Factors Affecting Early Services for Children Who Are Hard of Hearing.
To describe factors affecting early intervention (EI) for children who are hard of hearing, we analyzed (a) service setting(s) and the relationship of setting to families' frequency of participation, and (b) provider preparation, caseload composition, and experience in relation to comfort with skills that support spoken language for children who are deaf and hard of hearing (CDHH). Participants included 122 EI professionals who completed an online questionnaire annually and 131 parents who participated in annual telephone interviews. Most families received EI in the home. Family participation in this setting was significantly higher than in services provided elsewhere. EI professionals were primarily teachers of CDHH or speech-language pathologists. Caseload composition was correlated moderately to strongly with most provider comfort levels. Level of preparation to support spoken language weakly to moderately correlated with provider comfort with 18 specific skills. Results suggest family involvement is highest when EI is home-based, which supports the need for EI in the home whenever possible. Access to hands-on experience with this population, reflected in a high percentage of CDHH on providers' current caseloads, contributed to professional comfort. Specialized preparation made a modest contribution to comfort level.


Growth and nutrients accumulation potentials of giant reed (Arundo donax L.) in different habitats in Egypt.
Arundo donax L. has a high biomass production and a tendency toward community dominance in many habitats and thereby a tolerance to a wide range of environmental conditions. Therefore, the present study investigated the potentiality of A. donax to accumulate nutrients and trace metals in its biomass. Six main habitats (Nile Bank, Drain Bank, Canal Bank, Field Edges, Railways and Roadsides) were recognized. At each habitat, six quadrats (each 1 m(2)), distributed equally in two sites, were selected for growth measurements (e.g., density, shoot height, diameter, leaf area and biomass), plant and soil analyses. Plants from Nile, Canal and Drain Banks had the highest values of most growth measurements, while those from Railways and Roadsides had the lowest. Canal Bank plants accumulated the highest concentrations of P, Cu and Pb in their leaves; Zn in the stem; and Mg, Cd and Fe in the rhizome. The bioaccumulation factor (BF) of A. donax, for Cd, Fe, Mn and Zn, was greater than 1, while the translocation factor (TF) of most trace metals was less than unity in most habitats. In conclusion, A. donax showed morphological plasticity in response to habitat heterogeneity, and its growth was most vigorous in the riparian habitats. The high BF, as well as the significant positive correlations between trace metals, especially Cd, in soil and plant, renders A. donax a powerful phytoremediator.


Protein-Protein Interactions: Gene Acronym Redundancies and Current Limitations Precluding Automated Data Integration.
Understanding protein interaction networks and their dynamic changes is a major challenge in modern biology. Currently, several experimental and in silico approaches allow the screening of protein interactors in a large-scale manner. Therefore, the bulk of information on protein interactions deposited in databases and peer-reviewed published literature is constantly growing. Multiple databases interfaced from user-friendly web tools recently emerged to facilitate the task of protein interaction data retrieval and data integration. Nevertheless, as we evidence in this report, despite the current efforts towards data integration, the quality of the information on protein interactions retrieved by in silico approaches is frequently incomplete and may even list false interactions. Here we point to some obstacles precluding confident data integration, with special emphasis on protein interactions, which include gene acronym redundancies and protein synonyms. Three human proteins (choline kinase, PPIase and uromodulin) and three different web-based data search engines focused on protein interaction data retrieval (PSICQUIC, DASMI and BIPS) were used to explain the potential occurrence of undesired errors that should be considered by researchers in the field. We demonstrate that, despite the recent initiatives towards data standardization, manual curation of protein interaction networks based on literature searches are still required to remove potential false positives. A three-step workflow consisting of: (i) data retrieval from multiple databases, (ii) peer-reviewed literature searches, and (iii) data curation and integration, is proposed as the best strategy to gather updated information on protein interactions. Finally, this strategy was applied to compile bona fide information on human DREAM protein interactome, which constitutes liable training datasets that can be used to improve computational predictions.


Physical dependence on clonazepam in dogs.
Six dogs were, under constant environmental conditions, treated for 7 weeks with clonazepam (0.5 mg/kg b.i.d. orally). Already after 1 week of treatment, slight symptoms of withdrawal could be elicited by intravenous injection of flumazepil (Ro 15-1788). When clonazepam was finally withdrawn, a self-limiting abstinence syndrome was observed in all dogs, consisting of behavioral alterations (listlessness, wet dog shakes, dorsal recumbency), tremor, a severe clonic-tonic seizure in 1 case, hyperthermia, and weight loss. The syndrome was most pronounced on days 2 and 3 after withdrawal, after 1 week all signs of physical dependence had disappeared.


Inpatient Goals-of-Care Conversations Reduce Intensive Care Unit Transfers in High-Risk Patients.
Despite an aging population and an increase in the prevalence of chronic severe illness, many patients will not have end-of-life care discussions with their outpatient physicians. This very likely contributes to considerable hospital utilization toward the end of life, without any clear benefit. At our medical center, we noticed a very high rate of floor-to-intensive care unit (ICU) transfers for patients with life-limiting illness and poor prognosis. We initiated a quality assessment and improvement project aimed at increasing goals-of-care conversations for high-risk patients early in their hospital stays. Patients were identified using a risk assessment score combined with presence of life-limiting illness and alerting the inpatient attending physician to the patient's severity of illness. Inpatient attending physicians were encouraged to expeditiously initiate and document goals-of-care discussions with their patients and families or to consult palliative care. Patient data were extracted retrospectively from high-risk patients prior to and during the intervention period. Analysis showed a significant increase in overall goals-of-care discussions and a significant reduction in floor-to-ICU transfers during initial admission. There was no change in mortality at 1 year, but there was a trend toward more in-home deaths for those patients who died within the year. Early inpatient goals-of-care conversations may reduce ICU utilization at index hospitalization and may reduce overall health-care utilization near the end of life.


Different Peoples, Different Inebriations: The Recognition of Different Cultures of Intoxication in Early Modern English Medicine.
In early modern Europe, the global dimensions of the drug trade and the introduction of new substances contributed to the development of new cultures of intoxication. This process was particularly evident in England, where a new intoxication culture emerged from the recognition of how different substances produced similar reactions. Medical travel literature provides a critical source for examining alternative methods of drug consumption in the non-Western world in this period: culturally embedded practices like Turkish opium eating or Native American tobacco smoking became significant benchmarks for comparing with Western habits of alcohol consumption. This article argues that the early modern Western medical community relied on comparisons of intoxication in other contexts in an effort to describe its own culturally embedded practices of alcohol intoxication.


The assessment between IL-6 and IL-8 and anthropometric status in malnourished children.
To evaluate the correlations between the pro-inflammatory interleukins IL-6 and IL-8 and the anthropometric measurements in malnourished vs. non-malnourished children. We have examined 219 children from Pediatric Clinic I, University of Medicine and Pharmacy of Tirgu Mures, Romania, during January 1, 2012-March 1, 2013 and divided according to Body Mass Index (BMI kg/m(2)) in the following two groups: 164 with normal nutritional status - control group (BMI between -2SD and +2SD), and 55 children with malnutrition (BMI <-2SD). All the children were evaluated anthropometric: BMI, weight for age (W/A), height for age (H/A), mid-upper-arm circumference (MUAC), tricipital skinfold (TSF) and paraclinical: IL-6 and IL-8 levels. From 219 children, 25.1% were malnourished. The mean age was 5.16 years in malnourished. IL-6 and IL-8 mean levels were 2.54 pg/mL, respectively 6.83 pg/mL in malnourished and 6.02 pg/mL, respectively 9.06 pg/mL in non-malnourished. By statistically comparing IL-6 in malnourished group vs. control group, we observed decreased values (p<0.0001) and also significantly lower values for IL-8. We also obtained statistical differences between the two groups in BMI, W/A, MUAC and TSF. The BMI SD have an increasing trend line, from -4SD in newborn malnourished to -2SD in near 18-year-old malnourished; the trend line had only a slight ascension in non-malnourished children. The interleukin levels and BMI, W/A, MUAC and TSF are significantly lower in malnourished children than in non-malnourished. This functional impairment may be involved in the malnutrition to develop a specific immune response in these children.


Prospects for enhancement of the soluble antioxidants, ascorbate and glutathione.
Ascorbic acid (vitamin C) and the tripeptide thiol, glutathione gamma-glutamyl cysteinyl glycine (glutathione) are the major low molecular weight soluble antioxidants in plant cells. The pathway of glutathione biosynthesis is similar in animals and plants while that of ascorbate biosynthesis differs considerably between the two kingdoms. The potential for obtaining substantial constitutive changes in the tissue contents of these antioxidants by manipulation of the biosynthetic enzymes has been demonstrated. Moreover, the concentrations of ascorbate and glutathione are greatly modified in response to a variety of environmental triggers, particularly those that cause increased oxidative stress. It is essential that the signals and associated signal transduction pathways that trigger enhanced antioxidant accumulation are elucidated as these offer an important alternative means of achieving greater nutritional value in edible plant organs.


Infection after total hip arthroplasty.
Total hip joint replacement offers dramatic improvement in the quality of life but deep infection is the most feared complication of this procedure. The infection threatens the function of the joint, the preservation of the limb, and occasionally even the life of the patient. For the surgeon it is a disastrous anticlimax, which follows a procedure that may have given the patient freedom from pain and increased mobility.


Copper cytotoxicity impairs DNA synthesis but not protein phosphorylation upon growth stimulation in LEC mutant rat.
Long-Evans Cinnamon (LEC) mutant rat, which possesses a genetic defect of the block of copper exclusion pathway in the hepatocytes, is a good model for studying the mechanism of cellular copper toxicity. We have examined effects of copper toxicity on DNA synthesis and protein phosphorylation upon growth stimulation by treating LEC rat primary-cultured hepatocytes with EGF and insulin. The proportion of DNA-synthesizing S-phase cells in LEC rat markedly decreased when compared to that of normal rat. However, the electrophoretic pattern and the signal intensity of 32P-labeled nuclear proteins in LEC rat were indistinguishable from those of normal rat. These results suggest that a cellular event other than protein phosphorylation required for the initiation of DNA synthesis upon growth stimulation is impaired by copper cytotoxicity.


What's Normal? Immune Profiling of Human Milk from Healthy Women Living in Different Geographical and Socioeconomic Settings.
Human milk provides a very wide range of nutrients and bioactive components, including immune factors, human milk oligosaccharides, and a commensal microbiota. These factors are essential for interconnected processes including immunity programming and the development of a normal infant gastrointestinal microbiome. Newborn immune protection mostly relies on maternal immune factors provided through milk. However, studies dealing with an in-depth profiling of the different immune compounds present in human milk and with the assessment of their natural variation in healthy women from different populations are scarce. In this context, the objective of this work was the detection and quantification of a wide array of immune compounds, including innate immunity factors (IL1β, IL6, IL12, INFγ, TNFα), acquired immunity factors (IL2, IL4, IL10, IL13, IL17), chemokines (IL8, Groα, MCP1, MIP1β), growth factors [IL5, IL7, epidermal growth factor (EGF), granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor, TGFβ2], and immunoglobulins (IgA, IgG, IgM), in milk produced by healthy women of different ethnicities living in different geographic, dietary, socioeconomic, and environmental settings. Among the analyzed factors, IgA, IgG, IgM, EGF, TGFβ2, IL7, IL8, Groα, and MIP1β were detected in all or most of the samples collected in each population and, therefore, this specific set of compounds might be considered as the "core" soluble immune factors in milk produced by healthy women worldwide. This approach may help define which immune factors are (or are not) common in milk produced by women living in various conditions, and to identify host, lifestyle, and environmental factors that affect the immunological composition of this complex biological fluid. Clinical Trial Registration: www.ClinicalTrials.gov, identifier NCT02670278.


Evidence that beta-amyloid protein in Alzheimer's disease is not derived by normal processing.
The beta-amyloid protein (beta/A4), derived from a larger amyloid precursor protein (APP), is the principal component of senile plaques in Alzheimer's disease. APP is an integral membrane glycoprotein and is secreted as a carboxyl-terminal truncated molecule. APP cleavage, which is a membrane-associated event, occurred at a site located within the beta/A4 region. This suggests that an intact amyloidogenic beta/A4 fragment is not generated during normal APP catabolism. Therefore, an early event in amyloid formation may involve altered APP processing that results in the release and subsequent deposition of intact beta/A4.


Trust increases euthanasia acceptance: a multilevel analysis using the European Values Study.
This study tests how various kinds of trust impact attitudes toward euthanasia among the general public. The indication that trust might have an impact on euthanasia attitudes is based on the slippery slope argument, which asserts that allowing euthanasia might lead to abuses and involuntary deaths. Adopting this argument usually leads to less positive attitudes towards euthanasia. Tying in with this, it is assumed here that greater trust diminishes such slippery slope fears, and thereby increases euthanasia acceptance. The effects of various trust indicators on euthanasia acceptance were tested using multilevel analysis, and data from the European Values Study 2008 (N = 49,114, 44 countries). More precisely, the influence of people's general levels of trust in other people, and their confidence in the health care system, were measured--both at the individual and at the country level. Confidence in the state and the press were accounted for as well, since both institutions might monitor and safeguard euthanasia practices. It was shown that the level of trust in a country was strongly positively linked to euthanasia attitudes, both for general trust and for confidence in health care. In addition, within countries, people who perceived their fellow citizens as trustworthy, and who had confidence in the press, were more supportive of euthanasia than their less trusting counterparts. The pattern was, however, not true for confidence in the state and for confidence in the health care system at the individual level. Notably, all confirmative effects held, even when other variables such as religiosity, education, and values regarding autonomy were controlled for. Trust seems to be a noteworthy construct to explain differences in attitudes towards euthanasia, especially when drawing cross-country comparisons. Therefore, it should be added to the existing literature on correlates of euthanasia attitudes.


Effect of different fractions of macromolecules upon triggering of calcium oxalate and calcium phosphate crystal formation in whole urine.
Macromolecules were removed from whole urine samples by sequential ultrafiltration using molecular weight cut-offs of 300,000, 100,000 and 10,000 dalton. The whole urine samples and ultrafiltrates were evaporated to 1,250 mosm/kg at pH 5.3 and 6.8 to study calcium oxalate and calcium phosphate crystal formation, respectively. While all the ultrafiltrates removed Tamm-Horsfall proteins and most of the crystal formation, there was some 10% of the crystal-promoting powers in the macromolecules in the fraction between molecular weight 100,000 and 300,000 dalton. This demonstrates the existence of a second crystal-promoting substance in the macromolecules of whole urine.


Lipophilic prodrugs of apomorphine I: preparation, characterisation, and in vitro enzymatic hydrolysis in biorelevant media.
Apomorphine, a subcutaneously administered drug for Parkinson's disease with short half-life requires frequent administration leading to patient non-compliance. This study aimed at synthesising and purifying lipophilic diesters of apomorphine, and investigating their in vitro degradation in biorelevant media before and after incorporating them into self-emulsifying drug delivery systems (SEDDS) for oral delivery. Two apomorphine diester prodrugs were synthesised: dilauroyl apomorphine (DLA) and dipalmitoyl apomorphine (DPA). The in vitro enzymatic hydrolysis of diesters was performed using biorelevant media with pancreatin to catalyse the diester degradation. The synthesised and purified diesters were found to be free from reactants as impurities confirmed by LC/MS and NMR. DLA and DPA were degraded into corresponding monoesters and free apomorphine within 5 min after adding pancreatin, leaving about 4% and 28% of the intact diester, respectively. The incorporation of the diesters into SEDDS reduced the enzymatic degradation of diesters. In addition, the chain length of diester and the type of oil used in formulations affected diester hydrolysis. The lipophilic apomorphine diesters were substrates of lipases present in pancreatin, and the degree of diester degradation can be controlled by selecting suitable lipid excipients. Therefore, diesters of apomorphine are promising prodrugs for oral delivery aiming at lymphatic transport.


The relevance of metabolic and endocrine responses to anesthesia and surgery.
The development of anesthesia has reached a stage where the evaluation of the usefulness of metabolic and endocrine responses is highly important. At present, these responses are commonly modulated in patients known to benefit most (e.g. patients with ischemic cardiovascular disease and patients undergoing major abdominal surgery), but no methods of totally response-free anesthesia and surgery are available, nor are there methods for the modulation of the responses on a wide clinical scale. Fortunately, in most patients undergoing conventional elective operations good anesthetic care is sufficient for blunting of the responses. Better methods of modulating the responses may be available in the future, which will greatly change anesthesia practice.


Mechanisms of thrombin-Induced myometrial contractions: Potential targets of progesterone.
Intrauterine bleeding during pregnancy is a major risk factor for preterm birth. Thrombin, the most abundant coagulation factor in blood, is associated with uterine myometrial contraction. Here, we investigated the molecular mechanism and signaling of thrombin-induced myometrial contraction. First, histologic studies of placental abruption, as a representative intrauterine bleeding, revealed that thrombin was expressed within the infiltrating hemorrhage and that thrombin receptor (protease-activated receptor 1, PAR1) was highly expressed in myometrial cells surrounding the hemorrhage. Treatment of human myometrial cells with thrombin resulted in augmented contraction via PAR1. Thrombin-induced signaling to myosin was then mediated by activation of myosin light chain kinase- and Rho-induced phosphorylation of myosin light chain-2. In addition, thrombin increased prostaglandin-endoperoxidase synthase-2 (PTGS2 or COX2) mRNA and prostaglandin E2 and F2α synthesis in human myometrial cells. Thrombin significantly increased the mRNA level of interleukine-1β, whereas it decreased the expressions of prostaglandin EP3 and F2α receptors. Progesterone partially blocked thrombin-induced myometrial contractions, which was accompanied by suppression of the thrombin-induced increase of PTGS2 and IL1B mRNA expressions as well as suppression of PAR1 expression. Collectively, thrombin induces myometrial contractions by two mechanisms, including direct activation of myosin and indirect increases in prostaglandin synthesis. The results suggest a therapeutic potential of progesterone for preterm labor complicated by intrauterine bleeding.


Histidinol-mediated improvement in the specificity of 1-beta-D-arabinofuranosylcytosine and 5-fluorouracil in L 1210 leukemia-bearing mice.
We have demonstrated previously that L-histidinol, a structural analogue of the essential amino acid L-histidine, protects a variety of phenotypically normal cell lines from certain proliferation-dependent anticancer drugs without decreasing the toxicity of these agents for corresponding tumorigenic derivatives of the normal cells. Histidinol modulates the toxicity of selected anticancer drugs in tissue culture systems by its ability to arrest, specifically and reversibly, cells of normal phenotype in a G0-like, noncycling state while allowing continued cell cycle transit in most of their tumorigenic counterparts. Thus, in the presence of comparable levels of histidinol, the toxicities of the proliferation-dependent anticancer drugs 1-beta-D-arabinofuranosylcytosine and 5-fluorouracil are eliminated for a variety of normal cell lines but significantly increased for a number of tumorigenic lines. We report here that histidinol confers substantial protection upon the bone marrow cells of DBA/2J mice from the drugs 1-beta-D-arabinofuranosylcytosine and 5-fluorouracil. The protective responses were evaluated by quantitative cell survival assays and by animal survival studies. We report also that the histidinol-mediated protection to bone marrow cells persists in L1210 leukemia-bearing DBA/2J mice treated with combinations of histidinol and 1-beta-D-arabinofuranosylcytosine or 5-fluorouracil without diminishing the toxicities of these agents for in situ leukemia cells.


INDOOR RADON (222RN) MEASUREMENTS AND ESTIMATION OF ANNUAL EFFECTIVE DOSE IN MVANGAN LOCALITY, SOUTH CAMEROON.
The present work was aimed at measuring indoor radon activity concentrations in dwellings in Mvangan locality, South Cameroon, in order to assess the extent of measures that may be necessary for controlling public indoor radon exposure in this area. Measurements were carried out using passive solid-state nuclear track detectors (RADONAVA Inc., RadTrak2, Sweden) following ISO 11665-4 standard. Radon concentration ranged between 36 ± 20 and 150 ± 30 Bq m-3 with arithmetic and geometric means values of 64 ± 25 and 60 ± 1 Bq m-3, respectively. These mean values were greater than worldwide values presented by United Nations Scientific Committee on the Effects of Atomic Radiation (UNSCEAR), which are, respectively, 40 and 30 Bq m-3. 96% of dwellings that have radon concentrations below the World Health Organization (WHO) reference level of 100 Bq m-3, whereas 4% of dwellings have radon concentrations higher than this level but lower than 300 Bq m-3, the International Commission on Radiological Protection (ICRP) reference level. Annual effective doses due to indoor radon ranged between 0.7 and 2.8 mSv y-1 with an arithmetic mean value of 1.2 ± 0.5 mSv y-1. These values were below the lower limit of the ICRP-recommended action level interval 3-10 mSv y-1. It has been observed that annual effective dose received by residents in cement bricks dwellings were not significantly different (P-value = 0.565) than those received by residents in mud dwellings in Mvangan locality. The mean number of persons expected to be diagnosed with or die from cancer (solid cancers and leukemia) were 162 ± 48 (61 ± 25 for males and 101 ± 41 for females) and 82 ± 24 (33 ± 13 for males and 49 ± 20 for females), respectively. The results obtained in this study prove that the populations of Mvangan locality are exposed to a relatively low potential risk of cancer incidence and mortality.


The value of forceps biopsy and core needle biopsy in prediction of pathologic complete remission in locally advanced rectal cancer treated with neoadjuvant chemoradiotherapy.
Patients with pathological complete remission (pCR) after treated with neoadjuvant chemoradiotherapy (nCRT) have better long-term outcome and may receive conservative treatments in locally advanced rectal cancer (LARC). The study aimed to evaluate the value of forceps biopsy and core needle biopsy in prediction of pCR in LARC treated with nCRT. In total, 120 patients entered this study. Sixty-one consecutive patients received preoperative forceps biopsy during endoscopic examination. Ex vivo core needle biopsy was performed in resected specimens of another 43 consecutive patients. The accuracy for ex vivo core needle biopsy was significantly higher than forceps biopsy (76.7% vs. 36.1%; p < 0.001). The sensitivity for ex vivo core needle biopsy was significantly lower in good responder (TRG 3) than poor responder (TRG ≤ 2) (52.9% vs. 94.1%; p = 0.017). In vivo core needle biopsy was further performed in 16 patients with good response. Eleven patients had residual cancer cells in final resected specimens, among whom 4 (36.4%) patients were biopsy positive. In conclusion, routine forceps biopsy was of limited value in identifying pCR after nCRT. Although core needle biopsy might further identify a subset of patients with residual cancer cells, the accuracy was not substantially increased in good responders.


EXTRACELLULAR POLYSACCHARIDE OF MUCOID LACTOBACILLUS BIFIDUS.
Wang, Marian (University of Pennsylvania, Philadelphia), Edward Steers, and Robert F. Norris. Extracellular polysaccharide of mucoid Lactobacillus bifidus. J. Bacteriol. 86:898-903. 1963.-The extracellular polysaccharide produced by the "Jackson-mucoid" strain of Lactobacillus bifidus was isolated and purified by three different procedures. The component sugars of the polysaccharide were identified by paper chromatography and confirmed by infrared analysis. Galacturonic acid, galactose, glucose, and 6-deoxy-talose were identified. Contrary to a previous report from this laboratory, fucose was not found to be a component of this polysaccharide.


A Brief Overview of the Cerebrospinal Fluid System and Its Implications for Brain and Spinal Cord Diseases.
A comprehensive understanding of the cerebrospinal fluid (CSF) system is essential for our understanding of health and disease within the central nervous system (CNS). The system of CSF refers to all components involved in CSF production, movement, and absorption. In recent years, extensive research has resulted in vastly improved understanding of the CSF system in health and disease. Yet, several aspects remain to be fully clarified, notably along the spinal cord as the preponderance of research has focused on the brain. This review briefly summarizes the CSF system and its implications for CNS diseases and highlights the knowledge gaps that require further research.


Breast problems.
This article deals with improving the clinical examination of breasts, benign breast disorders, and breast cancer. The early detection of cancer is emphasized.


Ethanol reduces neural precursor cells and inhibits neuronal and glial differentiation in zebrafish embryos.
To investigate the influence of exposure to different concentrations of ethanol on neural progenitor cells and the differentiation of neurons and glial cells in zebrafish embryos. Zebrafish embryos were exposed to 1%, 2%, and 2.5% (V/V) ethanol at 5 hpf by adding ethanol to the egg water. In situ hybridization and real-time PCR were used to detect the changes in the mRNA expression profiles of the markers of different cells to examine the effects of alcohol on neural development. The number of neural precursor cells, neurons and mature glial cells was significantly reduced in the zebrafish embryos following ethanol exposure, and this reduction became more prominent as the ethanol concentration increased. The expression of the early glial marker slc1a3a was down-regulated in the spinal cord but increased in the brain after exposure to increased ethanol concentrations. The expression of the mature glial markers was significantly lowered in response to exposure to increasing ethanol concentrations. Ethanol can reduce neural precursor cells and inhibits neuronal and glial differentiation in zebrafish embryos.


Myocardial and peripheral concentrations of beta-endorphin before and following myocardial ischemia and reperfusion during coronary angioplasty.
There is substantial evidence indicating that endogenous opioid peptides are involved in the pathophysiology of myocardial ischemia and reperfusion. We measured the myocardial and peripheral concentrations of beta-endorphin before and following myocardial ischemia and reperfusion during coronary angioplasty. The results indicate that in patients with coronary artery disease, there was an augmented myocardial concentration of beta-endorphin. Moreover, there was an increased peripheral concentration of beta-endorphin following myocardial ischemia and reperfusion. The data support the previous notion that endogenous opioid peptides are involved in the pathophysiology of ischemic heart disease.


Spectrally efficient multi-service fiber-wireless access in low-cost direct-detection THz system at 300 GHz.
This Letter demonstrates a novel, to the best of knowledge, overlapping single-sideband (OSSB) transmission scheme for spectrally efficient multi-service fiber-wireless (FiWi) access in a low-cost direct-detection (DD) THz system. Utilizing the proposed OSSB scheme, user data from different services can share the same spectrum resource yet can be successfully demodulated via one cost-effective DD THz receiver in conjunction with the Kramers-Kronig (KK) based SSB field reconstruction and look-up table (LUT) enabled signal separation algorithms. A proof-of-principle experiment is conducted. Based on an IQ modulator and a single THz zero-bias diode (ZBD), two independent 10-GBd quadrature phase shift keying (QPSK) signals with an overlapped spectrum are successfully demodulated after 20-km fiber and up to 3-m wireless transmission at the 300-GHz band. To the best of our knowledge, this is the first demonstration of multi-service FiWi access with an OSSB format in a 300-GHz DD THz system.


Analysis of the interactions of immunosuppressive drugs with cyclosporine in inhibiting DNA proliferation.
Though the high immunosuppressive efficacy of cyclosporine has revolutionized clinical transplantation, renal, hepatic, and neural toxicities limit its therapeutic potential. One approach to this problem is to combine CsA therapy with immunosuppressive agents that act synergistically with it, thereby permitting lower doses and mitigating drug-induced toxicity. The present study examines the in vitro interactions of various immunosuppressive agents--namely, 6-mercaptopurine (6MP), dexamethasone (Dexa), FK506, and Enisoprost (EP)--with CsA. These investigations dissect the impact of the drug combinations in inhibiting 3H-thymidine incorporation into DNA by normal human peripheral blood lymphocytes activated by mitogens or by alloantigens in mixed lymphocyte culture responses. The median-effect equation was used to analyze the dose-effect relationships of immunosuppressive drugs either alone or in combination. The interactions were quantified by calculation of combination indices (CI). CI values less than 1, greater than 1, and equal to 1 represent synergistic, antagonistic, and additive interactions, respectively. In combination with CsA, 6MP showed modest and Dexa profound synergism, while EP displayed modest and FK506 marked antagonism. These findings confirm the clinical impression of in vivo synergism between CsA and Dexa. They suggest that in vitro analysis of drug interactions may distinguish synergistic drug combinations potentially applicable to clinical practice.


[Differential diagnosis in descending perineum syndrome].
Clinical symptoms in descending perineum syndrome show considerable variations, ranging from obstructed defecation to combined fecal and urinary incontinence and including different types of prolapse. Differential diagnosis has to compete with this complexity. Common pelvic floor disorders associated with descending perineum are rectocele, rectal prolapse, enterocele, and sigmoidocele. Standardized diagnostic tools include detailed history and clinical examination with proctorectoscopy as well as anorectal manometry, endoanal ultrasound, defecography, and dynamic MR of the pelvic floor. The diagnosis and proposed therapy have to be developed within an interdisciplinary concept.


Community-based rehabilitation cadres: their motivation for volunteerism.
Volunteer workers, or cadres, are critical to the successful implementation of community-based rehabilitation (CBR) programmes. To date, relatively little research has examined the importance of motivation in health volunteers in general, and especially CBR workers. This paper reports the major findings of a field study in rural Indonesia. A multimethod design within a broad qualitative research framework which focused on the personal experiences of CBR volunteers was utilized. Descriptive data were obtained from written questionnaires, focus groups and key informant interviews. Research findings indicated that volunteer cadres perform considerable duties and face numerous difficulties in the course of their CBR activities. Incentives also play an important role in determining the motivation and ultimate performance of volunteer cadres. Developing an understanding of what it is like to be a volunteer CBR cadre has important implications for rehabilitationists interested in developing and sustaining CBR programmes and is clearly critical to any evaluation of CBR.


No causal association between plasma cystatin C and cardiovascular diseases: Mendelian randomization analyses in UK biobank.
We aimed to determine whether the plasma cystatin C is a causal risk factor for cardiovascular events, stroke, myocardial infarction (MI), and cardiovascular disease (CVD) mortality by conducting Mendelian randomization (MR) designs. Our study included 277,057 individuals free of CVDs or cancer at baseline in the UK Biobank. The genetic scores of plasma cystatin C comprising 67 single-nucleotide polymorphisms were calculated on the basis of data from a large genome-wide association study. By stratifying the genetic score, we conducted cox regression to assess the relationship between plasma cystatin C and CVDs. In this study, linear MR analysis was used to estimate the causal association between plasma cystatin C and CVDs. Observational analyses showed that plasma cystatin C concentrations were associated with the risk of CVDs [hazard ratios (HR) per standard deviation (SD) 1.09, 95% confidence interval (CI); 1.07-1.10] and CVD mortality (1.14, 1.11-1.17). Among CVDs, plasma cystatin C were associated with stroke (1.10, 1.08-1.11) and MI (1.08, 1.07-1.10). Linear MR analysis did not provide evidence of a causal association between plasma cystatin C and the risk of CVDs [odds ratio (OR) per SD 0.96, 95% CI;0.90-1.03], stroke (0.96, 0.93-1.01), MI (0.97, 0.91-1.03), and CVD mortality (0.98, 0.96-1.01), with consistent estimates from sensitivity analyses. Observational findings indicated that higher plasma cystatin C is associated with a higher risk of CVDs; According to MR studies, there is no causal association between plasma cystatin C and the risk of CVDs and CVD mortality.


Importance of physical rehabilitation before and after cardiac transplantation in a patient with myotonic dystrophy: a case report.
Patients with muscular dystrophy and concomitant cardiomyopathy are only reluctantly accepted for heart transplantation because of the perioperative risk secondary to respiratory muscle weakness. We describe a man with Steinert's disease (myotonic dystrophy) who received a cardiac allograft because of end-stage dilated cardiomyopathy. This case shows the importance of uninterrupted physiotherapeutic training and assistance to minimize respiratory infections and ventilatory insufficiency in patients with muscle diseases under high-dose immunosuppression. To our knowledge, this is the first heart transplantation reported in a patient with Steinert's disease who has clinically overt muscular impairment.


Olfactory impairment in patients with the fibromyalgia syndrome and systemic sclerosis.
Patients with autoimmune diseases often present with olfactory impairment. The aim of the study was to assess the olfactory functions of female patients with fibromyalgia (FM) compared with patients with systemic sclerosis (SSc) and with healthy female controls. Olfactory functions were assessed in 24 patients with FM, 20 patients with SSc and 21 age-matched healthy controls. The sense of smell was evaluated using the Sniffin' Sticks test including the three stages of smell: threshold, discrimination, and identification (TDI) of the different odors. The severity of fibromyalgia was assessed using the fibromyalgia impact questionnaire (FIQ). The short form 36 (SF-36) questionnaire was also completed in order to seek a relationship between the patients perception of quality of life and the different aspects of the smell sense. Depression was evaluated in both FM and SSc patients utilizing the Beck depression inventory-II (BDI-II) questionnaire. Patients with FM had significantly lower TDI smell scores compared with both SSc patients and healthy controls (p < 0.005, One-Way ANOVA). Hyposmia (defined as TDI scores below 30) were observed in 14 of 24 (42 %) patients with FM compared to 3 of 20 (15 %) patients with SSc and 1 of the healthy controls (4.3 %) (p < 0.02). FM patients had significantly lower thresholds of smell compared to both healthy controls and patients with SSc (p < 0.001), whereas for patients with SSc only the ability to discriminate between odors was impaired (p < 0.006). We could not detect any statistical correlation between smell abilities and clinical manifestation of SSc or the FIQ and SF-36 scores among FM patients. However the correlation between depression, defined by the BDI-II score, and the sense of smell differed between patients with FM and patients with SSc. As only among SSc patients a lower sense of smell correlated with a higher BDI-II score (p = 0.02). Our findings suggest that there is a decrease in the sense of smell both in FM and SSc patients compared with healthy controls. However these impairments differ between patients group and might represent different mechanisms that affect the sense of smell.


A randomized trial of amnioreduction versus septostomy in the treatment of twin-twin transfusion syndrome.
Left untreated, severe twin-to-twin transfusion syndrome (TTTS) presenting in the early second trimester of pregnancy is often associated with significant maternal morbidity and almost universal perinatal loss. Removal of excessive amounts of amniotic fluid through serial amniocenteses (amnioreduction) has been the mainstay of therapy. We sought to compare amnioreduction to intentional perforation of the intervening twin membrane (septostomy). Pregnant women with TTTS before 24 weeks' gestation were randomly assigned to serial amnioreduction or septostomy. A single puncture technique under ultrasound guidance was used for the septostomy. The primary outcome measure was survival to neonatal discharge, and was assessed based on the number of pregnancies or the number of fetuses as appropriate. The study was terminated at the planned interim analysis stage after 73 women were enrolled. This was because the rate of survival of at least 1 infant was similar in the amnioreduction group compared to the septostomy group (78% vs 80% of pregnancies, respectively; RR=0.94, 95%CI 0.55-1.61; P=.82). Patient undergoing septostomy were more likely to require a single procedure for treatment (64% vs 46%; P=.04). Although overall perinatal survival is not enhanced, septostomy offers the advantage of often requiring a single procedure compared to serial amnioreduction in the treatment of severe twin-to-twin transfusion syndrome.


[From limited to extensive radical operation in thyroid carcinoma].
The incidence of malignant thyroid tumors in Germany is about 1-2 cases per 100,000 inhabitants and year with a preponderance of female to male 3:1. Thus malignant thyroid tumors are rare and account for about 0.5% to 1% of all malignancies. Special consideration, however, has to be paid to the fact, that thyroid lesions associated with the risk of malignancy are much more frequent. Therefore identification of patients with particular risk for thyroid malignancy out of the 15% to 20% of the German population with thyroid lesions has to be the main scope. Prognosis of differentiated thyroid carcinomas is excellent and requires operative procedures adapted to histological tumor type and tumor stage. Hemithyroidectomy for small papillary tumors can be as adequate as total thyroidectomy including bilateral neck dissection plus mediastinal lymph node dissection in medullary thyroid carcinoma. Generally radical resection of tumor is the aim. Palliative modalities in distant metastatic disease or undifferentiated tumors are indicated to optimize additive or adjuvant therapy resp. to improve prognosis.


Performance evaluation of two multiplex qualitative RT-PCR assays for detection of respiratory infection in paediatric population.
Acute respiratory infection (ARI) contributes to significant mortality and morbidity worldwide and is usually caused by a wide range of respiratory pathogens. This study aims to describe the performance of QIAstat-Dx® Respiratory Panel V2 (RP) and RespiFinder® 2SMART assays for respiratory pathogens detection. A total of 110 nasopharyngeal swabs (NPS) were collected from children aged one month to 12 years old who were admitted with ARI in UKMMC during a one-year period. The two qPCR assays were conducted in parallel. Ninety-seven samples (88.2%) were positive by QIAstat-Dx RP and 86 (78.2%) by RespiFinder assay. The overall agreement on both assays was substantial (kappa value: 0.769) with excellent concordance rate of 96.95%. Using both assays, hRV/EV, INF A/H1N1 and RSV were the most common pathogens detected. Influenza A/H1N1 infection was significantly seen higher in older children (age group > 60 months old) (53.3%, p-value < 0.05). Meanwhile, RSV and hRV/EV infection were seen among below one-year-old children. Co-infections by two to four pathogens were detected in 17 (17.5%) samples by QIAstat-Dx RP and 12 (14%) samples by RespiFinder, mainly involving hRV/EV. Bacterial detection was observed only in 5 (4.5%) and 6 (5.4%) samples by QIAstat-Dx RP and RespiFinder, respectively, with Mycoplasma pneumoniae the most common detected. The overall performance of the two qPCR assays was comparable and showed excellent agreement. Both detected various clinically important respiratory pathogens in a single test with simultaneous multiple infection detection. The use of qPCR as a routine diagnostic test can improve diagnosis and management.


In Vitro Selection of Cancer Cell-Specific Molecular Recognition Elements from Amino Acid Libraries.
Differential cell systematic evolution of ligands by exponential enrichment (SELEX) is an in vitro selection method for obtaining molecular recognition elements (MREs) that specifically bind to individual cell types with high affinity. MREs are selected from initial large libraries of different nucleic or amino acids. This review outlines the construction of peptide and antibody fragment libraries as well as their different host types. Common methods of selection are also reviewed. Additionally, examples of cancer cell MREs are discussed, as well as their potential applications.


The production and use of evidence in health care service innovation: a qualitative study.
The focus of this article is on a range of concepts of evidence employed by health care innovators in pursuing service innovations and in demonstrating their success. In-depth, semi-structured interviews were conducted with 18 key informants in the United Kingdom who had won Health Service Journal awards for successfully implementing 15 service innovations. Four concepts of evidence were identified: (a) evidence of effectiveness-both direct and indirect, (b) evidence of efficiency, (c) evidence of innovation acceptance, and (d) evidence of relevance. The results suggest that the innovators articulated evidential concepts from the main approaches prevailing in the British National Health Service, namely clinical trials and improvement cycles. Most aspired to "better" evidence than they were able to obtain, while the approach to evidence gathering was very pragmatic and was more aligned with the improvement-cycle framework. Developing supporting mechanisms for assisting innovation evaluation is an important challenge if service innovation is to be routinely attempted and achieved in health care.


A Review of IoT Sensing Applications and Challenges Using RFID and Wireless Sensor Networks.
Radio frequency identification (RFID) and wireless sensors networks (WSNs) are two fundamental pillars that enable the Internet of Things (IoT). RFID systems are able to identify and track devices, whilst WSNs cooperate to gather and provide information from interconnected sensors. This involves challenges, for example, in transforming RFID systems with identification capabilities into sensing and computational platforms, as well as considering them as architectures of wirelessly connected sensing tags. This, together with the latest advances in WSNs and with the integration of both technologies, has resulted in the opportunity to develop novel IoT applications. This paper presents a review of these two technologies and the obstacles and challenges that need to be overcome. Some of these challenges are the efficiency of the energy harvesting, communication interference, fault tolerance, higher capacities to handling data processing, cost feasibility, and an appropriate integration of these factors. Additionally, two emerging trends in IoT are reviewed: the combination of RFID and WSNs in order to exploit their advantages and complement their limitations, and wearable sensors, which enable new promising IoT applications.


Nonfunctional gut? Try a probiotic food.
This month's Nutrition column discusses the problem of antibiotic-associated diarrhea. The overgrowth of the "good" bacteria, Clostridium difficile, can cause severe abdominal pain, fever, and diarrhea. This article examines the benefits of including probiotics in a meal plan when the use of antibiotics is medically indicated.


A comparison of the predictive performance of different methods of kidney function estimation in a well-characterized HIV-infected population.
Glomerular filtration rate (GFR) estimation equations have never been validated in the HIV population. This pilot study aimed to compare all currently available methods of kidney function assessment with nuclear GFR in HIV-infected adults. Patients underwent GFR measurement with (99m)Tc-diethylenetriaminepentaacetic acid (Tc-99m Pentetate), and measured values were compared with results of creatinine-based estimation equations [abbreviated 4-variable Modification of Diet in Renal Disease (MDRD) formula and Cockcroft-Gault (CG) formulae], 24-hour urine creatinine clearance and estimated cystatin C GFR. Twenty-seven HIV-infected adults were studied. Most were male and Caucasian, with a mean age of 52 years. Median CD4 was 290 cells/mm(3), 70% of patients had HIV RNA <50 copies/ml and all were receiving highly active antiretroviral therapy (median 5 drugs). Median Tc-99m Pentetate-GFR was 91 ml/min/1.73 m(2). Despite greater bias and similar accuracy, the MDRD formula was more precise than the CG formula, regardless of whether CG estimations were corrected for ideal body weight or body surface area. Relative accuracy within 30% of nuclear GFR was greater for the MDRD formula than for all other methods. The performance of 24-hour urine creatinine clearance was similar to that of the MDRD formula for patients with GFR <90 ml/min/1.73 m(2), although it performed less well at higher GFR. The performance of cystatin C GFR was inferior to that of all the creatinine-based methods. While no method of kidney function estimation performed highly, both 24-hour urine creatinine clearance and the MDRD formula performed with a level of precision and accuracy sufficient for clinical decision making. Our findings support the preferential use of the MDRD formula in the treated HIV population and suggest that there are no HIV-specific factors that limit equation applicability. Larger validation studies are needed to confirm our findings and allow generalization to the HIV population at large.


Limb reduction defects in over one million consecutive livebirths.
Limb reduction defects occurring among 1,213,913 consecutive livebirths in British Columbia during the period 1952-1984 inclusive were reviewed. A total of 659 cases of limb reduction defects were identified, 393 of them involving the long bones and 190 of them more than one limb. The time period 1966-1984, during which ascertainment was consistent, was evaluated, and an incidence of 5.97 per 10,000 livebirths (1 in 1,692 live births) was found. The data were evaluated for trends over time, sex ratio, and regional and ethnic distribution. Associated anomalies of other organ systems in these cases were analyzed, and overall about one-half of the cases have additional defects. The majority of these additional defects affect the musculoskeletal system and include such entities as clubfoot, hip dislocation, and congenital contractures. Defects are also frequent in other organ systems, such as the cardiovascular, gastrointestinal, and genitourinary systems. By far the most common limb defects are terminal longitudinal defects then terminal transverse defects. Of all cases of limb defects, 75% are upper limb and 25% lower limb. We found no evidence that one side is affected more frequently. About 6.5% of cases had another family member registered with a skeletal defect; 12.9% of cases died within the first year of life, the majority (85%) of those dying having additional defects. Etiological considerations are discussed for some subgroups.(ABSTRACT TRUNCATED AT 250 WORDS)


[Review on farmer's climate change perception and adaptation].
As the most serious challenge that the humankind is facing, climate change has been strengthened vulnerability in many countries and regions, and how to scientifically adapt to climate change has become the global issue of common concern to the international community today. The impact of climate change on farming people depending on the nature resource is especially remarkable, and understanding farmers' adaptation mechanism and process is very important to effectively make the adaptation policy. As the basis of understanding the human response action, public perception has provided a new perspective to verify the farmers' adaptation mechanism and process about climate change. Based on the recent theoretical and empirical developments of farmers' perception and adaptation, the impact of climate change on the farmers' livelihood was analyzed, and the main adaptation obstacles which the farmers faced in response to climate change were summarized systematically. Then, we analyzed the relationship between the farmers' climate change perception and adaptation, illuminated the key cognitive elements in the process of the farmers' climate change adaptation and introduced the framework to analyze the relationship between the farmers' climate change perception and adaptation. At last, this review put forward the key questions which should be considered in study on the relationship between the farmers' climate change perception and adaptation.


In vivo evaluation of a dexamethasone/PLGA microsphere system designed to suppress the inflammatory tissue response to implantable medical devices.
The purpose of this research effort was to evaluate in vivo a newly developed dexamethasone/PLGA microsphere system designed to suppress the inflammatory tissue response to an implanted device, in this case a biosensor. The microspheres were prepared using an oil/water (O/W) emulsion technique. The microsphere system was composed of drug-loaded microspheres (including newly formulated and predegraded microspheres) and free dexamethasone. The combination of the drug and drug-loaded microspheres provided burst release of dexamethasone followed by continuous release from days 2-14. Continuous release to at least 30 days was achieved by mixing predegraded and newly formulated microspheres. The ability of our mixed microsphere system to control tissue reactions to an implant then was tested in vivo using cotton thread sutures to induce inflammation subcutaneously in Sprague-Dawley rats. Two different in vivo studies were performed, the first to find the dosage level of dexamethasone that effectively would suppress the acute inflammatory reaction and the second to show how effective the dexamethasone delivered by PLGA microspheres was in suppressing chronic inflammatory response to an implant. The first in vivo study showed that 0.1 to 0.8 mg of dexamethasone at the site minimized the acute inflammatory reaction. The second in vivo study showed that our mixed microsphere system suppressed the inflammatory response to an implanted suture for at least 1 month. This study has proven the viability of microsphere delivery of an anti-inflammatory to control the inflammatory reaction at an implant site.


Barriers and facilitators in health education for adults with intellectual disabilities--a qualitative study.
The aim of this study was to explore barriers and facilitators in the implementation of a health course for adults with mild or moderate intellectual disabilities. An inductive qualitative design was used. Data were collected from a health course conducted in 16 study groups with 83 participants in Stockholm, Sweden by unstructured observations in course sessions, a group discussion with course leaders and evaluation notes from the course leaders. The data were analysed by qualitative content analysis. Four categories were identified: (i) 'individual characteristics', implying various needs, (ii) 'pedagogical strategies' used to meet those needs, (iii) 'interaction within the course', dealing with active and less active participation and (iv) 'structures', including learning climate and organizing. The overarching theme 'creating an individualized supportive context' describes the challenge of educating people with intellectual disabilities towards an empowered and well informed decision making regarding their own health. Therefore, there is a need for support not only within the course but also from the social and physical environment as well.


Comprehensively characterizing ophthalmic freeform lenses with contour plots and astigmatic axis.
An accurate evaluation method is proposed for comprehensively characterizing ophthalmic freeform lenses (OFLs) by computing the curvatures of the freeform surface at an arbitrary direction in the transformed Cartesian coordinates based on space analytic geometry. The proposed method could especially produce the astigmatic axis, which is an indispensable characteristic of OFLs. An OFL designed with an analytical formula is characterized by our comprehensive method, not only with power and astigmatism contour plots that are consistent with the results from the conventional method, but also with the astigmatic axis, which can be analytically confirmed by combining a conventional quadratic equation with directional derivatives. Benefiting from the astigmatic axis, the comprehensive method could produce the combined astigmatism of both surfaces for double OFLs, which is not possible with the conventional method. The evaluation results of a double OFL are also presented and can be experimentally verified by fabrication and measurement. This might provide a new idea and a more comprehensive methodology for evaluatiing OFLs with high precision.


Expression of the RON receptor tyrosine kinase and its association with gastric carcinoma versus normal gastric tissues.
Recepteur d'origine nantais (RON) is a receptor tyrosine kinase that is activated by a serum-derived, macrophage stimulating protein (MSP) growth factor and is expressed in many malignant tumors. The aim of the present study was to reveal the protein expression profile of RON and its relationship with clinicopathological characteristics of gastric carcinoma and prognosis. Gastric carcinoma tissue from 98 patients, along with 29 specimens of paraneoplastic tissue and 10 specimens of normal gastric mucosa, were examined by immunohistochemistry (IHC). Western blot analysis of 19 samples of gastric carcinoma tissue and corresponding paraneoplastic tissue, 8 specimens of normal gastric mucosa, and 2 specimens of normal lymph node samples also detected expression of a splice variant of RON, RONDelta165. All samples obtained were accompanied by patient follow-up data that ranged from 3 to 89 months (median time: 22 months). The rate of positive RON expression differed significantly between gastric carcinoma tissues [56.1%, (55/98)] and paraneoplastic tissues [25.6%, (8/29)] (p = 0.007). In contrast, RON expression was absent in normal gastric mucosa samples. RON expression positively correlated with the invasive depth of the tumor (p = 0.019), perigastric lymph nodes metastasis (p = 0.019), and TNM stage (p = 0.001). However, RON expression was independent of tumor growth pattern according to Bormann criteria (p = 0.209), histopathological grade (p = 0.196), and incidence of distant metastasis (p = 0.400). RON expression was not related to a patient's survival rate (p = 0.195). RONDelta165 was strongly expressed in fresh gastric carcinoma tissue, corresponding paraneoplastic tissue, and perigastric lymph nodes with metastatic carcinoma. In contrast, expression of RONDelta165 was not observed in normal gastric mucosa and normal lymph node tissue samples. RON expression is significant in gastric carcinoma tissue and corresponding paraneoplastic tissue, but is not expressed in normal gastric mucosa. Expression of RONDelta165 was similarly observed in gastric carcinoma tissue and in metastases present in lymph node tissues. We hypothesize that RON and its splice variant play an important role in the occurrence, progression, and metastasis of gastric carcinoma, and therefore may represent a useful marker to evaluate the biological activity of gastric carcinoma.


(57)Fe ENDOR spectroscopy on the iron-sulfur cluster involved in substrate reduction of heterodisulfide reductase.
Heterodisulfide reductase (Hdr) from methanogenic archea is an iron-sulfur protein that catalyzes the reversible two-electron reduction of the mixed disulfide CoM-S-S-CoB to the thiol coenzymes, coenzyme M (CoM-SH) and coenzyme B (CoB-SH). It is unusual that this enzyme uses an iron-sulfur cluster to mediate disulfide reduction in two one-electron steps via site-specific cluster chemistry. Upon half-reaction of the oxidized enzyme with CoM-SH in the absence of CoB-SH, an iron-based paramagnetic intermediate is formed, designated CoM-Hdr. In this Communication we report 57Fe pulsed ENDOR at two very different frequencies, 9 and 94 GHz, that identify the iron sites of CoM-Hdr. We find direct evidence for a [4Fe-4S]3+ cluster, and we determine the sign of the 57Fe hyperfine couplings. The 57Fe isotropic hfc values suggest a complex interaction between the cluster and the CoM-SH substrate.


A Study of the Therapeutic Effects of Resveratrol on Blunt Chest Trauma-Induced Acute Lung Injury in Rats and the Potential Role of Endocan as a Biomarker of Inflammation.
The present study focused on the therapeutic effects of resveratrol in a rat model of blunt chest trauma-induced acute lung injury and the potential role of endocan as a biomarker of inflammation. They were randomly divided into the following four groups (n = 7 in each group): control group (no treatment or trauma); trauma group (trauma-induced group); resveratrol group (resveratrol [0.3 mg/kg] administered via the i.p. route group); and resveratrol + trauma group (resveratrol [0.3 mg/kg] administered via the i.p. route 1 h prior to the induction of trauma At the end of the 24 h, all the experimental rats were sacrificed. Lung lobe and blood samples were collected for biochemical, histopathological, and immunohistochemical investigations. Serum endocan levels were found to be significantly higher in the travma, resveratrol, and resveratrol + trauma groups than in the control group (p < 0.001, p < 0.001, p < 0.001). Moreover, in resveratrol + trauma group, endocan showed a significant increase compared to trauma and resveratrol group (p < 0.001, p < 0.001). Serum MDA level was significantly higher in the trauma group than in the control group (p = 0.017). SOD showed a significant increase in resveratrol and resveratrol + trauma groups compared to control group (p < 0.001, p < 0.001). The present study suggested that resveratrol exerted antioxidant properties in a rat model of lung injury after blunt chest trauma. Thus, it may have therapeutic potential in cases of blunt chest trauma-induced lung injury. Serum levels of endocan were not correlated with the inflammation response. The clinical use of endocan as a biomarker of inflammation in lung injury caused by blunt chest trauma is not recommended.


Multi-System Physical Exercise Intervention for Fall Prevention and Quality of Life in Pre-Frail Older Adults: A Randomized Controlled Trial.
Effective interventions for indicated fall prevention are necessary for older adults with frailty. We aimed to determine the effectiveness of a Multi-system Physical Exercise (MPE) for fall prevention and Health-Related Quality of Life (HRQOL) in pre-frail older adults. This randomized control trial with allocation concealment included 72 adults aged 65 and above, identified as pre-frailty and with mild and moderate fall risk scores measured by the Physiological Profile Assessment (PPA). Randomly, using block randomization, participants were divided into two groups: an MPE group (n = 36) and a control group (n = 36). The intervention consisted mainly of proprioception, muscle strengthening, reaction time, and balance training and was carried out three days per week for 12 weeks. The primary outcome was fall risk assessed using PPA at 12 weeks post-baseline and at a 24 week follow-up. Significant differences were found in the improvement in fall risk, proprioception, muscle strength, reaction time and postural sway, and fear of fall scores in the MPE group compared with controls at week 12 and 24. In addition, HRQOL had increased significantly in the MPE group in comparison to controls. The MPE program significantly increased muscle strength and improved proprioception, reaction time, and postural sway leading to fall risk reduction in older adults with pre-frailty. Therefore, the MPE program is recommended for used in day-to-day primary care practice in the pre-frail population.


Rational polypharmacy in schizophrenia.
Approximately 10 to 30% of patients with schizophrenia show poor response to neuroleptics alone. An initial evaluative and treatment approach to these patients is outlined, and the literature on adjunctive treatments, which seek to augment neuroleptic effects, is reviewed. The greatest evidence for efficacy has been shown for lithium, benzodiazepines, carbamazepine, reserpine, and electroconvulsive therapy, although individual patients may also respond to propranolol, clonidine, valproic acid, and L-dopa. Antidepressants may also be useful for treating comorbid depression in nonacutely psychotic patients. One general theme is that no one adjunctive treatment benefits all patients; indeed, only a minority of patients responds to any given agent. Therefore, the choice of specific treatments is best guided by the clinical characteristics of the individual patient. These observations raise the possibility that subgroups of schizophrenia exist; delineation of differences in clinical response to biochemically distinct agents may help elucidate such underlying differences between patient groups.


Factors affecting ability of TB patients to follow treatment guidelines - applying a capability approach.
Negotiating anti-Tuberculosis treatment is a complicated process comprising daily consumption of multiple medications at stipulated times and dosages, as well as periodic follow-ups and investigations, may not be uniform for all Tuberculosis (TB) patients and some may perform better than others. In this context, we conducted a study in Thiruvananthapuram district, Kerala to ascertain the ability of those suffering from TB to follow treatment guidelines. This study used an embedded mixed methods design. We collected cross-sectional data from 135 drug sensitive pulmonary TB patients aged 18 years or above in Thiruvananthapuram, Kerala using a structured questionnaire to get the proportion of patients following all treatment guidelines. We also did eight in-depth interviews (four men and four women) from within the survey sample. The in-depth interviews were inductively analysed for getting deeper insights about reasons for the choices people made regarding the treatment guidelines. Written informed consent was taken from all participants and the study was implemented after the necessary programmatic and ethical clearances. Of the 105 men and 30 women studied, uninterrupted daily drug consumption was reported by 80 persons (59.3%, 95% Confidence Intervals (CI) 50.8-67.2%). Overall, 38 (28.2%, 95% CI 21.3%-36.3%) persons were able to follow all seven aspects of advised guidelines. Living in an extended/ joint family (Adjusted Odds ratio (AOR) 2.6, 95% CI 1.1-6.0), approximate monthly household expenditure of over rupees 13,500 (AOR 2.9, 95% CI 1.3-6.7) and no perceived delay in seeking initial care (AOR 3.2, 95% CI 1.2-8.7) were significantly associated with following all aspects of treatment guidelines. In-depth interviews revealed reflective treatment related behaviours were influenced by bodily experiences, moral perceptions, social construct of TB, programmatic factors and substance use. Sometimes behaviours were non-reflective also. Programmatic stress was on individual agency for changing behaviour but capability and opportunity for these were influenced social aspects like stigma, gender roles and poverty. TB patients live amidst a syndemic of biomedical and social problems. These problems influence the capabilities and opportunities of such TB patients to follow treatment guidelines. Interventions should balance focus on individual agency and social abd economic factors.


Jasmonic acid methyl ester induces the synthesis of a cytoplasmic/nuclear chito-oligosaccharide binding lectin in tobacco leaves.
In contrast to animal lectins, no evidence has indicated the occurrence of plant lectins, which recognize and bind "endogenous" receptors and accordingly are involved in recognition mechanisms within the organism itself. Here we show that the plant hormone jasmonic acid methyl ester (JAME) induces in leaves of Nicotiana tabacum (var. Samsun NN) the expression of a lectin that is absent from untreated plants. The lectin specifically binds to oligomers of N-acetylglucosamine and is detected exclusively in the cytoplasm and the nucleus. Both the subcellular location and specificity indicate that the Nicotiana tabacum agglutinin (called Nictaba) may be involved in the regulation of gene expression in stressed plants through specific protein-carbohydrate interactions with regulatory cytoplasmic/nuclear glycoproteins. Searches in the databases revealed that many flowering plants contain sequences encoding putative homologues of the tobacco lectin, which suggest that Nictaba is the prototype of a widespread or possibly ubiquitous family of lectins with a specific endogenous role.


Effects of supplemental manganese on performance of growing-finishing pigs and pork quality during retail display.
Crossbred barrows and gilts (n = 168) were used to test the effects of supplemental Mn during the growing-finishing period on performance, pork carcass characteristics, and pork quality during 7 d of retail display. Pigs were blocked by BW and allotted within blocks to pens (5 pigs/pen in blocks 1, 2, 5, and 6, and 4 pigs/pen in blocks 3 and 4). A total of 36 pens was randomly assigned to 1 of 6 dietary treatments, where the basal diets were formulated with (PC) or without (NC) Mn in the mineral premix, and supplemented with 0 or 350 ppm (as-fed basis) of Mn from MnSO4 or a Mn-AA complex (AvMn). Pigs were slaughtered at a commercial pork packing plant when the lightest block of pigs averaged 113.6 kg. During fabrication, boneless pork loins were collected and transported to Oklahoma State University, where 2.5-cm-thick LM chops were packaged in a modified atmosphere (80% O2 and 20% CO2) and subsequently placed in display cases (2 to 4 degrees C) under continuous fluorescent lighting (1,600 lx) for 7 d. Pig performance was not (P > or = 0.44) affected by supplemental Mn; however, during the grower-II phase, pigs fed the basal diets including Mn consumed less (P < 0.02) feed and tended to be more efficient (P < 0.09) than pigs fed the basal diets devoid of Mn. Throughout the entire feeding trial, neither dietary nor supplemental Mn altered (P > or = 0.22) ADG, ADFI, or G:F. Chops from pigs fed the diets supplemented with MnSO4 received greater (P < or = 0.05) lean color scores and had a redder (greater a* and hue angle values), more vivid color than chops from pigs fed the diets supplemented with AvMn. Additionally, LM chops from pigs fed the PC diets supplemented with MnSO4 were darker (lower L* values; P < 0.05) than chops from pigs fed the NC diets or PC diets supplemented with 0 or 350 ppm of AvMn. Even though discoloration scores were similar during the first 4 d of display, chops from pigs fed the PC diets supplemented with MnSO4 were less (P < 0.05) discolored on d 6 and 7 of retail display than chops from pigs fed the PC or NC diets and diets supplemented with AvMn (dietary treatment x display time, P = 0.04). Results of this study indicate that feeding an additional 350 ppm of Mn from MnSO4 above the maintenance requirements of growing-finishing pigs does not beneficially affect live pig performance but may improve pork color and delay discoloration of pork during retail display.


Silkworm (Bombyx mori) hemocytes do not produce reactive oxygen metabolites as a part of defense mechanisms.
To investigate whether hemocytes of Bombyx mori (Lepidoptera) larvae produce reactive oxygen species (ROS) as part of the oxidative killing of invading pathogens, the production of ROS was measured as a luminol- and lucigenin-enhanced chemiluminescence of unstimulated or stimulated (zymosan particles, phorbol myristate acetate, calcium ionophore, rice starch or Xenorhabdus nematophila) hemolymph. No detectable ROS production was found. The spontaneous and activated ROS production measured with hemocytes, i.e. under the conditions when the antioxidative potential of hemolymph plasma was eliminated, was again undetectable. Likewise, ROS production by isolated hemocytes was observed by spectrophotometric (NBT test, cytochrome c assay) and fluorimetric (using dihydrorhodamine and hydroethidine probes) methods. Hence none of the experimental approaches used indicated the production of ROS by hemocytes of B. mori larvae as part of their immune response.


Determination of tamoxifen and endoxifen in dried blood spots using LC-MS/MS and the effect of coated DBS cards on recovery and matrix effects.
We developed an HPLC-MS/MS method to quantify tamoxifen (2.5-250 ng/ml) and its metabolite (Z)-endoxifen (0.5-50 ng/ml) in dried blood spots. Extraction recovery of both analytes from Whatman DMPK-A cards was 100% and consistent over time, however, recovery of (Z)-endoxifen from Whatman 903 cards was incomplete and increased upon storage. When SDS, a constituent of the DMPK-A coating, was present during the extraction, recovery improved. The method using DMPK-A cards was validated using bioanalytical guidelines. Additionally, influence of haematocrit (0.29-0.48 L/L), spot volume (20-50 µl) and homogeneity was within limits and both analytes were stable in DBS for at least 4 months. The method for the quantification of tamoxifen and (Z)-endoxifen in DBS collected on DMPK-A cards was successfully validated.


Proteus syndrome: a case report with bone scintigraphy findings.
Proteus syndrome is an extremely rare genetic disorder characterized by an asymmetrical overgrowth of skin, bones, muscles, fatty tissues, and blood and lymphatic vessels. We present a case of a six-year-old boy with proteus syndrome who underwent bone scintigraphy for suspected osteomyelitis. Bone scintigraphy ruled out osteomyelitis and suggested cellulitis. In addition, it demonstrated striking characteristic deformities, which need to be emphasized. Knowledge of these findings will avoid misinterpretation of bone scintigraphy in patients with proteus syndrome.


Biology of Incidental Catch Sea Star Stellaster childreni Gray, 1840 (Echinodermata: Asteroidea), from Malaysian Borneo Exclusive Economic Zone.
Sea star (class Asteroidea, phylum Echinodermata) is one of the most successful marine organisms inhabiting a wide range of habitats. As one of the key stone species, sea stars are responsible for maintaining much of the local diversity of species within certain communities. Malaysian Exclusive Economic Zone (EEZ) Resource Survey had been carried out from 16th Aug to 6th Nov 2015 and one of the invertebrate by-catch organisms is sea star Stellaster childreni Gray, 1840. This study documents morphological characters and diet of the sea star, besides providing brief descriptions of the habitats based on particle size analysis and vessel log data sheet. A total of 217 individuals had been examined throughout this study. Fragments of flora and fauna were found in the gut including Mollusca (gastropod, bivalves, and scaphopods), sponge seagrass, and seaweed as well as benthic Foraminifera. Stellaster childreni were found at depth of 45 m to 185 m in the South China Sea off Sarawak Malaysia, with various sea bottom substrata. Approximately 41% of S. childreni were found at a mixture of sandy and muddy substratum, followed by mixture of sandy and coral (19.3%), muddy substratum (17.5%), coral substratum (11.5%), and sandy areas (10.6%). The widely distributed sea star on different types of sea beds suggested healthy deep sea ecosystem; thus Malaysia should explore further potential fisheries resources in the EEZ off Sarawak coast.


Creating calm amid confrontation.
In my first year of training, I had a placement on a challenging behaviours unit for people with a learning disability. One night shift at about 11.30pm a service user, who I will call Charlotte, became physically and verbally aggressive towards staff members. This was due to an incident earlier in the day with another service user.


Predictive model of weapon carrying among urban high school students: results and validation.
The purpose of this study was to identify the behavioral, psychosocial, and demographic predictors of self-reported weapon carrying among secondary school students who attend urban public schools. Self-reported weapon carrying was measured in a schoolwide anonymous health survey conducted in two demographically comparable high schools in 1992, in Boston, Massachusetts. Indicators of self-perception, depression, stressful life events, and adolescent risk behaviors of substance use and sexual behavior, along with self-reported weapon carrying, were measured. The students in both schools were racially heterogeneous, with the majority of about 80% from black or Hispanic backgrounds. A predictive model was developed using a forward stepwise logistic regression model in one inner-city high school, and tested in a second high school. Self-reported lifetime weapon carrying was 32% overall. The major predictors of weapon carrying among urban secondary school students are a combination of demographic, psychosocial, behavioral, and school-related factors. This analysis indicates consistency in eight markers predictive of weapon carrying: lower age, male gender, regular marijuana use, sexual experience, having witnessed a crime, having skipped school, suicidal ideation, and having hit or "beat up" someone. Race parental education, and family composition were not significant predictors. Significant predictors of weapon carrying were marijuana use and sexual experience, each of which was consistently high in both schools. The model-building and validation presented in this study provide empirical evidence for three important conclusions. First, weapon carrying is associated with multiple and interrelated factors which include demographic, psychosocial, behavioral, and school-related characteristics of high school-age adolescents. Second, students with more risk factors are more likely to carry a weapon, suggesting that the variables are independent markers. Third, this study identified marijuana use and being sexually experienced as both highly predictive of weapon carrying. Implications of this study for prevention point to the need for comprehensive multidisciplinary services in high school that include mental health counseling as well as health education efforts aimed at behavior change.


Utilization of electromyography during selective obturator neurotomy to treat spastic cerebral palsy accompanied by scissors gait.
Selective obturator neurotomy is a commonly used neurosurgical intervention for spastic cerebral palsy with scissors gait. Here we report the use of surface electromyography to assess the accuracy and effect of selective obturator neurotomy procedures. Selective obturator neurotomy was carried out on 18 patients while using intraoperative electromyography. Contractions of adductor muscles were recorded by electromyography before and after neurotomy and assessed using root mean square and integrated electromyography tests. Passive and voluntary movements were recorded for all patients. Our results show that adductor spasms and adductive deformity of hip were improved in all patients with spastic cerebral palsy. Adductor muscle spatiality was improved significantly, confirmed by a significant decrease in the values of root mean square and integrated electromyography in both passive and voluntary movements after surgery. We show that electromyography is an effective tool for accurately and safely targeting nerve tracts during selective obturator neurotomy. Thus, we demonstrate a valuable noninvasive method to objectively evaluate the effect of treatment in spastic cerebral palsy patients.


Self-propagating, protease-resistant, recombinant prion protein conformers with or without in vivo pathogenicity.
Prions, characterized by self-propagating protease-resistant prion protein (PrP) conformations, are agents causing prion disease. Recent studies generated several such self-propagating protease-resistant recombinant PrP (rPrP-res) conformers. While some cause prion disease, others fail to induce any pathology. Here we showed that although distinctly different, the pathogenic and non-pathogenic rPrP-res conformers were similarly recognized by a group of conformational antibodies against prions and shared a similar guanidine hydrochloride denaturation profile, suggesting a similar overall architecture. Interestingly, two independently generated non-pathogenic rPrP-res were almost identical, indicating that the particular rPrP-res resulted from cofactor-guided PrP misfolding, rather than stochastic PrP aggregation. Consistent with the notion that cofactors influence rPrP-res conformation, the propagation of all rPrP-res formed with phosphatidylglycerol/RNA was cofactor-dependent, which is different from rPrP-res generated with a single cofactor, phosphatidylethanolamine. Unexpectedly, despite the dramatic difference in disease-causing capability, RT-QuIC assays detected large increases in seeding activity in both pathogenic and non-pathogenic rPrP-res inoculated mice, indicating that the non-pathogenic rPrP-res is not completely inert in vivo. Together, our study supported a role of cofactors in guiding PrP misfolding, indicated that relatively small structural features determine rPrP-res' pathogenicity, and revealed that the in vivo seeding ability of rPrP-res does not necessarily result in pathogenicity.


Prevalence and Mechanisms of Carbapenem Resistance in Klebsiella pneumoniae and Escherichia coli: A Systematic Review and Meta-Analysis of Cross-Sectional Studies from Iran.
Introduction: Carbapenem-resistant Enterobacteriaceae (CRE) represents an urgent threat worldwide. We aimed to investigate the frequency of carbapenem-resistant Klebsiella pneumoniae and Escherichia coli in Iran. Materials and Methods: PubMed/Medline, Embase, Scopus, Web of Sciences, and Iranian databases were searched to find potentially relevant articles. Statistical analyses were performed using STATA version 14. Results: Forty-nine studies fulfilled the inclusion criteria. The pooled rates of resistance to carbapenem in K. pneumoniae and E. coli were 24.0% (95% confidence interval [CI] 18.0-31.0) and 5.0% (95% CI 2.0-8.0), respectively. blaOXA-48 gene was the most common cause of carbapenem resistance in K. pneumoniae and E. coli. Conclusions: CRE is prevalent in Iran, which confers the importance of strength prevention and control measures.


Centrally mediated antihyperalgesic and antiallodynic effects of zonisamide following partial nerve injury in the mouse.
Some antiepileptic drugs are used clinically to relieve neuropathic pain. We have evaluated the effects and investigated the possible mechanisms of action of zonisamide, an antiepileptic drug, on thermal hyperalgesia and tactile allodynia in a murine chronic pain model that was prepared by partial ligation of the sciatic nerve. Subcutaneously administered zonisamide (10 and 30 mg/kg) produced antihyperalgesic and antiallodynic effects in a dose-dependent manner; these effects were manifested by elevation of the withdrawal threshold in response to a thermal (plantar test) or mechanical (von Frey) stimulus, respectively. Similar analgesic effects were obtained in both the plantar and von Frey tests when zonisamide was injected either intracerebroventricularly (i.c.v., 10 and 30 microg) or intrathecally (i.t., 10 and 30 microg). It is thought that this elevation of the thermal and mechanical withdrawal thresholds after local injection of zonisamide is not generated secondarily via impaired motor activity, since zonisamide (30 microg, i.c.v. or i.t.) did not affect locomotor activity, as assessed in sciatic-nerve-ligated mice. Moreover, the nitric oxide synthase inhibitor L-NAME, when injected either i.c.v. or i.t., potentiated the analgesic effects of zonisamide. In contrast, neither i.c.v. nor i.t. zonisamide produced antinociceptive effects against acute thermal and mechanical nociception in non-ligated mice. Together, following peripheral nerve injury, it appears that zonisamide produces centrally mediated antihyperalgesic and antiallodynic effects partly via the blockade of nitric oxide synthesis.


Development of advanced biantibiotic loaded bone cement spacers for arthroplasty associated infections.
The incidence increase of infections in patients with hip or knee implants with resistant pathogens (mainly some S. coagulase-negative and gram positive bacteria) demands advanced antibiotic loaded formulations. In this paper, we report the design of new biantibiotic acrylic bone cements for in situ delivery. They include a last generation antibiotic (daptomycin or linezolid) in combination with vancomycin and are performed based on a novel modification of the Palacos R® acrylic bone cement, which is based on two components, a liquid (methyl methacrylate) and a solid (polymeric phase). Hence, the solid component of the experimental formulations include 45wt% of microparticles of poly(D,L-lactic-co-glycolic) acid, 55wt% of poly(methyl methacrylate) beads and supplements (10wt-% each) of antibiotics. These formulations provide a selective and excellent control of the local release of antibiotics during a long time period (up to 2 months), avoiding systemic dissemination. The antimicrobial activity of the advanced spacers tested against S. aureus shows that single doses would be enough for the control of the infection. In vitro biocompatibility of cements on human osteoblasts is ensured. This paper is mainly focused on the preparation and characterization of cements and the studies of elution kinetics and bactericidal effects. Developed formulations are proposed as spacers for the treatment of infected arthroplasties, but also, they could be applied in other antibiotic devices to treat relevant bone-related infection diseases.


[Long-term efficacy of high-dose aerosol corticotherapy in the treatment of severe asthma].
Forty-five patients with severe, poorly controlled asthma, including 23 corticosteroid-dependent patients, were treated with a preparation of beclomethasone dipropionate aerosol delivering 250 mcg per puff. The daily dose ranged from 1000 to 2000 mcg. The mean follow-up period was 14 +/- 7 months, and 11 patients have now been followed up for more than 2 years. Forty-two patients were improved, and total withdrawal of continuous steroid therapy could be achieved in 13 cases. Treatment remained effective in long term use, provided a minimum of 1000 mcg/day was given. However, despite clinical improvement the obstructive syndrome persisted in 65% of the patients.


Providing written information increases patient satisfaction: a web-based questionnaire survey of Japanese cancer survivors.
The Institute of Medicine (IOM) of the United States recommends that all cancer survivors be provided with a survivorship care plan (SCP), which includes a patient treatment summary and a follow-up care plan. However, SCPs have not been widely adopted in Japan. To provide basic data necessary for implementing SCPs in Japan, we aimed to investigate the forms of clinical and survivorship-related information that Japanese cancer survivors receive from their healthcare providers, and to examine whether written information increases their satisfaction. We performed a cross-sectional online survey of cancer survivors who underwent acute cancer treatment and had at least one follow-up with a physician in the past year. Cancer survivors provided the elements and forms (verbally and/or written) of information they received, as well as the degree of satisfaction with the information provided. Responses were obtained from 545 cancer survivors. Information elements such as surgical procedure (98.3%), surgical outcome (98.1%), and names of administered chemotherapy agents (97.8%) were commonly provided, whereas mental care resources and providers (29.7%), effects on marital relationship and sexual health (35.7%), and effects on fertility (43.4%) were less common. A large proportion of cancer survivors received verbal information only. For 18 of 20 elements, except for effects on fertility and duration of hormonal therapy, satisfaction was significantly higher when both forms of information were provided (P < 0.05). Providing written and verbal explanations of clinical and survivorship-related information can better meet the needs of Japanese cancer survivors.


SUMO targets the APC/C to regulate transition from metaphase to anaphase.
Signal transduction by small ubiquitin-like modifier (SUMO) regulates a myriad of nuclear processes. Here we report on the role of SUMO in mitosis in human cell lines. Knocking down the SUMO conjugation machinery results in a delay in mitosis and defects in mitotic chromosome separation. Searching for relevant SUMOylated proteins in mitosis, we identify the anaphase-promoting complex/cyclosome (APC/C), a master regulator of metaphase to anaphase transition. The APC4 subunit is the major SUMO target in the complex, containing SUMO acceptor lysines at positions 772 and 798. SUMOylation is crucial for accurate progression of cells through mitosis and increases APC/C ubiquitylation activity toward a subset of its targets, including the newly identified target KIF18B. Combined, our findings demonstrate the importance of SUMO signal transduction for genome integrity during mitotic progression and reveal how SUMO and ubiquitin cooperate to drive mitosis.


Impact of time interval between radical hysterectomy with pelvic node dissection and initial adjuvant therapy on oncological outcomes of early stage cervical cancer.
To determine the impact of time interval (TI) from radical hysterectomy with pelvic node dissection (RHND) to adjuvant therapy on oncological outcomes in cervical cancer. The study included 110 stage IA2-IB1 cervical cancer patients who underwent RHND and adjuvant therapy. The patients were divided into 2 groups based on the cut-off points of TI of 4 and 6 weeks, respectively. The associations of TI and clinicopathologic factors with oncological outcomes were evaluated using Cox proportional-hazards regression. The median TI was 4.5 weeks. There were no statistical differences in 5-year recurrence-free survival (RFS) (89.2% vs. 81.0%, and 83.2% vs. 100.0%) or 5-year overall survival (OS) rates (90.9% vs. 97.2%, and 93.2% vs. 100.0%) between patients according to TI (≤4 vs. >4, and ≤6 vs. >6 weeks, respectively). Deep stromal invasion (p=0.037), and parametrial involvement (PI) (p=0.002) were identified as independent prognostic factors for RFS, together with the interaction between TI and squamous cell carcinoma histology (p<0.001). In patients with squamous cell carcinoma, a TI longer than 4 weeks was significantly associated with a worse RFS (hazard ratio [HR]=15.8; 95% confidence interval [CI]=1.4-173.9; p=0.024). Univariate analysis showed that only tumor size (p=0.023), and PI (p=0.003) were significantly associated with OS. Delay in administering adjuvant therapy more than 4 weeks after RHND in early stage squamous cell cervical cancer results in poorer RFS.


Social Support, Activities of Daily Living, and Depression among Older Japanese and Koreans Immigrants in the U.S.
This study investigates the relationship between social support, activities of daily living (ADL), and depression among older Japanese and Koreans living in the U.S. Data were collected from 207 older Japanese and 210 older Koreans in various long-term care settings in Honolulu and Los Angeles. A hierarchical regression analysis indicated that social support was a significant factor of depressive symptoms in both groups and ADL was significantly associated with depressive symptoms among older Japanese. Based on our findings, we recommend means for social workers to address depression among older Japanese and Korean immigrants by improving social support and ADL.


Volatile anesthetic agents inhibit choline uptake into rat synaptosomes.
Acetylcholine is an excitatory neurotransmitter associated with the maintenance of consciousness. Choline uptake is the rate-limiting step in acetylcholine synthesis and may be a target for the action of volatile anesthetic agents. [Methyl-3H]choline uptake was investigated using rat cortical synaptosomes. The preparation was exposed to air, as control, or equipotent partial pressures (2.4 rat MAC) of enflurane, halothane or isoflurane. In addition, the dose-response relation for halothane on [methyl-3H]choline uptake was studied. The maximum rate of uptake was reduced significantly by 24% in the presence of enflurane (5.5%, 2.4 rat MAC) and isoflurane (3.5%, 2.4 rat MAC) and by 38% in the presence of halothane (3%, 2.4 rat MAC) with no change in Michaelis constant in the presence of each agent. A linear relation between the inhibition of [methyl-3H]choline uptake and the concentration of halothane was observed up to 3% halothane above which there was no further inhibition. The concentration of halothane resulting in half-maximum inhibition of total choline uptake was 1.5%. Noncompetitive inhibition of [methyl-3H]choline uptake by volatile anesthetic agents has been demonstrated in the in vitro synaptosome preparation. If present in vivo reduction in anesthetic-sensitive choline uptake may reduce the presynaptic availability of acetylcholine and hence contribute to the process of anesthesia.


Pollution characteristics of surface runoff under different restoration types in manganese tailing wasteland.
A great deal of manganese and associated heavy metals (such as Ni, Cu, Zn, Cd, Pb, etc.) was produced in manganese mining, smelting, and other processes and weathering and leaching of waste slag, which entered rainwater runoff by different means under the action of rainfall runoff. It caused heavy metal pollution in water environment to surrounding areas, and then environmental and human health risks were becoming increasingly serious. In the Xiangtan manganese mine, we studied the characteristics of nutritional pollutants and heavy metals by using the method of bounded runoff plots on the manganese tailing wasteland after carrying out some site treatments using three different approaches, such as (1) exposed tailings, the control treatment (ET), (2) external-soil amelioration and colonization of Cynodon dactylon (Linn.) Pers. turf (EC), and (3) external-soil amelioration and seedling seeding propagation of Cynodon dactylon (Linn.) Pers. (ES). The research showed that the maximum runoff occurred in 20,140,712 rainfall events, and the basic law of runoff was EC area > ET area > ES area in the same rainfall event. The concentration of total suspended solids (TSS) and chemical oxygen demand (COD) of three ecological restoration areas adopted the following rule: ET area > EC area > ES area. Nitrogen (N) existed mainly in the form of water soluble while phosphorus (P) was particulate. The highest concentrations of total nitrogen (TN) and total phosphorus (TP) were 11.57 ± 2.99 mg/L in the EC area and 1.42 ± 0.56 mg/L in the ET area, respectively. Cr, Ni, Pb, Zn, Mn, and Cu in surface runoff from three restoration types all exceeded the class V level of the environmental quality standard for surface water except Cu in EC and ES areas. Pollution levels of heavy metals in surface runoff from three restoration areas are shown as follows: ET area > EC area > ES area. There was a significant positive correlation between TSS and runoff, COD, and TP. And this correlation was significant between total dissolved nitrogen (TDN), TN, total dissolved phosphorus (TDP), and TP. The six heavy metals (Cu, Ni, Pb, Zn, Mn, and Cr) in surface runoff of different ecological restoration areas were strongly related to each other, and were significantly related to the TSS.


X-ray linear birefringence and linear dichroism in a cobalt crystal measured with a tunable X-ray polarimeter.
X-ray linear birefringence and linear dichroism spectra have been measured simultaneously and quantitatively for the first time. The sample was a hexagonal cobalt single-crystal foil. The apparatus used was an energy-tunable X-ray polarimeter, consisting of a polarizer, a phase retarder and an analyser. The X-ray energy was scanned over a range of 350 eV near the K-absorption edge. The Kramers-Kronig relation between the refraction and absorption anisotropy has been confirmed on an absolute scale. The phase-difference sensitivity of the polarimeter as a polarization inferometer is as small as 2pi/10000, which is about 100 times smaller than that of the Bonse-Hart inferometer.


Towards evidence-based emergency medicine: best BETs from the Manchester Royal Infirmary. Use of aspirin in acute stroke.
A short-cut review was carried out to establish whether the administration of aspirin before computed tomography scanning improved outcome in patients with symptoms suggestive of stroke. In all, 866 papers were found using the reported searches, two of which presented the best evidence to answer the clinical question. The author group, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of these best papers are tabulated. If a computed tomography scan is to be carried out within 48 h of onset of symptoms, then it is prudent to await the result before starting aspirin.


Materials science. Dynamic mechanical behavior of multilayer graphene via supersonic projectile penetration.
Multilayer graphene is an exceptional anisotropic material due to its layered structure composed of two-dimensional carbon lattices. Although the intrinsic mechanical properties of graphene have been investigated at quasi-static conditions, its behavior under extreme dynamic conditions has not yet been studied. We report the high-strain-rate behavior of multilayer graphene over a range of thicknesses from 10 to 100 nanometers by using miniaturized ballistic tests. Tensile stretching of the membrane into a cone shape is followed by initiation of radial cracks that approximately follow crystallographic directions and extend outward well beyond the impact area. The specific penetration energy for multilayer graphene is ~10 times more than literature values for macroscopic steel sheets at 600 meters per second.