Inhibin subunit gene expression and distribution in the ovaries of immature, young adult, middle-aged, and old female rats.
In young adult female rats, the patterns of inhibin subunit mRNA expression during the estrous cycle are regulated by cyclic changes in gonadotropin secretion and follicular development. Since there are distinct alterations in profiles of both hormone secretion and folliculogenesis during the reproductive lifespan of the female rat, we have characterized the gene expression and distribution of inhibin subunit mRNAs in immature (22 days), young adult cyclic (3-4 months), middle-aged cyclic (9-10 months), and old (12-13 months) persistent estrous (PE) rat ovaries. Northern blot analyses revealed that in contrast to young adult cyclic rats, inhibin alpha- and beta A-subunit mRNA levels in the ovaries of middle-aged cyclic rats remained substantially elevated after the proestrous gonadotropin surges and ovulation. Likewise, acyclic immature and old PE rats showed high levels of inhibin alpha- and beta A-subunit transcripts in their ovaries. In situ hybridization analyses demonstrated that inhibin alpha- and beta A mRNAs were abundantly expressed in maturing follicles of both young and middle-aged cyclic females, while high levels of alpha-subunit transcripts were only detected in the ovarian stroma of middle-aged animals. The ovaries of old PE rats had numerous large cystic follicles (with variable layers of granulosa cells) and few degenerating cyst-like structures (completely devoid of granulosa cells). Inhibin subunit transcripts were expressed abundantly in both the granulosa (alpha and beta A-subunits) and theca interna (alpha-subunit only) layers of large follicles, but were absent from degenerating cysts devoid of granulosa cells. The ovarian stroma of PE rats also expressed very high levels of inhibin-alpha, but not beta A mRNA. The ovaries of immature rats contained large numbers of uniformly developing secondary follicles. High levels of inhibin-alpha mRNA were expressed homogeneously in the granulosa layer of all growing follicles, whereas inhibin beta A mRNAs were only detected in selectively larger follicles with multiple layers of granulosa cells. Hormone RIAs of serum samples from these same groups of animals showed that basal levels of serum FSH were substantially higher in immature, middle-aged cyclic, and old PE rats than in young adult rats. These results demonstrate that enhanced ovarian inhibin subunit gene expression in the female rat is associated with increased serum FSH levels regardless of chronological age. On the other hand, aging appears to selectively enhance inhibin alpha, but not beta A, gene expression in the ovarian stroma, such that it may gradually become a major secondary site of alpha-subunit mRNA production in addition to the follicular compartments.


Iodine-125 Brachytherapy for Uveal Melanoma: A Systematic Review of Radiation Dose.
To investigate whether lower radiation doses may yield similar outcome measures to those from the COMS trial. A literature review of English language articles was performed using the PubMed database of the U.S. National Library of Medicine and the Cochrane Central Register of Controlled Trials using the following keywords: uveal melanoma, choroidal melanoma, primary uveal malignant melanoma, iodine-125 brachytherapy, local recurrence, local treatment failure, and local tumor control. The relationships between study local recurrence rate and median dosage were tested by linear regression, with each study weighted by the number of patients included. Fifteen retrospective and prospective studies were selected for systematic review (2,662 patients). Ranges of reported mean or median radiation dose to tumor apex were 62.5-104.0 Gy. Local recurrence rates ranged from 0 to 24%. A 1.0-Gy increase in the average study dose was associated with a 0.14% decrease in local recurrence rate, which was not statistically significant (p value 0.336). The gold standard empirically derived 85.0-Gy radiation dose for the treatment of uveal melanoma could be tested in a randomized study.


Efficacy of indirect ELISA for serodiagnosis of melioidosis using immunodominant antigens from non-pathogenic Burkholderia thailandensis.
Melioidosis caused by gram negative bacteria, B. pseudomallei, is a fatal disease in the tropical and sub-tropical regions. However, sporadic cases have been reported in elsewhere. Early detection is imperative to reduce the mortality rate. Serological tests have being substantially developed using recombinant proteins as specific targeted antigens to melioidosis antibodies. In the present study, we focus on a truncated flagellin fragment (FLAG300) and outer membrane protein A (OmpABT) of B. thailandensis E264 as potential antigens for developing indirect ELISA to improve the serodiagnosis of melioidosis. Recombinant proteins were overexpressed and purified by immobilized metal affinity chromatography with denaturing conditions. The sensitivity and specificity of individual test were calculated within culture-confirmed melioidosis sera (n = 42) and non-melioidosis serum samples (n = 241) using the cut-off point at average of absorbance plus 2 standard deviations. The results demonstrated that a FLAG 300 based indirect ELISA showed 90.48 % sensitivity and 87.14 % specificity and an OmpABT based this assay revealed sensitivity of 80.95 % and specificity of 89.21 %. Their use in a double-antigen ELISA resulted in improve specificity (92.95 %) and still high degree of sensitivity (85.71 %). These data suggest a facile method for serodiagnosis of melioidosis by the use of antigens from a non-pathogenic strain.


Early hospital discharge and the timing of newborn metabolic screening.
Cost containment measures have reduced dramatically the length of stay for normal newborns, in some cases jeopardizing the ability to obtain appropriate newborn screens. In our hospital, we found that an unacceptable number of patients had mistakenly been screened before 24 hours of age. As pressures to shorten hospitalization increase, health-care providers must examine the impact of such changes on their ability to obtain adequate newborn screens. Potential solutions include continued vigilance in gathering specimens after 24 hours of age, interpretation of time-sensitive tests in an age-adjusted manner, and repeating newborn screens after 24 hours of age.


Identification of plectin as a substrate of p34cdc2 kinase and mapping of a single phosphorylation site.
Plectin is an in vitro substrate for various kinases present in cell lysates from mitotic and interphase Chinese hamster ovary cells. Sensitivity of plectin kinase activity to the inhibitor olomoucine, and two-dimensional tryptic peptide mapping of plectin phosphorylated by various kinase preparations suggested that the major plectin kinase activity in mitotic extracts is related to the cell cycle regulator kinase p34cdc2. Bacterial expression of various truncated plectin mutant proteins comprising different domains of the molecule and their phosphorylation by purified p34cdc2kinase revealed that the target site of this kinase resided within plectin's C-terminal globular domain. Among the subdomains of the C-terminal region (six repeats and a short tail sequence), only repeat 6 and the tail were phosphorylated by p34cdc2 kinase. As shown by two-dimensional phosphopeptide mapping, repeat 6, but not the tail, contained a mitosis-specific phosphorylation site targeted by p34cdc2 kinase in intact plectin molecules. By performing site-directed mutagenesis of a potential p34cdc2 recognition sequence motif within the repeat 6 domain, threonine 4542 was identified as the major target for the kinase. Protein kinase A, phosphorylating plectin also within repeat 6, targeted sites that were clearly different from those of p34cdc2 kinase.


[Clinical, immunohistochemical, and molecular genetic prognostic factors in adult patients with glioblastoma].
Glioblastoma is the most common primary malignant glial tumor of the brain in adult patients. to define the prognostic value of isocitrate dehydrogenase-1 (IDH-1) mutation and methylguanine-DNA methyltransferase (MGMT) methylation status in patients with glioblastoma (GB) and to analyze the impact of clinical data (gender, age, and tumor site), histological variants of the tumor structure, and time to development of recurrences on the course of the disease. The investigation enrolled 63 GB patients aged 18 to 71 years who had received combined treatment (surgery, chemo- and radiotherapy) at the N.I. Burdenko Research Institute of Neurosurgery, Ministry of Health of the Russian Federation, in the period 2008 to 2011. The investigators performed a morphological examination of all tumor tissue samples and an immunohistochemical examination using anti-IDH-1 R-132 antibody clone («Dianova», Germany) and defined MGMT methylation status by a polymerase chain reaction using the CpGenome DNA Modification Kit («Chemicon International», USA). The data were statistically processed using a package of Statistica 6.0 programs. Patient age, time to development of recurrent glioblastoma, mutations in the IDH-1 gene and MGMT were found to be prognostic factors for overall survival among adult patients in this category. Analysis of clinical findings and identification of molecular genetic aberrations in the tumor cells will be able to elaborate an individual approach to treating patients with glioblastoma in order to increase their survival rates and to improve quality of life.


Low-density lipoprotein receptor gene mutations and cardiovascular risk in a large genetic cascade screening population.
A large cohort of patients with familial hypercholesterolemia (FH), free from selection for cardiovascular disease (CVD), and their unaffected relatives was collected by genetic cascade screening and examined for the influence of different mutations of the LDL receptor gene on lipoprotein levels and the risk of CVD. Multivariate analyses with adjustment for age, sex, and specific family ties were performed. Significant variation of LDL levels was observed among 399 patients with FH with different mutations. Null alleles were associated with more severely elevated LDL cholesterol, whereas the frequent N543H/2393del9 mutation led to less elevated LDL cholesterol. The type of mutation did not influence HDL cholesterol levels. Patients with FH had CVD 8.5 times more often compared with their unaffected relatives (RR, 8.54; 95% CI, 5.29 to 13.80). The N543H/2393del9 mutation was associated with a smaller increase of risk compared with other mutations (P<0.0001). After exclusion of families with the N543H/2393del9 mutation, null alleles and other allele mutations no longer differed with regard to LDL cholesterol levels and CVD risk. LDL receptor mutations only partly contributed to the variation of LDL cholesterol levels and cardiovascular burden in FH. Additional, so far unidentified, familial risk factors must underlie the differences of CVD risk, most likely independent of lipids and lipoproteins.


Use of Sniff nasal-inspiratory force to predict survival in amyotrophic lateral sclerosis.
Respiratory muscle weakness is the usual cause of death in amyotrophic lateral sclerosis. The prognostic value of the forced vital capacity (FVC), mouth-inspiratory force, and sniff nasal-inspiratory force were established in a group of 98 patients with amyotrophic lateral sclerosis who were followed trimonthly for 3 years. Sniff nasal-inspiratory force correlated with the transdiaphragmatic pressure (r = 0.9, p < 0.01). Sniff nasal-inspiratory force was most likely to be recorded at the last visit (96% of cases), compared with either the FVC or mouth-inspiratory force (86% and 81%, respectively, p < 0.01). A sniff nasal-inspiratory force less than 40 cm H(2)O was significantly related with nocturnal hypoxemia. When sniff nasal-inspiratory force was less than 40 cm H(2)O, the hazard ratio for death was 9.1 (p = 0.001), and the median survival was 6 +/- 0.3 months. The sensitivity of FVC < 50% for predicting 6-month mortality was 58% with a specificity of 96%, whereas sniff nasal-inspiratory force less than 40 H(2)O had a sensitivity of 97% and a specificity of 79% for death within 6 months. Thus the sniff nasal-inspiratory force test is a good measure of respiratory muscle strength in amyotrophic lateral sclerosis, it can be performed by patients with advanced disease, and it gives prognostic information.


Uropathogenic Escherichia coli are more likely than commensal E. coli to be shared between heterosexual sex partners.
Because uropathogenic Escherichia coli are better adapted than other E. coli to the urethra, periurethra, and vagina, the authors reasoned that uropathogenic E. coli would be more likely than commensal E. coli to be shared between sex partners. In this 1996-1999 Michigan study, the genetic identity of E. coli isolated from 166 women with E. coli urinary tract infection (UTI) and 94 women without UTI and their sex partners was determined by pulsed-field gel electrophoresis. Rectal isolates were considered uropathogenic E. coli if genetically identical to the urinary isolate causing UTI. All eight urinary isolates from men with UTI partners were identical to the E. coli found in the urine or vagina of their sex partner. When the 550 unique rectal E. coli isolates from couples were considered the unit of analysis, E. coli that caused UTI were nine times (odds ratio (OR) = 8.87, 95% confidence interval (CI): 5.41, 14.54) more likely than other E. coli to be shared between sex partners. Sharing occurred twice as frequently (OR = 1.87, 95% CI: 1.13, 3.08) if the E. coli had P pili or if the couples engaged in oral sex (OR = 2.09, 95% CI: 1.09, 4.00). Uropathogenic E. coli are more likely than commensal E. coli to be shared with a current heterosexual sex partner. Both sexual behaviors and a bacterial virulence factor, P pili, modified sharing.


Randomized Clinical Trial of an Internet-Based Adolescent Depression Prevention Intervention in Primary Care: Internalizing Symptom Outcomes.
Approximately 20% of people will experience a depressive episode by adulthood, making adolescence an important developmental target for prevention. CATCH-IT (Competent Adulthood Transition with Cognitive-behavioral, Humanistic, and Interpersonal Training), an online depression prevention intervention, has demonstrated efficacy in preventing depressive episodes among adolescents reporting elevated symptoms. Our study examines the effects of CATCH-IT compared to online health education (HE) on internalizing symptoms in adolescents at risk for depression. Participants, ages 13-18, were recruited across eight US health systems and were randomly assigned to CATCH-IT or HE. Assessments were completed at baseline, 2, 6, 12, 18, and 24 months. There were no significant differences between groups in change in depressive symptoms (b = -0.31 for CATCH-IT, b = -0.27 for HE, p = 0.80) or anxiety (b = -0.13 for CATCH-IT, b = -0.11 for HE, p = 0.79). Improvement in depressive symptoms was statistically significant (p < 0.05) for both groups (p = 0.004 for CATCH-IT, p = 0.009 for HE); improvement in anxiety was significant for CATCH-IT (p = 0.04) but not HE (p = 0.07). Parental depression and positive relationships with primary care physicians (PRPC) moderated the anxiety findings, and adolescents' externalizing symptoms and PRPC moderated the depression findings. This study demonstrates the long-term positive effects of both online programs on depressive symptoms and suggests that CATCH-IT demonstrates cross-over effects for anxiety as well.


Efficacy and safety of a new angiotensin-converting enzyme inhibitor, ramipril, vs. enalapril in essential hypertension: a multicenter trial.
The antihypertensive effect of ramipril, a new angiotensin-converting enzyme (ACE) inhibitor, was evaluated and compared to enalapril in a double-blind, randomized, controlled trial. Subjects received either 2.5, 5, or 10 mg of ramipril given once daily or 5, 10, or 20 mg of enalapril once daily for 4 weeks. Significant decreases from baseline in supine and standing diastolic blood pressures were seen in all dosage groups at end point. There were significant decreases at end point for supine and standing systolic blood pressures at the higher doses. Side effects were minimal and were similar for all treatment groups.


Expression of P-glycoprotein in high-grade osteosarcomas in relation to clinical outcome.
Increased levels of P-glycoprotein occur in some osteosarcomas. In this study we determined the relation between P-glycoprotein status and outcome in patients with high-grade osteosarcoma. P-glycoprotein status was determined immunohistochemically in specimens of osteosarcoma of the extremities (stage II) from 92 patients who were treated with surgery and chemotherapy. The P-glycoprotein status was analyzed in relation to the length of event-free survival. The presence of increased levels of P-glycoprotein in the osteosarcoma was significantly associated with a decreased probability of remaining event-free after diagnosis (P = 0.002). In a multivariate analysis, P-glycoprotein status (P = 0.001) and the extent of tumor necrosis after preoperative chemotherapy (P = 0.04) were independent predictors of clinical outcome. The risk of adverse events was increased substantially (rate ratio, 3.37; 95 percent confidence interval, 1.60 to 7.10) among patients with increased levels of P-glycoprotein in tumor cells, as compared with patients who did not have increased levels of P-glycoprotein in tumor cells. In patients with high-grade osteosarcoma treated with surgery and chemotherapy, the presence of increased levels of P-glycoprotein in tumor cells is associated with a significantly increased risk of adverse events and is independent of the extent of necrosis after preoperative chemotherapy.


Maintaining paediatric cardiac services during the COVID-19 pandemic in a developing country in sub-Saharan Africa: guidelines for a "scale up" in the face of a global "scale down".
The COVID-19 pandemic is currently ravaging the globe and the African continent is not left out. While the direct effects of the pandemic in regard to morbidity and mortality appear to be more significant in the developed world, the indirect harmful effects on already insufficient healthcare infrastructure on the African continent would in the long term be more detrimental to the populace. Women and children form a significant vulnerable population in underserved areas such as the sub-Saharan region, and expectedly will experience the disadvantages of limited healthcare coverage which is a major fall out of the pandemic. Paediatric cardiac services that are already sparse in various sub-Saharan countries are not left out of this downsizing. Restrictions on international travel for patients out of the continent to seek medical care and for international experts into the continent for regular mission programmes leave few options for children with cardiac defects to get the much-needed care.There is a need for a region-adapted guideline to scale-up services to cater for more children with congenital heart disease (CHD) while providing a safe environment for healthcare workers, patients, and their caregivers. This article outlines measures adapted to maintain paediatric cardiac care in a sub-Saharan tertiary centre in Nigeria during the COVID-19 pandemic and will serve as a guide for other institutions in the region who will inadvertently need to provide these services as the demand increases.


Identification and characterization of dual inhibitors for phospholipid transfer protein and microsomal triglyceride transfer protein.
Phospholipid transfer protein (PLTP) plays an important role in atherogenesis and lipoprotein metabolism. PLTP exerts its functions intracellularly and extracellularly. Both PLTP and microsomal triglyceride transfer protein (MTP) have been shown to regulate the secretion of apolipoprotein B (apoB) in hepatocytes. We have previously reported the characterization of inhibitors that selectively inhibit PLTP activity and reduce apoB secretion in hepatocytes. In the present study, we identified more compounds that inhibit both PLTP and MTP activity to various extents. These dual inhibitors are structurally different from the PLTP-selective inhibitors. In human hepatoma cell lines, dual inhibitors seem to be more effective in reducing apoB secretion than selective PLTP or MTP inhibitors. Furthermore, the dual inhibitors markedly reduced triglyceride secretion from hepatocytes. In the absence of PLTP, the dual inhibitors can further reduce apoB secretion, whereas selective PLTP inhibitors had no effect. We conclude that MTP and PLTP may work coordinately in the process of hepatic apoB assembly and secretion. To avoid liver toxicity mediated by MTP inhibition, selective PLTP inhibitors should be pursued.


Bone morphogenetic protein receptor signaling is necessary for normal murine postnatal bone formation.
Functions of bone morphogenetic proteins (BMPs) are initiated by signaling through specific type I and type II serine/threonine kinase receptors. In previous studies, we have demonstrated that the type IB BMP receptor (BMPR-IB) plays an essential and specific role in osteoblast commitment and differentiation. To determine the role of BMP receptor signaling in bone formation in vivo, we generated transgenic mice, which express a truncated dominant-negative BMPR-IB targeted to osteoblasts using the type I collagen promoter. The mice are viable and fertile. Tissue-specific expression of the truncated BMPR-IB was demonstrated. Characterization of the phenotype of these transgenic mice showed impairment of postnatal bone formation in 1-mo-old homozygous transgenic mice. Bone mineral density, bone volume, and bone formation rates were severely reduced, but osteoblast and osteoclast numbers were not significantly changed in the transgenic mice. To determine whether osteoblast differentiation is impaired, we used primary osteoblasts isolated from the transgenic mice and showed that BMP signaling is blocked and BMP2-induced mineralized bone matrix formation was inhibited. These studies show the effects of alterations in BMP receptor function targeted to the osteoblast lineage and demonstrate a necessary role of BMP receptor signaling in postnatal bone growth and bone formation in vivo.


Genomic analysis and temperature-dependent transcriptome profiles of the rhizosphere originating strain Pseudomonas aeruginosa M18.
Our previously published reports have described an effective biocontrol agent named Pseudomonas sp. M18 as its 16S rDNA sequence and several regulator genes share homologous sequences with those of P. aeruginosa, but there are several unusual phenotypic features. This study aims to explore its strain specific genomic features and gene expression patterns at different temperatures. The complete M18 genome is composed of a single chromosome of 6,327,754 base pairs containing 5684 open reading frames. Seven genomic islands, including two novel prophages and five specific non-phage islands were identified besides the conserved P. aeruginosa core genome. Each prophage contains a putative chitinase coding gene, and the prophage II contains a capB gene encoding a putative cold stress protein. The non-phage genomic islands contain genes responsible for pyoluteorin biosynthesis, environmental substance degradation and type I and III restriction-modification systems. Compared with other P. aeruginosa strains, the fewest number (3) of insertion sequences and the most number (3) of clustered regularly interspaced short palindromic repeats in M18 genome may contribute to the relative genome stability. Although the M18 genome is most closely related to that of P. aeruginosa strain LESB58, the strain M18 is more susceptible to several antimicrobial agents and easier to be erased in a mouse acute lung infection model than the strain LESB58. The whole M18 transcriptomic analysis indicated that 10.6% of the expressed genes are temperature-dependent, with 22 genes up-regulated at 28°C in three non-phage genomic islands and one prophage but none at 37°C. The P. aeruginosa strain M18 has evolved its specific genomic structures and temperature dependent expression patterns to meet the requirement of its fitness and competitiveness under selective pressures imposed on the strain in rhizosphere niche.


Antibacterial Efficacy of Iron-Oxide Nanoparticles against Biofilms on Different Biomaterial Surfaces.
Biofilm growth on the implant surface is the number one cause of the failure of the implants. Biofilms on implant surfaces are hard to eliminate by antibiotics due to the protection offered by the exopolymeric substances that embed the organisms in a matrix, impenetrable for most antibiotics and immune cells. Application of metals in nanoscale is considered to resolve biofilm formation. Here we studied the effect of iron-oxide nanoparticles over biofilm formation on different biomaterial surfaces and pluronic coated surfaces. Bacterial adhesion for 30 min showed significant reduction in bacterial adhesion on pluronic coated surfaces compared to other surfaces. Subsequently, bacteria were allowed to grow for 24 h in the presence of different concentrations of iron-oxide nanoparticles. A significant reduction in biofilm growth was observed in the presence of the highest concentration of iron-oxide nanoparticles on pluronic coated surfaces compared to other surfaces. Therefore, combination of polymer brush coating and iron-oxide nanoparticles could show a significant reduction in biofilm formation.


Elucidation of the internal physical and chemical microstructure of pharmaceutical granules using X-ray micro-computed tomography, Raman microscopy and infrared spectroscopy.
X-ray micro-computed tomography (XMCT) was used in conjunction with confocal Raman mapping to measure the intra-granular pore size, binder volumes and to provide spatial and chemical maps of internal granular components in α-lactose monohydrate granules formulated with different molecular weights of polyvinyl pyrrolidone (PVP). Infrared spectroscopy was used to understand the molecular association of binder domains. Granules were prepared by high-shear aqueous granulation from α-lactose monohydrate and PVP K29/32 or K90. XMCT was used to visualise the granule microstructure, intra-granular binder distribution and measure intra-granular porosity, which was subsequently related to intrusion porosimetry measurements. Confocal Raman microscopy and infrared microscopy were employed to investigate the distribution of components within the granule and explore the nature of binder substrate interactions. XMCT data sets of internal granule microstructure provided values of residual porosity in the lactose:PVP K29/32 and lactose:PVP K90 granules of 32.41 ± 4.60% and 22.40 ± 0.03%, respectively. The binder volumes of the lactose:PVP K29/32 and lactose:PVP K90 granules were 2.98 ± 0.10% and 3.38 ± 0.07%, respectively, and were attributed to PVP-rich binder domains within the granule. Confocal Raman microscopy revealed anisotropic domains of PVP between 2 μm and 20 μm in size surrounded by larger particles of lactose, in both granule types. Raman data showed that PVP domains contained various amounts of lactose, whilst IR microscopy determined that the PVP was molecularly associated with lactose, rather than residual water. The work shows that XMCT can be applied to investigate granular microstructure and resolve the porosity and the excipient and binder volumes. Combining this technique with vibrational techniques provides further structural information and aids the interpretations of the XMCT images. When used complementarily, these techniques highlighted that porosity and binder volume were the most significant microstructural differences between the α-lactose monohydrate granules formulated with the different grades of PVP.


Overlap connective tissue syndromes.
Twenty six children with overlapping features of more than one connective tissue disorder are reported. The median age of onset was 9.5 years and median duration of follow up 7.5 years. Common presenting symptoms included arthritis, tenosynovitis. Raynaud's phenomenon, myositis, and rashes. At follow up 14 patients had developed sclerodermatous skin changes, but significant systemic involvement was uncommon. Only 16 of the 26 cases had antibodies to nuclear ribonucleoprotein; therefore, 10 did not satisfy criteria for mixed connective tissue disease. It was not possible to differentiate clinical patterns by the presence or absence of any particular antibody profile.


Sonographic features of peritoneal lymphomatosis in 4 cats.
The metastatic spread of feline lymphoma to the peritoneum ("lymphomatosis") has been rarely reported in the literature. The sonographic features specific to this rare disease manifestation have not been described and have important treatment and prognostic considerations prompting definitive diagnosis. To describe the ultrasonic features of feline peritoneal lymphomatosis. Four cats with alimentary lymphoma and peritoneal metastasis confirmed using cytology, histology, or both. The sonographic features described include either a nonobstructive, focally diffuse, and circumferential intestinal mass, or an eccentric, focally diffuse, gastric mass. The intestinal and gastric lesions exhibited hypo-to-anechoic transmural wall thickening with loss of wall layering in association with discrete-to-coalescing plaques or sheets of thickened, hypoechoic tissue throughout the mesentery or omenta. All cases exhibited only small volumes of anechoic free peritoneal fluid. Three of the 4 cats also had multiple small hypoechoic nodular foci on the parietal and/or visceral peritoneal surfaces. Two cats had bilateral renomegaly because of lymphoma invasion (2/4) and 1 cat had local lymphadenopathy secondary to lymphoma invasion (1/4). Peritoneal lymphomatosis is a rare manifestation of lymphoma metastasis and to date appears to be associated specifically with B-cell alimentary lymphoma.


[Beta-endorphin and substance P in the perioperative period].
The modifying impact of anaesthesia on the stress reaction related to surgical trauma was investigated on the basis of the neuropeptidergic parameters of 66 patients who had to undergo a gynaecological radical operation. Anaesthesia was either performed as neuroleptanaesthesia or as epidural analgesia by using bupivacaine in combination with general anaesthesia. The plasma concentrations of substance P and beta-endorphin were taken as neuropeptidergic parameters. Both regulatory peptides show numerous corresponding synergisms. An acceleration of these neuropeptide systems is assumed to be present in severe disturbance of homeostasis. Plasma concentrations of substance P and beta-endorphin were examined at 11 measuring points in the perioperative and intraoperative periods. The plasma concentration of substance P significantly declines in the preoperative period while the concentration of beta-endorphin in the plasma remains at a relatively constant level. In the dynamics of beta-endorphin in the plasma significant differences between the two anaesthetic techniques become apparent in the intraoperative period. Those patients given epidural analgesia have a significantly higher maximum concentration at a later date. This difference is attributed to the possible loss of the adrenal medullary function due to partial sympathetic blocking. Single observations in patients pregnant in the last trimester testify to an extraordinary adaptability at the end of pregnancy.


Distance effects on sequential dependencies in categorical judgments.
Two forms of sequential dependency have been found in an auditory identification experiment: assimilation produced by the previous response and contrast caused by the preceding stimulus. The strength of these phenomena partly depends on the distance between stimuli and responses. For example, the strength of assimilation brought about by the previous response decreases with increased separation between successive stimuli. An inverse distance effect was observed for contrast caused by the preceding stimulus, which is equivalent to that found in the case of contrast produced by extraserial anchors. Observed response probabilities exhibit complicated dependencies on the current stimulus and the previous response that are not explained by existing models. An alternative model is suggested that is capable of accounting for these dependencies and for the distance effects. This model contains two mechanisms to explain sequential dependencies: The trace of the preceding stimulus acts as an internal standard, and the previous response influences a guessing strategy.


Structural alterations in small resistance arteries in obesity.
In cardiovascular and metabolic diseases, small resistance arteries may show the presence of structural alterations. In particular, in essential hypertension, an increased media-to-lumen ratio of subcutaneous small arteries with no change in the total amount of vascular wall tissue (eutrophic remodelling) has already been described several years ago. Similar alterations have been demonstrated also in patients with diabetes mellitus and obesity; in this case, however, a more evident contribution of vascular smooth muscle cell growth (hypertrophic remodelling) is present. This review addresses the effects of obesity on small resistance artery structure. Similar to diabetic patients, obese patients show an increased media-to-lumen ratio of subcutaneous small arteries, which appears associated with hypertrophic remodelling, as demonstrated by an increase in media cross-sectional area. Endothelial dysfunction evaluated as vasodilator response to acetylcholine has also been observed. Several studies have shown that increased media-to-lumen ratio of subcutaneous small resistance arteries possesses a prognostic significance in relation to cardiovascular outcome. Appropriate antihypertensive treatment may improve microvascular alterations both in essential hypertension and in type 2 diabetes mellitus. In obesity, a pronounced weight loss may improve microvascular structure. However, further studies are needed to elucidate the effects of other pharmacological and non-pharmacological interventions in obesity.


Identification of blood parasites in old world warbler species from the Danube River Delta.
Warbler species of the families Sylviidae and Acrocephalidae occurring in the Danube river delta are frequently exposed to blood-sucking arthropods that transmit avian blood parasites. We investigated infections by three genera of hemosporidian parasites in blood samples from six warbler species. Altogether in 17 (32.6%) of 52 blood samples, a PCR product was amplified. The great reed warbler (Acrocephalus arundinaceus) had the highest prevalence, with 63.6% (7/11) infected individuals, whereas no infection was detected in marsh warbler (Acrocephalus palustris). The most common parasite genus was Haemoproteus, which was found in 15.4% (8/52) of individuals. Seven known parasite lineages (five Haemoproteus and two Plasmodium) and two new lineages were recorded (one Leucocytozoon and one Plasmodium).


Persistence of Intracellular Bacterial Pathogens-With a Focus on the Metabolic Perspective.
Persistence has evolved as a potent survival strategy to overcome adverse environmental conditions. This capability is common to almost all bacteria, including all human bacterial pathogens and likely connected to chronic infections caused by some of these pathogens. Although the majority of a bacterial cell population will be killed by the particular stressors, like antibiotics, oxygen and nitrogen radicals, nutrient starvation and others, a varying subpopulation (termed persisters) will withstand the stress situation and will be able to revive once the stress is removed. Several factors and pathways have been identified in the past that apparently favor the formation of persistence, such as various toxin/antitoxin modules or stringent response together with the alarmone (p)ppGpp. However, persistence can occur stochastically in few cells even of stress-free bacterial populations. Growth of these cells could then be induced by the stress conditions. In this review, we focus on the persister formation of human intracellular bacterial pathogens, some of which belong to the most successful persister producers but lack some or even all of the assumed persistence-triggering factors and pathways. We propose a mechanism for the persister formation of these bacterial pathogens which is based on their specific intracellular bipartite metabolism. We postulate that this mode of metabolism ultimately leads, under certain starvation conditions, to the stalling of DNA replication initiation which may be causative for the persister state.


Ciclesonide: long-term treatment of persistent asthma--no clear progress.
Inhaled corticosteroids such as beclometasone are the drugs of choice for long-term treatment of patients with persistent asthma. There is no tangible difference in efficacy among inhaled corticosteroids, but we have the most experience with beclometasone. Ciclesonide (Alvesco, Nycomed then Takeda), another inhaled cortico-steroid, has been tested in three double-blind trials versus budesonide and six trials versus fluticasone but none versus beclometasone. These trials showed the "non-inferiority" of ciclesonide, mainly in terms of a surrogate endpoint: the change in forced expiratory volume in one second (FEV1) after 12 or 24 weeks of treatment (primary endpoint). However, the doses of ciclesonide used in these trials were higher than the standard doses while doses of the comparator corticosteroids were lower than the standard doses, thus favouring ciclesonide. Local adverse effects of inhaled corticosteroids include oral candidiasis, sore throat and hoarseness. A systematic review conducted by a Cochrane group suggests that ciclesonide does not have a better adverse effect profile than other inhaled corticosteroids used at equivalent doses. Corticosteroid inhalation can also lead to systemic absorption. The practical advantage of once-daily dosing with ciclesonide seems minor. In practice, ciclesonide is neither more effective than the inhaled corticosteroids with which it has been compared, nor does it have fewer adverse effects. It is better to continue to use beclometasone, a drug with which there is more experience.


Recent advances in arthroscopic repair of traumatic anterior glenohumeral instability.
Traumatic anterior instability is the most common type of glenohumeral instability. Although surgical treatment with an open technique has produced excellent results, there has been a trend toward arthroscopic treatment. As understanding of instability advances along with improvements in surgical techniques and instrumentation, arthroscopic results are fast approaching those seen with open procedures. Studies done at the authors' institution showed a 97% satisfactory outcome at short-term followup with 93% stable shoulders in a patient population with high physical demands. Others recently reported similar results. As more surgeons become familiar with the techniques, it is thought that arthroscopic Bankart reconstructions will be the preferred method in the future.


[Economic burden and economic risk of five major chronic diseases among Chinese urban residents].
To provide scientific evidence for medical insurance and health policies allocating the limited health resources in China. Based on the data of the national household survey by the State Council Pilot Urban Resident Basic Medical Insurance Evaluation from Nov.2007 to Nov.2011, a two-step model and the human capital method were used to estimate the economic burden of five major chronic diseases among urban residents in China. According to the economic burden, the relative economic risk (relative risk, RR) and adjusted RR were calculated. The five chronic diseases were hypertension, cardiovascular, diabetes, arthritis or rheumatism and chronic lung diseases. More than 50% of the residents with these five chronic diseases were the over 65-year-old and retired. 90% of the residents with these five chronic diseases had medical insurance except the residents with chronic lung diseases. Average co-pay from the outpatient department and the pharmacy was more than 60%, and about 50% from the inpatient department. Annual total cost per capita was the highest 8 954.29 Yuan among the residents with cardiovascular disease and the second highest 8 914.36 Yuan among the residents with diabetes. The adjusted RR of the residents with cardiovascular and diabetes were greater than 1, respectively 1.36 and 1.15. The retired take up the largest percentage of population with chronic diseases, and the influence of the major five chronic diseases is more serious in north-west China. The main expenditure is from the outpatient department and the pharmacy, in which the availability of drugs reimbursed needs to be improved. The patients with cardiovascular and diabetes experience both higher economic burden and economic risk.


Cytoplasmic 3-hydroxy-3-methylglutaryl coenzyme A synthase from the hamster. I. Isolation and sequencing of a full-length cDNA.
We here report the isolation and nucleotide sequencing of a full-length 3.3-kilobase cDNA for the cytoplasmic form of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) synthase, a regulated enzyme in the cholesterol biosynthetic pathway. The cDNA was isolated from UT-1 cells, a compactin-resistant line of Chinese hamster ovary cells. UT-1 cells produce large amounts of mRNA for HMG-CoA synthase and the next enzyme in the pathway, HMG-CoA reductase, as a result of growth in the presence of compactin, a competitive inhibitor of the reductase. The identity of the cDNA for HMG-CoA synthase was confirmed through comparison of the NH2-terminal amino acid sequence predicted from the cDNA with that determined chemically from the purified enzyme. Anti-peptide antibodies directed against the amino acid sequence predicted from the cDNA precipitated HMG-CoA synthase activity from liver cytoplasm. The feeding of cholesterol to hamsters led to a decrease of more than 85% in the amount of mRNA for HMG-CoA synthase and HMG-CoA reductase in hamster liver. These data indicate that the mRNAs for cytoplasmic HMG-CoA synthase and for HMG-CoA reductase, two sequential enzymes in the cholesterol biosynthetic pathway, are coordinately regulated by cholesterol.


A test of Leiter's process model of burnout.
This study among Dutch nurses (N = 156) tested Leiter's 1993 process model of burnout. The LISREL results of this study partially support Leiter's model. It appeared that emotional exhaustion was primarily related with the demand variable work overload while depersonalization was, to a lesser degree, associated with the resource variable coworker support. Personal accomplishment was significantly related with coping and emotional exhaustion was associated with depersonalization. However, Leiter's model did not fit to the data in all respects. Modifications indices provided by LISREL 8 suggested to relax the relationship between: (1) coping and depersonalization and (2) social support and emotional exhaustion. Because these relationships were supported by both theory and existing empirical evidence, they were successively added to the model. Eventually, the model improved considerably and all selected criteria were met. Several relationships in the final model, however, were nonsignificant (e.g., the relationship between personal accomplishment and autonomy and participation, respectively).


Abscisic Acid transport coefficients of phaseolus root systems.
Diffusive and convective transport coefficients of Phaseolus vulgaris L. cv. Ouray root systems for abscisic acid for (ABA) were measured. The convective coefficient (reflection coefficient or osmotic efficiency factor) sigma was determined to be 0.96 for ABA while the diffusive coefficient, omega, was found to be 1.44 x 10(-11) mole per square centimeter per second per bar. Steady-state concentrations of ABA in the root system exudates were not achieved until at least three hours after the applications suggesting either a slow saturation of binding sites or equilibration with tissues surrounding the xylem.


Sterility of non-preservative eye drops.
To assess microbial contamination of common non-preservative eye drops stored at 4 degrees C and non-preservative fortified antibiotic eye drops used in a hospital inpatient setting. A prospective study of the sterility of non-preservative eye drops was examined by dividing the patients into 2 groups. Group 1 composed of 5 samples of each ophthalmic preparation, which consisted of fortified antibiotics (vancomycin, cefazolin, gentamicin, and amikacin), non-preservative steroid eye drops (1% methylprednisolone and 0.01% dexamethasone), and 20% autologous serum stored at 4 degrees C. Group 2 was composed of 28 samples of fortified vancomycin and 23 samples of fortified amikacin used in an inpatient setting for 1 week and kept in 4 degrees C for 28 days. The contamination was assessed at the day of preparation and then at day 4, 7, 14, 21, 28 of all medications except autologous serum was done up to day 84. The sterility was examined by the culturing on tryptic soy broth and thioglycolate broth. In group 1 and 2, no contamination was detected in any samples within 4 weeks and up to 12 weeks for autologous serum. Non- preservative topical eye drops can be safely kept at 4 degrees C without contamination for 4 weeks and 12 weeks for 20% autologous serum drop. For topical antibiotics, under a strict protocol for preparation and usage might be used without significant risk of bacterial contamination for 4 weeks.


Review article: migraine and pregnancy.
A 27-year-old woman with no family or personal history of migraine presented with headache associated with unilateral paresthesias and blurred vision. This was her first, and so far only, attack of migraine with aura and led to the diagnosis of her pregnancy and to this review. Migraine can begin for the first time with pregnancy, particularly in the first trimester. Cases of migraine with aura are the most commonly reported. Preexisting migraine usually improves with pregnancy, particularly if it was associated with menstrual migraine. Headache occurs frequently in the post-partum period, particularly in known migraineurs. Migraineurs have no increased risk of complications during pregnancy and their children have no increased incidence of birth defects.


Red blood cell-mimicking synthetic biomaterial particles.
Biomaterials form the basis of current and future biomedical technologies. They are routinely used to design therapeutic carriers, such as nanoparticles, for applications in drug delivery. Current strategies for synthesizing drug delivery carriers are based either on discovery of materials or development of fabrication methods. While synthetic carriers have brought upon numerous advances in drug delivery, they fail to match the sophistication exhibited by innate biological entities. In particular, red blood cells (RBCs), the most ubiquitous cell type in the human blood, constitute highly specialized entities with unique shape, size, mechanical flexibility, and material composition, all of which are optimized for extraordinary biological performance. Inspired by this natural example, we synthesized particles that mimic the key structural and functional features of RBCs. Similar to their natural counterparts, RBC-mimicking particles described here possess the ability to carry oxygen and flow through capillaries smaller than their own diameter. Further, they can also encapsulate drugs and imaging agents. These particles provide a paradigm for the design of drug delivery and imaging carriers, because they combine the functionality of natural RBCs with the broad applicability and versatility of synthetic drug delivery particles.


Peptidomic analysis of blood plasma after in vivo treatment with protease inhibitors--a proof of concept study.
Native peptides can be regarded as surrogate markers for protease activity in biological samples. Analysis of peptides by peptidomics allows to monitor protease activity in vivo and to describe the influence of protease inhibition. To elucidate the potential of peptides as markers for in vivo protease inhibition we analyzed plasma samples from animals treated with either the indirect FXa inhibitor FONDAPARINUX or the dipeptidylpeptidase IV inhibitor AB192. Signals correlating with the treatment were subsequently identified and assessed with respect to protease-dependent consensus cleavage motifs and occurrence of downstream targets. It could be shown that regulated peptides were either substrates, products or downstream targets of the inhibited protease. The results from the present study demonstrate that the in vivo analysis of peptides by peptidomics has the potential to broaden the knowledge of inhibitor related effects in vivo and that this method may pave the way to develop predictive biomarkers.


A model building exercise of mortality risk for Taiwanese women with breast cancer.
The accurate estimation of outcome in patients with malignant disease is an essential component of the optimal treatment, decision-making and patient counseling processes. The prognosis and disease outcome of breast cancer patients can differ according to geographic and ethnic factors. To our knowledge, to date these factors have never been validated in a homogenous loco-regional patient population, with the aim of achieving accurate predictions of outcome for individual patients. To clarify this topic, we created a new comprehensive prognostic and predictive model for Taiwanese breast cancer patients based on a range of patient-related and various clinical and pathological-related variables. Demographic, clinical, and pathological data were analyzed from 1 137 patients with breast cancer who underwent surgical intervention. A survival prediction model was used to allow analysis of the optimal combination of variables. The area under the receiver operating characteristic (ROC) curve, as applied to an independent validation data set, was used as the measure of accuracy. Results were compared by comparing the area under the ROC curve. our model building exercise of mortality risk was able to predict disease outcome for individual patients with breast cancer. This model could represent a highly accurate prognostic tool for Taiwanese breast cancer patients.


ANA position statement on privatization and for-profit conversion. American Nurses Association.
The American Nurses Association (ANA) believes that the health of communities benefits from a mix of health care facilities, including both public and nonprofit private facilities where feasible. ANA is concerned by the rate of conversion of nonprofit facilities and plans to for-profit status. Privatization of public facilities and the conversion of nonprofit facilities and health plans to for-profit status requires careful public oversight to ensure continued access to affordable, quality services, including a maintenance of uncompensated care; a fair accounting of the assets of the entity being privatized or converted; and an assurance that converted assets are used to maintain and improve access to affordable, safe and quality health care services. The rights and benefits of employees must be carefully safe-guarded in any privatization or conversion move. All hospitals, regardless of ownership or tax status, should be held accountable for the delivery of safe, quality services, and should be required to disclose data regarding staffing, patient outcomes, cost and delivery of uncompensated care. Continued data collection will be necessary to guide further development of public policy to address privatization and for-profit conversion.


A proposal for a practical treatment guideline designed for the initial two-hours of the management of patients with acute severe asthma and COPD using the principles of evidence-based medicine.
We have proposed a clinical treatment guideline for the management of acute, severe asthma and chronic obstructive pulmonarydisease (COPD) using the principles of evidence-based medicine. The content is based upon practical clinical issues in need of consensus. A previous study has shown that this particular area is in serious need of quality control. Based on a strict 2 h time schedule with a unified treatment plan for both asthma and COPD, it is possible to secure for the patients a well-documented medical therapy promoting decision-making and clarification of the patient within this time limit. A summary of the statements is presented in a one-page, user-friendly format in order to cope with the clinician's need of having access to published evidence quickly and easily. A website (www.phanareth.dk or a website provided by Respiratory Medicine) has been established providing regular updates. A strategy for the implementation and the evaluation process has been planned after the publication of this paper. We believe this approach to be an important step towards an increase in the quality of guidelines and also a tool to make "guideline writers" aware of the responsibility of making their recommendations work.


CKS1B as Drug Resistance-Inducing Gene-A Potential Target to Improve Cancer Therapy.
Cancer is a threat to human health and life. Although previously centered on chemical drug treatments, cancer treatment has entered an era of precision targeted therapy. Targeted therapy entails precise guidance, allowing the selective killing of cancer cells and thereby reducing damage to healthy tissues. Therefore, the need to explore potential targets for tumor treatment is vital. Cyclin-dependent kinase regulatory subunit 1B (CKS1B), a member of the conserved cyclin kinase subunit 1 (CKS1) protein family, plays an essential role in cell cycling. A large number of studies have shown that CKS1B is associated with the pathogenesis of many human cancers and closely related to drug resistance. Here, we describe the current understanding of the cellular functions of CKS1B and its underlying mechanisms, summarize a recent study of CKS1B as a target for cancer treatment and discuss the potential of CKS1B as a therapeutic target.


Omeprazole vs ranitidine in the healing of duodenal ulcer.
To assess the comparative efficacy of omeprazole 20 mg in the morning versus ranitidine 150 mg twice a day, in the healing of duodenal ulcer, 43 endoscopically verified cases were randomly allocated to 2 or 4 weeks (if ulcer did not heal at 2 weeks) treatment. Two cases were excluded due to deviation from the protocol. Of 21 cases treated with omeprazole 15 (71%) healed at two weeks and all (100%) at 4 weeks. Similarly of 20 cases treated with ranitidine, 14 (70%) healed at 2 and 18 (90%) at 4 weeks (P = NS). Two patients who did not heal with ranitidine, when crossed over to omeprazole healed at 4 weeks. No significant difference in the rate of pain relief, clinical or laboratory parameters or adverse effects were noted in either group. Both the drugs were well tolerated and were potent healer of duodenal ulcer; but omeprazole appears to be superior in the healing of resistent ulcers.


In silico molecular docking study of Andrographis paniculata phytochemicals against TNF-α as a potent anti-rheumatoid drug.
Tumor necrosis factor-α (TNF-α) is a proinflammatory cytokine which plays a crucial role in controlling inflammatory responses. The pathway of Rheumatoid arthritis (RA) leading to TNF-alpha is activated by macrophages and quite often by natural killer cells and lymphocytes. In the inflammatory phase, it is believed to be the main mediator and to be anchored with the progression of different diseases such as ankylosing spondylitis, Crohn's disease, and Rheumatoid arthritis (RA). The major goal of this study is to use in silico docking studies to investigate the anti-inflammatory potential of a bioactive molecule from the medicinal plant Andrographis paniculata. The three-dimensional structures of different phytochemicals of A. paniculata were obtained from PubChem database, and the receptor protein was derived from PDB database. Docking analysis was executed using AutoDock vina, and the binding energies were compared. Bisandrographolide A and Andrographidine C revealed the highest score of -8.6 Kcal/mol, followed by, Neoandrographolide (-8.5 Kcal/mol). ADME and toxicity parameters were evaluated for these high scoring ligands and results showed that Andrographidine C could be a potent drug, whereas Neoandrographolide and Bisandrographolide A can be modified in in vitro and can lead to a promising drug. Further, the top scorer (Andrographidine C) and control drug (Leflunomide) were subjected to 100 ns MD Simulation. The protein complex with Andrographidine C had more stable confirmation with lower RMSD (0.28 nm) and higher binding energy (-133.927 +/- 13.866 kJ/mol). In conclusion, Andrographidine C may be a potent surrogate to the disease-modifying anti-rheumatic drugs (DMARD's) & Non-steroidal anti-inflammatory drugs (NSAID's) that has fewer or minor adverse effects and can aid in RA management.


Engineering of stable bispecific antibodies targeting IL-17A and IL-23.
Bispecific antibodies (bsAbs) present an attractive opportunity to combine the additive and potentially synergistic effects exhibited by combinations of monoclonal antibodies (mAbs). Current challenges for engineering bsAbs include retention of the binding affinity of the parent mAb or antibody fragment, the ability to bind both targets simultaneously, and matching valency with biology. Other factors to consider include structural stability and expression of the recombinant molecule, both of which may have significant impact on its development as a therapeutic. Here, we incorporate selection of stable, potent single-chain variable fragments (scFvs) early in the engineering process to assemble bsAbs for therapeutic applications targeting the cytokines IL-17A/A and IL-23. Stable scFvs directed against human cytokines IL-23p19 and IL-17A/A were isolated from a human Fab phage display library via batch conversion of panning output from Fabs to scFvs. This strategy integrated a step for shuffling V regions during the conversion and permitted the rescue of scFv molecules in both the V(H)V(L) and the V(L)V(H) orientations. Stable scFvs were identified and assembled into several bispecific formats as fusions to the Fc domain of human IgG1. The engineered bsAbs are potent neutralizers of the biological activity of both cytokines (IC(50) < 1 nM), demonstrate the ability to bind both target ligands simultaneously and display stability and productivity advantageous for successful manufacture of a therapeutic molecule. Pharmacokinetic analysis of the bsAbs in mice revealed serum half-lives similar to human mAbs. Assembly of bispecific molecules using stable antibody fragments offers an alternative to reformatting mAbs and minimizes subsequent structure-related and manufacturing concerns.


[Comparison of partial sequencing of 5' non-coding region of seven HGV strains isolated from different areas in China].
To explore the variation of Chinese hepatitis G virus (HGV) strains. HGV RNA was detected by reverse transcription nested polymerase chain reaction (RT-nPCR) with a designed primer derived from the 5' non-coding region of Chinese HGV strains. HGV cDNA was sequenced in seven samples with positive products by ABI prism 377 DNA automatic sequencer. Homology of nucleotide sequence of the 5' non-coding region of HGV strains in seven Chinese strains was 88.26%, 85.92%, 88.26%, 85.45%, 86.85%, 85.92% and 88.26%, respectively, as compared with the African strains GBV-C (u 36380), and 92.02%, 86.85%, 86.67%, 89.02%, 89.67%, 89.67% and 91.55%, respectively, as compared with the strains isolated from the U.S. (u 44402). Homology of nucleotide sequence was 92.02% to 97.18% between HGV strains isolated in China. Genotypes of Chinese HGV strains differ from those of GBV-C and HGV subtypes reported in the U.S.


Identification of coronary artery disease by 99mTc-MIBI myocardial perfusion single photon emission computed tomography: evaluation using Diamond's method and segmental score system.
Three hundred and eighty-one consecutive patients referred to our Nuclear Medicine Service from the Cardiology Department during a period of two years have been studied to evaluate Coronary Artery Disease (CAP) using 99mTc-MIBI single photon emission computed tomography (SPECT). The sensitivity and specificity for detecting CAD in the whole group of patients, referred (n = 161) or not (n = 220) for coronary angiography, were calculated following Diamond's method, and were found to be 87% and 92%, respectively. Diamond's method estimates these values from those obtained in the subset of patients with angiography referral (sensitivity 91% and specificity 85%) and the pattern of SPECT responses of both groups (69% and 52%, respectively). A new segmental score system was used to evaluate the location and extent of CAD in the catheterized group. The sensitivity for detecting individual artery disease was 69% and specificity was 81%. The sensitivity in patients with single, double and triple-vessel disease was 90%, 96% and 89%, respectively. In the subgroup of patients without infarction (n = 66) the sensitivity and specificity were 76% (19/25) and 90% (37/41).


Interleukin-37 ameliorates myocardial ischaemia/reperfusion injury in mice.
Innate immune and inflammatory responses are involved in myocardial ischaemia/reperfusion (I/R) injury. Interleukin (IL)-37 is a newly identified member of the IL-1 family, and functions as a fundamental inhibitor of innate immunity and inflammation. However, its role in myocardial I/R injury remains unknown. I/R or sham operations were performed on male C57BL/6J mice. I/R mice received an injection of recombinant human IL-37 or vehicle, immediately before reperfusion. Compared with vehicle treatment, mice treated with IL-37 showed an obvious amelioration of the I/R injury, as demonstrated by reduced infarct size, decreased cardiac troponin T level and improved cardiac function. This protective effect was associated with the ability of IL-37 to suppress production of proinflammatory cytokines, chemokines and neutrophil infiltration, which together contributed to a decrease in cardiomyocyte apoptosis and reactive oxygen species (ROS) generation. In addition, we found that IL-37 inhibited the up-regulation of Toll-like receptor (TLR)-4 expression and nuclear factor kappa B (NF-kB) activation after I/R, while increasing the anti-inflammatory IL-10 level. Moreover, the administration of anti-IL-10R antibody abolished the protective effects of IL-37 in I/R injury. In-vitro experiments further demonstrated that IL-37 protected cardiomyocytes from apoptosis under I/R condition, and suppressed the migration ability of neutrophils towards the chemokine LIX. In conclusion, IL-37 plays a protective role against mouse myocardial I/R injury, offering a promising therapeutic medium for myocardial I/R injury.


Analyses of aerodynamic characteristics of the oropharynx applying CBCT: obstructive sleep apnea patients versus control subjects.
To determine the most relevant aerodynamic characteristic of the oropharynx related to the collapse of the upper airway in obstructive sleep apnea (OSA) patients; and to determine the correlation between the most relevant aerodynamic characteristic(s) of the oropharynx and anatomical characteristics of the oropharynx in OSA patients. 31 mild to moderate OSA patients (mean ± SD age = 43.5 ± 9.7 years) and 13 control subjects (mean ± SD age = 48.5 ± 16.2 years) were included in this prospective study. The diagnosis of OSA patients was based on an overnight polysomnographic recording. To exclude the presence of OSA in the control subjects, they were asked to fill out a validated questionnaire to determine the risk of OSA. NewTom5G cone beam CT (CBCT) scans were obtained from both OSA patients and control subjects. Computational models of the oropharynx were reconstructed based on CBCT images. The aerodynamic characteristics of the oropharynx were calculated based on these computational models. Pearson correlation analysis was used to analyse the correlation between the most relevant aerodynamic characteristic(s) and anatomical characteristics of the oropharynx in OSA patients. Compared with controls, the airway resistance during expiration (Rex) of the OSA patients was significantly higher (p = 0.04). There was a significant negative correlation between Rex and the minimum cross-sectional area (CSAmin) of the oropharynx (r = -0.41, p = 0.02), and between Rex and the volume of the oropharynx (r = -0.48, p = 0.01) in OSA patients. After excluding an outlier, there is only significant correlation between Rex and the CSAmin of the oropharynx (r = -0.45, p = 0.01). Within the limitations of this study, we concluded that the most relevant aerodynamic characteristic of the oropharynx in the collapse of the upper airway in OSA patients is Rex. Therefore, the repetitive collapse of the upper airway in OSA patients may be explained by a high Rex, which is related to the CSAmin of the oropharynx.


The recent progress on metal-organic frameworks for phototherapy.
Some infectious or malignant diseases such as cancers are seriously threatening the health of human beings all over the world. The commonly used antibiotic therapy cannot effectively treat these diseases within a short time, and also bring about adverse effects such as drug resistance and immune system damage during long-term systemic treatment. Phototherapy is an emerging antibiotic-free strategy to treat these diseases. Upon light irradiation, phototherapeutic agents can generate cytotoxic reactive oxygen species (ROS) or induce a temperature increase, which leads to the death of targeted cells. These two kinds of killing strategies are referred to as photodynamic therapy (PDT) and photothermal therapy (PTT), respectively. So far, many photo-responsive agents have been developed. Among them, the metal-organic framework (MOF) is becoming one of the most promising photo-responsive materials because its structure and chemical compositions can be easily modulated to achieve specific functions. MOFs can have intrinsic photodynamic or photothermal ability under the rational design of MOF construction, or serve as the carrier of therapeutic agents, owing to its tunable porosity. MOFs also provide feasibility for various combined therapies and targeting methods, which improves the efficiency of phototherapy. In this review, we firstly investigated the principles of phototherapy, and comprehensively summarized recent advances of MOF in PDT, PTT and synergistic therapy, from construction to modification. We expect that our demonstration will shed light on the future development of this field, and bring it one step closer to clinical trials.


A novel ion chromatographic method based on cation-exchange and acid-base interactions for the simultaneous determination of total alkalinity and monovalent cations in samples of microliter volume.
An ion chromatographic (IC) method based on the use of titrant (strong acid) as the stationary phase was developed for simultaneous determination of total alkalinity (TA) and monovalent cations. The titrant used in this study was obtained by initially loading lithium dodecylsulfate (Li-DS) onto a reversed-phase material and then conditioning the column with a slightly acidified aqueous LiCl solution (a mixture of 50.0 mM LiCl and 0.1 mM H2SO4). When a small amount of a basic sample was injected onto a column prepared in this way, the basic species (Bn-) reacted predominantly with H+ on the stationary phase and the reaction with the eluent phase was negligible due to the very low concentration of eluent H+ (in the eluent, a molar ratio of [Li+]/[H+] = 250:1 applied). The stationary phase H+ consumed in the acid-base reaction was then re-supplied by H+ from the eluent. By monitoring the conductance of the eluent using conductivity, an induced peak resulting from the basic species was observed. Calibration graphs of peak areas vs. molar concentration of the basic species for OH-, HCO3- and H2PO4- were found to be identical. CO3(2-), HPO4(2-), and B4O7(2-) also gave identical calibration curves but their slope values were twice those for HCO3-. The detection limit for HCO3- was less than 3.2 microM and the calibration curve was linear up to 12.3 mM (injection volume, 100 microL). Seawater was directly analyzed and its total alkalinity was found to be 2.87 mM (RSD 0.53%, n = 5), which was in good agreement with the result of 2.88 mM (RSD 3.2%, n = 5) obtained using auto-potentiometric titration. Na+ and K+ were determined simultaneously and the concentrations were 481.6 and 10.6 mM, respectively.


Acrania: report of the first surviving case.
The first known surviving case of acrania is presented. The patient was the first child of a 29-year-old Japanese woman. Fetal ventriculomegaly was documented in the 35th gestational week. Prenatal sonography and magnetic resonance imaging suggested hydrocephalus with a wide encephalomeningocele. The baby was born at 38 weeks of gestational age by vaginal delivery. The patient had no calvarium, but did have a complete skull base with a partial defect in the occipital scalp and an underlying dural defect. Subsequently, the patient underwent repair of the scalp defect. At 3 months of age, after hydrocephalus developed, a subduro-peritoneal shunt was placed because of cosmetic and nursing problems. His developmental quotient was 10 at 3 years.


PDGF-AA promotes gap junction intercellular communication in chondrocytes via the PI3K/Akt pathway.
Gap junction intercellular communication (GJIC) plays an important role in cell growth, development and homeostasis. Connexin 43 (Cx43) is an important half-channel protein responsible for gap junction formation. Platelet-derived growth factor AA (PDGF-AA) regulates the proliferation, migration, metabolism, apoptosis and cell cycle of chondrocytes. However, the role of PDGF-AA in gap junction intercellular communication in chondrocytes is not fully understood. In the current study, we performed experiments to explore the effect of PDGF-AA on GJIC and its underlying biomechanical mechanism. qPCR was performed to determine the expression of PDGF, PDGFR and connexin family genes in chondrocytes and/or cartilage. A scrape loading/dye transfer assay was used to determine GJIC. Western blot analysis was applied to detect the expression of Cx43 and PI3K/Akt signaling pathway proteins. Immunofluorescence staining was utilized to examine protein distribution. Scanning electron microscopy was used to delineate the morphology of chondrocytes. Expression of PDGF-A mRNA was highest among the PDGF family in chondrocytes and cartilage tissues. PDGF-AA promoted functional GJIC formation in chondrocytes by upregulating the expression of Cx43. Enhanced functional GJIC formation in chondrocytes induced by PDGF-AA occurred through the activation of PI3K/Akt signaling and its nuclear accumulation. For the first time, this study provides evidence demonstrating the role of PDGF-AA in cell-to-cell communication in chondrocytes through mediating Cx43 expression.


Towards understanding the electronic structure of Fe-doped CeO2 nanoparticles with X-ray spectroscopy.
This study reports on the electronic structure of Fe-doped CeO2 nanoparticles (NPs), determined by coupled X-ray absorption spectroscopy and X-ray emission spectroscopy. A comparison of the local electronic structure around the Ce site with that around the Fe site indicates that the Fe substitutes for the Ce. The oxygen K-edge spectra that originated from the hybridization between cerium 4f and oxygen 2p states are sensitive to the oxidation state and depend strongly on the concentration of Fe doping. The Ce M(4,5)-edges and the Fe L(2,3)-edges reveal the variations of the charge states of Ce and Fe upon doping, respectively. The band gap is further obtained from the combined absorption-emission spectrum and decreased upon Fe doping, implying Fe doping introduces vacancies. The oxygen vacancies are induced by Fe doping and the spectrum reveals the charge transfer between Fe and Ce. Fe(3+) doping has two major effects on the formation of ferromagnetism in CeO2 nanoparticles. The first, at an Fe content of below 5%, is that the formation of Fe(3+)-Vo-Ce(3+) introduces oxygen deficiencies favoring ferromagnetism. The other, at an Fe content of over 5%, is the formation of Fe(3+)-Vo-Fe(3+), which favors antiferromagnetism, reducing the Ms. The defect structures Fe(3+)-Vo-Ce(3+) and Fe(3+)-Vo-Fe(3+) are crucial to the magnetism in these NPs and the change in Ms can be described as the effect of competitive interactions of magnetic polarons and paired ions.


Complex interactions between polyamines and calpain-mediated proteolysis in rat brain.
Polyamine synthesis is induced by various extracellular signals, and it is widely held that this biochemical response participates in cell growth and differentiation. Certain of the triggers for synthesis in brain tissues also increase the breakdown of high-molecular-weight structural proteins, apparently by activating calcium-dependent proteases (calpains). The present experiments tested the possibility that calpain activity is modulated by polyamines. Spermine, spermidine, and putrescine all increased calcium-dependent proteolysis of [14C]casein by soluble fractions of rat brain. The order of potency was spermine greater than spermidine greater than putrescine, with apparent affinities of 30, 300, and 6,000 microM, respectively. Each of the three polyamines at physiological concentrations also potentiated the calcium-dependent breakdown of two endogenous high-molecular-weight structural proteins known to be substrates of calpain, in both supernatant and membrane fractions. The thiol protease inhibitor leupeptin, a known calpain inhibitor, also inhibited calcium-dependent proteolysis in the presence and absence of polyamines. The polyamines did not increase the activity of purified calpain I or calpain II determined with either [14C]casein or purified spectrin as the substrate, nor did they interfere with the inhibitory effects of calpastatin, an endogenous inhibitor of calpain. However, polyamines potentiated the stimulation of endogenous but not purified calpain activity produced by an endogenous calpain activator. These results suggest a role for polyamines in protein degradation as well as protein synthesis.


Effect of interactions between C peptide levels and insulin treatment on clinical outcomes among patients with type 2 diabetes mellitus.
A recently halted clinical trial showed that intensive treatment of type 2 diabetes mellitus was associated with increased mortality. Given the phenotypic heterogeneity of diabetes, therapy targeted at insulin status may maximize benefits and minimize harm. In this longitudinal cohort study, we followed 503 patients with type 2 diabetes who were free of cardiovascular disease from 1996 until data on mortality and cardiovascular outcomes were censored in 2005. Phenotype-targeted therapy was defined as use of insulin therapy in patients with a fasting plasma C peptide level of 0.2 nmol/L or less and no insulin therapy in patients with higher C peptide levels. The mean age of the cohort was 54.4 (standard deviation 13.1) years, and 56% were women. The mean duration of diabetes was 4.6 years (range 0-35.9 years). Of the 503 patients, 110 (21.9%) had a low C peptide level and 111 (22.1%) were given insulin. Based on their C peptide status, 338 patients (67.2%) received phenotype-targeted therapy (non-insulin-treated, high C peptide level [n = 310] or insulin-treated, low C peptide level [n = 28]), and 165 patients (32.8%) received non-phenotype-targeted therapy (non-insulin-treated, low C peptide level [n = 82] or insulin-treated, high C peptide level [n = 83]). Compared with the insulin-treated, low-C-peptide referent group, the insulin-treated, high-C-peptide group was at a significantly higher risk of cardiovascular events (hazard ratio [HR] 2.85, p = 0.049) and death (HR 3.43, p = 0.043); the risk was not significantly higher in the other 2 groups. These differences were no longer significant after adjusting for age, sex and diabetes duration. Patients with low C peptide levels who received insulin had the best clinical outcomes. Patients with normal to high C peptide levels who received insulin had the worst clinical outcomes. The results suggest that phenotype-targeted insulin therapy may be important in treating diabetes.


[A case of secondary hyperparathyroidism with an ectopic intrathyroid gland successfully diagnosed and controlled by percutaneous ethanol injection therapy (PEIT)].
Secondary hyperparathyroidism (II HPT) is a major complication in chronic dialysis patients, and percutaneous ethanol injection therapy (PEIT) has become a useful alternative treatment for II HPT. However, the existence of ectopic parathyroid glands is a major problem when conducting PEIT. Ectopic parathyroid gland accepts 10-35% of II HPT, and the missing glands cannot be detected consistently by any imaging techniques, including scintigraphy. Intrathyroid parathyroid gland is as rare as about 1% and recurrence of missing glands after parathyroidectomy (PTx) has been reported in some cases. We report here a 52-year-old female in whom an ectopic parathyroid gland was defected successfully and intact-PTH controlled by tentative PEIT. At the first examination, a left parathyroid adenoma and a right thyroid goiter were pointed out by ultrasonography, CT and scintigraphy. PEIT was applied twice to the left parathyroid adenoma, but intact-PTH was not decreased. Ultrasonography, CT, 201Tl-99mTc subtraction scintigraphy and fine needle aspiration biopsy (FNAB) were performed again to search for the existence of ectopic glands. The results suggested that the right intrathyroid tumor was an ectopic parathyroid gland. Consequently, tentative PEIT was applied to the right intrathyroid tumor, and successful control of intact-PTH and serum Ca was eventually achieved. To our knowledge, this is the first reported case of secondary hyperparathyroidism with an ectopic intrathyroid gland that was successfully controlled by PEIT. In this case, it was suggested that tentative PEIT of intrathyroid tumor was a useful method for detecting an ectopic parathyroid gland.


High-precision soft x-ray polarimeter at Diamond Light Source.
The development and performance of a high-precision polarimeter for the polarization analysis in the soft x-ray region is presented. This versatile, high-vacuum compatible instrument is supported on a hexapod to simplify the alignment with a resolution less than 5 μrad, and can be moved with its own independent control system easily between different beamlines and synchrotron facilities. The polarimeter can also be used for the characterization of reflection and transmission properties of optical elements. A W/B(4)C multilayer phase retarder was used to characterize the polarization state up to 1200 eV. A fast and accurate alignment procedure was developed, and complete polarization analysis of the APPLE II undulator at 712 eV has been performed.


Mesp1 patterns mesoderm into cardiac, hematopoietic, or skeletal myogenic progenitors in a context-dependent manner.
Mesp1 is regarded as the master regulator of cardiovascular development, initiating the cardiac transcription factor cascade to direct the generation of cardiac mesoderm. To define the early embryonic cell population that responds to Mesp1, we performed pulse inductions of gene expression over tight temporal windows following embryonic stem cell differentiation. Remarkably, instead of promoting cardiac differentiation in the initial wave of mesoderm, Mesp1 binds to the Tal1 (Scl) +40 kb enhancer and generates Flk-1+ precursors expressing Etv2 (ER71) and Tal1 that undergo hematopoietic differentiation. The second wave of mesoderm responds to Mesp1 by differentiating into PDGFRα+ precursors that undergo cardiac differentiation. Furthermore, in the absence of serum-derived factors, Mesp1 promotes skeletal myogenic differentiation. Lineage tracing revealed that the majority of yolk sac and many adult hematopoietic cells derive from Mesp1+ precursors. Thus, Mesp1 is a context-dependent determination factor, integrating the stage of differentiation and the signaling environment to specify different lineage outcomes.


Rate of interfacial electron transfer through the 1,2,3-triazole linkage.
The rate of electron transfer is measured to two ferrocene and one iron tetraphenylporphyrin redox species coupled through terminal acetylenes to azide-terminated thiol monolayers by the Cu(I)-catalyzed azide-alkyne cycloaddition (a Sharpless "click" reaction) to form the 1,2,3-triazole linkage. The high yield, chemoselectivity, convenience, and broad applicability of this triazole formation reaction make such a modular assembly strategy very attractive. Electron-transfer rate constants from greater than 60,000 to 1 s(-1) are obtained by varying the length and conjugation of the electron-transfer bridge and by varying the surrounding diluent thiols in the monolayer. Triazole and the triazole carbonyl linkages provide similar electronic coupling for electron transfer as esters. The ability to vary the rate of electron transfer to many different redox species over many orders of magnitude by using modular coupling chemistry provides a convenient way to study and control the delivery of electrons to multielectron redox catalysts and similar interfacial systems that require controlled delivery of electrons.


Laparoscopic colectomy for colorectal cancer patients with previous abdominal surgery.
Laparoscopic colectomy has been widely accepted as a standard operation for colorectal cancer. The use of this procedure for patients with previous abdominal surgery is now well established. The aim of this study was to evaluate the peri-operative and long-term outcomes of such patients, and to compare them to patients without previous surgery. Data on a consecutive 121 cases of laparoscopic colectomy performed for colorectal cancer from 1995-1999 in Shikoku Cancer Center were analyzed retrospectively for peri-operative and long-term outcomes. Twenty one cases (17%) of laparoscopic colectomy were performed for colorectal cancer patients with previous surgery. Although the operation time for the previous surgery group was significantly longer than that of the control group, there was no significant difference in the peri-operative complications and the overall survival between the 2 groups. Although the previous abdominal surgery increases the time it takes to perform the laparoscopic colectomy, the peri-operative and long-term outcomes were comparable to those from patients without previous surgery.


[Effects of gender on irritable bowel syndrome].
Irritable bowel syndrome (IBS) is one of the most common functional bowel disorders, with prevalence between 10% and 15%, which predominates in female. Two-thirds of IBS patients are female, and the prevalence of condition range from 14% to 24%. In addition to sex hormone, the other factors, i.e.) visceral perception, autonomic nervous system and pharmacological treatment response, are associated with gender differences in IBS. Recent studies indicate that pain thresholds to visceral stimulation are lower in females with IBS compared with males with IBS. It is also indicated that males with IBS have greater sympathovagal balance in response to visceral stimulation. Further elucidation of gender differences in IBS may contribute to treatment of IBS.


Polarization-Induced Interface and Sr Segregation of in Situ Assembled La0.6Sr0.4Co0.2Fe0.8O3-δ Electrodes on Y2O3-ZrO2 Electrolyte of Solid Oxide Fuel Cells.
Application of cobaltite-based electrodes such as La0.6Sr0.4Co0.2Fe0.8O3-δ (LSCF) on Y2O3-ZrO2 (YSZ) electrolyte in solid oxide fuel cells (SOFCs) generally requires the use of a doped ceria barrier layer to prevent the interaction between LSCF and YSZ during sintering at high temperatures. In this paper, we report for the first time an in situ assembly approach to directly incorporate LSCF cathode to YSZ electrolyte without the use of a doped ceria barrier layer and without presintering at high temperatures. A Ni-YSZ anode-supported YSZ electrolyte cell with an in situ assembled LSCF electrode exhibits a peak power density of 1.72 W cm-2 at 750 °C. However, the cell performance degrades significantly at 500 mAcm-2 and 750 °C. The results indicate that cathodic polarization not only induces the formation of the interface but also accelerates the Sr segregation. The segregated Sr migrates to the LSCF electrode/YSZ electrolyte surface and forms an SrO layer. Using a Sr-free LaCoO3-δ composite cathode overcomes the Sr segregation problem, showing an excellent peak power density of 1.2 Wcm-2 and good stability at 750 °C for over 100 h. The present study shows that cobaltite-based perovskites can be directly used on YSZ-based electrolyte via the in situ assembly providing an effective means to advance the application of highly active mixed ionic/electronic conducting cathodes to YSZ electrolyte-based SOFCs.


Enter as an outsider: Teaching organizational humility.
The concept of cultural humility acknowledges the enormous task of becoming culturally competent by encouraging curiosity about the context within which others live. For physicians, this includes curiosity about the organizations in which they work as Outsiders in settings such as a new hospital or patients' homes. However, efforts to train healthcare professionals in cultural competence are often de-emphasized due to the pressure learners feel to acquire Medical Knowledge and clinical skills. Little time is devoted to address the significance of cultural humility for fully appreciating the experiences of others. Efforts to educate physicians-in-training about the cultural aspects of care require innovative approaches that help them recognize bias without provoking defensiveness. Enter as an Outsider is a highly focused activity which fosters a culturally humble approach to an often neglected problem, organizational bias. This article describes how cultural humility is explained to learners and small group activities are used to explore the thoughts and feelings of an organization's Insiders and Outsiders. This program relies on instructor self-disclosure to facilitate learning and on a video vignette from popular-culture media to illustrate being an Outsider in a healthcare setting. Participants in this training have improved their ability to recognize when they are Outsiders where they provide care. They have developed a better understanding that cultural humility in organizations is a gateway to providing quality care. They have begun the process of committing to respectfully learn from the organization's Insiders.


[In vitro virucidal activity of antiseptics and disinfectants. III. Dilution-ultrafiltration-reconcentration technic].
The method for in vitro investigation of virucidal activity of antiseptics (ATS) of disinfectants (DSF) using dilution-ultrafiltration-reconcentration includes two phases following contact of the virus with ATS or DSF: termination of antiviral activity by sudden cold dilution, and one or more filtrations on an immersible molecule separator designed to bring the tested agent's concentration below the cytotoxic level and to reconcentrate the treated viral suspension. Advantages of this technique are the following: precision of time of contact between virus and ATS or DSF, reconcentration of the viral suspension which partly offsets the termination dilution, relative simplicity, and study of true virucidal activity. Drawbacks are: inappropriateness for some agents such as povidone-iodine, and, in some instances, unreliability of immersible separators. Apart for those obtained with povidone-iodine, results are comparable to those yielded by simple dilution or gel filtration, particularly for glutaraldehyde, chlorhexidine and noxythiolin.


[Malnutrition in patients on chronic hemodialysis: prevalence, pathogenesis, and treatment].
Malnutrition is common in patients on hemodialysis and is a strong predicor of morbidity and mortality. Much progress has been made in recent years in identifying the causes and pathogenesis of malnutrition in hemodialysis patients as well as in recognizing the link between malnutrition and morbidity and mortality. Nevertheless, there is no consensus concerning its management. Conventional interventions such as nutritional counseling, oral nutritional supplements and intradialytic parenteral nutrition and novel preventive and therapeutic strategies such as appetite stimulants, growth hormone, androgenic anabolic steroids, and antiinflammatory drugs have been tested with contradictory and inconclusive results. Malnutrition still remains an important challenge for the nephrologist in the third millennium.


Managing disability from stroke.
Strokes are the single greatest neurological cause of disability, yet many stroke patients do not ever reach a specialized stroke rehabilitation unit. For those remaining in the hospital to which they were first admitted, active medical involvement may decline dramatically once the diagnosis has been made. However, the family physician can play an active role in managing post-stroke patients, enhancing their functional recovery and achieving successful discharge back into the community. This article describes post-diagnosis management of stroke, discharge planning, and post-discharge follow-up.


[Multidisciplinary approach in urology. Laser technologies: faster, simpler, more efficient].
Laser technology has taken a place among the methods of treatment of various urological diseases. The new laser devices are being developed in addition to commonly used. Physicists of the russian NTO "IRE Polus" in collaboration with doctors from Sechenov University have developed a new generation laser device - thulium fiber laser. It has been actively used since 2017 for laser enucleation of prostate. Later the laser was used for treatment of bladder tumor, lithotripsy. The device has already managed to prove its efficacy in in-vitro experiments and clinical practice surpassing foreign analogues.


Rapid evolution of pre-zygotic reproductive barriers in allopatric populations.
A population diversifies into two or more species-such a process is known as speciation. In sexually reproducing microorganisms, which barriers arise first-pre-mating or post-mating? In this work, we quantify the relative strengths of these barriers and demonstrate that pre-mating barriers arise first in allopatrically evolving populations of yeast, Saccharomyces cerevisiae. These defects arise because of the altered kinetics of mating of the participating groups. Thus, our work provides an understanding of how adaptive changes can lead to diversification among microbial populations.


A Randomized, Waiting-List-Controlled Study Shows That Brief, Mindfulness-Based Psychological Interventions Are Effective for Treatment of Women's Low Sexual Desire.
We evaluated two treatment conditions for low sexual desire in women: one where participants were administered a mindfulness-based treatment protocol and another with exercises focusing on scheduled sex and motivations for sex in addition to the aforementioned protocol. Seventy women (Mage 39.2, SD = 9.8) with complaints of low sexual desire were randomly allocated to one of these treatment conditions or a waiting-list condition. Participants attended four individual sessions and completed homework exercises. Questionnaire data were collected before and after treatment and at follow-ups three and six months later. Primary outcomes were the Female Sexual Function Index (FSFI) desire subdomain and the Sexual Interest and Desire Inventory-Female (SIDI-F). Secondary outcomes were the Female Sexual Distress Scale-Revised (FSDS-R), the Revised Dyadic Adjustment Scale (RDAS), the Perceived Relationship Quality Components Inventory (PRQC), and the Brief Symptom Inventory-18 (BSI-18). Women in both treatment conditions reported significantly higher sexual desire (FSFI desire d = 0.75 to 1.06) immediately following treatment, compared to the waiting list. Improvements were sustained at follow-up, accompanied by improvements in some secondary outcomes. We found no significant differences between the treatment conditions in terms of treatment effectiveness. Our study adds to the literature suggesting that mindfulness-based treatments are suitable options for treating low sexual desire in women.


Acid-insoluble human dentin as carrier material for recombinant human BMP-2.
The aim of this study is to estimate the increase of bone-inductive potency by human demineralized dentin matrix (DDM) with recombinant human bone morphogenetic protein-2 (BMP-2). Human teeth were crushed, completely demineralized in 0.6M HCl, and freeze-dried. The tooth-derived material is called DDM. The shape of DDM was a particle type and its size varied from 0.4 to 0.8 mm. The BMP-2 dose-dependent study in the rat subcutaneous tissues demonstrated that the volume of induced bone and marrow increased at a dose-dependent manner. The time-course study of bone induction by the BMP-2 (5.0 μg)/DDM (70 mg) was estimated histologically and biochemically. Histological findings showed that the BMP-2/DDM increased bone and marrow sequentially between the DDM particles. Calcium content in the BMP-2/DDM-induced tissue was compatible to the histological findings. ALP activity in the BMP-2/DDM showed a maximal value at 1 week and gradually decreased. The morphometric analysis demonstrated that the BMP-2/DDM showed 66.9%, 79.0% in the volume of bone and marrow, and 32.4%, 21.0% in that of DDM at 8, 32 weeks, respectively. We confirmed that BMP-2 significantly accelerated bone formation in the acid-insoluble human-dentin carriers. These results indicate that human DDM should be an effective carrier for delivering BMP-2 and superior scaffold for bone-forming cells.


Molecular analysis of the polymorphisms of thymidylate synthase on cell-free circulating DNA in blood of patients with advanced colorectal carcinoma.
As a key enzyme in folate metabolism, the thymidylate synthase (TS) is important for the synthesis of nucleotides. Its polymorphisms may affect the TS gene expression and the susceptibility for Fluoropyrimidine (FU)-based chemotherapies. In this study, we assessed the relationship between the TS genotypes and clinical outcome to 5-FU-based chemotherapy, and examined whether cell-free circulating DNA is applicable for these molecular analyses. We combined the variable number tandem repeat (VNTR) and single nucleotide (SNP) polymorphisms of the TS promoter and the deletion variants (1494del6) in the 3'UTR with the occurrence of loss of heterozygosity (LOH) at the microsatellite markers D18S59, D18S1140, and D18S976 mapped up- and downstream to the TS locus. Cell-free blood DNA, tumor tissues, and leukocytes of 51 patients with advanced colorectal cancer were used. Genotyping revealed linkage disequilibrium between TS promoter and 3'UTR (p = 0.03) in blood and leukocytes. Inverse associations of the response to therapy with the number of polymorphisms (p = 0.05) and the 494del6 polymorphism (p < 0.02) were detected on serum DNA. The quantification of serum DNA showed significant correlations with the 1494del6 variant (p = 0.006) in tumor tissues and the combined polymorphisms in leukocytes (p < 0.04). In contrast to the low LOH frequency in blood, LOH spanned more than one marker in the primary tumor of the majority of the patients suggesting the loss of the entire TS locus. Our data provide insight into the molecular diversity of the regulation of the TS gene expression. This is the first study that compares multi-variant TS genotypes in different clinical specimens.


Strong resonance enhancement of a single harmonic generated in the extreme ultraviolet range.
We report the demonstration of strong resonance enhancement of a single high-order harmonic in the extreme ultraviolet (XUV) region generated from the interaction of a femtosecond pulse with low-ionized In ablation. A strong 13th harmonic (61.2 nm) of Ti:sapphire laser radiation with output intensity almost two orders of magnitude higher than neighboring harmonics was observed in these studies. The high conversion efficiency of the 13th harmonic (8 x 10(-5)) is attributed to multiple collisions of electron trajectories with the origin due to multiphoton resonance with the In ion.


Long-pulse excimer laser with a variable reflectivity mirror resonator.
The performance of a 1-J XeCl excimer laser with a variable reflectivity mirror unstable resonator optical cavity is described. The output beam exhibits a flat profile in the near field and a far-field energy distribution with approximately 63% of the energy contained within an angle of 39 microrad (1/e(2) spot size).


Anticoagulant-resistant thrombophilia in a patient with polycythemia vera: a case report.
Mechanical valve thrombosis is a rare condition in an adequately anticoagulated patient in the absence of underlying thrombophilia. We report a case of a 76-year-old male with mechanical prosthetic mitral valve thrombosis as the presenting feature of polycythemia vera. The patient was treated with thrombolysis at the time of acute presentation and subsequently maintained on low molecular weight heparin, low-dose aspirin, phlebotomy and hydroxyurea. Hemoglobin, leucocytosis and platelet count were controlled for almost 4 years after which the patient suffered a second, fatal episode in the setting of therapeutic anti-Xa level. This case report highlights the thrombotic risks associated with polycythemia vera. The proposed mechanisms of hypercoagulability in polycythemia vera are reviewed. To the best of our knowledge, mechanical valve thromboses as the presenting feature of polycythemia vera has not been reported previously.