Two decades of socioeconomic inequalities in the prevalence of untreated dental caries in early childhood: Results from three birth cohorts in southern Brazil.
To estimate the socioeconomic disparities in untreated dental caries in early childhood according to socioeconomic characteristics in three birth cohorts in Southern Brazil. The socioeconomic data to this study were collected at the 48-month follow-up and oral health studies of 1993, 2004 and 2015 Pelotas birth cohort studies. The outcome was untreated dental caries in children aged 6 (1993 cohort), 5 (2004 cohort) and 4 years (2015 cohort), dichotomized into absence/presence. Analyses were stratified by maternal skin colour/race, maternal education and family income. For statistical purposes, the prevalence difference, relative risk and absolute and relative indices of health inequality (Slope Index of Inequality-SII and Concentration Index-CIX) were used. The prevalence of untreated dental caries in primary dentition was 63.4%, 45.5% and 15.6%, in 1993, 2004 and 2015 cohorts, respectively. The prevalence of untreated dental caries was concentrated in the poorest quintile and lower maternal education group in both absolute (SII) and relative (CIX) measures of inequality, being characterized as a pro-poor event. A higher risk of untreated caries was found in the poorest quintile of family income compared with the richest quintile in the 1993 cohort (RR 1.44 [95% CI 1.05; 1.98]). That risk was higher considering the 2004 Cohort (RR 1.78 [95% CI 1.42; 2.23]) and 2015 cohort (RR 4.20 [95% CI 2.97; 5.94]) data. Over the course of two decades, a higher prevalence of untreated dental caries is concentrated among the most socioeconomically deprived children.


Decitabine in the Treatment of Acute Myeloid Leukemia and Myelodysplastic Syndromes, Which Combined with Complex Karyotype Respectively.
We conducted a study exploring the clinical safety and efficacy of decitabine in patients with acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS), combined with a complex karyotype. From April 2009 to September 2013, a total of 35 patients with AML/MDS combined with a complex karyotype diagnosed in the First Affiliated Hospital of Soochow University were included for retrospective analysis. All patients were treated with decitabine alone (20 mg/m2 daily for 5 days) or combination AAG chemotherapy (Acla 20 mg qod*4d, Ara-C 10 mg/m2 q12h*7d, G-CSF 300 μg qd, the dose of G-CSF adjusted to the amount in blood routinely). In 35 patients, 15 exhibited a complete response (CR), and 6 a partial response (PR), the overall response rate (CR+PR) being 60% (21 of 35). Median disease-free survival was 18 months and overall survival was 14 months. In the 15 MDS patients with a complex karyotype, the CR rate was 53.3% (8 of 15); in 20 AML patients with complex karyotype, the overall response rate was 65% (13 of 20). The response rate of decitabine alone (22 cases) was 56.5% (13 of 22), while in the combination chemotherapy group (13 cases), the effective rate was 61.5% (8 of 13)(P>0.05). There are 15 patients with chromosome 7 aberration, after treatment with decitabine, 7 CR, 3 PR, overall response rate was 66.7% (10 of 15). Of 18 patients with 3 to 5 kinds of chromosomal abnormalities, 66.7% demonstrated a response; of 17 with more than 5 chromosomal abnormalities, 52.9% had a response. In the total of 35 patients, with one course (23 patients) and ≥two courses (12 patients), the overall response rate was 40.9% and 92.3% (P<0.05). Grade III to IV hematological toxicity was observed in 27 cases (75%). Grade III to IV infections were clinically documented in 7 (20%). Grades I to II non-hematological toxicity were infections (18 patients), haematuria (2 patients), and bleeding (3 patients). With follow-up until September 2013, 7 patients were surviving, 18 had died and 10 were lost to follow-up. In the 6 cases who underwent allogeneic hematopoietic stem cell transplantation (HSCT) all were still relapse-free survivors. Decitabine alone or combination with AAG can improve outcome of AML/MDS with a complex karyotype, there being no significant difference decitabine in inducing remission rates in patients with different karyotype. Increasing the number of courses can improve efficiency. This approach with fewer treatment side effects in patients with a better tolerance should be employed in order to create an improved subsequent chance for HSCT.


A Deep Learning-Based Radiomic Classifier for Usual Interstitial Pneumonia.
Because chest CT scan has largely supplanted surgical lung biopsy for diagnosing most cases of interstitial lung disease (ILD), tools to standardize CT scan interpretation are urgently needed. Does a deep learning (DL)-based classifier for usual interstitial pneumonia (UIP) derived using CT scan features accurately discriminate radiologist-determined visual UIP? A retrospective cohort study was performed. Chest CT scans acquired in individuals with and without ILD were drawn from a variety of public and private data sources. Using radiologist-determined visual UIP as ground truth, a convolutional neural network was used to learn discrete CT scan features of UIP, with outputs used to predict the likelihood of UIP using a linear support vector machine. Test performance characteristics were assessed in an independent performance cohort and multicenter ILD clinical cohort. Transplant-free survival was compared between UIP classification approaches using the Kaplan-Meier estimator and Cox proportional hazards regression. A total of 2,907 chest CT scans were included in the training (n = 1,934), validation (n = 408), and performance (n = 565) datasets. The prevalence of radiologist-determined visual UIP was 12.4% and 37.1% in the performance and ILD clinical cohorts, respectively. The DL-based UIP classifier predicted visual UIP in the performance cohort with sensitivity and specificity of 93% and 86%, respectively, and in the multicenter ILD clinical cohort with 81% and 77%, respectively. DL-based and visual UIP classification similarly discriminated survival, and outcomes were consistent among cases with positive DL-based UIP classification irrespective of visual classification. A DL-based classifier for UIP demonstrated good test performance across a wide range of UIP prevalence and similarly discriminated survival when compared with radiologist-determined UIP. This automated tool could efficiently screen for UIP in patients undergoing chest CT scan and identify a high-risk phenotype among those with known ILD.


Hemophagocytic Lymphohistiocytosis, an Unclear Nosologic Entity: Case Report of an Adult Man with Rising of Amylase and Lipase and Spinal Cord Infiltration.
Here we present the case of a 57-years old patient affected by hemophagocytic lymphohistiocytosis (HLH), a rare disease characterized by an uncontrolled immune activation, resulting in clinical and biochemical manifestations of extreme inflammation. In a previous hospitalization, the patient showed fever, hepato-splenomegaly, pancytopenia, hyperferrtitinemia, lymphadenopathy and cholestasis. No diagnosis was done, however, he totally recovered after splenectomy. Eight months later, he relapsed, showing also hypofibrinogenemia, hypertriglyceridemia, hemophagocytic signs in bone marrow, cholestatic jaundice, high LDH and high PT-INR. Interestingly, he presented increased levels of amylase and lipase in absence of radiologic signs of pancreatitis. He was treated with Dexamethasone and Cyclosporine according to HLH-2004 guidelines. The clinical and biochemical manifestations disappeared in a few weeks, but he was newly hospitalized for lower limbs hypotonia caused by a hemophagocytic lesion of the cauda equina and lumbar cord. The death occurred in a few days, despite the immunosuppressive treatment.


Familial disease of the renal medulla. A study of progeny in a family with medullary cystic disease.
Cystic disease of the renal medulla is rarely diagnosed before end-stage renal failure appears. To discover early signs of disease in an affected family, we studied renal function and intravenous pyelography in 12 asymptomatic children of three sisters with this disorder. Defects in urine concentrating ability and X-ray abnormalities indistinguishable from medullary sponge kidney were found. While these changes probably represent early manifestations of medullary cystic disease, a clear separation between medullary cystic disease and medullary sponge kidney cannot be made in our patients. We propose that the designation "familial disease of the renal medulla" be used for such patients, with further classification determined by evidence of progressive disease.


Quetiapine reduces irritability and risk of suicide in patients with agitated depression.
Patients who suffer from agitated depression accompanied by psychomotor agitation and irritability are prone to suicidal ideation and attempts and must therefore be diagnosed and treated with utmost care. Clinically, there have been more than a few cases of suicidal attempts that seemed to have been provoked by careless prescription of antidepressant medication. In the present study, administration of quetiapine to 3 patients in the acute phase of agitated depression resulted in rapid improvement in irritability and alleviation of depression. Depression in these 3 patients was caused by chronic (persistent) anxiety and tension. During the acute phase, the patients evidenced psychomotor agitation and irritability, often experiencing a sudden, overwhelming urge to commit suicide. Findings from the present study suggest that treatment with quetiapine in patients with this type of agitated depression can quickly alleviate symptoms of anxiety and irritability and reduce the risk of suicide.


Major histocompatibility complex class I-restricted activation of cloned T cells by a soluble protein in the absence of accessory cells.
A T-cell clone, 10BK.1, was established from the draining lymph nodes of (B10 x B10.BR)F1 mice immunized with ovalbumin (OVA) according to standard protocols. Upon coculture with the antigen, 10BK.1 cells reacted by production of lymphokines and by proliferation despite the absence of additional antigen-presenting cells. These T cells do not express major histocompatibility complex (MHC) class II molecules on the cell surface as assessed on the basis of several criteria: by cytofluorometric analysis I-A and I-E determinants were not detectable; 10BK.1 cells could not act as antigen-presenting cells for long-term-cultured MHC class II-restricted T-cell clones; and monoclonal antibodies directed at both MHC class II isotypic complexes (I-A, I-E) did not suppress their OVA-induced activation. In contrast, proliferation of 10BK.1 T cells in response to OVA was abrogated by antibodies directed at H-2Kb antigens. Inhibition experiments employing antibodies directed at Lyt-2 and L3T4 antigens in addition to cytofluorometric analysis revealed that T-cell clone 10BK.1 exhibits the Thy-1+,Lyt-2+,Ly-1-,L3T4- phenotype. 10BK.1 cells pulsed with OVA and fixed with glutaraldehyde induced proliferation of untreated 10BK.1 cells. These data support the theory that 10BK.1 T cells present the exogenous globular protein OVA to one another in an MHC class I-restricted manner, resulting in cell activation and proliferation independent of added accessory cells.


Comparison of subjective and fully automated methods for measuring mammographic density.
Background Breast radiologists of the Norwegian Breast Cancer Screening Program subjectively classified mammographic density using a three-point scale between 1996 and 2012 and changed into the fourth edition of the BI-RADS classification since 2013. In 2015, an automated volumetric breast density assessment software was installed at two screening units. Purpose To compare volumetric breast density measurements from the automated method with two subjective methods: the three-point scale and the BI-RADS density classification. Material and Methods Information on subjective and automated density assessment was obtained from screening examinations of 3635 women recalled for further assessment due to positive screening mammography between 2007 and 2015. The score of the three-point scale (I = fatty; II = medium dense; III = dense) was available for 2310 women. The BI-RADS density score was provided for 1325 women. Mean volumetric breast density was estimated for each category of the subjective classifications. The automated software assigned volumetric breast density to four categories. The agreement between BI-RADS and volumetric breast density categories was assessed using weighted kappa (kw). Results Mean volumetric breast density was 4.5%, 7.5%, and 13.4% for categories I, II, and III of the three-point scale, respectively, and 4.4%, 7.5%, 9.9%, and 13.9% for the BI-RADS density categories, respectively ( P for trend < 0.001 for both subjective classifications). The agreement between BI-RADS and volumetric breast density categories was kw = 0.5 (95% CI = 0.47-0.53; P < 0.001). Conclusion Mean values of volumetric breast density increased with increasing density category of the subjective classifications. The agreement between BI-RADS and volumetric breast density categories was moderate.


Wireless precision piezoelectric thermometer using an RF excitation-detection technique with an NMR probe.
Based on an inductive RF excitation-detection scheme, a quartz-crystal temperature-measuring device is described for applications in MRI and MRS scanners where strong electric and magnetic fields are present. A quartz-crystal resonator with a high temperature sensitivity (88 ppm/degrees C) is employed as the temperature sensor. Changes in the quartz resonance frequency reflecting temperature variations are detected by a NMR coil multiply tuned to the resonance frequencies of the quartz crystal and the nuclei of interest. This wireless probe is simple to build and is capable of measuring temperature changes from -50 to +150 degrees C. The high frequency linearity of the device in this temperature region ensures a simple calibration procedure and a constant temperature resolution.


Enhancement of Alkaline Hydrogen Oxidation Reaction of Ru-Ir Alloy Nanoparticles through Bifunctional Mechanism on Ru-Ir Pair Site.
Anion exchange membrane fuel cells (AEMFCs) are being developed for practical use. However, it is necessary to improve the hydrogen oxidation reaction (HOR) under alkaline conditions to enhance the performance of AEMFCs. In this study, carbon-supported Ru-Ir alloy nanoparticle catalysts (Ru-Ir/C) were developed because they offer higher HOR activity compared with the Pt-based catalysts. The mechanism of HOR enhancement on Ru-Ir/C was studied to reveal the effect of the surface composition of Ru/Ir on the HOR activity. The results showed that the HOR activity is related to the surface pair probability of Ru-Ir, Ru-Ru, and Ir-Ir but not to the hydrogen binding energy (HBE). In addition, the Ru-Ir pair site was found to be highly active, which can promote the HOR through a bifunctional mechanism that involves Ru-Ir pairs providing reactive OH- and H species, respectively.


Expression of the aquaporin 8 water channel in a rat salivary epithelial cell.
Aquaporins are a family of water channels considered to play an important role in fluid transport across plasma membranes. Among the reported isoforms, relatively little is known about the functional role of aquaporin 8 (AQP8), and there are no cell lines known to express the AQP8 protein. We report here that the rat submandibular epithelial cell line, SMIE, expresses AQP8. Using RT-PCR, the presence of mRNA for AQP8 was demonstrated in these cells. Confocal immunofluorescence experiments revealed that the AQP8 protein is primarily present in the apical membranes of SMIE cells. When grown as a polarized monolayer on collagen coated polycarbonate filters, and exposed on their apical surface to different hyperosmotic (440, 540, or 640 mOsm) solutions, net fluid movement across SMIE cells was 8-25-fold that seen under isosmotic conditions. Similarly, when grown on coverslips and then exposed to a hypertonic solution, SMIE cells shrunk as a function of time. Together, these results suggest that SMIE cells endogenously express functional AQP8 water channels.


[Activity of motorcycle taxi driver: risks and weaknesses self referred].
Descriptive research, with qualitative approach, that aimed to identify occupational hazards and weaknesses self-reported by motorcycle drivers. Data were collected in the first half of 2010 through interviews with twelve motorcycle drivers, invited to participate and work on two central points of a municipality in the state of Rio Grande do Sul, Brazil. Data were analyzed using thematic analysis, from which emerged five categories. According to subjects' perception, accidents and assaults represent the greatest risks of the profession. It can be inferred that the actions of health education and disease prevention should be governmental and no governmental strategies that would assign value to the health and safety of these workers.


[Primary Kaposi's sarcoma of the penis in a patient with acquired immunodeficiency syndrome].
Presentation of one case of a 40 year-old, homosexual, AIDS diagnosed male with extrapulmonary tuberculosis (lymphatic nodes) and prior history of gonococcal urethritis, brain toxoplasmosis, molluscum contagiosum and pneumonia by Pneumocystis carinii. A purpura-type lesion with inflammatory features appeared in the foreskin which was diagnosed as primary Kaposi's sarcoma of the penis. The article explains the clinical signs and symptoms, laboratory data, histological findings, and it reviews the literature.


Dietary Approaches to Stop Hypertension Diet, Weight Status, and Blood Pressure among Children and Adolescents: National Health and Nutrition Examination Surveys 2003-2012.
The Dietary Approaches to Stop Hypertension (DASH) diet is associated with lower blood pressure and reduced risk of cardiovascular disease among adults, but little is known about accordance with this dietary pattern or health benefits among children and adolescents. The objectives were to evaluate accordance with the DASH diet, differences over time, and the association with health attributes among a nationally representative sample of US children and adolescents. Cross-sectional data from the 2003-2012 National Health and Nutrition Examination Surveys (NHANES) were analyzed. Data from 9,793 individuals aged 8 to 18 years were examined. DASH accordance was estimated based on nine nutrient targets: total fat, saturated fat, protein, cholesterol, fiber, calcium, magnesium, potassium, and sodium; possible score range is 0 to 9. Accordance with the DASH diet across time was examined comparing the 2011-2012 to 2003-2004 NHANES surveys. The association between DASH score and weight status was examined using multinomial logistic regression, and the associations with waist circumference, systolic blood pressure, and diastolic blood pressure were examined using multivariable linear regression. Accordance with the DASH diet was low across the age groups, with a range of mean DASH scores from 1.48 to 2.14. There were no significant changes across time. DASH score was inversely associated with systolic blood pressure (mm Hg) among 14- to 18-year-olds (β=-.46; 95% CI -.83 to -.09) among the larger sample of participants who completed at least one dietary recall, but no significant differences were seen in other age categories. In the subsample of participants with both dietary recalls, a significant inverse association was seen between DASH score and systolic blood pressure for 11- to 13-year-olds (β=-.57; 95% CI -1.02 to -.12). There were no significant associations between this dietary pattern and weight status, waist circumference, or diastolic blood pressure. Few US children and adolescents have diets that are in alignment with the DASH diet. Future research should explore strategies to encourage fruit, vegetable, and whole-grain consumption, as well as sodium reductions to help meet DASH nutrient targets in children and adolescents, as well as examine the potential benefits of this eating pattern on health in this population group.


Ex-vivo lung perfusion: the model for the organ reconditioning hub.
Lung evaluation and reconditioning by ex-vivo lung perfusion (EVLP) is becoming increasingly established. We review strategies for broader implementation of this technology to transplant centers worldwide. The organ reconditioning hub model is a viable strategy for disseminating EVLP to small and large transplant centers given the well tolerated prolongation of preservation time afforded by EVLP. Regulatory and process issues remain hurdles to be overcome. EVLP demonstrates promise to increase lung utilization. Organ reconditioning hubs appear to be an efficient method of delivering this promise to all transplant centers, not necessarily only the largest ones. Organ allocation processes will need to adapt to this new paradigm of organ preservation and evaluation. Moreover, regulatory issues will need to be deliberated by the transplant community.


Energy gaps and stark effect in boron nitride nanoribbons.
A first-principles investigation of the electronic properties of boron nitride nanoribbons (BNNRs) having either armchair or zigzag shaped edges passivated by hydrogen with widths up to 10 nm is presented. Band gaps of armchair BNNRs exhibit family dependent oscillations as the width increases and, for ribbons wider than 3 nm, converge to a constant value that is 0.02 eV smaller than the bulk band gap of a boron nitride sheet owing to the existence of very weak edge states. The band gap of zigzag BNNRs monotonically decreases and converges to a gap that is 0.7 eV smaller than the bulk gap due to the presence of strong edge states. When a transverse electric field is applied, the band gaps of armchair BNNRs decrease monotonically with the field strength. For the zigzag BNNRs, however, the band gaps and the carrier effective masses either increase or decrease depending on the direction and the strength of the field.


Self-assessment of cancer competencies and physician assistant cancer education: instrument development and baseline testing.
Although the benefits of primary and secondary prevention of cancer are well recognized among health care providers, insufficient knowledge or skill often leads to inadequate assessment and management, particularly in the primary care setting. The scant literature on physician assistant (PA) cancer-related competencies suggests that PAs may not be well-prepared in this arena. Thus, curriculum reform in PA education is paramount for improving PAs' abilities to provide cancer risk assessment and management services. The Physician Assistant Cancer Education (PACE) project was designed for such a purpose. Following instrument development, baseline measurement of perceived abilities for cancer-related core competencies was assessed in a representative cohort of PA students. Literature search strategies, expert review, and a nationwide survey of PA program directors yielded the 26-item Competencies in Cancer Assessment and Management (C-CAM) instrument. Baseline self-efficacy data were gathered from students across eight PACE-affiliated PA programs. Statistical analysis focused upon instrument quality and comparisons of reported self-efficacy among respondent cohorts. Data were collected from 544 PA students. Overall instrument reliability was excellent (Chronbach's alpha 0.97). Exploratory factor analysis identified three factors explaining 72.83% of response variance. Mean values varied somewhat across institutional cohorts. Clinical students demonstrated higher self-efficacy than preclinical students. The C-CAM is an effective instrument to assess PA student self-efficacy in cancer prevention, risk assessment, and risk management competencies. Although a trend toward higher self-efficacy was observed among clinical students, further research is required to assess the extent to which reported self-efficacy may be expected to change over time.


Cephalothin. Its in vitro antibacterial spectrum as studied in a diagnostic laboratory.
Of 655 bacterial strains isolated in a routine clinical diagnostic laboratory, 564 (86 per cent) were found sensitive to cephalothin by disk sensitivity test. However, the fraction of sensitive Gram-negative bacilli and enterococci declined sharply at concentrations approximating those obtained in serum after the usual recommended dosages. Gram-positive bacteria remained sensitive throughout the entire range of testing concentrations. Unless very high dosages are used, cephalothin cannot be considered a broad-spectrum antibacterial agent for use while cultures are pending. Even with very high dosages all strains of Pseudomonas spp. and significant fractions of other Gram-negative bacillary species remain resistant to cephalothin. If used alone, the high potency cephalothin disk may yield inadequate information and should be supplemented by a lower potency disk, standardized measurements of zone diameters, or a screening plate.


Organochlorine pesticides and chlorinated hydrocarbon solvents in the blood of chemically sensitive patients [corrected]. A statistical comparison with therapeutic medication and natural hormones.
The blood levels of organochlorine pesticides and chlorinated hydrocarbon solvents were measured in 200 and 114 chemically sensitive patients respectively, and compared with blood concentrations of standard medication (non- chlorinated substances. Clonidine, Haloperidol) of comparable toxicity after therapeutically effective dosage, and with reference levels of highly potent chemicals in the blood such as hormones. It was shown that the average blood levels of the most toxic environmental pollutants are comparable with the therapeutic steady state average blood levels of medications which have similar toxicities in the animal model. In addition the toxicity levels of xenoestrogens are at least an order of magnitude higher than normal plasma estrogen or progesterone levels. These findings suggest the possibility of additive or synergistic effects of these chlorinated compounds and the aforementioned medications. Also, these findings suggest the possibility of hormone deregulation from exposure to the aforementioned toxic chlorinated compounds.


Dehydroepiandrosterone alters vitamin E status and prevents lipid peroxidation in vitamin E-deficient rats.
In humans, dehydroepiandrosterone and its sulfate ester metabolite DHEA-S are secreted predominantly from the adrenal cortex, and dehydroepiandrosterone is converted to steroid hormones, including androgens and estrogens, and neurosteroid. Dehydroepiandrosterone exerts protective effects against several pathological conditions. Although there are reports on the association between dehydroepiandrosterone and vitamins, the exact relationship between dehydroepiandrosterone and vitamin E remains to be determined. Therefore, we attempted to elucidate the effect of dehydroepiandrosterone on vitamin E status and the expression of various vitamin E-related proteins, including binding proteins, transporters, and cytochrome P450, in vitamin E-deficient rats. Plasma α-tocopherol levels in vitamin E-deficient rats increased in response to dehydroepiandrosterone administration. The expression of hepatic α-tocopherol transfer protein was repressed in vitamin E-deficient rats compared to that in control rats; however, dehydroepiandrosterone administration significantly upregulated this expression. Hepatic expression of CYP4F2, an α-tocopherol metabolizing enzyme, in vitamin E-deficient rats was decreased by dehydroepiandrosterone administration, whereas hepatic expression of ATP-binding cassette transporter A1, an α-tocopherol transporter, was not altered following dehydroepiandrosterone administration. Dehydroepiandrosterone repressed lipid peroxidation in the liver of vitamin E-deficient rats. Therefore, adequate dehydroepiandrosterone supplementation may improve lipid peroxidation under several pathological conditions, and dehydroepiandrosterone may modulate α-tocopherol levels through altered expression of vitamin E-related proteins.


A review of the use of stimulants and stimulant alternatives in treating bipolar depression and major depressive disorder.
Prescribers often consider the off-label use of stimulants or stimulant alternatives as adjunctive antidepressants. The authors reviewed the available literature on the efficacy of these agents for treatment of refractory unipolar and bipolar depression. PubMed, MEDLINE, and relevant English-language literature from 1988-2013 were searched. Keywords were dopaminergic, stimulant, augmentation, treatment refractory depression, dextroamphetamine, methylphenidate, modafinil, atomoxetine, and cardiovascular safety. All randomized controlled trials (RCTs) published during this time period were included. When RCTs were unavailable, open studies were summarized. Data on the efficacy of stimulants and stimulant alternatives as treatment augmentation for unipolar and bipolar depression were extracted. Three open studies showed positive findings for dopaminergic stimulants, and, although 2 RCTs showed negative findings, a recent RCT revealed positive results for lisdexamfetamine as an adjunctive agent. To date, dopaminergic stimulants have not been tested in bipolar depression RCTs. Four completed RCTs suggested that modafinil/armodafinil were beneficial as treatment adjuncts for unipolar and bipolar depression, with very low rates of mood switch in bipolar depression. One study was stopped prematurely due to safety concerns of increased suicidality. Modafinil and armodafinil are recommended treatment adjuncts for refractory unipolar and bipolar depression. Until recently, RCT data on dopaminergic stimulants were too limited to warrant their use as first-line treatment adjuncts. However, the promising results of 1 recent lisdexamfetamine RCT, when considered in the context of the deleterious effect of subsyndromal depression, suggest consideration of dopaminergic medications in treatment-refractory unipolar or bipolar depression when modafinil is cost prohibitive or otherwise contraindicated.


Virucidal efficacy of four new disinfectants.
Virucidal efficacy was evaluated for four recently available disinfectants: chlorine dioxide, potassium peroxymonosulfate, a quaternary ammonium compound, and citricidal (grapefruit extract). Sodium hypochlorite (3%) and tap water were used as positive and negative controls respectively. Feline herpesvirus, feline calicivirus, and feline parvovirus were exposed to the manufacturers' recommended dilutions of the evaluated disinfectants. Both chlorine dioxide and potassium peroxymonosulfate completely inactivated the three viruses used in this study. These disinfectants can aid in controlling nosocomial transmission of viruses with less of the deleterious effects of sodium hypochlorite. The quaternary ammonium compound evaluated in this study and citricidal were not effective against feline calicivirus and feline parvovirus.


[Diabetic osteoarthropathy (DO) of the forefoot].
In patients suffering from diabetic osteoarthropathy, a total of 97 forefeet were evaluated concerning their bone tissue and soft tissue transformations. The most prevalent forms of demineralisation were circumscribed osteoporosis (21%) and diffuse osteoporosis (20%). Subluxations (6.2%), dislocations (2.1%), erosions (8.3%), marginal usures (11.3%) or cysts of the bone (11.3%) were seen only rarely. Extensions of the articular space (10.3%) were more prevalent than disappearances of the articular space (4.1%). The MTP (26.8%) and PIP joints (10.3%) were confirmed to be preferred localisations. A sudden loss of articular surface (25%) and a fast transition to mutilation (23.5%) show the increasing tendency of the fast transition to advanced stages of destruction by omitting the earlier stages.


Piezo-phototronic mediated enhanced photodetection characteristics of plasmonic Au-g-C3N4/CdS/ZnO based hybrid heterojunctions on a flexible platform.
We have studied the piezo-phototronic induced enhancement in the photo-response of CdS/ZnO heterojunctions attached with plasmonic Au nanoparticle loaded 2D-graphitic carbon nitride (g-C3N4). The hybrid g-C3N4/CdS/ZnO heterojunction favours the charge carrier separation through the formation of a step-like band alignment. Furthermore, the integration of plasmonic Au loaded g-C3N4 nanosheets on the conventional CdS/ZnO heterojunction facilitates improved visible light absorption properties. The heterojunction device on a flexible platform under the application of a strain (∼0.017%) exhibits ∼102 times higher photoresponse over the control sample at a constant bias of ∼2 V. The variation in the photo-response under different bending conditions has been explained in terms of the improved charge transport through the modified energy bands at the interface of ZnO. The improved piezo-phototronic properties originated from the plasmonic properties of Au loaded g-C3N4 and the piezoelectric characteristics of c-axis oriented ZnO films may be used for future flexible photonic devices.


Potassium channel activators protect the N-methyl-D-aspartate-induced cerebral vascular dilation after combined hypoxia and ischemia in piglets.
Cerebral arteriolar dilation to N-methyl-D-aspartate (NMDA) is a neuronally mediated multistep process that is sensitive to cerebral hypoxia and ischemia (H/I). We tested the hypothesis that topical pretreatment with the selective potassium channel agonists NS1619 and aprikalim preserves the vascular response to NMDA after consecutive H/I. Pial arteriolar diameters were measured in anesthetized piglets with the use of a closed cranial window and intravital microscopy. Arteriolar responses to NMDA (10(-5), 5 x 10(-5), and 10(-4) mol/L) were recorded before and 1 hour after 10 minutes of hypoxia (8.5% O2 in N2) plus 10 minutes of ischemia (H/I). Ischemia was induced by increasing intracranial pressure. Subgroups were topically pretreated with 10(-5) mol/L NS1619, 10(-6) mol/L aprikalim, 10(-6) mol/L calcitonin gene-related peptide (CGRP), or 10(-5) mol/L papaverine. We also examined the effects of H/I on vascular responses to kainate (10(-4) mol/L) to assess specificity of neuronal injury. Arteriolar responses to NMDA were significantly attenuated after H/I. Baseline compared with post-H/I arteriolar diameters were 9+/-4% versus 3+/-2% at 10(-5) mol/L, 22+/-4% versus 4+/-2% at 5 x 10(-5) mol/L, and 33+/-4% versus 7+/-2% at 10(-4) mol/L (mean+/-SE; all P<.05, n=7). Pretreatment with NS1619 and aprikalim preserved the arteriolar responses to NMDA after H/I. For NS1619 (n=6), values were as follows: 9+/-2% versus 6+/-4% at 10(-5) mol/L, 19+/-6% versus 21+/-5% at 5 x 10(-5) mol/L, and 35+/-3% versus 31+/-5% at 10(-4) mol/L. For aprikalim (n=7), values were as follows: 6+/-2% versus 8+/-2% at 10(-5) mol/L, 22+/-6% versus 15+/-3% at 5 x 10(-5) mol/L, and 41+/-5% versus 32+/-6% at 10(-4) mol/L. In contrast, piglets pretreated with CGRP (n=6) or papaverine (n=5) showed no preservation of the vascular response to NMDA after H/I, although these compounds dilated the arterioles to an extent similar to that with NS1619/aprikalim. Kainate-induced arteriolar dilation (n=6) was largely preserved after H/I compared with preischemic responses. (1) Vascular responses of cerebral arterioles to NMDA after H/I are preserved by pretreatment with NS1619 or aprikalim, indicating a neuroprotective effect. (2) CGRP and papaverine do not preserve the vascular response to NMDA despite causing vasodilation similar to that with NS1619 or aprikalim. This suggests that activation of potassium channels on neurons accounts for the protective effect of potassium channel agonists. (3) Preserved arteriolar dilation to kainate suggests largely intact functioning of neuronal nitric oxide synthase after H/I.


Sensitivity to second dose of mivacurium.
The sensitivity of patients to a second dose of mivacurium has been studied following complete recovery of the twitch response after > 95% neuromuscular block produced by a systemic bolus of the drug. In further experiments we have excluded one arm from the effect of a systemic bolus ED95 dose of mivacurium for 100 s so as to obtain two different levels of neuromuscular block in the two arms of the same patient. Upon recovery from the block in the paralysed arm the dose response of both arms to a second dose of mivacurium was studied in order to investigate the effect of the amount and duration of block upon second dose sensitivity. An approximately 50% diminution in the ED95 dose requirement of mivacurium was found following complete recovery from an ED95 dose in spite of the rapid plasma clearance of this drug. A similar increase in sensitivity was observed in the arm that had been excluded for 100 s from the peak effect of the drug. It was concluded that the second dose sensitivity was not due to a receptor effect or to residual drug in plasma.


Protein permeability and immune complex deposition in glomerular capillary walls of rats.
The effect of reduced glomerular anionic charge on immune complex deposition in the glomerular basement membrane was studied in rats with Heymann nephritis. A reduction of the anionic charge was induced by lysozyme administration. The animals were divided into the following four groups: normal controls (group A), group B treated with lysozyme, group C treated with lysozyme and immunized with autologous tubular antigen, and group D immunized with the antigen. Proteinuria was marked in groups B, C and D as compared with group A, especially in group D. Development of Heymann nephritis by the tubular antigen was suppressed in group C. Stainings of anionic substances in the glomerular capillary walls by cationic probes were weakened in groups B, C and D. Immune complex deposited in the subepithelial area of the capillary wall was also stained by cationic probes. The findings suggest that reduced glomerular anionic charge by polycations results in suppressed immune complex deposition in the basement membrane, partially due to increased permeation of macromolecules across the glomerular capillary walls in rats.


Immunoinformatics and Molecular Docking Studies Predicted Potential Multiepitope-Based Peptide Vaccine and Novel Compounds against Novel SARS-CoV-2 through Virtual Screening.
Coronaviruses (CoVs) are enveloped positive-strand RNA viruses which have club-like spikes at the surface with a unique replication process. Coronaviruses are categorized as major pathogenic viruses causing a variety of diseases in birds and mammals including humans (lethal respiratory dysfunctions). Nowadays, a new strain of coronaviruses is identified and named as SARS-CoV-2. Multiple cases of SARS-CoV-2 attacks are being reported all over the world. SARS-CoV-2 showed high death rate; however, no specific treatment is available against SARS-CoV-2. In the current study, immunoinformatics approaches were employed to predict the antigenic epitopes against SARS-CoV-2 for the development of the coronavirus vaccine. Cytotoxic T-lymphocyte and B-cell epitopes were predicted for SARS-CoV-2 coronavirus protein. Multiple sequence alignment of three genomes (SARS-CoV, MERS-CoV, and SARS-CoV-2) was used to conserved binding domain analysis. The docking complexes of 4 CTL epitopes with antigenic sites were analyzed followed by binding affinity and binding interaction analyses of top-ranked predicted peptides with MHC-I HLA molecule. The molecular docking (Food and Drug Regulatory Authority library) was performed, and four compounds exhibiting least binding energy were identified. The designed epitopes lead to the molecular docking against MHC-I, and interactional analyses of the selected docked complexes were investigated. In conclusion, four CTL epitopes (GTDLEGNFY, TVNVLAWLY, GSVGFNIDY, and QTFSVLACY) and four FDA-scrutinized compounds exhibited potential targets as peptide vaccines and potential biomolecules against deadly SARS-CoV-2, respectively. A multiepitope vaccine was also designed from different epitopes of coronavirus proteins joined by linkers and led by an adjuvant. Our investigations predicted epitopes and the reported molecules that may have the potential to inhibit the SARS-CoV-2 virus. These findings can be a step towards the development of a peptide-based vaccine or natural compound drug target against SARS-CoV-2.


Predictors of outcome among young adult patients with anorexia nervosa in a randomised controlled trial.
The prognosis in cases of anorexia nervosa (AN) is unsatisfactory, and it is therefore important to examine pretreatment predictors of outcome. Female AN patients (N = 74) included in a randomised controlled trial receiving individual cognitive behavioural therapy (CBT) or family-based treatment (FBT) were included. Predictors of the outcome were explored using pretreatment eating disorder psychopathology. In the CBT group, lower levels of emotional dysregulation and greater deficits in identifying and coping with inner states were predictors of weight increase, explaining 37.7% of the variance. In the FBT group, lower interoceptive deficits predicted an increase in weight (explaining 17.7% of the variance), whereas bulimic behaviour (32.4%) and problems with emotional regulation (23.3%) were predictors of increased diagnostic symptoms. Bulimic symptoms and the ability to identify and cope with emotional states appear to be important aspects that should be addressed in the treatment of young adult patients with AN.


Synthesis and evaluation of monoclonal antibody against Plasmodium falciparum merozoite surface antigen 2.
To assess the quality of expressed MSP-2 and also to confirm the immune response against different domains of these proteins. Mice were immunized with a schizont extract to stimulate the immune system to make antibodies against different antigens of the late stage parasite including production of antibodies against different domains of Plasmodium falciparum (P. falciparum) MSP-2. B lymphocytes of immunized mice were extracted from the spleen and the fusion was performed using NS-1 myeloma cells and the hybridoma cells were assayed by ELISA either with a schizont extract or different domains of MSP-2 and/or by IFAT with whole schizont preparation. Fusion of NS-1 and spleen cells was performed. The positive hybrids were cloned and ELISA was applied against different dilutions. The positive clones were transferred to a small tissue culture flask and after developing they were assayed against schizont extract and the different MSP-2 domains. The positive clones were expanded to large (75 cm(2)) flask and cultured under the same conditions, checking them using both ELISA and IFAT and the positive cells were frozen as soon as possible. A total number of 7 fusions including 26 plates (2 496 wells) were performed, of which 1 336 hybrids were produced and the overall efficiency (1 336/2496 × 100) was about 53%. ELISA was performed to detect the positive hybrids against crude schizont extract by which the highest frequency to crude schizont extract was found for the supernatant of the hybrids produced in fusion number 3 (66 out of 315 hybrids). The supernatant of both B5 and F1 hybridoma cells were more positive against domain 2 of the MSP-2 recombinant protein in Western blotting test. Western blotting results also showed that different domains of the MSP-2 recombinant protein and also the MSP-2 of the P. falciparum parasite were recognized by some of the positive clones and also immune sera. Bringing together all the results of this study it has been confirmed that some clones have recognized both schizont extract and different domains of the MSP-2 recombinant protein and therefore confirming the quality of the MSP-2 domains.


Chronobiological analysis of changes in circadian rhythm of anterior pituitary hormones level during glycemia normalization by means of biostator.
We compared the circadian rhythms of anterior pituitary hormones in 15 patients with noncompensated insulin-dependent diabetes on first and second day treatment with Biostator. The rhythm was evaluated by means of a least squares analysis and presented as the circle of cosinors. In noncompensated diabetes the TSH and prolactin rhythm was maintained, whereas other hormones of the anterior pituitary showed no significant rhythm. In the course of one-day normalization of glycemia by means of Biostator the TSH and prolactin rhythm was maintained, whereas the circadian rhythm of growth hormone and ACTH levels appeared with acrophase at 18.47 and 19.59 hour, respectively. The LH rhythm did not exist, whereas the FSH rhythm was dubious. One may assume that noncompensated diabetes results in the impairment of certain pituitary hormonal rhythms and these disturbances are reversible after restoring of normoglycemia.


A new alternariol glucoside from fungus Alternaria alternate cib-137.
A new secondary metabolite, 2-O-methylalternariol 4-O-β-[4-methoxyl-glucopyranoside] (1), together with four known compounds alternariol methyl ether (2), altenuene (3), isoaltenuene (4) and 2-(2'S-hydroxypropyl)-5-methyl-7-hydroxychromone (5), was isolated from the fungus Alternaria alternate cib-137. Its structure was elucidated on the basis of spectroscopic data. Compounds 3 and 4 demonstrated moderate activity against Staphylococcus aureus.


The long reach of violence and aggression.
The immediately preceding issue of psychiatry focused on the effects of violence on children. Of particular concern was the immediate impact of violence in the community on psychiatric symptoms in young children. Also of concern was the relationship of community violence to violence and abuse of children in the home, and the short-term impact of violence on many facets of child development. A group of five papers in the current issue focuses on the long-term impact of violence, aggression, and trauma; its impact on development into late adolescence and on severe character pathology in adulthood. Also of concern in this section are some of the origins of violence and abusive behavior toward children.


Developmental specific expression and organelle targeting of the Escherichia coli fabD gene, encoding malonyl coenzyme A-acyl carrier protein transacylase in transgenic rape and tobacco seeds.
In both plants and bacteria, de novo fatty acid biosynthesis is catalysed by a type II fatty acid synthetase (FAS) system which consists of a group of eight discrete enzyme components. The introduction of heterologous, i.e. bacterial, FAS genes in plants could provide an alternative way of modifying the plant lipid composition. In this study the Escherichia coli fabD gene, encoding malonyl CoA-ACP transacylase (MCAT), was used as a model gene to investigate the effects of over-producing a bacterial FAS component in the seeds of transgenic plants. Chimeric genes were designed, so as not to interfere with the household activities of fatty acid biosynthesis in the earlier stages of seed development, and introduced into tobacco and rapeseed using the Agrobacterium tumefaciens binary vector system. A napin promoter was used to express the E. coli MCAT in a seed-specific and developmentally specific manner. The rapeseed enoyl-ACP reductase transit peptide was used successfully, as confirmed by immunogold labelling studies, for plastid targeting of the bacterial protein. The activity of the bacterial enzyme reached its maximum (up to 55 times the maximum endogenous MCAT activity) at the end of seed development, and remained stable in mature transgenic seeds. Significant changes in fatty acid profiles of storage lipids and total seed lipid content of the transgenic plants were not found. These results are in support of the notion that MCAT does not catalyse a rate-limiting step in plant fatty acid biosynthesis.


Prevalence of microalbuminuria and its associated cardiometabolic risk factors in Korean youth: Data from the Korea National Health and Nutrition Examination Survey.
Microalbuminuria is a known early predictive factor for renal and cardiovascular diseases, not only for patients with diabetes mellitus or hypertension but also in the general population. However, the prevalence and risk factors associated with microalbuminuria in Korean youth are unknown. The aims of this study are to evaluate the prevalence of microalbuminuria and the association between microalbuminuria and obesity or cardiometabolic risk factors in Korean children and adolescents without diabetes. This study examines data obtained from the Korea National Health and Nutrition Examination Survey (between 2011 and 2014). It includes a total of 1,976 participants aged between 10 and 19 years (boys 1,128 and girls 848). Microalbuminuria was defined as a urine albumin-to-creatinine ratio (UACR) of ≥ 30 mg/g and < 300 mg/g. Association between microalbuminuria and the risk factors for cardiometabolic diseases including insulin resistance was evaluated. The prevalence of microalbuminuria was found to be 3.0% in Korean children and adolescents over this time period. The mean UACR for non-obese youth was significantly greater than that found in obese youth (3.2 ± 0.1 mg/g in the non-obese group vs. 2.1 ± 0.2 mg/g in the obese group; P < 0.001). In multiple logistic regression analysis, microalbuminuria was associated with hyperglycemia (OR 2.62, 95% CI 1.09-6.30) and hemoglobin A1c (OR 3.34, 95% CI 1.09-10.17) in the non-obese group and hypertension (OR 14.10, 95% CI 1.12-177.98) and HbA1c (OR 6.68, 95% CI 1.87-23.95) in the obese group. The prevalence of microalbuminuria is not prominent in obese children and adolescents. Our findings demonstrated that the presence of hypertension and hyperglycemia was associated with microalbuminuria. Especially Hemoglobin A1c was associated with microalbuminuria in youths regardless of weight status. Microalbuminuria in pediatric population can be a helpful marker for the risk of cardiovascular disease.


Evaluation of homologous bone graft versus biomaterials in the aesthetic restoration of the middle third of the face.
Bone deficits of the midface can be observed following tumor surgery, facial traumas or malformations, and can determine aesthetic deformities requiring surgical corrections. The goal of this study is to illustrate the 23 years experience of the Maxillo-Facial Department of the "La Sapienza" University of Rome, in surgical correction of middle third bone loss for aesthetic improvement, and to compare postsurgical results from the use of biomaterials and homologous bone grafts. From January 1977 to January 2000, 18 patients were surgically treated with bone grafts for bone deficit of the midface requiring aesthetic improvements, and 23 received biomaterial placement in the same district. A retrospective analysis regarding aesthetic improvements following corrective (reconstructive) surgery was carried out in order to compare long-term results obtained with bone grafts and biomaterials. Of the 19 implants of the zygomatic bone, 1 patient suffered from infection, observ-ed on the 8th day, following iliac bone graft in the maxillary area. Of the 32 prostheses, 7 became infected and in 1 case the material became exposed: Proplast(R) became infected 2 times, Gore-tex(R) 3 times and 1 time became exposed; 2 of the 24 Medpor(R) implants resulted in infection. The employment of bone graft obtained a good short term aesthetic result. Medpor(R) employment, was evaluated as an optimal aesthetic improvement. We cannot evaluate the results obtained with Gore-tex(R) and Proplast(R) because of the few cases treated. Anyway we consider unsatisfactory the corrections obtained with these 2 materials. Homologous bone grafts are still considered as the best choice when a further fixture positioning is planned for prosthetic rehabilitation of the alveolar ridge of the upper jaw or mandible. At the present time, some biomaterials are the definitive solution for restoring facial harmony in the 3 spatial dimensions.


Back propagation neural network based control for the heating system of a polysilicon reduction furnace.
In this paper, the Back Propagation (BP) neural network based control strategy is proposed for the heating system of a polysilicon reduction furnace. It is applied to obtain the control signal I(d), which is used to adjust the heating power through operations of the silicon core temperature, furnace temperature, silicon core voltage, and resistance of the current control cycle. With the control signal I(d) the polycrystalline silicon can be heated from room temperature to the required temperature smoothly and steadily. The proposed BP network applied in this paper can obtain the accurate control signal I(d) and achieve the precise control purpose. This paper presents the principle of the BP network and demonstrates the effectiveness of the BP network in the heating system of a polysilicon reduction furnace by combining the simulation analysis with experimental results.


[Seminar for HPH coordinators (Health Promoting Hospitals) and WHO HPH Autumn School 2011 held in Prague].
Health Promoting Hospitals (HPH) is an international network of more than 800 health care subjects. The HPH initiative is based on an idea of a hospital being an appropriate place not only to treat illnesses, but also to actively promote health. It aims to improve the quality and safety of health care via specialized interventions targeting a few key areas, such as tobacco and other dependences, physical activity, psychological support, or patient-professional communication. Activities are oriented toward both patients and hospital staff and use only methods of evidence-based medicine. To facilitate programme implementation and evaluation, the hospital quality goals are summarized in five HPH standards. The present paper informs about the seminar for HPH coordinators in Czech Republic as well as about the WHO HPH Autumn School 2011 held in Prague.


Tacrolimus versus cyclosporin as primary immunosuppression for kidney transplant recipients.
Kidney transplantation is the treatment of choice for most patients with end-stage renal disease (ESRD). Standard protocols in use typically involve three drug groups each directed to a site in the T-cell activation or proliferation cascade which are central to the rejection process: calcineurin inhibitors (e.g. cyclosporin, tacrolimus), anti-proliferative agents (e.g. azathioprine, mycophenolate mofetil) and steroids (prednisolone). It remains unclear whether new regimens are more specific or simply more potent immunosuppressants. To compare the effects of tacrolimus with cyclosporin as primary therapy for kidney transplant recipients. MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, the Cochrane Renal Group's specialist register and conference proceedings were searched to identify relevant reports of randomised controlled trials (RCTs). Two reviewers assessed trials for eligibility, quality and extracted data independently. All RCTs where tacrolimus was compared with cyclosporin for the initial treatment of kidney transplant recipients Data were synthesised (random effects model) and results expressed as relative risk (RR), values <1 favouring tacrolimus, with 95% confidence intervals (CI). Subgroup analysis and meta-regression were used to examine potential effect modification by differences in trial design and immunosuppressive co-interventions. 123 reports from 30 trials (4102 patients) were included. At six months graft loss was significantly reduced in tacrolimus-treated recipients (RR 0.56, 95% CI 0.36 to 0.86), and this effect was persistent up to three years. Meta-regression showed that this benefit diminished as higher trough levels of tacrolimus were targeted (P = 0.04), after allowing for differences in cyclosporin formulation (P = 0.97) and cyclosporin target trough level (P = 0.38). At one year, tacrolimus patients suffered less acute rejection (RR 0.69, 95% CI 0.60 to 0.79), and less steroid-resistant rejection (RR 0.49, 95% CI 0.37 to 0.64), but more insulin-requiring diabetes mellitus (RR 1.86, 1.11 to 3.09), tremor, headache, diarrhoea, dyspepsia and vomiting. Cyclosporin-treated recipients experienced significantly more constipation and cosmetic side-effects. We demonstrated no differences in infection or malignancy. Tacrolimus is superior to cyclosporin in improving graft survival and preventing acute rejection after kidney transplantation, but increases post-transplant diabetes, neurological and gastrointestinal side effects. Treating 100 recipients with tacrolimus instead of cyclosporin would avoid 12 suffering acute rejection, two losing their graft but cause an extra five to become insulin-requiring diabetics.


Preterm birth leads to a decreased number of differentiated podocytes and accelerated podocyte differentiation.
Preterm birth was previously identified as a high-risk factor for the long-term development of chronic kidney disease. However, the detailed pattern of podocyte (PD) changes caused by preterm birth and the potential mechanism underlying this process have not been well clarified. In present study, a rat model of preterm birth was established by delivery of pups 2 days early and podometric methods were applied to identify the changes in PDs number caused by preterm birth. In addition, single-cell RNA sequencing (scRNA-seq) and subsequent bioinformatic analysis were performed in the preterm rat kidney to explore the possible mechanism caused by preterm birth. As results, when the kidney completely finished nephrogenesis at the age of 3 weeks, a reduction in the total number of differentiated PDs in kidney sections was detected. In addition, 20 distinct clusters and 12 different cell types were identified after scRNA-seq in preterm rats (postnatal day 2) and full-term rats (postnatal day 0). The numbers of PDs and most types of inherent kidney cells were decreased in the preterm birth model. In addition, 177 genes were upregulated while 82 genes were downregulated in the PDs of full-term rats compared with those of preterm rats. Further functional GO analysis revealed that ribosome-related genes were enriched in PDs from full-term rats, and kidney development-related genes were enriched in PDs from preterm rats. Moreover, known PD-specific and PD precursor genes were highly expressed in PDs from preterm rats, and pseudotemporal analysis showed that PDs were present earlier in preterm rats than in full-term rats. In conclusion, the present study showed that preterm birth could cause a reduction in the number of differentiated PDs and accelerate the differentiation of PDs.


Medial unicondylar knee arthroplasty combined to anterior cruciate ligament reconstruction.
The purpose of the present study was to retrospectively evaluate the outcomes of patients who underwent combined medial unicompartmental knee arthroplasty (UKA) and anterior cruciate ligament (ACL) reconstruction. The hypothesis was that this procedure would lead to a high success rate in patients affected by isolated medial unicompartmental osteoarthritis and concomitant ACL deficiency. Fourteen patients with primary ACL lesion and concomitant medial compartment symptomatic osteoarthritis treated from 2006 to 2010 were followed up for an average time of 26.7 months (SD 4.2). Assessment included KOOS score, Oxford Knee score, American Knee Society scores, WOMAC index of osteoarthritis, Tegner activity level and objective examination including instrumented laxity test with KT-1000 arthrometer. Radiological assessment was done with standard simple radiographs in order to get information about any presence of loosening of the components. KOOS score, OKS, WOMAC index and the AKSS improved significantly after surgery (p < 0.001). Regarding AKSS, improvement was noted both in the objective score and in the functional one (p < 0.001). There was no clinical evidence of instability in any of the knees as evaluated with clinical laxity testing. No pathologic radiolucent lines were observed around the components. In one patient signs of osteoarthritis in the lateral compartment were observed 28 months after surgery. UKA combined with ACL reconstruction is a valid therapeutic option for the treatment of combined medial unicompartmental knee osteoarthritis and ACL deficiency in young and active patients and confirms subjective and objective clinical improvement 2 years after surgery. The use of a fixed-bearing prosthesis represents a reliable feature as it allows to overcome problems of improper ligament tensioning during the implantation of the components. IV.


Survival-associated alternative splicing signatures in esophageal carcinoma.
Alternative splicing (AS), a major mechanism for the enhancement of transcriptome and proteome diversity, has been widely demonstrated to be involved in the full spectrum of oncogenic processes. High-throughput sequencing technology and the rapid accumulation of clinical data sets have provided an opportunity to systemically analyze the association between messenger RNA AS variants and patient clinical outcomes. Here, we compared differentially spliced AS transcripts between esophageal carcinoma (ESCA) and non-tumor tissues, profiled genome-wide survival-associated AS events in 87 patients with esophageal adenocarcinoma (EAC) and 79 patients with esophageal squamous cell carcinoma (ESCC) using The Cancer Genome Atlas (TCGA) RNA-seq data set, and constructed predictive models as well as splicing regulation networks by integrated bioinformatic analysis. A total of 2326 AS events in 1738 genes and 1812 AS events in 1360 genes were determined to be significantly associated with overall survival (OS) of patients in the EAC and ESCC cohorts, respectively, including some essential participants in the oncogenic process. The predictive model of each splice type performed reasonably well in distinguishing good and poor outcomes of patients with esophageal cancer, and values for the area under curve reached 0.942 and 0.815 in the EAC exon skip predictive model and the ESCC alternate acceptor site predictive model, respectively. The splicing regulation networks revealed an interesting correlation between survival-associated splicing factors and prognostic AS genes. In summary, we created prognostic models for patients with esophageal cancer based on AS signatures and constructed novel splicing correlation networks.


Role of Ca2+ and protein kinase C in shear stress-induced actin depolymerization and endothelin 1 gene expression.
Vascular endothelial cells adapt to changes in blood flow by altering the cell architecture and by producing various substances. We have previously reported that low shear stress induces endothelin 1 (ET-1) expression in endothelial cells and that this induction is mediated by depolymerization of actin fiber. In the present study, we examined the role of Ca2+ and protein kinase C (PKC) in shear stress-induced actin depolymerization and subsequent ET-1 gene expression. Exposure of cultured porcine aortic endothelial cells to low shear stress (5 dyne/cm2) for 3 hours increased the ratio of G-actin to total actin from 54 +/- 0.8% to 80 +/- 1.0%. This shear stress-induced actin depolymerization was completely blocked by chelation of extracellular Ca2+ with EGTA and partially inhibited by intracellular Ca2+ chelation with the tetraacetoxymethyl ester of BAPTA (BAPTA/AM). Pretreatment with staurosporine, a PKC inhibitor, or desensitization of PKC by treatment with 12-O-tetradecanoylphorbol 13-acetate (TPA) for 24 hours also resulted in partial inhibition of shear stress-induced actin depolymerization. Although PKC activation by TPA mildly increased G-actin content, the effect of TPA and shear stress on actin depolymerization was not additive. Moreover, shear stress-induced ET-1 gene expression was inhibited by EGTA, BAPTA/AM, and staurosporine to a degree similar to the inhibition of actin depolymerization. In contrast, ET-1 gene expression induced by cytochalasin B, an actin-disrupting agent, was not affected by staurosporine.(ABSTRACT TRUNCATED AT 250 WORDS)


Hippo Signaling Modulates the Inflammatory Response of Chondrocytes to Mechanical Compressive Loading.
Knee osteoarthritis (KOA) is a degenerative disease resulting from mechanical overload, where direct physical impacts on chondrocytes play a crucial role in disease development by inducing inflammation and extracellular matrix degradation. However, the signaling cascades that sense these physical impacts and induce the pathogenic transcriptional programs of KOA remain to be defined, which hinders the identification of novel therapeutic approaches. Recent studies have implicated a crucial role of Hippo signaling in osteoarthritis. Since Hippo signaling senses mechanical cues, we aimed to determine its role in chondrocyte responses to mechanical overload. Here we show that mechanical loading induces the expression of inflammatory and matrix-degrading genes by activating the nuclear factor-kappaB (NFκB) pathway in a Hippo-dependent manner. Applying mechanical compressional force to 3-dimensional cultured chondrocytes activated NFκB and induced the expression of NFκB target genes for inflammation and matrix degradation (i.e., IL1β and ADAMTS4). Interestingly, deleting the Hippo pathway effector YAP or activating YAP by deleting core Hippo kinases LATS1/2 blocked the NFκB pathway activation induced by mechanical loading. Consistently, treatment with a LATS1/2 kinase inhibitor abolished the upregulation of IL1β and ADAMTS4 caused by mechanical loading. Mechanistically, mechanical loading activates Protein Kinase C (PKC), which activates NFκB p65 by phosphorylating its Serine 536. Furthermore, the mechano-activation of both PKC and NFκB p65 is blocked in LATS1/2 or YAP knockout cells, indicating that the Hippo pathway is required by this mechanoregulation. Additionally, the mechanical loading-induced phosphorylation of NFκB p65 at Ser536 is blocked by the LATS1/2 inhibitor Lats-In-1 or the PKC inhibitor AEB-071. Our study suggests that the interplay of the Hippo signaling and PKC controls NFκB-mediated inflammation and matrix degradation in response to mechanical loading. Chemical inhibitors targeting Hippo signaling or PKC can prevent the mechanoresponses of chondrocytes associated with inflammation and matrix degradation, providing a novel therapeutic strategy for KOA.


Prediction of psychosocial recovery after head injury with cognitive tests and neurobehavioral ratings.
A series of 53 patients was studied using a battery of tests and a neurobehavioral rating scale on average 4 months after closed-head injury (CHI). Social outcome was assessed 1 year after injury by interviewing a family member. The results supported the hypothesis that tests of flexibility and programming rather than tests of cognitive skills predict psychosocial recovery after CHI. Spatial Learning with Self-Set Goals and Sorting were measures of flexibility and programming. Contrary to expectation, word fluency performance was unrelated to these measures, but was associated with conventional intelligence tests, which did not predict psychosocial recovery. Cognition/Energy deficit on the Neurobehavioral Rating Scale and increased age were useful predictors of poor psychosocial outcome, whereas computed tomography findings or the Glasgow Coma Score were weakly related to the outcome indices. Evidently, cognitive flexibility and mental programming are very important psychological prerequisites of social recovery after CHI.


High-quality thin-multiwalled carbon nanotubes synthesized by Fe-Mo/MgO catalyst based on a sol-gel technique: synthesis, characterization, and field emission.
We synthesized thin-multiwalled carbon nanotubes (t-MWCNTs) using Fe-Mo/MgO catalyst by citrate precursor method based on a simple sol-gel technique. Synthesis of high-quality t-MWCNTs with uniform diameters was achieved in large-scale by catalytic decomposition of methane over Fe-Mo/MgO catalyst prepared under Ar-atmosphere. The produced t-MWCNTs had the outer diameters in the range of 4-8 nm, with a Gaussian average diameter of 6.6 +/- 0.1 nm and wall numbers in the range of of 4-7 graphenes. The product yield of the as-synthesized t-MWCNTs was over 450% relative to the used Fe-Mo/MgO catalyst, and TGA showed purity about 85%. The t-MWCNTs showed the low turn-on field about 1.24 V/microm, corresponding to the current density of 0.1 microA/cm2, and the high emission Current density of 10 mA/cm2 at the applied electric field of 2.6 V/microm. The t-MWCNTs indicate good emission stability without any fluctuation of emission current through a lifetime measurement for 20 h. It was confirmed that the field emission performance of t-MWCNTs was similar to DWCNTs and the field emission stability of t-MWCNTs was similar to MWCNTs.


Emerging biomedical applications of nano-chitins and nano-chitosans obtained via advanced eco-friendly technologies from marine resources.
The present review article is intended to direct attention to the technological advances made in the 2010-2014 quinquennium for the isolation and manufacture of nanofibrillar chitin and chitosan. Otherwise called nanocrystals or whiskers, n-chitin and n-chitosan are obtained either by mechanical chitin disassembly and fibrillation optionally assisted by sonication, or by e-spinning of solutions of polysaccharides often accompanied by poly(ethylene oxide) or poly(caprolactone). The biomedical areas where n-chitin may find applications include hemostasis and wound healing, regeneration of tissues such as joints and bones, cell culture, antimicrobial agents, and dermal protection. The biomedical applications of n-chitosan include epithelial tissue regeneration, bone and dental tissue regeneration, as well as protection against bacteria, fungi and viruses. It has been found that the nano size enhances the performances of chitins and chitosans in all cases considered, with no exceptions. Biotechnological approaches will boost the applications of the said safe, eco-friendly and benign nanomaterials not only in these fields, but also for biosensors and in targeted drug delivery areas.


[Low-frequency rhythmic electrocutaneous stimulation during slow-wave sleep: physiological and therapeutic effects].
Neocortical EEG slow wave activity (SWA) in the delta frequency band (0.5-4.0 Hz) is a hallmark of slow wave sleep (SWS) and its power is a function of prior wake duration and an indicator of a sleep need. SWS is considered the most important stage for realization of recovery functions of sleep. Possibility of impact on characteristics of a night sleep by rhythmic (0.8-1.2 Hz) subthreshold electrocutaneous stimulation of a hand during SWS is shown: 1st night--adaptation, 2nd night--control, 3d and 4th nights--with stimulation during SWA stages ofa SWS. Stimulation caused significant increase in average duration of SWS and EEG SWA power (in 11 of 16 subjects), and also well-being and mood improvement in subjects with lowered emotional tone. It is supposed that the received result is caused by functioning of a hypothetical mechanism directed on maintenance and deepening of SWS and counteracting activating, awakening influences of the afferent stimulation. The results can be of value both for understanding the physiological mechanisms of sleep homeostasis and for development of non-pharmacological therapy of sleep disorders.


Effects of tris (2-chloroethyl) phosphate (TCEP) on survival, growth, histological changes and gene expressions in juvenile yellow catfish Pelteobagrus fulvidraco.
Tris (2-chloroethyl) phosphate (TCEP) is an emerging aquatic environmental pollutant. In the present study, juvenile yellow catfish (Pelteobagrus fulvidraco) were exposed to environmentally relevant concentrations of TCEP for 30 days. The results showed that TCEP exposure decreased the survival rate (100 μg/L), body weight (10 and 100 μg/L) and specific growth rate (10 and 100 μg/L) of juvenile yellow catfish. Exposure to TCEP resulted in pronounced damages of gill structures. Gene transcription analysis showed that the antioxidant capacity of the liver and gills was affected; CYP1A1 might contribute to phase I metabolism of TCEP in the liver rather than CYP1B1; TCEP stress might increase the demand of ion transport in fish gill; TCEP could stimulate the immune response and might induce apoptosis via a p53-Bax pathway and caspase-dependent pathway in gills. Collectively, these findings provide new insights into the toxic effects of TCEP on fish.


Management of hepatocellular adenoma: solitary-uncomplicated, multiple and ruptured tumors.
While hepatocellular adenomas (HAs) have often been studied as a unique entity, we aimed to better define current management of the various forms of HAs. Twenty-five consecutive patients operated for solitary-uncomplicated (9), multiple (6), and ruptured (10) HAs were reviewed according to management strategies and outcomes. All solitary-uncomplicated HAs (ranged 2.2-14 cm in size) were removed. Out of 25 HAs, 2 (8%) included foci of carcinoma. In the multiple HA group, previously undiagnosed tumors were identified during surgery in 5/6 cases. In three cases with multiple spread HA, several lesions had to be left unresected. They remained unmodified after 4-, 6-, and 6-year radiological follow-up. Patients with ruptured HA (ranged 1.7-10 cm in size) were initially managed with hemodynamic support and angiography, allowing the embolization of actively bleeding tumors in two patients. All ruptured tumors were subsequently removed 5.5 d (range 4-70 d) after admission. Tumors suspected of HA, regardless of the size, should be resected, because of high chances of rupture causing bleeding, and/or containing malignant foci. Although it is desirable to remove all lesions of multiple HA, this may not be possible in some patients, for whom long-term radiological follow-up is advised. Ruptured HA can be managed by hemodynamic support and angiography, allowing scheduled surgery.


Can we measure serum thyroglobulin?
Measurement of serum thyroglobulin (Tg) by immunoassay is used to monitor the treatment of differentiated thyroid cancer. An understanding of the disease process and the biochemistry of Tg allows the laboratory to determine the characteristics of suitable Tg assays. There are a number of key analytical issues: standardization, long-term assay stability, minimum detection limit, working range and the effect of endogenous Tg antibodies (TgAb). There are significant limitations to the methods used to determine TgAb interference. Clinicians should be aware of the limitations of immunoassays for this tumour marker.


SPECT in avulsion injury of the multifidus and rotator muscles of the lumbar region.
A 37-year-old man was investigated for a work-related back injury with plain radiography, CT scan, bone scintigraphy, and SPECT. SPECT was able to demonstrate multiple sites of increased isotope uptake not seen on plain radiographs, CT scan, or planar images. Consequently, the diagnosis of avulsion injury of the multifidus and rotator muscles of the lumbar region was made. SPECT appears to have a role in the specific diagnosis of work-related back injuries.


Distribution and degranulation of airway mast cells in normal and asthmatic subjects.
It was hypothesized that the distribution and activation of mast cells across the airway wall may reflect their function in asthma. The density of mast cells (intact and degranulated) within airway compartments in cartilaginous and membranous airways, obtained from autopsies on patients with fatal asthma, nonfatal asthma, and nonasthmatic control cases have been examined. In cartilaginous airways, the mean+/-SE density of mast cells in control cases was 27+/-9 cells x mm(-2). It was similar in nonfatal asthma (24+/-2 cells x mm(-2)) but reduced (p<0.05) in fatal asthma cases (16+/-2 cells x mm(-2)). In membranous airways, the density of mast cells in control cases was 155+/-21 cells x mm(-2) and was higher (p<0.05) in cases of nonfatal (270+/-51 cells x mm(-2)) and fatal asthma (219+/-26 cells x mm(-2)). Mast-cell density was greatest on the smooth muscle and mucous glands in cartilaginous airways and on the smooth muscle and outer airway wall in membranous airways. The percentage of degranulated mast cells was higher (p<0.05) in cases of asthma, related to disease severity, and was higher in cartilaginous than membranous airways. Degranulation was greatest on the smooth muscle in fatal asthma cases. Mast-cell distribution and degranulation varies between cartilaginous and membranous airways and across the airway wall. Degranulation of mast cells is related to asthma severity. The increased degranulation in proximal airways may reflect stimulation via the inhaled route.


Modulation of chemokine receptor expression and chemotactic responsiveness during differentiation of human naive T cells into Th1 or Th2 cells.
Chemokines and their receptors direct movements and encounters of lymphocytes and professional APC into specific microenvironments of lymphoid tissues. Chemokine receptors such as CCR7, CXCR5 and CCR4 that are differentially expressed and modulated in distinct subsets of T cells contribute to establish functionally and spatially segregated microenvironments within secondary lymphoid tissues where T cell activation and differentiation occur. Here, we have explored the modulation of CCR7, CCR4, CCR8 and CXCR5 expression and chemotactic responsiveness to their ligands during commitment of human naive T cells along the Th1 or Th2 differentiation pathway in vitro. Our results document that activation of human naive T cells and differentiation in Th1 or Th2 cells result in progressive down-modulation of CCR7 expression and CCL19 responsiveness. By contrast, expression of CCR4 and responsiveness to CCL22 is rapidly induced at the early stages of both Th1/Th2 cell development. However, while CCR4 expression is further up-regulated upon differentiation into Th2 cells, it is lost on fully differentiated Th1 cells. CCR8 is detected at later time points than CCR4 and exclusively on differentiated Th2 cells as revealed by analysis of mRNA expression and responsiveness to CCL1. Expression of CXCR5 is transiently induced at the early stages of Th cell differentiation, but with distinct kinetics in developing Th1 and Th2 cells. Analysis of human tonsillar CD4(+) T cells reveals a consistent pattern of chemotactic responsiveness and chemokine receptor expression in distinct transitional stages of human T cell activation and differentiation in vivo.


Adherence to Mediterranean dietary pattern and menopausal symptoms in relation to overweight/obesity in Spanish perimenopausal and postmenopausal women.
This study aims to assess the relationship of adherence to the Mediterranean dietary pattern, as well as the presence of menopausal symptoms, with overweight/obesity in Spanish perimenopausal and postmenopausal women. Participants in this cross-sectional study were 8,954 Spanish perimenopausal or postmenopausal women. Anthropometric measurements were recorded, and all women were interviewed to assess their adherence to the Mediterranean dietary pattern, using a validated questionnaire and the Menopause and Health subscale of the validated Cervantes Scale. A logistic regression model was used to investigate the association between categories of adherence to the Mediterranean diet and the odds of being overweight/obese. Multinomial logistic regression was used to study the association between menopausal symptoms and the odds of being overweight/obese (reference categories: participants in the low-adherence category and participants with no menopausal problems). After adjustment for relevant confounders, the odds ratio (95% CI) for being overweight/obese among women in the highest category of adherence to the Mediterranean dietary pattern was 0.68 (0.60-0.78; P for trend <0.001). The odds ratio (95% CI) for being overweight/obese was 3.05 (1.98-4.71) for the category "severe problems" in comparison with the category "no problems." Higher adherence to a healthy dietary pattern (Mediterranean diet) is inversely associated with overweight/obesity in perimenopausal and postmenopausal women. The occurrence of low to severe problems during perimenopause or postmenopause is positively associated with overweight/obesity. Therefore, high adherence to the Mediterranean dietary pattern and a body mass index of 25kg/m(2) or lower might improve quality of life in women at these stages.


Electrical status epilepticus during sleep in a child with Prader-Willi syndrome: a case report.
Prader-Willi syndrome (PWS) is a rare and complex genomic imprinting disorder caused by an absence of expression of paternal genes from chromosome 15q11.2-q13. Clinical manifestations of PWS depends on age. In early infancy, PWS patients is characterized by hypotonia and failure to thrive. Later in life, they can also exhibit hyperphagia, obesity, short stature, hypogonadism, behavioral issues and cognitive disability. Multiple sleep abnormalities including obstructive and/or central sleep apnea, daytime hypersomnolence, and impaired responses to hypercapnia and hypoxia have been described in patients with PWS. Recent studies also demonstrated an increased risk of seizures in PWS patients. Electrical status epilepticus in sleep (ESES) is an age-limited epilepsy with various seizure types, neurophysiological and motor impairment. The classic electroencephalogram (EEG) pattern of ESES involves continuous epileptic activity at 2-3 Hz occupying greater than 85% of non-rapid eye movement (REM) sleep. Treatment of the ESES syndrome consists of anti-epileptic drugs in routine cases, and corticosteroids, gamma globulins, the ketogenic diet, and surgery in refractory cases. In this project, we describe ESES during polysomnography in a 5-year-old female with PWS and no history of seizure disorder. To the best of our knowledge, this is the first case report on ESES in a PWS patient.


Infection Of Permanent Pacemaker's Pocket, What Do We Do?
With increased rate of permanent pacemaker's (PPM) implantation, the rate of complication also increased many folds. Infection in pacemakers is one of the dreaded complications which need a multidisciplinary approach in its management. All patients with permanent pacemakers, who presented with infection of device, were admitted in our unit. The infected device was explanted and wound left open. The same device was used as a temporary pacemaker with a new PPM screwing lead from internal jugular approach. Once the infection was under control, a new device was implanted on the other side and temporary wire (PPM screwing lead) pulled out. Wound on both side closed and patient kept on antibiotics for a week. Total 10 cases of infected device received. Single chambers devices with infection were six and dual chamber pacemakers were four. One case with infection had tine lead and nine patients presented with screwing leads. Male and female ratio was 2.3:1. All leads were explanted in our department with conventional gadgets using rotation and traction maneuvers. Culture sensitivity in all cases remained negative. Patients were kept on broad spectrum antibiotics till the wound was clear. One patient had small pericardial effusion soon after explantation of tine lead, which was treated conservatively. No other major or minor complication documented.. Scrupulous planning and preparation before system extraction and later on new Cardiac implantable electronic device re-implantation is essential for better patient outcome.


The ADAM17 protease promotes tobacco smoke carcinogen-induced lung tumorigenesis.
Lung cancer is the leading cause of cancer-related mortality, with most cases attributed to tobacco smoking, in which nicotine-derived nitrosamine ketone (NNK) is the most potent lung carcinogen. The ADAM17 protease is responsible for the ectodomain shedding of many pro-tumorigenic cytokines, growth factors and receptors, and therefore is an attractive target in cancer. However, the role of ADAM17 in promoting tobacco smoke carcinogen-induced lung carcinogenesis is unknown. The hypomorphic Adam17ex/ex mice-characterized by reduced global ADAM17 expression-were backcrossed onto the NNK-sensitive pseudo-A/J background. CRISPR-driven and inhibitor-based (GW280264X, and ADAM17 prodomain) ADAM17 targeting was employed in the human lung adenocarcinoma cell lines A549 and NCI-H23. Human lung cancer biopsies were also used for analyses. The Adam17ex/ex mice displayed marked protection against NNK-induced lung adenocarcinoma. Specifically, the number and size of lung lesions in NNK-treated pseudo-A/J Adam17ex/ex mice were significantly reduced compared with wild-type littermate controls. This was associated with lower proliferative index throughout the lung epithelium. ADAM17 targeting in A549 and NCI-H23 cells led to reduced proliferative and colony-forming capacities. Notably, among select ADAM17 substrates, ADAM17 deficiency abrogated shedding of the soluble IL-6 receptor (sIL-6R), which coincided with the blockade of sIL-6R-mediated trans-signaling via ERK MAPK cascade. Furthermore, NNK upregulated phosphorylation of p38 MAPK, whose pharmacological inhibition suppressed ADAM17 threonine phosphorylation. Importantly, ADAM17 threonine phosphorylation was significantly upregulated in human lung adenocarcinoma with smoking history compared with their cancer-free controls. Our study identifies the ADAM17/sIL-6R/ERK MAPK axis as a candidate therapeutic strategy against tobacco smoke-associated lung carcinogenesis.


Coronary Flow in Patients With Myocardial Bridges, Coronary Fistulae in the Setting of Unstable Non-Obstructive Coronary Disease.
Оbjective Our aim was to describe the difference in epicardial coronary flow at baseline on background anti-ischaemic therapy and following intracoronary glyceryl trinitrate in patients with acute coronary syndrome and non-obstructive coronary disease with and without myocardial bridges and coronary artery fistulae. Materials and methods Coronary flow was characterized in a group of 88 patients with coronary stenoses <50% diagnosed with acute coronary syndrome using the corrected Thrombolysis in Myocardial Infarction frame count (cTFC) method at coronary angiography at baseline and after the application of 200 µg glyceryl trinitrate. Results Тhe patients with myocardial bridges and coronary artery fistulae accounted for 4.4% (n=4) and 2.2% (n=2), respectively, of the patients with acute coronary syndrome. Sixty-two (70%) of all patients demonstrated slow progression of the contrast media (cTFC>25 frames) in at least one coronary artery. Coronary flow was similarly impaired in the patients with myocardial bridges, coronary artery fistulae, and those without coronary anomalies and variants. After the intracoronary infusion of glyceryl trinitrate, the epicardial flow improved in the patients with myocardial bridges and to a lesser degree in the cases with coronary fistulae. Most of the patients who responded to glyceryl trinitrate were on background therapy with calcium channel blockers. Conclusion The epicardial coronary flow of patients with non-obstructive coronary disease with myocardial bridges and acute coronary syndrome showed less impairment compared to baseline in response to intracoronary glyceryl trinitrate applied at background anti-ischaemic therapy that included calcium channel blockers.


A quantitative immunofluorescence test for detection of serum antibody to Sendai virus in mice.
A simple, semi-automated immunofluorescence assay, (TRACK XI), was developed for the detection and quantitation of circulating antibodies to Sendai virus in mice. The assay was validated by selecting Sendai virus-free and naturally infected mice from six different colonies and testing each serum in both ELISA and quantitative immunofluorescence (QIF) assays. The QIF test utilizes Sendai viral proteins immobilized within a dried colloid gel and permits serum antibody quantitation in 30 minutes. Using a dedicated fluorometer, antibody titers in test sera are calculated automatically from a three-point best fit calibration line. The QIF test gave 92.9% agreement with the ELISA and proved to be a reproducible, accurate and convenient assay for the quantitative measurement of serum antibody to Sendai virus in mice.


The requirement for DNAM-1, NKG2D, and NKp46 in the natural killer cell-mediated killing of myeloma cells.
Recent evidence suggests a role for natural killer (NK) cells in the control of multiple myeloma. We show that expression of the NK cell receptor DNAM-1 (CD226) is reduced on CD56(dim) NK cells from myeloma patients with active disease compared with patients in remission and healthy controls. This suggested that this receptor might play a role in NK-myeloma interactions. The DNAM-1 ligands Nectin-2 (CD112) and the poliovirus receptor (PVR; CD155) were expressed by most patient myeloma samples analyzed. NK killing of patient-derived myelomas expressing PVR and/or Nectin-2 was DNAM-1 dependent, revealing a functional role for DNAM-1 in myeloma cell killing. In myeloma cell lines, cell surface expression of PVR was associated with low levels of NKG2D ligands, whereas cells expressing high levels of NKG2D ligands did not express PVR protein or mRNA. Furthermore, NK cell-mediated killing of myeloma cell lines was dependent on either DNAM-1 or NKG2D but not both molecules. In contrast, the natural cytotoxicity receptor NKp46 was required for the killing of all myeloma cell lines analyzed. Thus, DNAM-1 is important in the NK cell-mediated killing of myeloma cells expressing the cognate ligands. The importance of NKp46, NKG2D, and DNAM-1 in myeloma killing mirrors the differential expression of NK cell ligands by myeloma cells, reflecting immune selection during myeloma disease progression.


Laparoscopic Simple Prostatectomy: A Single Center Experience with A Long-Term Follow Up.
The aim of this retrospective study is to assess the long-term outcomes and safety of laparoscopic simple prostatectomy. Between 2012 and 2019 80 patients with prostates volumes ≥ 80 mL were treated with laparoscopic simple prostatectomy at our department. Uroflowmetry, post void residual volume and standardized questionnaires were assessed pre- and postoperatively. Perioperative complications were categorized using the Clavien-Dindo classification. The mean specimen weight was 83 grams, and the mean operation time was 156 minutes. At a mean follow-up time of 40 months patients showed a significant improvement of Qmax (P = .002), IPSS (P < .001) and QoL (P < .001). Post void residual volumes decreased significantly. Complications occurred in 11 patients (13.8%), nine had mild (grade 1 - 2) and two had severe (grade 3b - 4a) complications. One conversion to open surgery due to massive prostatic adherence from previous abscess formation was recorded and one patient needed blood transfusion intraoperatively. laparoscopic simple prostatectomy is an effective and safe procedure for large volume prostate glands with a significant and stable long term symptoms improvement.


Effect of remote signal propagation in an empirical brain network.
Increasing evidence has shown that brain functions are seriously influenced by the heterogeneous structure of a brain network, but little attention has been paid to the aspect of signal propagation. We here study how a signal is propagated from a source node to other nodes on an empirical brain network by a model of bistable oscillators. We find that the unique structure of the brain network favors signal propagation in contrast to other heterogeneous networks and homogeneous random networks. Surprisingly, we find an effect of remote propagation where a signal is not successfully propagated to the neighbors of the source node but to its neighbors' neighbors. To reveal its underlying mechanism, we simplify the heterogeneous brain network into a heterogeneous chain model and find that the accumulation of weak signals from multiple channels makes a strong input signal to the next node, resulting in remote propagation. Furthermore, a theoretical analysis is presented to explain these findings.


Evaluating extraction methods to study canine urine microbiota.
The urinary microbiota is the collection of microbes present in urine that may play a role in host health. Studies of urine microbiota have traditionally relied upon culturing methods aimed at identifying pathogens. However, recent culture-free sequencing studies of the urine microbiota have determined that a diverse array of microbes is present in health and disease. To study these microbes and their potential role in diseases like bladder cancer or interstitial cystitis, consistent extraction and detection of bacterial DNA from urine is critical. However, urine is a low biomass substrate, requiring sensitive methods to capture DNA and making the risk of contamination high. To address this challenge, we collected urine samples from ten healthy dogs and extracted DNA from each sample using five different commercially available extraction methods. Extraction methods were compared based on total and bacterial DNA concentrations and bacterial community composition and diversity assessed through 16S rRNA gene sequencing. Significant differences in the urinary microbiota were observed by dog and sex but not extraction method. The Bacteremia Kit yielded the highest total DNA concentrations (Kruskal-Wallis, p = 0.165, not significant) and the highest bacterial DNA concentrations (Kruskal-Wallis, p = 0.044). Bacteremia also extracted bacterial DNA from the greatest number of samples. Taken together, these results suggest that the Bacteremia kit is an effective option for studying the urine microbiota. This work lays the foundation to study the urine microbiome in a wide range of urogenital diseases in dogs and other species.


Interventions for Subjects with Depressive Symptoms with or without Unhealthy Alcohol Use: Are There Different Patterns of Change?
Background: It has been suggested that alcohol problems negatively affect therapeutic interventions for depression. This study examines the patterns of change in depressive symptoms following an intervention for depression, in participants with or without comorbid unhealthy alcohol use. Methods: Depressive symptoms (BDI-II), perceived control of depressive symptoms (UNCONTROL) and unhealthy alcohol use (AUDIT) were assessed in 116 patients before and after attending a cognitive behavioral psychoeducational intervention for depression. At pretest the mean score of AUDIT was 8.1, indicating a, on average, risk of harmful level of alcohol abuse. At pretest the majority of the total sample had a moderate degree of depressive symptoms, with a mean BDI-II score of 25.1 and 36.2% had a risky use of alcohol as measured with AUDIT score at 8 points or above. To assess the relationship between depressive symptoms, perceived uncontrollability of depression and alcohol use across time, a cross-lagged panel model was estimated. Results: A clinical significant reduction of depressive symptoms, and a parallel and statistically significant increase in the perceived control of depressive symptoms, was identified after attending a cognitive behavioral psychoeducational intervention for depression. At posttest, the mean BDI-II score was 17.8, demonstrating a statistically significant decrease of 7.3 points in depressive symptoms from before starting the course to 6 months later. The effect size (d-value) of 0.83 can be interpreted as a large decrease in depressive symptoms. In this sample alcohol use and depressive symptoms seemed to be unrelated. The cross-lagged correlation panel analysis indicated that a high degree of perceived control of depressive symptoms leads to a reduction in depressive symptoms, and not vice versa. Conclusion: We found that this intervention for depression were effective in reducing depressive symptoms. The patterns of change seemed to be independent of risky use of alcohol, although leaving the study was systematically associated with higher AUDIT-scores. As participants with or without unhealthy alcohol use show the same patterns of change regarding reduction of depressive symptoms and perceived control of depression, both groups could be offered the same cognitive behavioral psychoeducational interventions for depression.


Discrimination of G-quadruplexes from duplex and single-stranded DNAs with fluorescence and energy-transfer fluorescence spectra of crystal violet.
G-rich nucleic acid sequences with the potential to form G-quadruplex structures are common in biologically important regions. Most of these sequences are present with their complementary strands, so the development of a sensitive biosensor to distinguish G-quadruplex and duplex structures and to determine the competitive ability of quadruplex to duplex structures has received a great deal of attention. In this work, the interactions between two triphenylmethane dyes (malachite green (MG) and crystal violet (CV)) and G-quadruplex, duplex, or single-stranded DNAs were studied by fluorescence spectroscopy and energy-transfer fluorescence spectroscopy. Good discrimination between quadruplexes and duplex or single-stranded DNAs can be achieved by using the fluorescence spectrum of CV or the energy-transfer fluorescence spectra of CV and MG. In addition, by using energy-transfer fluorescence titrations of CV with G-quadruplexes, the binding-stoichiometry ratios of CV to G-quadruplexes can be determined. By using the fluorescence titrations of G-quadruplex-CV complexes with C-rich complementary strands, the fraction of G-rich oligonucleotide that engages in G-quadruplex structures in the presence of the complementary sequence can be measured. This study may provide a simple method for discrimination between quadruplexes and duplex or single-stranded DNAs and for measuring G-quadruplex percentages in the presence of the complementary C-rich sequences.