Stress and development of depression and heavy drinking in adulthood: moderating effects of childhood trauma.
Studies suggest that childhood trauma is linked to both depression and heavy drinking in adulthood, and may create a lifelong vulnerability to stress. Few studies have explored the effects of stress sensitization on the development of depression or heavy drinking among those who have experienced traumatic childhood events. This study aimed to determine the effect of childhood trauma on the odds of experiencing depression or heavy drinking in the face of an adult life stressor, using a large population-based Canadian cohort. A total of 3,930 participants were included from the National Population Health Survey. The associations among childhood trauma, recent stress and depression/heavy drinking from 1994/1995 to 2008/2009 were explored using logistic regression, as were interactions between childhood trauma and recent stress. A generalized linear mixed model was used to determine the effects of childhood trauma and stressful events on depression/heavy drinking. Analyses were stratified by sex. Childhood trauma significantly increased the odds of becoming depressed (following 1 event: OR = 1.66; 95%CI 1.01, 2.71; 2+ events, OR = 3.89; 95%CI 2.44, 6.22) and drinking heavily (2+ events: OR = 1.79; 95%CI 1.03, 3.13). Recent stressful events were associated with depression, but not heavy drinking. While most interaction terms were not significant, in 2004/2005 the association between recent stress and depression was stronger in those who reported childhood trauma compared to those with no childhood trauma. Childhood trauma increases risk for both depression and heavy drinking. Trauma may moderate the effect of stress on depression; the relationship among trauma, stress and heavy drinking is less clear.


Rhes deletion is neuroprotective in the 3-nitropropionic acid model of Huntington's disease.
Although the mutated protein causing Huntington's disease (HD) is expressed throughout the body, the major pathology of HD is localized to the striatum of the brain. We previously reported that the striatal-enriched protein Rhes binds the mutated huntingtin protein and enhances its cytotoxicity. We now demonstrate that Rhes-deleted mice are dramatically protected from neurotoxicity and motor dysfunction in a striatal-specific model of HD elicited by 3-nitropropionic acid. This finding suggests that Rhes may, in part, determine the striatal selectivity of HD.


Differentiating hemispheric contributions to syntax and semantics in patients with left-hemisphere lesions.
Understanding the relationship between brain and cognition critically depends on data from brain-damaged patients since these provide major constraints on identifying the essential components of brain-behavior systems. Here we relate structural and functional fMRI data with behavioral data in 21 human patients with chronic left hemisphere (LH) lesions and a range of language impairments to investigate the controversial issue of the role of the hemispheres in different language functions. We address this issue within a dual neurocognitive model of spoken language comprehension in which core linguistic functions, e.g., syntax, depend critically upon an intact left frontotemporal system, whereas more general communicative abilities, e.g., semantics, are supported by a bilateral frontotemporal system and may recover from LH damage through normal or enhanced activity in the intact right hemisphere. The fMRI study used a word-monitoring task that differentiated syntactic and semantic aspects of sentence comprehension. We distinguished overlapping interactions between structure, neural activity, and performance using joint independent components analysis, identifying two structural-functional networks, each with a distinct relationship with performance. Syntactic performance correlated with tissue integrity and activity in a left frontotemporal network. Semantic performance correlated with activity in right superior/middle temporal gyri regardless of tissue integrity. Right temporal activity did not differ between patients and controls, suggesting that the semantic network is degenerately organized, with regions in both hemispheres able to perform similar computations. Our findings support the dual neurocognitive model of spoken language comprehension and emphasize the importance of linguistic specificity in investigations of language recovery in patients.


Abscisic acid-induced secretory proteins in suspension-cultured cells of winter wheat.
In suspension-cultured cells of winter wheat (Triticum aestivum L. cv. Chihokukomugi), the accumulation of soluble secretory proteins in the culture medium was promoted by ABA treatment in comparison with non-treated cells. The total amount of secretory proteins in ABA-treated cells was 1.7-fold higher than that in non-treated cells. The analysis of two-dimensional electrophoresis revealed that at least twelve secretory proteins were induced by ABA, and these were named WAS (wheat ABA-induced secretory) proteins 1 to 12. N-terminal amino acid sequence analysis of WAS proteins revealed the sequences of WAS-2 and WAS-3. Homology searches showed that WAS-2 had 55% identity with the N-terminus of the wheat chemically induced gene (WCI-5 gene) product. WAS-3 was also shown to have 93% identity with the N-terminus of the barley protein R, a typical member of thaumatin-like proteins (TLPs). Immunoblot analysis also suggested that WAS-3 was related to protein R. These results suggest that exogenous ABA induces some basic secretory proteins that are related to the plant defense system in wheat.


Bacteriologic status of necrotic tissue in necrotizing pancreatitis.
To confirm the accuracy of guided percutaneous aspiration (GPA) in distinguishing sterile from infected pancreatic necrosis, we have performed Brown-Brenn tissue Gram stains on pancreatic and peripancreatic necrotic tissue removed operatively in 15 patients. In eight patients judged to have sterile necrosis on the basis of negative cultures of pancreatic exudate obtained first preoperatively (by GPA) and then intraoperatively, necrotic tissue debrided at surgery was also free of bacteria. In seven patients judged to have infected necrosis on the basis of positive cultures of pancreatic exudate obtained first preoperatively (by GPA) and then intraoperatively, necrotic tissue debrided at surgery harbored a considerable number of bacteria. We conclude that GPA targeted to areas of necrosis accurately distinguishes infected necrosis from sterile necrosis, and in infected necrosis, the solid necrotic tissue as well as the fluid component contains bacteria. We therefore believe that infected necrosis is not likely to be eradicated by catheter drainage and should be treated by surgical debridement.


Exact quantum dynamics of a bosonic Josephson junction.
The quantum dynamics of a one-dimensional bosonic Josephson junction is studied by solving the time-dependent many-boson Schrödinger equation numerically exactly. Already for weak interparticle interactions and on short time scales, the commonly employed mean-field and many-body methods are found to deviate substantially from the exact dynamics. The system exhibits rich many-body dynamics such as enhanced tunneling and a novel equilibration phenomenon of the junction depending on the interaction, which is attributed to a quick loss of coherence.


Inflammatory ulcers.
A large number of diseases can eventuate in cutaneous ulceration. This article will review inflammatory disorders which by their nature can directly produce cutaneous breakdown and ulcer formation. Major emphasis is given to those disorders where recent knowledge has improved our understanding of the condition or where new therapeutic agents or maneuvers have become available. This later group consists of vasculitis, disorders caused by small vessel thrombi or embolus and pyoderma gangrenosum.


A comparison of coulometric titration and potentiometric determination of chloride concentration in rumen fluid.
The concentration of chloride ions in rumen fluid is a useful measure of obstructive gastrointestinal disease in ruminants and camelids. However, rumen fluid is very different from other biological fluids in its bacterial populations, consistency, and concentrations of various anions. Two methods of determining the chloride concentration in biological fluids were compared using centrifuged and filtered rumen fluid containing different amounts of sodium chloride. Although coulometric titration and potentiometric electrode analysis yielded results that had a strong linear relationship, the results of potentiometry were consistently and significantly higher, by about 20 mEq/L. This difference was investigated further by analyzing a series of fluids containing different concentrations of sodium acetate. Acetate was detected as chloride (0.21 chloride molecules per acetate molecule) by potentiometry but not by coulometric titration. Therefore, the acetate concentration of rumen fluid was the most likely cause of the discrepancy between tests in the original trial. In conclusion, the coulometric procedure may be more accurate than the potentiometric procedure for measuring rumen chloride when the concentrations of possible confounding ions are unknown.


The harderian gland of the frog, Rana esculenta, during the annual cycle: histology, histochemistry and ultrastructure.
The Harderian gland in Rana esculenta has been studied during the annual cycle at the histological, histochemical and ultrastructural levels. The Harderian gland has an acinar structure and is the only orbital gland in anuran amphibia. It develops at the medial corner of the orbit from the conjunctival epithelium at the premetamorphic stage. In the adult the glandular secretion reaches a maximum during the months of July and August, drops in September and resumes slowly from October onwards. The secretion is seromucoid and the secretory granules are released into the acinar lumen, mainly by exocytosis. Porphyrins were not detected. No sexual dimorphism was observed in the glandular cells. The resumption of secretory activity in October and the enhancement of secretion in May are marked by the appearance of "blue nuclei" (Mallory stain) in a relatively high percentage of glandular cells. This unusual blue colour, using the Mallory stain (by which nuclei stain red), disappears after digestion of paraffin sections with RNAase, but not with DNAase and trypsin. The blue staining may, therefore, indicate an increased amount of nuclear RNA. The Harderian gland in the frog most probably serves to lubricate and moisten the eye in the absence of the lacrimal gland. However, the gland may also represent an immunoactive organ owing to the presence of numerous mast cells and plasma cells in the interacinar spaces.


Glucocorticoid Alleviates Mechanical Stress-Induced Airway Inflammation and Remodeling in COPD via Transient Receptor Potential Canonical 1 Channel.
Increased airway resistance and hyperinflation in chronic obstructive pulmonary disease (COPD) are associated with increased mechanical stress that modulate many essential pathophysiological functions including airway remodeling and inflammation. Our present study aimed to investigate the role of transient receptor potential canonical 1 (TRPC1), a mechanosensitive cation channel in airway remodeling and inflammation in COPD and the effect of glucocorticoid on this process. In patients, we investigated the effect of pathological high mechanical stress on the expression of airway remodeling-related cytokines transforming growth factor β1 (TGF-β1), matrix metalloproteinase-9 (MMP9) and the count of inflammatory cells in endotracheal aspirates (ETAs) by means of different levels of peak inspiratory pressure (PIP) under mechanical ventilation, and analyzed their correlation with TRPC1. Based on whether patients regularly used inhaled corticosteroid (ICS), COPD patients were further divided into ICS group (n = 12) and non-ICS group (n=15). The ICS effect on the expression of TRPC1 was detected by Western blot. In vitro, we imitated the mechanical stress using cyclic stretch and examined the levels of TGF-β1 and MMP-9. The role of TRPC1 was further explored by siRNA transfection and dexamethasone administration. Our results revealed that the TRPC1 level and the inflammatory cells counts were significantly higher in COPD group. After mechanical ventilation, the expression of TGF-β1 and MMP-9 in all COPD subgroups was significantly increased, while in the control group, only high PIP subgroup increased. Meanwhile, TRPC1 expression was positively correlated with the counts of inflammatory cells and the levels of TGF-β1 and MMP-9. In vitro, mechanical stretch significantly increased TGF-β1 and MMP-9 levels and such increase was greatly attenuated by TRPC1 siRNA transfection and dexamethasone administration. Our results suggest that the increased TRPC1 may play a role in the airway inflammation and airway remodeling in COPD under high airway pressure. Glucocorticoid could in some degree alleviate airway remodeling via inhibition of TRPC1.


Hymenobacter coalescens sp. nov., isolated from wetland freshwater.
A non-motile and rod-shaped bacterium, designated strain WW84T, was isolated from freshwater collected from the Woopo wetland (Republic of Korea). Cells were Gram-stain-negative, aerobic, catalase-positive and oxidase-negative. The major fatty acids were C16 : 0, C18 : 0, iso-C15 : 0 and iso-C17 : 1I and/or anteiso-C17 : 1B. The strain contained MK-7 as the major isoprenoid quinone, phosphatidylethanolamine as the major polar lipid and sym-homospermidine as the major polyamine. The DNA G+C content was 59 mol%. A phylogenetic tree based on 16S rRNA gene sequences showed that strain WW84T forms an evolutionary lineage within the radiation including the members of the genus Hymenobacter with Hymenobactero cellatus Myx 2105T (96.96 % sequence similarity) as its nearest neighbor. A number of phenotypic characteristics distinguished strain WW84T from the related members of the genus Hymenobacter. On the basis of the evidence presented in this study, a novel species, Hymenobacter coalescens sp. nov. is proposed with strain WW84T (=KCTC 32530T=JCM 19493T) as the type strain.


Immunological findings in 14 cases of Langerhans cells histiocytosis.
We have studied humoral and cell immunity in 14 children, from 2 months to 15 years old, diagnosed with Langerhans cells histiocytosis who had not received immunosuppressant nor immunopotentiating treatment. At the time of diagnosis, children were found in the following Greenberger clinical stages: stage II (5), stage III (6), stage IV (3). The children in stage II had moderate alterations in immunity, with an increase in IgG, IgM, IgA, increase in T4 lymphocytes and decrease in T8 lymphocytes; the clinical evolution was good. In stage III, normal immunoglobulins were noted in 2 children, an increase in IgG, IgM, IgA in 1; an increase in IgM in 1, a decrease in IgM in 1 and absence of IgA in 1. In all a decrease was found in T8 lymphocytes and the T4 lymphocytes were decreased in 3 and normal in 3; delayed immune response and response to mitogens was decreased in 3. These findings were related to a bad prognosis; 2 children died and another developed chronic disease. In stage IV serious alterations were detected in the immune system with a decrease in IgG, IgM, IgA, an increase in IgE, a decrease in T, B, T4 and T8 lymphocytes and very slight delayed immune response and response to mitogens; the children died.


[Hygienic evaluation of the meat of pigs given a feed concentrate prepared from overflow active sludge].
The authors studied the chemical composition of the meat of pigs given the diet containing a feed concentrate obtained from excess active sludge and the effects on the laboratory animals of such meat fed for a year. As compared to the accepted standards, the meat of pigs given the feed concentrate showed high cadmium content in the kidneys and high lead content in the liver and muscles. Starting from the 6th month of being kept on the meat of experimental pigs, the rats demonstrated an appreciable increase in the count of peripheral blood reticulocytes which remained almost unchanged to the end of experiments. The data obtained indicate that excess trace elements including heavy metals contained by active sludge from the purification works of the city of Kiev interfere with its use on a large scale as a feed additive.


Evaluating Optical Clock Performance for GNSS Positioning.
Atomic clocks are highly precise timing devices used in numerous Positioning, Navigation, and Timing (PNT) applications on the ground and in outer space. In recent years, however, more precise timing solutions based on optical technology have been introduced as current technology capabilities advance. State-of-the-art optical clocks-predicted to be the next level of their predecessor atomic clocks-have achieved ultimate uncertainty of 1 × 10-18 and beyond, which exceeds the best atomic clock's performance by two orders of magnitude. Hence, the successful development of optical clocks has drawn significant attention in academia and industry to exploit many more opportunities. This paper first provides an overview of the emerging optical clock technology, its current development, and characteristics, followed by a clock stability analysis of some of the successfully developed optical clocks against current Global Navigation Satellite System (GNSS) satellite clocks to discuss the optical clock potentiality in GNSS positioning. The overlapping Allan Deviation (ADEV) method is applied to estimate the satellite clock stability from International GNSS Service (IGS) clock products, whereas the optical clock details are sourced from the existing literature. The findings are (a) the optical clocks are more stable than that of atomic clocks onboard GNSS satellites, though they may require further technological maturity to meet spacecraft payload requirements, and (b) in GNSS positioning, optical clocks could potentially offer less than a 1 mm range error (clock-related) in 30 s and at least 10 times better timing performance after 900 s in contrast to the Galileo satellite atomic clocks-which is determined in this study as the most stable GNSS atomic clock type used in satellite positioning.


Fungal invasion of normally non-phagocytic host cells.
Many fungi that cause invasive disease invade host epithelial cells during mucosal and respiratory infection, and subsequently invade endothelial cells during hematogenous infection. Most fungi invade these normally non-phagocytic host cells by inducing their own uptake. Candida albicans hyphae interact with endothelial cells in vitro by binding to N-cadherin on the endothelial cell surface. This binding induces rearrangement of endothelial cell microfilaments, which results in the endocytosis of the organism. The capsule of Cryptococcus neoformans is composed of glucuronoxylomannan, which binds specifically to brain endothelial cells, and appears to mediate both adherence and induction of endocytosis. The mechanisms by which other fungal pathogens induce their own uptake are largely unknown. Some angioinvasive fungi, such as Aspergillus species and the Zygomycetes, invade endothelial cells from the abluminal surface during the initiation of invasive disease, and subsequently invade the luminal surface of endothelial cells during hematogenous dissemination. Invasion of normally non-phagocytic host cells has different consequences, depending on the type of invading fungus. Aspergillus fumigatus blocks apoptosis of pulmonary epithelial cells, whereas Paracoccidioides brasiliensis induces apoptosis of epithelial cells. This review summarizes the mechanisms by which diverse fungal pathogens invade normally non-phagocytic host cells and discusses gaps in our knowledge that provide opportunities for future research.


Dual role of response regulator StyR in styrene catabolism regulation.
In Pseudomonas fluorescens ST, the promoter of the styrene catabolic operon, PstyA, is induced by styrene and repressed by the addition of preferred carbon sources. PstyA is regulated by the StyS/StyR two-component system. The integration host factor (IHF) also plays a positive role in PstyA regulation. Three distinct StyR binding sites, which have different affinities for this response regulator, have been characterized on PstyA. The high-affinity StyR binding site (STY2) is necessary for promoter activity. The DNA region upstream of STY2 contains a lower-affinity StyR binding site, STY1, that partially overlaps the IHF binding site. Deletion of this region, designated URE (upstream regulatory element), has a dual effect on the PstyA promoter, decreasing the styrene-dependent activity and partially relieving the glucose repression. The lowest-affinity StyR binding site (STY3) is located downstream of the transcription start point. Deletion of the URE region and inactivation of the STY3 site completely abolished glucose-mediated repression of PstyA. In the proposed model StyR can act either as an activator or as a repressor, depending on which sites it occupies in the different growth conditions. We suggest that the cellular levels of phosphorylated StyR, as determined by StyS sensor kinase activity, and the interplay of this molecule with IHF modulate the activity of the promoter in different growth conditions.


Geographical distribution of low pathogenic avian influenza viruses of domestic poultry in Vietnam and their genetic relevance with Asian isolates.
From the avian influenza virus (AIV) outbreaks and market surveillances in Vietnam during November 2011 and March 2012, a total of 196 AIV were isolated. Although H5N1 highly pathogenic avian influenza (HPAI) was the most prevalent subtype in Vietnam, 57 low pathogenic avian influenza (LPAI) viruses were identified from mainly domestic ducks and some chickens. Of note, various subtypes of LPAI viruses were isolated from domestic ducks in Vietnam: H3 (n = 16), H4 (n = 4), H6 (n = 24), H7 (n = 1), and H9 (n = 10). Geographically, the LPAI viruses were identified in different regions of Vietnam. Phylogenetic analysis of HA and NA genes in LPAIV in Vietnam showed that some H3 (group I) and H4 subtypes AIV clustered with the viruses of several Asian isolates from domestic poultry and wild birds. However, the H6, H9, and some H3 (group II and III) subtypes AIV were closely related to isolates from domestic poultry in Southern China. In addition, whereas the N2 and N6 subtypes AIV belonged to the Eurasian lineage, the N8 subtype AIV was classified to be both of Eurasian and American lineage. These findings revealed that the regional trade and wild birds play a key role transmission of LPAIV in domestic ducks in Vietnam. Further surveillance at the intercountry level is needed to understand the epidemiology of these viruses and to cope with emergence of novel AIV types.


Short-term follow-up of masticatory adaptation after rehabilitation with an immediately loaded implant-supported prosthesis: a pilot assessment.
When teeth are extracted, sensory function is decreased by a loss of periodontal ligament receptions. When replacing teeth by oral implants, one hopes to restore the sensory feedback pathway as such to allow for physiological implant integration and optimized oral function with implant-supported prostheses. What remains to be investigated is how to adapt to different oral rehabilitations. The purpose of this pilot study was to assess four aspects of masticatory adaptation after rehabilitation with an immediately loaded implant-supported prosthesis and to observe how each aspect will recover respectively. Eight participants with complete dentures were enrolled. They received an implant-supported acrylic resin provisional bridge, 1 day after implant surgery. Masticatory adaptation was examined by assessing occlusal contact, approximate maximum bite force, masticatory efficiency of gum-like specimens, and food hardness perception. Occlusal contact and approximate maximum bite force were significantly increased 3 months after implant rehabilitation, with the bite force gradually building up to a 72% increase compared to baseline. Masticatory efficiency increased by 46% immediately after surgery, stabilizing at around 40% 3 months after implant rehabilitation. Hardness perception also improved, with a reduction of the error rate by 16% over time. This assessment demonstrated masticatory adaptation immediately after implant rehabilitation with improvements noted up to 3 months after surgery and rehabilitation. It was also observed that, despite gradually improved bite force in all patients, masticatory efficiency and food hardness perception did not necessarily follow this tendency. The findings in this pilot may also be used to assess adaptation of oral function after implant rehabilitation by studying the combined outcome of four tests (occlusal contact, maximum bite force, masticatory efficiency, and food hardness perception).


A low-cost cementite (Fe3C) nanocrystal@N-doped graphitic carbon electrocatalyst for efficient oxygen reduction.
In this work, chitosan whiskers (CWs) were first extracted using low-cost and earth-abundant crab shells as materials by a series of chemical processes, and then assembled into chitosan whisker microspheres (CWMs) via a simple photochemical polymerization approach. Subsequently, a cementite (Fe3C) nanocrystal@N-doped graphitic carbon (Fe3C@NGC) nanocomposite was successfully fabricated by high temperature pyrolysis of CWMs adsorbed with ferric acetylacetonate (Fe(acac)3) at 900 °C. It was found that a suitable growth atmosphere generated inside CWMs during high temperature pyrolysis is critically important to form Fe3C nanocrystal cores, concurrently accompanying a structural transformation from chitosan whiskers to mesoporous graphitic carbon shells with natural nitrogen (N) doping properties, resulting in the formation of a core-shell structure Fe3C@NGC nanocomposite. The resulting samples were evaluated as electrocatalysts for oxygen reduction reaction (ORR). In comparison with sole N-doped graphitic carbon without Fe3C nanocrystals obtained by direct pyrolysis of chitosan whisker microspheres at 900 °C (CWMs-900), Fe3C@NGC showed significantly improved ORR catalytic activity. The tolerance to fuel cell molecules (e.g., methanol) and the durability of Fe3C@NGC are obviously superior to commercial Pt/C catalysts in alkaline media. The high ORR performance of Fe3C@NGC could be due to its large surface area (313.7 m(2) g(-1)), a synergistic role of Fe3C nanocrystals, N doping in graphitic carbon creating more catalytic active sites, and a porous structure of the nanocomposite facilitating mass transfer to efficiently improve the utilization of these catalytic active sites.


Comparing Patient Satisfaction and Intubating Conditions Using Succinylcholine or Low-Dose Rocuronium for Rigid Bronchoscopy: A Randomized Study.
Despite its serious side effects, succinylcholine is commonly used for neuromuscular relaxation in short procedures, such as rigid bronchoscopy and tracheobronchial interventions. The application of low-dose rocuronium reversed by low-dose sugammadex might be a modern alternative. The aim of this study was to compare patient satisfaction, incidence of postoperative myalgia (POM) as well as intubating conditions of these two muscle relaxants for rigid bronchoscopy. A single-center, prospective-randomized, blinded study of 95 patients, scheduled for rigid bronchoscopy and tracheobronchial intervention was conducted. The patients were anesthetized with propofol, remifentanil and either low-dose succinylcholine (S) (0.5 mg/kg) or low-dose rocuronium (0.25 mg/kg) with sugammadex (RS) (0.5 mg/kg). All patients were evaluated on the first and second postinterventional day for their satisfaction with the treatment (rigid bronchoscopy) using a Numeric Analog Rating Scale (NAS 0-10) and the presence and severity of POM (NAS 1-4). Intubating conditions were assessed as excellent, good, or poor on the basis of position of vocal cords and reaction to insertion of the rigid bronchoscope. Patients in the S group were less satisfied with the treatment than patients in RS group (72.7 vs. 93.7%, p = 0.007). The incidence of POM on the first day after intervention was significantly higher in the S group then in the RS group (56.9% vs. 4.3%, p < 0.001). Although the intubation was faster (p < 0.001) and the intubating conditions significantly superior (p < 0.003) with succinylcholine, acceptable conditions were also achieved with low-dose rocuronium in 75% of patients. The anesthetic drug costs were significantly higher in the RS group then in the S group (p < 0.001). The results suggest that low-dose rocuronium provided better patient satisfaction and less POM. But with the use of low-dose succinylcholine, the intubating conditions are more comfortable, and it is less expensive than rocuronium/sugammadex.


Characterizing Cardiac Molecular Mechanisms of Mammalian Hibernation via Quantitative Proteogenomics.
This study uses advanced proteogenomic approaches in a nonmodel organism to elucidate cardioprotective mechanisms used during mammalian hibernation. Mammalian hibernation is characterized by drastic reductions in body temperature, heart rate, metabolism, and oxygen consumption. These changes pose significant challenges to the physiology of hibernators, especially for the heart, which maintains function throughout the extreme conditions, resembling ischemia and reperfusion. To identify novel cardioadaptive strategies, we merged large-scale RNA-seq data with large-scale iTRAQ-based proteomic data in heart tissue from 13-lined ground squirrels (Ictidomys tridecemlineatus) throughout the circannual cycle. Protein identification and data analysis were run through Galaxy-P, a new multiomic data analysis platform enabling effective integration of RNA-seq and MS/MS proteomic data. Galaxy-P uses flexible, modular workflows that combine customized sequence database searching and iTRAQ quantification to identify novel ground squirrel-specific protein sequences and provide insight into molecular mechanisms of hibernation. This study allowed for the quantification of 2007 identified cardiac proteins, including over 350 peptide sequences derived from previously uncharacterized protein products. Identification of these peptides allows for improved genomic annotation of this nonmodel organism, as well as identification of potential splice variants, mutations, and genome reorganizations that provides insights into novel cardioprotective mechanisms used during hibernation.


The roles of Toll-like receptors in atherosclerosis.
Atherosclerosis is a chronic inflammatory disease of the arteries that is characterised by the activation of endothelial cells, the recruitment of monocytes into the vessel wall and the differentiation of recruited macrophages into cholesterol-laden foam cells. Recent evidence from a variety of experimental approaches has indicated that Toll-like receptors (TLRs), which serve to initiate inflammatory signalling in response to the detection of molecules associated with microbial infection or tissue damage, play key roles in the development of atherosclerosis. This review summarises the recent evidence implicating TLR-dependent signalling in the activation of vascular cells during atherogenesis, and the mechanisms by which TLR-signalling may promote the dysregulation of macrophage cholesterol metabolism that is a prerequisite for the formation of foam cells and lesion progressionin vivo. Particular attention is paid to the recent studies aimed at identifying potential ligands of the TLRs that may be relevant to atherogenesis, and the diverse mechanisms by which vascular tissues may become exposed to ligands of the TLRs.


Low-molecular-weight protein tyrosine phosphatase and human disease: in search of biochemical mechanisms.
A major challenge in the post-genomic era is to identify the physiological functions of genes and elucidate the molecular basis for human disease. Genetic polymorphisms offer a convenient avenue for these efforts by providing evidence for the involvement of a given gene in human pathophysiology. Here we review the current evidence linking the low-molecular-weight protein tyrosine phosphatase (LMPTP) to several common diseases, including allergy, asthma, obesity, myocardial hypertrophy, and Alzheimer's disease. Based on the known effects of the genetic polymorphisms on the alternative mRNA splicing and enzyme levels of LMPTP, we discuss the possible molecular mechanisms of LMPTP involvement in these diseases.


Effect of treatment on serum brain-derived neurotrophic factor levels in depressed patients.
Researchers have reported that serum brain-derived neurotrophic factor (sBDNF) of drug-free depressed patients are lower than those of healthy controls and proposed that low sBDNF levels might reflect failure of neuronal plasticity in depression. In this study, we compared sBDNF levels of depressed patients (n = 28) before and after 8 weeks of antidepressant treatment, with those of healthy controls (n = 18) to test the hypothesis that initially low sBDNF levels of drug-free depressed patients will increase parallel with their clinical response to antidepressant treatment. The severity of depression and response to treatment were assessed with Hamilton Rating Scale for Depression (HAM-D). sBDNF was assayed with the sandwich ELISA method. Baseline sBDNF levels of patients (mean, 20.8 ng/ml; [S.D., 6.7]) were significantly lower than those of controls (mean, 26.8 ng/ml; [S.D., 9.3]; p = 0.015), and were negatively correlated with HAM-D scores (r = -0.49, p = 0.007). After 8 weeks of treatment, sBDNF levels of patients had increased significantly (mean, 33.3 ng/ml; [S.D., 9.9]; p < 0.001) and no longer differed from those of controls. These results support the hypothesis that BDNF might play a critical role in the pathophysiology of major depressive disorder and successful antidepressant treatment increases the attenuated BDNF levels in depressed patients.


[The effect of physical and chemical environmental factors on the growth of Pseudomonas aeruginosa dissociants].
The growth rates of the R-, S-, and M-dissociants of a hydrocarbon oxidizing strain of Pseudomonas aeruginosa were comparatively studied under variable environmental conditions (aeration, temperature, pH, UV radiation, and concentration of NaCl). The R-dissociant was found to be more tolerant to UV radiation, high aeration, and temperature. The S-dissociant, which is the most effective in degrading hydrocarbons, gains a selection advantage under acidic conditions. The M-dissociant has advantages over the other dissociants under conditions of decreased aeration, low temperature, and high concentration of NaCl. The results of this work are important for optimizing microbial growth conditions and for identification of bacteria. Probably, the biological sense of dissociation is to broaden the boundaries within which a species can survive under changeable environmental conditions.


Genetic and environmental factors affect bone density variances of families of men and women with osteoporosis.
Our aim was to assess the relative impacts of genetics and environment in the families of osteoporotic patients and identify the best subgroup of patients to investigate the genes associated with osteoporosis. We recruited 36 men and 47 women with osteoporosis (probands), median age of 52 and 68 yr, and all their siblings (90) and offspring (83). The families were classified as young or old on the basis of the median age of the probands. We measured the bone mineral density at the femoral neck (FN) and lumbar spine (LS) adjusted for age and weight and standardized (Z-score). Physical activity, nutritional calcium, and alcohol and tobacco consumption were investigated. We compared the mean Z-score using linear mixed model and assessed the familial resemblance using intraclass correlation. The mean Z-scores of the families of osteoporotic patients were significantly negative at FN and LS, with no intergeneration or intergender differences. At FN, but not at LS, the mean Z-score was independently lower in the families of male probands (mean +/- SD: -0.57 +/- 0.96, female: -0.18 +/- 0.85, P = 0.012) and in young families (-0.58 +/- 0.94, old families: -0.11 +/- 0.83, P = 0.006). This suggested that the lower Z-score in the families of men with osteoporosis was related to their younger age. There was significant phenotypic resemblance among members in the families. In the families of female probands, the correlation between the probands and her siblings was weak and disappeared after adjustment on environment, and a resemblance appeared within their children (FN: r = 0.61) suggesting that different environment had masked the resemblance in this subgroup. In the families of male probands, a strong resemblance persisted after adjusting for environment, (proband-offspring at FN: r = 0.46 and within offspring at FN: r = 0.66, at LS: r = 0.61). This showed that resemblance was independent of a common measurable environment in these families of men with osteoporosis. In conclusion, mainly young osteoporotic patients, most of whom were male in our study, are affected by the genetic component.


British Gynaecological Cancer Society (BGCS) vulval cancer guidelines: Recommendations for practice.
The purpose of this guideline is to collate evidence and propose evidence-based guidelines for the diagnosis and management of adult patients with vulva carcinoma treated in the UK. Malignant melanoma may present via similar routes and will be discussed. The reader is referred to the Ano-uro-genital Mucosal Melanoma Full Guideline [1] for more detailed recommendations. The management of vulval sarcoma is outside of the scope of this guideline. For further information, including details of guideline development and GRADE of recommendations, please see BGCS website for details (https://www.bgcs.org.uk/professionals/guidelines-for-recent-publications/).


Survey of Difficult Experiences of Nurses Caring for Patients Undergoing Radiation Therapy: An Analysis of Factors in Difficult Cases.
The purpose of this study was to analyze the difficult experiences of nurses who cared for patients undergoing radiation therapy and factors related to patient feelings toward the progress and difficulties of treatment and the kind of care needed. A descriptive survey using a questionnaire. Anonymous self-report data were collected from a sample of 228 nurses who had 2-5 years of nursing experience in a National University Hospital in Japan. Years of working experience; knowledge and training in radiation therapy and difficult experiences of nurses caring for patients undergoing radiation therapy. In hospital "A", about 80% of the nurses had cared for patients undergoing radiation therapy, and about 40% had experience with difficult cases. The characteristics of competent nurses in radiation nursing were the following: while not having knowledge and experience, they were seriously facing their patients. However, the treatment process could not be predicted, skills related to the whole-human involvement of patients were insufficient, and communication was similar. In addition, the characteristics of competent nurses in radiation nursing became apparent. Although these nurses lacked knowledge and experience, they interacted with patients in a serious manner. However, the treatment process could not be predicted, and the skills related to the holistic involvement of patients were insufficient. Furthermore, communication between the nurses and patients was difficult. Competent nurses with 2-5 years of working experience, but lacking specific knowledge and experience regarding radiation therapy could cope with difficult radiation therapy cases. However, additional education, training, and mentoring from expert nurses would improve the quality of care for patients undergoing radiation therapy and reduce distress for nurses with less experience. In this study, the need for educational measures and a support system to help competent nurses face difficult cases were suggested.


Disfluency-Affirming Therapy for Young People Who Stutter: Unpacking Ableism in the Therapy Room.
Ableist messages are conveyed early in the life of a stutterer and are amplified throughout the school-age years. Increased recognition of the benefits of acceptance-based therapies for positive long-term outcomes has changed the narrative about stuttering and stutterers. Speech-language therapists are resonating with the ideas that "it is okay to stutter," socioemotional aspects of stuttering must be considered, and support and community are valuable. Despite the shift in understanding, messages conveyed to students and parents commonly encourage suppression of stuttering and masking of one's stuttering identity. The purpose of this article was to (a) expose unintentional ableist messages that perpetuate stigma and feeling "othered" in the therapy relationship and (b) offer suggestions for congruent messaging in stuttering therapy. Ableism in stuttering therapy contributes to the physical struggle and socioemotional challenges experienced by stutterers. The author offers ideas for revisioning therapy outcomes, language, and messaging to students to encourage a congruent, disfluency-affirming culture in schools and community. Introspection and advocacy by both therapists and the broader professional community, in collaboration with young people who stutter, will serve to reduce the stigma that fuels many of the daily challenges faced by school-age children who stutter.


Bioneutralization capacity of the antibodies generated in women by the beta subunit of human chorionic gonadotropin (beta hCG) and beta hCG associated with the alpha subunit of ovine luteinizing hormone linked to carriers.
Data is presented on the bioneutralization capacity per unit immunoactivity of 30 serum samples of women immunized with the beta-subunit of human chorionic gonadotropin (beta-hCG) or beta hCG associated noncovalently with the alpha-subunit of ovine luteinizing hormone (alpha-oLH), to form a heterospecies dimer (HSD), which were linked to carriers. The bioassays utilized were inhibition of radioiodinated hCG binding to rat testicular receptors in vitro and the inhibition of hCG induced testosterone production in mice. In both assays, antisera of women immunized with the HSD had a bioactivity to immunoactivity ratio that was about 25% higher, on an average, than antisera of women immunized with beta-hCG, suggesting a better bioneutralization capacity of sera raised by the HSD in women.


Differences in natural and recombinant interferon for herpes keratitis in two animal models.
Natural human leukocyte interferon (natural HuIFN-alpha) and recombinant leukocyte A interferon (recombinant A HuIFN-alpha) were tested for prophylactic and/or therapeutic effects in reducing the severity of keratitis in rabbit and monkey eyes infected with McKrae strain herpesvirus. The results showed that the two interferons acted differently in the rabbit eye; combined prophylactic and therapeutic administration of natural interferon mitigated the disease, while recombinant interferon had no effect. In monkeys, the two interferons acted similarly. Combined prophylactic and therapeutic administration reduced disease findings, while therapeutic administration alone had no effect. Thus, studies in rabbits are not accurate predictors of primate study results; whether or not nonhuman primate results can be extrapolated to humans remains to be seen.


Effects of skim milk, whole milk and light cream on serum tryptophan binding and brain tryptophan concentrations in rats.
One hour after rats fasted for 13 hours consume a single meal of skim milk, whole milk, or light cream, serum nonesterified fatty acid (NEFA) concentrations changed in direct proportion to the fat content of the diet: serum NEFA levels decreased in rats ingesting skim milk (0.09% fat) to 34% of fasting control values; in animals consuming whole milk (3.59% fat), levels dropped to 50% of fasting levels; these levels did not change significantly, however, in rats consuming light cream (18.26% fat). The percentages of total serum tryptophan not associated with albumin in rats ingesting skim milk, whole milk, or light cream were 22.2, 26.0, and 42.5%, respectively. These variations in serum free tryptophan were not accompanied by significant differences in brain tryptophan among the three treatment groups. These results thus confirm that, with a natural food source, (a) postprandial serum NEFA levels reflect the total fat content of the diet; (b) serum free tryptophan concentration shift proportionately with serum NEFA; and (c) serum free tryptophan concentrations do not reliably predict brain tryptophan levels.


Life events in the pathogenesis of hyperprolactinemia.
Little is known about the relationship between recent life events and onset of hyperprolactinemia, despite the well-known effect of acute psychological stress on prolactin levels in healthy subjects. Recent life events in patients with hyperprolactinemia compared with healthy controls were investigated. Case-control study. Fifty-two consecutive patients with hyperprolactinemia (45 females/7 males; mean age 34.9+/-10.1 years, range 18-60 years) and 52 healthy subjects matched for socio-demographic variables were studied. Nineteen patients (18 females/1 male) had no pituitary tumor and were diagnosed as suffering from idiopathic hyperprolactinemia. Patients with additional pathology or with high prolactin due to medications were excluded. All patients were interviewed by Paykel Interview for Recent Life Events while on remission after surgery or pharmacological treatment. The time period considered was the year preceding the first signs of hyperprolactinemia, and the year before interview for controls. Patients with hyperprolactinemia reported significantly more life events than control subjects (P<0.001). The same significant difference compared with controls applied to patients with (n=16) and without (n=36) depression. All categories of events (except events that were likely to be under the subject's control) were significantly more frequent. There were no significant differences between patients with prolactinoma (n=33) and those with idiopathic hyperprolactinemia (n=19). Within the complexity of phenomena implicated in the pathogenesis of hyperprolactinemia, our findings emphasize a potential role of emotional stress in either prolactin-secreting pituitary tumors or idiopathic hyperprolactinemia. Appraisal of life stress may have implications in clinical assessment (e.g. functional hyperprolactinemia) and decisions (e.g. termination of long-term pharmacological treatment).


[Successful treatment with prednisolone for air-leak syndrome following interstitial pneumonia after allogeneic hematopoietic stem cell transplantation].
A 13-year-old boy with T lymphoblastic leukemia underwent allogeneic bone marrow transplantation from an HLA-matched sibling in the second remission phase. After the dose of cyclosporine (CyA) was reduced, dyspnea appeared on Day 117. CT revealed diffuse interstitial shadows on the bilateral lungs. The results of broncho-alveolar lavage suggested Pneumocystis jirovecii pneumonia. The dose of trimethoprim-sulfamethoxazole was increased, and steroid therapy was started. The symptoms transiently subsided, but exacerbated with a reduction in the steroid dose. On Day 139, mediastinal and subcutaneous emphysema appeared. We considered that non-infectious interstitial pneumonia was primarily involved in the pathogenesis for the following reasons: the boy was negative for β-D-glucan early after onset, and there was a correlation between the steroid-dose reduction and condition. The steroid dose was again increased to 80 mg and the symptoms promptly subsided. When late-onset non-infectious pulmonary complications after hematopoietic stem cell transplantation lead to air-leak syndrome, the mortality rate is very high. However, survival may be achieved by intensifying immunosuppressive therapy in the early stage.


Grape seed and tea extracts and catechin 3-gallates are potent inhibitors of α-amylase and α-glucosidase activity.
This study evaluated the inhibitory effects of plant-based extracts (grape seed, green tea, and white tea) and their constituent flavan-3-ol monomers (catechins) on α-amylase and α-glucosidase activity, two key glucosidases required for starch digestion in humans. To evaluate the relative potency of extracts and catechins, their concentrations required for 50 and 90% inhibition of enzyme activity were determined and compared to the widely used pharmacological glucosidase inhibitor, acarbose. Maximum enzyme inhibition was used to assess relative inhibitory efficacy. Results showed that grape seed extract strongly inhibited both α-amylase and α-glucosidase activity, with equal and much higher potency, respectively, than acarbose. Whereas tea extracts and catechin 3-gallates were less effective inhibitors of α-amylase, they were potent inhibitors of α-glucosidase. Nongallated catechins were ineffective. The data show that plant extracts containing catechin 3-gallates, in particular epigallocatechin gallate, are potent inhibitors of α-glucosidase activity and suggest that procyanidins in grape seed extract strongly inhibit α-amylase activity.


The Effect of Conjugated Linoleic Acid Supplementation on Body Composition, Serum Insulin and Leptin in Obese Adults.
Studies have reported contradictory findings regarding the effect of a mixture of 2 conjugated linoleic acid (CLA) isomers on body weight and some serum indices. This study aims to investigate the effect of daily supplementation of these 2 isomers on body composition and serum leptin and insulin levels in obese adults. This randomized, double-blind clinical trial was performed on 54 adults with class I obesity. The subjects were randomly assigned into 2 groups of 27 and were followed for 3 months so that a total of 3000 mg of CLA supplement and placebo were administered in 3 daily doses in the intervention and control groups, respectively. Body composition indices as well as fasting serum levels of insulin and leptin were also measured. The paired t-test was used for evaluating within-group effects from baseline. The independent t-test was used to compare between-group differences for variables with normal distribution. Although body weight and body mass index (BMI) were not significantly decreased during intervention in groups, but the body fat mass (BFM) (P=0.034), body fat percentage (P=0.022) and trunk fat (P=0.027) decreased significantly during intervention with CLA. The fasting plasma sugar (P=0.042) and Homeostatic model assessment for insulin resistance (HOMA/IR) (P=0.044) in the intervention group declined during 12 weeks of intervention. Serum leptin was associated with a significant decrease during the intervention period (P=0.039). CLA supplementation could reduce body fat and serum leptin. Hence, it could be taken into account as a factor for weight loss but not to control or prevent diabetes.


Experimental infection of Gnathostoma spinigerum larvae in prawns and tadpoles.
Naturally captured Lanchester's freshwater prawns (Macrobrachium lanchesteri) and farm-bred Rana regulosa tadpoles were assessed for their capability of being the first or second intermediate hosts of Gnathostoma spinigerum. Seventy specimens from each animal group were randomized into a control group and investigated for larvae of G. spinigerum by pressing them between two pieces of glass and examination under stereomicroscope. No Gnathostoma larvae were found in the entire control group. Another 120 specimens of each animal were used in two treatment groups; 60 being exposed to the first-stage larvae, G. spinigerum, and 60 exposed to cyclops containing the third-stage larvae for 7 days. No larvae of G. spinigerum were found in the prawns of both treatment groups that resembled tadpoles exposed to the first-stage larvae. In contrast, 18.3% of tadpoles, which were exposed to cyclops containing third-stage larvae, were infected. Lanchester's freshwater prawns cannot serve as intermediate host of G. spinigerum, while R. regulosa can serve as the second intermediate host.


Renin-angiotensin system modulators in COVID-19 patients with hypertension: friend or foe?
Background: ACE2, a component of the non-classic renin-angiotensin system (RAS), acts as a functional receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV 2) spike protein, which enables the entry of the virus into the host cells. Non-classical ACE2 is one of two types of ACE2 that has a protective effect on vascular and respiratory cells. RAS modulators like angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) are among the first-line treatment for hypertensive patients. An upregulation in ACE2 levels with RAS modulators was observed in few preclinical studies, which raised concerns regarding possible increased infectivity among patients treated with RAS modulators.Method: For shortlisting the outcome effects, open-ended, English-restricted databases, published literature, and various clinical studies performed utilizing RAS modulators in COVID 19 patients were considered. Conclusion: Current evidence reveals no increased risk of COVID-19 infection among hypertensive patients on ACEIs/ARBs compared to other antihypertensive medications. Several studies have demonstrated no detrimental effects of RAS modulators on clinical severity, hospital/intensive care unit stay, ventilation and mortality. Hence, we can conclude that neither ARBs nor ACEIs treatment will cause any side effects or undesirable interactions in COVID-19 infected hypertensive patients.


Negative fetal fibronectin: who is still treating for threatened preterm labor and does it help?
Fetal fibronectin (fFN) has a high negative predictive value for delivery in the next seven days in patients at risk for preterm birth. Providers sometimes disregard a negative result and manage the patient for threatened preterm labor. Our objective was to identify the rate at which patients with a negative fFN were managed for threatened preterm labor and if delivery outcomes were improved with such management. Retrospective chart review of 111 patients at a single institution evaluated in the obstetrical triage unit for symptoms of threatened preterm labor with negative fFN results over a 19-month period between November 2004 and June 2006. Charts were reviewed for baseline patient characteristics such as gestational age at presentation to triage and fFN testing, prior obstetrical history, cervical examination and contraction frequency. Gestational age at delivery was documented. Rates of admission to the hospital and treatments for threatened preterm labor in this cohort were reviewed. Thirty-seven of patients (33%) with a negative fFN result were managed for threatened preterm labor (admitted to the hospital, given tocolytics, steroids, or intravenous antibiotics) by their provider. Patients undergoing these interventions were more likely to have cervical dilatation, effacement and were contracting more frequently. Only one of the patients delivered within 7 or 14 days of fFN testing. There was no advantage seen to management of threatened preterm labor in the setting of a negative fFN in terms of pregnancy prolongation, even when analyzing the patients with meaningful clinical findings (dilated 2 cm, effaced >or=80%, or contracting >or=12 times/h). Patients with meaningful clinical findings suspicious for preterm labor are more likely to undergo interventions by their physicians in the face of a negative fFN. This management does not improve length of gestation.


SGLT-2 Inhibitors: The Next-generation Treatment for Type 2 Diabetes Mellitus.
Type 2 diabetes mellitus (T2DM) has become a worldwide concern in recent years, primarily in highly developed Western societies. T2DM causes systemic complications, such as atherosclerotic heart disease, ischemic stroke, peripheral artery disease, kidney failure, and diabetes-related maculopathy and retinopathy. The growing number of T2DM patients and the treatment of long-term T2DM-related complications pressurize and exhaust public healthcare systems. As a result, strategies for combating T2DM and developing novel drugs are critical global public health requirements. Aside from preventive measures, which are still the most effective way to prevent T2DM, novel and highly effective therapies are emerging. In the spotlight of next-generation T2DM treatment, sodium-glucose co-transporter 2 (SGLT-2) inhibitors are promoted as the most efficient perspective therapy. SGLT-2 inhibitors (SGLT2i) include phlorizin derivatives, such as canagliflozin, dapagliflozin, empagliflozin, and ertugliflozin. SGLT-2, along with SGLT-1, is a member of the SGLT family of proteins that play a role in glucose absorption via active transport mediated by Na+ /K+ ATPase. SGLT-2 is only found in the kidney, specifically the proximal tubule, and is responsible for more than 90% glucose absorption. Inhibition of SGLT-2 reduces glucose absorption, and consequently increases urinary glucose excretion, decreasing blood glucose levels. Thus, the inhibition of SGLT-2 activity ultimately alleviates T2DM-related symptoms and prevents or delays systemic T2DM-associated chronic complications. This review aimed to provide a more detailed understanding of the effects of SGLT2i responsible for the acute improvement in blood glucose regulation, a prerequisite for T2DM-associated cardiovascular complications control.


Vaginal epithelial cell anti-Candida albicans activity is associated with protection against symptomatic vaginal candidiasis.
Vaginal epithelial cell (VEC) anti-Candida albicans activity, despite being measured in vitro, is considered an innate host defense mechanism. This was supported further by the fact that women protected from symptomatic infection following a live intravaginal Candida challenge had increased VEC anti-Candida activity compared to those who acquired a symptomatic infection.


Expression of nm23-H1 in uveal melanoma.
Uveal melanoma (UM) is the most common malignant intraocular tumor in adults. Despite the high accuracy of clinical diagnosis and advances in local treatment, more than 50% of UM patients develop metastasis within 10 years of initial diagnosis. NM23 is one of the human metastasis suppressor genes. Reduced nm23-H1 expression is correlated with high metastatic potential in many different cancers. The purpose of this study is to investigate the expression of nm23-H1 in UM and its potential value as a prognostic marker. Immunostaining of nm23-H1 was verified in five human UM cell lines with different metastatic potentials. The expression level of nm23-H1 mRNA was evaluated with one-step quantitative real-time PCR. The invasion ability of the cell lines was assessed before and after silencing nm23-H1 with small interference RNA. Thirty-two cases of paraffin-embedded specimens of human UM were immunostained with nm23-H1 monoclonal antibody. The immunostaining was evaluated in a semiquantitative fashion based on extent and intensity. The real-time PCR results of five human UM cell lines showed that expression of nm23-H1 was higher in cell lines with low metastatic potential compared with those with high metastatic potential (P<0.05). The invasive ability of the UM cell lines increased after silencing nm23-H1 expression with small interference RNA (P<0.05). The immunostaining of nm23-H1 was cytoplasmic in all cell lines and UM patients samples. The increased immunostaining intensity of nm23-H1 in patients' samples was associated with better survival rate (Kaplan-Meier test P=0.0097). The expression of nm23-H1 was not correlated with other prognostic factors. It can be concluded that nm23-H1 may be a prognostic marker to predict the survival rate of UM patients and it has the potential to identify high-risk patients.


Fine-needle aspiration biopsy of axillary lymph nodes: A reliable diagnostic tool for breast cancer staging.
Pathologic evaluation of sentinel lymph node biopsy (SLNB) samples is crucial for axillary staging in patients newly diagnosed with breast cancer. Patients with pathologic evidence of nodal metastasis scheduled for upfront surgery typically also undergo axillary lymph node dissection (ALND). Although SLNB is the gold standard method for detecting nodal metastasis, axillary lymph node fine-needle aspiration biopsy (FNAB) utility has not been thoroughly explored. Ultrasound-guided axillary lymph node FNAB samples along with concurrent ipsilateral breast tissue samples were searched and reviewed. The control group included histologic findings of axillary dissection or intraoperative SLNB results. A total of 354 axillary lymph node FNAB samples with matched histology were included. Of these, 187 (52.8%) were positive for metastatic carcinoma of breast origin; 143 (40.4%) were negative for metastasis; 12 (3.4%) showed atypical cells; six (1.7%) were suspicious for metastasis; and six (1.7%) were nondiagnostic because of a lack of lymphoid tissue and malignant cells. Of the 143 negative FNAB samples, 22 (15.4%) were positive on either intraoperative SLNB or ALND. When only the positive and negative FNAB samples were accounted for (n = 330; 93.2%), overall diagnostic sensitivity and specificity were 89.4% and 99.2%, respectively. Although axillary SLNB is the standard procedure for detecting nodal metastasis of breast origin, axillary lymph node FNAB appears to be a suitable alternative in a significant proportion of patients. A standard SLNB should be performed in cases of negative axillary lymph node FNAB findings, particularly nodes with abnormal imaging findings.


Potentiation of the action of warfarin by bezafibrate in patients with the nephrotic syndrome.
Nephrotic syndrome is associated with thromboembolic disease due to a variety of factors. In addition, therapy with anticoagulants is often met with poor response, to warfarin for example, which occurs due to factors such as reduced serum albumin and binding sites, increased free warfarin with rapid metabolism and clearance, and possible urinary loss. Bezafibrate is known to augment the action of warfarin and improve coagulation profile. In this article, we present three cases with severe nephrotic syndrome associated with hyperfibrinogenemia, hypercholesterolemia and thromboembolic disease who showed poor response to therapy with warfarin. They showed improvement of their coagulation profile upon concomitant administration of bezafibrate.


Parameterization and validation of an accurate force-field for the simulation of alkylamine functionalized silicon (111) surfaces.
The stretching, bending, and torsional force-field parameters for modelling Si (111) surfaces functionalized with alkylamines have been derived from energies, optimized geometries and harmonic frequencies obtained by accurate quantum mechanical calculations. Addition of inter-chain non-bonded parameters from a literature force field leads to computed energies in good agreement with their quantum mechanical counterparts for a large set of geometrical arrangements. The overall force-field was tested through molecular dynamics simulations performed on several models of Si functionalized surfaces, with different coverage percentages. Preliminary results indicate that the presence of a polar terminal amine group yields a surface coating of around 50%.


A statistical approach to the recognition of inferior wall myocardial infarction by the Q/R ratios.
To sharpen ECG criteria for diagnosis of inferior wall myocardial infarction (IWMI), the distribution of Q duration and Q/R ratios in leads 3 and aVF in four groups have been analyzed. Two of these groups are teaching samples (200 ECGs of patients with various diagnoses, but in whom no myocardial infarction was found on post-mortem, and 123 ECGs of patients in whom IWMI was found on post-mortem examinations) and two control samples (408 ECGs of healthy men and 60 ECGs of patients with clinically proved IWMI). The chosen combination of conditions Q/R3 greater than 25 percent and Q/RaVF greater than 10 per cent gives minimal number of errors for the teaching samples. The diagnostic rule gave 5-7 percent errors over the control samples. It is shown that use of Q duration greater than 0.04'' gives less satisfactory results in the diagnosis of IWMI.


Survey of health literacy level and related influencing factors in military college students in Chongqing, China: A cross-sectional analysis.
Health literacy (HL) has become an important public health issue and is receiving growing attention. However, the HL levels of military college students in China have never been analyzed. This study aimed to investigate the HL and related associate factors in military college students in Chongqing, China. Data was obtained with the "Chinese Citizen Health Literacy Questionnaire (2012 edition)" from 3183 military college students aged 16-28 years at Chongqing in December 2015. A total score of ≥80 points determined adequate HL, and HL level was defined as the proportion of students who had adequate HL out of the total number of participants. Multiple logistic regression analysis with a stepwise forward likelihood ratio (LR) method was used to determine the effects of sociodemographic characteristics, health-related behaviors, and family-related factors on HL level. The mean score of HL was 68.56, and the HL level of military college students was 21.05%; the overall knowledge rate was 71.33%. The independent factors that were associated with HL level were years in college, educational system, time playing online games, annual household income and father's education level. Senior (odds ratio [OR] = 1.229, 95% confidence interval [CI] 1.018∼1.484), undergraduate (OR = 1.509, 95% CI 1.151∼1.978), time played games more than 5 hours each week (OR = 0.638, 95% CI 0.486∼0.837), annual household incomes more than 50,000 yuan (OR = 1.231, 95% CI 1.027∼1.476) and father's education level (high school: OR = 2.327, 95% CI 1.186∼4.565; university: OR = 2.450, 95% CI 1.244∼4.825), were independently associated with higher HL level. HL levels of military college students in Chongqing need to be improved across the board. Our data suggests that special emphasis should be placed on students in junior and those in the specialist educational system. School departments may also benefit from incorporating health literacy into their curricula and helping students manage the time they spend playing online games.


Reasons given by female virgins for not having premarital intercourse.
By analyzing reasons given by virgin women for not engaging in premarital coitus, we can attain greater insight into the decision-making process involved in maintaining virginity as well as in the transition to nonvirginity. Among virgin women, there is a subgroup who are likely to have premarital coitus if they should meet the right person. On the other hand, women who give moral reasons for not engaging in coitus are the least likely to engage in premarital coitus even if they should become involved in a love relationship. Our results suggest that counsellors and educators should be aware of the diversity of reasons for not engaging in premarital intercourse as well as factors influencing these reasons in order to gain a more complete understanding of premarital sexual decision-making.


Trauma exposure and cigarette smoking: the impact of negative affect and affect-regulatory smoking motives.
Cognitive-affective mechanisms related to the maintenance of smoking among trauma-exposed individuals are largely unknown. Cross-sectional data from trauma-exposed treatment-seeking smokers (n = 283) were utilized to test a series of multiple mediator models of trauma exposure and smoking, as mediated by the sequential effects of negative affect and affect-modulation smoking motives. The sequential effects of both mediators indirectly predicted the effect of greater trauma exposure types on nicotine dependence, a biochemical index of smoking, perceived barriers to smoking cessation, and greater withdrawal-related problems during past quit attempts. Negative affect and affect-modulation motives for smoking may contribute to the trauma-smoking association.


Living cell functions and morphology revealed by two-photon microscopy in intact neural and secretory organs.
Laser light microscopy enables observation of various simultaneously occurring events in living cells. This capability is important for monitoring the spatiotemporal patterns of the molecular interactions underlying such events. Two-photon excited fluorescence microscopy (two-photon microscopy), a technology based on multiphoton excitation, is one of the most promising candidates for such imaging. The advantages of two-photon microscopy have spurred wider adoption of the method, especially in neurological studies. Multicolor excitation capability, one advantage of two-photon microscopy, has enabled the quantification of spatiotemporal patterns of [Ca(2+)](i) and single episodes of fusion pore openings during exocytosis. In pancreatic acinar cells, we have successfully demonstrated the existence of "sequential compound exocytosis" for the first time, a process which has subsequently been identified in a wide variety of secretory cells including exocrine, endocrine and blood cells. Our newly developed method, the two-photon extracellular polar-tracer imaging-based quantification (TEPIQ) method, can be used for determining fusion pores and the diameters of vesicles smaller than the diffraction-limited resolution. Furthermore, two-photon microscopy has the demonstrated capability of obtaining cross-sectional images from deep layers within nearly intact tissue samples over long observation times with excellent spatial resolution. Recently, we have successfully observed a neuron located deeper than 0.9 mm from the brain cortex surface in an anesthetized mouse. This microscopy also enables the monitoring of long-term changes in neural or glial cells in a living mouse. This minireview describes both the current and anticipated capabilities of two-photon microscopy, based on a discussion of previous publications and recently obtained data.


Tilt testing potentiated with sublingual nitroglycerin in children with unexplained syncope.
The aim of this prospective study was to assess the diagnostic value of a sublingual nitroglycerin (NTG) potentiated head-up tilt (HUT) testing protocol in children with unexplained syncope. One hundred and sixty-four consecutive paediatric patients with syncope of unknown origin and no evidence of organic heart disease (115 female, mean age 13 +/- 3 years) and 29 control children underwent a sublingual NTG-potentiated tilt testing protocol. Paediatric patients and controls were tilted at 60 degrees for 20 min and, if no symptom occurred, for other 15 min after sublingual 400 mug spray NTG administration. During the drug-free phase of the test, 13 patients (8%) and no controls had a positive response. After drug administration, a positive response occurred in another 88 patients (55%) and in four controls (14%), whereas an exaggerated response was observed in nine patients (5%) and in four controls (14%). Thus, the positive rate and specificity of sublingual NTG HUT test in children were 63 and 86%, respectively. No relevant adverse events were observed during the test. Tilt testing potentiated with sublingual NTG has proved to be effective and safe in unmasking the neurally mediated origin of unexplained syncope in children. The NTG challenge greatly increased the positive rate of passive tilt, with a small decrease in specificity.


Selection of the initial design for the two-stage continual reassessment method.
In the two-stage continual reassessment method (CRM), model-based dose escalation is preceded by a pre-specified escalating sequence starting from the lowest dose level. This is appealing to clinicians because it allows a sufficient number of patients to be assigned to each of the lower dose levels before escalating to higher dose levels. While a theoretical framework to build the two-stage CRM has been proposed, the selection of the initial dose-escalating sequence, generally referred to as the initial design, remains arbitrary, either by specifying cohorts of three patients or by trial and error through extensive simulations. Motivated by a currently ongoing oncology dose-finding study for which clinicians explicitly stated their desire to assign at least one patient to each of the lower dose levels, we proposed a systematic approach for selecting the initial design for the two-stage CRM. The initial design obtained using the proposed algorithm yields better operating characteristics compared to using a cohort of three initial design with a calibrated CRM. The proposed algorithm simplifies the selection of initial design for the two-stage CRM. Moreover, initial designs to be used as reference for planning a two-stage CRM are provided.


[Influence of drugs administered in general anesthesia and in pre- and post-operative periods on transiently evoked otoacoustic emissions (TEOAE) in children operated for congenital heart defects (part II)].
Outer hair cells are believed to be responsible for generation of otoacoustic emissions (OAEs). High sensitivity of OAE makes it possible to diagnose subclinical cochlear pathologies even if they have not yet been revealed by tonal audiometry. The aim of this study was to evaluate an influence of general anesthesia and other drugs administered in pre- and post-operative period on TEOAE in subjects operated on for various congenital heart defects in extracorporeal circulation. The investigated group consisted of 44 children with no pathology confirmed during ENT examination, in age ranging from 6 months to 19 years (average 9.3 years; +/- 5.9 years). The control group consisted of 14 otologically and cardiologically healthy subjects aged from 2-16 years (average 10.3 +/- 3.4 years). In the investigated group, TEOAEs were measured twice: one day before and 7-8 days following surgery. In the control group, TEOAEs were recorded in the same manner. Statistical analysis revealed no significant differences in the control group, between second and first TEOAE tests. Analysis of the influence of the drugs administered in general anesthesia did not show significant influence on post-operative TEOAEs. Among ototoxic drugs only acetylsalicylic acid affected TEOAE in post-operative tests. The authors conclude that general anaesthesia does not change the cochlear function, although, in children in whom acetylsalicylic acid was administered in post-operative period the cochlear function was affected. In these subjects the function of the cochlea should be monitored in post-surgical period.


High plasma levels of soluble endothelial protein C receptor are associated with increased mortality among children with cerebral malaria in Benin.
Loss of endothelial protein C receptor (EPCR) occurs at the sites of Plasmodium falciparum-infected erythrocyte sequestration in patients with or who died from cerebral malaria. In children presenting with different clinical syndromes of malaria, we assessed the relationships between endogenous plasma soluble EPCR (sEPCR) levels and clinical presentation or mortality. After adjustment for age, for treatment before admission, and for a known genetic factor, sEPCR level at admission was positively associated with cerebral malaria (P = .011) and with malaria-related mortality (P = .0003). Measuring sEPCR levels at admission could provide an early biological marker of the outcome of cerebral malaria.


Characterization of Tensile Mechanical Behavior of MSCs/PLCL Hybrid Layered Sheet.
A layered construct was developed by combining a porous polymer sheet and a cell sheet as a tissue engineered vascular patch. The primary objective of this study is to investigate the influence of mesenchymal stem cells (MSCs) sheet on the tensile mechanical properties of porous poly-(l-lactide-co-ε-caprolactone) (PLCL) sheet. The porous PLCL sheet was fabricated by the solid-liquid phase separation method and the following freeze-drying method. The MSCs sheet, prepared by the temperature-responsive dish, was then layered on the top of the PLCL sheet and cultured for 2 weeks. During the in vitro study, cellular properties such as cell infiltration, spreading and proliferation were evaluated. Tensile test of the layered construct was performed periodically to characterize the tensile mechanical behavior. The tensile properties were then correlated with the cellular properties to understand the effect of MSCs sheet on the variation of the mechanical behavior during the in vitro study. It was found that MSCs from the cell sheet were able to migrate into the PLCL sheet and actively proliferated into the porous structure then formed a new layer of MSCs on the opposite surface of the PLCL sheet. Mechanical evaluation revealed that the PLCL sheet with MSCs showed enhancement of tensile strength and strain energy density at the first week of culture which is characterized as the effect of MSCs proliferation and its infiltration into the porous structure of the PLCL sheet. New technique was presented to develop tissue engineered patch by combining MSCs sheet and porous PLCL sheet, and it is expected that the layered patch may prolong biomechanical stability when implanted in vivo.


Infidelity in couples seeking marital therapy.
The revelation of an affair is often an emotionally explosive event for a couple, yet little is known about specific individual and relationship factors that accompany infidelity. The present study examined the qualities of individuals and couples that differentiate couples with (n = 19) and without (n = 115) infidelity using couples from a randomized clinical trial of marital therapy. Findings indicated that couples with infidelity showed greater marital instability, dishonesty, arguments about trust, narcissism, and time spent apart. Gender also proved to be a significant moderator of several effects. Men who had participated in affairs showed increased substance use, were older, and were more sexually dissatisfied. Results offer initial clues to concomitants of affairs for couple therapists.


Lysophosphatidic acid induces integrin activation in vascular smooth muscle and alters arteriolar myogenic vasoconstriction.
In vascular smooth muscle cells (VSMC) increased integrin adhesion to extracellular matrix (ECM) proteins, as well as the production of reactive oxygen species (ROS) are strongly stimulated by lysophosphatidic acid (LPA). We hypothesized that LPA-induced generation of ROS increases integrin adhesion to the ECM. Using atomic force microscopy (AFM) we determined the effects of LPA on integrin adhesion to fibronectin (FN) in VSMC isolated from rat (Sprague-Dawley) skeletal muscle arterioles. In VSMC, exposure to LPA (2 μM) doubled integrin-FN adhesion compared to control cells (P < 0.05). LPA-induced integrin-FN adhesion was reduced by pre-incubation with antibodies against β1 and β3 integrins (50 μg/ml) by 66% (P < 0.05). Inhibition of LPA signaling via blockade of the LPA G-protein coupled receptors LPAR1 and LPAR3 with 10 μM Ki16425 reduced the LPA-enhanced adhesion of VSCM to FN by 40% (P < 0.05). Suppression of ROS with tempol (250 μM) or apocynin (300 μM) also reduced the LPA-induced FN adhesion by 47% (P < 0.05) and 59% (P < 0.05), respectively. Using confocal microscopy, we observed that blockade of LPA signaling, with Ki16425, reduced ROS by 45% (P < 0.05), to levels similar to control VSMC unexposed to LPA. In intact isolated arterioles, LPA (2 μM) exposure augmented the myogenic constriction response to step increases in intraluminal pressure (between 40 and 100 mm Hg) by 71% (P < 0.05). The blockade of LPA signaling, with Ki16425, decreased the LPA-enhanced myogenic constriction by 58% (P < 0.05). Similarly, blockade of LPA-induced ROS release with tempol or gp91 ds-tat decreased the LPA-enhanced myogenic constriction by 56% (P < 0.05) and 55% (P < 0.05), respectively. These results indicate that, in VSMC, LPA-induced integrin activation involves the G-protein coupled receptors LPAR1 and LPAR3, and the production of ROS, and that LPA may play an important role in the control of myogenic behavior in resistance vessels through ROS modulation of integrin activity.


High performance liquid chromatographic assay for the quantitation of total glutathione in plasma.
A simple and widely used homocysteine HPLC procedure was applied for the HPLC identification and quantitation of glutathione in plasma. The method, which utilizes SBDF as a derivatizing agent utilizes only 50 microl of sample volume. Linear quantitative response curve was generated for glutathione over a concentration range of 0.3125-62.50 micromol/l. Linear regression analysis of the standard curve exhibited correlation coefficient of 0.999. Limit of detection (LOD) and limit of quantitation (LOQ) values were 5.0 and 15 pmol, respectively. Glutathione recovery using this method was nearly complete (above 96%). Intra-assay and inter-assay precision studies reflected a high level of reliability and reproducibility of the method. The applicability of the method for the quantitation of glutathione was demonstrated successfully using human and rat plasma samples.


Subtraction MR images in a multiple sclerosis multicenter clinical trial setting.
To explore the applicability of subtraction magnetic resonance (MR) images to (a) detect active multiple sclerosis (MS) lesions, (b) directly quantify lesion load change, and (c) detect treatment effects (distinguish treatment arms) in a placebo-controlled multicenter clinical trial by comparing the subtraction scheme with a conventional pair-wise comparison of nonregistered MR images. Forty-six pairs of MR studies in 40 patients (31 women; mean age, 31.9 years) from a multicenter clinical trial were used. The clinical trial was approved by local ethics review boards, and all subjects gave written informed consent. Active MS lesions were scored by two independent raters, and lesion load measurements were conducted by using semiautomated software. Lesion counts were evaluated by using the Wilcoxon signed rank test, interrater agreement was evaluated by using the intraclass correlation coefficient (ICC), and treatment (interferon beta-1b) effect was evaluated by using the Mann-Whitney U test. When subtraction images were used, there was a 1.7-fold increase in the detection of positive active lesions, as compared with native image pairs, and significantly greater interobserver agreement (ICC = 0.98 vs 0.91, P < .001). Subtraction images also allowed direct quantification of positive disease activity, a measure that provided sufficient power to distinguish treatment arms (P = .012) compared with the standard measurement of total lesion load change on native images (P = .455). MR image subtraction enabled detection of higher numbers of active MS lesions with greater interobserver agreement and exhibited increased power to distinguish treatment arms, as compared with a conventional pair-wise comparison of nonregistered MR images.


Stability, delay, and chaotic behavior in a lotka-volterra predator-prey system.
We consider the following Lotka-Volterra predator-prey system with two delays: x '( t ) = x ( t ) [ r(1) - ax ( t - tau(1) ) - by( t ) ] y '( t ) = y ( t ) [ - r(1) + cx ( t ) - dy( t - tau(2) ) ] ( E ) We show that a positive equilibrium of system ( E ) is globally asymptotically stable for small delays. Critical values of time delay through which system ( E ) undergoes a Hopf bifurcation are analytically determined. Some numerical simulations suggest an existence of subcritical Hopf bifurcation near the critical values of time delay. Further system (E) exhibits some chaotic behavior when tau(2) becomes large.


Energy losses at three-way circular drop manholes under surcharged conditions.
Energy loss at manholes is of importance in the design of storm sewer networks and in flood-analysis. Some researchers have already investigated the energy loss at three-way manholes under surcharged conditions. However, formulation to calculate the energy loss at manholes, including all variables of structural elements of the pipes and of the manhole has not yet been accomplished. Therefore, more study to formulate the energy loss at three-way drop manholes is needed. In this study, the ratio of the diameter between inflow pipes and an outflow pipe, the ratio of flow rates between those pipes, water depth in a manhole and the drop gaps between those pipes are considered and the energy loss at three-way circular drop manholes is examined. Finally, a modified formula, more accurate than that in the U.S. Federal Highway Administration's 2001 Urban Drainage Design Manual is proposed. The proposed formula takes the influence of the ratio of the diameter between inflow pipes and outflow pipe and drop gaps between those pipes into consideration. The calculated energy loss coefficients in both straight-through and lateral pipes successfully reproduce the measured values.


[vCJD epidemiology in France].
Variant Creutzfeldt-Jakob disease (vCJD) is the only form of prion diseases linked to bovine spongiform encephalopathy (BSE). The disease was first described in the United-Kingdom (UK) and France is the second affected country with 21 cases. Clinical, genetic and neuropathological features are the same in both countries. Comparison of the total number of cases in France and in the UK, according to dates of onset, shows that, in France, the maximum incidence seems to be five years delayed and that, in the UK, the number of vCJD cases regularly decreases since 1999. Delayed exposure to contaminated beef products in France compared to the UK could explain this temporal gap. Three cases of vCJD after transfusion of labile blood products were observed in the UK. No such of cases were observed in France but three patients developing signs of vCJD in 2004 were blood donors. A total of 42 recipients were identified with 17 recipients still alive.


A Deep Learning Approach for Detecting Colorectal Cancer via Raman Spectra.
Objective and Impact Statement. Distinguishing tumors from normal tissues is vital in the intraoperative diagnosis and pathological examination. In this work, we propose to utilize Raman spectroscopy as a novel modality in surgery to detect colorectal cancer tissues. Introduction. Raman spectra can reflect the substance components of the target tissues. However, the feature peak is slight and hard to detect due to environmental noise. Collecting a high-quality Raman spectroscopy dataset and developing effective deep learning detection methods are possibly viable approaches. Methods. First, we collect a large Raman spectroscopy dataset from 26 colorectal cancer patients with the Raman shift ranging from 385 to 1545 cm -1. Second, a one-dimensional residual convolutional neural network (1D-ResNet) architecture is designed to classify the tumor tissues of colorectal cancer. Third, we visualize and interpret the fingerprint peaks found by our deep learning model. Results. Experimental results show that our deep learning method achieves 98.5% accuracy in the detection of colorectal cancer and outperforms traditional methods. Conclusion. Overall, Raman spectra are a novel modality for clinical detection of colorectal cancer. Our proposed ensemble 1D-ResNet could effectively classify the Raman spectra obtained from colorectal tumor tissues or normal tissues.


Aortic calcification on plain chest radiography increases risk for coronary artery disease.
To determine whether an association exists between aortic calcification viewed on plain chest radiography and coronary artery disease. Retrospective review of all chest radiographs obtained from consecutive patients undergoing coronary angiography at a primary cardiac center during 1999. Plain chest radiographs were reviewed by blinded radiologists, and interobserver consistency was measured. The presence or absence of aortic arch calcification was abstracted and compared with the results of coronary angiography. Of 654 cases, 329 of 360 patients with aortic arch calcification vs. 241 of 294 patients without aortic arch calcification had coronary artery disease demonstrated on angiography. The 9% absolute difference in proportions was significant (p = 0.0003). The relative risk (measured by risk ratio) was 1.11 (95% confidence interval, 1.05 to 1.19). Several objective signs (e.g., hypertension, hyperlipidemia, and ECG changes) have been associated previously with the presence of coronary artery disease. This study further suggests an association between coronary disease and aortic arch calcification on plain chest radiography. These results may assist primary-care providers performing routine health assessments as well as emergency practitioners evaluating patients with potential angina.


Evaluation of PEGylated exendin-4 released from poly (lactic-co-glycolic acid) microspheres for antidiabetic therapy.
Peptide-based therapies have the potential to induce antibody formation if the molecules differ from a native human peptide. Several reports have disclosed the occurrence of antibody generation in a patient treated with exenatide. The immune response can be problematic from a clinical stand point, particularly if the antibodies neutralize the efficacy of the biotherapeutic agent or cause a general immune reaction. To overcome this limit, PEGylated exendin-4 analogs were designed and examined for metabolic stability and biological activity. To develop an extended release delivery system for exendin-4 for the safe and effective delivery of bioactive exendin-4 without peptide acylation and immunogenicity, PEGylated exendin-4 was encapsulated into poly (lactic-co-glycolic acid) (PLGA) microspheres by w/o/w double emulsion solvent evaporation method. Peptide-loaded microspheres were characterized in terms of morphology, particle diameter, and peptide encapsulation efficiency. Then, the release profile of the peptide from PLGA microspheres and the acylated products from PLGA polymer degradation was determined. The results obtained showed that the stability of exendin-4 was greatly improved by PEGylation. Moreover, eliminated acylation during PLGA polymer degradation in vitro and reduced immunogenicity in vivo were observed. The findings demonstrate that PEGylated exendin-4-loaded microspheres may be a safe and biocompatible system for clinical development.


Prognostic Factors in Primary Vaginal Cancer: A Single Institute Experience and Review of Literature.
Primary vaginal carcinoma is rare, accounting for 1-2 % of all gynecological malignancies. Being rare, most observations are based on retrospective and comparative analyses. This study was aimed to retrospectively analyze the prognostic factors and its relevance in the outcomes of primary vaginal cancers. Medical records of all cases of primary vaginal cancers, presented to Department of Oncology, from 2004 to 2012, at a tertiary care center in southern India, were retrieved from electronic medical records, and were analyzed. The total number of cases was 32. Median age at presentation was 64.28 years. Squamous histology accounted for 84.4 %, with the rest being adenocarcinoma. Surgery was offered for five (15.6 %), and concurrent chemotherapy for 14 (43.8 %) patients. Three patients had only surgery. All others received radiotherapy. Twenty received external beam radiation (EBRT) and vaginal brachytherapy (VBT); seven only EBRT and two, adjuvant radiation. Five patients had residual disease; two, stage III, and three stage IV. Median follow-up was 55.83 months. Twelve patients were alive at last follow-up (37.5 %), while 14 were dead (43.8 %-8 of disease and 6 of other causes). Six patients were lost to follow-up (18.8 %). Twenty patients were disease free. Seven had recurrence, three loco-regional and four distant. Median overall survival (OS) was 86.1 months, disease-free survival (DFS) 90.17 months, and disease-specific survival (DSS) 97.13 months. When well and moderately differentiated tumors were taken together, the 5-year OS, DFS, and DSS rates were, 56.6, 64.3, and 82.3 %. For poorly differentiated tumors, median OS, DFS, and DSS were, 20.9, 14.6, and 20.9 months, with statistically significant advantage for better grade tumors, for DSS (p 0.050). Better 5-year OS, DFS, and DSS rates were observed for stage I + II group, with 54.9, 79.8, and 78.9 %, compared with advanced stage where the same were 54.8, 38.2, and 68.6 % (DFS-p 0.003, DSS-p 0.009). Grade and stage of tumor had statistically significant predictive value over the outcomes, while tumor size showed a significant trend. Patients treated with combination of EBRT and VBT fared well. Our study could conclude that grade of differentiation was a significant predictor of poor survival as was stage of disease. Combination of VBT and external beam radiotherapy provides good DFS.


Localization of acidic fibroblast growth factor (aFGF) mRNA in mouse and bovine retina by in situ hybridization.
Acidic fibroblast growth factor (aFGF) mRNA has been detected in adult mouse or bovine retina by in situ hybridization with bovine aFGF cDNA clones. It is localized on ganglion cell layer, inner nuclear layer, photoreceptors and slightly on pigmented epithelium. This synthesis of aFGF in highly specialized retinal cell types is discussed in the framework on current views about the role of FGF in retinal cell biology.


Bruce/apollon promotes hippocampal neuron survival and is downregulated by kainic acid.
Prolonged or excess stimulation of excitatory amino acid receptors leads to seizures and the induction of excitotoxic nerve cell injury. Kainic acid acting on glutamate receptors produces degeneration of vulnerable neurons in parts of the hippocampus and amygdala, but the exact mechanisms are not fully understood. We have here investigated whether the anti-apoptotic protein Bruce is involved in kainic acid-induced neurodegeneration. In the rat hippocampus and cortex, Bruce was exclusively expressed by neurons. The levels of Bruce were rapidly downregulated by kainic acid in hippocampal neurons as shown both in vivo and in cell culture. Caspase-3 was activated in neurons exhibiting low levels of Bruce causing cell death. Likewise, downregulation of Bruce using antisense oligonucleotides decreased viability and enhanced the effect of kainic acid in the hippocampal neurons. The results show that Bruce is involved in neurodegeneration caused by kainic acid and the downregulation of the protein promotes neuronal death.


Sequential solvent induced phase transition extraction for profiling of endogenous phytohormones in plants by liquid chromatography-mass spectrometry.
In the current study, a novel method for high-throughput and sensitive determination of 12 phytohormones in plants was developed by using sequential solvent induced phase transition extraction (SIPTE) coupled with ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). In sequential SIPTE, 0.1% formic acid (v/v) and 50mM NaHCO3 aqueous solution were used for enrichment and purification of alkaline and acidic phytohormones from the acetonitrile extract of plant tissues in sequence, in which hydrophobic solvent (toluene) was added to the acetonitrile aqueous mixture for driving the phase separation. Under optimized sequential SIPTE conditions, the phytohormones in acetonitrile extract of plant tissues could be effectively enriched and purified, which was in favor of the following UPLC-MS/MS analysis with less matrix effect. The phytohormones could be detected using the developed sequential SIPTE-UPLC-MS/MS method with the limits of the detection (LODs) ranging from 0.56 to 438.60pgmL(-1) and linear range over 2 orders of magnitude with correlation coefficients (r)>0.9970. The relative recoveries of the detected phytohormones were in the range of 85.1-114.6%. Finally, the proposed method was applied to simultaneous determination of endogenous phytohormones in different tissues of model plants (Oryza sativa and Arabidopsis thaliana) with small amount of sample size (5mg, fresh weight). The proposed method may be suitable for studying the distribution of phytohormones in model plants.


Hydrothermal Synthesis in Gap: Conformal Deposition of Textured Hematite Thin Films for Efficient Photoelectrochemical Water Splitting.
Obtaining high performance of hematite (α-Fe2O3) in a photoelectrochemical (PEC) water splitting cell is a challenging task because of its poor electrical conductivity and extremely short carrier lifetime. Here, we introduce a new hydrothermal method, called gap hydrothermal synthesis (GAP-HS), to obtain textured hematite thin films with an outstanding PEC water oxidation performance. GAP-HS proceeds in a precursor-solution-filled narrow gap to induce an anisotropic ion supply. This gives rise to an interesting phenomenon associated with the growth of nanomaterials that reflect the texture of the used substrates. Also, GAP-HS causes the preferential growth of hematite crystal along the [110] direction, leading to improved electrical conductivity within the (001) basal plane. The hematite thin films obtained via GAP-HS exhibit a very high photocurrent of more than 1.3 mA cm-2 at 1.23 V with respect to the reversible hydrogen electrode with 550 °C annealing only. It is the highest photocurrent, to the best of our knowledge, obtained for the hydrothermally synthesized pristine hematite photoanode. Because the low-temperature annealing allows avoiding of substrate deformation, the hematite thin films obtained via GAP-HS are expected to be advantageous for tandem-cell configuration.


First human systemic infection caused by Spiroplasma.
Spiroplasma species are organisms that normally colonize plants and insects. We describe the first case of human systemic infection caused by Spiroplasma bacteria in a patient with hypogammaglobulinemia undergoing treatment with biological disease-modifying antirheumatic agents. Spiroplasma turonicum was identified through molecular methods in several blood cultures. The infection was successfully treated with doxycycline plus levofloxacin.