Low-temperature recovery strategies for the isolation of bacteria from ancient permafrost sediments.
Permafrost represents a unique ecosystem that has allowed the prolonged survival of certain bacterial lineages at subzero temperatures. To better understand the permafrost microbial community, it is important to identify isolation protocols that optimize the recovery of genetically diverse bacterial lineages. We have investigated the impact of different low-temperature isolation protocols on recovery of aerobic bacteria from northeast Siberian permafrost of variable geologic origin and frozen for 5000 to 3 million years. Low-nutrient media enhanced the quantitative recovery of bacteria, whereas the isolation of diverse morphotypes was maximized on rich media. Cold enrichments done directly in natural, undisturbed permafrost led not only to recovery of increased numbers of bacteria but also to isolation of genotypes not recovered by means of liquid low-temperature enrichments. On the other hand, direct plating and growth at 4 degrees C also led to recovery of diverse genotypes, some of which were not recovered following enrichment. Strains recovered from different permafrost samples were predominantly oligotrophic and non-spore-forming but were otherwise variable from each other in terms of a number of bacteriological characteristics. Our data suggest that a combination of isolation protocols from different permafrost samples should be used to establish a culture-based survey of the different bacterial lineages in permafrost.


[Reproducibility in induced sputum in children with asthma].
In asthmatic children sputum-induction with hypertonic saline is useful to quantify the eosinophilic inflammation. However, only few data are available about feasibility and safety of the procedure in children. Therefore, taking 9 non-atopic healthy control children (mean age 11.8 years) and 34 asthmatic children (mean age 11.4 years), inhaling n = 25 Budesonid (400-1200 micrograms/die) and n = 9 DNCG (60 mg/die), sputum induction was performed twice within 6 weeks. Briefly, 10 minutes after inhalation of 200 micrograms salbutamol subjects inhaled hypertonic saline (3, 4 and 5%) for in all 30 minutes, while all 5 minutes lung function was checked and expectoration of sputum was supported. Adequate sputum plugs were separated from contaminating saliva and processed immediately employing native chamber and cytospin cell count as well as measurement of eosinophilic cationic protein (ECP). Sputum-induction could be performed in 84 out of 86 planed tests (97.7%) without any objective clinical adverse effects. The mean fall in FEV1 was 3.0%, the maximum 11.0%. The reproducibility of eosinophil, neutrophil and lymphocyte differential cell count (5-95%-values Test1: 0.0-4.2%, 0.8-11.4%, and 3.2-35.1%, respectively) was moderate for eosinophils and neutrophils (Intraclass-Correlation-Coefficient (ICC) 0.41) as well as for lymphocytes (ICC = 0.49). For ECP 5-95%-values Test1: 39.8-8000.0 micrograms/l) only a fair reproducibility (ICC = 0.24) was found. The ICC levels for total cell count (ICC = 0.31) and for weight of the sputum plug (ICC = 0.30) were also fair. Based on the procedure presented induced sputum is a feasible and safe method in childhood. The differential sputum cell count of eosinophils, neutrophils and lymphocytes can be recommended as parameters with moderate reproducibility.


Familial infantile olivopontocerebellar atrophy.
Infantile olivopontocerebellar atrophies are rare progressive, fatal, neurologic conditions characterized pathologically by loss of neurons and gliosis in the cerebellum, pons, and inferior olivary nuclei in early life. The clinical and pathologic features of 2 brothers who presented in early infancy with failure to thrive and neurologic deterioration leading to death by the age of 5 months are reported. Magnetic resonance imaging of the brain of Patient 1 disclosed progressive pontocerebellar atrophy. Both siblings had identical patterns of neuronal loss consistent with olivopontocerebellar atrophy at postmortem examination. Serum biochemical abnormalities of low thyroid binding globulin, hypoalbuminemia, and low cholesterol, suggestive of the carbohydrate-deficient glycoprotein syndrome, were also present in both patients.


Toxicity of a traditional Chinese medicine, Ganoderma lucidum, in children with cancer.
Cancer is one of the most common severe diseases in Canadian children, and chemotherapy treatment leads to numerous, potentially fatal, adverse side effects including febrile neutropenia and leukopenia. In an attempt to prevent opportunistic infections, Ganoderma lucidum, a mushroom that has been used in Traditional Chinese Medicine for thousands of years, is being used by some people as an adjunctive to chemotherapy to help boost the immune system. Although extensive research is being conducted to determine its immunostimulatory properties, there is essentially no data on toxicity. The purpose of this study was to determine toxicity of low and high concentrations of 3 different extracts of G. lucidum (GL, Reishi and PSGL) on the viability of 1) Jurkat E6.1 cells, 2) LG2 cells, and 3) PBMCs isolated from a) healthy adults, b) healthy children, and c) paediatric patients undergoing chemotherapy. When Jurkat E6.1 and LG2 cells were treated with increasing concentrations of the 3 extracts, both time- and concentration- dependent decreases in cell viability were observed. However, when human PBMCs were treated with the same extracts, variable results were obtained. Although there was no consistent pattern, toxicity was observed in PBMCs. This is the first study that examines the toxicity of 3 different extracts of G. lucidum in both adultsâ and children's PBMCs. Contrary to previous belief, our results suggest that extracts of G. lucidum should be used with caution as there appears to be potential for toxicity.


Combining ring-closing metathesis and hydroformylation strategies: a novel approach to spirocyclic gamma-butyrolactones.
Di- or tetrahydropyrans with a vinyl side chain are obtained by diastereoselective ring-closing metathesis or by addition of vinylmagnesium chloride to an appropriately functionalized tetrahydropyranone. The resulting allylic alcohols are converted to spirocyclic hemiacetals under hydroformylation conditions. Oxidation yields the corresponding lactones.


Methodological and Reporting Quality of Comparative Studies Evaluating Health-Related Quality of Life of Colorectal Cancer Patients and Controls: A Systematic Review.
Health-related quality of life is an important outcome measure in patients with colorectal cancer. Comparison with normative data has been increasingly undertaken to assess the additional impact of colorectal cancer on health-related quality of life. This review aimed to critically appraise the methodological details and reporting characteristics of comparative studies evaluating differences in health-related quality of life between patients and controls. A systematic search of English-language literature published between January 1985 and May 2014 was conducted through a database search of PubMed, Web of Science, Embase, and Medline. Comparative studies reporting health-related quality-of-life outcomes among patients who have colorectal cancer and controls were selected. Methodological and reporting quality per comparison study was evaluated based on a 11-item methodological checklist proposed by Efficace in 2003 and a set of criteria predetermined by reviewers. Thirty-one comparative studies involving >10,000 patients and >10,000 controls were included. Twenty-three studies (74.2%) originated from European countries, with the largest number from the Netherlands (n = 6). Twenty-eight studies (90.3%) compared the health-related quality of life of patients with normative data published elsewhere, whereas the remaining studies recruited a group of patients who had colorectal cancer and a group of control patients within the same studies. The European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaire Core 30 was the most extensively used instrument (n = 16; 51.6%). Eight studies (25.8%) were classified as "probably robust" for clinical decision making according to the Efficace standard methodological checklist. Our further quality assessment revealed the lack of score differences reported (61.3%), contemporary comparisons (36.7%), statistical significance tested (38.7%), and matching of control group (58.1%), possibly leading to inappropriate control groups for fair comparisons. Meta-analysis of differences between the 2 groups was not available. In general, one-fourth of comparative studies that evaluated health-related quality of life of patients who had colorectal cancer achieved high quality in reporting characteristics and methodological details. Future studies are encouraged to undertake health-related quality-of-life measurement and adhere to a methodological checklist in comparison with controls.


Asthmatic children and risk factors at a province in the southeast of Turkey.
The prevalence of asthma appears to be on the increase and the risk factors are not well established. Environmental and demographic characteristics of asthmatic children were investigated to identify the risk factors accompanying asthma. 140 asthmatic children aged at 3-15 years were compared with 96 age-matched control subjects admitted to the paediatric outpatient clinics of Dicle University Hospital. Information about the children were obtained from parents and patients'charts. Patients with asthma were most frequently admitted in May-June and November-January months. Association of the disease with allergic rhinitis was found in 84 children (60 %), allergic conjunctivitis in 63 (45 %), atopic dermatitis in 29 (21 %) and gastrointestinal symptoms in 18 (13 %). Mean age of the cases was 6.8 3.3 and 6.9 3.2 years (p > 0.05); male to female ratios were 91/49 and 43/53 (p = 0.002) in the study and control groups, respectively. There were significant differences at number of cases stated to have any symptoms induced by air pollution (25.6 %, 3.1 %, p < 0,001), exercise (47.5 %, 4.2 %, p < 0.001) and cold exposure (33 %, 15.6 %, p = 0.03), but not by damp, dust, indoor smoking, foods, drugs, and animal contact (p > 0.05) between the study and the control groups, respectively. Family history of atopy was 66 % and 8.4 %, (p < 0.001) in the study and control groups, respectively. Family crowding index, duration of breast feeding, parental education and number of consanguineous married parents were not different between both groups. History of upper respiratory tract infections were more frequent in asthmatic children than controls. Children with an earlier age of onset (</= 5 years) in the study group was more frequently associated with allergic rhinitis in comparison with the asthmatic children with an age of onset > 5 years. Many risk factors, both individual and environmental are associated with asthmatic children in Diyarbakr. Among many risk factors that aggrevating asthma in children in Diyarbakr, air pollution, cold exposure and upper respiratory infections are preventable.


Embryonic brain precursors transplanted into kainate lesioned rat spinal cord.
Embryonic day 14 rat cerebral cortex-derived precursors were expanded with FGF2 and labeled with BrdU prior to being transplanted into the kainic acid-lesioned adult rat spinal cord. While these precursors give rise to cells with neuronal, astrocytic and oligodendroglial phenotypes vitro, they remained largely undifferentiated up to 12 weeks in vivo. Numerous BrdU-labeled cells were found in injured gray matter, and also lining the dilated central canal that sometimes accompanies these lesions. BrdU-labeled cells never co-expressed Map2ab, rarely co-expressed GFAP but often co-expressed nestin, even after 12 weeks in vivo. These observations suggest that the environment of the kainic acid-injured spinal cord is not hostile to transplanted embryonic cerebral cortex-derived precursors, but also is not conducive to their neuronal differentation.


A new monoclonal antibody (CH-F42) recognizes a CD7- subset of normal T lymphocytes and circulating malignant cells in adult T-cell lymphoma-leukemia and Sézary syndrome.
We describe a new rat immunoglobulin M monoclonal antibody (CH-F42) that recognizes a subset (1.5% to 8%) of normal peripheral blood T lymphocytes. The phenotype of these cells was determined, using dual-color immunofluorescence, to be CD2+, CD3+, CD4+, CD5+, CD7-, CD8-. They do not express T-cell activation markers, and are positive for UCHL1 (CD45RO), but negative for 2H4 (CD45RA). The antigen was expressed on circulating malignant cells in Sézary syndrome (four of four cases) and adult T-cell lymphoma-leukemia (ATLL) (four of six cases) and negative in a variety of other hematologic malignancies tested. These included chronic and acute lymphoid leukemias of B and T lineage, together with chronic and acute myeloid leukemias. However, normal CH-F42+ cells do not display any of the ultrastructural features associated with Sézary or ATLL cells. The marked similarities between these conditions together with the shared expression of an otherwise very restricted surface antigen (CH-F42) provide strong evidence for the existence of a common normal counterpart. Preliminary characterization studies of the antigen, which is also expressed by K562 and Jurkat cells, suggest the CH-F42 antigen is an O-linked, sialated glycan on a glycoprotein.


Seeing the Patient and Family Through: Nurses and Physicians Experiences With Withdrawal of Life-Sustaining Therapy in the ICU.
Withdrawal of life-sustaining therapy at the end of life is a complex phenomenon. Intensive care nurses and physicians are faced with caring for patients and supporting families, as these difficult decisions are made. The purpose of this study was to explore and describe the experience of critical care nurses and physicians participating in the process of withdrawal of life-sustaining therapy. A hermeneutic phenomenological approach was used to guide this qualitative investigation. Interviews were conducted with critical care nurses and physicians from 2 medical centers. An inductive approach to data analysis was used to understand similarities between the nurses and the physicians' experiences. Methodological rigor was established, and data saturation was achieved. The main categories that were inductively derived from the data analysis included from novice to expert, ensuring ethical care, uncertainty to certainty, facilitating the process, and preparing and supporting families. The categories aided in understanding the experiences of nurses and physicians, as they worked individually and together to see patients and families through the entire illness experience, withdrawal of life-sustaining therapy decision-making process and dying process. Understanding the perspectives of health-care providers involved in the withdrawal of life-sustaining therapy process will help other health-care providers who are striving to provide quality care to the dying and to their families.


Quantitation and validation of fluoroquinolones in eggs using liquid chromatography/tandem mass spectrometry.
Fluoroquinolone antibiotics are labeled for very limited veterinary use for treatment of some animals and pets, but they are not authorized for food animals in Canada, including egg-producing birds. Because they are approved for other animals, however, fluoroquinolones may appear in eggs through off-labeling or accidental use. This method is capable of quantitating and confirming the presence of 4 fluoroquinolones, ciprofloxacin, danofloxacin, enrofloxacin, and sarafloxacin, over the concentration range 1 to 60 microg/kg (ppb) using 2 internal standards, norfloxacin or lomefloxacin. The compounds are extracted with acidic acetonitrile, isolated using Oasis HLB solid-phase extraction, and quantitated by liquid chromatography/tandem mass spectrometry at 2 transitions. The limits of detection (microg/kg) were evaluated from between-day experiments as: ciprofloxacin, 0.22; danofloxacin (m/z 314), 0.32; enrofloxacin, 0.22; and sarafloxacin, 0.31. The values for the decision limit, CCalpha were 0.33, 0.36, 0.30, and 0.45 microg/kg, respectively.


Role of downregulation of galectin-9 in the tumorigenesis of gastric cancer.
Galectin-9 (Gal-9), a member of the β-galactoside-binding galectin family, plays a role in immune response, apoptosis, cell proliferation and cell death. Recent studies have shown that abnormal expression of Gal-9 is involved in certain primary cancers. The present study is the first investigation of the role of Gal-9 gene expression in clinically diagnosed primary gastric cancer tissues. Gal-9 mRNA expression was assessed in 44 clinically diagnosed frozen primary cancer tissue samples using quantitative PCR (qPCR). Analysis of the qPCR data revealed a significant reduction (>2-fold decreased) of Gal-9 gene expression in gastric cancer tissues in 77% (34/44) of patients. In patients with gastric cancer, although no statistically significant difference was found between adjacent (<2 cm away from the cancer tissue) and normal tissues (>5 cm away from the cancer tissue), a >2-fold reduction in Gal-9 expression was observed in the adjacent tissues of 34% of the patients. Compared to matched normal or adjacent tissues, the gene expression of Gal-9 was significantly decreased in tumor tissues (p<0.001). The correlation of Gal-9 expression and clinicopathological features in gastric cancer was analyzed according to the TNM classification system using AJCC stage grouping. In patients with gastric cancer, clinical staging, tumor pathological stage (pT stage), tumor cell differentiation, lymph node metastasis and survival rate were found to be associated with Gal-9 expression. However, no significant association was found between Gal-9 expression and distant metastasis (p>0.05). No significant difference was found between patients of different genders, levels of cell differentiation, distant metastasis status or different survival time of patients. Compared to normal tissues, >2-fold reduction of Tim-3 expression in gastric cancer tissues occurred in 59% of patients, but no correlation was found between Gal-9 and Tim-3 in gastric cancer. These results strongly suggest that Gal-9 is involved in tumorigenesis of gastric cancer.


Differentiation of the body wall musculature in Macrostomum hystricinum marinum and Hoploplana inquilina (Plathelminthes), as models for muscle development in lower Spiralia.
Recent studies on the differentiation of the body wall musculature in a medicinal leech and in the free-living plathelminth Macrostomum hystricinum marinum, Beklemischev 1950 provide the first evidence of a complex developmental signalling pattern, possibly involving stem cells and the nervous system, in the organization of the muscle grid formed by developing myocytes. To enhance further our understanding of the ontogenetic and phylogenetic origin of such muscle grids, which consist of circular, longitudinal and diagonal muscle fibres, we have undertaken a study of muscle development in the polyclad flatworm Hoploplana inquilina Wheeler 1894 in collaboration with the Marine Biological Laboratory, Woods Hole. We have also continued our examination of the development of the body wall musculature in M. hystricinum. Both species were studied using rhodamine-phalloidin staining and transmission electron microscopy. Additional visualization of the fluorescent whole mount preparations was performed with confocal laser microscopy and digital image processing. The results of our investigation suggest that: (1) the mechanism of muscle development in H. inquilina supports the deeply rooted concept of bilateral symmetry (right and left longitudinal founder muscle), and (2) a first circular muscle in this species develops on the border between an anterior body unit and the main body; a caudalmost region is less obvious. The presence of a spiral muscle functioning as a circular muscle system of the "head region" points to a separate developmental mechanism for this region and the trunk. In contrast to H. inquilina, where the larval stage forces an intermediate restructuring of the musculature of the body wall before the adult body shape is finally developed, the formation of the body wall musculature of M. hystricinum already seems constrained by the adult body shape.


[Confusable species of traditional Chinese drugs in Gansu Province and their quality: (1). A survey of drugs customarily used in Gansu Province].
This paper systematically investigates the confusable species of the traditional Chinese drugs in Gansu Province, and reports the sources, places of production and existing main problems of 58 species presently in production and circulation.


Combined thyroidectomy and renal denervation suppress renin expression and secretion in fetal sheep.
Activity of the fetal renin-angiotensin system (RAS) is developmentally regulated, increasing in late gestation toward term. Thyroid hormone and the renal nerves are both important modulators of renal RAS maturation; however, ablation of either influence alone does not totally block the aforementioned developmental late gestation increase in RAS in fetal sheep. In the current study, we used the technique of thyroidectomy combined with bilateral renal denervation (TX+D), which removes thyroid hormone from the circulation and abolishes effects of renal nerve activity, to determine if simultaneous removal of their effects on the kidney would markedly alter renin expression and secretion in late gestation. TX+D was performed at 120 days of gestation age (dGA). Control fetuses were sham-operated. Immediately before necropsy (approximately 138 dGA), fetuses were infused with isoproterenol to examine plasma active and prorenin changes in response to beta-adrenergic stimulation. TX+D decreased plasma thyroid hormone concentrations, renal renin mRNA, renal active and prorenin levels, and plasma active and prorenin concentrations. Isoproterenol-induced increases in plasma active renin were also reduced in TX+D fetuses. TX+D did not alter renal angiotensin (Ang) II subtype receptor (AT2) expression close to term. These findings suggest that TX+D synergize in the suppression of fetal renin expression.


Isolation and characterisation of segment 1 of the infectious salmon anaemia virus genome.
The isolation and characterisation of the largest genomic segment of infectious salmon anaemia virus (ISAV) is reported. Following identification of ISAV-specific clones from a cDNA library, a rapid amplification of cDNA ends-PCR strategy was designed to obtain the sequence of the full length mRNA transcript. The full length open reading frame (ORF) of this gene was shown to be 2169 nucleotides in length, encoding a putative protein of 722 aa. This sequence was demonstrated by RT-PCR to be specific to ISAV-infected cell cultures. The start codon of this ORF was preceded by the ISAV consensus sequence 5' GCTAAGA 3' indicating the full 5' end of the gene to have been obtained. Based on protein size and amino acid composition, this protein was shown to be similar to the PB2 protein of other orthomyxoviruses. Furthermore, a bipartite nuclear localisation signal was identified in the C-terminus of the protein as is found on all of the influenza virus P proteins. Expression of the putative PB2 as a green fluorescent marker protein-fusion protein confirmed that this protein exhibited nuclear localisation in a fish cell line. Sequences of the ISAV segment 1 gene were obtained from Scottish, Norwegian and Canadian ISAV isolates. Analyses confirmed the close genetic relationship between Norwegian and Scottish ISAV and indicated that this segment was among the most conserved of the ISAV genes identified to date. Thus, this evidence strongly suggests that the genomic segment 1 of ISAV encodes a polymerase protein which is thought to be analagous in function to the PB2 protein of influenza viruses.


Cross-reactivity between sensitivity to thimerosal and photosensitivity to piroxicam in guinea pigs.
Piroxicam (PXM) is a nonsteroidal anti-inflammatory drug which may induce a photosensitive eruption shortly after administration. We examined whether animals sensitized to thimerosal developed a photosensitivity to PXM. Male Hartley strain guinea pigs were sensitized to thimerosal, thiosalicylate and PXM separately. The open patch test was used to evaluate sensitization to each drug and cross-reactions between the drugs. Animals sensitized to thimerosal exhibited positive patch test reactions to thiosalicylate and positive photopatch test reactions to PXM. Both those sensitized to thiosalicylate and to PXM showed positive patch test reactions to PXM. This study demonstrated that thimerosal induces cross-sensitivity to PXM in vivo and that the common active component among these compounds may be thiosalicylate.


Liver X receptor activation decreases the severity of experimental autoimmune encephalomyelitis.
Agonists of liver X receptors (LXR), members of the nuclear hormone receptor superfamily, alter secretion of proinflammatory cytokines, suggesting potential antiinflammatory effects. A synthetic LXR agonist inhibited T-cell proliferation and cytokine release in a dose-dependent manner. Treatment of mice during induction of experimental autoimmune encephalomyelitis reduced clinical symptoms, central nervous system cellular inflammation, and major histocompatibility class II expression on microglia, as well as demyelination. In contrast to in vitro analysis, no reductions in peripheral neuroantigen specific T-cell responses were detected in comparing ligand and vehicle treated mice. These data suggest that LXR agonists play an important protective role in the regulation of T-cell-mediated inflammatory disease of the central nervous system.


Madelung disease: manifestations of CT and MR imaging.
The purpose of the present study was to assess the head and neck imaging features of Madelung disease on computerized tomography (CT) and magnetic resonance imaging (MRI), delineate the effects of the fatty deposits on underlying structures, and tabulate the anatomic sites where the neck fat was deposited. Sixteen Chinese patients with Madelung disease in our hospital were reviewed. The CT manifestations of the 16 cases and the MRI manifestations of 1 case were analyzed retrospectively. The imaging features of the fatty distribution in the head and neck area were studied. Cross-sectional CT showed that the excess fat was symmetric and unencapsulated, mainly deposited at the anterior or posterior subcutaneous tissue of the neck, was deep under the sternocleidomastoid and trapezius muscles, was situated in the posterior cervical triangle, and was around the salivary glands. It was also found to be situated in supraclavicular fossa, around the paraspinal muscles and larynx, and so on. The accumulated fat at superficial sites was situated at the napex and/or at the anterior neck, forming small or large fatty masses to protrude backwards locally or sometimes at submentum; the markedly thickened neck might appear tubby or oval in anteroposterior diameter. The accumulated fat at deep sites compressed adjacent muscles, salivary glands, and great vessels and caused them to shift and deform. The distinctive appearance was that marked thickening of fat caused sternocleidomastoid muscles and submaxillary glands to shift forward obviously, like a bird spreading its wings. The density of the abnormally proliferated fat was equal to that of normal fat. In MRI, the distribution of the excess fat was equal to that seen with CT. The signal intensity of the excess fat was equal to that of normal fat. Besides the accumulation of the neck fat tissue, CT and MRI did not show other abnormal soft tissue masses. The use of CT and MRI can accurately show the excess fat based on density of CT and signal intensity of MRI. The density and signal intensity of the excess fat are equal to those of normal fat. The excess fat, mainly deposited at the anterior or posterior subcutaneous tissue of the neck, was deep under the sternocleidomastoid and trapezius muscles, was situated in the posterior cervical triangle, and was around the salivary gland, and so on. CT and MRI can also show compression, shift, and deformation of surrounding salivary glands, great vessels, and muscles caused by the excess fat. The CT and MRI can accurately diagnose the disease and exclude other soft tissue tumors.


bcl-2 and p53 expression in resectable pancreatic adenocarcinomas: association with clinical outcome.
The bcl-2 proto-oncogene and the p53 tumor suppressor gene are important determinants of tumor cell susceptibility to apoptosis. bcl-2 and mutant p53 proteins inhibit apoptosis in vitro and can provide prognostic information in certain tumor types. We analyzed bcl-2 and p53 expression in archival pancreatic (n = 35) and ampullary (n = 6) adenocarcinomas, resected for cure, and their relationship to overall survival. Patients were treated with 5-fluorouracil and irradiation either pre- (n = 21) or postoperatively (n = 15); 5 patients received surgery alone. Using specific monoclonal antibodies, cytoplasmic bcl-2 and nuclear p53 proteins were detected in 22 of 40 (55%) and 20 of 37 (54%) tumors, respectively. No relationship was found between bcl-2 and p53 expression. Neither bcl-2 nor p53 correlated with histological response to preoperative chemoradiation. Lymph node involvement predicted poor overall survival (P = 0.02). A trend toward improved survival was seen in well-differentiated (P = 0.08) tumors and in those with increased bcl-2 expression (P = 0.06). p53 expression was not related to clinical outcome. In a multivariate analysis, nodal status was the single most important predictor of overall survival. Of note, the combined variable of bcl-2 expression and histological grade was a stronger prognostic variable than nodal status alone. Unlike nodal status, these features can potentially be evaluated in preoperative biopsy specimens.


Suppression of viral transformation in rat embryo fibroblast cells immortalized with transforming genes of human papillomavirus type 16.
The E6 and E7 genes of human papillomavirus type 16 (HPV16) immortalize rat primary embryo fibroblast cells (REF) but do not transform them, irrespective of the expressions of the two genes. Previously, we reported that REF cells suppress the transformed phenotypes of a rat cell line transformed by the E6 and E7 genes of HPV16 in somatic hybrid cells. REF cells immortalized by HPV16 E6E7 genes (671 cells) also retained the ability to suppress E6E7-mediated transformation. Transformation of 671 cells by retroviruses containing middle T of polyomavirus, v-K-ras, or v-mos was also suppressed. 671 cells infected with retrovirus having middle T of polyomavirus (PyMLV) expressed sufficient middle T protein to transform a rat cell line. Cell fusion experiments showed that 671 cells suppressed transformation by middle T of polyomavirus without affecting the expression of middle T. These results suggest that REF cells immortalized by HPV16 E6E7 genes possess an intracellular function that suppresses transformation not only by E6E7 genes but also by other viral oncogenes including middle T of polyomavirus.


Central projections of Tömösváry's organ in Lithobius forficatus (Chilopoda, Lithobiidae).
Afferents of Tömösváry's organ innervate multiple synaptic sites within the ipsilateral protocerebrum, i.e. neuropil areas proximal to the 2nd optic neuropil, in the dorsolateral protocerebrum, and surrounding the pedunculus of the "mushroom bodies". Sensory input via Tömösváry's organ in Lithobius appears to follow a peculiar neuronal pathway bypassing the deutocerebrum and tritocerebrum which are innervated by many head sensilla in arthropods.


Structural basis for the GSK-3beta binding affinity and selectivity against CDK-2 of 1-(4-aminofurazan-3yl)-5-dialkylaminomethyl-1H-[1,2,3] triazole-4-carboxylic acid derivatives.
A novel structural class of glycogen synthase kinase-3beta inhibitors is modeled using quantum mechanics, automated docking, and molecular dynamics simulations. The proposed binding modes identify important hydrogen bonds and salt-bridges with the ATP-binding pocket of the kinase. The modeled complexes justify the observed structure-activity relationships and provide a structural basis for the high selectivity of these inhibitors against cyclin dependent kinase-2.


Tracheal neurilemmoma mimicking bronchial asthma--a dilemma of difficult diagnosis: case report.
Tracheal tumors are often overlooked as a cause of pulmonary symptoms until they reach an advanced state. They are often presented with a prolonged cough and shortness of breath. Most tracheal tumors in adults are cancerous (80% to 90%). Benign tracheal tumors are rare in adult patients. A case history is presented of a 19-year-old patient with a rare tracheal neurilemmoma. He was treated as having bronchial asthma initially, but his signs and symptoms did not improve with traditional therapy. The possibility of the presence of an upper airway obstruction was not raised until the typical "inspiratory tubular sound" was heard. Flow-volume loop testing, bronchoscopy, and three-dimensional computed tomography (3-D CT) confirmed the diagnosis of upper airway obstruction caused by a tracheal tumor. Therefore, surgical intervention rather than bronchoscopic removal was performed without difficulty. The patient was leading a stable life 8 months after a surgical resection. The presence of an upper airway obstruction can be proven by flow-volume loop testing and 3-D CT. Further pathologic confirmation can be accomplished by bronchoscopy. High suspicion of an upper airway obstruction such as a tracheal lesion should be raised when bronchial asthma patients fail to respond to conventional treatment.


Reinforcement learning and decision making in monkeys during a competitive game.
Animals living in a dynamic environment must adjust their decision-making strategies through experience. To gain insights into the neural basis of such adaptive decision-making processes, we trained monkeys to play a competitive game against a computer in an oculomotor free-choice task. The animal selected one of two visual targets in each trial and was rewarded only when it selected the same target as the computer opponent. To determine how the animal's decision-making strategy can be affected by the opponent's strategy, the computer opponent was programmed with three different algorithms that exploited different aspects of the animal's choice and reward history. When the computer selected its targets randomly with equal probabilities, animals selected one of the targets more often, violating the prediction of probability matching, and their choices were systematically influenced by the choice history of the two players. When the computer exploited only the animal's choice history but not its reward history, animal's choice became more independent of its own choice history but was still related to the choice history of the opponent. This bias was substantially reduced, but not completely eliminated, when the computer used the choice history of both players in making its predictions. These biases were consistent with the predictions of reinforcement learning, suggesting that the animals sought optimal decision-making strategies using reinforcement learning algorithms.


Maternal and fetal factors which affect fetometry: use of in vitro fertilization and birth register data.
Fetometry dating of gestational age is the gold standard in most developed countries but may have some inborn errors. Dating pregnancies after in vitro fertilization can be used for the evaluation of fetometric studies and for studies of variables which may affect them. We compared the actual gestational age of 9543 singleton and 869 twin pregnancies with estimates based on second-trimester fetometry. Mean gestational age, percentage of births classified as preterm, and skewness of the distribution of differences between actual and estimated gestational age were studied. Subanalyses were made of data on singletons for males and females, for infants born to overweight or obese women or to smoking women, for infants judged to be small or large for gestational age, and on twins. In the majority of cases, good agreement was found between actual and estimated gestational age but in singletons there was an excess of positive differences resulting in a moderate over-estimate of the rate of preterm births (8%), more marked for females (11%) than for males (6%) and increased for infants born to overweight (7%) or obese (16%) mothers. Singleton infants born small for gestational age also showed an excess of positive differences (3%). These differences were less marked for twins. In most IVF pregnancies, routine fetometry correctly predicts gestational age but deviations exist which indicate that ultrasound underestimates the age of fetuses that will be born small for gestational age and when the woman is obese. The differences between actual age and estimates based on fetometry seem to be smaller than those between estimates based on last menstrual period and fetometry.


A new species of Leioseius (Acari: Ascidae) from Brazil, redescription of Leioseius basis and a key for separation of the world species of the genus.
Leioseius Berlese is known in South America only from one especies described from Chile. Leioseius cananeiensis n. sp. is described based on the morphology of adult females found in association with barnacles (Crustacea, Cirripedia) on roots of Laguncularia racemosa (L.) (Combretaceae) collected in Cananéia, São Paulo State, Brazil. Leioseius basis Karg is redescribed based on the holotype female, one paratype female and two sparatype males. A key for the separation of females of the 19 recognisable world Leioseius species is provided.


A study of impact of shift work on fatigue level of workers in a sanitary-ware factory using a fuzzy set model.
Work generally affects workers in terms of both physical and mental health. Workers must adapt their life pattern to match shift-work styles which can result in family problems, increased fatigue level, lower work efficiency, higher accident rate, illnesses, and lower productivity. The project obtained an entry permission to study the impact of shift work on fatigue level of workers in a sanitary-ware factory. The objectives were: 1) to evaluate fatigue levels of workers who worked in the morning shift and night shift, and 2) to prioritize contributing factors affecting fatigue levels using a model of fuzzy set theory. Twelve male workers participated in the study. Four subjects were recruited from each of 3 departments, i.e., glazing, baking and quality inspection. The measurement was conducted before and after the shift for both shifts. Variables included heart rate monitoring throughout the work shift, critical flicker fusion frequency, reaction time response, hand-grip strength, and wet-bulb globe temperature. Results were analyzed using a computerized statistical package. It was concluded from this study that mental fatigue from working in the morning shift was significantly higher than the one for working in the night shift. The same indication was also true in the case of physical fatigue, though it was not statistically significant. From the fuzzy set analysis, it was confirmed that working in the morning shift resulted in a higher fatigue level than working in the night shift and the temperature of the work environment was the most important factor contributing to the higher fatigue level.


Enhancing antitumor activity of silver nanoparticles by modification with cell-penetrating peptides.
Recently, silver nanoparticles (AgNPs) have been used for cancer treatment. To achieve a successful anticancer activity, AgNP needs to be delivered sufficiently to the cells. Cell-penetrating peptides (CPPs) are small cationic peptides that have ability to transport various cargos across cell membranes. In this study, a strategy was developed for cancer treatment, where AgNP modified with CPPs displayed dramatically antitumor activity in MCF-7 cell lines. Peptides-modified AgNPs showed significant enhancement in killing tumor cells by increasing the uptake of AgNP into cell lines and could be a new class of nano-drug for cancer treatment.


Structural function of MIP/aquaporin 0 in the eye lens; genetic defects lead to congenital inherited cataracts.
Aquaporin 0 (AQP0) was originally characterized as a membrane intrinsic protein, specifically expressed in the lens fibers of the ocular lens and designated MIP, for major intrinsic protein of the lens. Once the gene was cloned, an internal repeat was identified, encoding for the amino acids Asp-Pro-Ala, the NPA repeat. Shortly, the MIP gene family was emerging, with members being characterized in mammals, insects, and plants. Once Peter Agre's laboratory developed a functional assay for water channels, the MIP family became the aquaporin family and MIP became known as aquaporin 0. Besides functioning as a water channel, aquaporin 0 also plays a structural role, being required for maintaining the transparency and optical accommodation of the ocular lens. Mutations in the AQP0 gene in human and mice result in genetic cataracts; deletion of the MIP/AQP0 gene in mice results in lack of suture formation required for maintenance of the lens fiber architecture, resulting in perturbed accommodation and focus properties of the ocular lens. Crystallography studies support the notion of the double function of aquaporin 0 as a water channel (open configuration) or adhesion molecule (closed configuration) in the ocular lens fibers. The functions of MIP/AQP0, both as a water channel and an adhesive molecule in the lens fibers, contribute to the narrow intercellular space of the lens fibers that is required for lens transparency and accommodation.


[Indications and complications of systemic corticosteroid therapy in treatment of uveitis].
Systemic steroids is often the first choice of immunosuppressive therapy for severe endogenous uveitis. The aim of this study was to analyse the indications of steroid therapy, complications and side-effects. Charts from all patients that received oral steroid therapy were reviewed for this purpose and a questionnaire was sent out to all patients to record their subjective complaints. From January 1990 to March 1993, 63 out of the 435 new patients seen at the uveitis clinic received oral prednisone. In 4 cases severe complications occurred that did however not lead to discontinuation of therapy. In 2 cases of intolerance cyclosporine (CsA) had to be added to the treatment regimen to lower the steroid doses and in one case steroids had to be stopped because of intolerance. The questionnaire showed a high rate of subjective side-effects to steroids. In our collective oral steroids were associated with complications, intolerance and side-effects in a high proportion of cases. It is important to explain the possible side-effects to the patient before starting the therapy. The preventable collateral effects like weight gain and decalcification should be addressed by diet recommendations and modern calcium sparing therapy.


[Optimization of hydroxylating DHEA to 7alpha,15alpha-diOH-DHEA by compound mutation and fermentation optimization].
Combined with method of ketoconazole resistance screening, a 7alpha,15alpha-diOH-DHEA high-producing mutant Colletotrichum lini ST-1 was obtained by compound mutation of NTG and low energy N+ ion beam implantation. With the substrate concentration of 10 g/L DHEA, the molar yield of 7alpha,15alpha-diOH-DHEA reached 34.2%, increased by 46.2% than that of the original strain. Then we optimized the medium. First, Plackett-Burman design was used to evaluate the effects of medium components on molar yield of the product. Results show that glucose, yeast extract and MgSO4 x 7H2O were the important parameters for the biotransformation process. Subsequently, the path of steepest ascent was used to approach the optimal levels. To obtain the optimal levels, central composite design and response surface analysis were carried out. The optimal medium was as follows (g/L): glucose 26.34, yeast extract 12.15, corn flour 3.00, FeSO4 x 7H2O 0.015, MgSO4 x 7H2O 0.14, KH2PO4 0.90. Under the optimal conditions, the molar yield of 7alpha,15alpha-diOH-DHEA reached 49.3%, which was 44.2% higher than that of using the medium before optimization.


[Eras protocol for laparoscopic Frey procedure (in Russian only)].
To assess the use of ERAS in laparoscopic Frey procedure. From August 2012 to November 2017 laparoscopic Frey procedure were performed in 35 patients. Fully laparoscopic were performed 31 (88.5%) procedures. We use fast-track protocol from 13 patients. We included from statistic analyses patients where procedure was changed or was conversion or was simultaneous procedure. The total number of patients analyzed was 27. The patients were divided into two groups: I - before the fast-track protocol (n=11), II - after the protocol implementation (n=16). The operating time was 460 (365-530) minutes in I group and 420 (295-540) minutes in II group. Blood loss was 150 (5-300) and 150 (40-700) ml. The median postoperative stay period was 10 (5-25) days and 6.5 (3-11) days (p=0.007). The combination of laparoscopic technologies and fast-track protocol reduces the duration of the postoperative stay period.


A new species of pentastomida infecting Tropidurus hispidus (Squamata: Tropiduridae) from Caatinga in Northeastern Brazil.
This article describes a new species of Brazilian Raillietiella Sambon, 1910 from lungs of Tropidurus hispidus (Spix, 1825). Between July and October 2005 eighteen specimens of T. hispidus were actively captured with elastic rubber slings in granite outcrops (lajeiros) (06 degrees 59' S and 39 degrees 31' W) from caatinga formations in the municipality of Farias Brito, State of Ceará, Northeastern Brazil. One female and one male of T. hispidus had lungs infected by Raillietiella mottae sp. nov. (prevalence 11.1% and mean intensity of infection 6.0 +/- 1.4, range 5-7). The parasite's main diagnostic characteristics include the dimensions of sharp hooks and strongly curved or "C-shaped" male copulatory spicules with knob-like posterior projection from the base towards the inner curvature of the spicule.


Biomimetic synthesis and structural refinement of the macrocyclic dimer aminoglycoside 66-40C--the remarkably selective self-condensation of a putative aldehyde intermediate in the submerged culture medium producing sisomicin.
Aminoglycoside 66-40C, an unprecedented 16-membered bis-azadiene macrocyclic natural product isolated from the Micromonospora producer of the antibiotic sisomicin, was synthesized following a biomimetic strategy which definitively established its origin as arising from a remarkably selective non-enzymatic macro-dimerization.


Hemifacial paralysis in a child treated for leukemia: unusual side effect of omeprazole?
We report a hemifacial paralysis as an adverse drug reaction possibly related to the use of omeprazole in a patient with acute lymphoblastic leukemia. We believe that this case, although very rare, is clinically significant and worth mentioning, owing to the frequent use of omeprazole in the oncology setting.


A unique case of rituximab-related posterior reversible encephalopathy syndrome in a heart transplant recipient with posttransplant lymphoproliferative disorder.
Rituximab is commonly used as a first line therapy to treat posttransplant lymphoproliferative disorders (PTLDs). It has also proved useful in the management of refractory antibody mediated graft rejection. We report an unusual case in which a heart transplant recipient being treated with rituximab for PTLD developed altered mental status, hallucinations and visual symptoms and magnetic resonance imaging (MRI) findings of symmetrical enhancement suggestive of posterior reversible leukoencephalopathy syndrome (PRES). Resolution of these clinical symptoms and radiological findings after discontinuation of therapy confirmed the diagnosis. This is the first case of PRES seen due to rituximab in a heart transplant recipient. Another unique feature of the case is the development of PRES after second cycle of rituximab as compared to prior reports in nonheart transplant patients in which the syndrome developed after first dose administration. The objective of this case report is to increase the awareness of this rare entity amongst immunocompromised transplant patients.


[Differences between morning and afternoon in the assessment of nutritional status by bioelectric impedance in children].
The aim of this study was to examine if there were differences in the assessment of the nutritional status between values of bioelectric impedance (BI) measured in the morning (08:30) and in the afternoon (17:00). We have studied 30 boys between 6.5 and 10.9 years of age. Weight, stature, skinfold thickness and total body impedance (Z) were measured at 08:30 and at 17:00 on the same day. In 28 of 30 boys, Z at 17:00 was lower than Z at 08:30. The mean decrease in Z was 4.64% of the morning result (p = 0.0001). At 17:00 there was an increase in total body water (TBW) and fat-free mass (FFM) measured by BI, 0.681, and 0.93 Kg, respectively (p = 0.0001), compared with morning values. We did not find differences between skinfold thickness values in the morning and in the afternoon, except for the suprailiac skinfold, which was a bit larger in the afternoon (p = 0.05). In the morning and afternoon there was a high correlation between FFM measured by skinfold thickness and values of TBW and FFM measured by BI. Z in boys decrease in the afternoon (17:00) compared with morning values (08:30). This fact must be considered by the pediatrician when IB is used for the assessment of nutritional status in children.


Characterization of DNA fragmentation events caused by genotoxic and non-genotoxic agents.
Leukemic cells have been shown to generate several classes of DNA fragments after treatment with cytotoxic cancer chemotherapy agents. However, it is unclear which of these fragmentation events are a direct effect of DNA-damaging chemotherapy agents, and which fragmentation events are caused by downstream processes, such as apoptosis. We have performed a detailed analysis of DNA fragmentation events which occur following cytotoxic chemotherapy in four representative leukemic cell lines (HL-60, Jurkat, K562, and Molt-4). We used a DNA topoisomerase II inhibitor (etoposide), an alkylating agent (melphalan), a nucleoside analog (cytosine arabinoside), and a non-genotoxic agent (N-methylformamide) to induce cell death. We studied high molecular weight and low molecular weight DNA fragmentation events, as well as the specific cleavage of the MLL breakpoint cluster region (bcr). The DNA fragments produced at late time points were largely independent of the agents used, while those generated at earlier time points showed clear differences in terms of fragment size and relative abundance, depending on the agent used. In addition, there were clear differences between cell lines in terms of size, relative abundance, and rate at which DNA fragments were produced by treatment with the same agents. We think that this survey documents the importance of studying several different cell lines, time points, and assays before reaching conclusions about the types of DNA fragments produced during treatment with cytotoxic agents, and provides a useful framework for studying a wide range of DNA fragments produced by cytotoxic agents.


16PF-E Structure using Radial Parcels Versus Items.
The Sixteen Personality Factor Questionnaire (16PF) was factored with the use of groups of items called radial parcels and was subsequently compared with an item factoring of the same data. This was done in order to verify the 16PF (Form E) primary factors and to investigate the use of radial parcels in that process. Ss were 449 physically or mentally handicapped men and women who were part of a rehabilitation counseling process. Results indicated that with some familiar exceptions factor identification and verification were complete. Moreover, the use of radial parcels maintained the dimensionality found in the items. Also, rotation toward simple structure proceeded more rapidly with parcels than with items.


Chronic lymphadenopathies and human herpes virus type 8.
Human herpes virus type 8 (HHV-8) is predominantly associated with Kaposi's sarcoma. Nothing is known about its manifestation in primary infection. We report an HIV-negative patient with chronic polyadenitis and lymphocytosis that may have been related to a primary HHV-8 infection.


Heterogeneity of serum creatine kinase isoenzyme-MM in acute myocardial infarction.
Isoelectric focusing of serum creatine kinase (CK;EC 2.7.3.2) reveals up to 14 CK-MM subbands following acute myocardial infarction (AMI). The "normal" subbands 1 (pI 6.91), 2 (pI 6.65) and 3 (pI 6.35) are faintly present in normal serum and the "abnormal" subbands c (pI 7.25), e (pI 6.85), g (pI 6.50), i (pI 6.28), j (pI 6.20) and k (pI 6.15) are prominently detected in sera with elevated CK. "Abnormal" subbands a (pI 7.55),b(pI7.35),d(pI7.05),f(pI6.72) and h(pI6.40) have only been detected in AMI. The "abnormal" subbands appear, and reach maximum intensity (together with CK-MM 1-3), 3-12 h after infarction, and become faint and anodally convert (as do CK-MM 1-3) within 36 h. Similar changes are detected by nonequilibrium pH gradient electrophoresis which combines CK-MM and CK-MB analysis. In vitro incubation of serum with 0.015 M 2-mercaptoethanol induces conversion of CK-MM 1, 2 and 3 to b and c, d and e, and f and g, respectively. Thus, the complexity of the patterns is explained by a secondary conversion of "normal" to "abnormal" subbands superimposed upon anodal conversion of CK-MM 1----3. The clinical significance of these findings is discussed.


Using smart mobile devices in social-network-based health education practice: a learning behavior analysis.
Virtual communities provide numerous resources, immediate feedback, and information sharing, enabling people to rapidly acquire information and knowledge and supporting diverse applications that facilitate interpersonal interactions, communication, and sharing. Moreover, incorporating highly mobile and convenient devices into practice-based courses can be advantageous in learning situations. Therefore, in this study, a tablet PC and Google+ were introduced to a health education practice course to elucidate satisfaction of learning module and conditions and analyze the sequence and frequency of learning behaviors during the social-network-based learning process. According to the analytical results, social networks can improve interaction among peers and between educators and students, particularly when these networks are used to search for data, post articles, engage in discussions, and communicate. In addition, most nursing students and nursing educators expressed a positive attitude and satisfaction toward these innovative teaching methods, and looked forward to continuing the use of this learning approach.


Probing treatment response of glutaminolytic prostate cancer cells to natural drugs with hyperpolarized [5-(13) C]glutamine.
The correlation between glutamine metabolism and oncogene expression in cancers has led to a renewed interest in the role of glutamine in cancer cell survival. Hyperpolarized [5-(13) C]glutamine is evaluated as a potential biomarker for noninvasive metabolic measurements of drug response in prostate cancer cells. Hyperpolarized [5-(13) C]glutamine is used to measure glutamine metabolism in two prostate cancer cell lines (PC3 and DU145) before and after treatment with the two natural anticancer drugs resveratrol and sulforaphane. An invasive biochemical assay simulating the hyperpolarized experiment is used to independently quantify glutamine metabolism. Glutamine metabolism is found to be 4 times higher in the more glutaminolytic DU145 cells compared with PC3 cells under proliferating growth conditions by using hyperpolarized [5-(13) C]glutamine as a noninvasive probe. A significant decrease in glutamine metabolism occurs upon apoptotic response to treatment with resveratrol and sulforaphane. Hyperpolarized NMR using [5-(13) C]glutamine as a probe permits the noninvasive observation of glutaminolysis in different cell lines and under different treatment conditions. Hyperpolarized [5-(13) C]glutamine metabolism thus is a promising biomarker for the noninvasive detection of tumor response to treatment, as it directly monitors one of the hallmarks in cancer metabolism - glutaminolysis - in living cells.


Masculinity and barriers to seeking counseling: The buffering role of self-compassion.
Less than 1/3 of college men seek psychological help per year when experiencing mental health concerns. Many believe this is because socialized masculine norms are incongruent with help-seeking decisions. In line with this, adherence to masculine norms, like emotional control and self-reliance, is consistently linked to factors associated with lower use of counseling. Identifying constructs that buffer, or reduce, the relationship between masculine norm adherence and common barriers to seeking help, like help-seeking self-stigma and resistance to self-disclosing, could shed light on mechanisms through which effective interventions could be developed. As such, this study examined whether self-compassion, or the ability to show oneself kindness and understanding in the face of challenges, moderated the relationship between masculine norm adherence and both help-seeking self-stigma and the risks associated with self-disclosing to a counselor in a sample of 284 undergraduate men (Mage = 19.68, range = 18-30). Results indicate that self-compassion is associated with lower levels of help-seeking self-stigma and disclosure risks. Additionally, and perhaps more importantly, self-compassion buffered the relationship between overall masculine norm adherence and each of these barriers. Furthermore, when specific masculine norms were examined, self-compassion buffered the relationship between emotional control and disclosure risks. These results support the need for future research focused on the development and assessment of self-compassion based interventions aimed at decreasing the barriers undergraduate men experience toward seeking psychological help. (PsycINFO Database Record


Eastern Baltic region vs. Western Europe: modelling age related changes in the pubic symphysis and the auricular surface.
Objectives. The present study addresses the following two main questions: a) Is the pattern of skeletal ageing observed in well-known western European reference collections applicable to modern eastern Baltic populations, or are population-specific standards needed? b) What are the consequences for estimating the age-at-death distribution in the target population when differences in the estimates from reference data are not taken into account? Materials and methods. The dataset consists of a modern Lithuanian osteological reference collection, which is the only collection of this type in the eastern Baltic countries (n = 381); and two major western European reference collections, Coimbra (n = 264) and Spitalfields (n = 239). The age-related changes were evaluated using the scoring systems of Suchey-Brooks (Brooks & Suchey 1990) and Lovejoy et al. (1985), and were modelled via regression models for multinomial responses. A controlled experiment based on simulations and the Rostock Manifesto estimation protocol (Wood et al. 2002) was then carried out to assess the effect of using estimates from different reference samples and different regression models on estimates of the age-at-death distribution in the hypothetical target population. Results. The following key results were obtained in this study. a) The morphological alterations in the pubic symphysis were much faster among women than among men at comparable ages in all three reference samples. In contrast, we found no strong evidence in any of the reference samples that sex is an important factor to explain rate of changes in the auricular surface. b) The rate of ageing in the pubic symphysis seems to be similar across the three reference samples, but there is little evidence of a similar pattern in the auricular surface. That is, the estimated rate of age-related changes in the auricular surface was much faster in the LORC and the Coimbra samples than in the Spitalfields sample. c) The results of simulations showed that the differences in the estimates from the reference data result in noticeably different age-at-death distributions in the target population. Thus, a degree bias may be expected if estimates from the western European reference data are used to collect information on ages at death in the eastern Baltic region based on the changes in the auricular surface. d) Moreover, the bias is expected to be more pronounced if the fitted regression model improperly describes the reference data. Conclusions. Differences in the timing of age-related changes in skeletal traits are to be expected among European reference samples, and cannot be ignored when seeking to reliably estimate an age-at-death distribution in the target population. This form of bias should be taken into consideration in further studies of skeletal samples from the eastern Baltic region.


Disease Severity Estimates-Effects of Rater Accuracy and Assessment Methods for Comparing Treatments.
Assessment of disease severity is required for several purposes in plant pathology; most often, the estimates are made visually. It is established that visual estimates can be inaccurate and unreliable. The ramifications of biased or imprecise estimates by raters have not been fully explored using empirical data, partly because of the logistical difficulties involved in different raters assessing the same leaves for which actual disease has been measured in a replicated experiment with multiple treatments. In this study, nearest percent estimates (NPEs) of Septoria leaf blotch (SLB) on leaves of winter wheat from nontreated and fungicide-treated plots were assessed in both 2006 and 2007 by four raters and compared with assumed actual values measured using image analysis. Lin's concordance correlation (LCC, ρc) was used to assess agreement between the two approaches. NPEs were converted to Horsfall-Barratt (HB) midpoints and were compared with actual values. The estimates of SLB severity from fungicide-treated and nontreated plots were analyzed using generalized linear mixed modeling to ascertain effects of rater using both the NPE and HB values. Rater 1 showed good accuracy (ρc = 0.986 to 0.999), while raters 3 and 4 were less accurate (ρc = 0.205 to 0.936). Conversion to the HB scale had little effect on bias but reduced numerically both precision and accuracy for most raters on most assessment dates (precision, r = -0.001 to -0.132; and accuracy, ρc = -0.003 to -0.468). Interrater reliability was also reduced slightly by conversion of estimates to HB midpoint values. Estimates of mean SLB severity were significantly different between image analysis and raters 2, 3, and 4, and there were frequently significant differences among raters (F = 151 to 1,260, P = 0.001 to P < 0.0001). Only on 26 June 2007 did conversion to the HB scale change the means separation ranking of rater estimates. Nonetheless, image analysis and all raters were able to differentiate control and treated-plot treatments (F = 116 to 1,952, P = 0.002 to P < 0.0001, depending on date and rater). Conversion of NPEs to the HB scale tended to reduce F values slightly (2006: NPEs, F = 116 to 276, P = 0.002 to 0.0005; and, for the HB-converted values, F = 101 to 270, P = 0.002 to 0.0005; 2007: NPEs, F = 164 to 1,952, P = 0.001 to P < 0.0001; and, for HB-converted values, F = 126 to 1,633, P = 0.002 to P < 0.0001). The results reaffirm the need for accurate and reliable disease assessment to minimize over- or underestimates compared with actual disease, and the data we present support the view that, where multiple raters are deployed, they should be assigned in a manner to reduce any potential effect of rater differences on the analysis.


An 18-mo randomized trial of a low-glycemic-index diet and weight change in Brazilian women.
Despite interest in the glycemic index diets as an approach to weight control, few long-term evaluations are available. The objective was to investigate the long-term effect of a low-glycemic-index (LGI) diet compared with that of a high-glycemic-index (HGI) diet; all other dietary components were equal. After a 6-wk run-in, we randomly assigned 203 healthy women [body mass index (in kg/m2): 23-30] aged 25-45 y to an LGI or an HGI diet with a small energy restriction. The primary outcome measure was weight change at 18 mo. Secondary outcomes included hunger and fasting insulin and lipids. Despite requiring a run-in and the use of multiple incentives, only 60% of the subjects completed the study. The difference in glycemic index between the diets was approximately 35-40 units (40 compared with 79) during all 18 mo of follow-up, and the carbohydrate intake from energy remained at approximately 60% in both groups. The LGI group had a slightly greater weight loss in the first 2 mo of follow-up (-0.72 compared with -0.31 kg), but after 12 mo of follow-up both groups began to regain weight. After 18 mo, the weight change was not significantly different (P = 0.93) between groups (LGI: -0.41 kg; HGI: -0.26 kg). A greater reduction was observed in the LGI diet group for triacylglycerol (difference = -16.4 mg/dL; P = 0.11) and VLDL cholesterol (difference = -3.7 mg/dL; P = 0.03). Long-term weight changes were not significantly different between the HGI and LGI diet groups; therefore, this study does not support a benefit of an LGI diet for weight control. Favorable changes in lipids confirmed previous results.


Postmortem MR imaging in the fetal and neonatal period.
Postmortem imaging has become an increasingly important part in the examination of deceased fetuses and neonates. This article discusses how to perform magnetic resonance (MR) imaging autopsy, including such technical determinators as field strength, and factors influencing image quality. Also included is a discussion on the indications for MR autopsy, including stillborns and terminations of pregnancy, and natural and unexplained death.


Bacteriocin diversity: ecological and evolutionary perspectives.
The bacteriocin family is the most abundant and diverse group of bacterial defense systems. Bacteriocins range from the well-studied narrow spectrum, high molecular weight colicins produced by Escherichia coli and the short polypeptide lantibiotics of lactic acid bacteria to the relatively unknown halocins produced almost universally by the haolobacteria. The abundance and diversity of this potent arsenal of weapons is clear. Less clear is their evolutionary origins and the role they play in mediating microbial interactions. The goal of this review is to explore what we know about the evolution and ecology of the best-characterized family of bacteriocins, the colicins. We summarize current knowledge of how such extraordinary protein diversity arose and is maintained in microbial populations and what role these toxins play in mediating microbial population-level and community-level dynamics.


Human brain methionine- and leucine-enkephalins and their receptors during ageing.
Brain Met- and Leu-enk levels were investigated with radioimmunoassay and their binding to enkephalin receptors was studied with [3H]Met- and [3H]Leu-enkephalin in 56 human subjects (4-93 yr). Of the brain areas investigated, the head of the caudate nucleus and pallidum showed an age-associated decline for both Met- and Leu-enk content. In the substantia nigra and in putamen, no significant age-effect was seen. Binding of the enkephalins, which was studied in the head of the caudate nucleus and hippocampus, did not show significant age dependency. In conclusion, ageing affects human brain enkephalin levels but not their receptor binding, at least in brain areas investigated in the present study.


Studying of telomeric protein-protein interactions by Bi-molecular fluorescence complementation (BiFC) and peptide array-based assays.
Studying protein-protein interactions is critical to our understanding of the signaling pathways. The Telomere Interactome is assembled around the telomeres and consists of proteins and factors from diverse pathways. Dissecting how this protein network contributes to telomere protection and length regulation requires the elucidation of the complex and dynamic interactions between the proteins within the interactome. Here, we focus on the Bi-molecular fluorescence complementation (BiFC) and peptide array methods that have proven vital in our studies of telomere protein interaction networks.


[The frontal lobe and psychoses].
Manic-depressive illness may be explained as an alteration of the normally existing equilibrium to be found between two antagonist brain mechanisms located in the prefrontal isocortex area. Each mechanism, located in the middle frontal area, deriving from the hippocampal allocortex, is responsible for tendencies to change. Its predominance leads to clinical patterns of mania. The other mechanism--located in the lateral orbital area, deriving from the olfactory allocortex, is responsible for tendencies to perseveration. Its predominance leads to clinical patterns of depression. Any alteration in the frontal lobe morphogenesis is likely to cause a permanent unbalance between both mechanisms. Consequently, an oscillation between opposite tendencies--i.e. a tendency to change, and a tendency to perseveration, may be expected which, clinically speaking, appears as mania, and depression phases. In this connection, the following points are discussed, namely (a) prefrontal functions, (b) peri-allocortex frontal zones participating in affective behaviors, (c) the problem of differences between brain hemispheres, and the probability of an anatomic basis for temperament. Eventually, features of a psychiatric science based on brain anatomy are enhanced.


Pathways to childhood depressive symptoms: the role of social, cognitive, and genetic risk factors.
Childhood depressive conditions have been explored from multiple theoretical approaches but with few empirical attempts to address the interrelationships among these different domains and their combined effects. In the present study, the authors examined different pathways through which social, cognitive, and genetic risk factors may be expressed to influence depressive symptoms in 300 pairs of child twins from a longitudinal study. Path analysis supported several indirect routes. First, risks associated with living in a step- or single-parent family and punitive parenting did not directly influence depressive outcome but were instead mediated through maternal depressive symptoms and child negative attributional style. Second, the effects of negative attributional style on depressive outcome were greatly exacerbated in the presence of precipitating negative life events. Third, independent of these social and cognitive risk mechanisms, modest genetic effects were also implicated in symptoms, with some indication that these risks are expressed through exposure to negative stressors. Together, these routes accounted for approximately 13% of total phenotypic variance in depressive symptoms. Theoretical and analytical implications of these results are discussed in the context of several design-related caveats.


Effect of leukocyte compatibility on neutrophil increment after transfusion of granulocyte colony-stimulating factor-mobilized prophylactic granulocyte transfusions and on clinical outcomes after stem cell transplantation.
The primary limitations of granulocyte transfusions include low component cell dose and leukocyte incompatibility. Component cell dose improved with granulocyte colony-stimulating factor (G-CSF) mobilization, and the transfusion of G-CSF-mobilized, human leukocyte antigen (HLA)-matched granulocyte components resulted in significant, sustained absolute neutrophil count (ANC) increments. However, the effect of leukocyte compatibility on outcomes with G-CSF-mobilized granulocyte transfusions is unclear. The objectives were to determine the effect of leukocyte compatibility on ANC increments and selected clinical outcomes after transfusion of prophylactic, G-CSF-mobilized granulocyte components into neutropenic recipients of autologous peripheral blood stem cell (PBSC) transplants. Beginning on transplant day 2, 23 evaluable recipients were scheduled to receive 4 alternate-day transfusions of granulocyte components apheresed from a single donor given G-CSF. G-CSF was also given to recipients after transplantation. Recipient ANC was determined before and sequentially after each granulocyte transfusion to determine the peak ANC increment. Leukocyte compatibility was determined at study entry only by a lymphocytotoxicity screening assay (s-LCA) against a panel of HLA-defined cells. Eight recipients had positive s-LCA. On days 2 and 4, the mean peak ANC increments after granulocyte transfusion were comparable between the cohorts with positive and negative s-LCA. However, the mean peak ANC increments on day 6 (246/microL vs 724/microL; P =.05) and day 8 (283/microL vs 1079/microL; P =.06) were lower in the cohort with positive s-LCA, in spite of the transfusion of comparable component cell doses. Adverse reactions occurred with only 5 of 87 (5.7%) granulocyte transfusions and were not associated with leukocyte compatibility test results. Platelet increments, determined 1 hour after granulocyte transfusion, were comparable between the cohorts. Although the 2 cohorts received PBSC components with similar CD34(+) cell doses, the cohort with a positive s-LCA had delayed neutrophil engraftment and a greater number of febrile days and required more days of intravenous antibiotics and platelet transfusions. Leukocyte incompatibility adversely affected ANC increments after the transfusion of G-CSF-mobilized granulocyte components and clinical outcomes after PBSC transplantation.


Validation of a new homogeneous immunoassay for the detection of carisoprodol in urine.
The objective of this project was to validate a new high-throughput homogeneous enzyme immunoassay (HEIA) for the rapid detection of carisoprodol in human urine. Carisoprodol (Soma(®)) and meprobamate are widely prescribed as musculoskeletal pain relief drugs and are listed as one of the 10 most frequently identified drugs associated with DUI cases. Carisoprodol has a short elimination half-life of 1-3 h; however, its major active metabolite, meprobamate, has a longer elimination half-life of 6-17 h. As a result, it is important for an immunoassay to cross-react with both compounds. The advantage of this new assay is that cutoff concentrations can be adjusted between 100 and 500 ng/mL. The reportable range was 25 to 1000 ng/mL for carisoprodol and 50 to 10,000 ng/mL for meprobamate. The intraday coefficient of variation (% CV) for the semi-quantitative assay was less than 1%. The homogeneous assay was validated with a total of 86 urine samples previously analyzed by liquid chromatography-tandem mass spectrometry with carisoprodol concentrations ranging from 50 to 10,000 ng/mL. The accuracy was found to be 100% when immunoassay cutoff concentrations of carisoprodol and meprobamate were set at 100 and 1000 ng/mL, respectively.


New Flavonol Glucuronides from the Flower Buds of Syzygium aromaticum (Clove).
Repeated chromatography of the EtOAc-soluble fraction from the 70% EtOH extract of the flower buds of Syzygium aromaticum (clove) led to the isolation and characterization of four new flavonol glucuronides, rhamnetin-3-O-β-d-glucuronide (1), rhamnazin-3-O-β-d-glucuronide (2), rhamnazin-3-O-β-d-glucuronide-6″-methyl ester (3), and rhamnocitrin-3-O-β-d-glucuronide-6″-methyl ester (4), together with 15 flavonoids (5-19) having previously known chemical structures. The structures of the new compounds 1-4 were determined by interpretation of spectroscopic data, particularly by 1D- and 2D-NMR studies. Six flavonoids (6, 7, 9, 14, 18, and 19) were isolated from the flower buds of S. aromaticum for the first time in this study. The flavonoids were examined for their cytotoxicity against human ovarian cancer cells (A2780) using MTT assays. Among the isolates, pachypodol (19) showed the most potent cytotoxicity on A2780 cells with an IC50 value of 8.02 μM.


Psychological consequences of DES exposure in utero.
Between the 1950s and the late 1970s, millions of women worldwide took diethylstilbestrol (DES) during pregnancy. It was claimed that DES prevented miscarriage, even though a clinical trial was interrupted in 1953 when an interim analysis showed no beneficial effect in the prevention of miscarriage. In 1971, it emerged that DES exposure in utero was associated with somatic effects in adulthood, including female genital abnormalities with obstetric consequences, vaginal cancer, and male urogenital disorders. This article examines the psychological effects of exposure to DES in utero, based on a review of the literature using the standard Prescrire methodology. In two experimental studies, mice exposed to DES during gestation were found to be more aggressive than unexposed mice. A randomised clinical trial and epidemiological studies have pointed to a risk of psychological disorders during adolescence and adulthood after DES exposure in utero. A placebo-controlled randomised trial of DES was conducted in London in the 1950s but was never published. In the 1980s, a research team recovered some of the original data and obtained information on the adult health status of the persons exposed in utero. Compared to the placebo group, psychological disorders were twice as frequent in the adults who were likely to have been exposed to DES in utero. Three large epidemiological studies were also conducted. One study showed that major depressive episodes were about 1.5 times more frequent in women exposed to DES in utero than in unexposed women; the second showed that exposed women had an episode of major weight loss more often than unexposed women; while the third showed no significant difference between the groups in terms of depressive episodes. Smaller studies also suggest that depressive episodes tend to be more frequent after DES exposure in utero. In practice, these data suggest that persons exposed to DES in utero have an increased risk of experiencing psychological disorders and should be monitored accordingly.


Upper extremity injuries in young athletes.
Injuries are becoming increasingly prevalent in pediatric athletes. Many of these injuries are diagnosed clinically and do not require imaging for diagnosis, but the sheer increase in numbers of injuries means that radiologists are evaluating more of them. Some injuries that young athletes sustain are simply due to trauma, such as falls, and may be experienced outside sports just as easily; however, others are peculiar to athletic activities. Many of the latter are chronic overuse injuries as opposed to acute injuries and have characteristic appearances. The types of injuries young athletes incur often change based on the stage of skeletal maturity of the patient, and it serves the radiologist well to keep in mind the typical appearances expected at different ages.


Comparison of MS clinical phenotypes using conventional and magnetization transfer MRI.
To identify differences in pathology between the principal clinical phenotypes of MS using conventional and magnetization transfer (MT) MRI. T1-weighted and T2-weighted images as well as MT scans were obtained from 20 controls, 21 patients presenting with clinically isolated syndromes suggestive of MS, and 93 MS patients with relapsing-remitting, secondary progressive, benign, or primary progressive course. Metrics considered: hypointense T1 and T2 lesion volumes, average lesion MT ratio, average brain MT ratio, peak height and position from MT histograms. MS patients had lower MT metrics than controls. Patients with clinically isolated syndromes had MT measures similar to controls, whereas primary progressive MS patients had lower histogram peak height with normal peak position. Relapsing-remitting MS patients had lower MT measures, higher T2 lesion load and ratio of hypointense T1 to T2 lesion volumes than patients with clinically isolated syndromes, and lower MT ratio and peak height than benign MS patients. Benign MS patients were similar to controls and patients with clinically isolated syndromes. Secondary progressive MS patients had the lowest MT measures and highest lesion loads. Pathology in patients with clinically isolated syndromes is confined to modest tissue damage in the lesions seen on T2-weighted scans. Severe damage is important for the later development of disability. However, microscopic damage in normal-appearing white matter may be a major contributor to disability in primary progressive MS.


Magnetic molecularly imprinted polymer for the selective extraction of quercetagetin from Calendula officinalis extract.
A new magnetic molecularly imprinted polymers (MMIPs) for quercetagetin was prepared by surface molecular imprinting method using super paramagnetic core-shell nanoparticle as the supporter. Acrylamide as the functional monomer, ethyleneglycol dimethacrylate as the crosslinker and acetonitrile as the porogen were applied in the preparation process. Fourier transform infrared spectrometer (FT-IR), X-ray diffraction (XRD) and Vibrating sample magnetometer (VSM) were applied to characterize the MMIPs, and High performance liquid chromatography (HPLC) was utilized to analyze the target analytes. The selectivity of quercetagetin MMIPs was evaluated according to their recognition to template and its analogues. Excellent binding for quercetagetin was observed in MMIPs adsorption experiment, and the adsorption isotherm models analysis showed that the homogeneous binding sites were distributed on the surface of the MMIPs. The MMIPs were employed as adsorbents in solid phase extraction for the determination of quercetagetin in Calendula officinalis extracts. Furthermore, this method is fast, simple and could fulfill the determination and extraction of quercetagetin from herbal extract.


Adalimumab in the management of cutaneous and oral lichen planus.
Lichen planus (LP) is a common, chronic, inflammatory dermatosis that may involve the skin as well as oral and genital mucosa. Characterized by distinctive purplish papules often featuring white reticular scale, LP commonly is resistant to treatment. My patient presented with extensive, violaceous, and lacelike whitish lesions on the distal extremities, including the hands and feet, and the vulva. Approximately 10% to 12% of her body surface area (BSA) was involved, and her condition became progressively worse over time, with thick plaques developing on the buccal mucosa and tongue. After several conventional therapies failed, the patient underwent treatment with adalimumab, a tumor necrosis factor (TNF) antagonist. An almost clear response was noted by week 6, and the patient's lesions remained almost fully resolved after week 22. Additional studies are warranted to investigate the efficacy and safety of adalimumab for the treatment of LP.


Impact of new methicillin-resistant Staphylococcus aureus carriage postoperatively after living donor liver transplantation.
Preoperative carriage of methicillin-resistant Staphylococcus aureus (MRSA) is associated with an increased risk of MRSA infection after liver transplantation. It is not known, however, whether new MRSA carriage postoperatively also increases the risk of MRSA infection after liver transplantation. We retrospectively reviewed the data from 242 adult patients who underwent living donor liver transplantation (LDLT) including microbiological and medical records from admission to 3 months after LDLT. Uni and multivariate analyses were performed to identify independent risk factors for postoperative MRSA infection among preoperative noncarriers of MRSA. Postoperative MRSA infection occurred in 18 of 219 preoperative noncarriers of MRSA by median postoperative day 26. Operation time of at least 16 hours and postoperative colonization with MRSA independently predicted postoperative MRSA infection. Postoperative surveillance cultures should be performed periodically after liver transplantation to identify high-risk candidates for postoperative MRSA infection, even among preoperative noncarriers of MRSA.


Can CT and MR Shape and Textural Features Differentiate Benign Versus Malignant Pleural Lesions?
The study aimed to identify a radiomic approach based on CT and or magnetic resonance (MR) features (shape and texture) that may help differentiate benign versus malignant pleural lesions, and to assess if the radiomic model may improve confidence and accuracy of radiologists with different subspecialty backgrounds. Twenty-nine patients with pleural lesions studied on both contrast-enhanced CT and MR imaging were reviewed retrospectively. Three texture and three shape features were extracted. Combinations of features were used to generate logistic regression models using histopathology as outcome. Two thoracic and two abdominal radiologists evaluated their degree of confidence in malignancy. Diagnostic accuracy of radiologists was determined using contingency tables. Cohen's kappa coefficient was used to assess inter-reader agreement. Using optimal threshold criteria, sensitivity, specificity, and accuracy of each feature and combination of features were obtained and compared to the accuracy and confidence of radiologists. The CT model that best discriminated malignant from benign lesions revealed an AUCCT = 0.92 ± 0.05 (P < 0.0001). The most discriminative MR model showed an AUCMR = 0.87 ± 0.09 (P < 0.0001). The CT model was compared to the diagnostic confidence of all radiologists and the model outperformed both abdominal radiologists (P < 0.002), whereas the top discriminative MR model outperformed one of the abdominal radiologists (P = 0.02). The most discriminative MR model was more accurate than one abdominal (P = 0.04) and one thoracic radiologist (P = 0.02). Quantitative textural and shape analysis may help distinguish malignant from benign lesions. A radiomics-based approach may increase diagnostic confidence of abdominal radiologists on CT and MR and may potentially improve radiologists' accuracy in the assessment of pleural lesions characterized by MR.


Targeting of proteins to the Golgi apparatus.
The proteins that reside in the Golgi carry out functions associated with post-translational modifications, including glycosylation and proteolytic processing, membrane transport, recycling of endoplasmic reticulum proteins and maintenance of the structural organisation of the organelle itself. The latter includes Golgi stacking, interconnections between stacks and the microtubule-dependent positioning of the organelle within the cell. There are a number of distinct groups of Golgi membrane proteins, including glycosyltransferases, recycling trans-Golgi network (TGN) proteins, peripheral membrane proteins and receptors. Considerable effort has been directed at understanding the basis of the localisation of Golgi glycosyltransferases and recycling TGN proteins; in both cases there is increasing evidence that multiple signals may be involved in their specific localisation. A number of models for the Golgi retention of glycosyltransferases have been proposed including oligomerisation, lipid-mediated sorting and intra-Golgi retrograde transport. More information is required to determine the contribution of each of these potential mechanisms in the targeting of different glycosyltransferases. Future work is also likely to focus on the relationship between the localisation of resident Golgi proteins and the maintenance of Golgi structure.


Predicting genotype compositions in norovirus seasons in Japan.
Noroviruses cause acute gastroenteritis. Since multiple genotypes of norovirus co-circulate in humans, changing the genotype composition and eluding host immunity, development of a polyvalent vaccine against norovirus in which the genotypes of vaccine strains match the major strains in circulation in the target season is desirable. However, this would require prediction of changes in the genotype composition of circulating strains. A fitness model that predicts the proportion of a strain in the next season from that in the current season has been developed for influenza A virus. Here, such a fitness model that takes into account the fitness effect of herd immunity was used to predict genotype compositions in norovirus seasons in Japan. In the current study, a model that assumes a decline in the magnitude of cross immunity between norovirus strains according to an increase in the divergence of the major antigenic protein VP1 was found to be appropriate for predicting genotype composition. Although it is difficult to predict the proportions of genotypes accurately, the model is effective in predicting the direction of change in the proportions of genotypes. The model predicted that GII.3 and GII.4 may contract, whereas GII.17 may expand and predominate in the 2015-2016 season. The procedure of predicting genotype compositions in norovirus seasons described in the present study has been implemented in the norovirus forecasting system (NOROCAST).


Smallholder Farmer Adoption of Climate-Related Adaptation Strategies: The Importance of Vulnerability Context, Livelihood Assets, and Climate Perceptions.
Despite increased research characterizing the adaptive capacity of households and communities, there are few empirical studies that test why farmers adopt costly climate-related adaptive strategies, which strategies are implemented, and farmers' perceptions of climate changes. In this study, we analyzed determinants for smallholder farmer adoption of adaptation strategies in Chiapas, Mexico. We conducted 291 surveys with landowners in eight coffee farming communities. Farmers were asked which of 21 adaptation strategies they had engaged in, within five categories: migration, storage, land use diversification, community investment, and market exchange. We found the most frequent strategies included planting shade coffee, diversifying crop varieties, shifting sow date, building living walls, reforesting, or engaging in soil conservation. Although many farmers have experienced natural disasters like hurricanes and earthquakes, they were most concerned by long-term threats to crops like coffee rust and higher temperatures, that require costly adaptive investments. We find farmers adapt to climate events because of their vulnerability context (i.e., experience with disasters and distance to markets). Land holdings (i.e., natural capital), farm equipment (i.e., physical capital), and group membership (i.e., social capital), were also key factors influencing adaptation. Finally, farmers with strong perceptions of drought and temperature change were most likely to adapt. These results suggest policy makers should have a multi-pronged approach to: improve farmers' resource base through explicitly promoting adaptation strategies like crop and income diversification; inform climate perceptions through workshops on climate and weather; and strengthen participation in community and producer organizations to increase smallholder adaptation.


Estradiol metabolites are potent mitogenic substances for human ovarian cancer cells.
The etiology of ovarian cancer appears to be associated with a long-term influence of estrogens. However, evidence is accumulating that certain estradiol metabolites may play a decisive role in the carcinogenesis of estrogen-dependent diseases. In the present study we examined the effect of estradiol metabolites on the proliferation and apoptosis of human ovarian cancer cells in comparison to the effect of their parent substance. The ovarian cancer cell line OVCAR-3 was used for the experiments. 17Beta-estradiol (E2), 2-hydroxyestradiol (2-OHE2), 4-hydroxyestradiol (4-OHE2) and 16alpha-hydroxyestrone (16-OHE1) were incubated for seven days in the concentration range of 0.01 nM to 10 nM. Proliferation and apoptosis were measured by commercially available assay kits. E2 enhanced proliferation rate and concomitantly reduced apoptotic rate of the ovarian cancer cells at physiological concentrations. 2-OHE2 had no significant effect, whereas 4-OHE2 elicited similar effects on proliferation and apoptotic rate as E2. The greatest proliferative and antiapoptotic effect was observed for 16-OHE1, the values being significantly different to the effects of E2. The pattern of endogenous estradiol metabolism may play a role in defining ovarian cancer risk. This may be of importance in certain predisposed women who are treated with hormone therapy in postmenopause.


The effect of otitis media in childhood on the development of middle ear admittance on reaching adulthood.
To determine the long-term change in static admittance values of subjects with a positive or negative history of otitis media (OM) and ventilation tube (VT) insertion; and to investigate the association between static admittance values and tympanic membrane abnormalities. Prospective follow-up study. A total of 358 subjects with or without a history of OM (OM+ or OM-) and VT insertion (VT+ or VT-) derived from a birth cohort that had been observed from preschool to adulthood. Otomicroscopic and tympanometric data obtained at subject ages 8 and 18 years. Static admittance values generally increased with age. At age 8 years, static admittance values were highest in OM+VT+ ears and lowest in OM- ears. At age 18 years, the difference between OM+VT+ and OM+VT- ears was larger, while the difference in static admittance values between OM+VT- and OM- ears had disappeared. In the group of VT+ subjects, the proportion of extreme static admittance values increased from 16% to 35% between ages 8 and 18 years. Correlation coefficients of individual static admittance values at 8 and 18 years were high in all groups and ranged from 0.61 to 0.85. We could not demonstrate an intermediate role of tympanic membrane abnormalities in the relation between VTs and static admittance at young adult age, except for atrophy. The static admittance value at age 8 years was a strong predictor for the value at age 18 years. A VT+ status was associated with a larger increase in static admittance than can be explained on the basis of age alone.


General characteristics of food in developing regions-a situational diagnostic assessment.
Since the founding of the Food and Agriculture Organization of the United Nations in 1946, it has reported on the serious problem of hunger in the world and has undertaken various initiatives for eradicating this problem; however, they have ended in failure. The number of people suffering from hunger has increased from 500 to 800 million in a period of six decades, despite constant growth in world food production, which has been more than sufficient to cover the needs of all of humanity since the 1970s. This paper analyses FAO initiatives in the framework of the evolution of the nutritional situation in developing countries and identifies national and regional contexts in which technical solutions may be successful, as well as those requiring the implementation of economic, political and social measures.


The effects of inflammation, aging and oxidative stress on the pathogenesis of diabetes mellitus (type 2 diabetes).
Diabetes mellitus is seen to be prevalent among the different epidemics. The prevalence rate of the diabetes mellitus is seen to be increasing in different regions of the world. Type 2 diabetes mellitus is the most common form of the disease that causes the defect in the production of insulin. It is associated with the disruption in the metabolism of fat, proteins and carbohydrates. Different complications that are associated with T2DM includes the retinopathy, neuropathy, nephropathy and weakness and other issues. Due to the loss of the function of the insulin, the metabolism is disturbed. . It is needed to consider the effects of inflammation aging and the oxidative stress on the diabetes mellitus. Therefore this review has dealt with this particular issue in great detail. The predominant aim of this review was to evaluate the effects of inflammation aging and oxidative stress on the T2DM. It was achieved through correlating and comparing the studies of different researchers. This review article has reviewed this topic in great detail considering the different researches related to the inflammation aging, oxidative stress and their impact on the diabetes mellitus.


Mining environmental toxicology information: web resources.
Environmental toxicology is the study of the ecological effects of anthropogenic substances released into the environment. It is a relatively diverse field addressing impacts to aquatic and terrestrial organisms and communities. The determination of potential risk associated with toxic agents is of interest to government regulators, industry, researchers, private organizations and citizen groups. In assessing the ecological risk associated with a chemical stressor, it is important to establish linkages between likely exposure concentrations and adverse effects to ecological receptors. To do so requires access to reliable information resources. The proper application of such data requires familiarity with the scientific literature and keeping abreast of new and emerging issues as well as state-of-the-art research findings and methods. In addition, an understanding of government regulations as they relate to environmental issues is also of primary interest. The advent of the Web has made these tools accessible at computer desktops. This review focuses on currently available free Web resources related to environmental toxicology, specifically those which address available empirical data sources, predictive tools and publications of interest such as standard test methods, guidance documents and governmental regulations.