Interaction between clenbuterol and run training: effects on exercise performance and MLC isoform content.
The purpose of this study was to determine the separate and combined effects of clenbuterol (CB) administration and interval training on running performance and myosin light-chain (MLC) isoform expression in mouse skeletal muscle. Mice were randomly assigned to one of four treatment groups: 1) control (Con), 2) exercise (Ex), 3) drug (CB), or 4) exercise + drug (Ex + CB). CB and Ex + CB mice were given CB (1.6 mg/kg) orally 4 days/wk. Ex and Ex + CB mice were trained 4 days/wk on a motorized treadmill (3 sets of 3 min, 36-40 m/min, 10-17% grade, 30-s recovery). After 8 wk of treatment, exercise conditioning increased total work performed 58% in the Ex group during a run-to-exhaustion treadmill test, whereas CB decreased total work by 25% in the CB group; in combination with exercise training, CB treatment eliminated the Ex-induced increase in work. Polyacrylamide gel electrophoresis indicated that run training, CB treatment, or a combination did not (P > 0.01) promote changes in fast and slow MLC isoforms in the soleus, gastrocnemius, or tibialis anterior muscles. Although not different from each other after 8 wk, CB and Ex + CB treatments produced significantly greater values than Con and Ex for the following variables: muscle mass (17-46%), total protein (22-50%), and myofibrillar protein (19-53%). It was concluded that CB decreases exercise performance and that the combination of Ex and CB have antagonistic effects on running performance; the two treatments do not interact to diminish the anabolic effects of CB on skeletal muscle and do not alter MLC isoform profiles.


The Role of Non-Cognate T Cell Stimulation during Intracellular Bacterial Infection.
Intra-macrophage bacterial infections cause significant morbidity and mortality in both the developed and developing world. Protective host immune responses to these infections initially requires the activation and expansion of pathogen-specific CD4 Th1 cells within lymphoid tissues and subsequent relocation of these effector cells to sites of infection. After entering infected tissues, the elicitation of Th1 bactericidal activity can be triggered by cognate or non-cognate signals that are delivered by locally infected antigen-presenting cells and innate cells. However, the contribution of non-cognate stimulation to the resolution of bacterial infection remains poorly understood, especially in the context of a Th1 response. Here, we review the current data on Th1 cell activation and expansion in mouse models of Salmonella and Chlamydia infection and discuss the potential role of non-cognate Th1 cell stimulation in these disease models. Greater understanding of this pathway of T cell activation may lead to the design of therapeutics or vaccines to combat intra-macrophage pathogens.


Plant leaf mucilage/carrageenan/Eudragit® NE30D blended films: Optimization, characterization, and pharmaceutical application.
Mucilage of C. pareira leaves was utilized, being manufactured for use in pharmaceutical products. Carrageenan and Eudragit® NE30D were used to combined. Glycerin was used as a plasticizer at a concentration of 20 % w/w based on the amount of polymer used. Computer software optimized its characteristics, including tensile properties, moisture uptake, and erosion; the optimal formulation was 1.4:1.2:2.8. The percentages of optimization error ranged from 8.48 to 13.80 %. Propranolol HCl was mixed to an optimal formulation. The film layer was tight, homogeneous, and smooth, with no holes. DSC thermogram showed no interaction peaks at 101.33 °C and 170.50 °C. Propranolol HCl concentration in the film ranged from 2.18 to 2.20 mg/cm2. Propranolol HCl was quickly released from the film. The kinetic model for the release profile was first-order kinetic. Although propranolol HCl had a high-release profile, its skin permeation was limited. The permeation lag time, Jss, and Kp were 1.60-2.65 h, 0.0182-0.0338 μg/cm2/h, and 9.10-15.35 cm/h, respectively. A significant amount of propranolol HCl residue was found on the skin's surface. Glycerin appeared to influence propranolol HCl permeability. Therefore, the plant leaf mucilage/carrageenan/Eudragit® NE30D blended film can be utilized in pharmaceutical applications to control drug release from its film layer.


The test of time: predictors and effects of duration in youth mentoring relationships.
The effects and predictors of duration in youth mentor relationships were examined. The study included 1,138 young, urban adolescents (Mean age 12.25), all of whom applied to Big Brothers Big Sisters programs. The adolescents were randomly assigned to either the treatment or control group, and administered questions at baseline and 18 months later Adolescents in relationships that lasted a year or longer reported the largest number of improvements, with progressively fewer effects emerging among youth who were in relationships that terminated earlier. Adolescents who were in relationships that terminated within a very short period of time reported decrements in several indicators of functioning. Older adolescents, as well as those who had been referred for services or had sustained emotional, sexual or physical abuse, were most likely to be in early terminating relationships, as were married volunteers aged 26-30 and those with lower incomes. Several dyadic factors were also found to be related to earlier terminations, including race, gender, and relationship quality.


Crossed and uncrossed visual topography in dorsal lateral geniculate nucleus of the pigmented rat.
1. The representation of the retinocentric visual field within the dorsal lateral geniculate nucleus (dLGN) was assessed electrophysiologically by recording multicellular responses from anesthetized pigmented rats. Separate experiments examined the representation through either the contralateral or ipsilateral eye along the dorsoventral, mediolateral, and rostrocaudal dimensions of the nucleus. 2. The crossed projection displays an orderly representation of the visual field, mapping eccentricities out to 100 degrees from the optic disk. There is, however, a marked absence of eccentricities greater than 60 degrees representing upper nasal visual space. The uncrossed projection also displays an orderly representation of the visual field but is limited in extent to upper nasal visual space at far eccentricities of 50-90 degrees. 3. The ipsilateral projection, which represents far eccentric upper nasal visual space, occupies a region in the contralateral representation corresponding with upper nasal visual space at reduced eccentricity. It is these two regions that are considered binocularly conjugate: the temporal crescent of each eye with another crescent (the conjugate central crescent) lying between the optic disk and the temporal crescent of the opposite eye. It is suggested that the crossed and uncrossed representations are aligned in the dLGN so that projection lines for discrete regions of the binocular visual field course through the nucleus from rostroventral to caudodorsal. Although the dLGN of the rat lacks the cytoarchitecturally distinct laminae associated with the regions of afferent input from each eye, as is seen in the primate and cat dLGN, the organizing principle of apposing the representation of the visual field through each eye is similar.


An update on the GLOB blood group system (and former GLOB collection).
The main change that has occurred in the GLOB blood group system since the GLOB review published in this journal in 2013 is the addition of an antigen. The high-prevalence PX2 antigen, originally recognized as the x2 glycosphingolipid, is expressed on red blood cells of most individuals and is elevated in the rare PP1Pk-negative p blood group phenotype. P synthase, encoded by B3GALNT1, was found to elongate paragloboside to PX2 by adding the terminal β3GalNAc moiety. Hence, PX2 was moved from the GLOB collection to the GLOB system. The presence of naturally-occurring anti-PX2 was noted in P1k and P2k individuals exhibiting nonfunctional P synthase. Although the clinical significance of this specificity remains unclear, a recommendation to avoid transfusing Pk patients with p phenotype blood has been made. Currently, 13 mutations at the highly conserved B3GALNT1 locus have been found to abolish P synthase function and are recognized as null alleles by the International Society of Blood Transfusion. A new allele with a missense mutation but resulting in normal expression of P has been assigned GLOB*02. Finally, the GLOB collection was made obsolete after the move of LKE antigen to the 901 series.


Early clamp release during laparoscopic partial nephrectomy: Implications for preservation of renal function.
Intraoperative warm ischemic time (WIT), associated with hilar clamping during partial nephrectomy (PN), is an established modifiable risk factor for renal dysfunction. We assessed early clamp release (ECR) as a strategy to reduce WIT and assess its impact on renal function and bleeding. We retrospectively assessed patients who underwent minimally invasive PN by a single surgeon at our centre since December 2011. Comparing the standard technique to an ECR modification, WIT, complications, change in estimated glomerular filtration rate (eGFR), and change in differential function as demonstrated by MAG-3 nuclear renography were assessed. Followup blood work and renograms were performed at 6-12 weeks postoperatively and compared to baseline in 70 patients (35 ECR: 35 control). The ECR and control groups were similar in age, sex, and tumour size, with only patient weight being higher in the ECR group (91.6 vs. 81.6 kg; p<0.05). WIT was significantly lower in ECR group compared to control (18.8 vs. 31.5 minutes; p<0.05). Although there was no significant difference in change from baseline eGFR in the early postoperative period (Day 3) or in followup (6-12 weeks), the control group had a significantly greater loss of ipsilateral renal function from baseline compared to the ECR group (9 vs. 4% change; p<0.05). Blood loss and complication rate were similar between groups. The ECR technique offers a safe, reproducible alternative that reduces WIT during laparoscopic PN. ECR demonstrates a reduction in overall ipsilateral renal dysfunction, without increasing complication or intraoperative bleeding risk.


The Langerhans cell.
In all mammalian species so far examined, Langerhans cells or their precursors are the only epidermal cells expressing Ia antigens or their equivalents. In man, xeno-antisera raised in rabbits against purified B-lymphocyte cell membrane antigens were utilized to stain the Langerhans cells by either fluorescent or immunoferritin methods. As high proportion of the indeterminate cells in the epidermis also expressed HLA-DR antigens, and a relationship to Langerhans cells is suggested. Confirmation of these results was obtained in mouse. Alloantisera raised against I-A and I-EC subregion products again stained only Langerhans cells. Fluorescent, immunoperoxidase, and immunoferritin methods were used and confirmation of the specificity of the reaction was achieved at the electron microscope level. Langerhans cells were shown by ATPase staining to be absent from the epithelium of the central cornea, but present in the limbus. Population of the entire corneal epithelium surface was induced by application of irritants or contact sensitizing agents such as DNCB. Grafting of corneas either deficient or populated with Langerhans cells, to skin beds, may answer the question of the influence of such cells on allograft rejection.


[Immune-regulating Th1- and Th2-cytokines in chronic infections caused by hepatitis B and C viruses].
The serum levels of Th1 (gamma-IFN and sIL-2r) and of Th2 (IL-10) cytokines were measured in 33 patients (23 males and 10 females, mean age 23.1 +/- 1.9) with chronic viral hepatitis (CVH) according to a disease etiology (6 patients with hepatitis B--CVHB, 15 patients with hepatitis C--CVHC, and 12 patients with a mixed form of chronic hepatitis B and C--HBV + HCV). Besides, the contents of the studied cytokines were compared with the traditional infection markers and the presence of viremia. The similar indices taken from 10 healthy persons served as controls. The concentration of gamma-IFN was found to be reliably higher (p < 0.05) in patients of all three groups (0.32 +/- 0.07, 0.34 +/- 0.09 and 0.25 +/- 0.06 pg/ml, respectively) regardless of a disease etiology and as compared with the control value (0.09 +/- 0.04) pg/ml). At the same time, the levels of gamma-IFN, sIL-2r and IL-10 (0.25 +/- 0.06 pg/ml, 166.5 +/- 31.3 IU/ml and 48.1 +/- 8.4 pg/ml, respectively) was found to be reliably (p < 0.05 and p < 0.01) higher, as compared to the controls (0.09 +/- 0.04, 57.1 +/- 5.6 and 10.8 +/- 7.8, respectively), only in patients with the mixed infection of hepatitis. Like in our previous study, a trend was established towards the growing mean values of the IL-r level from its lowest parameters in the group of CVHB patients towards its highest parameters in the group with the mixed hepatitis form. According to our data, the IL-2r level correlated reliably with the activity of AlAt (r = 0.452; p < 0.05), while the gamma-IFN content correlated reliably with the IL-10 concentration (r = 0.805; p < 0.05), and the gamma-IFN content correlated with the IL-10 concentration (r = 0.805; p < 0.01) irrespective of disease pathology.


Methylomarinovum caldicuralii gen. nov., sp. nov., a moderately thermophilic methanotroph isolated from a shallow submarine hydrothermal system, and proposal of the family Methylothermaceae fam. nov.
A novel methane-oxidizing bacterium, strain IT-9(T), was isolated from a shallow submarine hydrothermal system occurring in a coral reef in Japan. Strain IT-9(T) was a Gram-negative, aerobic, motile, coccoid or oval-shaped bacterium with the distinctive intracytoplasmic membrane arrangement of a type I methanotroph. Strain IT-9(T) was a moderately thermophilic, obligate methanotroph that grew on methane and methanol at 30-55 °C (optimum 45-50 °C). The strain possessed the particulate methane monooxygenase (pMMO). The ribulose monophosphate pathway was operative for carbon assimilation. NaCl was required for growth within a concentration range of 1-5 % (optimum 3 %). The hao gene encoding hydroxylamine oxidoreductase (HAO) involved in nitrification was detected by a PCR experiment. The major phospholipid fatty acids were C16 : 0 and C18 : 1ω7c. The major isoprenoid quinone was Q-8. The DNA G+C content was 66.0 mol%. The 16S rRNA gene sequence of strain IT-9(T) was only moderately related to the sequences of members of the closest genera Methylohalobius (94.1 % similarity) and Methylothermus (91.7-91.9 % similarity); however, those sequences formed a deeply branching monophyletic group within the order Methylococcales. Phylogenies based on 16S rRNA gene sequences, deduced partial PmoA sequences and deduced partial Hao sequences and physiological and chemotaxonomic characteristics revealed that strain IT-9(T) represents a novel species of a new genus, for which the name Methylomarinovum caldicuralii gen. nov., sp. nov. is proposed. The type strain of Methylomarinovum caldicuralii is IT-9(T) ( = JCM 13666(T) = DSM 19749(T)). In addition, we propose a new family, Methylothermaceae fam. nov., in the order Methylococcales, to accommodate the genera Methylothermus, Methylohalobius and Methylomarinovum. The genera Methylothermus and Methylohalobius have been recognized as being distinct from other genera in the methane-oxidizing order Methylococcales in the class Gammaproteobacteria. These genera form a distinctive monophyletic lineage within the order on the basis of 16S rRNA gene sequence phylogeny. This seems consistent with their distinctive physiological traits; the genus Methylothermus includes the most thermophilic species, and the genus Methylohalobius includes the most halophilic species, within the order. Although these two genera include only three species at the time of writing, similar sequences of 16S rRNA genes and pmoA genes encoding pMMO have been detected in a geothermal area or deep-sea hydrothermal vent fields by studies using culture-independent techniques. This suggests that unknown methanotrophs of this lineage inhabit various extreme environments.


Majorana bound states and nonlocal spin correlations in a quantum wire on an unconventional superconductor.
We study theoretically the proximity effect of a one-dimensional metallic quantum wire (in the absence of spin-orbit interaction) lying on top of an unconventional superconductor. Three different material classes are considered as a substrate: (i) a chiral superconductor in class D with broken time-reversal symmetry and a class DIII superconductor (ii) with and (iii) without a nontrivial Z(2) number. Interestingly, we find degenerate zero energy Majorana bound states at both ends of the wire for all three cases. They are unstable against spin-orbit interaction in case (i), while they are topologically protected by time-reversal symmetry in cases (ii) and (iii). Remarkably, we show that nonlocal spin correlations between the two ends of the wire can be simply controlled by a gate potential in our setup.


Recent advances in improving the effectiveness and reducing the complications of abortion.
When conducted in a legal setting and under safe conditions, abortion is an extremely effective and safe procedure. Tragically, almost half of all abortions that take place in the world are conducted under unsafe conditions, mostly in countries where abortion is illegal or highly restricted. These unsafe abortions are a major cause of maternal death and disability. Restricting a woman's access to abortion does not prevent abortion but simply leads to more unsafe abortions. Barriers to safe abortion are many but include legal barriers, health policy barriers, shortages of trained healthcare workers, and stigma surrounding abortion. This commentary will consider some recent advances to improve access to safe abortion as well as refinements in abortion methods and service delivery in settings where safe abortion is available that further improve the care and wellbeing of women who seek abortion.


[Persistent follicle syndrome: a forgotten clinical entity?].
There is no evidence that morphologic alterations of the ovaries cause symptoms of hormonal imbalance and a deficit in ovarian hormones in a case of micro-cystic degeneration of the ovaries. Similarly, fertility does not have to be impeded, since follicular development may be unaffected. In absence of functional disturbances, such as amenorrhea or anovulation, no therapy is needed. A different approach is, however, required when the ovaries contain larger, hormone-producing cysts which can persist for a long time. In contrast to micro-cystic ovaries the presence of persistent ovarian follicles can entail marked risks of endometrial hyperplasia, severe uterine bleeding, and anemia.


Atypical amplification of chromosome region 22q12 in melanoma: A case report.
Morphological, ultrastructural and immunohistochemical characteristics of clear cell sarcoma (CCS) of the soft tissue frequently overlap with those of malignant melanoma. Thus, the differential diagnosis between the two lesions represents an important diagnostic dilemma. However, a number of genetic factors can be used to differentiate the two tumors; in particular, the t(12;22)(q13;q12) chromosomal translocation is typical of CCS, resulting in fusion of the EWSR1 gene on chromosome 22q12 and the ATF1 gene on chromosome 12q13. The detection of this molecular alteration has proved useful in the differential diagnosis of the two lesions. The present study reports the case of a 71-year-old male patient with a suspicious lymph node mass. Immunohistochemical analysis of the lesion indicated a diagnosis of metastatic melanoma, however, cytogenetic analysis using fluorescence in situ hybridization was additionally performed to investigate the chromosomal rearrangements of the 22q12 region and completely exclude the possibility of CCS. The current case did not demonstrate the presence of the translocation, supporting the diagnosis of melanoma. However, a clear orange amplification signal was observed relative to an ~500-kb region adjacent to the EWSR1 gene in the centromeric direction of chromosome 22q12. To the best of our knowledge, this is the first description of a 22q12 chromosomal alteration in melanoma. Furthermore, despite the presence of numerous genes in this region, their amplification has not previously been associated with the pathogenesis of melanoma.


Judgments of exocentric direction in large-scale space.
Judgments of exocentric direction are quite common, especially when judging where others are looking or pointing. To investigate these judgments in large-scale space, observers were shown two targets in a large open field and were asked to judge the exocentric direction specified by the targets. The targets ranged in egocentric distance from 5 to 20 m with target-to-target angular separations of 45 degrees, 90 degrees, and 135 degrees. Observers judged exocentric direction using two methods: (i) by judging which point on a distant fence appeared collinear with the two targets, and (ii) by orienting their body in a direction parallel with the perceived line segment. In the collinearity task, observers had to imagine the line connecting the targets and then extrapolate this imagined line out to the fence. Observers indicated the perceived point of collinearity on a handheld 360 degrees panoramic cylinder representing their vista. The two judgment methods gave similar results except for a constant bias associated with the body-pointing response. Aside from this bias, the results of these two methods agree with other existing research indicating an effect of relative egocentric distance to the targets on judgment error--line segments are perceived as being rotated in depth. Additionally, verbal estimates of egocentric and exocentric distance suggest that perceived distance is not the cause for the systematic errors in judging exocentric direction.


Exercise and recovery in frog muscle: metabolism of PCr, adenine nucleotides, and related compounds.
The effects of exercise (swimming), fatigue, and recovery on the intracellular pH (pHi), energy-rich phosphates, and related metabolites were studied in the gastrocnemius muscle of common frogs (Rana temporaria) at 20 degrees C. Exercise caused a rapid decrease in the content of phosphocreatine (PCr) and a corresponding increase in that of Pi. The ATP level remained virtually constant for 1 min; its precipitous decrease during the following minute was associated with a rise in the contents of inosine 5'-monophosphate (IMP) and NH4+, indicating a marked activation of AMP deaminase. Five minutes of swimming caused severe fatigue, which was correlated with decreases in muscle PCr (-85%), ATP (-42%), and pHi (-0.8 units). Recovery appeared almost complete within 2 h, and the frogs were then induced to swim again. During the initial 10 s of this second exercise, ATP synthesis was as high as in the first exercise, but the rate decreased more rapidly between 10 and 60 s, thus indicating that repeated exercise caused increased metabolic stress. IMP formation in working muscle was not strictly correlated with the pHi or the tissue contents of Pi, AMP and ADP, although from studies in vitro AMP deaminase is known to be modulated by these parameters.


Haplotype block partitioning and tag SNP selection using genotype data and their applications to association studies.
Recent studies have revealed that linkage disequilibrium (LD) patterns vary across the human genome with some regions of high LD interspersed by regions of low LD. A small fraction of SNPs (tag SNPs) is sufficient to capture most of the haplotype structure of the human genome. In this paper, we develop a method to partition haplotypes into blocks and to identify tag SNPs based on genotype data by combining a dynamic programming algorithm for haplotype block partitioning and tag SNP selection based on haplotype data with a variation of the expectation maximization (EM) algorithm for haplotype inference. We assess the effects of using either haplotype or genotype data in haplotype block identification and tag SNP selection as a function of several factors, including sample size, density or number of SNPs studied, allele frequencies, fraction of missing data, and genotyping error rate, using extensive simulations. We find that a modest number of haplotype or genotype samples will result in consistent block partitions and tag SNP selection. The power of association studies based on tag SNPs using genotype data is similar to that using haplotype data.


Effects of imidazoline and non-imidazoline alpha-adrenergic agents on canine platelet aggregation.
Aggregatory and antiaggregatory effects of imidazol(in)e and non-imidazol(in)e alpha-adrenergic agents on canine platelets were examined turbidimetrically in citrated platelet-rich plasma or washed platelet solution. Each alpha-adrenoceptor agonist alone did not induce aggregation, but adrenaline and noradrenaline potentiated dose-dependently aggregation stimulated by ADP, collagen or thrombin. Small potentiation of ADP- or collagen-stimulated aggregation was also observed in response to oxymetazoline. The alpha2-adrenoceptor antagonists and/or imidazol(in)e alpha-adrenergic agents inhibit dose-dependently adrenaline-potentiated aggregation, whereas alpha1-adrenoceptor antagonists, a beta-adrenoceptor antagonist and non-imidazol(in)e alpha-adrenergic agents were no or less effective in inhibiting adrenaline-potentiated aggregation. The alpha2-adrenoceptor agonists did not reduce inhibitory effect of alpha2-adrenoceptor antagonists for adrenaline-potentiated aggregation. The alpha2-adrenoceptor antagonists and/or imidazol(in)es were no or less effective in inhibiting aggregation induced by ADP or thrombin alone. These results demonstrated that alpha2-adrenoceptor-blocking agents and/or imidazol(in)e alpha-adrenergic agents inhibit effectively the adrenaline-potentiated platelet aggregation.


Superficial juvenile granular dystrophy.
Seventeen cases of a superficial corneal dystrophy are presented. The lesions are subepithelial, limited mainly to Bowman's layer. This dystrophy, although clinically different from classic granular dystrophy, is pathologically similar to it. Treatment, consisting of superficial keratectomy to 15% to 20% of corneal thickness, did not require lamellar grafting and produced good visual results. A new classification of granular dystrophy is proposed.


IL-4 Up-Regulates MiR-21 and the MiRNAs Hosted in the CLCN5 Gene in Chronic Lymphocytic Leukemia.
Interleukin 4 (IL-4) induces B-cell differentiation and survival of chronic lymphocytic leukemia (CLL) cells. MicroRNAs (miRNAs) regulate mRNA and protein expression, and several miRNAs, deregulated in CLL, might play roles as oncogenes or tumor suppressors. We have studied the miRNA profile of CLL, and its response to IL-4, by oligonucleotide microarrays, resulting in the detection of a set of 129 mature miRNAs consistently expressed in CLL, which included 41 differentially expressed compared to normal B cells (NBC), and 6 significantly underexpressed in ZAP-70 positive patients. IL-4 stimulation brought about up-regulation of the 5p and 3p mature variants of the miR-21 gene, which maps immediately downstream to the VMP1 gene, and of the mature forms generated from the miR-362 (3p and 5p), miR-500a (3p), miR-502 (3p), and miR-532 (3p and 5p) genes, which map within the third intron of the CLCN5 gene. Both genes are in turn regulated by IL-4, suggesting that these miRNAs were regulated by IL-4 as passengers from their carrier genes. Their levels of up-regulation by IL-4 significantly correlated with cytoprotection. MiR-21 has been reported to be leukemogenic, associated to bad prognosis in CLL, and the miRNA more frequently overexpressed in human cancer. Up-regulation by IL-4 of miR-21 and the miRNAs hosted in the CLCN5 locus may contribute to evasion of apoptosis of CLL cells. These findings indicate that the IL-4 pathway and the miRNAs induced by IL-4 are promising targets for the development of novel therapies in CLL.


Pulmonary involvement in systemic sclerosis: associations with genetic, serologic, sociodemographic, and behavioral factors.
To determine the relative contributions of genetic, clinical, serologic, sociodemographic, and behavioral/psychological variables to early pulmonary involvement in the Genetics versus Environment in Scleroderma Outcome Study cohort. At the baseline visit (V0), 203 patients with systemic sclerosis (SSc) were examined (104 whites, 39 African Americans, and 60 Hispanics). We obtained sociodemographic, behavioral/psychological (illness behavior, social support, learned helplessness, smoking, drinking), clinical, serologic (autoantibodies), and genetic (HLA class II and FBN1 genotypes) factors; pulmonary function test results; electrocardiograms; and chest radiographs. Data analysis included Fisher's exact test, chi-square test, Student's t-test, analysis of variance, and stepwise linear and logistic regression methods. Significant pulmonary involvement was seen in 25% of patients within 2.8 years of SSc diagnosis. At V0, pulmonary fibrosis was significantly higher in African Americans compared with whites or Hispanics. African Americans had significantly lower percent predicted forced vital capacity (FVC) and forced expiratory volume in 1 second (FEV(1)) compared with whites and significantly lower percent predicted diffusing capacity for carbon monoxide (DLCO) compared with whites and Hispanics. Significant, independent associations impacting early pulmonary involvement included African American ethnicity, skin score, serum creatinine and creatine phosphokinase values, hypothyroidism, and cardiac involvement. Anticentromere antibody seropositivity was a significant, independent, protective factor for restrictive lung disease and FVC or DLCO values. African Americans had significantly increased frequencies of anti-topoisomerase I, fibrillarin, and RNP autoantibodies compared with whites. African Americans scored significantly lower on the Interpersonal Support Evaluation List and significantly higher on the Illness Behavior Questionnaire. Early pulmonary involvement in SSc appears to be influenced by several factors delineated by ethnicity, including racial, socioeconomic, behavioral, and serologic determinants.


Pore size regulates mesenchymal stem cell response to Bioglass-loaded composite scaffolds.
Composite scaffolds fabricated from synthetic polymers and bioceramics such as bioactive glasses are promising alternatives to autogenous bone grafts for treatment of bone defects. Compared to other bioceramics, we previously demonstrated that bioactive glass (Bioglass 45S®, BG) further enhances the osteogenic program of bone-forming osteoblasts when incorporated into poly(lactide-co-glycolide) (PLG) macroporous scaffolds. However, cell response is dependent on parameters beyond scaffold composition including pore size and bioceramic availability to cells. We hypothesized that the osteogenic potential of human mesenchymal stem/stromal cells (MSCs) seeded on BG composite scaffolds was dependent upon pore diameter. Composite BG scaffolds were formed with three pore diameters - 125-300 μm, 300-500 μm, and 500-850 μm - by controlling porogen size. To determine the contribution of pore size to composite scaffold osteogenic potential, we characterized the biophysical properties, bioceramic distribution within the scaffold, and the osteogenic response of MSCs. All composite scaffolds were approximately 2-fold stiffer than the PLG control, and scaffolds with 500-850 μm pore diameters induced the greatest osteogenic response. The enhanced response of MSCs to scaffolds fabricated with large pores resulted from increased presentation of Bioglass along pore surfaces, enabling increased interaction between the cells and bioceramic. These data indicate that cellular behavior is dependent upon both pore size and material composition, confirming that the role of pore size should be considered in the development of new materials designed for bone repair.


Biopharmaceutical Understanding of Excipient Variability on Drug Apparent Solubility Based on Drug Physicochemical Properties: Case Study-Hypromellose (HPMC).
Identification of the biopharmaceutical risks of excipients and excipient variability on oral drug performance can be beneficial for the development of robust oral drug formulations. The current study investigated the impact of Hypromellose (HPMC) presence and varying viscosity type, when used as a binder in immediate release formulations, on the apparent solubility of drugs with wide range of physicochemical properties (drug ionization, drug lipophilicity, drug aqueous solubility). The role of physiological conditions on the impact of excipients on drug apparent solubility was assessed with the use of pharmacopoeia (compendial) and biorelevant media. Presence of HPMC affected drug solubility according to the physicochemical properties of studied compounds. The possible combined effects of polymer adsorption (drug shielding effect) or the formation of a polymeric viscous layer around drug particles may have retarded drug dissolution leading to reduced apparent solubility of highly soluble and/or highly ionized compounds and were pronounced mainly at early time points. Increase in the apparent solubility of poorly soluble low ionized drugs containing a neutral amine group was observed which may relate to enhanced drug solubilization or reduced drug precipitation. The use of multivariate data analysis confirmed the importance of drug physicochemical properties on the impact of excipients on drug apparent solubility and revealed that changes in HPMC material properties or amount may not be critical for oral drug performance when HPMC is used as a binder. The construction of a roadmap combining drug, excipient, and medium characteristics allowed the identification of the cases where HPMC presence may present risks in oral drug performance and bioavailability.


Microbial Bioconversion of Phenolic Compounds in Agro-industrial Wastes: A Review of Mechanisms and Effective Factors.
Agro-industrial wastes have gained great attention as a possible source of bioactive compounds, which may be utilized in various industries including pharmaceutics, cosmetics, and food. The food processing industry creates a vast amount of waste which contains valuable compounds such as phenolics. Polyphenols can be found in soluble (extractable or free), conjugated, and insoluble-bound forms in various plant-based foods including fruits, vegetables, grains, nuts, and legumes. A substantial portion of phenolic compounds in agro-industrial wastes is present in the insoluble-bound form attached to the cell wall structural components and conjugated form which is covalently bound to sugar moieties. These bound phenolic compounds can be released from wastes by hydrolysis of the cell wall and glycosides by microbial enzymes. In addition, they can be converted into unique metabolites by methylation, carboxylation, sulfate conjugation, hydroxylation, and oxidation ability of microorganisms during fermentation. Enhancement of concentration and antioxidant activity of phenolic compounds and production of new metabolites from food wastes by microbial fermentation might be a promising way for better utilization of natural resources. This review provides an overview of mechanisms and factors affecting release and bioconversion of phenolic compounds in agro-industrial wastes by microbial fermentation.


Retrograde venous coil embolization prior to transarterial chemoembolization in hepatocellular carcinoma with arterio-hepatic venous shunts.
PURPOSE This study explored the clinical efficacy of transcatheter retrograde shunt occlusion with coils to prevent pulmonary oil or particle embolization prior to transarterial chemoembolization (TACE) in patients with artero-hepatic venous shunts (AHVS) secondary to hepatocellular carcinoma (HCC). METHODS From July 2017 to January 2021, 6 patients with advanced, unresectable HCC were found to have an AHVS by hepatic arteriography at the time of attempted TACE. The AHVS was embolized ret rogradely with metal coils through a transfemoral or transjugular venous approach. After venous embolization and confirmation of the absence of the AHVS, TACE was performed using an emul sion of iodized oil and doxorubicin or drug-eluting beads. Follow-up computed tomography (CT) was performed within 1 month after the first TACE to evaluate the results and complications. RESULTS Hepatic angiography after venous embolization showed that AHVS had utterly disappeared in all patients during the operation. The immediate technical success of the retrograde venous embo lization was 100%. The AHVS had disappeared entirely during the follow-up period through triple-phase enhancement CT scanning. According to the modified response evaluation criteria in solid tumors, TACE in all 6 patients had a disease control response rate of 100% (6/6) with complete response in 2 patients and partial response in 4 patients. One patient died during the 6-month follow-up, and the other 5 were still alive. No complications related to pulmonary embolism occurred. CONCLUSION Retrograde venous coil embolization of AHVS via the draining hepatic vein appears to be a safe, feasible, and effective treatment to allow TACE treatment without pulmonary embolic events. This approach appears to provide better tumor control and effectively decreases the occurrence of pulmonary embolism.


Early voice therapy in patients with unilateral vocal fold paralysis.
The purpose of this work was to study the efficacy of early voice therapy in the management of patients with unilateral vocal fold paralysis. Three groups of patients suffering from unilateral vocal fold paralysis were subjected to a protocol of voice evaluation including auditory-perceptual voice analysis, the Dysphonia Severity Index (DSI) and the 20-item Voice Problem Self-Assessment Scale (VPSS-20). Patients were also examined using video laryngostroboscopy. The early voice therapy group was enrolled in a voice therapy program for 16 sessions as soon as the patients were diagnosed; the second group of patients did not receive voice therapy during the course of their ailment. The late voice therapy group was enrolled in a voice therapy after a period of at least 6 months following the onset of vocal fold paralysis. All studied patients were reevaluated after a period of 2 months. The early voice therapy group showed better outcomes regarding VPSS-20 scores, auditory-perceptual voice analysis as well as the DSI. Early onset of voice therapy may enhance the reduction in glottal gap and improvement of voice quality by hindering the development of faulty hyperfunctional compensatory behaviors; early voice therapy may therefore enhance the patient's quality of life.


Accuracy of diagnostic classification algorithms using cognitive-, electrophysiological-, and neuroanatomical data in antipsychotic-naïve schizophrenia patients.
A wealth of clinical studies have identified objective biomarkers, which separate schizophrenia patients from healthy controls on a group level, but current diagnostic systems solely include clinical symptoms. In this study, we investigate if machine learning algorithms on multimodal data can serve as a framework for clinical translation. Forty-six antipsychotic-naïve, first-episode schizophrenia patients and 58 controls underwent neurocognitive tests, electrophysiology, and magnetic resonance imaging (MRI). Patients underwent clinical assessments before and after 6 weeks of antipsychotic monotherapy with amisulpride. Nine configurations of different supervised machine learning algorithms were applied to first estimate the unimodal diagnostic accuracy, and next to estimate the multimodal diagnostic accuracy. Finally, we explored the predictability of symptom remission. Cognitive data significantly classified patients from controls (accuracies = 60-69%; p values = 0.0001-0.009). Accuracies of electrophysiology, structural MRI, and diffusion tensor imaging did not exceed chance level. Multimodal analyses with cognition plus any combination of one or more of the remaining three modalities did not outperform cognition alone. None of the modalities predicted symptom remission. In this multivariate and multimodal study in antipsychotic-naïve patients, only cognition significantly discriminated patients from controls, and no modality appeared to predict short-term symptom remission. Overall, these findings add to the increasing call for cognition to be included in the definition of schizophrenia. To bring about the full potential of machine learning algorithms in first-episode, antipsychotic-naïve schizophrenia patients, careful a priori variable selection based on independent data as well as inclusion of other modalities may be required.


Prevalence of chronic conditions among Medicare Part A beneficiaries in 2008 and 2010: are Medicare beneficiaries getting sicker?
Medicare beneficiaries who have chronic conditions are responsible for a disproportionate share of Medicare fee-for-service expenditures. The objective of this study was to analyze the change in the health of Medicare beneficiaries enrolled in Part A (hospital insurance) between 2008 and 2010 by comparing the prevalence of 11 chronic conditions. We conducted descriptive analyses using the 2008 and 2010 Chronic Conditions Public Use Files, which are newly available from the Centers for Medicare and Medicaid Services and have administrative (claims) data on 100% of the Medicare fee-for-service population. We examined the data by age, sex, and dual eligibility (eligibility for both Medicare and Medicaid). Medicare Part A beneficiaries had more chronic conditions on average in 2010 than in 2008. The percentage increase in the average number of chronic conditions was larger for dual-eligible beneficiaries (2.8%) than for nondual-eligible beneficiaries (1.2%). The prevalence of some chronic conditions, such as congestive heart failure, ischemic heart disease, and stroke/transient ischemic attack, decreased. The deterioration of average health was due to other chronic conditions: chronic kidney disease, depression, diabetes, osteoporosis, rheumatoid arthritis/osteoarthritis. Trends in Alzheimer's disease, cancer, and chronic obstructive pulmonary disease showed differences by sex or dual eligibility or both. Analyzing the prevalence of 11 chronic conditions by using Medicare claims data provides a monitoring tool that can guide health care providers and policy makers in devising strategies to address chronic conditions and rising health care costs.


Diminishing Democracy in Health Policy: Partisanship, the Courts, and the End of Health Politics as We Knew It.
Despite unprecedented partisanship, the Affordable Care Act (ACA) traced a familiar political arc: a loud debate full of dramatic symbols, a messy legislative process, clashes over implementation, a slow rise in popularity, entrenchment as part of the health care system, and growing support that blocked Congress from repealing. The politics of the ACA looked, from one angle, like a louder version of health politics as usual. But something new was stirring. Opponents pushed the debate outside the elected branches of government and into the courts-a move that reflects past eras of highly racialized conflict. A federal court marked the ACA's tenth anniversary by doing what Congress could not: it struck down the law, although the litigation continues to wend its way through the court system. The ongoing challenge to the ACA rests on a fundamental critique of the entire New Deal dispensation in jurisprudence. The consequence could be a new era in health care politics.


Facile synthesis of S, N co-doped carbon dots and investigation of their photoluminescence properties.
A facile one-pot approach to prepare photoluminescent carbon dots (CDs) was developed through hydrothermal treatment of cysteine and citric acid. The obtained CDs show stable and bright blue emission with a quantum yield of 54% and an average lifetime of 11.61 ns. Moreover, the two-photon induced upconversion fluorescence of the CDs was observed and demonstrated. Interestingly, both down and up conversion fluorescence of the CDs show excitation-independent emission, which is quite different from most of the previously reported CDs. Ultrafast spectroscopy was also employed here to study the photoluminescence (PL) properties of the CDs. After characterization using various spectroscopic techniques, a unique PL mechanism for the as-prepared CDs' fluorescence was proposed accordingly. In addition, the influence of various metal ions on the CD fluorescence was examined and no quenching phenomena were observed. Meanwhile, gold nanoparticles (Au NPs) were found to be good quenchers of CD fluorescence and their quenching behavior was fitted to the Stern-Volmer equation. This provides new opportunities for fluorescence sensor designs and light energy conversion applications. Finally, the as-prepared CDs were inkjet-printed to form a desirable pattern, which is useful for fluorescent patterns, and anti-counterfeiting labeling.


MEDICAL OUTREACH AND IMPROVED ACCESS TO SPECIALIST SERVICES FOR THE RURAL COMMUNITY OF BAUCHI STATE, NIGERIA: THE REQUIREMENTS FOR SUSTAINABILITY.
The West African College of Physicians (Nigeria) conducted its Annual General and Scientific Meeting (AGSM) in Bauchi State, Nigeria on 11th-15th of July, 2023. The theme of the AGM is HEALTH-RELATED SDGs IN NIGERIA: THE PROGRESS SO FAR. The sub- themes included challenges of health care in the face of Disaster and the menace of brain drain on health care manpower and medical education. Part of the activities for the AGSM was a medical outreach conducted at Durum community of Bauchi LGA, Bauchi State on Saturday, 8th July, 2023 between 8:00AM to 5:00PM at Durum primary school premises. We examined the role of specialist medical outreach in supporting primary health care services and overcoming the barriers to health care faced by the rural dwellers and also examined issues affecting sustainability. Durum community was chosen from the list of 3 rural communities submitted to the Local Organizing Committee (LOC). A community entry was conducted to the relevant stakeholders. A descriptive cross-sectional design was used for the study. A semi-structured data form was used to collect information from 1062 participants. The activities included health talk and consultations on common health problems in the community as well as referral services. Relevant screenings tests for HBV, HCV, DM, Kidney diseases (Urinalysis), HIV and Tuberculosis were conducted. Medications for common diseases affecting the community were prescribed by the Doctors and dispensed during the outreach. The data were analyzed using SPSS version 26 at 5% significance level and 95% confidence interval. A total of 1,062 filled forms were retrieved. The results show that majority of the participants are females 615(58%) while 447(42%) are males. Half of the respondents are illiterate 526(50%) and only 1%(11) attended tertiary institution. Majority are unemployed 646(61%) and only 1%(13) are civil servants. The commonest existing chronic medical conditions among the participants are hypertension 43(4%) and diabetes 15(1%). The commonest presenting complaints of the respondents are fever 404(38%), headache 170(16%), cough 53(%), dizziness 53(5%), skin rashes 43 (4%), abdominal pain 159 (15%), diarrhoea 53(5%) and vaginal discharge 127(12%). Regarding medical check-up, 481(45%) of the respondents have never ever had a medical check-up. 44(4%) had a check-up in the last preceding month, 41(4%) had check-up in the last preceding week, 40(4%) had check up in the last 6 months, while 34(3%) had check-up in the last one year. 84(42%) and 81(41%) among those tested had positive results for hepatitis B and C respectively and were counseled and referred. None tested positive for Tuberculosis and 1(1%) tested positive for HIV among those screened. 301(80%) among those tested had positive results for malaria and were counseled and offered treatment. The commonest health problems in the community were malaria (41%), enteric fever (26%), PUD/Dyspepsia (19%), UTI (9%) and skin diseases (5%). The study found out that half of the participants are illiterate and unemployed. The commonest health problems in the community were malaria, enteric fever, PUD/Dyspepsia, UTI, skin diseases, Hepatitis B & C. Thus, we recommend that the Primary Health Care Centre in the community should continue to provide the basic health services to the community. The Drug Revolving Fund (DRF) of the facility should be upgraded with relevant drugs and medical consumables at an affordable cost and a Doctor should be posted to the centre on temporary basis. These require the support of Ward Development Committee, Department of Primary Health Care of Bauchi Local Government Area, Bauchi State Primary Health Care Development Agency and the Bauchi State Ministry of Health. In addition, the State Government should improve the allowances for the health care personnel working in the rural areas and support the community in educational enrollment and poverty alleviation as well as collaborating with health institutions like the WACP in providing quality services to the State.


Filarial nematode infection in eclectus parrots (Eclectus roratus) in Taiwan.
A total of 166 psittacines belonging to 22 species were received by the Animal Hospital of National Pingtung University of Science & Technology (NPUST) from 2013 to 2015. Only eclectus parrots (Eclectus roratus) were identified as hosts for microfilariae. All eclectus parrots were adult birds and had been kept in Taiwan for more than three years. The relevance of filariae to eclectus parrots is evident as indicated by the 35.7% (5/14) infection rate. At necropsy, adult filarial nematodes 57-75 mm in length and 0.4-0.7 mm in width were found in the hepatic veins. The microfilariae were 170-230 μm in length. Histopathological examination confirmed that eggs and larvae were observed in the ovaries and uteri of female filariae. These nematodes were closely related to an unidentified Filaria sp. (KJ612514.1) as indicated by polymerase chain reaction (PCR) analysis and phylogenetic analysis of nucleotide sequences from 18S ribosomal DNA gene (18S rDNA), mitochondrial cytochrome c oxidase subunit 1 (COX1) gene, and internal transcribed spacers 1-5.8S ribosomal DNA gene (ITS 1-5.8S rDNA). However, structurally the filarial nematodes were similar to that of the Pelecitus sp. Eclectus parrot species are important pet birds and are highly traded, resulting in high uncertainty of the origin of the parasite infection. This study is the first of its kind to report the presence and potential impact of filarial nematode infection on eclectus parrots, suggesting parasite inspection prior to the international trade of these pet birds.


Celiac Plexus Neurolysis Is Associated With Decreased Survival in Patients With Pancreatic Cancer: A Propensity Score Analysis.
The aim of this study was to investigate survival in patients who received celiac plexus neurolysis (CPN) compared with patients who received opioids. The Surveillance, Epidemiology and End Results-Medicare database was used to identify patients older than 65 years diagnosed with pancreatic cancer between 2007 and 2015. We used claims data to identify patients with a history of CPN and opioid use within 1 year of diagnosis, and other demographic, clinical, and treatment variables. Kaplan-Meier analyses and inverse propensity-weighted adjusted Cox proportional hazard ratios were used to evaluate survival. We identified 648 patients who underwent CPN (19.0%) compared with 2769 patients who received opioids (81.0%). The median survival and interquartile range for patients who received CPN was 4.0 months (2.0-8.0 months) compared with 7.0 months (3.0-12.0 months) for opioid users (P < 0.0001). After adjusting for confounders and propensity score, the patients who received CPN showed worsened survival (hazard ratio, 1.69; 95% confidence interval, 1.59-1.79). Pancreatic cancer patients who underwent CPN had decreased survival compared with opioid users. This suggests that opioid sparing methods to reduce pancreatic cancer pain may actually be harmful. Future prospective studies should investigate whether other opioid sparing therapies impact pancreatic cancer survival.


Advanced musculoskeletal physiotherapists in post arthroplasty review clinics: a state wide implementation program evaluation.
To evaluate outcomes following a state-wide implementation of post arthroplasty review (PAR) clinics for patients following total hip and knee arthroplasty, led by advanced musculoskeletal physiotherapists in collaboration with orthopaedic specialists. A prospective observational study analysed data collected by 10 implementation sites (five metropolitan and five regional/rural centres) between September 2014 and June 2015. The Victorian Innovation and Reform Impact Assessment Framework was used to assess efficiency, effectiveness (access to care, safety and quality, workforce capacity, utilisation of skill sets, patient and workforce satisfaction) and sustainability (stakeholder engagement, succession planning and availability of ongoing funding). 2362 planned occasions of service (OOS) were provided for 2057 patients. Reduced patient wait times from referral to appointment were recorded and no adverse events occurred. Average cost savings across 10 sites was AUD$38 per OOS (Baseline $63, PAR clinic $35), representing a reduced pathway cost of 44%. Average annual predicted total value of increased orthopaedic specialist capacity was $11,950 per PAR clinic (range $6149 to $23,400). The Australian Orthopaedic Association review guidelines were met (8/10 sites, 80%) and patient-reported outcome measures were introduced as routine clinical care. High workforce and patient satisfaction were expressed. Eighteen physiotherapists were trained creating a sustainable workforce. Eight sites secured ongoing funding. The PAR clinics delivered a safe, cost-efficient model of care that improved patient access and quality of care compared to traditional specialist-led workforce models.


Whole blood mRNA in prostate cancer reveals a four-gene androgen regulated panel.
Due to increased sensitivity, the expression of circulating nucleotides is rapidly gaining popularity in cancer diagnosis. Whole blood mRNA has been used in studies on a number of cancers, most notably two separate studies that used whole blood mRNA to define non-overlapping signatures of prostate cancer that has become castration independent. Prostate cancer is known to rely on androgens for initial growth, and there is increasing evidence on the importance of the androgen axis in advanced disease. Using whole blood mRNA samples from patients with prostate cancer, we have identified the four-gene panel of FAM129A, MME, KRT7 and SOD2 in circulating mRNA that are differentially expressed in a discovery cohort of metastatic samples. Validation of these genes at the mRNA and protein level was undertaken in additional cohorts defined by risk of relapse following surgery and hormone status. All the four genes were downregulated at the mRNA level in the circulation and in primary tissue, but this was not always reflected in tissue protein expression. MME demonstrated significant differences in the hormone cohorts, whereas FAM129A is downregulated at the mRNA level but is raised at the protein level in tumours. Using published ChIP-seq data, we have demonstrated that this may be due to AR binding at the FAM129A and MME loci in multiple cell lines. These data suggest that whole blood mRNA of androgen-regulated genes has the potential to be used for diagnosis and monitoring of prostate cancer.


Attenuation of the vaccine Oka strain of varicella-zoster virus and role of glycoprotein C in alphaherpesvirus virulence demonstrated in the SCID-hu mouse.
The SCID-hu mouse implanted with human fetal tissue is a novel model for investigating human viral pathogenesis. Infection of human skin implants was used to investigate the basis for the clinical attenuation of the varicella-zoster virus (VZV) strain, V-Oka, from which the newly licensed vaccine is made. The pathogenicity of V-Oka was compared with that of its parent, P-Oka, another low-passage clinical isolate, strain Schenke (VZV-S), and VZV-Ellen, a standard laboratory strain. The role of glycoprotein C (gC) in infectivity for human skin was assessed by using gC-negative mutants of V-Oka and VZV-Ellen. Whereas all of these VZV strains replicated well in tissue culture, only low-passage clinical isolates were fully virulent in skin, as shown by infectious virus yields and analysis of implant tissues for VZV DNA and viral protein synthesis. The infectivity of V-Oka in skin was impaired compared to that of P-Oka, providing the first evidence of a virologic basis for the clinical attenuation of V-Oka. The infectivity of V-Oka was further diminished in the absence of gC expression. All strains except gC-Ellen retained some capacity to replicate in human skin, but cell-free virus was recovered only from implants infected with P-Oka or VZV-S. Although VZV is closely related to herpes simplex virus type 1 (HSV-1) genetically, experiments in the SCID-hu model revealed differences in tropism for human cells that correlated with differences in VZV and HSV-1 disease. VZV caused extensive infection of epidermal and dermal skin cells, while HSV-1 produced small, superficial lesions restricted to the epidermis. As in VZV, gC expression was a determinant for viral replication in skin. VZV infects human CD4+ and CD8+ T cells in thymus/liver implants, but HSV-1 was detected only in epithelial cells, with no evidence of lymphotropism. These SCID-hu mouse experiments show that the clinical attenuation of the varicella vaccine can be attributed to decreased replication of V-Oka in skin and that tissue culture passage alone reduces the ability of VZV to infect human skin in vivo. Furthermore, gC, which is dispensable for replication in tissue culture, plays a critical role in the virulence of the human alphaherpesviruses VZV and HSV-1 for human skin.


Effect of aminophylline on fatigue of the sternomastoid muscle in man.
The effect of intravenous aminophylline on the contractility of the sternomastoid muscle was measured in the fresh state and after the induction of significant fatigue in five normal subjects. Fatigue was produced by repetitive isometric neck flexion, for two seconds every four seconds at 70% of the maximum voluntary contractile force, continued until exhaustion. Each subject performed three experiments, one to two weeks apart, in random order. In experiment 1 fatiguing exercise and recovery were completed without aminophylline; in experiment 2 intravenous aminophylline was started 30 minutes before exercise and continued throughout the 60 minute recovery period; and in experiment 3 intravenous aminophylline was started immediately after the end of exercise. Aminophylline did not influence the frequency-force relationships, relaxation rate, or maximum voluntary contractile force in the fresh muscle. After fatiguing exercise there was a relatively selective reduction in force response to stimulation frequencies of less than 30 Hz, with little alteration in forces at higher frequencies--that is, low frequency fatigue--and this effect was present for the entire one hour study period. Aminophylline given before or immediately after fatigue did not influence the recovery of either low frequency fatigue or maximum voluntary contractile force. Aminophylline at therapeutic concentrations had no significant effect on the contractility or fatiguability of the normal human sternomastoid muscle.


Embryo selection in IVF.
To optimize success rates of IVF, selection of the most viable embryo(s) for transfer has always been essential, as embryos that are cryopreserved are thought to have a reduced chance of implanting after thawing. Recent developments challenge this concept. Evidence is accumulating that all embryos can now be cryopreserved and transferred in subsequent cycles without impairing pregnancy rates or maybe even with an improvement in pregnancy rates. In such a scenario no selection method will ever lead to improved live birth rates, as, by definition, the live birth rate per stimulated IVF cycle can never be improved when all embryos are serially transferred. In fact, selection could then only lower the live birth rate after IVF. The only parameter that could possibly be improved by embryo selection would be time to pregnancy, if embryos with the highest implantation potential are transferred first.


[The effect of chronic social conflicts on the indices of nonspecific resistance in mice].
Male mice C57BL/6J were divided into victors and losers in daily confrontations. After 10 confrontations, the losers developed a leukopenia, a decrease in the Thymus index, protein concentration and immunoglobulins class G, as well as a decrease in the agglutinins titres to the ram erythrocytes in the blood plasma. The same changes occurred to a minimal extent in the victors. The changes seem to reflect a stress sensitivity degree.


Investigation of vibrational manner of carbon nanotubes in the vicinity of ultrasonic argon flow using molecular dynamics simulation.
Among various types of nanostructures, carbon nanotube (CNT) is one of the most important nanostructures. These nanostructures have been considered due to their mechanical, thermal, and vibrational properties. In this research, this nanostructure's vibrational behavior in the vicinity of argon flow in the vicinity of ultrasonic velocity was investigated. The effect of factors such as the stability of atomic structures, the atomic manner of carbon nanotubes in the presence of ultrasonic fluid, the influence of carbon nanotubes' length, and the chirality of carbon nanotubes on vibrational behavior was studied by molecular dynamics simulation. The MD simulations display an enhance in amplitude and a decrease in the oscillation frequency. Physically, these simulations' results indicated the appropriate mechanical strength of carbon nanotubes in the presence of argon fluid. Numerically, the simulated carbon nanotubes' minimum oscillation amplitude and frequency were equal to 2.02 nm and 10.14 ps-1. On the other hand, the maximum physical quantities were expressed as 4.03 nm and 13.01 ps-1.


Postoperative atrial fibrillation in patients undergoing coronary artery bypass grafting or cardiac valve surgery: intraoperative use of landiolol.
Landiolol hydrochloride is a new β-adrenergic blocker with a pharmacological profile that suggests it can be administered safely to patients who have sinus tachycardia or tachyarrhythmia and who require heart rate reduction. This study aimed to investigate whether intraoperative administration of landiolol could reduce the incidence of atrial fibrillation (AF) after cardiac surgery. Of the 200 consecutive patients whose records could be retrieved between October 2006 and September 2007, we retrospectively reviewed a total of 105 patients who met the inclusion criteria: no previous permanent/persistent AF, no permanent pacemaker, no renal insufficiency requiring dialysis, and no reactive airway disease, etc. Landiolol infusion was started after surgery had commenced, at an infusion rate of 1 μg/kg/min, titrated upward in 3-5 μg/kg/min increments. The patients were divided into 2 groups: those who received intraoperative β-blocker therapy with landiolol (landiolol group) and those who did not receive any β-blockers during surgery (control group). An unpaired t test and Fisher's exact test were used to compare between-group differences in mean values and categorical data, respectively. Seventeen of the 105 patients (16.2%) developed postoperative atrial fibrillation: 5/57 (8.8%) in the landiolol group and 12/48 (25%) in the control group. There was a significant difference between the two groups (P=0.03). The incidence of AF after valve surgery and off-pump coronary artery bypass grafting was lower in the landiolol group, although the difference between the groups was not statistically significant. Our retrospective review demonstrated a marked reduction of postoperative AF in those who received landiolol intraoperatively. A prospective study of intraoperative landiolol for preventing postoperative atrial fibrillation is warranted.


Individually assessed boldness predicts Perca fluviatilis behaviour in shoals, but is not associated with the capture order or angling method.
Selectivity of recreational angling on fish behaviour was studied by examining whether capture order or lure type (natural v. artificial bait) in ice-fishing could explain behavioural variation among perch Perca fluviatilis individuals. It was also tested if individually assessed personality predicts fish behaviour in groups, in the presence of natural predators. Perca fluviatilis showed individually repeatable behaviour both in individual and in group tests. Capture order, capture method, condition factor or past growth rate did not explain variation in individual behaviour. Individually determined boldness as well as fish size, however, were positively associated with first entrance to the predator zone (i.e. initial risk taking) in group behaviour tests. Individually determined boldness also explained long-term activity and total time spent in the vicinity of predators in the group. These findings suggest that individual and laboratory-based boldness tests predict boldness of P. fluviatilis in also ecologically relevant conditions, i.e. in shoals and in the presence of natural predators. The present results, however, also indicate that the above-mentioned two angling methods may not be selective for certain behavioural types in comparison to each other.


Influence of Interval Between Postharvest Lettuce Residue Management and Subsequent Seeding of Broccoli on Cabbage Maggot (Diptera: Anthomyiidae) Infestation on Broccoli.
Larval stages of cabbage maggot, Delia radicum (L.) (Diptera: Anthomyiidae), attack the roots of Brassica crops and cause severe economic damage. In the Salinas Valley of California, Brassica crops are often planted after successive lettuce (Lactuca sativa L.) crops. The interval between postharvest soil incorporation of lettuce residue and the subsequent Brassica crop can be as short as 7 d, which could influence D. radicum infestation on broccoli (Brassica oleracea var. italica Plenck). In 2014 and 2015, the effect of intervals between crops (IBC) on D. radicum infestation was evaluated. The treatments were 7, 20, 33, and 48 d IBC, and NL (no lettuce), 7, 21, 36, and 49 d IBC in 2014 and 2015, respectively. Insect counts and feeding damage on broccoli was assessed during 3-6 wk after planting. Adult Delia fly captures were significantly greater at 7 d than 36-49 d IBC in both years. In both years, D. radicum eggs collected were significantly greater at 7 d than at 33 d or 36 d IBC plots. Larvae collected were significantly greater at 7 d IBC than all other treatments in 2014, but not in 2015. Similarly, severity of feeding injury was significantly greater in 7 d than 33 d or 48 d IBC in 2014, but not in 2015. In 2015, broccoli with no prior lettuce had significantly lower Delia flies and D. radicum egg densities than 7 d or 21 d IBC. The implication of these results as a cultural control tactic for D. radicum infestation is discussed.


Venous Thromboembolism and Renal Impairment: Insights from the SWIss Venous ThromboEmbolism Registry (SWIVTER).
Renal impairment (RI) has increased substantially over the last decades. In the absence of data from confirmatory research, real-life data on anticoagulation treatment and clinical outcomes of venous thromboembolism (VTE) in patients with RI are needed. In the SWIss Venous ThromboEmbolism Registry (SWIVTER), 2,062 consecutive patients with objectively confirmed VTE were enrolled. In the present analysis, we compared characteristics, initial and maintenance anticoagulation, and adjusted 90-day clinical outcomes of those with (defined as estimated creatinine clearance < 30 mL/min) and without severe RI. Overall, 240 (12%) patients had severe RI; they were older, and more frequently had chronic and acute comorbidities. VTE severity was similar between patients with and without severe RI. Initial anticoagulation in patients with severe RI was more often performed with unfractionated heparin (44 vs. 24%), and less often with low-molecular-weight heparin (LMWH) (52 vs. 61%) and direct oral anticoagulants (DOACs; 4 vs. 12%). Maintenance anticoagulation in patients with severe RI was more frequently managed with vitamin K antagonists (70 vs. 60%) and less frequently with DOAC (12 vs. 21%). Severe RI was associated with increased risk of 90-day mortality (9.2 vs. 4.2%, hazard ratio [HR]: 2.27, 95% confidence interval [CI]: 1.41-3.65), but with similar risk of recurrent VTE (3.3 vs. 2.8%, HR: 1.19, 95% CI: 0.57-2.52) and major bleeding (2.1 vs. 2.0%, HR: 1.05, 95% CI: 0.41-2.68). In patients with severe RI, the use of LMWH versus any other treatment was associated with reduced mortality (HR: 0.37; 95% CI: 0.14-0.94; p = 0.036) and similar rate of major bleeding (HR: 0.59, 95% CI: 0.17-2.00; p = 0.39). Acute or chronic comorbidities rather than VTE severity or recurrence may explain increased early mortality in patients with severe RI. The higher rate of VTE recurrence, specifically fatal events, than major bleeding reinforces the need for effective anticoagulation in VTE patients with severe RI.


Sequential combination of glucocorticosteroids and alfa interferon versus alfa interferon alone for HBeAg-positive chronic hepatitis B.
Chronic hepatitis B has serious effects on morbidity and mortality. Alfa interferon has been shown to increase the rates of HBeAg-clearance as well as seroconversion to anti-HBe, but response rates are unsatisfactory. Glucocorticosteroid pretreatment may increase the response to alfa interferon. The objectives were to assess the effects of the sequential combination of glucocorticosteroids and alfa interferon versus alfa interferon alone in hepatitis B 'e' antigen positive chronic hepatitis B on mortality, virological response, biochemical response, liver histology, quality of life, and adverse events. Eligible trials were identified through searches of The Cochrane Hepato-Biliary Controlled Trials Register (May 2005), The Cochrane Central Register of Controlled Trials in The Cochrane Library (Issue 2, 2005), MEDLINE (1950 to May 2005), EMBASE (Excerpta Medica Database) (1980 to May 2005), BIOSIS (1969 to May 2005), and reference lists of relevant articles. Further trials were sought through correspondence with authors of trials and pharmaceutical companies. Randomised clinical trials comparing identical alfa interferon treatment regimens with and without glucocorticosteroid pretreatment for hepatitis B 'e' antigen positive chronic hepatitis. We included trials irrespective blinding, publication status, or language. Three authors selected the trials independently and one extracted the data, which were then validated. We performed assessments of the outcome measures at the end of treatment and at six months and at maximal follow-up after the end of treatment with alfa interferon. We included a total of 13 randomised trials with 790 patients. Loss of hepatitis B 'e' antigen (OR 1.41, 95% confidence interval 1.03 to 1.92, P = 0.03) and hepatitis B virus DNA (OR = 1.51, 95% confidence interval 1.12 to 2.05, P = 0.008) were significantly more frequent among patients treated with the sequential combination of glucocorticosteroids and alfa interferon than among patients treated with alfa interferon alone. Glucocorticosteroid pretreatment did not significantly influence seroconversion from hepatitis B 'e' antigen to antibodies to hepatitis B 'e' antigen, loss of hepatitis B surface antigen, normalisation of alanine aminotransferase/aspartate aminotransferase activities, and severity of adverse events. Glucocorticosteroid pretreatment did not significantly affect mortality and adverse events. The effect of glucocorticosteroid pretreatment on liver histology and quality of life could not be assessed due to insufficient data. Pretreatment with glucocorticosteroids before treatment with alfa interferon in patients with hepatitis B 'e' antigen positive chronic hepatitis B may be more effective than treatment with alfa interferon alone with regard to loss of hepatitis B 'e' antigen and hepatitis B virus DNA, but evidence for effect on clinical outcomes is lacking.


Epidermal growth factor receptor signalling in human breast cancer cells operates parallel to estrogen receptor α signalling and results in tamoxifen insensitive proliferation.
Tamoxifen resistance is a major problem in the treatment of estrogen receptor (ER) α -positive breast cancer patients. Although the mechanisms behind tamoxifen resistance are still not completely understood, clinical data suggests that increased expression of receptor tyrosine kinases is involved. Here, we studied the estrogen and anti-estrogen sensitivity of human breast cancer MCF7 cells that have a moderate, retroviral-mediated, ectopic expression of epidermal growth factor receptor (MCF7-EGFR). Proliferation of MCF7-EGFR and parental cells was induced by 17β-estradiol (E2), epidermal growth factor (EGF) or a combination of these. Inhibition of proliferation under these conditions was investigated with 4-hydroxy-tamoxifen (TAM) or fulvestrant at 10(-12) to 10(-6) M. Cells were lysed at different time points to determine the phosphorylation status of EGFR, MAPK1/3, AKT and the expression of ERα. Knockdown of target genes was established using smartpool siRNAs. Transcriptomics analysis was done 6 hr after stimulation with growth factors using Affymetrix HG-U133 PM array plates. While proliferation of parental MCF7 cells could only be induced by E2, proliferation of MCF7-EGFR cells could be induced by either E2 or EGF. Treatment with TAM or fulvestrant did significantly inhibit proliferation of MCF7-EGFR cells stimulated with E2 alone. EGF treatment of E2/TAM treated cells led to a marked cell proliferation thereby overruling the anti-estrogen-mediated inhibition of cell proliferation. Under these conditions, TAM however did still inhibit ERα- mediated transcription. While siRNA-mediated knock-down of EGFR inhibited the EGF- driven proliferation under TAM/E2/EGF condition, knock down of ERα did not. The TAM resistant cell proliferation mediated by the conditional EGFR-signaling may be dependent on the PI3K/Akt pathway but not the MEK/MAPK pathway, since a MEK inhibitor (U0126), did not block the proliferation. Transcriptomic analysis under the various E2/TAM/EGF conditions revealed that E2 and EGF dependent transcription have little overlap and rather operate in a parallel fashion. Our data indicate that enhanced EGFR-driven signalling is sufficient to overrule the TAM- mediated inhibition of E2-driven cell proliferation. This may have profound implications for the anti-estrogen treatment of ER-positive breast cancers that have increased levels of EGFR.


Pre-service and In-service Teachers' Metacognitive Knowledge of Learning Strategies.
Research in cognitive psychology has suggested that difficulties are often desirable for learning: learning strategies that create difficulties for learners during practice often produce durable learning. Prominent examples of effective learning strategies that introduce desirable difficulties are testing as a means of learning, spacing study sessions over time, and interleaving practice of different topics. Previous research has suggested that, generally, undergraduates' metacognitive knowledge about the effectiveness of these learning strategies is inaccurate. The goal of the current study was to extend the examination of metacognitive knowledge of learning strategies to pre-service and in-service teachers, and further examine whether teachers' metacognitive knowledge is related to their teaching experience. Pre-service teachers enrolled in a university teacher training program (N = 83) and in-service elementary, junior-high, and high school teachers (N = 82) were presented with learning scenarios and predicted which of two learning strategies would yield the better outcome. Results suggested that, overall, both pre-service and in-service teachers failed to predict the advantages of testing, spacing, and interleaving as learning strategies. Furthermore, their knowledge of learning strategies failed to increase with teaching experience. It is, therefore, recommended that explicit instruction about the benefits of empirically supported learning strategies should be included in teacher training and development programs.


How does barley supplementation in lambs grazing alfalfa affect meat sensory quality and authentication?
Excessive flavour in lamb meat is undesirable for consumers and can prompt purchase resistance. Volatile indoles responsible for off-flavours accumulate more in the fat of lambs on pasture than on grain and are enhanced when lambs graze alfalfa. Here, we investigated whether barley supplementation of lambs grazing alfalfa influences meat sensory quality. Using three groups of 12 male Romane lambs, we compared three feeding regimes: alfalfa grazing (AG), alfalfa grazing + daily supplementation with barley (29 g/kg live weight0.75, AGS) and stall feeding with concentrate and hay (SF). As some of the compounds involved in meat sensory traits may act as dietary biomarkers, we also investigated potential implications for meat authentication. Although barley represented 38% of the diet in AGS lambs, it did not offer any advantage for animal average daily gain or parasitism level. Animal performance, carcass weight and fatness did not differ between feeding regimes. Dorsal fat firmness tended to be greater in AG than AGS and greater in AGS than SF. Skatole and indole concentrations in perirenal and dorsal fat were lower in SF lambs than in AG and AGS lambs (P<0.01 to P<0.0001), but did not differ between AG and AGS lambs. Yellowness, chroma and hue angle of perirenal fat were lower in SF lambs than in AG and AGS lambs (P<0.001), but did not differ between AG and AGS lambs. Absolute value of the mean integral for both perirenal fat and subcutaneous caudal fat (AVMIPF and AVMISC), quantifying the intensity of light absorption by carotenoids in perirenal and subcutaneous caudal fat, respectively, were lower in SF lambs than in AG and AGS lambs (P<0.0001 for both comparisons), but did not differ between AG and AGS lambs. Meat colour was unaffected by the treatment. We confirm that lambs grazing alfalfa accumulate high levels of volatile indoles in their fat, but we show that barley supplementation to lambs grazing alfalfa is not effective in reducing fat volatile indoles concentration and excessive odour/flavour in the meat. We also confirm that both perirenal fat skatole concentration and AVMIPF are of interest for discriminating lambs that grazed alfalfa from lambs that were stall-fed, and we show that they are not effective for discriminating supplemented from non-supplemented grazing lambs.


The European nitrogen case.
The N budget for Europe (excluding the former Soviet Union) indicates that the 3 principal driving forces of the acceleration of the European N cycle are fertilizer production (14 Mt (mill. tonnes) N yr-1), fossil fuel combustion and other industry (3.3 Mt N yr-1) and import of N in various products (7.6 Mt N yr-1). The various leaks of reactive N species from European food, energy and industrial production systems are estimated and their effects on human health and terrestrial and aquatic ecosystems are assessed. Future European environmental policy measures to close the N cycle and to reduce leaks of reactive N can best focus on the three major driving forces, taking into consideration the possible consequences in the N cascade. Critical loads may be useful tools in determining N-emission ceilings and developing integrated policies for regulating N flows such as fertilizer use and imports and N levels.


Reduced acute inpatient care was largest savings component of Geisinger Health System's patient-centered medical home.
Early evidence suggests that the patient-centered medical home has the potential to improve patient outcomes while reducing the cost of care. However, it is unclear how this care model achieves such desirable results, particularly its impact on cost. We estimated cost savings associated with Geisinger Health System's patient-centered medical home clinics by examining longitudinal clinic-level claims data from elderly Medicare patients attending the clinics over a ninety-month period (2006 through the first half of 2013). We also used these data to deconstruct savings into its main components (inpatient, outpatient, professional, and prescription drugs). During this period, total costs associated with patient-centered medical home exposure declined by approximately 7.9 percent; the largest source of this savings was acute inpatient care ($34, or 19 percent savings per member per month), which accounts for about 64 percent of the total estimated savings. This finding is further supported by the fact that longer exposure was also associated with lower acute inpatient admission rates. The results of this study suggest that patient-centered medical homes can lead to sustainable, long-term improvements in patient health outcomes and the cost of care.


Screening, triage, and referral of patients who report suicidal thought during a primary care visit.
Suicidal youths are rarely identified in primary care settings. We describe here a care process that includes a computerized screen, colocated social workers, and a coordinated suicide-prevention team at a specialty mental health unit. Patients were 1547 youths aged 11 to 20 years seen in an urban primary care system during 2005 and 2006. We performed an observational study of services provided to youths who screened positive for suicidal ideation on a computerized behavioral health screen during visits to pediatric primary care clinics. Data included clinical records, provider notes, and patients' responses to the screen. A total of 209 (14%) youths reported suicidal thought in the previous month. Suicidal thought was more common among girls, younger youths, substance users, depressed youths, youths who carried weapons, and those who had been in fights; 87% reported at least 1 other serious behavioral health problem. Social workers were able to triage 205 (98%) youths. Triage occurred on the visit day for 193 youths (94%). Mental health evaluations were recommended for 152 (74%) of the triaged youths. Of the 109 subjects referred to a clinic with records accessible for review, 71 (65%) received a mental health service within 6 months. Pediatric primary care is a feasible setting in which to screen for suicidal youths and link them with mental health services. Youths who visit primary care clinics are willing to disclose suicidal ideation on a computerized screen. Youths who screen positive for suicide have many associated behavioral health needs. The use of information technology, colocated physician extenders, and a coordinated team on the mental health side can facilitate rapid, personal contact between the family and mental health service providers, and has the potential to overcome barriers to care for youths with suicidal ideation in the primary care setting.


Access to health care as a human right in international policy: critical reflections and contemporary challenges.
Using the United Nations (UN) and its subordinate body, the World Health Organization (WHO), as a frame of reference, this article explores access to healthcare as a human right in international intergovernmental policies. First, we look at how the theme of health is treated within the UN, focusing on the concept of global health. We then discuss the concept of global health from a human rights perspective and go on to outline the debate surrounding universal coverage versus universal access as a human right, addressing some important ethical questions. Thereafter, we discuss universal coverage versus universal access using the critical and constructivist theories of international relations as a frame of reference. Finally, it is concluded that, faced with the persistence of huge global health inequalities, the WHO began to reshape itself, leaving behind the notion of health as a human right and imposing the challenge of reducing the wide gap that separates international intergovernmental laws from reality.


Sample Preparation Free Mass Spectrometry Using Laser-Assisted Rapid Evaporative Ionization Mass Spectrometry: Applications to Microbiology, Metabolic Biofluid Phenotyping, and Food Authenticity.
Mass spectrometry has established itself as a powerful tool in the chemical, biological, medical, environmental, and agricultural fields. However, experimental approaches and potential application areas have been limited by a traditional reliance on sample preparation, extraction, and chromatographic separation. Ambient ionization mass spectrometry methods have addressed this challenge but are still somewhat restricted in requirements for sample manipulation to make it suitable for analysis. These limitations are particularly restrictive in view of the move toward high-throughput and automated analytical workflows. To address this, we present what we consider to be the first automated sample-preparation-free mass spectrometry platform utilizing a carbon dioxide (CO2) laser for sample thermal desorption linked to the rapid evaporative ionization mass spectrometry (LA-REIMS) methodology. We show that the pulsatile operation of the CO2 laser is the primary factor in achieving high signal-to-noise ratios. We further show that the LA-REIMS automated platform is suited to the analysis of three diverse biological materials within different application areas. First, clinical microbiology isolates were classified to species level with an accuracy of 97.2%, the highest accuracy reported in current literature. Second, fecal samples from a type 2 diabetes mellitus cohort were analyzed with LA-REIMS, which allowed tentative identification of biomarkers which are potentially associated with disease pathogenesis and a disease classification accuracy of 94%. Finally, we showed the ability of the LA-REIMS system to detect instances of adulteration of cooking oil and determine the geographical area of production of three protected olive oil products with 100% classification accuracy.


Quantitative trait loci for growth and body size in the nine-spined stickleback Pungitius pungitius L.
Body size is an ecologically important trait shown to be genetically variable both within and among different animal populations as revealed by quantitative genetic studies. However, few studies have looked into underlying genetic architecture of body size variability in the wild using genetic mapping methods. With the aid of quantitative trait loci (QTL) analyses based on 226 microsatellite markers, we mapped body size and growth rate traits in the nine-spined stickleback (Pungitius pungitius) using an F2 -intercross (n = 283 offspring) between size-divergent populations. In total, 17 QTL locations were detected. The proportion of phenotypic variation explained by individual body size-related QTL ranged from 3% to 12% and those related to growth parameters and increments from 3% to 10%. Several of the detected QTL affected either early or late growth. These results provide a solid starting point for more in depth investigations of structure and function of genomic regions involved in determination of body size in this popular model of ecological and evolutionary research.


Variation at the Calpain 3 gene is associated with meat tenderness in zebu and composite breeds of cattle.
Quantitative Trait Loci (QTL) affecting meat tenderness have been reported on Bovine chromosome 10. Here we examine variation at the Calpain 3 (CAPN3) gene in cattle, a gene located within the confidence interval of the QTL, and which is a positional candidate gene based on the biochemical activity of the protein. We identified single nucleotide polymorphisms (SNP) in the genomic sequence of the CAPN3 gene and tested three of these in a sample of 2189 cattle. Of the three SNP genotyped, the CAPN3:c.1538+225G>T had the largest significant additive effect, with an allele substitution effect in the Brahman of alpha = -0.144 kg, SE = 0.060, P = 0.016, and the polymorphism explained 1.7% of the residual phenotypic variance in that sample of the breed. Significant haplotype substitution effects were found for all three breeds, the Brahman, the Belmont Red, and the Santa Gertrudis. For the common haplotype, the haplotype substitution effect in the Brahman was alpha = 0.169 kg, SE = 0.056, P = 0.003. The effect of this gene was compared to Calpastatin in the same sample. The SNP show negligible frequencies in taurine breeds and low to moderate minor allele frequencies in zebu or composite animals. These associations confirm the location of a QTL for meat tenderness in this region of bovine chromosome 10. SNP in or near this gene may be responsible for part of the overall difference between taurine and zebu breeds in meat tenderness, and the greater variability in meat tenderness found in zebu and composite breeds. The evidence provided so far suggests that none of these tested SNP are causative mutations.


[Gliomas induced in mammals by Rous sarcoma virus (RSV) (author's transl)].
Studies concerning the induction of gliomas in a variety of animal species by an oncogenic avian virus (Rous sarcoma virus) were presented. Experimental conditions (age of inoculation, doses of virus) were reviewed. Preliminary attempts to localize viral antigens in the tumors in vivo using labelled antibodies were discussed.


Focus on social functioning in depression.
Depressive disorders represent a significant global health burden. By the year 2020 the contribution of psychiatric and neurological conditions to the global burden of disease is predicted to reach 15%. Despite this, depression is frequently unrecognized and undertreated; most depressed people do not seek treatment for their depression, and of those who do, most do not receive adequate treatment. Depression is a debilitating condition and the effects of the illness extend beyond the classically defined symptoms to almost every facet of an individual's life, including their social interactions; and even beyond the individual, to close relatives. The treatment of impaired social functioning has not been widely adopted as a therapeutic principle in depression, although it is recognized as an important part of the treatment of schizophrenia. However, depressed individuals experience more functional impairment than patients with other chronic medical conditions such as diabetes and hypertension. Early studies have suggested that antidepressants, in addition to improving the core symptoms of depression, are effective in the treatment of impaired social functioning; but few studies have directly compared different classes of antidepressants. This paper seeks to raise awareness of the key issues relating to the treatment of impaired social functioning in depression and to provide a basis for wider discussion of the topic prior to the establishment of treatment guidelines.


[The effects of 6 months' multimodal training on functional performance, strength, endurance, and body mass index of older individuals. Are the benefits of training similar among women and men?].
Good functional performance in elderly people greatly improves their changes of independence and well-being. Conversely, bad functional performance can impair their capability of managing the activities of daily life.. The main goal of this study was to investigate the effects of a 6-months' multimodal training intervention on the physical performance of males and females, possible gender differences and the outcome 6 and 12 months after its completion. This study examined 71-90 year old healthy seniors (n=117) participating in the AGES Reykjavik Study. It was a randomized and controlled cross-over trial, conducted in three 6-months' phases (time-points). After enrollment and baseline assessments, the study group was divided in two. Group 1 received 6-months' training while group 2 served as a control. In the second 6 months' phase, group 1 received no formal training while group 2 did. In the third phase, neither group received training. The groups' physical conditions were assessed after each phase. After 6-months' training, 32% improvement was seen in physical activity among males (p<0.001) and 39% among females (p<0.001). In physical performance, 5% improvement was seen for males (p<0.01) and 7% for females (p<0.001). Strength increased by 8% for males (p<0.001) and 13% for females (p<0.001). For both sexes, about 10% increase was seen in dynamic balance in the 8-foot up-and-go test (p<0.001) and 5-6% in walking distance for both sexes in the six minutes walking test (p<0.001). For both sexes, body mass index decreased by about 2% (p<0.001). No difference was seen between the sexes.in the training results. Both sexes retained long-term effects of the training on physical performance and dynamic balance for at least 12 months. Multimodal training intervention has positive effects on physical performance in older individuals, the sexes respond similarly to the training and retain achieved improvement for at least 12 months. The research indicates that moderate and systemic training for this age group could be a part of conventional health service for this age group.


A novel human rotavirus serotype with dual G5-G11 specificity.
Rotavirus serotype G5 isolates were recently recovered from children with diarrhoea in Brazil. Like most human strains, they exhibited long electropherotypes and subgroup II and Wa-like VP4 specificity. We report the successful propagation and the molecular and antigenic characterization of one of these isolates (IAL-28). Cross-neutralization of IAL-28 and a single gene reassortant, UK x IAL-28, which contains the gene encoding the IAL-28 VP7 in the UK genomic background, with prototype G1 to G14 rotaviruses demonstrated that IAL-28 has antigenic determinants specific for both G5 and G11 serotypes. Sequence analysis of the gene encoding VP7 suggested that one or two amino acid substitutions at positions 96 and 100 on IAL-28 VP7 were possibly responsible for the additional G11 specificity. G5 rotaviruses are found in horses and predominate in piglets, whereas G11 has been identified exclusively as a swine pathogen.


[Morphofunctional changes in the cardiovascular system in nitroglycerin poisoning].
The cardiovascular system was examined in acute, subacute and chronic intoxications with nitroglycerin. It was revealed that morphofunctional alterations were uniform in nature, being more demonstrable in chronic exposure during 6 months. Myocardial alterations were characterized by disturbed hemodynamics, dystrophy, focal myocarditis, changes in the activity of enzymes, and changes in the electrocardio- and rheovasographic readings. Prolonged intoxication produced more profound and stable alterations.


Beyond abstinence and relapse II: momentary relationships between stress, craving, and lapse within clusters of patients with similar patterns of drug use.
Given that many patients being treated for opioid-use disorder continue to use drugs, identifying clusters of patients who share similar patterns of use might provide insight into the disorder, the processes that affect it, and ways that treatment can be personalized. We applied hierarchical clustering to identify patterns of opioid and cocaine use in 309 participants being treated with methadone or buprenorphine (in a buprenorphine-naloxone formulation) for up to 16 weeks. A smartphone app was used to assess stress and craving at three random times per day over the course of the study. Five basic patterns of use were identified: frequent opioid use, frequent cocaine use, frequent dual use (opioids and cocaine), sporadic use, and infrequent use. These patterns were differentially associated with medication (methadone vs. buprenorphine), race, age, drug-use history, drug-related problems prior to the study, stress-coping strategies, specific triggers of use events, and levels of cue exposure, craving, and negative mood. Craving tended to increase before use in all except those who used sporadically. Craving was sharply higher during the 90 min following moderate-to-severe stress in those with frequent use, but only moderately higher in those with infrequent or sporadic use. People who share similar patterns of drug-use during treatment also tend to share similarities with respect to psychological processes that surround instances of use, such as stress-induced craving. Cluster analysis combined with smartphone-based experience sampling provides an effective strategy for studying how drug use is related to personal and environmental factors.