factors affecting survival were analyzed. The mean follow-up after diagnosis was 180 days. IL-6 levels increased in 48 (68%) of 71 patients. According to the subjective global assessment, 28 (39%) patients were well nourished and 43 (61%) were malnourished. Of the 43 malnourished patients, 29 (41%) were moderately malnourished or suspected of being malnourished and 14 (20%) were severely malnourished. The IL-6 level was related to impaired performance status (P = 0.0001), severe malnutrition (P = 0.004), increased C-reactive protein (P = 0.013), higher growth hormone (P = 0.025) and transferrin (P = 0.03) levels. On univariate analysis, impaired performance status, moderate and severe malnutrition, decreased serum albumin and transferrin, a raised IL-6 and lactate dehydrogenase levels were the significant prognostic factors for survival. Multivariate analysis indicated that a raised IL-6, severe malnutrition and a low serum level of albumin were independent prognostic factors for survival in patients with advanced non-small cell lung cancer. IL-6 secretion may play a role in the pathophysiology of malnutrition in advanced lung cancer. Results show a relation between elevated IL-6 serum levels and malnutrition, poor performance status, acute phase response and shorter survival in patients affected by advanced non-small cell lung cancer.


Modern Data Acquisition Approaches in Proteomics Based on Dynamic Instrument Control.
Traditionally, data acquisition in mass spectrometry-based proteomics is directed by user-defined parameters and relatively simple decision making, such as selection of the highest MS1 peaks for fragmentation. In recent years, access to two-way-communication with instrument codebases has led to a surge in algorithms instructing more complex decision processes on-the-fly. A closer matching between the time windows for monitoring peptides in targeted proteomics and their actual chromatographic elution peaks has been addressed through dynamic retention time scheduling and through triggered acquisition. Strategies based on real-time database searching and spectral matching have, among others, been used to adjust acquisition parameters for selected peptides for improved quantitative accuracy. While initial studies were mainly performed on a proof-of-concept level, dynamic acquisition approaches recently became more broadly available through software and increasing integration into standard instrument control and are likely to transform the field of proteomics in the coming years.


Towards another major reform? Implications of the Swedish pension scheme of 1913.
The welfare systems established before or shortly after the Second World War are presently on trial. Changes of strategy appear to be as necessary as they did in Sweden in 1913, but the circumstances are definitely different. One crucial difference is that since 1913 the State has delivered solemn promises which are intended to materialize a life-time from now, but life-times tend to grow longer with each year that passes! The Swedish pension reform of 1913 was overdue, but the next one may prove harder to achieve. Those promises cannot be withdrawn. They form a major element in the present situation, perhaps the one that will prove most fatal to the future of the welfare state and its elderly.


Iron in multiple myeloma.
Multiple myeloma is a non-curable B-cell malignancy in which iron metabolism plays an important role. Patients with this disorder almost universally suffer from clinically significant anemia, which is often symptomatic, and which is due to impaired iron utilization. Recent studies have indicated that the proximal cause of dysregulated iron metabolism and anemia in these patients is cytokine-induced upregulation of hepcidin expression. Malignant myeloma cells are dependent on an increased influx of iron, and therapeutic efforts are being made to target this requirement. The studies detailing the characteristics and biochemical abnormalities in iron metabolism causing anemia and the initial attempts to target iron therapeutically are described in this review.


Bone loss in C57BL/6J-OlaHsd mice, a substrain of C57BL/6J carrying mutated alpha-synuclein and multimerin-1 genes.
The inbred mouse strain C57BL/6 is commonly used for the generation of transgenic mouse and is a well established strain in bone research. Different vendors supply different substrains of C57BL/6J as wild-type animals when genetic drift did not incur any noticeable phenotype. However, we sporadically observed drastic differences in the bone phenotype of "WT" C57BL/6J mice originating from different labs and speculated that these variations are attributable, at least in part, to the variation between C57BL/6J substrains, which is often overlooked. C57BL/6J-OlaHsd is a commonly used substrain that despite a well defined deletion in the alpha-synuclein (Snca) and multimerin-1 (Mmrn1) genes, was reported to display no obvious phenotype and is used as WT control. Here, we compared the bone phenotype of C57BL/6J-OlaHsd (6J-OLA) to C57BL/6J-RccHsd (6J-RCC) and to the original C57BL/6J (6J-JAX). Using μCT analysis, we found that 6J-OLA mice display a significantly lower trabecular bone mass compared to 6J-RCC and 6J-JAX. PCR analysis revealed that both the Snca and Mmrn1 genes are expressed in bone tissue of 6J-RCC animals but not of 6J-OLA mutants, suggesting either one or both genes play a role in bone metabolism. In vitro analysis demonstrated increase in osteoclasts number and decreased osteoblast mineralization in cells derived from 6J-OLA compared with 6J-RCC. Our data may shed light on unexplained differences in basal bone measurements between different research centers and reiterate the importance of specifying the exact substrain type. In addition, our findings describe the physiological role for Mmrn1 and/or Snca in bone remodeling.


The Development and Effect of Systemic Hypertension on Clinical and Radiological Outcome in Adult Moyamoya Angiopathy Following Revascularization Surgery: Experience of a Single European Institution.
Patients with Moyamoya Angiopathy (MMA) display structurally altered vessels with decreased cerebral autoregulatory capacity, so aggressive lowering of systemic hypertension may aggravate ischemic symptoms, whereas uncontrolled hypertension may promote hemorrhage. This study provides an in-depth analysis of the role of hypertension in adult MMA patients including long-term analysis of clinical and radiological development. In this single-center retrospective analysis of 137 adult MMA patients with 206 surgically treated hemispheres angiographic images, clinical/operative data were reviewed and scored. Univariate Cox-regression analysis was performed to evaluate hypertension as a predictor for negative angiographic and clinical outcomes following revascularization surgery. A total of 50% of patients were being treated for hypertension prior to the first surgery. Patients with and without hypertension did not differ in terms of age, gender, diagnosis, symptom onset or disease severity (Berlin and Suzuki Grades). Although hypertension did not statistically significantly affect postoperative collaterals, moyamoya vessels or STA-MCA bypass patency, patients with hypertension showed higher rates of bypass patency and better bypass filling compared to those without hypertension. No significant differences in adverse events were found in patients with and without systemic hypertension and the presence of systemic hypertension was not found to predict negative clinical or radiological outcomes. In conclusion, the rate of systemic hypertension in MMA patients appears to be higher than the general population; however, this is not associated with an increased risk of postoperative complications or negative angiographic development following revascularization procedures. Systemic hypertension may also positively influence the rate of bypass patency and filling following revascularization procedures.


Predicting binge-drinking behaviour using an extended TPB: examining the impact of anticipated regret and descriptive norms.
To investigate the utility of an extended Theory of Planned Behaviour (TPB), including descriptive norms and anticipated regret, in predicting binge-drinking intentions and behaviour. A total of 178 undergraduates completed a questionnaire containing measures of TPB variables, descriptive norms, anticipated regret, and previous binge-drinking behaviour. One week later, 104 students completed a measure of binge-drinking behaviour. Hierarchical regression demonstrated that attitudes (beta = 0.30, P < 0.001) and anticipated regret (beta = 0.47, P < 0.001) were significant predictors of intentions, with the final equation accounting for 58% of the variance. Hierarchial regression found that intentions (beta = -0.21, P < 0.05) and previous binge-drinking behaviour (beta = 0.36, P < 0.01) predicted current drinking behaviour, accounting for 33% of the variance. The study suggests that modifying attitudes and inducing regret may be effective strategies for reducing binge-drinking intentions among undergraduates, which should reduce subsequent binge-drinking behaviour.


Patency and transmission of Filaroides hirthi infection.
Filaroides hirthi lungworm infection was diagnosed by the recovery of 1st-stage larvae from the faeces of dogs with heavy, artificially induced infections using zinc sulphate flotation. Diagnosis of low-grade natural infections was infrequently achieved. Zinc sulphate flotation was demonstrated to be about 100 times as efficient as the Baermann technique in concentrating F. hirthi larvae from dog faeces. Larvae recovered from faeces proved to be infective when fed to a pup and it was concluded that F. hirthi infection can be transmitted directly and immediately by fresh faecal contamination. Mongrel dogs of diverse ancestry were readily infected by feeding 1st-stage larvae from lung tissue. Thus, F. hirthi infection was shown not to be limited to the Beagle breed by biological restrictions. The observations that 1st-stage larvae pass through the alimentary tract on their way out of the body and that larvae are found in the mesenteric lymph nodes long after a single exposure to infection support the hypothesis that there is an autogenous re-infection of the host by a proportion of these larvae.


Behavioral effects of the systemically active delta opioid agonist BW373U86 in rhesus monkeys.
The behavioral effects of (+-)-4-((alpha R*)-alpha-((2S*,5R*)-4-allyl-2,5-dimethyl-1-piperazinyl)-3- hydroxybenzyl)-N,N-diethylbenzamide dihydrochloride (BW373U86), a nonpeptidic, systemically active, delta opioid agonist, were examined in rhesus monkeys. BW373U86, the mu agonist alfentanil and the kappa agonist U69,593 [(5 alpha,7 alpha,8 beta)-(-)-N-methyl-N-(7-(1-pyrrolidinyl)-1-oxaspiro- (4,5)dec-8-yl)benzeneacetamide] all produced a dose-dependent suppression of response rates maintained under a fixed ratio 30 schedule of food presentation. The rate-suppressing effects of BW373U86 lasted 1 to 2 hr and were no longer apparent after 4 hr. The selective delta antagonist naltrindole (NTI) antagonized the effects of BW373U86 with relatively high potency (pKB = 6.5) and the antagonist effects of NTI against BW373U86 lasted approximately 4 hr. NTI was less potent in antagonizing alfentanil (pKB = 5.1) and the highest dose of NTI examined (10.0 mg/kg) did not antagonize U69,593. BW373U86 did not generalize to the discriminative stimulus effects of the mu agonist alfentanil or the kappa agonist ethylketocyclazocine. BW373U86 also did not produce antinociceptive effects in the warm-water tail-withdrawal procedure, significant respiratory depressant effects in monkeys breathing either air or 5% CO2 or reinforcing effects in a self-administration procedure. The highest dose of BW373U86 examined (1.78 mg/kg) produced convulsions in one monkey. The high relative potency of NTI to antagonize the rate-suppressing effects of BW373U86 was consistent with the characterization of BW373U86 as a systemically active, delta-selective agonist in rhesus monkeys. Under the conditions evaluated in the present study, the delta receptors to which BW373U86 binds do not appear to mediate antinociceptive, respiratory depressant or reinforcing effects in monkeys.


Integrated Stress Response as a Therapeutic Target for CNS Injuries.
Central nervous system (CNS) injuries, caused by cerebrovascular pathologies or mechanical contusions (e.g., traumatic brain injury, TBI) comprise a diverse group of disorders that share the activation of the integrated stress response (ISR). This pathway is an innate protective mechanism, with encouraging potential as therapeutic target for CNS injury repair. In this review, we will focus on the progress in understanding the role of the ISR and we will discuss the effects of various small molecules that target the ISR on different animal models of CNS injury.


Hodgkin's disease and pemphigus.
The second case of pemphigus associated with Hodgkin's disease is reported. Circulating pemphigus auto-antibodies were detected in this patient and cell-mediated (T cell) immunity was markedly depressed. It is postulated that this T-cell immunodepression predisposed the patient to the development of pemphigus.


Preferential use of unmutated immunoglobulin heavy variable region genes in Boxer dogs with chronic lymphocytic leukemia.
Human chronic lymphocytic leukemia (CLL) is a clinically heterogeneous disease, and immunoglobulin heavy variable region (IGHV) gene mutational status is an important prognostic marker. IGHV mutational status has not been previously examined in canine CLL. We sequenced the IGHV-D-J rearrangements from 55 canine patients with CLL, including 36 non-Boxer and 19 Boxer dogs. The majority of non-Boxers (75%) had mutated IGHV genes, whereas the majority of Boxers (79%) had unmutated IGHV genes. IGHV3-41 and IGHV3-67 gene usage was significantly higher in Boxers with CLL compared to non-Boxers. Additionally, 11 Boxers with large B-cell lymphoma and the normal IGHV repertoire of six control dogs (three Boxers and three non-Boxers) were sequenced. IGHV3-41 was preferentially used in Boxers with other forms of lymphoma and without lymphoproliferative disease. However, preferential use of unmutated IGHV genes was unique to Boxers with CLL, suggesting Boxers may be a valuable model to investigate unmutated CLL.