New Horizons for Phenotyping Behavior in Rodents: The Example of Depressive-Like Behavior.
The evolution of the field of behavioral neuroscience is significantly dependent on innovative disruption triggered by our ability to model and phenotype animal models of neuropsychiatric disorders. The ability to adequately elicit and measure behavioral parameters are the fundaments on which the behavioral neuroscience community establishes the pathophysiological mechanisms of neuropsychiatric disorders as well as contributes to the development of treatment strategies for those conditions. Herein, we review how mood disorders, in particular depression, are currently modeled in rodents, focusing on the limitations of these models and particularly on the analyses of the data obtained with different behavioral tests. Finally, we propose the use of new paradigms to study behavior using multidimensional strategies that better encompasses the complexity of psychiatric conditions, namely depression; these paradigms provide holistic phenotyping that is applicable to other conditions, thus promoting the emergence of novel findings that will leverage this field.


Comparison of Eustachian tube function measured by the microflow method and a new quantitative impedance method.
Eustachian tube function in 25 applicants for flight training was tested during simulated flights using two methods alternately; the integrating microflow method with a stationary pressure chamber, and a new quantitative impedance method in combination with a new mobile pressure chamber. All ears were tested by both methods. The results of the various tests did not differ significantly between methods. The reliability of the measurements was good and almost equal in both methods. Several practical advantages with the new impedance method in combination with the mobile pressure chamber make it preferable.


Development and initial validation of a novel thread design for nonlocking cancellous screws.
High failure rates have been associated with nonlocking cancellous screws with a typical buttress thread in patients with osteoporotic bone. This study aimed to develop a novel thread design and compare its fixation stability with that of a typical buttress thread. Nonlocking cancellous screws with a novel thread design (proximal flank angle of 120 degrees, a flat crest feature, a tip-facing undercut feature) and nonlocking cancellous screws with a typical buttress thread were manufactured using stainless steel. Fixation stabilities were evaluated individually by the axial pullout and lateral migration tests, and they were evaluated in pairs together with a dynamic compression plate in an osteoporotic bone substitute (10 PCF polyurethane foam per ASTM F1839) under cyclic craniocaudal and torsional loadings. Pullout strength and lateral migration resistance for the individual screw test and the force, torque, and number of cycles required to achieve specific displacement and torsion for the multi-screw test were comparatively analyzed between both screw types. A finite element analysis model was constructed to analyze the stress distributions in the bone tissue adjacent to the threads. The biomechanical test revealed the novel undercut thread had superior axial pullout strength, lateral migration resistance, and superior fixation stability when applied to a dynamic compression plate under cyclic craniocaudal loading and torsional loading than those in the typical buttress thread. The finite element analysis simulation revealed that the novel thread can distribute stress more evenly without high-stress concentration at the adjacent bone tissue when compared to that of a typical buttress thread.


Catalytic properties of MIL-101.
A very high catalytic activity in the cyanosilylation reaction was observed for MIL-101, a chromium based metal-organic framework; moreover, MIL-101 is also a remarkably stable support for palladium in hydrogenation reactions, with significantly higher activity than e.g. palladium on activated carbon.


How numbers mean: Comparing random walk models of numerical cognition varying both encoding processes and underlying quantity representations.
How do people derive meaning from numbers? Here, we instantiate the primary theories of numerical representation in computational models and compare simulated performance to human data. Specifically, we fit simulated data to the distributions for correct and incorrect responses, as well as the pattern of errors made, in a traditional "relative quantity" task. The results reveal that no current theory of numerical representation can adequately account for the data without additional assumptions. However, when we introduce repeated, error-prone sampling of the stimulus (e.g., Cohen, 2009) superior fits are achieved when the underlying representation of integers reflects linear spacing with constant variance. These results provide new insights into (i) the detailed nature of mental numerical representation, and, (ii) general perceptual processes implemented by the human visual system.


Pelvic exenteration.
Exenteration, or complete excision of the pelvic viscera, is an ultra-radical surgical procedure intended for curative treatment of the patient with advanced pelvic malignancy--primary or recurrent. At the time of introduction of this procedure, enthusiasm for its use was marred by the high incidence of serious surgical morbidity and mortality, which approached the five-year survival rate. With more careful physiological and psychological selection of patients, concentration of this kind of procedure in centres familiar with its use, improved urinary conduit techniques and careful attention to covering the pelvic floor with omentum and/or synthetic materials, the morbidity and mortality rate has been significantly reduced thus making exenteration a more acceptable treatment option to a wider spectrum of patients. More sophisticated haemodynamic monitoring, both intra- and postoperatively, intravenous hyperalimentation, prophylactic antibiotics and low-dose heparin are undoubtedly important adjuncts to the improvements in surgical technique and judgment. Psychosexual 'rehabilitation' in the broadest sense must be an integral part of patient care for those undergoing exenteration and in most instances necessitates involvement of the patient's partner. Exenteration has only a very limited role in palliation and all attempts should be made to avoid this procedure when cure is clearly not a possibility.


Template Matching and Matrix Profile for Signal Quality Assessment of Carotid and Femoral Laser Doppler Vibrometer Signals.
Background: Laser-Doppler Vibrometry (LDV) is a laser-based technique that allows measuring the motion of moving targets with high spatial and temporal resolution. To demonstrate its use for the measurement of carotid-femoral pulse wave velocity, a prototype system was employed in a clinical feasibility study. Data were acquired for analysis without prior quality control. Real-time application, however, will require a real-time assessment of signal quality. In this study, we (1) use template matching and matrix profile for assessing the quality of these previously acquired signals; (2) analyze the nature and achievable quality of acquired signals at the carotid and femoral measuring site; (3) explore models for automated classification of signal quality. Methods: Laser-Doppler Vibrometry data were acquired in 100 subjects (50M/50F) and consisted of 4-5 sequences of 20-s recordings of skin displacement, differentiated two times to yield acceleration. Each recording consisted of data from 12 laser beams, yielding 410 carotid-femoral and 407 carotid-carotid recordings. Data quality was visually assessed on a 1-5 scale, and a subset of best quality data was used to construct an acceleration template for both measuring sites. The time-varying cross-correlation of the acceleration signals with the template was computed. A quality metric constructed on several features of this template matching was derived. Next, the matrix-profile technique was applied to identify recurring features in the measured time series and derived a similar quality metric. The statistical distribution of the metrics, and their correlates with basic clinical data were assessed. Finally, logistic-regression-based classifiers were developed and their ability to automatically classify LDV-signal quality was assessed. Results: Automated quality metrics correlated well with visual scores. Signal quality was negatively correlated with BMI for femoral recordings but not for carotid recordings. Logistic regression models based on both methods yielded an accuracy of minimally 80% for our carotid and femoral recording data, reaching 87% for the femoral data. Conclusion: Both template matching and matrix profile were found suitable methods for automated grading of LDV signal quality and were able to generate a quality metric that was on par with the signal quality assessment of the expert. The classifiers, developed with both quality metrics, showed their potential for future real-time implementation.


Depression in Parkinson's disease: convergence from voxel-based morphometry and functional magnetic resonance imaging in the limbic thalamus.
Depression is the most frequent psychiatric disorder in Parkinson's disease (PD). Although evidence suggests that depression in PD is related to the degenerative process that underlies the disease, further studies are necessary to better understand the neural basis of depression in this population of patients. In order to investigate neuronal alterations underlying the depression in PD, we studied thirty-six patients with idiopathic PD. Twenty of these patients had the diagnosis of major depression disorder and sixteen did not. The two groups were matched for PD motor severity according to Unified Parkinson Disease Rating Scale (UPDRS). First we conducted a functional magnetic resonance imaging (fMRI) using an event-related parametric emotional perception paradigm with test retest design. Our results showed decreased activation in the left mediodorsal (MD) thalamus and in medial prefrontal cortex in PD patients with depression compared to those without depression. Based upon these results and the increased neuron count in MD thalamus found in previous studies, we conducted a region of interest (ROI) guided voxel-based morphometry (VBM) study comparing the thalamic volume. Our results showed an increased volume in mediodorsal thalamic nuclei bilaterally. Converging morphological changes and functional emotional processing in mediodorsal thalamus highlight the importance of limbic thalamus in PD depression. In addition this data supports the link between neurodegenerative alterations and mood regulation.


Neurosurgery and the Internet: a critical analysis and a review of available resources.
Thanks to the development of computers and telecommunication, the concept of communication is undergoing radical changes. Scientific collaboration among medical professionals has evolved rapidly in the last few years toward the use of Internet, a new tool which will change the world of health. It is impossible to predict at present where this new type of scientific collaboration will lead us, but what is certain is that in the next decade, the so-called electronic communities will be created and will develop at an extraordinary rate. The increase in the capacity of image processing in computers and in the rate of transmission of data over the net will make possible applications such as the remote medical visit, video conferences, surgical simulation or even remote virtual surgery. However, while some medical professionals are dreaming of this type of electronic communication in the future, others are using it right now, taking advantage of all of its benefits. In fact, electronic communities are already a reality, being accessible today, and not a future goal. Being inside or outside these communities will make the difference between health professionals. It is well worth therefore being in contact with these new fields so as not to miss the boat of technological development. We present a comprehensive listing of neurosurgical resources available on the Internet, and some ideas on the present and future applications of the Internet in the world of Health Care.


Dynamic changes in gene expression during in vitro differentiation of mouse embryonic stem cells.
The expression pattern of protein tyrosine kinases (PTK) and phosphatases (PTP) was determined during the first eight days of in vitro differentiation of mouse embryonic stem (ES) cells. DNA fingerprinting of catalytic domains amplified from cDNA revealed dynamic changes in expression of previously described genes. A novel PTP is expressed in undifferentiated ES cells, and is down-regulated during in vitro differentiation.


Evaluation and Optimization of Interface Force Fields for Water on Gold Surfaces.
The structure and dynamics of water at gold surfaces are important for a variety of applications, including lab on a chip and electrowetting. Classical molecular dynamics (MD) simulations are frequently used to investigate systems with water-gold interfaces, such as biomacromolecules in gold nanoparticle dispersions, but the accuracy of the simulations depends on the suitability of the force field. Density functional theory (DFT) calculations of a water molecule on gold were used as a benchmark to assess force field accuracy. It was found that Lennard-Jones potentials did not reproduce the DFT water-gold configurational energy landscape, whereas the softer Morse and Buckingham potentials allowed for a more accurate representation. MD simulations with different force fields exhibited rather different structural and dynamic properties of water on a gold surface. This emphasizes the need for experimental data and further effort on the validation of a realistic force field for water-gold interactions.


Valvular heart disease. Identifying and managing mitral and aortic lesions.
Evaluation and treatment of valvular heart disease (table 1) are in evolution. Echocardiography is the principal diagnostic tool. In general, mitral and aortic stenotic lesions warrant surgical treatment when symptoms appear. Such intervention is also indicated in symptomatic patients with a regurgitant mitral or aortic lesion. Some patients with regurgitant lesions require surgical treatment even before the onset of symptoms, such as when left ventricular dysfunction or dilatation supervenes. Surgical treatment of valvular lesions consists of repair or replacement, except in the case of mitral stenosis, where PBMC is a reasonable alternative. In general, medical therapy has a very limited role in the treatment of valvular heart disease. Severe aortic insufficiency is an exception. In such cases, afterload reduction has proved beneficial in the long-term prognosis.


Mono- to Octa-chlorinated PCDD/Fs in stack gas from typical waste incinerators and their implications on emission.
Mono- to octa-chlorinated dibenzo-p-dioxins and dibenzofurans (mono- to octa-CDD/Fs) were determined in 14 stack gas samples from two municipal solid waste incinerators and two medical waste incinerators. The total PCDD/F concentrations were 5.1-390 ng/Nm(3), and the mono- to trichlorinated homologues contributed 53.2-94.5% of the total concentrations. The homologue profiles were dominated by the MoCDF, ranged from 1.51 to 113.1 ng/Nm(3), and the proportion that each PCDF homologue group contributed to the total concentration decreased with increasing chlorination level. The toxic equivalent concentrations (I-TEQs) were 0.01-2.81 ng I-TEQ/Nm(3), with 2,3,4,7,8-PeCDF being the biggest contributor, at 30.6-60.0%. Correlations were found among the PCDD/PCDF ratios (D/F ratios), the degree of chlorination, and the TEQ. Stack gases with low I-TEQs had higher proportions of the less chlorinated homologues and lower D/F ratios, which could be attributed to the removal of the more chlorinated isomers by the air pollution control systems used by the incinerators. 2,8-DiCDF, 2,4,8-TrCDF, DiCDF, and TrCDF can be used as TEQ indicators for monitoring PCDD/Fs. 2,8-DiCDF and 2,4,8-TrCDF correlated well with the TEQ because they strongly correlated with 2,3,4,7,8-PeCDF, implying possible correlations in their formation mechanisms.


T-plate for middle carpal and carpometacarpal arthrodesis in a dog.
Partial arthrodesis was performed for carpal hyperextension injury in a dog. T-plate application for middle carpal and carpometacarpal arthrodesis was associated with low patient morbidity and allowed normal pet activity without clinical lameness. Radiography revealed bony healing of arthrodesed joints, reactive bone formation over the dorsal aspect of the plate, and periarticular osteophyte formation. A guarded prognosis is advised for degenerative joint disease that may lead to decreased range of motion of the antebrachiocarpal joint.


Preparing children for travel to tropical and developing regions.
Visiting a grandparent for a first time, exploring the ruins of an ancient civilization in a distant country, or river rafting through a tropical jungle are all moments that are never forgotten. Illness, visits to the doctor, and disability should not be a part of these experiences. Diseases such as malaria, yellow fever, travelers' diarrhea, and hepatitis A are preventable. Through the use of vaccines, prophylactic medications, and disease-prevention education, clinicians may help ensure their pediatric patients have enjoyable and rewarding travel experiences.


Bacteria-Mediated Intracellular Click Reaction for Drug Enrichment and Selective Apoptosis of Drug-Resistant Tumor Cells.
Functionalized biocarriers that can perform bio-orthogonal reactions in tumor cells may provide solutions to overcome the efflux of the chemotherapeutic agent from drug-resistant tumor cells. Herein, we report the enrichment of therapeutic drugs in tumor cells through intracellular click reaction with functionalized bacteria. Specifically, an intracellular bioactive drug enrichment template (OPV@Escherichia coli) is constructed by combining positively charged oligo(phenylene-vinylene)-alkyne (OPV-C≡CH) with E. coli via electrostatic interaction. After the cell uptake of OPV@E. coli and Cu(II)-based complex, Cu(I) generated in situ can catalyze the bio-orthogonal click reaction to covalently anchor the azide-bearing molecules of cyanine 5 (Cy5-N3) and paclitaxel (PTX-N3) on OPV@E. coli. These molecules and their functions were retained and enriched inside the drug-resistant tumor cells A549T, which can label cells with fluorescent probes and selectively induce the apoptosis of drug-resistant tumor cells.


Frequent inactivation of the p73 gene by abnormal methylation or LOH in non-Hodgkin's lymphomas.
p73 is a candidate tumor suppressor and imprinted gene that shares significant homology with the p53 gene. It is located on 1p36, a region frequently deleted in neuroblastoma and other tumors. To investigate the pattern of inactivation of this gene in human lymphomas, we studied 59 tumors to identify abnormal methylation in exon 1 and loss of heterozygosity (LOH) at this locus. p73 was methylated in 13/50 (26%) B cell lymphomas. There was no evidence of p73 methylation in the 9 T cell lymphomas analyzed. Burkitt's lymphomas showed the highest proportion of methylated cases (36%), although this alteration also affected other aggressive lymphomas such as diffuse large cell and some marginal zone lymphomas. LOH at the p73 locus was detected in 4/34 (11%) B and 1/9 (11%) T cell lymphomas. The p73 expression analysis showed absence or low level of p73 product in methylated lymphomas, whereas p73 was always detected in unmethylated tumors. We found monoallelic expression in normal peripheral blood samples, consistent with imprinting. None of the tumors showed LOH and methylation of the remaining allele simultaneously, suggesting that alteration of the expressed allele could lead to the total inactivation of the gene. Our results show that deletion or methylation of the p73 gene could be important mechanisms in suppressing p73 expression in B cell non-Hodgkin's lymphomas.


Decreased susceptibility of cardiac function to hypoxia-reoxygenation in renin-angiotensinogen transgenic rats.
We tested the hypothesis that the renin-angiotensin system (RAS) protects the contractile function of the myocardium against the damaging effect of hypoxia-reoxygenation. For this purpose, the contractility of isolated papillary muscles from wild-type (WT) rats and from rats expressing human renin and angiotensinogen as transgenes (TGR) was compared. After 15 min of hypoxia, peak force (PF) was decreased to 24 +/- 5% of the normoxic values in TGR (n = 10) and to 18 +/- 1% in WT rats (n = 12). PF and relaxation rates recovered completely in TGR but not in WT rats during 45 min of reoxygenation. Improved contractility of the papillary muscles from TGR during hypoxia-reoxygenation correlated with increased glutathione peroxidase activities and creatine kinase (CK)-MB and CK-BB isoenzyme levels. On the other hand, inhibition of the RAS with ramipril (1 mg/kg body wt for 3 wk) in WT animals resulted in deterioration of the contractile function of the papillary muscles during reoxygenation compared with untreated rats. These findings suggest that activation of the RAS protects contractile function of the cardiac muscle against hypoxia-reoxygenation, possibly through changes in CK isoenzymes and enhanced antioxidant capacity.


Genetic and environmental factors in prostate cancer genesis: identifying high-risk cohorts.
Prostate cancer is the most common malignancy found in males; however, little is as yet known regarding what initiates the disease. The incidence is highest among American Blacks and lowest in the East Asian population. Subtypes of the disease include familial clustering and a hereditary form (9%) supporting genetic events to be involved in prostate cancer pathogenesis. Chromosomal abberations so far identified as being frequently occurring in this disease seem to be related to later phases of disease progression. However, research finding the responsible promoting genetic alteration is rapidly progressing. To explain the varied geographical distribution of the disease, the environment also has to be taken into account. Risk factors identified so far include obesity, animal fat, red meat consumption and certain toxins containing cadmium, while vegetables, cereals and vitamin D seem to be protective. It is reasonable to believe that, in the near future, we will be able to identify persons at risk of acquiring the disease and then inform them how to adjust their lifestyle to avoid early progression of the malignancy.


Therapeutic strategy for cracked teeth.
The management of cracked teeth represents a difficulty because their diagnosis is complex and there is no consensus concerning their treatment. The present article explains this pathology within enamel and dentin and also focuses on the clinical consequences of crack development in dental tissue. As cracks have both biologic and mechanical implications, a complete review of the literature on the subject has enabled the development of a comprehensive diagnostic approach to identify cracked teeth and optimize their management. The elements of diagnosis are the bite test, transillumination, the pulp sensitivity test, the periodontal test, radiologic examinations, removal of existing restorations, and the use of quantitative light-induced fluorescence. Finally, the management of biologic and mechanical imperatives relating to the treatment of cracked teeth has allowed the proposal of a reliable and reproducible therapeutic strategy based on two pillars: the arrest of bacterial infiltration using immediate dentin sealing, and the limitation of crack propagation using relative cuspal coverage. In this article, the proposed clinical protocol is explained through the use of a decision map and is illustrated by a clinical case example.


Epidemiology of Kaposi's Sarcoma.
Kaposi's sarcoma is an angioproliferative tumor caused by human herpesvirus 8 in the context of immunodeficiency, such as that induced by HIV infection or immunosuppressive therapy. Its incidence has dramatically fallen in patients living with HIV (PLHIV) since the introduction of potent antiretroviral combinations 25 years ago due to the restoration of immunity and better control of HIV replication. However, KS is still one of the most frequently occurring cancers in PLHIV, in particular in men who have sex with men and in sub-Saharan Africa, where it is still endemic. Even in the context of restored immunity, the risk of KS is still more than 30 times higher in PLHIV than in the general population. Recent evidence indicates that early initiation of antiretroviral treatment, which is recommended by current guidelines, may reduce the risk of KS but it needs to be accompanied by early access to care. This review mainly focuses on the recent epidemiological features of KS in the context of HIV infection.


Phosphoinositide 3'-Kinase γ Facilitates Polyomavirus Infection.
Polyomaviruses are small, non-enveloped DNA tumor viruses that cause serious disease in immunosuppressed people, including progressive multifocal leukoencephalopathy (PML) in patients infected with JC polyomavirus, but the molecular events mediating polyomavirus entry are poorly understood. Through genetic knockdown approaches, we identified phosphoinositide 3'-kinase γ (PI3Kγ) and its regulatory subunit PIK3R5 as cellular proteins that facilitate infection of human SVG-A glial cells by JCPyV. PI3Kα appears less important for polyomavirus infection than PI3Kγ. CRISPR/Cas9-mediated knockout of PIK3R5 or PI3Kγ inhibited infection by authentic JCPyV and by JC pseudovirus. PI3Kγ knockout also inhibited infection by BK and Merkel Cell pseudoviruses, other pathogenic human polyomaviruses, and SV40, an important model polyomavirus. Reintroduction of the wild-type PI3Kγ gene into the PI3Kγ knock-out SVG-A cells rescued the JCPyV infection defect. Disruption of the PI3Kγ pathway did not block binding of JCPyV to cells or virus internalization, implying that PI3Kγ facilitates some intracellular step(s) of infection. These results imply that agents that inhibit PI3Kγ signaling may have a role in managing polyomavirus infections.


Biological Mechanism on SIRT1/NLRP3/IL-18 Signaling Pathway of Acupuncture for Treatment of Ischemic Stroke with Center Poststroke Pain.
To evaluate the effect of acupuncture on an animal model of ischemic stroke with central poststroke pain (CPSP) through Sirtuin 1 (SIRT1)/NOD-like receptor thermal protein domain associated protein 3 (NLRP3)/interleukin-18 (IL-18) signaling pathway. Data mining was performed with R package "edgeR," "limma," "pathview," etc., from NCBI Gene Expression Omnibus (GEO) database. Sprague Dawley (SD) rats were divided into 4 groups: sham operation group (Sham group, n = 5), poststroke central pain group (CPSP group, n = 5), poststroke central pain + acupuncture group (AP group, n = 5), central pain after stroke + acupuncture + SIRT1 inhibitor EX527 group (EX527 group, n = 5). Pain behavior testing was performed to determine the mechanical withdrawal threshold (MWT). Quantitative real-time PCR (qRT-PCR) was performed to verify the data mining results from the GEO database. The KEGG key pathway map was created using the R package "pathview" package, demonstrating that the expression levels of NLRP3's downstream inflammatory factors IL-18 were downregulated in both of siSIRT1 group compared to the control group and the NLRP3 reconstituted group compared to NLRP3 KO group. QRT-PCR results on animal models of CPSP ischemic stroke showed that the expression levels of SIRT1 were downregulated, the activation of the NLRP3 inflammasome was upregulated, and the expression levels of IL-18 were upregulated in the brain tissues of the surrounding area of the injury. As the pain threshold of CPSP rats was increased, the expression level of S1RT1 was upregulated, and the activation of NLRP3 inflammasome was downregulated. The expression level of IL-18 was downregulated after acupuncture treatment. Acupuncture may inhibit CPSP in an animal model of ischemic stroke by upregulating SIRT1 expression levels, inhibition of the activation of the inflammasome, and downregulating IL-18 expression levels.


The effects of binge drinking and socio-economic status on sober driving behavior.
Drinking and driving is a primary cause of traffic fatalities and it has been suggested that binge drinkers comprise a major portion of those drivers involved in drinking and driving accidents. Although several experimental studies have investigated the driving behavior of binge drinkers (particularly college students and/or young adults) under the influence of alcohol, few studies have focused on a comparison of sober driving behavior of the general population between binge and non-binge drinkers with a consideration of drivers' income levels. In addition, these studies have not taken other potentially influential factors into account such as socio economic status. A driving simulator study was conducted with a 2 x 2 factorial design (binge vs. non-binge drinker; low vs. high income). Sixty-two participants who were not under the influence of alcohol or drugs were asked to operate a driving simulator following traffic rules. Multiple aspects of participants' driving behaviors were measured in a sober driving situation. To control the potential effects of confounding factors, factors (e.g., age, gender, etc.) that were significantly correlated to the driving behavior were all entered into the multivariate analysis of variance (MANOVA) as covariates. Significant interaction effects were found between effects of binge drinking and income levels. Analyses indicated that binge drinkers-independent of their income levels-exhibited more speeding exceedances and longer speeding duration than those of non-binge drinkers with a high income. Individuals characterized as non-binge drinkers with a low income also exhibited more speeding behaviors. Cognitive deficits and problems in vehicle control resulting from chronic alcohol consumption may impact binge drinkers' abilities to perform adequately, even in a sober driving situation. In addition, non-binge drinkers with a low income were more prone to make unsafe choices compared to non-binge drinkers with a high income. Further implications of the results in transportation safety and alcohol addiction were also discussed.


Meta-analysis of management effects on biodiversity in plantation and secondary forests of Japan.
Conservation of temperate forest biodiversity has historically focused on natural old-growth. Less than 3% of the world's temperate forests remain unmodified by humans, however, and much of temperate-forest biodiversity is held in the predominating planted and secondary forests. Japan provides a widely applicable model for examining how to maximize biodiversity in managed temperate forests, because of its richness of forestry research generated from its vast forest area, albeit largely in Japanese, and the wide practice of its dominant management interventions across the northern temperate zone. Management for plantations includes thinning, extended rotation cycles and clear-cutting. For secondary forests regenerating from past clearance, traditional management varies in its intensities, from clear-cutting as coppices to small-scale understory clearance. Here we provide a first synthesis of published research on biodiversity in planted and secondary forests of Japan, relevant to management of these types of forest in northern temperate regions. Systematic review and meta-analyses of papers published in English and Japanese quantified management impacts on species richness and abundance of several taxa, in relation to moderator variables including stand age and management intensity. Plantation thinning substantially increases the richness and abundance of several taxa. Effect sizes decline with time since thinning for the abundance of regenerating saplings and seedlings, necessitating repeated thinning treatments every 6 years to sustain this positive effect. Taxonomic groups exhibit variable relationships with stand age in both planted and secondary forests, indicating a need to include both young and old forest stands in managed forest mosaics. We find an insufficient evidence base is available to allow for a meaningful synthesis of low-intensity management effects in historically managed secondary forests, with studies varying widely in scale and reported outcomes. We outline an agenda for the research community to achieve a systematic evaluation of scale-dependent effects of traditional forest management on biodiversity.


Middle East respiratory syndrome coronavirus ORF4b protein inhibits TLR7- and TLR9-dependent alpha interferon induction.
The Toll-like receptor (TLR)7- and TLR9-dependent signalling cascade is responsible for production of a large amount of alpha interferon by plasmacytoid dendritic cells upon viral infection. Here, we show that Middle East respiratory syndrome coronavirus (MERS-CoV) accessory protein ORF4b has the most potential among the MERS-CoV accessory proteins to inhibit the TLR7/9-signaling-dependent alpha interferon production. ORF4b protein, which has a bipartite nuclear localization signal, was found to bind to IKKα, a kinase responsible for phosphorylation of interferon regulatory factor (IRF)7. This interaction caused relocation of a large proportion of IKKα from the cytoplasm to the nucleus. Studies using ORF4b and IKKα mutants demonstrated that ORF4b protein inhibited IKKα-mediated IRF7 phosphorylation by sequestering IKKα in the nucleus and by impeding the phosphorylation process of cytoplasmic IKKα.


Risk factors for microvascular complications of diabetes among South Indian subjects with type 2 diabetes--the Chennai Urban Rural Epidemiology Study (CURES) Eye Study-5.
This study assessed the relationship between and risk factors for microvascular complications of diabetes in an urban South Indian type 2 diabetes population. Subjects with diabetes (n = 1,736) were selected from the population-based Chennai Urban Rural Epidemiology Study (CURES) Eye Study conducted on a representative population of Chennai city in south India. Four-field stereo retinal color photography was done, and diabetic retinopathy (DR) was classified according to the Early Treatment DR Study grading system. Neuropathy was diagnosed if the vibratory perception threshold of the big toe using biothesiometry was ≥ 20V. Overt nephropathy was diagnosed if the subjects had persistent macroalbuminuria (urinary albumin excretion ≥ 300 μg/mg of creatinine) and microalbuminuria if it was between 30 and 299 μg/mg of creatinine. Among the 1,715 subjects with gradable fundus photographs, 1,608 individuals who had information on all test parameters were included. Overall, DR was present in 282 (17.5%), neuropathy in 414 (25.7%), overt nephropathy in 82 (5.1%), and microalbuminuria in 426 (26.5%) subjects. Eighteen subjects had all three microvascular complications of diabetes. The risk of nephropathy (odds ratio [OR] = 5.3, P<0.0001) and neuropathy (OR = 2.9, P<0.0001) was significantly higher among the subjects with sight-threatening DR compared to those without DR. Common risk factors identified for all the three microvascular complications of diabetes were age, glycated hemoglobin, duration of diabetes, and serum triglycerides. DR was associated with nephropathy after adjusting for age, gender, hemoglobin A1c, systolic blood pressure, serum triglycerides, and duration of diabetes (OR = 2.140, 95% confidence interval = 1.261-3.632, P = 0.005). This is the first population-based study from India to report on all microvascular complications of diabetes and reveals that the association between DR and nephropathy is stronger than that with neuropathy.


Vascular and microvascular changes--key factors in the development of acetic acid-induced gastric ulcers in rats.
The present study examined the time sequence and histologic and ultrastructural features of the formation and evolution of experimental, acetic acid-induced gastric ulcerations in rats. One hundred percent acetic acid was applied to the gastric serosa of 140 fasted male Sprague-Dawley rats through a polyethylene tube for 30 s. Gastric mucosal changes were evaluated at 1, 5, 15, and 30 min, 1 and 3 h, and 1, 2, 3, 5, 8, and 11 days after acetic acid application by visual inspection, by quantitative and qualitative light microscopy, and by transmission electron microscopy. Following exposure to acetic acid, the earliest morphologic changes occurred at 1 min and consisted of dilatation of large submucosal veins and arteries and mucosal collecting venules. Five to 15 minutes after injury, thrombi developed in submucosal veins and collecting venules, leading to microvascular stasis and mucosal necrosis. By 3 h, necrotic masses started to detach. By 24-48 h, necrotic changes penetrated the submucosa. By 72 h, most ulcers underwent transition into a "chronic" stage characterized histologically by the presence of granulation tissue at the bottom, and the appearance of a transitional healing zone at the margins. By 5 days, an increased amount of granulation tissue was observed and the gastric glands in transitional zones at the ulcer margin displayed cystic dilatation. Based on this study, we conclude that a key feature of acetic acid-induced ulcer formation is the early vascular and microvascular injury, which precedes glandular cell necrosis.


Clinical applications and implications of common and founder mutations in Indian subpopulations.
South Asian Indians represent a sixth of the world's population and are a racially, geographically, and genetically diverse people. Their unique anthropological structure, prevailing caste system, and ancient religious practices have all impacted the genetic composition of most of the current-day Indian population. With the evolving socio-religious and economic activities of the subsects and castes, endogamous and consanguineous marriages became a commonplace. Consequently, the frequency of founder mutations and the burden of heritable genetic disorders rose significantly. Specifically, the incidence of certain autosomal-recessive disorders is relatively high in select Indian subpopulations and communities that share common recent ancestry. Although today clinical genetics and molecular diagnostic services are making inroads in India, the high costs associated with the technology and the tests often keep patients from an exact molecular diagnosis, making more customized and tailored tests, such as those interrogating the most common and founder mutations or those that cater to select sects within the population, highly attractive. These tests offer a quick first-hand affordable diagnostic and carrier screening tool. Here, we provide a comprehensive catalog of known common mutations and founder mutations in the Indian population and discuss them from a molecular, clinical, and historical perspective.


Pharmacological characteristics of novel putative purinoceptors in vascular endothelium.
Using an isolated rat aorta with intact endothelium, a functional bioassay system was created as follows: pre-contract the isolated rat aorta with intact endothelium in the presence of 0.62 micromol/l of norepinephrine, and then add acetylcholine to obtain maximal endothelium-dependent relaxation. In the addition of low concentration of adenosine, a P(1) agonist or ATP, a P(2) agonist to this system, the rat aorta smooth muscle contraction was observed. This observation could not be explained in terms of the classic P(1) and P(2) receptor properties, suggesting that there may be a novel subtype of purinoceptors in the endothelium of the rat aorta. The P(1) and P(2) agonists-induced rat aorta smooth muscle contraction could be blocked by the pretreatments of the bioassay system with a G protein (Gi/o) inhibitor, PTX, and EDNO synthesis inhibitor, L-NAME and cyclooxygenase inhibitor, indomethacine. The data strongly support that this novel purinoceptor may couple with PTX-sensitive G protein, Gi or Go, and the novel purinoceptor-mediated rat aorta smooth muscle contraction is dependent on the endogenous nitric oxide and prostaglandin synthesis. In an additional observation, pathophysiological conditions, such as hypertension, altered the characteristics of the novel receptor. Hypertension caused the novel receptor insensitive to adensone and uncoupling to PTX-sensitive G-proteins and lost of ability to initiate the receptor-mediated prostaglandin synthesis. All together, the novel putative endothelial purinoceptor may play an important role in the control of vascular tone in physiological or pathophysiological statues.


Otolithic activation on visceral circulation in humans: effect of aging.
Engagement of the otolith organs elicits differential activation of sympathetic nerve activity and vascular responses to muscle and skin in humans. Additionally, aging attenuates the otolith organ-mediated increases in muscle sympathetic nerve activity in older adults. In this study, we hypothesized that 1) the vestibulosympathetic reflex (VSR) would elicit visceral vascular vasoconstriction and 2) visceral vascular response to the VSR would be attenuated in older subjects compared with young. To test these hypotheses, heart rate, mean arterial blood pressure, and renal, celiac trunk, and superior mesenteric arterial blood velocity (Doppler ultrasound) were measured in 22 young (25+/-1 yr) and 18 older (65+/-2 yr) healthy subjects during head-down rotation (HDR), which selectively activates the otolith organs. Mean arterial pressure and heart rate did not change from baseline during HDR in young or older subjects. Renal blood velocity (Delta -2+/-1 cm/s) and vascular conductance (Delta -0.03+/-0.01 cm.s(-1).mmHg(-1)) significantly decreased from baseline during HDR (P<0.05) in young subjects. In contrast, renal blood velocity and conductance did not change in older subjects (Delta -0.2+/-1 cm/s and Delta0.02+/-0.08 mmHg.cm(-1).s(-1), respectively) during HDR. Superior mesenteric and celiac blood velocity and vascular conductance did not change in response to HDR in either the young or older subjects. These data suggest that renal vasoconstriction occurs during otolith organ activation in young but not older humans. Together with our previous studies, we conclude that the VSR elicits a diverse patterning of sympathetic outflow that results in heterogeneous vascular responses in humans and that these responses are significantly attenuated in older humans.


Sarilumab plus methotrexate improves patient-reported outcomes in patients with active rheumatoid arthritis and inadequate responses to methotrexate: results of a phase III trial.
Sarilumab is a human monoclonal antibody directed against the alpha subunit of the interleukin-6 receptor complex. In the MOBILITY phase III randomized controlled trial (RCT), sarilumab + methotrexate (MTX) treatment resulted in clinical improvements at 24 weeks that were maintained at 52 weeks in adults with rheumatoid arthritis (RA), who have inadequate response to MTX (MTX-IR). These analyses indicate the effects of sarilumab + MTX versus placebo on patient-reported outcomes (PROs) in this RCT. Patients (n = 1197) were randomized to receive placebo, sarilumab 150 or 200 mg subcutaneously + MTX every 2 weeks for 52 weeks; after 16 weeks, patients without ≥20 % improvement from baseline in swollen or tender joint counts on two consecutive assessments were offered open-label treatment. PROs included patient global assessment of disease activity (PtGA), pain, health assessment questionnaire disability index (HAQ-DI), Short Form-36 Health Survey (SF-36), and functional assessment of chronic illness therapy-fatigue (FACIT-F). Changes from baseline at weeks 24 and 52 were analyzed using a mixed model for repeated measures. Post hoc analyses included percentages of patients reporting improvements equal to or greater than minimal clinically important differences (MCID) and normative values in the FACIT-F and SF-36. Pearson correlation between observed PRO scores and clinical measures of disease activity was tested at week 24. Both doses of sarilumab + MTX vs placebo + MTX resulted in improvement from baseline by week 24 in PtGA, pain, HAQ-DI, SF-36 and FACIT-F scores (p < 0.0001) that was clinically meaningful, and persisted until week 52. In post hoc analyses, the percentages of patients with improvement equal to or greater than the MCID across all PROs were greater with sarilumab than placebo (p < 0.05), with differences ranging from 11.6 to 26.2 %, as were those reporting equal to or greater than normative scores. In this RCT in patients with MTX-IR RA, sarilumab + MTX resulted in sustained improvement in PROs that were clinically meaningful, greater than placebo + MTX, and complement the previously reported clinical efficacy and safety of sarilumab. ClinicalTrials.gov. NCT01061736 . February 2, 2010.


Fibrosis with inflammation at one year predicts transplant functional decline.
Lack of knowledge regarding specific causes for late loss of kidney transplants hampers improvements in long-term allograft survival. Kidney transplants with both interstitial fibrosis and subclinical inflammation but not fibrosis alone after 1 year have reduced survival. This study tested whether fibrosis with inflammation at 1 year associates with decline of renal function in a low-risk cohort and characterized the nature of the inflammation. We studied 151 living-donor, tacrolimus/mycophenolate-treated recipients without overt risk factors for reduced graft survival. Transplants with normal histology (n = 86) or fibrosis alone (n = 45) on 1-year protocol biopsy had stable renal function between 1 and 5 years, whereas those with both fibrosis and inflammation (n = 20) exhibited a decline in GFR and reduced graft survival. Immunohistochemistry confirmed increased interstitial T cells and macrophages/dendritic cells in the group with both fibrosis and inflammation, and there was increased expression of transcripts related to innate and cognate immunity. Pathway- and pathologic process-specific analyses of microarray profiles revealed that potentially damaging immunologic activities were enriched among the overexpressed transcripts (e.g., Toll-like receptor signaling, antigen presentation/dendritic cell maturation, IFN-γ-inducible response, cytotoxic T lymphocyte-associated and acute rejection-associated genes). Therefore, the combination of fibrosis and inflammation in 1-year protocol biopsies associates with reduced graft function and survival as well as a rejection-like gene expression signature, even among recipients with no clinical risk factors for poor outcomes. Early interventions aimed at altering rejection-like inflammation may improve long-term survival of kidney allografts.


Characterization of a voltage-activated K-channel gene cluster on human chromosome 12p13.
The Shaker related alpha-subunit subfamily of human voltage-activated KCNA-channels is encoded by several genes in the human genome. We have isolated yeast artificial chromosomes (YACs) spanning approximately 1 Mb of human chromosome 12p13 DNA. Molecular biological characterization of the YAC-insert DNAs revealed that three KCNA genes--KCNA1, KCNA5, KCNA6--are clustered within approximately 300 kb of insert-DNA derived from chromosome 12p13. The KCNA gene cluster has been conserved between mouse and human. The three KCNA genes in the cluster are transcribed from the same DNA strand being arranged in a head-to-tail fashion in the order KCNA6-KCNA1-KCNA5. Northern blot analyses of the KCNA1, KCNA5 and KCNA6 mRNAs in different human brain areas show that the genes are distinctly expressed. Therefore, they may be transcribed independently of each other.


FPIN's Clinical Inquiries. Aspirin use in children for fever or viral syndromes.
Aspirin should not be used to treat acute febrile viral illness in children. (Strength of Recommendation [SOR]: C, based on case-control studies). Although no causal link has been proven, data from case-control and historic cohort studies demonstrate an association between aspirin use and Reye syndrome. The risk of Reye syndrome decreases with age, becoming extremely rare by the late teenage years. Other nonsteroidal anti-inflammatory drugs are effective antipyretics and are not associated with the constellation of symptoms seen in Reye syndrome, which includes nausea, vomiting, headache, excitability, delirium, combativeness, and coma. Aspirin use in children younger than 19 years should be limited to diseases in which aspirin has a proven benefit, such as Kawasaki disease and the juvenile arthritides. (SOR: C, based on expert opinion).


Strong Anisotropic Spin-Orbit Interaction Induced in Graphene by Monolayer WS_{2}.
We demonstrate strong anisotropic spin-orbit interaction (SOI) in graphene induced by monolayer WS_{2}. Direct comparison between graphene-monolayer WS_{2} and graphene-bulk WS_{2} systems in magnetotransport measurements reveals that monolayer transition metal dichalcogenide can induce much stronger SOI than bulk. Detailed theoretical analysis of the weak antilocalization curves gives an estimated spin-orbit energy (E_{so}) higher than 10 meV. The symmetry of the induced SOI is also discussed, and the dominant z→-z symmetric SOI can only explain the experimental results. Spin relaxation by the Elliot-Yafet mechanism and anomalous resistance increase with temperature close to the Dirac point indicates Kane-Mele SOI induced in graphene.


Effects of harvest date and growth stage on triticale forages in the southwest United States: agronomic characteristics, nutritive value, energy density, and in vitro disappearance of dry matter and fiber.
Recently, there has been increased interest in including triticale (X Triticosecale Wittmack) or other winter cereals within forage programs throughout the southwest United States. Our objectives were to screen 14 diverse triticale cultivars for agronomic and nutritive characteristics with specific emphasis on identifying normal, as well as deviant, responses to the calendar date and plant maturity for forages seeded in December and harvested from late February throughout May at Maricopa, AZ. Fourteen cultivars were established in a randomized complete block design with each cultivar represented within each of three field blocks. Plots were clean tilled and established on December 18, 2018, and then harvested at 2-wk intervals beginning on February 27 and ending May 23, 2019. Across all harvest dates, forage (N = 315) energy density (NEL) exhibited strong negative correlations with growth stage (r = -0.879), plant height (r = -0.913), head weight (r = -0.814), and estimated dry matter (DM) yield (r = -0.886) but was positively associated with percentages of leaf (r = 0.949), and weakly associated with percentages of the stem (r = 0.138). Through April 10, similar correlations were observed within individual harvest dates (N = 45) for growth stage, leaf percentage, and plant height but not for stem or head-weight percentages. Within later harvest dates, only sporadic correlations with NEL were observed. Primarily cubic regression relationships for neutral detergent fiber, acid detergent lignin, 30- and 48-h in vitro disappearance of DM and fiber, and NEL were fit for the mean or typical cultivar using both days from February 1 and growth stage as independent variables. Coefficients of determination (R2 ≥ 0.860) in all cases indicated a good fit for the polynomial models. For NEL, deviation from the typical cultivar when days from February 1 was used as the independent regression variable was largely affected by cultivar maturation rate. When the growth stage was substituted as the independent variable, plant height, stem percentage beginning at anthesis, and low grain-head percentage were associated with the maximum negative deviant cultivar (Merlin Max). The 0.23 Mcal/kg difference between maximum positive and negative deviant cultivars at a common late-boot/early-heading stage of growth suggests that some attention should be placed on cultivar selection as well as forage inventory needs and overall cropping goals.


Partial Purification, Photoaffinity Labeling, and Properties of Mung Bean UDP-Glucose:Dolicholphosphate Glucosyltransferase.
UDP-glucose:dolichylphosphate glucosyltransferase has been purified 734-fold from Triton X-100 solubilized mung bean (Phaseolus aureus) microsomes. The partially purified enzyme has broad pH optima of activity from 6.0 to 7.0 and is maximally stimulated with 10 millimolar MgCl(2). The K(m) for UDP-glucose was determined as 27 micromolar, and the K(m) for dolichol-P was 2 micromolar. Using the UDP-glucose photoaffinity analog, 5-azido-UDP-glucose, a polypeptide of 39 kilodaltons on sodium dodecyl sulfate-polyacrylamide gels was identified as the catalytic subunit of the enzyme. Photoinsertion into this 39-kilodalton polypeptide with [(32)P]5-azido-UDP-glucose was saturable, and was maximally protected with the native substrate UDP-glucose. 5-Azido-UDP-glucose behaves competitively with UDP-glucose in enzyme assays, and upon photolysis inhibits activity in proportion to its concentration. This study represents the first subunit identification of a plant glycosyltransferase involved in the biosynthesis of the lipid-linked oligosaccharides that are precursors of N-linked glycoproteins.


A prospective controlled randomized study of arthroscopic lavage in acute primary anterior dislocation of the shoulder: one-year follow-up.
Traumatic primary anterior shoulder dislocation has a very high recurrence rate among young people. This has supplied the motivation for studies to find methods of treatment that might become an alternative to traditional therapy. A prospective controlled study was performed to test the hypothesis that acute arthroscopic lavage might have a positive effect on recurrence rate as well as on shoulder stability, range of motion and mobilization. 30 consecutive patients between 18 and 30 years of age were randomized into 2 groups, 1 control group treated conservatively and 1 group treated with acute arthroscopic lavage within 10 days. Clinical examination was made by an independent observer at 1, 6 and 12 months. Results at 6- and 12-month check-ups showed a statistically significantly lower rate of redislocation and a wider range of motion for the group treated with acute arthroscopic lavage. Functional assessment according to the Lysholm shoulder score also indicated better functioning of the joint. Our 1-year follow-up shows very promising and interesting results.


Recent advances in auxin research in rice and their implications for crop improvement.
Auxin is essential for various aspects of plant development, and modulation of auxin pathways has great potential for crop improvement. Although the current understanding of auxin biology including auxin biosynthesis, transport, and signaling mainly originated from studies in Arabidopsis, several key auxin genes were first discovered in rice, indicating that it is useful to employ several plant systems for auxin research. In this review, we summarize the recent advances in auxin biology in rice, highlight the main contributions of rice research to auxin biology, and discuss the potential for crop improvement through modulating auxin pathways.


Effects of Lonicera japonica Thunb. on Type 2 Diabetes via PPAR-γ Activation in Rats.
Lonicera japonica Thunb. (Caprifoliaceae) is a traditional herbal medicine and has been used to treat diabetic symptoms. Notwithstanding its use, the scientific basis on anti-diabetic properties of L. japonica is not yet established. This study is designed to investigate anti-diabetic effects of L. japonica in type 2 diabetic rats. L. japonica was orally administered at the dose of 100 mg/kg in high-fat diet-fed and low-dose streptozotocin-induced rats. After the treatment of 4 weeks, L. japonica reduced high blood glucose level and homeostatic model assessment of insulin resistance in diabetic rats. In addition, body weight and food intake were restored by the L. japonica treatment. In the histopathologic examination, the amelioration of damaged β-islet in pancreas was observed in L. japonica-treated diabetic rats. The administration of L. japonica elevated peroxisome proliferator-activated receptor gamma and insulin receptor subunit-1 protein expressions. The results demonstrated that L. japonica had anti-diabetic effects in type 2 diabetic rats via the peroxisome proliferator-activated receptor gamma regulatory action of L. japonica as a potential mechanism.


Phosphoinositide 3-kinase gamma is an essential amplifier of mast cell function.
Mast cells are key regulators in allergy and inflammation, and release histamine upon clustering of their IgE receptors. Here we demonstrate that murine mast cell responses are exacerbated in vitro and in vivo by autocrine signals through G protein-coupled receptors (GPCRs) and require functional phosphoinositide 3-kinase gamma (PI3Kgamma). Adenosine, acting through the A(3) adenosine receptor (A(3)AR) as well as other agonists of G(alphai)-coupled GPCRs, transiently increased PtdIns(3,4,5)P(3) exclusively via PI3Kgamma. PI3Kgamma-derived PtdIns(3,4,5)P(3) was instrumental for initiating a sustained influx of external Ca(2+) and degranulation. Mice lacking PI3Kgamma did not form edema after intradermal injection of adenosine and when challenged by passive systemic anaphylaxis. PI3Kgamma thus relays inflammatory signals through various G(i)-coupled receptors and is central to mast cell function.


Effects of obesity surgery on non-insulin-dependent diabetes mellitus.
Most individuals who have non-insulin-dependent diabetes mellitus are obese. The obese population has proved a frustrating entity regarding weight loss and diabetes control. Results of medical weight loss programs, medications, and behavior therapy have proved disappointing. Bariatric surgery is the most effective method of diabetes management and cure in the morbidly obese population. Surgical procedures to cause malabsorption provide a more dramatic effect on diabetes owing to the imparted bypass of the hormonally active foregut. Pertinent journal articles spanning the last 40 years, as well as textbooks. Bariatric surgical procedures have proven a much more successful method of weight loss and diabetes control in the obese population than conservative methods. These surgical procedures have proven safe with reported mortality rates of 0% to 1.5%. Bariatric operations may be divided based on the method of weight loss and effect on diabetes. The first category is restrictive and includes vertical banded gastroplasty and adjustable silicone gastric banding. These operations improve diabetes by decreasing food intake and body weight with a slowing of gastric emptying. The second category not only contains restrictive components but also elements of malabsorption. This category includes the Roux-en-Y gastric bypass and biliary-pancreatic diversion, which bypass the foregut. Although all of the surgical procedures for obesity offer improved weight loss and diabetes control compared with conservative methods, the Roux-en-Y gastric bypass and biliary-pancreatic diversion offer superior weight loss and resolution of diabetes. The more dramatic effect seen in the surgical procedures to cause malabsorption is likely secondary to the bypass of the foregut resulting in increased weight loss and elevation of the enteroglucagon level.


Esophageal stem cells--a review of their identification and characterization.
The incidence of adenocarcinoma of the esophagus has increased faster than any other internal malignancy over the last 40 years. Despite this, surprisingly little is known about the basic biology of this tissue, particularly with regards to the organization of cell proliferation within the epithelium. This is a matter of crucial importance for our understanding of the pathogenesis of esophageal cancer. Nevertheless, significant advances have recently been made in the identification and functional characterization of both murine and human esophageal stem cells and their progeny in recent years. This places investigators in an exciting position to gain further insights into the processes of tissue renewal and repair on the one hand and the development of dysplasia and malignancy on the other.


[Using GnRH-agonists (Zoladex) in the treatment of genital endometriosis].
The study is prospective and involves 112 patients suffering from pelvic endometriosis aging from 19-38 years. (28.6 average age). The disease was diagnosed via laparoscopy and the stage was determined using the revised AFS classification. Zoladex (Goserelin depot--3.6 mg) is being applied every 28 days for 6 months in the hypodermic tissue of the front abdomen wall. All patients are being examined monthly after every Zoladex application (for subjective complaints--dysmenorrheal, dyspareunea, pelvic pain; serum estradyol-E2; amenorrhea; side effects) and every 24 months (recuperation of the menstrual cycle, pregnancy). In 88% of the patients amenohrea is obsereved in the first eight weeks of therapy. The menstrual cycle takes an avarege of 68 (31-139) after the last Zoladex application to reappear. At the end of the first month after the first application the serum level of estradyol E2 is lowered to a menopause level (from 750-800 to 120-130 Pmol/L) and it remains as low till the end of the treatment. Eight weeks after the completion of the therapy it goes back to its normal values. During the course of the first month of amenorrhea condition a 38% fall in the level of complaints (dysmenorrheal, dyspareunea, pelvic pain) is observed. After the 6th month 88% of the patients have no complaints. Side effects observed during the course of treatment include warm waves, sweating, vaginal dehydration (60-80%) which do not in any way disturb the patients to the point of quitting the therapy and do disappear with its end. The focus group contains 54 infertile patients with endometrioses willing to get pregnant. In 12 months after the completion of the treatment 16 of the patients become pregnant, followed by 12 more in the next one year. Zoladex causes amenorrhea, which lasts till the end of the treatement. It causes a rapid drop of the serum consentration to a menopause level. Causes a strong and durable treatment of the symptoms of endometriosis. The side effects disappear with the end of the therapy. The treatment is easy to go through and there no cases of a quitting patient. The treatment has a curable effect over the endometriosys and in cases of infertility provides a possibility for pregnancy.


Mesomorphism, isomerization, and dynamics in a new series of pyramidic liquid crystals.
Nona-alkanoyloxy tribenzocyclononene (CTV-n, where n is the number of carbons in the side chains) were prepared for n = 2 to 14. The homologues of this series appear in two stable isomeric forms, rigid crown and flexible saddle. We report on their isomerization equilibria and dynamics in solution and on their mesomorphic properties in the neat state. The crown-saddle equilibrium and interconversion kinetics of the CTV-8 isomers were studied in dimethyl formamide solutions using high-resolution (1)H NMR in the temperature range from 50 to 130 degrees C. At lower temperatures, the isomerization is too slow to measure. In this range the equilibrium saddle fraction increases from approximately 0.40 to approximately 0.65, whereas the isomerization rate increases from approximately 10(-)(4) to approximately 1 s(-)(1). The saddle isomer undergoes fast pseudorotation at room temperature, but below about -50 degrees C, it becomes slow enough to affect the NMR line width. The rate parameters for this process were estimated from the carbon-13 spectra in methylene chloride solutions to be, k(p)(-100 degrees C) approximately 1.7 x 10(3) s(-)(1) and E(a) approximately 9.6 kJ/mol. The slow crown-saddle isomerization at room temperature (half-life of about one year) allows quantitative separation (by chromatography) of the two isomers and their separate investigation. When the alkanoyloxy side chains are sufficiently long both isomers are mesogenic (n >or= 4 for the saddle and n >or= 5 for the crown), exhibiting hexagonal columnar mesophases. The structure, dynamics, and mesomorphic properties of these mesophase were investigated by X-ray diffraction, optical polarizing microscopy, differential scanning calorimetry, and NMR. The lattice parameters of the crown and saddle mesophases of corresponding homologues are almost identical and increase monotonically with increasing length of the side chains. The clearing temperatures of the saddle isomers are consistently lower than those of the corresponding crowns. Within each series, the clearing temperatures are almost independent of the length of the side chains (156 to 170 degrees C for the crown and 115 to 148 degrees C for the saddle). The thermal and kinetic properties of the neat compounds lead to peculiar phase sequences, as observed in the polarizing microscope and in the DSC thermogram, involving repeated, back and forth, interconversion between the two isomers. Carbon-13 MAS NMR measurements of the crown and saddle mesophases of several homologues were carried out. The spectra of the crown mesophase exhibit dynamic features consistent with planar 3-fold molecular jumps about the column axes. A quantitative analysis for the CTV-8 crown homologue yielded the following Arrhenius parameters, A = 3.1 x 10(22)s(-)(1) and E(a) = 130.1kJ/mol. These unusually high values suggest that the barrier to the jump process is temperature dependent, decreasing with increasing temperature. The rate of this 3-fold jump process is slower for the lower homologues and faster for the higher ones. In contrast, the saddle isomers in the mesophase do not show dynamic effects in their carbon-13 MAS spectra. They do not undergo pseudorotation, and it appears that the molecules remain locked within the columns in a saddle conformation, up to the clearing temperature. However, on (super-)cooling to room temperature and below, selective line broadening is observed in their carbon-13 MAS spectra. This suggests that the saddle conformation is twisted in the mesophase and undergoes fast high-amplitude jumps between the twisted forms. On cooling, these high-amplitude librations freeze out to give an orientationally disordered state. On a very long time scale (of the order of days at 100 degrees C), the saddle mesophase transforms into that of the crown, apparently by sublimation.


A multi-label learning framework for predicting antibiotic resistance genes via dual-view modeling.
The increasing prevalence of antibiotic resistance has become a global health crisis. For the purpose of safety regulation, it is of high importance to identify antibiotic resistance genes (ARGs) in bacteria. Although culture-based methods can identify ARGs relatively more accurately, the identifying process is time-consuming and specialized knowledge is required. With the rapid development of whole genome sequencing technology, researchers attempt to identify ARGs by computing sequence similarity from public databases. However, these computational methods might fail to detect ARGs due to the low sequence identity to known ARGs. Moreover, existing methods cannot effectively address the issue of multidrug resistance prediction for ARGs, which is a great challenge to clinical treatments. To address the challenges, we propose an end-to-end multi-label learning framework for predicting ARGs. More specifically, the task of ARGs prediction is modeled as a problem of multi-label learning, and a deep neural network-based end-to-end framework is proposed, in which a specific loss function is introduced to employ the advantage of multi-label learning for ARGs prediction. In addition, a dual-view modeling mechanism is employed to make full use of the semantic associations among two views of ARGs, i.e. sequence-based information and structure-based information. Extensive experiments are conducted on publicly available data, and experimental results demonstrate the effectiveness of the proposed framework on the task of ARGs prediction.


Cervical kinematics in patients with vestibular pathology vs. patients with neck pain: A pilot study.
Research has consistently shown cervical kinematic impairments in subjects with persistent neck pain (NP). It could be reasoned that those with vestibular pathology (VP) may also have altered kinematics since vestibular stimulation via head movement can cause dizziness and visual disturbances. However, this has not been examined to date. This pilot study investigated changes in cervical kinematics between asymptomatic control, NP and VP subjects using a Virtual Reality (VR) system. It was hypothesised that there would be altered kinematics in VP subjects, which might be associated with dizziness and visual symptoms. Pilot cross sectional observational study. Twenty control, 14 VP and 20 NP subjects. Not applicable. Measures included questionnaires (neck disability index, pain on movement, dizziness and pain intensity, visual disturbances) and cervical kinematics (range, peak and mean velocity, smoothness, symmetry, and accuracy of cervical motion) using a virtual reality system. Results revealed significantly decreased mean velocity and symmetry of motion in both planes in those with NP but no differences in accuracy or range of motion. No significant differences were seen between VP subjects and asymptomatic controls. However, correlation analysis showed some moderate correlations between dizziness to selected kinematics in both the NP and the VP groups. These results support that cervical kinematics are altered in NP patients, with velocity most affected. There is potential for VP subjects to also have altered kinematics, especially those who experience dizziness. More research is required.


CD3-positive B cells: a storage-dependent phenomenon.
The majority of clinical studies requires extensive management of human specimen including e.g. overnight shipping of blood samples in order to convey the samples in a central laboratory or to simultaneously analyze large numbers of patients. Storage of blood samples for periods of time before in vitro/ex vivo testing is known to influence the antigen expression on the surface of lymphocytes. In this context, the present results show for the first time that the T cell antigen CD3 can be substantially detected on the surface of human B cells after ex vivo storage and that the degree of this phenomenon critically depends on temperature and duration after blood withdrawal. The appearance of CD3 on the B cell surface seems to be a result of contact-dependent antigen exchange between T and B lymphocytes and is not attributed to endogenous production by B cells. Since cellular subsets are often classified by phenotypic analyses, our results indicate that ex vivo cellular classification in peripheral blood might result in misleading interpretations. Therefore, in order to obtain results reflecting the in vivo situation, it is suggested to minimize times of ex vivo blood storage after isolation of PBMC. Moreover, to enable reproducibility of results between different research groups and multicenter studies, we would emphasize the necessity to specify and standardize the storage conditions, which might be the basis of particular findings.


The interfacility transport of critically ill newborns.
The practice of paediatric/neonatal interfacility transport continues to expand. Transport teams have evolved into mobile intensive care units capable of delivering state-of-the-art critical care during paediatric and neonatal transport. While outcomes are best for high-risk infants born in a tertiary care setting, high-risk mothers often cannot be safely transferred. Their newborns may then have to be transported to a higher level of care following birth. The present statement reviews issues relating to transport of the critically ill newborn population, including personnel, team competencies, skills, equipment, systems and processes. Six recommendations for improving interfacility transport of critically ill newborns are highlighted, emphasizing the importance of regionalized care for newborns.


[A case-control study on the risk factors for inguinal hernia in children].
Inguinal hernia is a common birth defect in children, but there is limited information about the risk factors for this disorder. The study aimed to explore the risk factors for the development of this disorder in children. A frequency matching case-control study based on hospital group data was performed. One hundred and thirty-two 0-6 years old children with inguinal hernia and 132 aged-matched controls were enrolled. Children's general characteristics and their mothers' general characteristics before and during pregnancy were obtained by a questionnaire survey. Risk factors for inguinal hernia were investigated by logistic regression analysis. Multivariate logistic regression analysis showed that the development of inguinal hernia was related to children's cry and unease records (OR=3.70195%CI1.724-7.945), maternal consumption for pickles (OR=2.53495%CI: 1.279-5.021) and maternal anemia (OR=3.76195%CI1.497-9.450) one year before pregnancy and during the first 3 months of pregnancy, and the family history of inguinal hernia (OR=13.50595%CI5.825-31.307). Children's cry and unease records, maternal anemia and pickle consumption one year before pregnancy and during the first 3 months of pregnancy, and family history of inguinal hernia are risk factors for the development of inguinal hernia in children.


Male Surgical Neck Rejuvenation.
Patients who are aging, with weight gain, and increased skin laxity, request dermatologists to improve their neck area. Surgical and nonsurgical options are reviewed as well as benefits and side effects. This article will focus on how surgical techniques can be applied for male patients in particular. To review surgical neck rejuvenation therapies available currently to find the best option for male patients. Surgical treatment of the male neck to improve mandibular contour and loose neck skin requires tightening of the platysmal muscle and usually skin removal in the postauricular sulcus and into the hairline. Most patients choose to have this performed underline tumescent anesthesia when given the choice of sedation versus local anesthesia. The other surgical variations of improving the neck contour on a male include using a direct excision by a midline incision starting in the submental crease and extending down the anterior neck. This approach allows for maximum tightening of the platysmal bands. The incision line can be minimized using intraoperative laser resurfacing immediately after suturing. Chin implants are necessary in some patients to give good neck improvement. The isolated neck lift is one the most common procedures requested by men asking for neck improvement.


[Determining the Prevalence of Norovirus Infection in Diarrheal Patients and Evaluation of Different Diagnostic Methods].
Norovirus is one of the viruses that cause gastroenteritis in humans, characterized by symptoms of vomiting and diarrhea. The prevalence of norovirus, known as the leading cause of epidemic gastroenteritis, is remarkable in sporadic cases. Easy-to-apply diagnostic methods based on antigen detection such as enzyme immunoassay (EIA) and immunochromatography (ICG) used to diagnose norovirus infections generally have high specificity rates but lower sensitivity rates that can change according to the conditions. In this study it was aimed to determine the prevalence of norovirus and other gastroenteritis causative viruses in diarrheal patients and determine the sensitivity and specificity rates of EIA and ICG methods in sporadic cases by the chosen gold standard molecular reference method real-time reverse transcriptase polymerase chain reaction (rRT-PCR). In this study, 184 stool samples that met the study criteria and sent to İstanbul University İstanbul Faculty of Medicine Medical Microbiology Laboratory for routine bacteriological culture between January-July 2018 were included. All samples were evaluated with diagnostic kits BD MAX Enteric Viral Panel (Becton Dickinson, Canada) for rRT-PCR, RIDASCREEN Norovirus 3rd Generation (C1401) (R-Biopharm, Germany) for EIA, RIDAQUICK Norovirus Test (N1402) (R-Biopharm, Germany) for ICG, according to the manufacturer instructions. In terms of the presence of norovirus in 184 stool samples, 7 (3.8%) positive results were obtained by EIA method, 8 (4.3%) by ICG method, and 14 (7.6%) by rRT-PCR method. By accepting the rRT-PCR as a reference method, the sensitivity and specificity of the EIA method were determined as 50% and 100% and of the ICG method as 57% and 100%, respectively. The numbers and percentages of positivity for rotavirus, sapovirus, astrovirus and adenovirus, including coinfections were 30 (16.3%), 5 (2.7%), 2 (1%), 1 (0.5%), respectively. In this study, it was determined that norovirus, alone or together with other viral agents is frequently detected in patients with diarrhea and there was no difference in the frequency between age groups and genders. This causative agent which is not routinely investigated in our country should be considered when evaluating patients with diarrhea and/or vomiting. It seems that EIA and ICG methods are easy to apply, have high specificity but have limited sensitivity in sporadic cases in the diagnosis of norovirus. It is thought that the detection of the true frequency of norovirus and high sensitivity rates can only be achieved by preferring rRT-PCR in the diagnosis. It would be useful for the laboratories to choose the method to be used in the diagnosis of norovirus according to the characteristics of the cases and diagnostic methods.


Retrospective and new records of ticks (Acari: Argasidae, Ixodidae) from the state of Maranhão, an Amazon-Cerrado transition area of Brazil.
The Brazilian state of Maranhão is located in a transition area of the Amazon and Cerrado biomes, where there is a rich fauna of vertebrates. This study aimed to update the list of the ticks occurring in Maranhão, through a compilation of literature records and examination of three tick collections, plus the addition of unpublished collections of ticks from road-killed animals during recent years. Our results indicate that the tick fauna of Maranhão includes 26 species: seven in the family Argasidae (Antricola guglielmonei, Argas miniatus, Ornithodoros cavernicolous, Ornithodoros hasei, Ornithodoros mimon, Ornithodoros rietcorreai and Ornithodoros rudis); and 19 in the family Ixodidae (Amblyomma auricularium-provisional, Amblyomma cajennense sensu stricto, Amblyomma calcaratum, Amblyomma dissimile, Amblyomma geayi, Amblyomma longirostre, Amblyomma naponense, Amblyomma nodosum, Amblyomma oblongoguttatum, Amblyomma ovale, Amblyomma parvum, Amblyomma rotundatum, Amblyomma sculptum, Amblyomma triste, Dermacentor nitens, Ixodes luciae, Haemaphysalis juxtakochi, Rhipicephalus microplus, and Rhipicephalus sanguineus sensu lato). Eleven of the above species are reported for the first time in Maranhão. We consider previous reports of Ornithodoros talaje and Amblyomma pseudoconcolor in Maranhão as misidentification with O. hasei and A. auricularium, respectively. Until 1958, only 11 tick species were reported in Maranhão, with no additional reports until 2009. During 2010-2019, 15 additional species were reported. We also highlight the importance of ticks for public and veterinary health in Maranhão.


Mast cell tumours and other skin neoplasia in Danish dogs--data from the Danish Veterinary Cancer Registry.
The Danish Veterinary Cancer Registry (DVCR) was established in May 2005 to gather information about neoplasms in the Danish dog and cat populations. Practitioners from more than 60 clinics throughout Denmark have submitted data on these species. The objectives of the current study were, with a special focus on mast cell tumours (MCT) to investigate the occurrence, gender distribution, biological behaviour, locations, types, the diagnostic method used and treatment of skin neoplasms in dogs based on information reported to the DVCR. From May 15th 2005 through February 29th 2008, reports on a total of 1,768 canine cases of neoplasia in the skin, subcutis or adnexa were submitted.) Of these, 765 cases (43%) were confirmed by cytology or histopathology. The majority of dogs had a benign neoplasm (66%) while 21% were cases of malignant neoplasia. The most commonly encountered malignant neoplasms were MCT and soft tissue sarcomas and for benign neoplasms, lipomas and histiocytomas were the most common. The location of the neoplasms were primarily in the cutis, subcutis or in the perianal region. The occurrence, gender distribution, biological behaviour and location of canine skin neoplasias in Denmark were similar to earlier reports, although some national variations occurred. A correlation between grade of MCT and the proportion of cases treated surgically was observed. Population based cancer registries like the DVCR are of importance in the collection of non-selected primary information about occurrence and distribution of neoplasms. The DVCR provides detailed information on cases of skin neoplasms in dogs and may serve as a platform for the study of sub-sets of neoplastic diseases (e.g. MCT) or subgroups of the canine population (e.g. a specific breed).


[Analysis of lymph node dissection patterns in D2 radical gastrectomy by hand-assisted laparoscopic technique].
To summarize the experience of lymph node dissection patterns in hand-assisted laparoscopic radical gastrectomy. One hundred and eleven patients with gastric carcinoma between December 2010 and September 2012 were operated by hand-assisted laparoscopic system designed by us. Clinical data were analyzed retrospectively. The lymph nodes were dissected from left to right together with total tumor resection(reverse lymph nodes scavenge pattern), then digestive tract was reconstructed. Total gastrectomy, distal gastrectomy and proximal gastrectomy were performed in 57, 46 and 8 cases respectively. Combined cholecystectomy and lateral segment of left liver lobe were needed in 4 and 2 patients respectively, and 1 case underwent combined splenectomy and pancreatic body and tail resection. TNM staging of patients in I(, II(, III(A, III(B, and IIII( were 16, 8, 35, 14, and 38, respectively. Histological type was poorly differentiated in 78 cases, moderate differentiation in 26 cases and good differentiation in 7 cases. The incision length was(6.8±0.3) cm, blood loss was(238.4±113.6) ml, operative time was (171.9±23.3) min, number of removed lymph node was 17.2±5.7, hospital stay was (10.1±3.7) d, postoperative complication rate was 9.0%. One case died during perioperative time. Hand-assisted laparoscopic D2 radical gastrectomy(reverse lymph nodes scavenge pattern) can avoid the multiple conversion of open-laparoscopic operation model, and is beneficial to the standardization for surgical procedure.


Pathological mechanism of lumbar disc herniation resulting in neurogenic muscle hypertrophy.
We present a 33-year-old man with 5-year history of low back pain who presented with an enlarging right calf. The patient underwent an extensive workup including biopsy without diagnosis. The patient's examination was significant for diminished pinprick sensation in the right L5/S1 dermatome. Reflexes were absent in the right ankle. The circumference of the right calf (58 cm) was twice that of the left. MRI revealed a herniated lumbar disc at the L5/S1 level. He then underwent a L5/S1 microdiscectomy. Following this surgery, the patient noted complete resolution of all sensory deficits in his lower extremity. His calf circumference had decreased by 5 cm at 4 months and by a total of 8 cm at his 2-year post-operative visit. Histological examination of the affected muscle demonstrated severe grouped atrophy of both type I and type II fibers. There was also evidence of compensatory fiber hypertrophy as well as fiber splitting. We concluded that the patient suffered from a herniated lumbar disc causing radiculopathy with calf hypertrophy (neurogenic hypertrophy). To our knowledge this is the first report of both grouped atrophy and compensatory hypertrophy of both muscle fiber types seen in this phenomenon.


Roles for soluble guanylate cyclase and a thiol oxidation-elicited subunit dimerization of protein kinase G in pulmonary artery relaxation to hydrogen peroxide.
We have previously provided evidence that hydrogen peroxide (H(2)O(2)) stimulates soluble guanylate cyclase (sGC) under conditions where it relaxes isolated endothelium-removed bovine pulmonary arteries (BPAs). Since it was recently reported that H(2)O(2) induces coronary vasorelaxation associated with a nitric oxide/cGMP-independent thiol oxidation/subunit dimerization-elicited activation of protein kinase G (PKG), we investigated whether this mechanism participates in the relaxation of BPAs to H(2)O(2). BPAs precontracted with serotonin (incubated under hypoxia to lower endogenous H(2)O(2)) were exposed to increasing concentrations of H(2)O(2). It was observed that 0.1-1 mM H(2)O(2) caused increased PKG dimerization and relaxation. These responses were associated with increased phosphorylation of vasodilator-stimulated phosphoprotein (VASP) at the serine-239 site known to be mediated by PKG. Treatment of BPAs with 1 mM DTT attenuated PKG dimerization, VASP phosphorylation, and relaxation to H(2)O(2). An organoid culture of BPAs for 48 h with 10 μM 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), a heme oxidant inhibitor of sGC activation, depleted sGC expression by 85%, associated with a 67% attenuation of VASP phosphorylation and 48% inhibition of relaxation elicited by 100 μM H(2)O(2). Thus both a sGC activation/cGMP-dependent and a thiol oxidation subunit dimerization/cGMP-independent activation of PKG appear to contribute to the relaxation of BPAs elicited by H(2)O(2).


Direct observation of an electrically degenerate interface layer in a GaN/sapphire heterostructure.
An electrically degenerate layer deteriorates the optoelectric performance of a wide band gap semiconductor grown on an insulator substrate. This detrimental effect can be passively avoided by using a buffer layer to harbor various lattice defects. However, the longstanding scientific questions regarding the microscopic origin of the degenerate interface layer and the effect of local changes in the atomic structure and chemical environment at an interface on the functionality of a desired film have remained unanswered. Moreover, this is key information for the development of ultrathin optoelectronic devices. In this study, we discuss the direct observation of a degenerate interface phase at the GaN/sapphire interface on an atomic scale. By combining high-resolution transmission electron microscopy and electron energy loss spectroscopy, we detect the presence of an ultrathin (∼6.5 Å) α-Ga2O3-x layer near the GaN/sapphire interface, which is subjected to ∼4.5% biaxial compressive strain and contains many oxygen vacancies. Density functional theory calculations show that the presence of a defective α-Ga2O3-x thin layer in the GaN and sapphire heterostructure remarkably reduces the band offset between the α-Ga2O3-x conduction band and the GaN valence band, thereby exerting a significant influence on the conductivity enhancement of the interface. Our results provide an unprecedented integrated picture of the degenerate interface phenomenon on an atomic scale, which would evolve the fundamental understanding about a wide band gap semiconductor heterostructure system.


BBS7 and TTC8 (BBS8) mutations play a minor role in the mutational load of Bardet-Biedl syndrome in a multiethnic population.
Bardet Biedl syndrome is a genetically heterogeneous ciliopathy with fourteen genes currently identified. To date, mutations in BBS7 and TTC8 (BBS8) were reported in 4.2% and 2.8% of BBS families respectively. We sequenced the coding regions of BBS7 and TTC8 in 35 BBS families of diverse ancestral backgrounds. In addition, the role of putative modifier genes on phenotype severity; NXNL1 and MGC1203 c.430C>T, was assessed. Genotype-phenotype correlation was explored in patients with identified mutations. Four novel pathogenic BBS7 changes were identified in 2/35 families (5.7%). In one family with two affected individuals with BBS7 mutations, a more severe phenotype was observed in association with a third mutation in BBS4. The overall retinal phenotype appeared more severe than that seen in patients with BBS1 mutations. This study confirms the small role of BBS7 and TTC8 in the overall mutational load of BBS patients. The variability of the ocular phenotype observed, could not be explained by the putative modifier genes; NXNL1 and MGC1203 c.430C>T.


The role of different chemical modifications of superoxide dismutase in preventing a prolonged muscular ischemia/ reperfusion injury.
It is well know that a long period of ischemia followed by reperfusion can create an irreversible tissue damage, also due to the excessive generation of oxygen-derived free radicals. A possibility for avoiding this syndrome is represented by the use of free radical scavengers, such as the superoxide dismutase (SOD). The current authors compared the results achieved through different modifications of this enzyme in an experimental rat hind limb model of ischemia/reperfusion. 60 rats that had a 4 hour and 30 minute ischemia of the left hind limb were divided into four groups of 15 each and treated using a physiological solution (control group), native SOD, monomethoxypolyethylene-glycol-SOD (mPEG-SOD) or poly(acryloilmorpholine)-SOD (PAcM-SOD). The outcomes obtained in terms of limb survival (p < 0.05), as well as histomorphologic studies (p < 0.0005), revealed a superior capacity of mPEG-SOD when compared with the other three substances.


[The toxic and immunomodulating properties of the somatic O-antigen polysaccharide of typhoid bacteria].
In experiments on random bred mice and mice of various strains it was shown that when administered parenterally typhoid bacteria O-somatic antigen polysaccharide possesses the immunomodulatory properties. It stimulates the non-specific resistance of the organism to bacterial infection, produces the polyclonal activation of beta-lymphocytes, possesses the adjuvant properties, activates cells of the mononuclear phagocytic system. At administration in therapeutic doses the drug is not toxic, possesses no carcinogenic, mutagenic and allergenic properties.


CsHgNO3Cl2: A New Nitrate UV Birefringent Material Exhibiting an Optimized Layered Structure.
Developing effective strategies to design novel, excellent birefringent materials has become an emerging challenge. Herein, we report a new UV nitrate birefringent material, CsHgNO3Cl2, which is an analogue of the known UV carbonate nonlinear optical crystal KCaCO3F. In CsHgNO3Cl2, a perfect layered structure was produced owing to the alliance of a planar π-conjugated anion NO3- and highly electropolarized Hg2+ cation. The optimized layered structure that is beneficial in enlarging the optical anisotropy induced a large birefringence (Δn = 0.145@546 nm) for CsHgNO3Cl2, even superior to that of the well-known commercial birefringent material α-BBO in the UV region. The strategy that the optimization of planar functional group arrangement is able to boost birefringence is expected to guide the development of high-performance birefringent materials in the future, especially in the field of UV.


Efficiency of the Green Synthesized Nanoparticles as New Tools in Cancer Therapy: Insights on Plant-Based Bioengineered Nanoparticles, Biophysical Properties, and Anticancer Roles.
The aim of this work is to review the current knowledge on the efficiency of plant-based synthesized nanoparticles in medical field, particularly in the prevention, diagnosis, and therapy of cancer. For this, we examine the advantages of nanotechnological tools. Besides, a particular attention was given to understand the mechanism by which plant-based bioengineered nanoparticles can interact with components of cancerous cells. Green biosynthesized nanoparticles seem to be novel tool for prognostic biomarkers for cancer diagnosis and drug delivery in tumor cells. They can act either by leading to the damage of tumor cells, or by the protection of healthy cells, via mechanisms involving the specific properties of nanoparticles themselves and the antioxidative and antitumor properties found in plants. However, special attention should be given to the choice of plant species, extracts, and the toxic dose of some phytocompounds during the biosynthesis process. An increase in metal or trace element release from metal and metal oxide biosynthesized nanoparticles can lead to greater oxidative stress, which is associated with higher risk of cancer. Hence, plant-based nanosystems should be more developed to increase their specific targeting of the cancerous cells, in order to preserve the healthy ones.


Clinical implications of the molecular genetics of chronic lymphocytic leukemia.
Genetics and molecular genetics have contributed to clarify the biological bases of the clinical heterogeneity of chronic lymphocytic leukemia. In recent years, our knowledge of the molecular genetics of chronic lymphocytic leukemia has significantly broadened, offering potential new clinical implications. Mutations of TP53 and ATM add prognostic information independently of fluorescence in situ hybridization cytogenetic stratification. In addition, next generation sequencing technologies have allowed previously unknown genomic alterations in chronic lymphocytic leukemia to be identified. Mutations of NOTCH1, SF3B1 and BIRC3 have been associated with short time to progression and survival. Each of these lesions recognizes a different distribution across different clinical phases and biological subgroups of the disease. The clinical implications of these molecular lesions are in some instances well established, such as in the case of patients with TP53 disruption, who should be considered for alternative therapies/allogeneic stem cell transplant upfront, or in patients with ATM disruption, who are candidates to rituximab-based immunochemotherapy. On the contrary, NOTCH1, SF3B1 and BIRC3 mutations appear to have a specific significance, the clinical value of which is currently being validated, i.e. association to Richter syndrome transformation for NOTCH1 mutations, and short progression-free survival after treatment for SF3B1 mutations. Certainly, these new lesions have helped clarify the molecular bases of chronic lymphocytic leukemia aggressiveness beside TP53 disruption. This review covers the recent advancements in our understanding of the molecular genetics of chronic lymphocytic leukemia and discusses how they are going to translate into clinical implications for patient management.


Skeletal lesions in a population of Virginia opossums (Didelphis virginiana) from Baldwin County, Georgia.
Antemortem skeletal lesions were analyzed in 61 Virginia opossums (Didelphis virginiana) collected as roadkill from Baldwin County, Georgia, USA. As evidenced by bridging fracture calluses, misalignments, bone-surface depressions, perforations, localized superficial calluses, periosteal proliferations, and bony bridges across intervertebral disk spaces, 64% of the individuals had signs of one or more healed injuries. Within the subset of skeletons with bone lesions, 54% had healed rib fractures and 23% had scapular, 21% pelvic, 18% fibular, 18% vertebral, 13% dentary, 10% tibial, and 10% podial lesions. Bone lesions occurred most frequently in the cranial portion of the skeletons and averaged approximately four per individual. The majority of the skeletal injuries appeared to be inconsistent with those caused by falls or automobile collisions. The nature and position of the bone lesions suggested that nonfatal predator attacks, possibly from domestic dogs, may be a significant contributor to bodily injury in this species.


Protein composition of human prespliceosomes isolated by a tobramycin affinity-selection method.
Detailed knowledge of the composition and structure of the spliceosome and its assembly intermediates is a prerequisite for understanding the complex process of pre-mRNA splicing. To this end, we have developed a tobramycin affinity-selection method that is generally applicable for the purification of native RNP complexes. By using this method, we have isolated human prespliceosomes that are ideally suited for both biochemical and structural studies. MS identified >70 prespliceosome-associated proteins, including nearly all known U1 and U2 snRNP proteins, and expected non-snRNP splicing factors. In addition, the DEAD-box protein p68, RNA helicase A, and a number of proteins that appear to perform multiple functions in the cell, such as YB-1 and TLS, were detected. Several previously uncharacterized proteins of unknown function were also identified, suggesting that they play a role in splicing and potentially act during prespliceosome assembly. These data provide insight into the complexity of the splicing machinery at an early stage of its assembly.


With peppermints you're not my prince: aroma modulates self-other integration.
Recent studies showed that self-other integration, as indexed by the joint Simon effect (JSE), can be modulated by biasing participants towards particular (integrative vs. exclusive) cognitive-control states. Interestingly, there is evidence suggesting that such control states can be induced by particular odors: stimulating odors (e.g., peppermint aroma) seem to induce a more focused, exclusive state; relaxing odors (e.g., lavender aroma) are thought to induce a broader, more integrative state. In the present study, we tested the possible impact of peppermint and lavender aromas on self-other integration. Pairs of participants performed the joint Simon task in an either peppermint- or lavender-scented testing room. Results showed that both aromas modulated the size of the JSE, although they had a dissociable effect on reaction times (RTs) and percentage of errors (PEs). Whilst the JSE in RTs was found to be less pronounced in the peppermint group, compared to the lavender and no-aroma groups, the JSE in PEs was significantly more pronounced in the lavender group, compared to the peppermint and no-aroma group. These results are consistent with the emerging literature suggesting that the degree of self-other integration does not reflect a trait but a particular cognitive state, which can be biased towards excluding or integrating the other in one's self-representation.