Higher rates of cigarette smoking in male adolescents before the onset of schizophrenia: a historical-prospective cohort study.
The prevalence of cigarette smoking among schizophrenia patients is significantly higher than in the general population; this may reflect self-medication of symptoms and/or adverse effects of neuroleptics. The authors examined the prevalence of cigarette smoking in apparently healthy adolescents later hospitalized for schizophrenia. Each year, a random sample of male Israeli military recruits, who have been screened and found not to be suffering from major psychopathology, complete a smoking questionnaire. Through the Israeli National Psychiatric Hospitalization Case Registry, 14,248 of these adolescents were followed to determine later psychiatric hospitalization. Of the 14,248 adolescents assessed, 4,052 (28.4%) reported smoking at least one cigarette a day. Over a 4-16-year follow-up, the prevalence of schizophrenia in the entire cohort was 0.3% (N=44). Smokers were at greater risk for later schizophrenia; the adjusted relative risk was 1.94, and the 95% confidence interval (CI) was 1.05-3.58. The number of cigarettes smoked was significantly associated with the risk for schizophrenia. Compared to nonsmokers, adolescents who smoked 1-9 cigarettes/day were 1.38 times (95% CI=0.48-4.00) as likely to be hospitalized later for schizophrenia, and adolescents who smoked 10 cigarettes/day or more were 2.28 times (95% CI=1.19-4.34) as likely; the latter difference was statistically significant. Taken together with the existing data on abnormalities in nicotinic transmission in patients and their relatives, this higher prevalence of smoking in future schizophrenia patients, before the onset of their illness, might indicate that impaired nicotinic neurotransmission is involved in the pathophysiology of schizophrenia.


Effects of laboratory maintenance on the nature of surface reactive antigens of Neisseria gonorrhoeae.
The extensive in vitro cultivation methods used in propagating and maintaining gonococcal cells were found to affect their virulence, antigenicity, and ultrastructure. Adapting a laboratory-maintained strain of gonococci to animal virulence resulted in two lines of pilated cells with similar colonial morphologies. The animal-adapted cells, however, had a greater amount of extracellular pili and a more prominent peptidoglycan cell wall layer. They were also more resistant to the bactericidal effects of guinea-pig complement and more reactive in macroagglutination and bactericidal tests with strain-specific gonococcal antibody. In comparative guinea-pig protection trials, formalin-fixed cells of the animal-adapted cell line were 500 times more effective as immunogens than the laboratory-maintained cell line.


Apolipoprotein e gene variability and cognitive functions at age 79: a follow-up of the Scottish mental survey of 1932.
Apolipoprotein E (APOE) genotype is a possible influence on nonpathological cognitive aging. The authors studied 462 community-dwelling, 79-year-old people born in 1921, whose childhood IQ had been assessed in the Scottish Mental Survey of 1932 (Scottish Council for Research in Education, 1933). Adjusting for sex, childhood IQ, and self-reported illnesses, the authors found that those with an APOE e4 allele had significantly lower Wechsler Logical Memory (D. Wechsler, 1987) scores than those without an e4 allele. Those people with APOE s2/e3 genotypes had significantly higher Wechsler Logical Memory scores than e3/s3, who were significantly higher than e3/e4. Neither nonverbal reasoning nor verbal fluency were affected. In this sample, APOE genotype contributed to verbal memory in old age.


Living-related liver transplantation for multiple liver metastases from rectal carcinoid tumor: a case report.
A 42-year-old woman was admitted to our hospital because of multiple liver tumors detected by ultrasonography. Colonoscopy revealed submucosal tumor in the rectum, which was considered the primary lesion. Endoscopic mucosal resection followed by histopathological examination revealed that the tumor was carcinoid. The resected margin of the tumor was positive for malignant cells. Two courses to transcatheter arterial chemotherapy for liver metastasis were ineffective. Accordingly, the rectal tumor and metastatic lymph nodes were surgically resected. One month after the operation, she received liver transplantation (left lateral segment and caudate lobe) from her son. No recurrent lesion has been observed at two years after the liver transplantation. Liver transplantation should be considered as a treatment option even in advanced case of carcinoid metastasis to the liver. We also discuss the literature on liver transplantation for metastatic carcinoid tumor.


PONDR-FIT: a meta-predictor of intrinsically disordered amino acids.
Protein intrinsic disorder is becoming increasingly recognized in proteomics research. While lacking structure, many regions of disorder have been associated with biological function. There are many different experimental methods for characterizing intrinsically disordered proteins and regions; nevertheless, the prediction of intrinsic disorder from amino acid sequence remains a useful strategy especially for many large-scale proteomic investigations. Here we introduced a consensus artificial neural network (ANN) prediction method, which was developed by combining the outputs of several individual disorder predictors. By eight-fold cross-validation, this meta-predictor, called PONDR-FIT, was found to improve the prediction accuracy over a range of 3 to 20% with an average of 11% compared to the single predictors, depending on the datasets being used. Analysis of the errors shows that the worst accuracy still occurs for short disordered regions with less than ten residues, as well as for the residues close to order/disorder boundaries. Increased understanding of the underlying mechanism by which such meta-predictors give improved predictions will likely promote the further development of protein disorder predictors. Access to PONDR-FIT is available at www.disprot.org.


Nice guideline on thyroid disease: where does it take us with liothyronine?
The new NICE guidelines on thyroid disease and its management do not recommend the routine use of liothyronine, but do not completely rule it out either. Guidelines from the British and European Thyroid Associations are open to a "trial of liothyronine" on an individual basis. Some patients do not feel well on L-thyroxine despite a serum TSH in the reference range. Key issues to consider in such patients include establishing whether the patient had established hypothyroidism initially, and whether the L-thyroxine has been titrated carefully enough, possibly using small increments, to achieve a careful balance between symptoms and serum TSH concentrations. Patients should also be considered for other causes of the symptoms which may be wide-ranging. Meta-analyses of several, but small, randomised control trials show no advantage, or disadvantage of liothyronine over L-thyroxine. However, detailed sub-analysis identifies some tantalising results eg on preferential weight loss, patient preference, and possibly genetic markers. Although linked with plausible theoretical explanations, these results may be over-interpreted. The key questions are whether a short-term trial treatment is worthwhile and safe, and whether in the future sub-groups of patients can be identified who may benefit from liothyronine. These questions remain divisive but require additional focussed research. It could be argued that inflated costs of liothyronine in some countries have either distracted from or helped focus on the science. Costs need to be addressed. However better biomarkers of tissue level thyroid action, and a better understanding of the impact of genetic polymorphisms will help to make progress when choosing if there is a place for liothyronine in the future. (words: 262).


European union water policy--tasks for implementing "Water Framework Directive" in pre-accession countries.
Water Framework Directive aiming to maintain and improve the aquatic environment in the EU was launched by the European Parliament in 2000. According to this directive, control of quantity is an ancillary element in securing good water quality and therefore measures on quantity, serving the objective of ensuring good quality should also be established. Accordingly, it is a comprehensive and coordinated package that will ensure all European waters to be protected according to a common standard. Therefore, it refers to all other Directives related to water resources management such as Urban Wastewater Treatment Directive Nitrates Directive, Drinking Water Directive, Integrated Pollution Prevention Control etc. Turkey, as a candidate state targeting full-membership, should comply the necessary preparations for the implementation of the "Water Framework Directive" as soon as possible. In this study, the necessary legislative, political, institutional, and technical attempts of the pre-accession countries have been discussed and effective recommendations have been offered for future activities in Turkey.


Proteomics approach reveals urinary markers for early pregnancy diagnosis in buffaloes.
This study aimed to compare urine proteomics from non- and pregnant buffaloes in order to identify potential biomarkers of early pregnancy. Forty-four females underwent hormonal ovulation synchronization and were randomly divided into two experimental groups: inseminated (n = 30) and non-inseminated (n = 14). The pregnant females were further divided into two groups: pregnant at Day 12 (P12; n = 8) and at Day 18 (P18; n = 8) post-ovulation. The non-pregnant group was also subdivided into two groups: non-pregnant at Day 12 (NP12; n = 7) and at Day 18 (NP18; n = 7). Urine was collected from all females on Days 12 or 18. The samples were processed for proteomics. A total of 798 proteins were reported in the urine considering all groups. The differential proteins play essential roles during pregnancy, acting in cellular transport and metabolism, endometrial remodeling, embryonic protection, and degradation of defective proteins. We suggest that some proteins from our study can be considered biomarkers for early pregnancy diagnosis, since they were increased in pregnant buffaloes. SIGNIFICANCE: Macromolecules have been studied for early pregnancy diagnosis, aiming to increase reproductive efficiency in cattle and buffaloes. Direct methods such as rectal palpation and ultrasonography have been considered late. Thus, this study aimed to compare urine proteomics from non- and pregnant buffaloes to identify potential biomarkers of early pregnancy. The differential proteins found in our study play essential roles during pregnancy, acting in cellular transport and metabolism, endometrial remodeling, embryonic protection, and degradation of defective proteins. We suggest that these proteins can be considered possible biomarkers for early pregnancy diagnosis since they were increased in the pregnant buffaloes.


Human glandular kallikrein 2 (hK2) expression in prostatic intraepithelial neoplasia and adenocarcinoma: a novel prostate cancer marker.
We describe the expression of a potentially new tumor marker, human glandular kallikrein 2 (hK2), that may be useful as an adjunct to prostate-specific antigen (PSA) in the diagnosis and monitoring of prostate cancer. We evaluated 257 radical prostatectomy specimens removed at the Mayo Clinic with pathologic Stage 12 adenocarcinoma to compare the cytoplasmic expression of hK2, PSA, and prostatic acid phosphatase (PAP) in benign tissue, high-grade prostatic intraepithelial neoplasia (PIN), and adenocarcinoma. Two monoclonal antibodies, hK2-A523 and hK2-G586, specific for hK2 were used, as well as antibodies against PSA (PSM-773) and PAP (polyclonal). Intense epithelial cytoplasmic immunoreactivity was observed in every case for hK2-A523, hK2-G586, PSA, and PAP (100% of cases, respectively). The intensity and extent of hK2 expression for both antibodies were greater in cancer than high-grade PIN; furthermore, high-grade PIN was greater than benign epithelium. Cases of Gleason primary grade 4 and 5 cancer showed hK2 staining in almost every cell, whereas there was greater heterogeneity of staining in lower grades of cancer. In marked contrast to hK2, PSA and PAP immunoreactivity was most intense in benign epithelium and stained to a lesser extent in PIN and carcinoma. The number of immunoreactive cells for hK2 and PSA was not predictive of cancer recurrence. hK2 was expressed in every cancer, and the expression incrementally increased from benign epithelium to high-grade PIN and adenocarcinoma. PSA and PAP displayed inverse immunoreactivity compared with hK2. The expression of hK2 and PSA was not predictive of cancer recurrence in patients with Stage T2 carcinoma. Expression of hK2 indicates that this kallikrein antigen is both prostate localized and tumor associated. Tissue expression of hK2 appears to be regulated independently of PSA and PAP. Further studies are needed to determine whether tissue immunoreactivity of hK2 will prove clinically useful in the diagnosis and monitoring of prostate cancer.


[Features of the healing of suppurative wounds in patients undergoing treatment with collagen preparations (histochemical and electron-microscopic study)].
The dynamics of purulent wound healing developing in patients surgically treated for phlegmons or abscesses was studied histochemically and electron microscopically on the material of successive biopsies. It was shown that purulent wound healing is characterized by the desynchronization of inflammation and regeneration associated with the reduced macrophagal response and disturbances of the microcirculation system. Collagen sponge reduces inflammatory changes, activates the macrophage reaction, restores intercellular interactions, normalizes the microcirculation system, enhances proliferation and differentiation of fibroblasts, collagen synthesis and secretion, processes of fibrillogenesis, maturation of granulation tissue, epithelialization.


Composite GO/Ceramic Membranes Prepared via Chemical Attachment: Characterisation and Gas Permeance Properties.
Graphene oxide (GO) oligo-layered laminates were self-assembled on porous ceramic substrates via their simple dip-coating into aqueous GO dispersions. To augment the stability of the developed composite GO/ceramic membranes and control the morphology and stacking quality of the formed laminate, short-((3-glycidoxypropyl)trimethoxy silane-GLYMO, (3-aminopropyl)triethoxy silane-APTES), and long-chain (polydopamine-PDA) molecules were involved and examined as interfacial linkers. A comparative study was performed regarding the linker's capacity to enhance the interfacial adhesion between the ceramic surface and the GO deposit and affect the orientation and assemblage characteristics of the adjacent GO nanosheets that composed the formed oligo-layered laminates. Subsequently, by post-filtrating a GO/H2O suspension through the oligo-layered laminate membranes, the respective multi-layered ones have been developed, whereas ethylenediamine (EDA) was used in the suspension as an efficient molecular linker that strongly bonds and interlocks the GO nanosheets. The definition of the best linker and approach was conducted on macroporous α-alumina disks, due to the use of inexpensive raw materials and the ability to fabricate them in the lab with high reproducibility. To validate the concept at a larger scale, while investigating the effect of the porous substrate as regards its micrometer-scale roughness and surface chemistry, specific chemical modifications that yielded membranes with the best gas permeability/selectivity performance were replicated on a commercial single-channel monolith with a ZrO2 microfiltration layer. XRD, Raman, ATR, FESEM, and XPS analyses were conducted to study the structural, physicochemical, surface, and morphological properties of the GO/ceramic composite membranes, whereas permeance results of several gases at various temperatures and trans-membrane pressures were interpreted to shed light on the pore structural features. Concerning the short-chain linkers, the obtained results ascertain that GLYMO causes denser and more uniform assembly of GO nanosheets within the oligo-layered laminate. PDA had the same beneficial effect, as it is a macromolecule. Overall, this study shows that the development of gas-separating membranes, by just dipping the linker-modified substrate into the GO suspension, is not straightforward. The application of post-filtration contributed significantly to this target and the quality of the superficially deposited, thick GO laminate depended on this of the chemically attached oligo-layered one.


Expression spectrum of melanoma antigen-encoding gene family members in colorectal carcinoma.
The 12 members of the human melanoma antigen-encoding (MAGE) gene family encode tumor-specific peptide antigens. Some antigens coded by the MAGE genes are potentially useful for cancer-specific immunotherapy. However, little information on the expression of these genes in human colon carcinomas is available. We investigated the expression of 10 of the 12 genes in human colon tissue. Eighty pairs of tumor and normal tissue samples from the human colon were studied by means of reverse transcription-polymerase chain reaction. None of the genes was expressed in the 80 control samples of normal tissue. On the other hand, expression was recognized in tumor samples, ranging from 5% of samples for MAGE-6 to 44% for MAGE-8. Seventy of the 80 tumor samples (88%) expressed at least 1 of the 10 MAGE genes. The frequency of liver metastasis was significantly higher in cases with tumor samples that expressed MAGE-3 than in those that did not express this gene. This tendency was not observed for other members of the MAGE gene family. No significant differences were observed in the other clinicopathologic factors between any MAGE-positive and -negative tumor cases. The MAGE genes were exclusively expressed in carcinoma tissues and not in normal tissues of the colon. The finding that nearly 90% of tumors expressed at least one MAGE gene indicates the possible clinical use of this gene for both immunotherapy and molecular diagnosis.


A novel phosphatidylcholine which contains pentadecanoic acid at sn-1 and docosahexaenoic acid at sn-2 in Schizochytrium sp. F26-b.
Docosahexaenoic acid (DHA, 22:6n-3)-containing phospholipids are a ubiquitous component of the central nervous system and retina, however their physiological and pharmacological functions have not been fully elucidated. Here, we report a novel DHA-containing phosphatidylcholine (PC) in a marine single cell eukaryote, Schizochytrium sp. F26-b. Interestingly, 31.8% of all the fatty acid in F26-b is DHA, which is incorporated into triacylglycerols and various phospholipids. In phospholipids, DHA was found to make up about 50% of total fatty acid. To identify phospholipid species containing DHA, the fraction of phospholipids from strain F26-b was subjected to normal phase high-performance liquid chromatography (HPLC). It was found that DHA was incorporated into PC, lyso-PC, phosphatidylethanolamine, and phosphatidylinositol. The major DHA-containing phospholipid was PC in which 32.5% of the fatty acid was DHA. The structure of PC was analyzed further by phospholipase A2 treatment, fast atom bombardment mass spectrometry, and 1H- and 13C-NMR after purification of the PC with reverse phase HPLC. Collectively, it was clarified that the major PC contains pentadecanoic acid (C15:0) at sn-1 and DHA at sn-2; the systematic name of this novel PC is therefore "1-pentadecanoyl-2-docosahexaenoyl-sn-glycero-3-phosphocholine."


Microalgae's polysaccharides, are they potent antioxidants? Critical review.
The scientific community continue to explore novel bioactive molecules by investigating natural origins; microalgae are photosynthetic organisms considered as a sustainable resource to use in many fields. They present a high diversity in species and richness in terms of attractive bio-compounds. The aim of this review is to (1) provide first an overview of current issues related to oxidative stress, and propose a natural metabolite derived from eukaryotic and prokaryotic microalgae; 'polysaccharides' as a powerful antioxidant agent, then, (2) organize the available data on the antioxidant potential of polysaccharides derived from the main microalgal groups (red microalgae, green microalgae, and cyanobacteria) and especially highlighted the key species of each group (Porphyridium sp., Chlorella sp., and Arthrospira sp., respectively), meanwhile, (3) we described the chemical composition of polysaccharides from each class, and (4) we cite briefly the most factors affecting the antioxidant activity of these molecules. Finally, we explored the major challenges and gaps found to require more investigation.


Microbial infection causes the appearance of hemocytes with extreme spreading ability in monolayers of the tobacco hornworm Manduca sexta.
The ability to adhere to and spread on a surface is a common property of insect blood cells. Spreading on a glass surface by insect hemocytes is often used as a measure of immune fitness that can be inhibited by some insect pathogens and parasites. Here, we report that upon infection of the tobacco hornworm Manduca sexta with either a fungus (Beauveria bassiana) or a bacterium (Photorhabdus luminescens), a new type of hemocyte, not previously observed in healthy insects, was found in hemocyte monolayers. These cells have a distinctive morphology, characterised by extreme spreading ability. They achieve a diameter of up to 120 microm after 1 h on glass coverslips and are therefore extremely thin. These hyper-spreading cells first appear in fungal-infected insects prior to hyphal growth. Their numbers later fall to zero as the pathogen begins to proliferate. The same hyper-spreading cells are induced after a 24 h delay following an injection of laminarin, a source of the fungal cell wall polymer beta-1,3-glucans. Wounding, on the other hand, did not cause the appearance of hyper-spreading cells. Evidence is presented here that is consistent with these spreading cells having a role in the cellular immune response of nodule formation.


Metabolism of [14C]-2,4,6-trinitrotoluene in tobacco cell suspension cultures.
The metabolism of 2,4,6-trinitrotoluene (TNT) was investigated in tobacco cell suspension cultures amended with [14C]-TNT. Five metabolites were purified and characterized. Temporal evolution of metabolites was monitored during a 120 h incubation period. Metabolites structure was identified by acid and enzymatic hydrolysis, followed by electrospray ionization mass spectrometry and 1H and 13C NMR spectroscopy analyses. The majority of metabolites were conjugates formed by glycose conjugation on the hydroxylamine group of either 2-hydroxylamino-4,6-dinitrotoluene (2-HADNT) or 4-hydroxylamino-2,6-dinitrotoluene (4-HADNT), which led to monoglycoside then to diglycoside. Various diglycosides were observed with gentiobioside or sophoroside formation. Bound residues represented a small fraction (<10% of initial 14C) irrespective of the interval after TNT amendment. Free ADNT was detected only in the medium. This study highlights the central role played by HADNT in the TNT metabolic pathway in tobacco cell suspension culture, and the key role of these compounds and of glycosyltransferases in TNT phytoremediation processes.


Does psychomotor agitation in major depressive episodes indicate bipolarity? Evidence from the Zurich Study.
Kraepelin's partial interpretation of agitated depression as a mixed state of "manic-depressive insanity" (including the current concept of bipolar disorder) has recently been the focus of much research. This paper tested whether, how, and to what extent both psychomotor symptoms, agitation and retardation in depression are related to bipolarity and anxiety. The prospective Zurich Study assessed psychiatric and somatic syndromes in a community sample of young adults (N = 591) (aged 20 at first interview) by six interviews over 20 years (1979-1999). Psychomotor symptoms of agitation and retardation were assessed by professional interviewers from age 22 to 40 (five interviews) on the basis of the observed and reported behaviour within the interview section on depression. Psychiatric diagnoses were strictly operationalised and, in the case of bipolar-II disorder, were broader than proposed by DSM-IV-TR and ICD-10. As indicators of bipolarity, the association with bipolar disorder, a family history of mania/hypomania/cyclothymia, together with hypomanic and cyclothymic temperament as assessed by the general behavior inventory (GBI) [15], and mood lability (an element of cyclothymic temperament) were used. Agitated and retarded depressive states were equally associated with the indicators of bipolarity and with anxiety. Longitudinally, agitation and retardation were significantly associated with each other (OR = 1.8, 95% CI = 1.0-3.2), and this combined group of major depressives showed stronger associations with bipolarity, with both hypomanic/cyclothymic and depressive temperamental traits, and with anxiety. Among agitated, non-retarded depressives, unipolar mood disorder was even twice as common as bipolar mood disorder. Combined agitated and retarded major depressive states are more often bipolar than unipolar, but, in general, agitated depression (with or without retardation) is not more frequently bipolar than retarded depression (with or without agitation), and pure agitated depression is even much less frequently bipolar than unipolar. The findings do not support the hypothesis that agitated depressive syndromes are mixed states. The results are limited to a population up to the age of 40; bipolar-I disorders could not be analysed (small N).


Associated systemic factors in cerebrovascular ischemia.
Systemic disorders (eg, cardiac, hematologic) are commonly recognized as predisposing and sometimes actual precipitating events in cerebral ischemia. From available studies, the incidence of precipitation is not clear. To determine this, we undertook a comprehensive investigation of all patients with ischemic brain disease for a one-year period. Results reveal that brain ischemia is more commonly precipitated by systemic illness than usually supposed, particularly transient ischemic attacks of the vertebrobasilar circulation and completed infarcts in the carotid distribution. Cardiac disorders outnumber all other precipitating events. As they are more amenable to therapy than atherosclerosis, a diligent search for such precipitating events is warranted in patients with ischemic symptoms.


Toward New Paradigms in the Follow Up of Adult Patients With Celiac Disease on a Gluten-Free Diet.
Gluten free diet is the only available treatment for celiac disease (CeD). Patients with CeD who do not adhere to a strict gluten-free diet (GFD) have been found to have complications involving nutritional deficiencies, increased risk of bone fractures, increased risk of mortality, and certain types of cancers. Complete removal of gluten from the diet in a patient with CeD often results in symptomatic, serologic, and histologic remission. However, strict compliance with the diet is challenging. Long-term follow-up care is needed to assure treatment compliance and positive health outcomes. Monitoring celiac specific serology, nutrient deficiencies, bone mineral density, and assessment of GFD compliance have been recommended in clinical practice. However, there is no consensus on which specific tests and how often they should be performed during the follow up. Here, we have performed a review of the literature on current strategies to follow up patients with CeD. There are new tools for monitoring adherence to the GFD which could change some paradigms in following up treated patients.


Lymphokine-mediated bone resorption requires endogenous prostaglandin synthesis.
Enhanced synthesis of prostaglandin (PG) E by explanted fetal rat bones was initiated by lymphocyte-conditioned media but not by physiological levels of parathyroid hormone. Rapid release of PGE from bone occurred only when the lymphokine was present. Synthesis of PGE preceded and was necessary for the bone resorption caused by the lymphokine preparation. Local production of prostaglandins in response to inflammatory cell or tumor-derived factors may in part be responsible for the localized bone loss that occurs in certain pathological states.


Risk Estimation for ICU Patients with Personalized Anomaly-Encoded Bedside Patient Data.
We propose a novel framework to estimate intensive care unit patients' health risk continuously with anomaly-encoded patient data. This framework consists of two modules. In the first module, we use Gaussian process models to learn change trend and day-night circulation in temporal patient data and annotate abnormal data. Such models provide dynamically adaptable bedside patient monitoring instead of conventional threshold-based monitoring. In the second module, we use the abnormal data together with the learned Gaussian models to estimate patients' risk level by predicting their in-hospital mortality and remaining length of stay in ICU ward. We show that prediction models with anomaly-encoded data have better performance than those with raw patient measurements, and they are comparable with state-of-art prediction models.


Detection and serotyping of human adenoviruses from patients with influenza-like illness in mongolia.
Human adenoviruses (HAdVs) are responsible for approximately 5%-10% of acute respiratory infections. The serotypes of commonly detected respiratory HAdV in Asian countries are diverse. However, there are no well-documented reports of circulating HAdV serotypes in Mongolia. Between January 2010 and May 2011, 1,950 influenza-negative samples from patients with influenza-like illness, including eye swabs from patients with eye symptoms, were screened for HAdV, and 40 samples (2.1%) were positive for HAdVs. Among these 40 samples, 31 samples were positive for the hexon gene used in phylogenetic analysis, as determined by PCR. We identified 7 different serotypes. We constructed the phylogenetic trees of HAdV-B7 and HAdV-B3, the 2 most commonly detected serotypes in this study. All detected HAdV-B7 and -B3 Mongolian strains had identical sequences. HAdV-D8, known to be associated with epidemic keratoconjunctivitis (EKC), was detected from nasopharyngeal and eye swabs. There was no difference between the amino acid sequences of the hexon and fiber genes that may affect tissue tropism in Mongolian strains and those in EKC-causing strains.


Do critical illness survivors with multimorbidity need a different model of care?
There is currently a lack of evidence on the optimal strategy to support patient recovery after critical illness. Previous research has largely focussed on rehabilitation interventions which aimed to address physical, psychological, and cognitive functional sequelae, the majority of which have failed to demonstrate benefit for the selected outcomes in clinical trials. It is increasingly recognised that a person's existing health status, and in particular multimorbidity (usually defined as two or more medical conditions) and frailty, are strongly associated with their long-term outcomes after critical illness. Recent evidence indicates the existence of a distinct subgroup of critical illness survivors with multimorbidity and high healthcare utilisation, whose prior health trajectory is a better predictor of long-term outcomes than the severity of their acute illness. This review examines the complex relationships between multimorbidity and patient outcomes after critical illness, which are likely mediated by a range of factors including the number, severity, and modifiability of a person's medical conditions, as well as related factors including treatment burden, functional status, healthcare delivery, and social support. We explore potential strategies to optimise patient recovery after critical illness in the presence of multimorbidity. A comprehensive and individualized approach is likely necessary including close coordination among healthcare providers, medication reconciliation and management, and addressing the physical, psychological, and social aspects of recovery. Providing patient-centred care that proactively identifies critical illness survivors with multimorbidity and accounts for their unique challenges and needs is likely crucial to facilitate recovery and improve outcomes.


Effect of Gender and Physical Activity on Internet Addiction in Medical Students.
To determine the effect of gender and physical activity on internet addiction in medical students. In this cross sectional, analytical study Young's internet addiction test questionnaire was distributed to 350 MBBS students of Army Medical College, Rawalpindi. The study was conducted from January to May 2015. A dichotomous response from students regarding physical activity was obtained which was verified from the sports department of the institution. Based upon total score, internet addiction was categorized as no addiction if the score was less than or equal to 49, moderate addiction when the score was 50 to 79 and severe when the score was 80 to 100. Out of 322 respondents 175 (54.3%) were males and 147 (42.7%) females with a mean age of 19.27±1.01 years. Total internet addiction score and frequency of internet addiction were similar between males and females (37.71±11.9 vs 38.63±14.00, p=0.18 and 25 vs 29, p=0.20). However, total score and frequency of internet addiction were higher in students lacking physical activity as compared to those with regular physical activity (40.37±15.05 vs 36.38±11.76, p=0.01 and 30 vs 24, p=0.01). Internet addiction is unrelated to gender however it is inversely related to physical activity.


Mutational analysis of Tyr-318 within the non-nucleoside reverse transcriptase inhibitor binding pocket of human immunodeficiency virus type I reverse transcriptase.
The highly conserved Tyr-318 is part of the non-nucleoside reverse transcriptase inhibitor (NNRTI)-specific lipophilic pocket of human immunodeficiency virus type I reverse transcriptase (RT) and makes contact within 4 A with the NNRTIs in all reported RT/NNRTI complexes. Using site-directed mutagenesis, six mutant RTs were constructed bearing the mutations Y318H, Y318K, Y318L, Y318C, Y318W, and Y318F. We found that only the Y318W and Y318F mutant RTs retained substantial RT activity, whereas the catalytic activities of the Y318K, Y318C, Y318H, and Y318L RT mutants were less than 5% of the wild-type activity. The Y318F mutant RT retained substantial sensitivity to the majority of NNRTIs tested, whereas the Y318W mutant RT showed varying degrees of resistance to NNRTIs. Subunit-specific site-directed mutagenesis revealed that there was no difference in the catalytic activity or resistance/sensitivity spectrum toward NNRTIs regardless of whether the Tyr-318 mutation was introduced in both subunits or only in the p66 subunit of RT. Recombinant viruses harboring the Y318F or Y318W mutation in the RT showed a similar resistance/sensitivity pattern to NNRTIs as their corresponding 318 mutant recombinant RTs. Our findings stress a functional or structural role for Tyr-318 in wild-type RT and argue for the design of novel NNRTIs that interact more closely with this amino acid in the NNRTI-specific pocket of human immunodeficiency virus type I RT.


Prediction of human observer performance by numerical observers: an experimental study.
Numerical observers are investigated for predicting the outcome of a free-response human observer study involving the detection of simulated pulmonary nodules in images reconstructed from low-dose computed tomography projection data by use of several reconstruction algorithms. A new way of calculating the figure of merit of a numerical observer is proposed wherein the detectability of signals in a particular image depends on the noise properties associated with that image and not the other images in the data set. The resulting variants of numerical observers are found to perform better than their traditional counterparts. In particular, the imagewise variant of the region-of-interest observer is found to predict best the rank ordering of algorithms by human observers for the free-response task.


NTP Toxicology and Carcinogenesis Studies of Dimethoxane (CAS No. 828-00-2) (Commercial Grade) in F344/N Rats and B6C3F1 Mice (Gavage Studies).
Dimethoxane is used as an antimicrobial agent in water-based paints, dyestuffs, fabric softeners, sizings, and spinning emulsions. In the past, it was used in lipsticks and other cosmetic preparations. Toxicology and carcinogenesis studies were conducted by administering commercial-grade dimethoxane (80% pure, none of these impurities exceeded 3%) in corn oil gavage to groups of F344/N rats and B6C3F1 mice of each sex one time or 5 days per week for 16 days, 13 weeks, 15 months, or 2 years. Clinical pathology analyses were performed at 15 months in the 2-year studies. Commercial-grade dimethoxane was studied because that is the grade to which humans are generally exposed. The same lot of commercial-grade dimethoxane was used in genetic toxicology tests for mutagenicity in Salmonella typhimurium, for sister chromatid exchanges (SCEs) and chromosomal aberrations in Chinese hamster ovary (CHO) cells, and for sex-linked recessive lethal mutations and translocation in Drosophila. Sixteen-Day Studies: In the 16-day studies, rats and mice received 0, 125, 250, 500, 1,000, or 2,000 mg/kg dimethoxane in corn oil per day. Deaths occurred in rats and in male mice that received 2,000 mg/kg. Body weights of rats and mice were similar to those of vehicle controls. Compound-related clinical signs were not seen in surviving rats. Hemorrhage and necrosis of the stomach were observed in rats in the 2,000 mg/kg group which died before the end of the studies. Lesions of the forestomach, including inflammation, hyperplasia, hyperkeratosis, and ulceration, occurred in rats that received 250-2,000 mg/kg. Mice that received 500-2,000 mg/kg dimethoxane had lesions of the forestomach including erosion, ulceration, hyperplasia, and hyperkeratosis. Forestomach lesions were not seen at 125 or 250 mg/kg. Thirteen-Week Studies: No compound-related deaths occurred in rats. Doses used were 0, 31, 62, 125, 250, or 500 mg/kg dimethoxane in corn oil by gavage. The final mean body weights of rats that received 500 mg/kg were 17% lower than that of vehicle controls for males and 5% lower for females. Ulceration, inflammation, and acanthosis with hyperkeratosis of the stratified squamous epithelium of the forestomach were seen in rats that received 500 mg/kg. Forestomach lesions were not seen in males that received 31 mg/kg or in females that received 31, 62, or 125 mg/kg. All mice lived to the end of the studies (doses used were 0, 31, 62, 125, 250, or 500 mg/kg dimethoxane in corn oil by gavage). Final mean body weights of dosed and vehicle control mice were similar. Minimal-to- mild acanthosis and hyperkeratosis of the squamous epithelium of the forestomach were seen in 4/10 high dose male and 1/10 high dose female mice. Because of the forestomach lesions observed in rats and mice and reduced body weight observed for male rats, doses selected for the 2-year studies were 0, 62.5, or 125 mg/kg dimethoxane in corn oil, given by gavage 5 days per week to groups of 60 male rats; 0, 125, or 250 mg/kg to groups of 60 female rats; and 0, 250, or 500 mg/kg to groups of 58 or 60 mice of each sex. Ten animals per sex and species from each dose group were killed 15 months after initiation of the studies to determine toxicity, pre-neoplastic lesions, and early induced neoplasia. Fifteen-Month Studies: Minimal diffuse acanthosis and hyperplasia of the forestomach were seen in 7/10 female rats at 250 mg/kg, 7/10 males at 125 mg/kg, and 1/9 male and 1/9 female vehicle controls. Acanthosis of the forestomach was seen in 7/10 male and 6/10 female mice at 500 mg/kg. Harderian gland adenomas were seen in one high dose male and one high dose female mouse. A harderian gland adenocarcinoma was seen in a second high dose female mouse. No compound-related effects were observed for clinical chemical or hematologic values or for organ weights for rats or mice. Body Weight and Survival in the Two-Year Studies: Mean body weights of dosed and vehicle control rats and mice of each sex were generally similar. No significant differences in survival were observed between any groups of rated between any groups of rats (male: vehicle control, 23/50; low dose, 28/50; high dose, 21/50; female: 30/50; 31/50; 24/50) or mice (male: 33/50; 27/48; 29/50; female: 36/50; 35/50; 34/50). Nonneoplastic and Neoplastic Effects in the Two-Year Studies: At no site was a significantly increased incidence of neoplastic lesions observed in dosed male or female rats or in dosed female mice. Acanthosis and hyperkeratosis were increased in the forestomach of high dose rats; acanthosis, hyperkeratosis, focal hyperplasia, and chronic active inflammation were increased in the forestomach of dosed mice. The incidence of squamous cell papillomas of the forestomach was increased in high dose male mice (vehicle control, 2/47; low dose, 3/47; high dose, 7/50). A squamous cell carcinoma of the forestomach was present in another high dose male mouse. Although the incidence of squamous cell papillomas in the high dose group was not significantly different from that in the vehicle controls, the incidence exceeded the highest observed in historical corn oil gavage vehicle controls (3/49). Other than a single squamous cell papilloma in the esophagus of a low dose male mouse, no hyperplastic or neoplastic lesions were seen outside the stomach of dosed mice which could be related to the administration of dimethoxane. Despite the observation of three harderian gland neoplasms in mice killed at 15 months, no increase in the incidences of harderian gland neoplasms was seen in dosed mice in the 2-year studies (male: 2/48; 2/48; 2/48; female: 2/48; 0/49; 2/50). Genetic Toxicity: Dimethoxane was mutagenic in strain TA100 of S. typhimurium in the presence but not the absence of exogenous metabolic activation; it was not mutagenic in strains TA98, TA1535, or TA1537 with or without activation. Dimethoxane induced SCEs and chromosomal aberrations in CHO cells both with or without exogenous metabolic activation. Dimethoxane induced sex-linked recessive lethal mutations in Drosophila when administered by abdominal injection to adult males; no induction of reciprocal translocations was observed in adult males after injection of dimethoxane. Conclusions: Under the conditions of these 2-year corn oil gavage studies, there was no evidence of carcinogenic activity of dimethoxane for male F344/N rats receiving 62.5 or 125 mg/kg or for female F344/N rats receiving 125 or 250 mg/kg per day. There was equivocal evidence of carcinogenic activity of dimethoxane for male B6C3F1 mice, as indicated by an increased incidence of forestomach neoplasms. There was no evidence of carcinogenic activity for female B6C3F1 mice receiving 250 or 500 mg/kg per day. Acanthosis and hyperkeratosis occurred at increased incidences in the forestomach of high dose rats. Inflammation, acanthosis with hyperkeratosis, and focal hyperplasia occurred at increased incidences in the forestomach of dosed mice. Synonyms: acetomethoxan; acetomethoxane; 6-acetoxy-2,4-dimethyl-m-dioxane; 2,6-dimethyl-m-dioxan-4-yl acetate; 2,6-dimethyl-m-dioxan-4-ol acetate; 2,6-dimethyl-1,3-dioxan-4-ol acetate


Effects of chemically characterized fractions from aerial parts of Echinacea purpurea and E. angustifolia on myelopoiesis in rats.
Echinacea species are used for beneficial effects on immune function, and various prevalent phytochemicals have immunomodulatory effects. Using a commercial E. purpurea (L.) Moench product, we have evaluated the myelopoietic effect on bone marrow of rats treated with various extracts and correlated this with their chemical class composition. Granulocyte/macrophage-colony forming cells (GM-CFCs) from femurs of female Sprague-Dawley rats were assessed at 24 h after 7 daily oral treatments. A 75% ethanolic extract at 50 mg dried weight (derived from 227 mg aerial parts) per kg body weight increased GM-CFCs by 70% but at 100 mg/kg was without effect. Ethanolic extracts from aerial parts of E. angustifolia DC. var. angustifolia and E. purpurea from the USDA North Central Regional Plant Introduction Station increased GM-CFCs by 3- and 2-fold, respectively, at 200 mg/kg (~1400 mg/kg plant material). Extract from another USDA E. angustifolia was inactive. Proton and APT NMR, MS, and TLC indicated alkylamides and caffeic-acid derivatives (CADs) present in ethanolic extracts of both the commercial and USDA-derived material. Cichoric and caftaric acids were prominent in both E. purpurea ethanolic extracts but absent in E. angustifolia. Aqueous extract of the commercial material exhibited polysaccharide and CAD signatures and was without effect on GM-CFCs. A methanol-CHCl3 fraction of commercial source, also inactive, was almost exclusively 1:4 nonanoic: decanoic acids, which were also abundant in commercial ethanolic extract but absent from USDA material. In conclusion, we have demonstrated an ethanolextractable myelostimulatory activity in Echinacea aerial parts that, when obtained from commercial herbal supplements, may be antagonized by medium-chain fatty acids presumably derived from a non-plant additive.


Bacterial 2,4-dioxygenases: new members of the alpha/beta hydrolase-fold superfamily of enzymes functionally related to serine hydrolases.
1H-3-hydroxy-4-oxoquinoline 2,4-dioxygenase (Qdo) from Pseudomonas putida 33/1 and 1H-3-hydroxy-4-oxoquinaldine 2,4-dioxygenase (Hod) from Arthrobacter ilicis Rü61a catalyze an N-heterocyclic-ring cleavage reaction, generating N-formylanthranilate and N-acetylanthranilate, respectively, and carbon monoxide. Amino acid sequence comparisons between Qdo, Hod, and a number of proteins belonging to the alpha/beta hydrolase-fold superfamily of enzymes and analysis of the similarity between the predicted secondary structures of the 2,4-dioxygenases and the known secondary structure of haloalkane dehalogenase from Xanthobacter autotrophicus GJ10 strongly suggested that Qdo and Hod are structurally related to the alpha/beta hydrolase-fold enzymes. The residues S95 and H244 of Qdo were found to be arranged like the catalytic nucleophilic residue and the catalytic histidine, respectively, of the alpha/beta hydrolase-fold enzymes. Investigation of the potential functional significance of these and other residues of Qdo through site-directed mutagenesis supported the hypothesis that Qdo is structurally as well as functionally related to serine hydrolases, with S95 being a possible catalytic nucleophile and H244 being a possible catalytic base. A hypothetical reaction mechanism for Qdo-catalyzed 2,4-dioxygenolysis, involving formation of an ester bond between the catalytic serine residue and the carbonyl carbon of the substrate and subsequent dioxygenolysis of the covalently bound anionic intermediate, is discussed.


[Relationship between temporomandibular disorders and malocclusions].
Regarding the relationship between malocclusions and temporomandibular disorders (TMD), from the leading cause to one of the local biological factors, the change in the understanding of the academic community since the 1980s has affected the clinical diagnosis, treatment behavior, and the direction of scientific research. At present, it is believed that the etiology of TMD is multifactor. The occlusal factors and the occurrence of TMD are weakly related, but there are some common malocclusions such as occlusal interference on non-working side, excessive sliding between maximum intercuspid position (MIP) and retruded contact position (RCP), unstable MIP and so on, may be risk factors that promote the disease. The occurrence of TMD symptoms is promoted under the combined action of behavior, biology, environment, social cognition, mentality and other comprehensive factors. In student education and clinical work, the risk of iatrogenic occlusal trauma in promoting the occurrence of TMD cannot be ignored. The impact of the patient's social and psychological environment on the TMD should be paid attention, and comprehensive treatment strategies is advocated.


A computerized bioskills system for surgical skills training in total knee replacement.
Although all agree that the results of total knee replacement (TKR) are primarily determined by surgical skill, there are few satisfactory alternatives to the 'apprenticeship' model of surgical training. A system capable of evaluating errors of instrument alignment in TKR has been developed and demonstrated. This system also makes it possible quantitatively to assess the source of errors in final component position and limb alignment. This study demonstrates the use of a computer-based system to analyse the surgical skills in TKR through detailed quantitative analysis of the technical accuracy of each step of the procedure. Twelve surgeons implanted a posterior-stabilized TKR in 12 fresh cadavers using the same set of surgical instruments. During each procedure, the position and orientation of the femur, tibia, each surgical instrument, and the trial components were measured with an infrared coordinate measurement system. Through analysis of these data, the sources and relative magnitudes of errors in position and alignment of each instrument were determined, as well as its contribution to the final limb alignment, component positioning and ligament balance. Perfect balancing of the flexion and extension gaps was uncommon (0/15). Under standardized loading, the opening of the joint laterally exceeded the opening medially by an average of approximately 4 mm in both extension (4.1 +/- 2.1 mm) and flexion (3.8 +/- 3.4 mm). In addition, the overall separation of the femur and the tibia was greater in flexion than extension by an average of 4.6 mm. The most significant errors occurred in locating the anterior/posterior position of the entry point in the distal femur (SD = 8.4 mm) and the correct rotational alignment of the tibial tray (SD = 13.2 degrees). On a case-by-case basis, the relative contributions of errors in individual instrument alignments to the final limb alignment and soft tissue balancing were identified. The results indicate that discrete steps in the surgical procedure make the largest contributions to the ultimate alignment and laxity of the prosthetic knee. Utilization of this method of analysis and feedback in orthopaedic training is expected rapidly to enhance surgical skills without the risks of patient exposure.


Laser-induced vapor nanobubbles for B16-F10 melanoma cell killing and intracellular delivery of chemotherapeutics.
The most lethal form of skin cancer is cutaneous melanoma, a tumor that develops in the melanocytes, which are found in the epidermis. The treatment strategy of melanoma is dependent on the stage of the disease and often requires combined local and systemic treatment. Over the years, systemic treatment of melanoma has been revolutionized and shifted toward immunotherapeutic approaches. Phototherapies like photothermal therapy (PTT) have gained considerable attention in the field, mainly because of their straightforward applicability in melanoma skin cancer, combined with the fact that these strategies are able to induce immunogenic cell death (ICD), linked with a specific antitumor immune response. However, PTT comes with the risk of uncontrolled heating of the surrounding healthy tissue due to heat dissipation. Here, we used pulsed laser irradiation of endogenous melanin-containing melanosomes to induce cell killing of B16-F10 murine melanoma cells in a non-thermal manner. Pulsed laser irradiation of the B16-F10 cells resulted in the formation of water vapor nanobubbles (VNBs) around endogenous melanin-containing melanosomes, causing mechanical cell damage. We demonstrated that laser-induced VNBs are able to kill B16-F10 cells with high spatial resolution. When looking more deeply into the cell death mechanism, we found that a large part of the B16-F10 cells succumbed rapidly after pulsed laser irradiation, reaching maximum cell death already after 4 h. Practically all necrotic cells demonstrated exposure of phosphatidylserine on the plasma membrane and caspase-3/7 activity, indicative of regulated cell death. Furthermore, calreticulin, adenosine triphosphate (ATP) and high-mobility group box 1 (HMGB1), three key damage-associated molecular patterns (DAMPs) in ICD, were found to be exposed from B16-F10 cells upon pulsed laser irradiation to an extent that exceeded or was comparable to the bona fide ICD-inducer, doxorubicin. Finally, we could demonstrate that VNB formation from melanosomes induced plasma membrane permeabilization. This allowed for enhanced intracellular delivery of bleomycin, an ICD-inducing chemotherapeutic, which further boosted cell death with the potential to improve the systemic antitumor immune response.


Autoimmune disease and subsequent risk of developing alimentary tract cancers among 4.5 million US male veterans.
Autoimmunity is clearly linked with hematologic malignancies, but less is known about autoimmunity and alimentary tract cancer risk, despite the specific targeting of alimentary organs and tissues by several autoimmune diseases. The authors therefore conducted the first systematic evaluation of a broad range of specific autoimmune diseases and risk for subsequent alimentary tract cancer. On the basis of 4,501,578 US male veterans, the authors identified 96,277 men who developed alimentary tract cancer during up to 26.2 years of follow-up. By using Poisson regression methods, the authors calculated relative risks (RRs) and 95% confidence intervals. A history of autoimmune disease with localized alimentary tract effects generally increased cancer risks in the organ(s) affected by the autoimmune disease, such as primary biliary cirrhosis and liver cancer (RR, 6.01; 95% confidence interval [CI], 4.76-7.57); pernicious anemia and stomach cancer (RR, 3.17; 95% CI, 2.47-4.07); and ulcerative colitis and small intestine, colon, and rectal cancers (RR, 2.53; 95% CI, 1.05-6.11; RR, 2.06; 95% CI, 1.70-2.48; and RR, 2.07; 95% CI, 1.62-2.64, respectively). In addition, a history of celiac disease, reactive arthritis (Reiter disease), and systemic sclerosis all were associated significantly with increased risk of esophageal cancer (RR, 1.86-2.86). Autoimmune diseases without localized alimentary tract effects generally were not associated with alimentary tract cancer risk, with the exception of decreased risk for multiple alimentary tract cancers associated with a history of multiple sclerosis. These findings support the importance of localized inflammation in alimentary tract carcinogenesis. Future research is needed to confirm the findings and improve understanding of underlying mechanisms by which autoimmune diseases contribute to alimentary tract carcinogenesis.


Poisoning mortality in the United States: comparison of national mortality statistics and poison control center reports.
To determine whether the distributions of age and poisoning categories for poisoning deaths are similar in death certificates as compiled by the National Center for Health Statistics (NCHS) and US poison control centers as reported by the Toxic Exposure Surveillance System (TESS). Data from both databases for 1994 were examined. Mortality data from NCHS were identified by applicable E-codes of the International Classification of Diseases-ninth revision (ICD-9). All fatalities described in the TESS report were coded to conform to the ICD-9 system. A total of 16,527 poisoning deaths were recorded by NCHS; 766 deaths were reported by TESS. For NCHS and TESS, respectively, the age distribution of unintentional drug poisonings (N=7,823; 155) and unintentional non-drug poisonings (N=1,234; 102) differed (P <.001), whereas those for intentional poisonings (N=5,320; 413) did not differ significantly. In the NCHS and TESS data sets, respectively, the relative distribution of death circumstances differed (P <.001) for unintentional drug poisonings (47% versus 20%), unintentional non-drug poisonings (8% versus 14%), intentional poisonings (32% versus 54%), and unknown or other circumstances (13% versus 12%). The distributions of poisoning circumstances and age categories were dependent on the data source (P <.001). There was no statistical agreement between the data sets in rankings of the 12 most frequent ICD-9 codes and toxins associated with poisoning deaths. Deaths reported in TESS represent 5% of the poisoning deaths tabulated by NCHS. Differences observed in the 2 data sets may lead to differing health policies to address poisoning hazards.


Dietary fish oil promotes colonic apoptosis and mitochondrial proton leak in oxidatively stressed mice.
An alteration of mitochondrial function can result in disruption of redox homeostasis and is associated with abnormal cancer cell growth. Manganese superoxide dismutase (SOD2) and glutathione peroxidase 4 (Gpx4) are two of the most important antioxidant defense enzymes that protect cells against oxidative stress. We had previously shown that n-3 polyunsaturated fatty acids (PUFA) promote colonocyte apoptosis, a marker of colon cancer risk, in part by enhancing phospholipid oxidation. To elucidate the mechanisms regulating oxidative stress-induced apoptosis in vivo, we fed heterozygous SOD2(Het), Gpx4(Het), and transgenic Gpx4(Tg) mice diets containing either 15% corn oil by weight (CO, enriched in n-6 PUFA) or 3.5% CO + 11.5% fish oil (FO, enriched in n-3 PUFA) for 4 weeks. Our data showed that (i) genetic predeposition to oxidative stress facilitates apoptosis in the mouse colon (Gpx4(Het) > SOD2(Het) > Wt > Gpx4(Tg)), (ii) dietary n-3 PUFA have an additive effect on the induction of apoptosis in Gpx4(Het) and SOD2(Het) mice; and (iii) dietary n-3 PUFA reverse the phenotype in oxidatively protected Gpx4(Tg) mice by elevating apoptosis to a level observed in wild-type (Wt; control) animals. Complimentary experiments examining colonic mitochondrial bioenergetic profiles indicate that FO-fed mice exhibit a significantly (P < 0.05) increased respiration-induced proton leak relative to control CO treatment. This finding was consistent with a loss of membrane potential in response to chronic oxidative stress and supports the contention that n-3 PUFA alter mitochondrial metabolic activity, thereby enhancing apoptosis and reducing colon cancer risk.


Benefits of liver transplantation surgical techniques in the management of extensive retroperitoneal tumors.
The potential for massive hemorrhage imposes additional challenge in the management of retroperitoneal tumors. This report details technical considerations for the management of upper retroperitoneal tumors using principles of liver transplantation. A retrospective chart review of patients who underwent surgery for extensive retroperitoneal tumors using techniques for liver transplantation from December 2002 to November 2007 was done. Twenty-four patients (14 males and 10 females with a mean age 57 years) underwent major retroperitoneal surgery. Renal cell carcinoma was the most common tumor seen in 17 patients. Mean tumor dimension was 12.4 cm. Abdominal exposure was achieved via bilateral subcostal incision with upper midline extension. Right hepatic lobe mobilization and isolation from the inferior vena cava (IVC) was performed in 23 cases. Fourteen patients had IVC involvement by tumor thrombus, which was infrahepatic in six, retrohepatic in five, and intra-atrial in three patients. Tumor thrombus was removed by cavotomy in seven cases, resection and plasty in four cases, IVC graft reconstruction in two cases, and one patient required IVC and atrial graft reconstruction. Liver resection was needed in seven patients to achieve R0 resection. The Pringle maneuver was used in three patients; total liver vascular isolation with venovenous bypass was required in two cases, transdiaphragmatic intrapericardial IVC control in one case, and cardiopulmonary bypass in one patient. There was no intraoperative or postoperative mortality and mean length of stay was 13 days. Liver transplantation surgical principles help achieve exposure and vascular control of major vascular structures that enable safe resection of these extensive retroperitoneal tumors.


Longer V1V2 region with increased number of potential N-linked glycosylation sites in the HIV-1 envelope glycoprotein protects against HIV-specific neutralizing antibodies.
Human immunodeficiency virus type 1 (HIV-1) has the ability to adapt to the host environment by escaping from host immune responses. We previously observed that escape from humoral immunity, both at the individual and at a population level, coincided with longer variable loops and an increased number of potential N-linked glycosylation sites (PNGS) in the viral envelope glycoprotein (Env) and, in particular, in variable regions 1 and 2 (V1V2). Here, we provide several lines of evidence for the role of V1V2 in the resistance of HIV-1 to neutralizing antibodies. First, we determined that the increasing neutralization resistance of a reference panel of tier-categorized neutralization-sensitive and -resistant HIV-1 variants coincided with a longer V1V2 loop containing more PNGS. Second, an exchange of the different variable regions of Env from a neutralization-sensitive HIV-1 variant into a neutralization-resistant escape variant from the same individual revealed that the V1V2 loop is a strong determinant for sensitivity to autologous-serum neutralization. Third, exchange of the V1V2 loop of neutralization-sensitive HIV-1 variants from historical seroconverters with the V1V2 loop of neutralization-resistant HIV-1 variants from contemporary seroconverters decreased the neutralization sensitivity to CD4-binding site-directed antibodies. Overall, we demonstrate that an increase in the length of the V1V2 loop and/or the number of PNGS in that same region of the HIV-1 envelope glycoprotein is directly involved in the protection of HIV-1 against HIV-specific neutralizing antibodies, possibly by shielding underlying epitopes in the envelope glycoprotein from antibody recognition.


The Volume-Regulated Anion Channel LRRC8/VRAC Is Dispensable for Cell Proliferation and Migration.
Cells possess the capability to adjust their volume for various physiological processes, presumably including cell proliferation and migration. The volume-regulated anion channel (VRAC), formed by LRRC8 heteromers, is critically involved in regulatory volume decrease of vertebrate cells. The VRAC has also been proposed to play a role in cell cycle progression and cellular motility. Indeed, recent reports corroborated this notion, with potentially important implications for the VRAC in cancer progression. In the present study, we examined the role of VRAC during cell proliferation and migration in several cell types, including C2C12 myoblasts, human colon cancer HCT116 cells, and U251 and U87 glioblastoma cells. Surprisingly, neither pharmacological inhibition of VRAC with 4-[(2-Butyl-6,7-dichloro-2-cyclopentyl-2,3-dihydro-1-oxo-1H-inden-5-yl)oxy]butanoic acid (DCPIB), carbenoxolone or 5-nitro-2-(3-phenylpropyl-amino)benzoic acid (NPPB), nor siRNA-mediated knockdown or gene knockout of the essential VRAC subunit LRRC8A affected cell growth and motility in any of the investigated cell lines. Additionally, we found no effect of the VRAC inhibition using siRNA treatment or DCPIB on PI3K/Akt signaling in glioblastoma cells. In summary, our work suggests that VRAC is dispensable for cell proliferation or migration.


[State of the pituitary-adrenal system of cosmonauts after orbital flights of different duration].
In order to assess the hypophyseal-adrenal system and glucocorticoid activity, excretion of total 17-hydroxycorticosteroids (17-HOCS) was measured before and at R + 1 day after a standard water load (20 ml/kg). Twenty-six cosmonauts were examined after flights of 2--140 days. Although the cosmonauts spent different time in weightlessness, the content and rate of glucocorticoid excretion in the urine during postflight water loads was 1.5--2 times higher than during preflight loads. This increased excretion of 17-HOCS was associated with their decreased reabsorption and/or increased glomerular secretion. The latter may be a manifestation of extrarenal action of ACTH due to its hyperproduction immediately postflight.


Multiple neurenteric cysts in the posterior fossa and cervical spinal canal--case report.
A 46-year-old woman presented with multiple neurenteric cysts in the posterior fossa and spinal canal. Neuroimaging demonstrated neurenteric cysts in the interspace between the left cerebellar hemisphere and vermis, the lateral side of the right cerebellar hemisphere, and the ventral side of the spinal cord at the C-2 and C-4 levels. Total resection of the paravermian cyst and partial removal of the spinal cyst at the C-4 level were performed. Histological examination showed the cyst wall consisted of single or multiple layers of columnar epithelial cells with secretory granules, with mucin secretion verified by periodic acid-Schiff staining. Immunohistochemical staining showed the walls were positive for the cytokeratin, epithelial membrane antigen, and carcinoembryonic antigen, and negative for glial fibrillary acidic protein and S-100 protein. These findings confirmed the endodermal origin. The diagnosis was neurenteric cyst. The paravermian cyst disappeared, but the spinal cyst at the C-4 level recurred 8 months later. Reoperation became necessary 16 months later. The other two cysts also showed enlargement at 6 or 15 months. Total removal of neurenteric cyst is recommended if possible.


Premarket evaluation of IDS RapID SS/u system for identification of urine isolates.
A total of 170 fresh clinical urine isolates were tested with a premarket configuration of the RapID SS/u system (Innovative Diagnostic Systems, Inc., Atlanta, Ga.), a qualitative micromethod for the identification of selected organisms commonly isolated from urine specimens. Results were compared with those obtained with conventional methods of identifying gram-positive isolates and with the AutoMicrobic system (Vitek Systems, Inc., Hazelwood, Mo.), utilizing Gram-Negative Identification cards for the identification of gram-negative rods. Organisms representing 12 taxa were included in the study. Of the 170 isolates, 163 (95.9%) were correctly identified. A total of 144 strains (84.7%) were correctly identified without additional testing, whereas 19 isolates (11.2%) required further testing. Seven isolates (4.1%) were incorrectly identified. The SS/u system required minimal hands-on time inoculate and interpret reactions. Discrepancies most often occurred with regard to misinterpretation of Escherichia coli and Enterobacter sp. as Citrobacter sp. The IDS RapID SS/u system may indeed prove valuable for the rapid manual identification of urine isolates.


A Poisson mixture model to identify changes in RNA polymerase II binding quantity using high-throughput sequencing technology.
We present a mixture model-based analysis for identifying differences in the distribution of RNA polymerase II (Pol II) in transcribed regions, measured using ChIP-seq (chromatin immunoprecipitation following massively parallel sequencing technology). The statistical model assumes that the number of Pol II-targeted sequences contained within each genomic region follows a Poisson distribution. A Poisson mixture model was then developed to distinguish Pol II binding changes in transcribed region using an empirical approach and an expectation-maximization (EM) algorithm developed for estimation and inference. In order to achieve a global maximum in the M-step, a particle swarm optimization (PSO) was implemented. We applied this model to Pol II binding data generated from hormone-dependent MCF7 breast cancer cells and antiestrogen-resistant MCF7 breast cancer cells before and after treatment with 17beta-estradiol (E2). We determined that in the hormone-dependent cells, approximately 9.9% (2527) genes showed significant changes in Pol II binding after E2 treatment. However, only approximately 0.7% (172) genes displayed significant Pol II binding changes in E2-treated antiestrogen-resistant cells. These results show that a Poisson mixture model can be used to analyze ChIP-seq data.


A new genus in the braconid subfamily Miracinae from the Oriental region, with descriptions of seven new species from India and Sri Lanka.
A new genus in the braconid subfamily Miracinae is described from the Oriental region including a new species from south India. Additionally, six new species of the genus Centistidea Rohwer is described from India and Sri Lanka. Taxonomic keys to separate the new genus from other miracine genera, to the extant species of Rugosimirax gen. nov. and to the Oriental species of Centistidea are provided.


A Rare Case of Unilateral Acute Idiopathic Maculopathy in Young Male.
Unilateral Acute Idiopathic Maculopathy (UAIM) is a rare disorder of Retinal Pigmentary Epithelium (RPE) that mainly affects the young healthy male. The variability of this disease can masquerade different entity, so diagnosis becomes cumbersome. We are reporting a case of young healthy male, who has reported to us with gross diminution of vision from right eye. Right eye examination showed a grayish yellow lesion with fluffy margins on the macula. Based on Optical Coherence Tomography (OCT) and Fundus Fluorescein Angiography (FFA) findings, he was diagnosed as a case of UAIM. He was started on topical anti-inflammatory eye drops with subsequent improvement of his vision.


Impact of Adjuvants on the Immunogenicity and Efficacy of Split-Virion H7N9 Vaccine in Ferrets.
An effective vaccine is urgently needed against the H7N9 avian influenza virus. We evaluated the immunogenicity and protective efficacy of a split-virion H7N9 vaccine with or without the oil-in-water adjuvants in ferrets. Ferrets were vaccinated with 2 doses of unadjuvanted, MF59 or AS03-adjuvanted A/Shanghai/2/2013 (H7N9) vaccine, and the induction of antibodies to hemagglutinin (HA) or neuraminidase proteins was evaluated. Ferrets were then challenged with wild-type H7N9 virus to assess the vaccine's protective efficacy. The vaccine composition and integrity was also evaluated in vitro. Adjuvanted vaccines stimulated robust serum antibody titers against HA and neuraminidase compared with the unadjuvanted vaccines. Although there was a difference in adjuvanticity between AS03 and MF59 at a lower dose (3.75 µg of HA), both adjuvants induced comparable antibody responses after 2 doses of 15 µg. On challenge, ferrets that received adjuvanted vaccines showed lower viral burden than the control or unadjuvanted vaccine group. In vitro examinations revealed that the vaccine contained visible split-virus particles and retained the native conformation of HA recognizable by polyclonal and monoclonal antibodies. The adjuvanted H7N9 vaccines demonstrated superior immunogenicity and protective efficacy against H7N9 infection in ferrets and hold potential as a vaccination regimen.


Platelet counting with the BD Accuri(TM) C6 flow cytometer.
The Accuri™ C6 is a compact flow cytometer that uses a peristaltic pump with a laminar flow fluidic system and can measure absolute cell counts. In this study we have evaluated this method with the International Reference Method (IRM) simultaneously measured on both the Accuri™ C6 and a reference flow cytometer. After optimisation of sample labelling conditions, final dilutions and flow cytometer settings, a comparison of the absolute fluorescent platelet count with the RBC/platelet ratio on the C6 and the IRM was then performed in 144 patient samples with a full range of platelet counts (range 2-650 × 10(9)/l). The platelet/RBC ratio method determined on the Accuri™ agreed well with the IRM (R(2)=0.99, bias=2.3 (Bland Altman) and R(2)=0.96, bias=1.02 at counts <50 × 10(9)/l). The absolute platelet count also agreed well with the IRM (R(2)=0.97, bias=-0.16 and R(2)=0.91, bias=3.7 at <50 × 10(9)/l). The C6 absolute platelet count and RBC/platelet ratio methods also agreed well (R(2)=0.99, bias=-2.5 and R(2)=0.95, bias=2.71 at counts <50 × 10(9)/l). Reproducibility studies on the C6 gave CVs of <5% for the RB/platelet ratio and <12% for the absolute cell counts. The C6 also demonstrated excellent linearity on diluted samples with both volume and ratio methods (R(2)=0.99). As one might expect, the absolute platelet count is therefore slightly more inaccurate than the RBC/platelet ratio particularly at platelet counts <50 × 10(9)/l as it is likely to be more sensitive to pipetting error. The Accuri™ C6 provides a simple, rapid and reliable method for measuring platelet counts by either the RBC/platelet or direct volume methods. The direct volume method can also be used to determine platelet counts within purified platelet preparations or concentrates in the absence of RBC.


START - introducing a novel assessment of consultant readiness in Paediatrics: the entry not the exit.
This article was migrated. The article was marked as recommended. The Royal College of Paediatrics and Child Health (RCPCH) developed a new end-of-training assessment held for the first time in 2012, known as START, the Specialty Trainee Assessment of Readiness for Tenure as a consultant. It is a novel, formative, multi-scenario, OSCE-style, out-of-workplace assessment using unseen scenarios with generic, external assessors undertaken in the trainees' penultimate training year. This paper describes the introduction and structure of this formative assessment. While many other colleges have summative exit exams the inception of this assessment was designed to be formative, providing feedback on consultant-readiness skills, and not a high-stakes hurdle towards the end of training, It was developed from the College's examinations question-setting group and following two pilots in 2009 and 2010, the assessment evolved and the first live diet was held in November 2012.


Increased propensity for amyloidogenesis in male mice.
The male sex is a risk factor for reactive amyloidogenesis in several disease entities. Environmental, socioeconomic or genetic factors may underlie this male preponderance. This study was aimed at discovering whether male sex predisposes to reactive amyloidosis also in mice and to elucidate some of the hormonal associations of this risk. Male and female Swiss mice were subjected to an established amyloid induction protocol and the amount of their splenic amyloid was determined and compared. The effect of estrogen, progesterone, testosterone and adrenalin on amyloidogenesis was studied in both sexes by administering these hormnones during amyloid induction and comparing the amount of splenic amyloid of the study mice with the control mice which received the amyloid induction protocol alone. Amyloid deposition appeared to be more abundant in male mice. This gender difference was not associated with any of the 3 sex hormones tested. Despite an expected increment, adrenalin caused an attenuation of amyloid deposition. The preferential expression of reactive amyloidosis in male mice seems to be unrelated to the common sex hormones. Increased production of other hormones such as adrenalin, or perhaps an augmented susceptibility to their effect, may cause gender differences by suppressing female amyloidogenesis. Our study favors the hypothesis of genetic predisposition as the mechanism leading to sex differences in amyloidogenesis. Further validation of our findings in gonadal ablated models and other amyloid induction protocols is warranted.


A comparison of the efficiency of the Nuclepore and Millipore filtration systems for detecting microfilariae.
Using Brugia pahangi or Dirofilaria immitis as the test organisms no significant difference could be detected between Nuclepore and Millipore filters. It was found that 0.7% of microfilariae passed through the Millipore and 1% through the Nuclepore filters. No microfilariae were lost from the Nuclepore membrane during the staining process.


IgG4-related autoimmune pancreatitis overlapping with Mikulicz's disease and lymphadenitis: a case report.
Autoimmune pancreatitis (AIP) is a form of chronic pancreatitis that is categorized as type 1 or type 2 according to the clinical profile. Type 1 AIP, which predominantly presents in a few Asian countries, is a hyper-IgG4-related disease. We report a case of IgG4-related AIP overlapping with Mikulicz's disease and lymphadenitis, which is rare and seldom reported in literature. A 63-year male from Northeast China was admitted for abdominal distension lasting for one year. He presented symmetric swelling of the parotid and submandibular glands with slight dysfunction of salivary secretion for 6 mo. He had a 2-year history of bilateral submandibular lymphadenopathy without pain. He underwent surgical excision of the right submandibular lymph node one year prior to admission. He denied any history of alcohol, tobacco, or illicit drug use. Serological examination revealed high fasting blood sugar level (8.8 mmol/L) and high level of IgG4 (15.2 g/L). Anti-SSA or anti-SSB were negative. Computed tomography of the abdomen showed a diffusely enlarged pancreas with loss of lobulation. Immunohistochemical stain for IgG4 demonstrated diffuse infiltration of IgG4-positive plasma cells in labial salivary gland and lymph node biopsy specimens. The patient received a dose of 30 mg/d of prednisone for three weeks. At this three-week follow-up, the patient reported no discomfort and his swollen salivary glands, neck lymph node and pancreas had returned to normal size. The patient received a maintenance dose of 10 mg/d of prednisone for 6 mo, after which his illness had not recurred.


Effect of pacing site on ventricular fibrillation initiation by shocks during the vulnerable period.
The critical point hypothesis for the upper limit of vulnerability (ULV) states that the site of S1 pacing should not affect the ULV S2 shock strength for a single S2 shock electrode configuration but may affect the S1-S2 interval at which sub-ULV shocks induce ventricular fibrillation (VF). Furthermore, early post-S2 activations leading to VF should arise in areas with low potential gradients of similar magnitude, regardless of the S1 site. This hypothesis was tested in 10 pigs by determining ULVs for three S1 sites [left ventricular apex (LVA), LV base (LVB), and right ventricular outflow tract (RVOT)] with one S2 configuration (LVA patch to superior vena cava catheter). T-wave scanning was performed with biphasic S2 shocks incremented from 60 V in 40-V steps and stepped up or down in 20- and 10-V steps. Activations and S2 potential gradients were recorded at 528 epicardial sites. Although shocks just below the ULV induced VF significantly earlier in the T wave when the S1 site was the RVOT than when it was the LVA or LVB, ULVs were not significantly different for the three S1 pacing sites. Early post-S2 activations arose closer to the S2 electrode for weak S2s but moved to distant low potential gradient areas as the S2 strengthened. Just below the ULV, early post-S2 activations arose in the RVOT when the S1 site was the LVA or LVB but arose along the RV base when the S1 site was the RVOT. Early site potential gradients were not significantly different just below the ULV (LVA: 8.2 +/- 4.1 V/cm; LVB: 8.6 +/- 4. 9 V/cm; RVOT: 8.7 +/- 4.4 V/cm). At the ULV, early post-S2 activations arose from the same areas but did not induce VF. The results support the critical point hypothesis for the ULV. For this S2 configuration, no single point in the T wave could be used to determine the ULV for all S1 sites.


Effects of transcranial direct current stimulation (tDCS) on cognition, symptoms, and smoking in schizophrenia: A randomized controlled study.
Schizophrenia is characterized by cognitive deficits which persist after acute symptoms have been treated or resolved. Transcranial direct current stimulation (tDCS) has been reported to improve cognition and reduce smoking craving in healthy subjects but has not been as carefully evaluated in a randomized controlled study for these effects in schizophrenia. We conducted a randomized double-blind, sham-controlled study of the effects of 5 sessions of tDCS (2 milliamps for 20minutes) on cognition, psychiatric symptoms, and smoking and cigarette craving in 37 outpatients with schizophrenia or schizoaffective disorder who were current smokers. Thirty subjects provided evaluable data on the MATRICS Consensus Cognitive Battery (MCCB), with the primary outcome measure, the MCCB Composite score. Active compared to sham tDCS subjects showed significant improvements after the fifth tDCS session in MCCB Composite score (p=0.008) and on the MCCB Working Memory (p=0.002) and Attention-Vigilance (p=0.027) domain scores, with large effect sizes. MCCB Composite and Working Memory domain scores remained significant at Benjamini-Hochberg corrected significance levels (α=0.05). There were no statistically significant effects on secondary outcome measures of psychiatric symptoms (PANSS scores), hallucinations, cigarette craving, or cigarettes smoked. The positive effects of tDCS on cognitive performance suggest a potential efficacious treatment for cognitive deficits in partially recovered chronic schizophrenia outpatients that should be further investigated.


[Comparison of climacteric symptoms among women in Mexico City and women of a Mayan community of Yucatan].
to compare the climacteric symptoms between women from Mexico City and those from a Mayan community of the state of Yucatan. In two groups of women, Group I) Spanish-speaking women from Mexico City and Group II) Maya speaking women from the state of Yucatan, 22 climacteric symptoms were evaluated using an analog visual scale (AVS) and the SUMEVA index. For statistical analysis t student test was used as well as Chi squared. 105 women, 50 of Mexico City and 55 of Maxcanu, Yucatan were studied. When comparing the groups no difference was found in age (52.5 +/- 6.5 vs 53.7 +/- 6.2, for group I and II respectively), the body mass index was significantly smaller in group I (29.7 +/- 5.0 vs 34.0 +/- 6.0, p < 0.001). In group 1, 15 of the 22 evaluated symptoms were significantly more intense in Group I, as well as the SUMEVA (Sum of Analog Visual Scale) index (71.4 +/- 44.5 vs 45.8 +/- 24.8, p < 0.001). The proportion of symptomatic women for each one of the symptoms was similar in both groups except for hair fall that was significantly greater in group I (74% vs 52%). climacteric symptoms were perceived with more intensity by Mexico City women, which allows suppose that western culture influence can be the responsible.


Effect of copper oxide concentration on the formation and persistency of environmentally persistent free radicals (EPFRs) in particulates.
Environmentally persistent free radicals (EPFRs) are formed by the chemisorption of substituted aromatics on metal oxide surfaces in both combustion sources and superfund sites. The current study reports the dependency of EPFR yields and their persistency on metal loading in particles (0.25, 0.5, 0.75, 1, 2, and 5% CuO/silica). The EPFRs were generated through exposure of particles to three adsorbate vapors at 230 °C: phenol, 2-monochlorophenol (2-MCP), and dichlorobenzene (DCBz). Adsorption resulted in the formation of surface-bound phenoxyl- and semiquinoine-type radicals with characteristic EPR spectra displaying a g value ranging from ∼ 2.0037 to 2.006. The highest EPFR yield was observed for CuO concentrations between 1 and 3% in relation to MCP and phenol adsorption. However, radical density, which is expressed as the number of radicals per copper atom, was highest at 0.75-1% CuO loading. For 1,2-dichlorobenzene adsorption, radical concentration increased linearly with decreasing copper content. At the same time, a qualitative change in the radicals formed was observed--from semiquinone to chlorophenoxyl radicals. The two longest lifetimes, 25 and 23 h, were observed for phenoxyl-type radicals on 0.5% CuO and chlorophenoxyl-type radicals on 0.75% CuO, respectively.


Vertically Aligned Single-Crystalline CoFe2O4 Nanobrush Architectures with High Magnetization and Tailored Magnetic Anisotropy.
Micrometer-tall vertically aligned single-crystalline CoFe2O4 nanobrush architectures with extraordinarily large aspect ratio have been achieved by the precise control of a kinetic and thermodynamic non-equilibrium pulsed laser epitaxy process. Direct observations by scanning transmission electron microscopy reveal that the nanobrush crystal is mostly defect-free by nature, and epitaxially connected to the substrate through a continuous 2D interface layer. In contrast, periodic dislocations and lattice defects such as anti-phase boundaries and twin boundaries are frequently observed in the 2D interface layer, suggesting that interface misfit strain relaxation under a non-equilibrium growth condition plays a critical role in the self-assembly of such artificial architectures. Magnetic property measurements have found that the nanobrushes exhibit a saturation magnetization value of 6.16 B/f.u., which is much higher than the bulk value. The discovery not only enables insights into an effective route for fabricating unconventional high-quality nanostructures, but also demonstrates a novel magnetic architecture with potential applications in nanomagnetic devices.


Novel and emerging technologies for endovascular thrombectomy.
Endovascular thrombectomy device improvements in recent years have served a pivotal role in improving the success and safety of the thrombectomy procedure. As the intervention gains widespread use, developers have focused on maximizing the reperfusion rates and reducing procedural complications associated with these devices. This has led to a boom in device development. This review will cover novel and emerging technologies developed for endovascular thrombectomy.


[Women's preventive healthcare and health policy from the gender mainstreaming perspective].
Feminist and gender mainstreaming perspectives can help expand consideration of women's health and preventive healthcare beyond maternal and reproductive care to encompass the multiple roles and life span experiences of women. Such a shift may encourage the adoption by nursing professionals of broader viewpoints that address contemporary women's health priorities and facilitate the delivery of more appropriate preventive healthcare. This article discusses the World Health Organization's gender mainstreaming and women's health policies, gender mainstreaming women's health policies in Taiwan, and the roles of nurses in women's preventive healthcare. Based on the Women's Health Policy White Paper proposed by Taiwan's Department of Health, when working with female clients, nurses should play multiple roles that include healthcare provider, information provider, educator, advocate, consultant and researcher. Strategies that may be employed to achieve these roles include: (1) Adjusting perceptions toward traditional reproduction; (2) Providing correct and sufficient medical information; (3) Considering possible adverse effects of medical interventions on women; (4) Considering the healthcare system as a probable stressor for women; (5) Considering women's medical environment and space; (6) Exploring the relationship between socio-culture and women's preventive healthcare and (7) Recruiting women as major subjects in healthcare research.


Markers of inflammation and coronary artery calcification: a systematic review.
The goal of this systematic review is to assess the cross-sectional relationship of inflammatory markers with the presence and extent of coronary artery calcium (CAC) to identify asymptomatic individuals with a higher risk of coronary heart disease (CHD). Markers of subclinical inflammation and subclinical atherosclerosis have both been used to improve detection of individuals at high risk of developing cardiovascular disease. CAC has emerged as a surrogate maker for underlying coronary atherosclerosis, and has been shown to predict future CHD events. Although inflammation is intimately associated with atherosclerosis, and levels of inflammatory markers predict cardiovascular risk, the relationship of subclinical inflammatory markers with the burden of coronary atherosclerosis is not clear. Medline and Pub Med databases were searched for all studies assessing the relationship of inflammatory markers with CAC published till July 2007. We found 12 studies that met our criteria. CRP, fibrinogen, metallic metalloproteinase-9 (MMP-9), monocyte chemotactic protein 1 (MCP-1), resistin, lipoprotein-associated phospholipase A(2) (Lp-PLA(2)), IL-6, tumor necrosis factor alpha (TNF-alpha) and beta-fibroblast growth factor (bFGF) were used as inflammatory markers. There was a wide variation among studies with regards to population size, inclusion criterias, age range and techniques. It was observed that in almost all studies the relationship between inflammatory markers and CAC was weak, and was mostly found upon univariate analysis in women. However, this association was lost after correction for obesity and BMI. The data on the relationship of inflammation and CAC with progression of atherosclerosis is scarce and did not show any predictive benefits for future CHD. Variable associations between CAC and inflammatory markers were identified. In most studies where a positive relationship was found, this relationship disappeared after appropriate correction for the presence of traditional risk factors. Our data suggests that an approach in which inflammatory markers are used to further characterize risk in individuals with an established coronary artery disease burden is more warranted than using biomarkers as sole risk predictors of future CHD events. Large, well-planned comprehensive studies are required to identify the combined role of measuring inflammatory markers in assessment of atherosclerotic disease.


Down-regulation of anandamide hydrolase in mouse uterus by sex hormones.
Endocannabinoids are an emerging class of lipid mediators, which mimic several effects of cannabinoids. Anandamide (arachidonoylethanolamide) is a major endocannabinoid, which has been shown to impair pregnancy and embryo development. The activity of anandamide is controlled by cellular uptake through a specific transporter and intracellular degradation by the enzyme anandamide hydrolase (fatty acid amide hydrolase, FAAH). We characterized FAAH in mouse uterus by radiochromatographic and immunochemical techniques, showing that the enzyme is confined to the epithelium and its activity decreases appreciably during pregnancy or pseudopregnancy because of lower gene expression at the translational level. Ovariectomy prevented the decrease in FAAH, and both progesterone and estrogen further reduced its basal levels, suggesting hormonal control of the enzyme. Anandamide was shown to induce programmed cell death in mouse blastocysts, through a pathway independent of type-1 cannabinoid receptor. Blastocysts, however, have a specific anandamide transporter and FAAH, which scavenge this lipid. Taken together, these results provide evidence of an interplay between endocannabinoids and sex hormones in pregnancy. These findings may also be relevant for human fertility, as epithelial cells from healthy human uterus showed FAAH activity and expression, which in adenocarcinoma cells was increased fivefold.


Preoperative Fibrinogen-Albumin Ratio Index (FARI) is a Reliable Prognosis and Chemoradiotherapy Sensitivity Predictor in Locally Advanced Rectal Cancer Patients Undergoing Radical Surgery Following Neoadjuvant Chemoradiotherapy.
Inflammatory response and nutritional status are associated with cancer development and progression. The purpose of this study was to explore whether the preoperative fibrinogen-albumin ratio index (FARI) is related to prognosis and chemoradiotherapy outcome of radical surgery after neoadjuvant chemoradiotherapy (NCRT) in patients with locally advanced rectal cancer (LARC). In total, 123 patients with LARC who underwent radical surgery after NCRT between June 2012 and December 2018 were collected in this study. Time-dependent receiver operating characteristic (ROC) curve analysis was made to evaluate the ability of the markers for forecasting prognosis. The correlation between FARI and clinicopathological parameters was analyzed. The Kaplan-Meier survival analysis, univariate and multivariate analysis based on Cox proportional hazards models, and subgroup analysis were performed to evaluate overall survival (OS) and disease-free survival (DFS). A nomogram was constructed to evaluate the predictive role of FARI in DFS. The ROC curve analysis showed that the ability of FARI on DFS prediction was superior to those of other inflammatory markers and carcinoembryonic antigen (CEA) (P<0.05). Based on the Youden's index, the optimal cut-off value of FARI was 8.8%. High FARI patients (>8.8%) showed a poor response to NCRT and a decreased DFS rate (P<0.05). In addition, multivariate analysis revealed that FARI (HR=3.098, P=0.033), neutrophil-to-lymphocyte ratio (NLR), and postoperative T stage were independent prognostic factors for DFS in TNM stage III LARC patients. However, FARI failed to distinguish patients with poor OS. Harrell's concordance index (C-index) of the nomogram containing FARI (0.807) was obviously higher than that without it (0.732) among LARC patients who underwent radical surgery after NCRT. Moreover, multivariate analysis revealed FARI (OR=3.044, P=0.012) as an independent predictor for response to NCRT. Among LARC patients who underwent radical surgery after NCRT, preoperative FARI is an independent prognostic factor for DFS and an independent predictor for response to NCRT.


New concepts and questions in gestational trophoblastic disease.
Hydatidiform moles can be divided into two distinct syndromes: partial, or transitional, and classic. Both classic and partial moles appear to result from abnormal fertilization but differ in the type of abnormal fertilization, karyotype, histology, epidemiology and malignant potential. Using chromosomal banding polymorphism, classic hydatidiform moles have been shown to be androgenetic in origin, developing from a sperm with the egg nucleus either absent or inactivated. No maternal chromosomes are transmitted to the classic mole. Studies using HLA and enzyme heterozygosity have suggested that fertilization occurs by a haploid sperm with duplication of its chromosomes and without cell division, giving the 46XX karyotype found in classic moles. About 4% of classic moles are 46XY and are also androgenetic but result from dispermic fertilization. The partial mole consists of hydropic villi, but some normal villi also are present. An embryo, cord and fetal membranes generally can also be found, and the karyotype frequently is aneuploid (usually triploid) and not the 46XX or 46XY of the classic mole. In contrast to the classic mole, the partial mole has a maternal chromosomal contribution. Preliminary data suggest that many partial moles arise from dispermic fertilization, with participation of the maternal genome giving a triploid karyotype. The malignant potential of the partial mole is still controversial, but preliminary data indicate that 2.1% of partial moles require treatment as compared to 10% of classic moles.


Facile Self-Assembly of Metallo-Supramolecular Ring-in-Ring and Spiderweb Structures Using Multivalent Terpyridine Ligands.
A series of metallo-supramolecular ring-in-ring structures was generated by assembling Cd(II) ions and the multivalent terpyridine ligands (L(1-3)) composed of one 60°-bent and two 120°-bent bis(terpyridine)s with varying alkyl linker lengths. The mechanistic study for the self-assembly process excluded an entropically templated pathway and showed that the intramolecularly complexed species is the key intermediate leading to ring-in-ring formation. The next-generation superstructure, a spiderweb, was produced in quantitative yield using the elongated decakis(terpyridine) ligand (L(5)).


Identification of Acinetobacter baumannii loci for capsular polysaccharide (KL) and lipooligosaccharide outer core (OCL) synthesis in genome assemblies using curated reference databases compatible with Kaptive.
Multiply antibiotic-resistant Acinetobacter baumannii infections are a global public health concern and accurate tracking of the spread of specific lineages is needed. Variation in the composition and structure of capsular polysaccharide (CPS), a critical determinant of virulence and phage susceptibility, makes it an attractive epidemiological marker. The outer core (OC) of lipooligosaccharide also exhibits variation. To take better advantage of the untapped information available in whole genome sequences, we have created a curated reference database of 92 publicly available gene clusters at the locus encoding proteins responsible for biosynthesis and export of CPS (K locus), and a second database for 12 gene clusters at the locus for outer core biosynthesis (OC locus). Each entry has been assigned a unique KL or OCL number, and is fully annotated using a simple, transparent and standardized nomenclature. These databases are compatible with Kaptive, a tool for in silico typing of bacterial surface polysaccharide loci, and their utility was validated using (a) >630 assembled A. baumannii draft genomes for which the KL and OCL regions had been previously typed manually, and (b) 3386 A. baumannii genome assemblies downloaded from NCBI. Among the previously typed genomes, Kaptive was able to confidently assign KL and OCL types with 100 % accuracy. Among the genomes retrieved from NCBI, Kaptive detected known KL and OCL in 87 and 90 % of genomes, respectively, indicating that the majority of common KL and OCL types are captured within the databases; 13 of the 92 KL in the database were not detected in any publicly available whole genome assembly. The failure to assign a KL or OCL type may indicate incomplete or poor-quality genomes. However, further novel variants may remain to be documented. Combining outputs with multilocus sequence typing (Institut Pasteur scheme) revealed multiple KL and OCL types in collections of a single sequence type (ST) representing each of the two predominant globally distributed clones, ST1 of GC1 and ST2 of GC2, and in collections of other clones comprising >20 isolates each (ST10, ST25, and ST140), indicating extensive within-clone replacement of these loci. The databases are available at https://github.com/katholt/Kaptive and will be updated as further locus types become available.