The Hospital Anxiety and Depression Rating Scale: a cross-sectional study of psychometrics and case finding abilities in general practice.
General practitioners' (GPs) diagnostic skills lead to underidentification of generalized anxiety disorders (GAD) and major depressive episodes (MDE). Supplement of brief questionnaires could improve the diagnostic accuracy of GPs for these common mental disorders. The aims of this study were to examine the usefulness of The Hospital Anxiety and Depression Rating Scale (HADS) for GPs by: 1) Examining its psychometrics in the GPs' setting; 2) Testing its case-finding properties compared to patient-rated GAD and MDE (DSM-IV); and 3) Comparing its case finding abilities to that of the GPs using Clinical Global Impression-Severity (CGI-S) rating. In a cross-sectional survey study 1,781 patients in three consecutive days in September 2001 attended 141 GPs geographically spread in Norway. Sensitivity, specificity, optimal cut off score, and Area under the curve (AUC) for the HADS and the CGI-S were calculated with Generalized Anxiety Questionnaire (GAS-Q) as reference standard for GAD, and Depression Screening Questionnaire (DSQ) for MDE. The HADS-A had optimal cut off > or =8 (sensitivity 0.89, specificity 0.75), AUC 0.88 and 76% of patients were correctly classified in relation to GAD. The HADS-D had by optimal cut off > or =8 (sensitivity 0.80 and specificity 0.88) AUC 0.93 and 87% of the patients were correctly classified in relation to MDE. Proportions of the total correctly classified at the CGI-S optimal cut-off > or =3 were 83% of patients for GAD and 81% for MDE. The results indicate that addition of the patients' HADS scores to GPs' information could improve their diagnostic accuracy of GAD and MDE.


Memory inception and preservation in slime moulds: the quest for a common mechanism.
Learning and memory are indisputably key features of animal success. Using information about past experiences is critical for optimal decision-making in a fluctuating environment. Those abilities are usually believed to be limited to organisms with a nervous system, precluding their existence in non-neural organisms. However, recent studies showed that the slime mould Physarum polycephalum, despite being unicellular, displays habituation, a simple form of learning. In this paper, we studied the possible substrate of both short- and long-term habituation in slime moulds. We habituated slime moulds to sodium, a known repellent, using a 6 day training and turned them into a dormant state named sclerotia. Those slime moulds were then revived and tested for habituation. We showed that information acquired during the training was preserved through the dormant stage as slime moulds still showed habituation after a one-month dormancy period. Chemical analyses indicated a continuous uptake of sodium during the process of habituation and showed that sodium was retained throughout the dormant stage. Lastly, we showed that memory inception via constrained absorption of sodium for 2 h elicited habituation. Our results suggest that slime moulds absorbed the repellent and used it as a 'circulating memory'. This article is part of the theme issue 'Liquid brains, solid brains: How distributed cognitive architectures process information'.


Problems persist in reporting of methods and results for the WOMAC measure in hip and knee osteoarthritis trials.
The Western Ontario and McMaster Universities Arthritis Index (WOMAC) is a commonly used outcome measure for osteoarthritis. There are different versions of the WOMAC (Likert, visual analogue or numeric scales). A previous review of trials published before 2010 found poor reporting and inconsistency in how the WOMAC was used. This review explores whether these problems persist. This systematic review included randomised trials of hip and/or knee osteoarthritis published in 2016 that used the WOMAC. Data were extracted on the version used, score range, analysis and results of the WOMAC, and whether these details were clearly reported. This review included 62 trials and 41 reported the WOMAC total score. The version used and item range for the WOMAC total score were unclear in 44% (n = 18/41) and 24% (n = 10/41) of trials, respectively. The smallest total score range was 0-10 (calculated by averaging 24 items scored 0-10); the largest was 0-2400 (calculated by summing 24 items scored 0-100). All trials reported the statistical analysis methods but only 29% reported the between-group mean difference and 95% confidence interval. Details on the use and scoring of the WOMAC were often not reported. We recommend that trials report the version of the WOMAC and the score range used. The between-group treatment effect and corresponding confidence interval should be reported. If all the items of the WOMAC are collected, the total score and individual subscale scores should be presented. Better reporting would facilitate the interpretation, comparison and synthesis of the WOMAC score in trials.


Computational models for 5αR inhibitors for treatment of prostate cancer: review of previous works and screening of natural inhibitors of 5αR2.
Taking into consideration the high importance of the drug target 5-α-reductase (5αR) in prostate cancer in this work we are going first to review previous works and discuss works related to the computer aided drug design of 5αR inhibitors. We report new results in the in silico screening of natural 5αR inhibitors. Traditionally, drugs were discovered by testing compounds synthesized in time consuming multi-step processes against a battery of in vivo biological screens. Promising compounds were then further studied in development, where their pharmacokinetic properties, metabolism and potential toxicity were investigated. Here we present a study on herbal lead compounds and their potential binding affinity to the effectors molecules of major disease like Prostate Cancer. Clinical studies demonstrate a positive correlation between the extent of 5αR type 2 (5αR2) and malignant progression of precancerous lesions in prostate. Therefore, identification of effective, well-tolerated 5αR inhibitors represents a rational chemo preventive strategy. This study has investigated the effects of naturally occurring non-protein compounds berberine and monocaffeyltartaric acid that inhibits 5αR type2. Our results reveal that these compounds use less energy to bind to 5αR and inhibit its activity. Their high ligand binding affinity to 5αR introduce the prospect for their use in chemopreventive applications; in addition they are freely available natural compounds that can be safely used to prevent prostate cancer.


Clarithromycin might attenuate the airway inflammation of smoke-exposed asthmatic mice via affecting HDAC2.
Smoke has been proved to be one of the most dangerous ingredients leading to the unsatisfying treatment response of asthmatics to inhaled corticosteroids (ICS) therapy. Macrolides, a class of antibiotics, possess the traits of immunomodulation and anti-inflammation besides antimicrobial activity. Given that studies on the efficacy of macrolides on the refractory asthma patient have diverting conclusions, this article was carried on to investigate the effects of macrolide on the airway inflammation of smoke-exposed asthmatic mice. BALB/c mice were chosen to be the subjects of this study. They were raised to establish asthma model (OVA group); and one asthma group were exposed to the smoke (SEA group), one asthma group were treat with clarithromycin (CAM group) after smoke exposure. Control group mice were used as parallel comparison. Total inspiratory resistance (RL), expiratory resistance of the lung (Re) and lung compliance (Cdyn) were the main index to evaluate airway hyperresponsiveness (AHR). The histopathological change was studied to assess lung tissue inflammation. Cell counts in bronchoalveolar lavage fluid (BALF) were also tested to represent airway inflammation. IL-4 and CXCL1 in BALF and serum were also used to evaluate the airway inflammation. Histone deacelytase2 (HDAC2) activity of lung tissues was measure by assay kit. HDAC2 expression in the lung tissue had been detected by western blot. Re, RL and Cdyn were monitored to represent airway responsiveness. All of the three indicators in SEA group were significantly different from control group, while clarithromycin improved airway responsiveness and the three indicator were statistically significant (P<0.01). Histopathology observation had showed massive infiltration of inflammatory cells in both OVA group and SEA group, while inflammation infiltration attenuated in CAM group. Total cell counts in SEA group was much higher than that in CAM group (P=0.019), so were neutrophils (P=0.022) and eosinophils (P=0.042); while macrophages in SEA group decreased when compared to CAM group (P=0.026), IL-4 and CXCL1 level in CAM group were significantly decreased in comparison to those in SEA group (P=0.031, P=0.017). HDAC2 activity in SEA group decreased significantly when compared to control group (P=0.010); while HDAC2 activity in CAM group was improved and significantly better than that in SEA group (P=0.038). The expression of HADC2 in CAM group improved significantly when compared to that in SEA group (P=0.022). Clarithromycin could improve AHR and attenuate airway inflammation in smoke exposed asthmatic mice which may involve HDAC2. Macrolides might have the potential to serve as the adjunctive treatment to some refractory asthmatics who are smokers or passive smokers.


Actinobacteria cyclophilins: phylogenetic relationships and description of new class- and order-specific paralogues.
Cyclophilins are folding helper enzymes belonging to the class of peptidyl-prolyl cis-trans isomerases (PPIases; EC 188.8.131.52) that catalyze the cis-trans isomerization of peptidyl-prolyl bonds in proteins. They are ubiquitous proteins present in almost all living organisms analyzed to date, with extremely rare exceptions. Few cyclophilins have been described in Actinobacteria, except for three reported in the genus Streptomyces and another one in Mycobacterium tuberculosis. In this study, we performed a complete phylogenetic analysis of all Actinobacteria cyclophilins available in sequence databases and new Streptomyces cyclophilin genes sequenced in our laboratory. Phylogenetic analyses of cyclophilins recovered six highly supported groups of paralogy. Streptomyces appears as the bacteria having the highest cyclophilin diversity, harboring proteins from four groups. The first group was named "A" and is made up of highly conserved cytosolic proteins of approximately 18 kDa present in all Actinobacteria. The second group, "B," includes cytosolic proteins widely distributed throughout the genus Streptomyces and closely related to eukaryotic cyclophilins. The third group, "M" cyclophilins, consists of high molecular mass cyclophilins ( approximately 30 kDa) that contain putative membrane binding domains and would constitute the only membrane cyclophilins described to date in bacteria. The fourth group, named "C" cyclophilins, is made up of proteins of approximately 18 kDa that are orthologous to Gram-negative proteobacteria cyclophilins. Ancestral character reconstruction under parsimony was used to identify shared-derived (and likely functionally important) amino acid residues of each paralogue. Southern and Western blot experiments were performed to determine the taxonomic distribution of the different cyclophilins in Actinobacteria.


[Can we influence the progression of chronic kidney disease?].
Chronic renal failure does not only involve the risk for the patient of becoming dependent on hemodialysis, but also increases the risk of premature death due to cardiovascular events. In most renal diseases, progressive chronic loss of renal function develops once a critical extent of renal damage has occurred, independent of the course of the underlying renal disease. The key factors driving the progressive loss of renal function are, apart from the underlying nephrological disease, arterial hypertension and diabetes mellitus. The loss of renal function is also promoted by other factors, such as increased intake of dietary proteins, chronic inflammation, smoking, and anemia. With the help of a multimodal therapeutic concept, the progression of chronic renal failure can be delayed effectively. This approach comprises strict blood pressure control with a target blood pressure of 130/80 mmHg in patients with micro-albuminuria and of 120/75 mmHg in patients with proteinuria of >1 g/d. The preferred drugs for the treatment of hypertension are ACE inhibitors and angiotensin receptor blockers. In diabetics with renal insufficiency, target HbA1c levels below 7% are to be aimed for. Dietary protein intake should be restricted to 0.8-1 g/kg body weight/d. Additional therapeutic targets include nicotine abstinence, early treatment of renal anemia, weight reduction, and, if indicated, lipid-lowering therapy.


Latent class models for utilisation of health care.
This paper explores different approaches to econometric modelling of count measures of health care utilisation, with an emphasis on latent class models. A new model is proposed that combines the features of the two most common approaches: the hurdle model and the finite mixture negative binomial. Additionally, the panel structure of the data is taken into account. The proposed finite mixture hurdle model is shown to fit the data substantially better than the existing models for a particular application to data from the RAND Health Insurance Experiment. The estimation results indicate a higher price effect for low users of health care. It is furthermore found that this results mainly from the difference of the price effects on the probability to visit a doctor, while the price effect on the conditional number of visits does not differ significantly between high and low users.


Late cholangitis after successful surgical repair of biliary atresia.
Bacterial cholangitis is a frequent complication of successful surgical repair of biliary atresia, occurring in 93% of patients before the age of 1 year, but thought to be rare after 2 years of age. Among 76 children free of jaundice more than 5 years after operation, four presented with late cholangitis (7 to 13.5 years old), consisting of fever, jaundice, and abdominal pain with biochemical features of an inflammatory process and cholestasis. Liver biopsy specimens consistently demonstrated histological features of cholangitis, growth of microorganism, or both. Cholangitis subsided spontaneously in one patient or in response to intravenous administration of antibiotics. Cholangiography consistently demonstrated biliary abnormalities but no definite obstruction to the bilioenteric anastomosis. All the children had good hepatic function 3 weeks to 4 years after the episode of cholangitis. These results suggest that cholangitis may occur several years after surgery but does not seem to alter prognosis.


Phase III trial of cetuximab, bevacizumab, and 5-fluorouracil/leucovorin vs. FOLFOX-bevacizumab in colorectal cancer.
Cetuximab (C), alone or with irinotecan, demonstrates activity in irinotecan-refractory colorectal cancer (CRC). Activity of 5-fluorouracil (5-FU), leucovorin (L), and bevacizumab (B), and preliminary data of cetuximab + bevacizumab, and toxicity profiles suggests that FOLF-CB (5-FU, L, C+B) may have activity with a favorable toxicity profile as first-line therapy. Eligible patients were randomized at registration to either arm A (mFOLFOX6-B) (modified, 5-FU. L (folinic acid), oxaliplatin (O) + bevacizumab), administered days 1 and 15 of each 28-day cycle as bevacizumab 5 mg/kg, oxaliplatin 85 mg/m(2), leucovorin 400 mg/m(2), and 5-FU 400 mg/m(2) then 1200 mg/m(2)/day for 48 hours, or arm B (FOLF-CB), which included bevacizumab, leucovorin, and 5-FU as in arm A and cetuximab 400 mg/m(2) day 1 cycle 1; all other weekly cetuximab doses were 250 mg/m(2). Two hundred forty-seven patients (arm A/arm B 124/123) were enrolled, and 239 were treated (118/121). Twelve-month progression-free survival (PFS) was 45%/32%, objective response rates (ORR) (complete response [CR] + partial response [PR]) were 52%/41%, disease control rates (CR+PR+stable disease [SD]) were 87%/83%, and median overall survival (OS) was 21/19.5 months, respectively. Grade 3-4 neutropenia was higher in arm A (28%/7%), as was grade 3 fatigue (12%/3%), and grade 3 neuropathy (11%/< 1%), whereas acneiform rash was confined to arm B. Retrospective analysis of KRAS mutational status did not demonstrate KRAS as a meaningful determinant of activity, except in arm B patients with KRAS-mutated tumors, which resulted in inferior PFS. Patient satisfaction favored the control (mFOLFOX6-B). FOLF-CB was not superior to mFOLFOX6-B in terms of 12-month PFS and ORR, and was not more acceptable to patients. This trial supports the conclusion of other recently reported trials that concurrent cetuximab+bevacizumab should not be routinely used in metastatic CRC.


Clinicopathologic considerations: how can we fine tune our approach to sarcoma?
Bone and soft tissue sarcomas are an uncommon and sundry group of solid tumors traditionally categorized together according to their presumed mesenchymal differentiation. They are histologically, behaviorally, and genetically diverse, and their pathogenesis is poorly understood. Moreover, treatment options are limited, with surgical resection continuing to provide the only possibility of cure in many cases. However, there has been tremendous progress in the last decade in understanding the behavior and molecular pathogenesis of sarcoma, which may ultimately lead to more effective therapy and prognostication for these rare malignancies. In this article, we address the histologic and molecular classification of sarcomas, with emphasis on the increasing role of molecular diagnostics in both classification and prognostication. In addition, we review recent advances in the understanding of critical cell signaling pathways involved in this group of malignancies, and how this knowledge relates to the potential role of newer targeted therapies in sarcoma treatment. The role and rationale for grading and staging of sarcomas is discussed, as well as more recent advances in the development of prognostic nomograms, based on clinical and histopathologic findings. Finally, we conclude with a discussion of the importance of multidisciplinary care, with integration of histologic, molecular, radiographic, and clinical data in the management of sarcoma.


Multiple initial culture conditions enhance the establishment of cell lines from primary ovarian cancer specimens.
To increase the efficiency of stable cell line establishment from primary ovarian cancer specimens, we simultaneously initiated cultures under multiple conditions, varying extracellular matrices and the inclusion of supplements (e.g., serum or serum albumin), while minimizing exposure to xenogeneic antigens (e.g., fetal calf serum). Primary cultures were initiated from 30 specimens; cell lines were established from 10 of these for a success rate of 33%. In some instances, multiple cell lines were established from the same specimen. Five lines were characterized extensively with respect to growth properties, antigen expression, and genomic alterations. Although these lines are all low-passage, marked heterogeneity was observed, even between lines derived from the same specimen. The culture approach outlined herein will facilitate generation of reagents useful for many aspects of ovarian cancer biology.


Variation of the Infrared Solar Spectrum Between 700 cm(-1) and 2240 cm(-1) with Altitude.
A grating spectrometer with a Ge: Cu detector was flown on three balloon flights. Spectra in the 4-14.3-micro region were obtained at various altitudes from the ground through 30 km with a resolution considerably better than that achieved in previous flights. Some of the spectra were obtained over long paths at float altitude, during the sunset. Data from these flights are presented with a discussion of the significant features of the observed absorptions. Special emphasis is put on the new features observed during the sunset.


Secular changes in human biological variables in Western countries: an updated review and synthesis.
This paper provides a review of the recent literature on some aspects of secular trends in Western countries. In particular, we discuss height variation, mainly on the basis of conscript data. There are still large height differences between European countries, and there is a marked trend for the tallest conscripts to be in northern Europe and the shortest ones in the southern part of the continent. The secular trend in adult height has come to a halt in northern Europe and Italy, while it is still in progress in Belgium, Spain and Portugal. The secular trend in height mainly depends on the increase of lower limb length. Obesity is now epidemic in Western countries, the USA population being the most affected. There is also a progressive anticipation of all the signs of puberty, namely age at menarche, appearance and development of the breasts, genitals and pubic and axillary hair, although there is ethnic/population variability in this regard. A tendency to later onset of menopause has also been recorded. Regarding secular trends in sport, there has been a progressive selection of athletes with larger body dimensions. Finally, the authors provide suggestions for future fruitful directions of the research of the secular trend in human biology.


Discovery of new 6-ureido/amidocoumarins as highly potent and selective inhibitors for the tumour-relevant carbonic anhydrases IX and XII.
A series of 6-ureido/amidocoumarins (5a-p and 7a-c) has been designed and synthesised to develop potent and isoform- selective carbonic anhydrase hCA XI and XII inhibitors. All coumarin derivatives were investigated for their CA inhibitory effect against hCA I, II, IX, and XII. Interestingly, target coumarins potently inhibited both tumour-related isoforms hCA IX (KIs: 14.7-82.4 nM) and hCA XII (KIs: 5.9-95.1 nM), whereas the cytosolic off-target hCA I and II isoforms have not inhibited by all tested coumarins up to 100 μM. These findings granted the target coumarins an excellent selectivity profile towards both hCA IX and hCA XII isoforms, supporting their development as promising anticancer candidates. Moreover, all target molecules were evaluated for their anticancer activities against HCT-116 and MCF-7 cancer cells. The 3,5-bis-trifluoromethylphenyl ureidocoumarin 5i, exerted the best anticancer activity. Overall, ureidocoumarins, particularly compound 5i, could serve as a promising prototype for the development of potent anticancer CAIs.


Bimodal gene expression patterns in breast cancer.
We identified a set of genes with an unexpected bimodal distribution among breast cancer patients in multiple studies. The property of bimodality seems to be common, as these genes were found on multiple microarray platforms and in studies with different end-points and patient cohorts. Bimodal genes tend to cluster into small groups of four to six genes with synchronised expression within the group (but not between the groups), which makes them good candidates for robust conditional descriptors. The groups tend to form concise network modules underlying their function in cancerogenesis of breast neoplasms.


VIPP1 Involved in Chloroplast Membrane Integrity Has GTPase Activity in Vitro.
VESICLE-INDUCING PROTEIN IN PLASTID1 (VIPP1) is conserved among oxygenic photosynthetic organisms and appears to have diverged from the bacterial PspA protein. VIPP1 localizes to the chloroplast envelope and thylakoid membrane, where it forms homooligomers of high molecular mass. Although multiple roles of VIPP1 have been inferred, including thylakoid membrane formation, envelope maintenance, membrane fusion, and regulation of photosynthetic activity, its precise role in chloroplast membrane quality control remains unknown. VIPP1 forms an oligomer through its amino-terminal domain and triggers membrane fusion in an Mg2+-dependent manner. We previously demonstrated that Arabidopsis (Arabidopsis thaliana) VIPP1 also exhibits dynamic complex disassembly in response to osmotic and heat stresses in vivo. These results suggest that VIPP1 mediates membrane fusion/remodeling in chloroplasts. Considering that protein machines that regulate intracellular membrane fusion/remodeling events often require a capacity for GTP binding and/or hydrolysis, we questioned whether VIPP1 has similar properties. We conducted an in vitro assay using a purified VIPP1-His fusion protein expressed in Escherichia coli cells. VIPP1-His showed GTP hydrolysis activity that was inhibited competitively by an unhydrolyzable GTP analog, GTPγS, and that depends on GTP binding. It is particularly interesting that the ancestral PspA from E. coli also possesses GTP hydrolysis activity. Although VIPP1 does not contain a canonical G domain, the amino-terminal α-helix was found to be important for both GTP binding and GTP hydrolysis as well as for oligomer formation. Collectively, our results reveal that the properties of VIPP1/PspA are similar to those of GTPases.


Molecular mechanisms underlying the effects of acupuncture on neuropathic pain.
Acupuncture has been used to treat neuropathic pain for a long time, but its mechanisms of action remain unknown. In this study, we observed the effects of electroacupuncture and manual acu-puncture on neuropathic pain and on ephrin-B/EphB signaling in rats models of chronic constriction injury-induced neuropathic pain. The results showed that manual acupuncture and elec-puncture significantly reduced mechanical hypersensitivity following chronic constriction injury, es-pecially electroacupuncture treatment. Real-time PCR results revealed that ephrin-B1/B3 and EphB1/B2 mRNA expression levels were significantly increased in the spinal dorsal horns of chronic constriction injury rats. Electroacupuncture and manual acupuncture suppressed the high sion of ephrin-B1 mRNA, and elevated EphB3/B4 mRNA expression. Electroacupuncture signifi-cantly enhanced the mRNA expression of ephrin-B3 and EphB3/B6 in the dorsal horns of neuro-pathic pain rats. Western blot results revealed that electroacupuncture in particular, and manual acupuncture, significantly up-regulated ephrin-B3 protein levels in rat spinal dorsal horns. The re-sults of this study suggest that acupuncture could activate ephrin-B/EphB signaling in neuropathic pain rats and improve neurological function.


Relationships between cholesterol, apolipoprotein E polymorphism and dementia: a cross-sectional analysis from the PAQUID study.
This study assesses the cross-sectional relationship between serum cholesterol level and dementia, controlling for apolipoprotein E (apoE) genotype, in a nested case-control study of 334 elderly French subjects aged 73 and over who participated in the PAQUID study (37 demented subjects and 297 nondemented controls). A diagnosis of dementia was established by two-step screening: (1) psychometric testing and DSM-III-R criteria and (2) neurologist's confirmation. Cholesterol, its fractions and apoE genotype were determined from a blood sample. Elevated high-density lipoprotein cholesterol was associated with a significantly decreased risk of dementia, independent of apoE status and other potential confounding variables, suggesting that cholesterol fractions could be involved in both Alzheimer's disease and vascular dementia.


Peptide vaccine from cancer-testis antigen ODF2 can potentiate the cytotoxic T lymphocyte infiltration through IL-15 in non-MSI-H colorectal cancer.
About 85% of patients with colorectal cancer (CRC) have the non-microsatellite instability-high (non-MSI-H) subtype, and many cannot benefit from immune checkpoint blockade. A potential reason for this is that most non-MSI-H colorectal cancers are immunologically "cold" due to poor CD8+ T cell infiltration. In the present study, we screened for potential cancer-testis antigens (CTAs) by comparing the bioinformatics of CD8+ T effector memory (Tem) cell infiltration between MSI-H and non-MSI-H CRC. Two ODF2-derived epitope peptides, P433 and P609, displayed immunogenicity and increased the proportion of CD8+ T effector memory (Tem) cells in vitro and in vivo. The adoptive transfer of peptide pool-induced CTLs inhibited tumor growth and enhanced CD8+ T cell infiltration in tumor-bearing NOD/SCID mice. The mechanistic study showed that knockdown of ODF2 in CRC cells promoted interleukin-15 expression, which facilitated CD8+ T cell proliferation. In conclusion, ODF2, a CTA, was negatively correlated with CD8+ T cell infiltration in "cold" non-MSI-H CRC and was selected based on the results of bioinformatics analyses. The corresponding HLA-A2 restricted epitope peptide induced antigen-specific CTLs. Immunotherapy targeting ODF2 could improve CTA infiltration via upregulating IL-15 in non-MSI-H CRC. This tumor antigen screening strategy could be exploited to develop therapeutic vaccines targeting non-MSI-H CRC.


Suppression of macrophage eicosanoid synthesis by atherogenic lipoproteins is profoundly affected by cholesterol-fatty acyl esterification and the Niemann-Pick C pathway of lipid trafficking.
Atheroma macrophages internalize large quantities of lipoprotein-derived lipids. While most emphasis has been placed on cholesterol, lipoprotein-derived fatty acids may also play important roles in lesional macrophage biology. Little is known, however, about the trafficking or metabolism of these fatty acids. In this study, we first show that the cholesterol-fatty acyl esterification reaction, catalyzed by acyl-CoA:cholesterol acyltransferase (ACAT), competes for the incorporation of lipoprotein-derived fatty acids into cellular phospholipids. Furthermore, conditions that inhibit trafficking of cholesterol from late endosomes/lysosomes to the endoplasmic reticulum (ER), such as the amphipathic amine U18666A and the Npc1+/- mutation, also inhibit incorporation of lipoprotein-derived fatty acids into phospholipids. The biological relevance of these findings was investigated by studying the suppression of agonist-induced prostaglandin E(2) (PGE(2)) and leukotriene C(4)/D(4)/E(4) production during lipoprotein uptake by macrophages, which has been postulated to involve enrichment of cellular phospholipids with non-arachidonic fatty acids (NAAFAs). We found that eicosanoid suppression was markedly enhanced when ACAT was inhibited and prevented when late endosomal/lysosomal lipid trafficking was blocked. Moreover, PGE(2) suppression depended entirely on acetyl-LDL-derived NAAFAs, not on acetyl-LDL-cholesterol, and was not due to decreased cPLA(2) activity per se. These data support the following model: lipoprotein-derived NAAFAs traffic via the NPC1 pathway from late endosomes/lysosomes to a critical pool of phospholipids. In competing reactions, these NAAFAs can be either esterified to cholesterol or incorporated into phospholipids, resulting in suppression of eicosanoid biosynthesis. In view of recent evidence suggesting dysfunctional cholesterol esterification in late lesional macrophages, these data predict that such cells would have highly suppressed eicosanoid synthesis, thus affecting eicosanoid-mediated cell signaling in advanced atherosclerosis.


Murine Colitis modeling using Dextran Sulfate Sodium (DSS).
Colitis can occur from viral or bacterial infections, ischemic insult, or autoimmune disorders; most notably Ulcerative Colitis and the colonic variant of Crohn's Disease - Crohn's Colitis. Acute colitis may present with abdominal pain and distention, malabsorption, diarrhea, hematochezia and mucus in the stool. We are beginning to understand the complex interactions between the environment, genetics, and epithelial barrier dysfunction in Inflammatory Bowel Disease and animal models of colitis have been essential in advancing our understanding of this disease. One popular model involves supplementing the drinking water of mice with low-molecular weight Dextran Sodium Sulfate (DSS), resulting in epithelial damage and a robust inflammatory response in the colon lasting several days.Variations of this approach can be used to model acute injury, acute injury followed by repair, and repeated cycles of DSS interspersed with recovery modeling chronic inflammatory diseases. After a single four-day treatment of 3% DSS in drinking water, mice show signs of acute colitis including weight loss, bloody stools, and diarrhea. Mice are euthanized at the conclusion of the treatment course and at necropsy dissected colons are processed and can be 'Swiss rolled" to allow microscopic analysis of the entire colon or infused with formalin as "sausages" to allow macroscopic analysis. Tissue is then embedded in paraffin, sectioned, and stained for histologic review.


The accuracy of incremental pre-operative breast MRI findings - Concordance with histopathology in the Swedish randomized multicenter POMB trial.
The Pre-Operative MRI of the Breast (POMB) trial was a randomized, prospective, multicenter trial evaluating the impact of pre-operative breast MRI on treatment regimens and short-term surgical outcomes in women up to 56 years of age with breast cancer. The purpose of this study was to evaluate the performance of pre-operative breast MRI in the POMB trial with respect to incremental MRI findings - over conventional breast imaging methods - and their concordance with histopathology. Two-hundred and ten patients (n = 210) participating in the POMB trial underwent pre-operative breast MRI at two Swedish breast units. Positive predictive values (PPV) for the incremental MRI findings were calculated for three subgroups of patients with: 1. alteration/alterations of treatment plan; 2. no alteration of treatment plan; and, 3. MRI-related conversion from BCS to mastectomy. Area under the receiver operating characteristic curve (AUC) was calculated using in-breast BI-RADS based ratings for the whole MRI group. After exclusions a total number of 99 incremental findings in 78 patients were eligible for statistical analysis resulting in a PPV = 74%: (95% CI 60-84%) in 39 patients with MRI related alterations of initial treatment plans and 27%: (95% CI 14-44%) in 39 patients without. Positive predictive values of incremental findings decisive for specific treatment alteration/s were 83% (95% CI 68-92%) in patients with any alteration of initial treatment plans and 91% (95% CI 70-98%) for patients (n = 20/22) with conversion from breast conserving surgery to mastectomy. The empirical AUC for the incremental findings in the whole MRI group was 85% (95% CI 78-91%). Breast MRI, performed and evaluated together with conventional breast imaging methods can provide relevant information at a high degree of accuracy in the pre-operative setting.


[Idiopathic granulomatous mastitis treated with steroids and methotrexate].
Idiopathic granulomatous mastitis is a rare inflammatory breast disease of unknown etiology. It manifests as breast mass of 6 cm on average (range 2-10 cm), often in upper outer quadrant of left breast, in another quadrant, right or bilateral breast. Clinical diagnosis by ultrasound or mammography and fine needle aspiration confuses with carcinoma; histopathology (gold standard) confirm the diagnosis after ruling out causes of granulomatous inflammation, mainly tuberculosis. Steroid treatment achieve complete remission, but adverse reactions and relapses after the descent and suspension. Methotrexate or azathioprine is added from the start to maintain remission. We report three cases of idiopathic granulomatous mastitis diagnosis and treatment based on prednisone until clinical improvement and methotrexate as maintenance therapy. Complete remission was obtained in three patients. The rheumatologist knows and handles autoimmune/inflammatory with these drugs, therefore, is suggested the multidisciplinary treatment of this disease with oncologists and gynecologists.


Does greater phonological storage capacity correlate with levels of intentionality and theory of mind?
Greater phonological storage capacity may be associated with levels of intentionality, and therefore by assumption, Theory of Mind. The participants were 34 high school students in the Midwest (15 girls, 19 boys; age range= 15 to 17 years). The measures were digits forward and digits backward from the Digit Span subtest of the Wechsler Adult Intelligence Scale-III and a measure purporting to assess Theory of Mind and Levels of Intentionality (Kinderman, Dunbar, & Bentall, 1998). There was found to be a weak nonsignificant correlation between digits forward and Levels of Intentionality, and a moderate and significant correlation between digits backward and Levels of Intentionality. The latter correlation was significantly larger. The digits backward test requires not only greater phonological storage capacity but also appears to tap working memory resources. Findings suggest that greater phonological storage capacity is associated with higher intentionality, and by implication, perhaps more elaborate Theory of Mind, but only when the phonological task requires working memory functions.


Influence of postnatal maternal stress on blood pressure and heart rate of juvenile and adult rat offspring.
Autonomic control of blood pressure (BP) and heart rate (HR) was tested in offspring of rat dams that were unmanipulated (controls) or exposed repeatedly to either (1) Postnatal restraint, (2) Postnatal s.c. injections of alkaline saline, or (3) Prenatal s.c. alkaline saline. Under urethane anesthesia, BP was higher than control in 20-day-old offspring of restrained dams and lower at 80 days. The magnitude of the BP response to autonomic ganglionic blockade (chlorisondamine) changed in parallel; the control HR accelerator response was reversed at 20 days and enhanced at 80 days. Postnatal maternal injections increased BP in 20-day-old offspring and lowered it at 80 days. The BP response to blockade was unchanged; HR acceleration was attenuated at 20 days and increased at 80 days. No influence of Prenatal maternal injections was seen in adult offspring. Post--not prenatal maternal stress disrupts BP and HR control in rat offspring; disruption is greater after restraint than injection. There is sympathetic hyperactivity in preweanlings and hypoactivity in adults.


Pharyngeal airway dimension in patients before and after treatment of myofascial pain syndrome.
Objective: This study aimed: (1) to assess the localization of the anatomic landmarks of the pharyngeal airway on cone beam computed tomography (CBCT) images; and (2) to evaluate if resolution of myofascial pain syndrome (MPS) changed the airway dimensions.Methods: Twenty-nine patients with pre- and post-treatment CBCT scans were randomly selected to locate five landmarks twice, with a two-week interval. The same landmarks were used to measure the airway volume and minimal cross-sectional area (CSAmin).Results: The intra-observer reliability (ICC) was 0.99-1.00 for volumetric and CSAmin measurements, based on the five landmarks used. The paired t test showed no significant difference in the airway volume (p = 0.68) and CSAmin (p = 0.96).Discussion: The outcomes showed that the landmarks used had excellent ICCs for the volumetric and CSAmin measurements. There was no change in volume and CSAmin of the pharyngeal airway after resolution of MPS.


Descriptive study of severe hospitalized cases of laboratory-confirmed influenza during five epidemic seasons (2010-2015).
The Plan of Information on Acute Respiratory Infections in Catalonia (PIDIRAC) included the surveillance of severe hospitalized cases of laboratory-confirmed influenza (SHCLCI) in 2009. The objective of this study was to determine the clinical, epidemiological and virological features of SHCLCI recorded in 12 sentinel hospitals during five influenza seasons. From a sample of SHCLCI recorded during the 5 influenza epidemics seasons from 2010-2011 to 2014-2015, Cases were confirmed by PCR and/or viral isolation in cell cultures from respiratory samples. A total of 1400 SHCLCI were recorded, 33% required ICU admission and 12% died. The median age of cases was 61 years (range 0-101 years); 70.5% were unvaccinated; 80.4% received antiviral treatment (in 79.6 and 24% of cases within 48 h after hospital admission and the onset of symptoms, respectively); influenza virus A [37.9% A (H1N1)pdm09, 29.3% A (H3N2)] was identified in 87.7% of cases. Surveillance of SHCLCI provides an estimate of the severity of seasonal influenza epidemics and the identification and characterization of at-risk groups in order to facilitate preventive measures such as vaccination and early antiviral treatment.


In vitro matrix assembly induced by critical assembly concentration (CAC).
L-2 cells are an immortalized cell line derived from yolk sac parietal endoderm cells, which are responsible for the production of Reichert's membrane, a thick basement membrane produced during rat gestation. Although the L-2 cells secrete all the major components of the basal lamina, they do not assemble a robust matrix in cell culture. We hypothesized that the reason L-2 cells fail to assemble a matrix in cell culture is because the concentrations of matrix components necessary for this matrix assembly do not reach a critical association concentration (CAC) under standard cell culture conditions. To limit the diffusion of secreted molecules while maintaining a nutrient-rich environment for the cells to thrive, we developed a technique that uses a dialysis membrane to limit protein diffusion in a 2-well plate format. This technique permits L-2 cells to assemble a robust matrix in as little as 24 hr that continues to be formed for at least 72 hr. This technique may address some of the physical limitations imposed by cell culture and could be readily applied to other cell types and medium conditions.


The Impact of Socio-Demographic Factors on the Functioning of Liver Transplant Patients.
(1) Background: The aim of this study was to evaluate the influence of socio-demographic factors and the time elapsed since liver transplantation on the functioning of patients after liver transplantation; (2) Methods: This is a survey-based prospective cohort study of 112 patients, performed using: The Inventory of Socially Supportive Behaviors (ISSB), The Acceptance of Illness Scale (AIS), the Beck Depression Inventory (BDI), and a questionnaire concerning sociodemographic data prepared using the Delphi method; (3) Results: Subjects under 40 years of age reported the highest social support. The longer the time since surgery, the lower the levels of adherence and support; (4) Conclusions: 1. In the study group, most support was received by women, people under 40 years of age, and those with secondary education. However, the level of social support decreased over time after the liver transplant operation. Patients who had undergone previous transplantation showed lower levels of adherence to therapeutic recommendations. 2. Patients who were in a relationship showed higher levels of illness acceptance than single ones. Women were more likely to experience depressive symptoms than men. 3. The time since liver transplantation is an important factor that affects patients' functioning. This is a time when patients need more care, social support, and assistance in maintaining adherence to therapeutic recommendations.


Lactic acid bacteria and Bacillus spp. as fungal biological control agents.
Fungal pathogens are one of the most important agents affecting crop production and food safety, and agrochemical application is one of the main approaches to reduce phytopathogenic fungi contamination in agricultural products. However, excessive and inadequate use can cause environmental damage, human and animal hazard, and increased phytopathogen resistance to fungicides. Biological control using lactic acid bacteria (LAB) and Bacillus spp. is an environmentally friendly strategy for phytopathogenic fungi management. Several molecules produced by these bacteria indeed affect fungal growth and viability in different plant crops. In this article, the activity spectra are reviewed along with the antifungal effect and antifungal compounds produced by LAB (e.g. organic acids, peptides, cyclic dipeptides, fatty acids, and volatile compounds) and Bacillus spp. (e.g. peptides, enzymes, and volatile compounds).


Heart disease, overweight, and cigarette smoking are associated with increased prevalence of extra-cranial venous abnormalities.
Most of the extra-cranial venous abnormalities have been previously described as truncular venous malformations. In this hypothesis-driven study, we evaluated possible association of risk/protective factors with the presence of truncular and functional venous abnormalities in internal jugular veins (IJVs) in a large cohort of volunteers without known central nervous system (CNS) pathology. The study included 240 controls who underwent physical and Doppler sonography (DS) examinations for the presence of intra- and extra-luminal structural and functional abnormalities of the IJVs, and were assessed with a physical examination and structured environmental questionnaire for demographic characteristics, presence of autoimmune and other concomitant diseases, vascular risk factors, environmental factors, and habits. Logistic regression analysis was used to test which risk/protective factors were associated with the presence and number of extra-cranial venous abnormalities. Subjects with heart disease (P<0·001), overweight (P = 0·005), and smoking (P = 0·016) had a significantly increased number of intra-luminal structural venous abnormalities. Presence of heart disease increased the risk of a malformed valve 12·9 times (95% CI: 5·4-31·3, P<0·001), while smoking increased it 2·21 times (95% CI: 1-4·9, P = 0·033). Being overweight (P = 0·003), a history of mononucleosis (P = 0·012) and smoking (P = 0·042) increased risk for presence of a flap. No association was found between the investigated risk factors and extra-luminal or functional venous abnormalities. However, use of dietary and herbal supplements had a protective role for the presence of functional venous abnormalities. There is a close association between intra-luminal, structural, extra-cranial, venous system pathology and the presence of heart disease, overweight, and smoking.


One-legged endurance training: leg blood flow and oxygen extraction during cycling exercise.
As a consequence of enhanced local vascular conductance, perfusion of muscles increases with exercise intensity to suffice the oxygen demand. However, when maximal oxygen uptake (VO(2)max) and cardiac output are approached, the increase in conductance is blunted. Endurance training increases muscle metabolic capacity, but to what extent that affects the regulation of muscle vascular conductance during exercise is unknown. Seven weeks of one-legged endurance training was carried out by twelve subjects. Pulmonary VO(2) during cycling and one-legged cycling was tested before and after training, while VO(2) of the trained leg (TL) and control leg (CL) during cycling was determined after training. VO(2) max for cycling was unaffected by training, although one-legged VO(2) max became 6.7 (2.3)% (mean ± SE) larger with TL than with CL. Also TL citrate synthase activity was higher [30 (12)%; P < 0.05]. With the two legs working at precisely the same power during cycling at high intensity (n = 8), leg oxygen uptake was 21 (8)% larger for TL than for CL (P < 0.05) with oxygen extraction being 3.5 (1.1)% higher (P < 0.05) and leg blood flow tended to be higher by 16.0 (7.0)% (P = 0.06). That enhanced VO(2) max for the trained leg had no implication for cycling VO(2) max supports that there is a central limitation to VO(2) max during whole-body exercise. However, the metabolic balance between the legs was changed during high-intensity exercise as oxygen delivery and oxygen extraction were higher in the trained leg, suggesting that endurance training ameliorates blunting of leg blood flow and oxygen uptake during whole-body exercise.


Therapeutic perspectives for melatonin agonists and antagonists.
Melatonin is a neurohormone synthesized in the pineal gland during the dark period in all species, including humans. The diversity and differences in melatonin receptor distribution in the brain and extracerebral organs suggest multiple functional roles for melatonin. Administration of melatonin agonists reduces neophobia and treatment with a melatonin antagonist during the dark period reverses the anxiolytic-like effect of endogenous melatonin. Chronic treatment with agonists prevents various perturbations induced by chronic mild stress. Melatonin in vivo directly constricts cerebral arterioles in rats and decreases the lower limit of cerebral blood flow autoregulation, suggesting that melatonin may diminish the risk of hypoperfusion-induced cerebral ischemia. At the extracerebral level, melatonin regulates intestinal motility in rats. The intestinal postprandial motor response is shorter in the dark phase than in the light phase and this reduction is reversed in animals pretreated with a melatonin antagonist. Moreover, melatonin reduces the duration of cholecystokinin excitomotor effect. Endogenous melatonin may modulate intestinal motility to coordinate intestinal functions such as digestion and transit and control the metabolism of the animal. An adipocyte melatonin binding site may also participate in this control. Melatonin is involved in a wide range of physiological functions. The question remains as to whether evolution, adaptation and diurnal life have modified the physiological role of melatonin in humans. Moreover, the functional role of each of the receptor subtypes has to be characterized to design selective ligands to treat specific diseases.


SIGNATURE: a workbench for gene expression signature analysis.
The biological phenotype of a cell, such as a characteristic visual image or behavior, reflects activities derived from the expression of collections of genes. As such, an ability to measure the expression of these genes provides an opportunity to develop more precise and varied sets of phenotypes. However, to use this approach requires computational methods that are difficult to implement and apply, and thus there is a critical need for intelligent software tools that can reduce the technical burden of the analysis. Tools for gene expression analyses are unusually difficult to implement in a user-friendly way because their application requires a combination of biological data curation, statistical computational methods, and database expertise. We have developed SIGNATURE, a web-based resource that simplifies gene expression signature analysis by providing software, data, and protocols to perform the analysis successfully. This resource uses bayesian methods for processing gene expression data coupled with a curated database of gene expression signatures, all carried out within a GenePattern web interface for easy use and access. SIGNATURE is available for public use at http://genepattern.genome.duke.edu/signature/.


Polydiacetylene vesicles functionalized with N-heterocyclic ligands for metal cation binding.
Self assembled poly diacetylene (PDA) based blue vesicles LS-Terpy, LS-DPA, LS-DP and LS-DEA with metal chelating sites have been prepared and characterized. Their response to the presence of metal cations in buffered aqueous solution has been investigated by monitoring changes of colour, UV-Vis absorption and emission. The addition of zinc, manganese, cadmium, mercury or silver salts to solutions of the vesicles induces a colour change from blue to red observable by the naked eye, while the addition of other metal salts, containing ions like Li(+), Na(+), K(+), Mg(2+), Ca(2+), Cr(2+), Ni(2+), Fe(2+), Co(2+), Cu(2+) or Pb(2+), failed to show any changes. The metal ion coordination selectivity of the ligands is slightly different for the vesicle surface immobilized ligands compared to the reported metal cation binding of the corresponding ligands in solution, which may be due to the special environment at the lipid-solution interface. The vesicles aggregate upon metal ion coordination to the embedded ligands as shown by dynamic light scattering (DLS) particle size analysis. The functionalized PDA vesicles retain their response to the presence of aqueous solutions of metal ions if immobilized in transparent polyvinyl alcohol films or on paper.


Surface Assessment via Grid Evaluation (SuAVE) for Every Surface Curvature and Cavity Shape.
The surface assessment via grid evaluation (SuAVE) software was developed to account for the effect of curvature in the calculations of structural properties of chemical interfaces regardless of the chemical composition, asymmetry, and level of atom coarseness. It employs differential geometry techniques, enabling the representation of chemical surfaces as fully differentiable. In this article, we present novel developments of SuAVE to treat closed surfaces and complex cavity shapes. These developments expand the repertoire of curvature-dependent analyses already available in the previous version of SuAVE (e.g., area per lipid, density profiles, membrane thickness, deuterium-order parameters, volume per lipid, and surface curvature angle) to include new functionalities applicable to soft matter (e.g., sphericity, average radius, principal moment of inertia, and roundness) and crystalline porous materials (e.g., pore diameter, internal void volume, total area, and the total void volume of the unit cell structure). SuAVE can accurately handle chemical systems with high and low atom density as demonstrated for two distinct chemical systems: the lipid A vesicle and a set of selected metal-organic frameworks. The SuAVE software v2.0 is fully parallel and benefits from a compiler that supports OpenMP. SuAVE is freely available from https://github.com/SuAVE-Software/source and https://www.biomatsite.net/.


Are we slipping them through the cracks? The insufficiency of norm-referenced assessments for identifying language weaknesses in children with hearing loss.
Children with hearing loss who use listening and spoken language increasingly reach performance within or above the average range on norm-referenced assessments of language ability prior to entering school; however, they continue to perform below expectations on language-based academic skills, such as reading. The purpose of this article was to identify limitations of making service provision decisions primarily on the basis of norm-referenced assessments for children with hearing loss. We offer evidence from a group of children with hearing loss who scored within 1.5 standard deviations of the mean on a norm-referenced omnibus language measure. These children with hearing loss performed more poorly than age-matched children with normal hearing on several measures derived from a naturalistic language sample. Based on the limitations of norm-referenced assessments and the findings of this study, we propose that language sample analysis should be used as primary evidence of language weakness for children with hearing loss.


BING: biomedical informatics pipeline for Next Generation Sequencing.
High throughput parallel genomic sequencing (Next Generation Sequencing, NGS) shifts the bottleneck in sequencing processes from experimental data production to computationally intensive informatics-based data analysis. This manuscript introduces a biomedical informatics pipeline (BING) for the analysis of NGS data that offers several novel computational approaches to 1. image alignment, 2. signal correlation, compensation, separation, and pixel-based cluster registration, 3. signal measurement and base calling, 4. quality control and accuracy measurement. These approaches address many of the informatics challenges, including image processing, computational performance, and accuracy. These new algorithms are benchmarked against the Illumina Genome Analysis Pipeline. BING is the one of the first software tools to perform pixel-based analysis of NGS data. When compared to the Illumina informatics tool, BING's pixel-based approach produces a significant increase in the number of sequence reads, while reducing the computational time per experiment and error rate (<2%). This approach has the potential of increasing the density and throughput of NGS technologies.


Immunogenicity and molecular characterisation of staphylococcal delta haemolysin.
In rabbit antisera to staphylococcal delta haemolysin the haemolysin-neutralising activity was associated with the IgG fraction as well as with the alpha and beta lipoproteins. On an equal-weight basis, the neutralising capacity of specific antibody was not significantly greater than that of serum alpha or beta lipoproteins. Anti-alpha haemolysin was not detected in any of the anti-delta-haemolysin antisera. Amino-acid analysis of delta haemolysin showed that lysine, aspartic acid, threonine and isoleucine were the predominant amino acids present; histidine, arginine, proline, cysteine and tyrosine were absent. The molecular weight of delta-haemolysin in phosphate-buffered saline was approximately 210 000.


Differentiation of acupuncture and nonacupuncture points by difference of associated opioids in the spinal cord in production of analgesia by acupuncture and nonacupuncture point stimulation, and relations between sodium and those opioids.
Antiserum of methionine-enkephalin (Met-Enk) applied intrathecally abolished acupuncture analgesia (AA) caused by low frequency stimulation of an acupuncture point (tibial muscle, APS) of rats, but antisera of leucine-enkephalin (Leu-Enk) and dynorphin (Dyn) did not. Antiserum of Dyn applied intrathecally abolished analgesia (NAA) produced by stimulation of a nonacupuncture point (NAPS) which was revealed by lesion in the analgesia inhibitory system (AIS), whereas antisera of Met-Enk and Leu-Enk did not. NAA was antagonized by the kappa-receptor antagonist, Mr2266, and analgesia was produced by the kappa-agonist, U50-488H, in the AIS lesioned rats. Potentials in the dorsal periaqueductal central gray (D-PAG) evoked by APS were antagonized by naloxone and antiserum of Met-Enk, and those in the lateral PAG (L-PAG) evoked by NAPS were antagonized by Mr2266 and antiserum of Dyn. After adrenalectomy, AA, potentials in the D-PAG, and analgesia caused by stimulation (SPA) of the D-PAG were abolished 12 hour; and NAA, potentials in the L-PAG, and SPA of the L-PAG were abolished in 24 hour. All were then restored one hour after intravenous application of 1 ml of 5% NaCl solution. AA and NAA which were augmented for several hours before their abolition after adrenalectomy were not antagonized by naloxone nor M 2266, respectively. However naloxone and Mr2266 did antagonize AA and NAA, respectively, one hour after treatment with 1 ml of 5% NaCl solution.


Proteomic biomarkers in body fluids associated with pancreatic cancer.
Pancreatic cancer (PC) is a highly malignant disease that represents the fourth leading cancer-related death worldwide. There has been very little improvement in survival rates over recent years, and surgical resection remains the only reliable curative approach. Factors that contribute to this dismal prognosis for PC include its rapid progression and invasion, the absence of specific symptoms, and the little impact of available chemotherapy. Importantly, the management of this malignancy is also limited by the lack of highly specific and sensitive biomarkers for its diagnosis and follow-up, and their identification is therefore considered a promising strategy to improve outcomes in these patients. Numerous translational studies have explored the usefulness of body fluids as a non-invasive source of PC-specific biomarkers, and innovations in proteomic methods and technologies have provided a myriad of protein biomarkers for different cancers. The adoption of a proteomic approach has improved understanding of the biology of PC and contributed to the potential identification of protein biomarkers for this disease. This review considers the most recent research efforts to develop novel proteomic biomarkers in body fluids for PC.


Direct fluorination of carbon nanocones and nanodiscs.
This work focuses on the reactivity of carbon nanodiscs and nanocones with respect to pure fluorine gas. The starting materials, as-synthesized without post-treatment, consist of a mixture of nanodiscs (approximately 70% w/w), nanocones (approximately 20% w/w) and amorphous carbons (approximately 10% w/w). In order to investigate their reactivity in pure F2 gas, two experiment sets have been performed: (i) in situ Thermo Gravimetric Analysis under diluted F2 and relative F2 pressure measurements, which highlight the temperature domain for an efficient fluorination, and then, allow the fluorination conditions to be optimized; (ii) the fluorination under pure F2 gas was performed at temperatures ranged between room temperature and 450 degrees C. Ex situ characterization was carried out using 13C and 19F solid state Nuclear Magnetic Resonance and Scanning Electron Microscopy. For the low reaction temperature (up to 300 degrees C), the chemical stability of these kinds of nanocarbons prevents from intensive fluorination. On the other hand, at temperature higher than 300 degrees C, the fluorination is important but competes with the material decomposition. The fluorination mechanism has been established taking into account NMR and SEM data.


The first catalytic asymmetric addition of dialkylzincs to alpha-ketoesters.
[formula: see text] The first catalytic, enantioselective addition of organoznic reagents to alpha-ketoesters is described. Modular bifunctional salen catalysts that contain Lewis acid and Lewis base activating groups accelerate the carbonyl addition to a much greater extent than the competing carbonyl reduction. alpha-Hydroxyesters containing new quaternary stereogenic centers are obtained in high yield and moderate enantiomeric excess. Enrichment to 98% ee can be effected by recrystallization of the corresponding alpha-hydroxy acid.


Baseline characteristics of participants in the Women's Health Study.
The Women's Health Study (WHS) is a randomized, double-blind, placebo-controlled trial designed to evaluate the balance of benefits and risks of low-dose aspirin and vitamin E in the primary prevention of cardiovascular disease and cancer in women. A total of 39,876 female health professionals, age 45 years or older and without a history of cardiovascular disease or cancer (other than nonmelanoma skin cancer), were randomized in a 2x2 factorial design to one of four treatment groups: active aspirin and vitamin E placebo, aspirin placebo and active vitamin E, both active agents, or both placebos. The process of randomization was successful, as evidenced by the equal distribution of a large number of baseline demographic, lifestyle, and health history characteristics among the four treatment groups. Similar distribution of known potential confounders, as well as the large sample size, provides reassuring evidence that unmeasured or unknown potential confounders are also equally distributed. As expected in a clinical trial, the women in the study are healthier in some respects than the general population, but they have very comparable rates of obesity, hypertension, and elevated cholesterol. With adequate duration of treatment and follow-up, this trial will provide important and relevant information on the balance of benefits and risks of aspirin and vitamin E supplementation in the primary prevention of cardiovascular disease and cancer in women.


Acute effect of repeated passive motion exercise on shoulder position sense in patients with hemiplegia: a pilot study.
To determine the effect of repeated passive motion (RPM) exercise on position sense of the shoulder joint in patients with hemiplegia. Shoulder flexion position sense was evaluated for the affected side of 15 patients with hemiplegia, using an assessment board set at five angles (30 degrees, 60 degrees, 90 degrees, 120 degrees and 150 degrees). First, the affected shoulder was positioned passively, twice at each angle. Then, with the patient blindfolded, a repositioning test was performed twice at each angle, presented in random order. The assessment score was calculated as the proportion of correct responses (PCRs) for repositioning. After the testing, the RPM exercise, consisting of scapular and shoulder motions, was performed in a supine position for 15 min, and the testing was repeated. After the RPM exercise, there was a significant difference in total PCR for right hemiplegia (p < 0.05) and in total PCR and PCR at 90 degrees for left hemiplegia (p < 0.05). However, the PCR was not significantly different between right and left hemiplegia at any angle. For all of the patients, the total PCR and the PCRs for every angle except 30 degrees and 150 degrees were significantly greater after the RPM exercise (p < 0.05). The RPM exercise was helpful in improving proprioception in patients with hemiplegia. Further studies are needed to generalize these findings.


Development of the Human Biceps Brachii Tendon and Coracoglenoid Ligament (7th-12th Week of Development).
The goal of this study is to clarify the development of the long head of the biceps brachii tendon (LHBT) and to verify the existence and development of the coracoglenoid ligament. Histological preparations of 22 human embryos (7-8 weeks of development) and 43 human fetuses (9-12 weeks of development) were studied bilaterally using a conventional optical microscope. The articular interzone gives rise to the LHBT, glenoid labrum, and articular capsule. During the fetal period, it was observed that in 50 cases (58%), the LHBT originated from both the glenoid labrum and the scapula, while in 36 cases (42%), it originated only from the glenoid labrum. The coracoglenoid ligament, first described by Sappey in 1867, is a constant structure that originates at the base of the coracoid process and projects toward the glenoid labrum zone, which is related to the origin of the LHBT. The coracoglenoid ligament was more easily identifiable in the 36 cases in which the LHBT originated only from the glenoid labrum. We suggest that the coracoglenoid ligament is a constant anatomical structure, is not derived from the articular interzone unlike the LHBT, and contributes to the fixation of the glenoid labrum in the scapula in cases in which the LHBT originated only from the glenoid labrum. We postulate that, when the LHBT is fixed only at the glenoid labrum, alterations in the coracoglenoid ligament could lead to a less sufficient attachment of the glenoid labrum to the scapula which could predispose to a superior labral lesion.


Sprague Dawley Rats Show More Severe Bone Loss, Osteophytosis and Inflammation Compared toWistar Han Rats in a High-Fat, High-Sucrose Diet Model of Joint Damage.
In animal models, joint degeneration observed in response to obesogenic diet varies in nature and severity. In this study, we compare joint damage in Sprague Dawley and Wistar-Han rats in response to a high-fat, high-sucrose (HFS) diet groove model of osteoarthritis (OA). Wistar Han (n = 5) and Sprague Dawley (n = 5) rats were fed an HFS diet for 24 weeks. OA was induced 12 weeks after the diet onset by groove surgery in the right knee joint. The left knee served as a control. Outcomes were OARSI histopathology scoring, bone changes by µCT imaging, local (synovial and fat pad) and systemic (blood cytokine) inflammation markers. In both rat strains, the HFS diet resulted in a similar change in metabolic parameters, but only Sprague Dawley rats showed a large, osteoporosis-like decrease in trabecular bone volume. Osteophyte count and local joint inflammation were higher in Sprague Dawley rats. In contrast, cartilage degeneration and systemic inflammatory marker levels were similar between the rat strains. The difference in bone volume loss, osteophytosis and local inflammation suggest that both rat strains show a different joint damage phenotype and could, therefore, potentially represent different OA phenotypes observed in humans.


CuCo2O4 Hollow Microspheres with Graphene Composite Targeting Superior Lithium-Ion Storage.
CuCo2O4, a type of promising lithium-ion storage material, exhibits high electrochemical properties in lithium-ion batteries and enormous economic benefits. However, its practical application is limited by problems such as structural collapse and electrochemical stability during the charging and discharging process. In this work, the reduced graphene oxide (rGO)-coated CuCo2O4 (CuCo2O4/rGO) hollow microspheres were successfully prepared by electrostatic self-assembly. The CuCo2O4/rGO electrode shows an outstanding capability for lithium-ion storage and a remarkable rate capacity, e.g., 445 mA h g-1 at 5 A g-1. After 150 cycles at 0.1 A g-1, the reversible capacity of the CuCo2O4/rGO electrode is as high as 1080 mA h g-1, and it can still retain about 530 mA h g-1 in the 400th cycle at 1 A g-1. The hollow microspheres with mesoporous shells can cause electrolyte penetration into the spherical shell to effectively shorten the transfer distance of lithium ions, and the encapsulation of graphene improves the conductivity and stability of CuCo2O4, which endows CuCo2O4/rGO with a wonderful Li+ storage performance. It is proved that this is an efficient method to improve the electrochemical performance of metal compounds for better applications in energy storage.


Brain perivascular macrophages and the sympathetic response to inflammation in rats after myocardial infarction.
Inflammation is associated with increased sympathetic drive in cardiovascular diseases. Blood-borne proinflammatory cytokines, markers of inflammation, induce cyclooxygenase 2 (COX-2) activity in perivascular macrophages of the blood-brain barrier. COX-2 generates prostaglandin E(2), which may enter the brain and increase sympathetic nerve activity. We examined the contribution of this mechanism to augmented sympathetic drive in rats after myocardial infarction (MI). Approximately 24 hours after acute MI, rats received an intracerebroventricular injection (1 microL/min over 40 minutes) of clodronate liposomes (MI+CLOD) to eliminate brain perivascular macrophages, liposomes alone, or artificial cerebrospinal fluid. A week later, COX-2 immunoreactivity in perivascular macrophages and COX-2 mRNA and protein had increased in hypothalamic paraventricular nucleus of MI rats treated with artificial cerebrospinal fluid or liposomes alone compared with sham-operated rats. In MI+CLOD rats, neither perivascular macrophages nor COX-2 immunoreactivity was seen in the paraventricular nucleus, and COX-2 mRNA and protein levels were similar to those in sham-operated rats. Prostaglandin E(2) in cerebrospinal fluid, paraventricular nucleus neuronal excitation, and plasma norepinephrine were less in MI+CLOD rats than in MI rats treated with artificial cerebrospinal fluid or liposomes alone but more than in sham-operated rats. Intracerebroventricular CLOD had no effect on interleukin 1beta and tumor necrosis factor-alpha mRNA and protein in the paraventricular nucleus or plasma interleukin-1beta and tumor necrosis factor-alpha, which were increased in MI compared with sham-operated rats. In normal rats, pretreatment with intracerebroventricular CLOD reduced (P<0.05) the renal sympathetic, blood pressure, and heart rate responses to intracarotid artery injection of tumor necrosis factor-alpha (0.5 microg/kg); intracerebroventricular liposomes had no effect. The results suggest that proinflammatory cytokines stimulate sympathetic excitation after MI by inducing COX-2 activity and prostaglandin E(2) production in perivascular macrophages of the blood-brain barrier.


Three-dimensional echocardiography: research toy or clinical tool?
Conventional 2D echocardiography is an excellent qualitative imaging method, but its use for quantitation is limited by test-retest reproducibility of image planes. The increasing sophistication of medical treatments for left ventricular dysfunction, hypertension and valvular heart disease has created the need for accurate and reproducible measurements of chamber dimensions. Similarly, improvements in valve repair and catheter-based interventions for valve lesions and septal defects have created the need for better visualisation of cardiac structures. The use of 31) echocardiography may decrease variability both in the quality and interpretation of complex pathology among investigators. Three-dimensional echocardiography is achieved by using a 3D spatial registration device with a conventional 21) scanner, or by using a high-speed, phased-array real-time scanner. The latter are still developmental, so that the technique currently requires use of a 21) scanner, combined with a 31) spatial coordinate system, which may be external or internal to the scanning transducer. An external system permits data acquired from several cardiac windows to be integrated and reconstructed. Image reconstruction is performed using a wire-frame model or surface rendering. Wire-frame models are formed by manual or automatic connection of boundary data points; this approach uses fewer data points than rendering, can be rapidly processed and is sufficient for quantitative analysis. Surface-rendering uses lighting and shading applied to a wire-frame model to produce a realistic 31) display, which may be useful for surgical planning and increasing understanding of anatomic relations. Three-dimensional echocardiography yields more accurate measurements of ventricular volume and function, as well as new measurements such as infarct area. With increased reproducibility and reliability, 3D echocardiography may well prove to be the essential tool required for the serial follow up of left ventricular mass and volume.


Respiratory syncytial virus fusion glycoprotein: nucleotide sequence of mRNA, identification of cleavage activation site and amino acid sequence of N-terminus of F1 subunit.
The amino acid sequence of respiratory syncytial virus fusion protein (Fo) was deduced from the sequence of a partial cDNA clone of mRNA and from the 5' mRNA sequence obtained by primer extension and dideoxysequencing. The encoded protein of 574 amino acids is extremely hydrophobic and has a molecular weight of 63371 daltons. The site of proteolytic cleavage within this protein was accurately mapped by determining a partial amino acid sequence of the N-terminus of the larger subunit (F1) purified by radioimmunoprecipitation using monoclonal antibodies. Alignment of the N-terminus of the F1 subunit within the deduced amino acid sequence of Fo permitted us to identify a sequence of lys-lys-arg-lys-arg-arg at the C-terminus of the smaller N-terminal F2 subunit that appears to represent the cleavage/activation domain. Five potential sites of glycosylation, four within the F2 subunit, were also identified. Three extremely hydrophobic domains are present in the protein; a) the N-terminal signal sequence, b) the N-terminus of the F1 subunit that is analogous to the N-terminus of the paramyxovirus F1 subunit and the HA2 subunit of influenza virus hemagglutinin, and c) the putative membrane anchorage domain near the C-terminus of F1.


Edible oil adulterants, argemone oil and butter yellow, as aetiological factors for gall bladder cancer.
Carcinogenic potential of argemone oil (AO) and butter yellow (BY), the adulterants encountered in edible oil, in gall bladder of Swiss albino mice was undertaken to investigate the potential aetiological factors of gall bladder carcinoma (GBC) in the Indo-Gangetic basin. Twice weekly intraperitoneal (ip) administration of AO (5 ml/kg body wt) and BY (25 mg/kg body wt) to Swiss albino male and female mice for 30 and 60 days indicated that females were more vulnerable to these adulterants in terms of responses to inflammatory markers. Subsequent experiments with dietary exposure of AO (1%) and BY (0.06%) for 6 months in female mice showed symptoms related to cachexia, jaundice and anaemia. High levels of total cholesterol, low density lipoprotein (LDL), TG, bilirubin and low level of high density lipoprotein (HDL) as well as gallstone formation was shown by AO exposure only, leading to the development of adenocarcinoma. BY exposure resulted in adenoma and hyperplasia without stone formation. The cyclooxygenase (COX-2) overexpression was found to be related to prostaglandin E2 (PGE2) production in AO treated mice but not in BY exposed animals, thereby indicating a differential pathway specific carcinogenicity. PGE2 stimulates the secretion of secreted mucins (MUC5AC), which is involved in stone formation following AO exposure. Enhanced secretion of membrane bound mucins (MUC4) in BY and AO exposed mice resulted in the activation of ErbB2 and downstream signalling such as p-AKT, p-ERK and p-JNK, which ultimately affects the target proteins, p53 and p21 leading to adenoma and adenocarcinoma, respectively. The study suggests that AO and BY are responsible for producing GBC in mice along with stone formation in the AO exposed animals.


Bias in patient satisfaction surveys: a threat to measuring healthcare quality.
Patient satisfaction surveys are an increasingly common element of efforts to evaluate the quality of healthcare. Many patient satisfaction surveys in low/middle-income countries frame statements positively and invite patients to agree or disagree, so that positive responses may reflect either true satisfaction or bias induced by the positive framing. In an experiment with more than 2200 patients in Nigeria, we distinguish between actual satisfaction and survey biases. Patients randomly assigned to receive negatively framed statements expressed significantly lower levels of satisfaction (87%) than patients receiving the standard positively framed statements (95%-p<0.001). Depending on the question, the effect is as high as a 19 percentage point drop (p<0.001). Thus, high reported patient satisfaction likely overstates the quality of health services. Providers and policymakers wishing to gauge the quality of care will need to avoid framing that induces bias and to complement patient satisfaction measures with more objective measures of quality.


Inflammatory pseudotumor of the spleen--a case report.
A 36-year-old woman had suffered from epigastric fullness for half a year. A splenic mass was found by ultrasonography. She was treated with splenectomy. Inflammatory pseudotumor of the spleen was diagnosed pathologically. This benign tumor in the spleen is extremely rare. To our knowledge, only 67 cases had been reported in the literature. Recognition of this rare entity is important because it may mimic splenic malignancy clinically and radiographically.


Myxoid Spindle Cell Sarcoma With LMNA-NTRK Fusion: Expanding the Morphologic Spectrum of NTRK-Rearranged Tumors.
Neurotrophic tyrosine receptor kinase (NTRK)-rearranged spindle cell neoplasm is a recently described soft tissue tumor entity that occurs predominantly in children and young adults. The diagnosis of this tumor is difficult due to the nonspecific and highly variable morphology, yet it is of clinical relevance because of the availability of highly effective TRK inhibitors. In this article, we report the case of a 40-year-old female who presented with a mass in the left calf. Histologic examination revealed a low-grade sarcoma consisting of monomorphic spindle cells accompanied by abundant myxoid stroma, a feature that had not been emphasized in the reported cases of NTRK-rearranged tumors. The tumor cells expressed CD34 and S100 but not SOX10, and they showed positive staining for pan-TRK. Next-generation sequencing showed the presence of LMNA-NTRK1 fusion. The patient developed several episodes of lung metastases that eventually became unresectable. TRK inhibitor was given that led to near-complete resolution of the tumors.


[Study of the psycho-emotional disorders' severity in patients with osteoporotic vertebral fractures and factors affecting them].
There are convincing data on the association of psycho-emotional disorders with the degree of bone mineral density (BMD) loss and the risk of fractures on the basis of osteoporosis (OP) but the nature of the causal relationship has not yet been clearly established. The study of this issue is important to substantiate the need and nature of psychological correction within the framework of comprehensive rehabilitation programs in patients with osteoporotic fractures. Study of the severity of symptoms of depression and anxiety in patients who have suffered compression fractures of the vertebrae (VF) of osteoporotic genesis who entered the II stage of medical rehabilitation, as well as the contribution to the development of psycho-emotional age disorders, the severity of OP, pain syndrome and the use of orthotics. The study sample consisted of 120 women 50 to 80 years old with an established diagnosis of OP based on the results of bone densitometry. The main group included 60 patients with OP complicated by at least one VF. The control group included 60 patients with OP without a history of osteoporotic fractures comparable in age, body mass index and BMD in the spine with the main group. The complex of examination included the collection of complaints, anamnesis of OP, previous fractures, assessment of pain syndrome according to VAS, BMD study and verification of VF by X-ray methods. To assess the level of depression (DL) we used the Tsung depression scale modified by T.I. Balashova, situational (SA) and personal anxiety (PA) - Spielberger-Khanin questionnaire. In the main group in comparison with the control group the proportion of patients without symptoms of depression was lower (66.7 and 88.3%, respectively; p=0.042), as well as the frequency of detection of high degree of SA was higher (85.0 and 73.4%, respectively; p=0.039). In patients with VF it was higher than in the control, DL - 46.0 [42.0; 54.5] (27-70) and 43.0 [38.0; 47.5] (25-65) points, respectively (p=0.0009), as well as the SA degree - 61.5 [54.0; 71.0] (20-75) and 52.5 [43.5; 64.0] (20-68) points, respectively (p=0.0006). Statistically significant direct correlation dependences of DL on age (r=0.317; p=0.00042), the duration of the postmenopausal period (r=0.325; p=0.0003), the number of VFs (g= -0.245; p=0.00013) were established. Moreover, the intensity of pain syndrome (g= -0.234; p=0.00034), as well as feedbacks of this indicator with BMD in the spine (r= -0.342; p=0.00017) and the duration of the use of thoracolumbar orthoses (r = -0.504; p = 0.00016). There were direct dependence of the SA degree on age (r=0.281; p=0.0019) and the intensity of pain syndrome (g=0.258; p=0.0044). Negative correlation of SA with body weight (r= -0.183; p=0.045), BMD in the spine (r= -0.207; p=0.026), duration of orthosis application (r= -0.327; p=0.0095) and the amount of VF in the lumbar spine (g= -0.214; p=0.044) were detected. There was a significant correlation between the degree of PA and BMD in the lumbar vertebrae (r= -0.18; p=0.046) and the intensity of pain syndrome (g=0.137; p=0.039). The results obtained indicate the need for psychological correction in the framework of the complex rehabilitation of women who underwent VF based on OP due to increased DL and SA especially in older age groups.


Taxonomic revision of the recent marine Corbulidae (Mollusca, Bivalvia) from Brazil.
The present study provides a taxonomic revision of living species of Corbulidae from Brazil based on shell characters, including the examination of the type material and specimens from different collections from Brazil, USA and Europe. There are twelve species of Corbulidae in Brazil belonging to Corbula, Caryocorbula, Juliacorbula, Tenuicorbula and Varicorbula. Caryocorbula chittyana, Caryocorbula marmorata, Caryocorbula luteola and Juliacorbula bicarinata are new occurrences in Brazil. Corbula dietziana, Caryocorbula swiftiana and Caryocorbula chittyana have identical shell morphologies to species from the Eastern Pacific possibly indicating closer phylogenetic relationships. Corbula tryoni and Corbula patagonica appear to be endemic to South America. These latter species are similar to Corbulidae from the Indo-Pacific. Based on comparisons with type material, the following synonymies are suggested: Corbula uruguayensis, traditionally considered a synonym of Caryocorbula swiftiana, is a specimen in pre-accretion stage of C. patagonica, and Corbula caribaea, Corbula barratiana and Corbula kjoeriana are synonyms of Caryocorbula swiftiana. Three species have great morphological variability, C. patagonica, C. swiftiana and Juliacorbula aequivalvis; most species exhibit great post-larval ontogenetic variability.


Neuronal Phenotype of col4a1 and col25a1: An Intriguing Hypothesis in Vertebrates Brain Aging.
Collagens are the most abundant proteins in vertebrates and constitute the major components of the extracellular matrix. Collagens play an important and multifaceted role in the development and functioning of the nervous system and undergo structural remodeling and quantitative modifications during aging. Here, we investigated the age-dependent regulation of col4a1 and col25a1 in the brain of the short-lived vertebrate Nothobranchius furzeri, a powerful model organism for aging research due to its natural fast-aging process and further characterized typical hallmarks of brain aging in this species. We showed that col4a1 and col25a1 are relatively well conserved during vertebrate evolution, and their expression significantly increases in the brain of N. furzeri upon aging. Noteworthy, we report that both col4a1 and col25a1 are expressed in cells with a neuronal phenotype, unlike what has already been documented in mammalian brain, in which only col25a1 is considered a neuronal marker, whereas col4a1 seems to be expressed only in endothelial cells. Overall, our findings encourage further investigation on the role of col4a1 and col25a1 in the biology of the vertebrate brain as well as the onset of aging and neurodegenerative diseases.


Aberrant P-cadherin expression: is it associated with estrogen-independent growth in breast cancer?
Breast carcinomas represent a heterogeneous group of tumors, with a diverse biologic behavior, outcome, and response to therapy. Recent studies have demonstrated that alterations in the expression of adhesion molecules in cancer cells are related to aggressiveness and poor prognosis. The aim of our study was to investigate the expression of P-cadherin in breast carcinomas and correlate it with estrogen receptor (ER) status. We selected 73 ductal carcinomas in situ (DCIS) and 149 invasive carcinomas of the breast, and assessed the expression of P-cadherin as well as other biologic markers. P-cadherin expression showed a strong inverse correlation with ER expression in both types of breast carcinoma (in situ and invasive). P-cadherin-positive and ER-negative tumors were related to a higher histologic grade, a high proliferation rate, and expression of c-erbB-2. We demonstrated that P-cadherin identifies a subgroup of breast carcinomas that lacks ER expression, and correlates with higher proliferation rates and other predictors of aggressive behavior. We believe that these tumors represent an advanced step in cancer progression, and our data support the hypothesis that an estrogen-independent pathway regulates P-cadherin expression.


Klinefelter syndrome with systemic lupus erythematosus in an Indian man.
Previously, cases of systemic lupus erythematosus (SLE) and Klinefelter syndrome (KS) in men have been reported in Western populations. We report the case of a 30-year-old man from southern India with known infertility who was diagnosed to have SLE and KS by fluorescence in-situ hybridization, as routine karyotype cultures failed. The diagnosis has implications in management and highlights the need for strong clinical suspicion and laboratory confirmation of KS by molecular methods when suspected in all men with SLE. Quicker, long-term remission and genetic counseling of such individuals can help in better management and coping with this chronic, potentially fatal disease. Lupus (2010) 19, 870-871.


Knockdown of p57 gene inhibits breast cancer cell proliferation.
The aim of the study was to investigate possible effects of p57 on the growth of the human MCF-7 and rat SHZ-88 breast cancer cell lines. Specific oligonucleotide sequences containing small hairpin structure were inserted into a small interfering RNA (siRNA) expression vector. The human MCF-7 and rat SHZ-88 breast cancer cell lines were transfected with recombinant plasmids. The p57 gene expression was blocked in the human MCF-7 breast and rat SHZ-88 breast cancer cells, using chemically modified siRNA. The p57 expression level was evaluated using quantitative polymerase chain reaction (qPCR) and western blot analysis. Immunofluorescence was conducted to detect p57 expression in the breast cancer cells. Tetrazolium blue (MTT) method was employed to detect the effect of p57 inhibition on the proliferation of the MCF-7 and SHZ-88 cell lines. Cell proliferation in the experimental group was significantly reduced. Immunofluorescence assay results showed p57 siRNA effectively inhibited the p57 level in the MCF-7 and SHZ-88 cells. RT-PCR results showed that 48 h after transfection, the p57 mRNA level in the transfected group was significantly lower compared with the control group. In conclusion, p57 effectively inhibited the proliferation of breast cancer after stable interference.


External levator resection for involutional ptosis: is intraoperative suture adjustment necessary for good outcomes?
Purpose: To directly compare an algorithmic external levator resection technique with the choice of intraoperative adjustment to the same technique without intraoperative adjustments. Methods: A sequential controlled prospective comparative cohort study. Two cohorts were compared: a historical control adjustment, and an experimental non-adjustment group. Fourteen patients, 25 eyelids, were in the historical cohort; and 15 patients, 23 eyelids, were in the non-adjustment cohort. Primary acquired ptosis patients who met inclusion criteria were considered. All patients underwent a standardized external levator resection technique. Intraoperative adjustments were performed only in the historical cohort. Age, follow-up time, surgical time, and marginal reflex distance 1 (MRD1) were collected. Statistical analysis was performed using the Mann-Whitney U test. Statistical significance was p < 0.05. Primary and secondary outcome measures were postoperative MRD1 minus goal MRD1, and surgical time, respectively. Results: Twenty-five historical eyelids were compared with 23 non-adjusted eyelids. The average patient age was 68.4 years (range 19-84) and 59.3 years (range 24-83) for the adjusted and non-adjusted groups. Six-month postoperative (postoperative minus goal) MRD1 was -0.1 mm (95% CI -0.3-0.1) and -0.2 mm (95% -0.5-0.0) (p = 0.33), and surgical time was 13.8 min (95% CI 12.6-15.1) and 9.5 min (95% CI 9.0-10.1) (p < 0.001) for the adjusted and non-adjusted cohort, respectively. Conclusions: The external levator resection, utilizing a standardized algorithm approach, is an efficacious technique for involutional eyelid ptosis. With sound technique, this method can be performed without the need for intraoperative adjustment, thereby saving operative time and achieving similar results.


Disruption of RNA Metabolism in Neurological Diseases and Emerging Therapeutic Interventions.
RNA binding proteins are critical to the maintenance of the transcriptome via controlled regulation of RNA processing and transport. Alterations of these proteins impact multiple steps of the RNA life cycle resulting in various molecular phenotypes such as aberrant RNA splicing, transport, and stability. Disruption of RNA binding proteins and widespread RNA processing defects are increasingly recognized as critical determinants of neurological diseases. Here, we describe distinct mechanisms by which the homeostasis of RNA binding proteins is compromised in neurological disorders through their reduced expression level, increased propensity to aggregate or sequestration by abnormal RNAs. These mechanisms all converge toward altered neuronal function highlighting the susceptibility of neurons to deleterious changes in RNA expression and the central role of RNA binding proteins in preserving neuronal integrity. Emerging therapeutic approaches to mitigate or reverse alterations of RNA binding proteins in neurological diseases are discussed.


Social anxiety disorder treatments: psychosocial therapies.
Controlled clinical trials in social anxiety disorder (SAD) have shown benefit with the use of medication and cognitive-behavioral therapies as well as incorporation of combined therapeutic modalities. This article briefly summarizes the literature on the outcome of group and individual cognitive-behavioral therapy for SAD and concludes that individual therapy is superior to group therapy. Finally, the article discusses comorbidity of depression and SAD and its implications for cognitive-behavioral therapy.


[Carotid-cavernous fistula successfully treated with embolization and radiation therapy: report of three cases].
Three cases of mixed internal and external carotid-cavernous fistula (CCF) were successfully treated with embolization of feeders from the external carotid artery (ECA) and focal irradiation to the cavernous sinus (CS). Cases 1 and 2 were females, 63 and 69 years old respectively, both with spontaneous left CCF. Case 3 was a 55 year old male with posttraumatic left CCF. Symptoms of case 1 were double vision, left chemosis and exophthalmos; those of case 2 were double vision, left retroobital pain, left forehead dysesthesia and blurred vision; and case 3 complained of double vision, left chemosis, left exophthalmos and pulsatile tinnitus. In all three cases, angiography disclosed left CCF fed by ipsilateral dural branches from the internal maxillary artery (IMA) and the internal carotid artery (ICA). In case 1, small branches from the ascending pharyngeal artery also fed the CS. In cases 2 and 3, feeders from the ECA were arising only from branches of the IMA. In case 3, hypertrophy of the meningohypophyseal trunk was visible. In cases 1 and 2, although the CS was opacified, feeders from the ICA were not clearly visible. Embolizations of branches of the IMA were performed in all cases using Ivalon under selective catheterization. In case 1, symptoms partially improved, but in cases 2 and 3, visual symptoms were transiently aggravated. Focal irradiation to the CS was done with total doses of 30, 30 and 40 Gy each for cases 1, 2, and 3 respectively. In case 1, clinical symptoms gradually improved about one third way through irradiation.(ABSTRACT TRUNCATED AT 250 WORDS)


Crystal structure and the Mott-Hubbard gap in YTiO(3) at high pressure.
The crystal structure of YTiO(3) at high pressures up to 30 GPa has been investigated by means of synchrotron x-ray powder diffraction (T = 295 K). The variation of the Ti-O bond lengths with pressure evidences a distinct change in the distortion of the TiO(6) octahedra at around 10 GPa, which is discussed in terms of a pressure-driven spatial reorientation of the occupied Ti 3d(t(2g)) orbitals. Mid-infrared synchrotron microspectroscopy has been used to determine quantitatively the pressure-induced reduction of the optical bandgap of YTiO(3), and the results are interpreted on the basis of the structural and possible orbital orientation changes.


The GWIPS-viz Browser.
GWIPS-viz is a publicly available browser that provides Genome Wide Information on Protein Synthesis through the visualization of ribosome profiling data. Ribosome profiling (Ribo-seq) is a high-throughput technique which isolates fragments of messenger RNA that are protected by the ribosome. The alignment of the ribosome-protected fragments or footprint sequences to the corresponding reference genome and their visualization using GWIPS-viz allows for unique insights into the genome loci that are expressed as potentially translated RNA. The GWIPS-viz browser hosts both Ribo-seq data and corresponding mRNA-seq data from publicly available studies across a number of genomes, avoiding the need for computational processing on the user side. Since its initial publication in 2014, over 1885 tracks have been produced across 24 genomes. This unit describes the navigation of the GWIPS-viz genome browser, the uploading of custom tracks, and the downloading of the Ribo-seq/mRNA-seq alignment data. © 2018 by John Wiley & Sons, Inc.


[Efforts of pharmacists in regimen management for safe cancer chemotherapy].
As a safe way to manage cancer chemotherapy, a regimen registration system of chemotherapies was started in our hospital in April of 2007. Only chemotherapies registered in the regimen system can be conducted. Beginning in July of 2007, to assure safer chemotherapy, a standard clinical value of laboratory data was established as the criteria to discontinue chemotherapies. The individual laboratory data have been checked according to the discontinuance criteria by pharmacists in our hospital. With the adoption of this regimen registration system for standardized procedures of various chemotherapies, laboratory data can be checked according to the criteria, and certain chemotherapies can now be discontinued. However, in certain cases some doctors proceeded chemotherapies although pharmacists suggested that laboratory data did not meet the criteria. It is important to keep checking the registered regimen and criteria. Pharmacists have to confirm the checking system based on the patient's condition and improve the regimen system of chemotherapy more clearly together with doctors and nurses.


Oxidative Stress as a Possible Target in the Treatment of Toxoplasmosis: Perspectives and Ambiguities.
Toxoplasma gondii is an apicomplexan parasite causing toxoplasmosis, a common disease, which is most typically asymptomatic. However, toxoplasmosis can be severe and even fatal in immunocompromised patients and fetuses. Available treatment options are limited, so there is a strong impetus to develop novel therapeutics. This review focuses on the role of oxidative stress in the pathophysiology and treatment of T. gondii infection. Chemical compounds that modify redox status can reduce the parasite viability and thus be potential anti-Toxoplasma drugs. On the other hand, oxidative stress caused by the activation of the inflammatory response may have some deleterious consequences in host cells. In this respect, the potential use of natural antioxidants is worth considering, including melatonin and some vitamins, as possible novel anti-Toxoplasma therapeutics. Results of in vitro and animal studies are promising. However, supplementation with some antioxidants was found to promote the increase in parasitemia, and the disease was then characterized by a milder course. Undoubtedly, research in this area may have a significant impact on the future prospects of toxoplasmosis therapy.