Laboratory evaluation of molluscicidal & mosquito larvicidal activities of leaves of Solanum nigrum L.
Indiscriminate use of synthetic pesticides has created serious problem for the aquatic flora and fauna, and also resulted in appearance of pesticide resistance in vector population. This study was designed to evaluate the biocontrol efficacy of aqueous and solvent extracts of mature leaves of Solanum nigrum L., against fresh water snail Lymnaea acuminata f. rufescens (Gray) (an intermediate host of parasites causing fasciolopsiasis) and larvae of Culex vishnui group (Reuben) (vector of Japanese encephalitis). Aqueous and solvent extracts of fresh, mature, green/shed dried leaves of S. nigrum were tested against adult L. acuminata and larvae of Cx. vishnui group. The lethal concentration was determined and the appropriate lethal concentration at 24 h of benzene extract was also studied on non target organisms such as Daphnia sp, Diplonychus annulatum and Chironomus circumdatus. A qualitative phytochemical analysis was carried out in search of active ingredient and the chemical nature of the active substance was also evaluated by infrared (IR) analysis. In a 72 h bioassay experiment with the aqueous extract, the highest mortality was recorded in 0.5 and 3 per cent extract against larvae of Cx. vishnui group and L. acuminata, respectivela. In the benzene solvent extract, the maximum mortality was recorded at a concentration of 150 ppm against L. acuminata and at 50 ppm against larvae of Cx. vishnui group with LC 50 values of 55.45 and 11.59 ppm, respectively at 72 h. The log probit analysis (95% confidence level) recorded lowest value at 72 h of exposure. Qualitative phytochemical analysis reported the presence of some biochemical compounds, such as saponin, flavonoids, steroid and tannin. Among these, the toxic compound was detected by IR analysis having Rf=0.87 (showed 66.70% and 76.70% mortality of L. acuminata and larvae of Cx. vishnui group, respectively). IR analysis provided preliminary information about the aliphatic amide nature of the active ingredient. The study results provide considerable scope in exploiting local indigenous plant resources for molluscicidal and mosquito larvicidal activities.


Prokaryotic expression and antimicrobial mechanism of XPF-St7-derived α-helical peptides.
XPF-St7 (GLLSNVAGLLKQFAKGGVNAVLNPK) is an antimicrobial peptide isolated from Silurana tropicalis. We developed an α-helical segment of XPF-St7 termed as XPF2. Using the XPF2 as a framework, we increased the positive net charge of XPF2 by amino acid substitutions, and thus obtained two novel antimicrobial peptides XPF4 and XPF6. These were each fused with an ubiquitin tag and successfully expressed in Escherichia coli. This ubiquitin fusion system may present a viable alternative for industrial production of antimicrobial peptides. XPF4 and XPF6 showed much better overall antimicrobial activity against both Gram-negative and Gram-positive bacteria than XPF2. The therapeutic index of XPF4 and XPF6 was 5.6-fold and 6.7-fold of XPF2, respectively. Bacterial cell membrane permeabilization and genomic DNA interaction assays were utilized to explore the mechanism of action of XPF serial peptides. The results revealed that the target of these antimicrobial peptides was the bacterial cytoplasmic membrane.


Enterourachal Fistula as an Initial Presentation in Crohn Disease.
Crohn disease has a wide spectrum of clinical presentations and rarely can present with complications such as a bowel stricture or fistula. In this case report, we describe a 17-year-old male who presented with a history of recurrent anterior abdominal wall abscesses and dysuria. He was diagnosed with Crohn disease and also found to have a fistulous communication between the terminal ileum and a patent urachus. An ileocecectomy with primary anastomosis and complete resection of the abscess cavity was performed. He is on azathioprine for maintenance therapy and currently in remission. Clinicians should have a high index of suspicion for this complication in Crohn disease patients presenting with symptoms suggestive of urachal anomalies such as suprapubic abdominal pain, dysuria, umbilical discharge, and periumbilical mass.


Vanadium-based pro-catalysts bearing depleted 1,3-calix[4]arenes for ethylene or ε-caprolactone polymerization.
Reaction of [V(X)(OR)(3)] (X = O, Np-tolyl, R = nPr, tBu) with 5,11,17,23-tBu-25,27-dihydroxycalix[4]arene (LH(2)) led to the formation of [V(X)(OR)L](2) X = O, R = nPr (1); X = Np-tolyl, R = nPr (2); X = Np-tolyl, R = tBu (3) as the major product. In the case of X = O, the minor hydrolysis product {[VO(OnPr)](2)(μ-O)L}(2) (4) has also been characterized. Complexes (1)-(4), in the presence of the co-catalyst dimethylaluminum chloride and the reactivator ethyltrichloroacetate, are highly active (≤16,400 g/mmol h bar), thermally stable pro-catalysts for the polymerization of ethylene. The use of silica supports with (1) and (2) under slurry conditions yielded polymer with activities ≤30 g/mmol h. Complexes (1)-(3) have also been screened as pro-catalysts for the ring-opening polymerization of ε-caprolactone; the conversion rate order (1) (94%) > (2) (46%) > (3) (20%) was observed at 80 °C over 72 h.


Alleviation of experimental septic shock in mice by acidic polysaccharide isolated from the medicinal mushroom Phellinus linteus.
This study reports that acidic polysaccharide (PL) isolated from Phellinus linteus alleviated the septic shock induced by high dose lipopolysaccharide (LPS) injection in mice. To examine the origin of this effect, we investigated cytokine production in serum and the expression of MHC II in B cells and macrophages in areas of inflammation. Pretreatment with PL 24 h before LPS administration resulted in a significant inhibition of up to 68% of circulating tumor necrosis factor (TNF)-alpha, a moderate reduction of 45% of interleukine (IL)-12 and 23% of IL-1beta, but no significant reduction in IL-6. In addition, the expression of MHC II in B cells and macrophages was examined. Our results show that LPS-stimulated cytokine release and the level of MHC II can be modulated by in vivo administration of soluble PL in mice. The decrease of IL-1beta, IL-12 and TNF-alpha in sera and the down-modulation of MHC II during septic shock may contribute to the long survival of mice by PL. Administration of PL in vivo decreases IL-2, IFN-gamma and TNF-alpha production in splencotyes and enhances spontaneous cell apoptosis in macrophages and lymphocytes stimulated with LPS in vitro. Thus, part of the anti-inflammatory effects of PL treatment in vivo may result from the enhanced apoptosis of a portion of the activated macrophages and lymphocytes. The ability of PL to significantly reduce the TNF-alpha production indicates the potential of the polysaccharides in possible therapeutic strategies that are based on down-regulation of TNF-alpha.


[Apoptosis in myocardial cells after macleaya cordata total alkaloids poisoning in rats].
To observe pathological changes and apoptosis in rats myocardial cells after Macleaya cordata total alkaloids poisoning, and to provide some references for Macleaya cordata total alkaloids poisoning detection. An experimental model of Macleaya cordata total alkaloids poisoning was established, and the technology of TUNEL staining was used.The results were analyzed by computer image analysis competitive system. Quantities of apoptosis in myocardial cells in poisoning groups were much more than those in the control groups at different tages (P<0.01). In addition the quantities of apoptosis were different after different poisoning duration. Although clinical symptoms was not obvious and could not be detected by poison analysis. Pathological changes induced by Macleaya cordata total alkaloids could be found through the apoptosis detection.


Nonlesions, unusual cell types, and postmortem artifacts in the central nervous system of domestic animals.
In the central nervous system (CNS) of domestic animals, numerous specialized normal structures, unusual cell types, findings of uncertain or no significance, artifacts, and various postmortem alterations can be observed. They may cause confusion for inexperienced pathologists and those not specialized in neuropathology, leading to misinterpretations and wrong diagnoses. Alternatively, changes may mask underlying neuropathological processes. "Specialized structures" comprising the hippocampus and the circumventricular organs, including the vascular organ of the lamina terminalis, subfornical organ, subcommissural organ, pineal gland, median eminence/neurohypophyseal complex, choroid plexus, and area postrema, are displayed. Unusual cell types, including cerebellar external germinal cells, CNS progenitor cells, and Kolmer cells, are presented. In addition, some newly recognized cell types as of yet incompletely understood significance and functionality, such as synantocytes and aldynoglia, are introduced and described. Unusual reactive astrocytes in cats, central chromatolysis, neuronal vacuolation, spheroids, spongiosis, satellitosis, melanosis, neuromelanin, lipofuscin, polyglucosan bodies, and psammoma bodies may represent incidental findings of uncertain or no significance and should not be confused with significant microscopic changes. Auto- and heterolysis as well as handling and histotechnological processing may cause postmortem morphological changes of the CNS, including vacuolization, cerebellar conglutination, dark neurons, Buscaino bodies, freezing, and shrinkage artifacts, all of which have to be differentiated from genuine lesions. Postmortem invasion of micro-organisms should not be confused with intravital infections. Awareness of these different changes and their recognition are a prerequisite for identifying genuine lesions and may help to formulate a professional morphological and etiological diagnosis.


High prevalence of GB virus C in Brazil and molecular evidence for intrafamilial transmission.
The prevalence of GB virus C (GBV-C) in candidate Brazilian blood donors with normal and elevated alanine aminotransferase levels was found to be 5.2% (5 of 95) and 6.5% (5 of 76), respectively. Among Brazilian patients, GBV-C was found in 9.5% (13 of 137) of cases of hepatitis not caused by hepatitis A virus (HAV), HBV, HCV, HDV, or HEV (non-A-E hepatitis) and in 18.2% (8 of 44) of individuals infected with HCV. Molecular characterization of GBV-C by partial sequencing of the NS3 region showed clustering between members of a single family, implying intrafamilial transmission. In conclusion, these results together suggest that contagion mechanisms which facilitate intrafamilial transmission of GBV-C may partially explain the high prevalence of viremic carriers worldwide.


Reflection color filters of the three primary colors with wide viewing angles using common-thickness silicon subwavelength gratings.
We fabricated reflection color filters of the three primary colors with wide viewing angles using silicon two-dimensional subwavelength gratings on the same quartz substrate. The grating periods were 400, 340, and 300 nm for red, green, and blue filters, respectively. All of the color filters had the same grating thickness of 100 nm, which enabled simple fabrication of a color filter array. Reflected colors from the red, green, and blue filters under s-polarized white-light irradiation appeared in the respective colors at incident angles from 0 to 50°. By rigorous coupled-wave analysis, the dimensions of each color filter were designed, and the calculated reflectivity was compared with the measured reflectivity.


Contrasting Effects of the Cytotoxic Anticancer Drug Gemcitabine and the EGFR Tyrosine Kinase Inhibitor Gefitinib on NK Cell-Mediated Cytotoxicity via Regulation of NKG2D Ligand in Non-Small-Cell Lung Cancer Cells.
Several cytotoxic anticancer drugs inhibit DNA replication and/or mitosis, while EGFR tyrosine kinase inhibitors inactivate EGFR signalling in cancer cell. Both types of anticancer drugs improve the overall survival of the patients with non-small-cell lung cancer (NSCLC), although tumors often become refractory to this treatment. Despite several mechanisms by which the tumors become resistant having been described the effect of these compounds on anti-tumor immunity remains largely unknown. This study examines the effect of the cytotoxic drug Gemcitabine and the EGFR tyrosine kinase inhibitor Gefitinib on the expression of NK group 2 member D (NKG2D) ligands as well as the sensitivity of NSCLC cells to the NK-mediated lysis. We demonstrate that Gemcitabine treatment leads to an enhanced expression, while Gefitinib downregulated the expression of molecules that act as key ligands for the activating receptor NKG2D and promote NK cell-mediated recognition and cytolysis. Gemcitabine activated ATM and ATM- and Rad-3-related protein kinase (ATR) pathways. The Gemcitabine-induced phosphorylation of ATM as well as the upregulation of the NKG2D ligand expression could be blocked by an ATM-ATR inhibitor. In contrast, Gefitinib attenuated NKG2D ligand expression. Silencing EGFR using siRNA or addition of the PI3K inhibitor resulted in downregulation of NKG2D ligands. The observations suggest that the EGFR/PI3K pathway also regulates the expression of NKG2D ligands. Additionally, we showed that both ATM-ATR and EGFR regulate MICA/B via miR20a. In keeping with the effect on NKG2D expression, Gemcitabine enhanced NK cell-mediated cytotoxicity while Gefitinib attenuated NK cell killing in NSCLC cells.


Effects of supplementing yeast fermentate in the feed or drinking water on stress susceptibility, plasma chemistry, cytokine levels, antioxidant status, and stress- and immune-related gene expression of broiler chickens.
This study aimed to elucidate the mechanism by which adding Saccharomyces cerevisiae-derived yeast fermentate to the feed (XPC) or drinking water reduces stress in poultry. Day-old male Cobb 500 broiler chicks were assigned to 1 of 3 treatments: stressed control (CS), stressed + XPC (1.25 kg/metric ton feed, day 0-43; XPC), or stressed + AviCare (160 mL/100 L drinking water, day 0-43; AVI). All birds were spray-vaccinated for coccidiosis (day 0), raised on reused litter, spray-vaccinated for Newcastle/Bronchitis (day 18), and exposed to heat stress (32°C-34°C) and feed/water withdrawal for 12 h (day 18). Blood samples were collected to assess plasma corticosterone (CORT) and heterophil/lymphocyte (H/L) ratio (60 birds/treatment; day 40); plasma biochemistry and growth hormone (12 birds/treatment; day 38); and serum serotonin and plasma prolactin, thyroid hormones, antioxidant capacity, and selected cytokines (12 birds/treatment; day 39). Composite asymmetry scores were obtained from 60 birds/treatment on day 41. Organs were collected from 20 birds/treatment on day 43 to measure gene expression of CYP1A2 and melanocortin 2 receptor (MC2R) in the adrenal glands and IL10 and AvBD1 in the spleen. Serotonin was lower in CS than XPC (P = 0.049), whereas AVI was intermediate. Plasma interleukin (IL)-1β was higher in AVI than CS (P = 0.009) and XPC (P = 0.009). The CS treatment had higher CORT than AVI (P = 0.013) and XPC (P = 0.037) and higher H/L ratios than AVI (P = 0.026) and XPC (P = 0.034). Expression of CYP1A2, MC2R, and IL10 was lower (P < 0.05) in XPC and AVI compared with CS. Furthermore, IL10 expression was lower in XPC than AVI (P < 0.05). Adding yeast fermentate to the feed or drinking water reduced measures of stress and MC2R gene expression in birds exposed to acute and rearing stressors. However, differences in IL10 gene expression and circulating serotonin and IL-1β suggest that supplementing yeast fermentate in the feed is slightly more effective than supplementation via the drinking water in mitigating the physiological effects associated with the stress response in broilers.


Restoration of Balance and Unilateral Hearing Using Alternating and Filtering Auditory Training in Shunt-Treated Hydrocephalus Following Subarachnoid Hemorrhage: A Case Report.
BACKGROUND Although rehabilitation for balance disorders is commonly undertaken following a stroke, hearing dysfunction is rarely investigated, even though hearing loss affects the ability to maintain balance. This report presents a case of restoration of balance and unilateral hearing using an alternating and filtering auditory training (AFAT) protocol in a patient with subarachnoid hemorrhage (SAH) and shunt-treated hydrocephalus. CASE REPORT A 54-year-old woman with a five-month history of SAH due to a ruptured aneurysm in the anterior communicating artery and hydrocephalus treated with a shunt was admitted to our unit for neurorehabilitation. The patient had a history of anorexia. Her initial neurological examination on admission for rehabilitation therapy showed postural instability, hemi-hyposthenia, proprioceptive left-sided ataxia, a confusional state including temporospatial disorientation, memory disorder and hearing loss. Two weeks after the start of her neurorehabilitation program the AFAT program was commenced. Pure tone audiometry (PTA) showed lower left hearing thresholds, extending from a hearing level (HL) of between 5-25 decibel (dB) or more when compared with the right ear. With a rapid and improved regain of unilateral hearing loss, balance, cognitive, and motor function also improved. CONCLUSIONS This case report supports that patients who undergo rehabilitation following stroke, SAH, and hydrocephalus might benefit from a rehabilitation program that includes hearing assessment and early improvement of hearing loss, leading to a shorter rehabilitation time.


The Risk Factors of Low Back Pain in Female High School Students.
A prospective cross-sectional study. The aim of this study was to evaluate the prevalence and associated factors with low back pain (LBP) in female adolescents of high school age. The prevalence of LBP in Tehran is high, and the majority of previous studies on LBP in adolescent and its risk factors have been performed in the developed countries. Therefore, identification of risk factors and planning appropriate protocols for prevention of LBP in adolescents may substantially decrease the prevalence of LBP and its burden in developing countries in future. In a prospective cross-sectional study, demographic characteristics, including age, body mass index (BMI), weight and mode of using backpack, family history of LBP in first degree relatives, and passive smoking status of the participants along with a history of LBP were recorded. Joint hypermobility was assessed using Beighton scale. Also, anthropometric measurements, spinal flexion, and hip joint range of motion were measured for each participant. In total, 372 students participated in the study. The mean (SD) age of the participants was 15.8 (0.9) years. The lifetime, more than 3 months, and last month history of LBP was 46.2%, 11.6%, and 31.2%, respectively. Positive history of LBP in the first-degree relatives was significantly associated with LBP in the participants (P < 0.01). The prevalence of passive smoking was significantly higher in the participants with last month history of LBP (P = 0.03). The prevalence of joint hypermobility was 15.9% and was significantly higher in those with the lifetime and last month history of LBP (P < 0.01). LBP is a common complaint among adolescent and high school girl students. The results of this study identified the prevalence and associated factors with LBP in high school students and will help develop strategies for prevention and treatment of LBP in the adolescent population. 3.


6-Pyruvoyl-tetrahydropterin synthase deficiency with generalized dystonia and diurnal fluctuation of symptoms: a clinical and molecular study.
We report the case of a 44-year-old woman with a partial 6-pyruvoyl tetrahydropterin synthase (6-PTS) deficiency, whose predominant clinical symptom was generalized dystonia with marked diurnal fluctuation. Dystonia was present in the eyelids, oromandibular region, trunk, and extremities (Meige syndrome plus double hemiplegia-like dystonia). A marked and sustained positive response to levodopa was observed. A molecular genetic study revealed a homozygous mutation (I114V) in the 6-PTS gene. This study indicates that genetic abnormality in the 6-PTS gene may be a hereditary dystonia disorder. We speculate that our patient has residual 6-PTS activity in the central nervous system, such as in the liver, and we suggest that residual, but insufficient production of tetrahydrobiopterin may play an important role in causing diurnal fluctuation of symptoms.


Association between two types of vitamin d receptor gene polymorphism and bone status in premenopausal Japanese women.
Polymorphisms in the vitamin D receptor (VDR) gene using ultrasound (US) bone mass and bone metabolic markers were investigated as potential genetic markers for osteoporosis in 126 premenopausal Japanese women aged 27.2 +/- 10.1 (mean +/- SD) years. The relationship between their VDR gene polymorphisms and bone states was determined. VDR genotypes were based on the absence (B) or presence (b) of the Bsm I restriction site (B polymorphism), and ATG (the M allele) and ACG (the m allele) sequences at the translation initiation site (M polymorphism). Genotype frequencies were 73.8%, bb; 24.6%, Bb; 1.6%, BB; 15.1%, MM; 51.6%, Mm and 33.3%, mm. The stiffness index of calcaneal bone minerals measured by an US bone densitometer was significantly higher in the mm types (P <0.05 versus MM) than in the Mm types (P <0.01 versus MM) and MM types. There was no significant difference between in B polymorphisms. Furthermore, bone mass was correlated with serum bone type alkaline phosphatase (ALP) activity and urinary deoxypyridinoline concentration in M polymorphisms. Because the distribution of B polymorphisms in each M polymorphism genotype did not differ, M polymorphisms were affected independently from B polymorphisms to bone mass or bone metabolic markers. No significant difference was observed in nutritional intake and food consumption among genotypes. In the MM and Mm types, the bone mass was closely related to the frequency of milk intake during the periods of elementary and junior high school. In contrast, bone mass was not associated with nutritional intake or the frequency of past milk intake in B polymorphisms. Therefore, the M polymorphism of the VDR gene is a stronger genetic indicator of osteoporosis than the B polymorphism in premenopausal Japanese woman.


Cumulative organophosphate pesticide exposure and risk assessment among pregnant women living in an agricultural community: a case study from the CHAMACOS cohort.
Approximately 230,000 kg of organophosphate (OP) pesticides are applied annually in California's Salinas Valley. These activities have raised concerns about exposures to area residents. We collected three spot urine samples from pregnant women (between 1999 and 2001) enrolled in CHAMACOS (Center for the Health Assessment of Mothers and Children of Salinas), a longitudinal birth cohort study, and analyzed them for six dialkyl phosphate metabolites. We used urine from 446 pregnant women to estimate OP pesticide doses with two deterministic steady-state modeling methods: method 1, which assumed the metabolites were attributable entirely to a single diethyl or dimethyl OP pesticide; and method 2, which adapted U.S. Environmental Protection Agency (U.S. EPA) draft guidelines for cumulative risk assessment to estimate dose from a mixture of OP pesticides that share a common mechanism of toxicity. We used pesticide use reporting data for the Salinas Valley to approximate the mixture to which the women were exposed. Based on average OP pesticide dose estimates that assumed exposure to a single OP pesticide (method 1), between 0% and 36.1% of study participants' doses failed to attain a margin of exposure (MOE) of 100 relative to the U.S. EPA oral benchmark dose(10) (BMD(10)), depending on the assumption made about the parent compound. These BMD(10) values are doses expected to produce a 10% reduction in brain cholinesterase activity compared with background response in rats. Given the participants' average cumulative OP pesticide dose estimates (method 2) and regardless of the index chemical selected, we found that 14.8% of the doses failed to attain an MOE of 100 relative to the BMD(10) of the selected index. An uncertainty analysis of the pesticide mixture parameter, which is extrapolated from pesticide application data for the study area and not directly quantified for each individual, suggests that this point estimate could range from 1 to 34%. In future analyses, we will use pesticide-specific urinary metabolites, when available, to evaluate cumulative OP pesticide exposures.


Inclusion practice in lung cancer trials.
This article presents the results of a qualitative study on the ethical aspects of inclusion practice for radiotherapy patients taking part in clinical research. The study focused on the standards and values of this process. Patients and physicians were interviewed about their views and experiences. Analysis of these interviews showed that candidate research participants need better protection from unwanted factors that could influence their choice about participation. Researchers need proper education about regulation, codes and directives in the field of research ethics, and they should be aware of the underlying ethical concepts of these regulations. A sound institutional ethics policy is necessary in order to guide medical staff in decisions about the inclusion of patients in trials.


Long noncoding RNAs in cardiovascular disease.
Here, we review recent findings on the role of long noncoding RNAs (lncRNAs) in cardiovascular disease (CVD). In addition, we highlight some of the latest findings in lncRNA biology, providing an outlook for future avenues of lncRNA research in CVD. Recent publications provide translational evidence from patient studies and animal models for the role of specific lncRNAs in CVD. The molecular effector mechanisms of these lncRNAs are diverse. Overall, cell-type selective modulation of gene expression is the largest common denominator. New methods, such as single-cell profiling and CRISPR/Cas9-screening, reveal additional novel mechanistic principles: For example, many lncRNAs establish RNA-based spatial compartments that concentrate effector proteins. Also, RNA modifications and splicing features can be determinants of lncRNA function. lncRNA research is passing the stage of enumerating lncRNAs or recording simplified on-off expression switches. Mechanistic analyses are starting to reveal overarching principles of how lncRNAs can function. Exploring these principles with decisive genetic testing in vivo remains the ultimate test to discern how lncRNA loci, by RNA motifs or DNA elements, affect CVD pathophysiology.


Photon dressed electronic states in topological insulators: tunneling and conductance.
We have obtained analytic results for the surface states of three-dimensional topological insulators in the presence of circularly polarized light. This electron-photon interaction results in an energy gap as well as a novel energy dispersion of the dressed electron-photon states, different from both graphene and the standard two-dimensional electron gas (2DEG). Additionally, we made calculations of the ballistic conductance and Klein tunneling in both two- and three-dimensional topological insulators as well as investigating how these phenomena are affected in the presence of circularly polarized light. We have found a critical energy for an incoming particle, separating two substantially different types of tunneling.


A novel isoform of syntaxin-binding protein homologous to yeast Sec1 expressed ubiquitously in mammalian cells.
munc-18/n-Sec1/rbSec1, a brain homologue of the yeast Sec1p protein, is thought to participate in regulating the docking and fusion of synaptic vesicles. We have screened the mouse cDNA library of an MIN6 cell line, derived from pancreatic beta cells, for its novel isoform and have identified a cDNA encoding a 593-amino acid protein having 63, 53, and 30% identity with munc-18/n-Sec1/rbSec1, Caenorhabditis elegans unc18, and Saccharomyces cerevisiae Sec1p, respectively. While munc-18/n-Sec1/rbSec1 expression has been reported to be neural-specific, RNA blot analysis has revealed that the novel isoform, which we refer to as muSec1 (mammalian ubiquitous Sec1), is expressed ubiquitously. We have also identified mouse munc-18/n-Sec1/rbSec1 from the MIN6 cDNA library, indicating that different isoforms of a protein participating in vesicular transport exist in a single cell. muSec1 bound to glutathione S-transferase-syntaxin 1A and, although with lower affinity, to glutathione S-transferase-syntaxin 4 fusion protein. These findings suggest that muSec1 is, via its binding to the syntaxin family, involved in the protein trafficking from the Golgi apparatus to the plasma membrane and that the fundamental mechanisms of protein trafficking have been conserved from yeast through virtually all mammalian cells.


The protein phosphatases of Drosophila melanogaster and their inhibitors.
Protein phosphatases-1, 2A and 2B have been identified in membrane and soluble fractions of Drosophila melanogaster heads. Similarities between Drosophila and mammalian protein phosphatase-1 included specificity for the beta subunit of phosphorylase kinase, sensitivity to inhibitor-1 and inhibitor-2, inhibition by protamine, retention by heparin-Sepharose and selective interaction with membranes. In addition, an inactive form of protein phosphatase-1, termed protein phosphatase-1I, was detected in the soluble fraction that could be activated by preincubation with MgATP and mammalian glycogen synthase kinase-3. Inhibitor-2 partially purified from Drosophila had an identical molecular mass to its mammalian counterpart, and recombined with mammalian protein phosphatase-1 to form a hybrid protein phosphatase-1I. Similarities between Drosophila and mammalian protein phosphatase-2A included preferential dephosphorylation of the alpha subunit of phosphorylase kinase, insensitivity to inhibitors-1 and -2, activation by protamine, exclusion from heparin-Sepharose and apparent molecular mass. A Ca2+-dependent calmodulin-stimulated protein phosphatase (protein phosphatase-2B) that was inhibited by trifluoperazine was identified in the soluble fraction. The remarkable similarities between Drosophila protein phosphatases and their mammalian counterparts are indicative of strict phylogenetic conservation and demonstrate that the procedures used to classify mammalian protein phosphatases have a wider application. Characterisation of the Drosophila phosphatases will facilitate genetic analysis of dephosphorylation systems and their possible roles in neuronal and behavioural plasticity in Drosophila.


[The strategy of determining the customized near addition lens for juvenile esophoric myopes].
To discuss accommodative lag and near phoria varying with the near addition lenses and establish the mathematic equations of near adds and accommodative lag, near phoria respectively in order to getting the optimal adds, which would create the least error in accommodative and convergence responses. To measure accommodative lag by Shin-Nippon and near phoria by Cover Test in 33 cm after providing 0D, +0.75D, +1.50D, +2.00D, +2.50D five near adds orderly to myopes after 110 simple myopes with esophoria have been corrected far vision wholly basing on MPMVA norm; to analyze the relation of near adds and accommodative lag, near phoria by linearity regression. While increasing dioptric value of the near adds, accommodative lag and esophoria decrease gradually. Both accommodative lag [F(262.76, 4), P < 0.01]and near phoria [F(223.45, 4), P < 0.01] show statistically significant difference among the five near adds. There is linearity correlation between the optimal adds and initial accommodative lag (r = 0.526, P < 0.01) and between the optimal adds and initial near phoria (r = 0.523, P < 0.01). The range of optimal near adds can be gotten basing on initial accommodative lag and near phoria of myopic individual, so that it can be provided referenced strategy of determining the customized near addition lens for juvenile esophoric myopes.


[Is there a correlation between the clinical, radiological and intrasurgical findings of osteoarthritis of the knee? A Prospective study on 103 patients].
The aim of this study was to compare the different diagnostic features (symptoms, physical examination, radiographic features and intraoperative findings) of osteoarthritis of the knee before total joint replacement and consequently relate them with each other. Patients with primary osteoarthritis of the knee, who where accepted for total joint replacement in our clinic, were integrated in our study. The medical conditions were recorded by using the Womac score, the knee subscore (KS) of the Knee Society Clinical Rating System and a visual analogue scale (VAS). A physical examination was also performed. The radiological evaluation was performed by using standardised radiographs. Joint space narrowing, subchondral sclerosis, osteophytes, knee alignment and the Kellgren score were recorded. During surgery an orthopaedic specialist documented the progression of cartilage lesions using the classification of chondromalacia described by Outerbridge. The analysis of correlation was performed by using the Spearman correlation (SpK) coefficient. 103 patients were integrated in the study (mean age: 68 years, 70 women). No significant correlation could be found between the Womac score or VAS and the results of the radiological examination (SpK [Womac - Kellgren score]: - 0.04; SpK [VAS - Kellgren score]: 0.08). There was a significant correlation between the KS and the results of the radiological examination as well as the progression of the cartilage lesions, caused by the results of the physical examination documented in the KS (SpK [KS - Kellgren score]: - 0.39). The radiographic features, with the exception of subchondral sclerosis, showed a significant correlation with the degree of chondromalacia (SpK [Kellgren score - chondromalacia]: 0.43). The amount of osteophytes correlated the most with the cartilage lesions: SpK: 0.43. The knee subscore appears to be an efficient method for staging the clinical progression of osteoarthritis of the knee for clinical practice as well as for clinical trials. The Womac score especially serves to record the level of pain. We were able to confirm that the presence of osteophytes is the most significant radiographic feature of osteoarthritis of the knee. The Kellgren score turned out to be a reliable method for monitoring the radiographic progression of osteoarthritis of the knee.


Androstenediol Reduces Demyelination-Induced Axonopathy in the Rat Corpus Callosum: Impact on Microglial Polarization.
Aims: We have previously shown that the neurosteroid androstenediol (ADIOL) promotes remyelination following gliotoxin-induced demyelination. However, the impact of this ADIOL on axonal recovery is not yet known. In the present study, we investigated the impact of ADIOL on axonal integrity following a focal demyelination in the corpus callosum. Methods: A 2 μl solution of either ethidium bromide (EB; 0.04%) or pyrogen-free saline were stereotaxically injected into the corpus callosum of Sprague Dawley rats. Each of these two rat groups was divided into two subgroups and received daily subcutaneous injections of either ADIOL (5 mg/kg) or vehicle. The brains were collected at 2, 7 and 14 days post-stereotaxic injection. Immunofluorescent staining was used to explore the impact of ADIOL on axonal integrity (neurofilament (NF)-M) and microglial activation (ionized calcium binding adapter molecule 1, Iba1). The inducible nitric oxide synthase (iNOS) and arginase-1 (arg-1), two major markers of microglial polarization towards the proinflammatory M1 and the regulatory M2 phenotypes respectively, were monitored using western blot. Results: ADIOL increased the density of NF fibers and decreased the extent of axonal damage in the vicinity of the demyelination lesion. ADIOL-induced decrease in axonal damage was manifested by decreased number of axonal spheroids at both 2 and 7 days post-demyelination insult. This reduced axonopathy was associated with decreased expression of iNOS and enhanced expression of arg-1 during the acute phase. Conclusion: These data strongly suggest that ADIOL reduces demyelination-induced axonal damage, likely by dampening the local inflammatory response in the white matter and shifting microglial polarization towards a reparative mode.


Menopausal hormone therapy and risk of breast cancer: a meta-analysis of epidemiological studies and randomized controlled trials.
We conducted meta-analyses to assess the impact of menopausal hormone therapy (MHT) on the risk of incident invasive breast cancer (BC) in cohort studies (CS), case-control studies (CCS) and randomized controlled trials (RCTs) published 1989-2004. We used published data providing information upon unopposed estrogen therapy (ET), estrogen-progestin therapy (EPT) or all MHT combined. Major outcomes were MHT-associated overall risk of BC and change of risk per year used. There is a linear increase of overall risk by midterm year of case ascertainment based upon data of all study types for MHT and to a larger extent for EPT, not for ET. Effects are larger in CS than in CCS. Meta-analyses stratified by <1992 versus > or =1992 as midterm year of case ascertainment indicate larger summary risks for the latter period for all MHT analysed, in particular for EPT. Annual increases in BC risk for EPT across study types are 0-9%, for ET 0-3%. In conclusion, there is evidence that relative risks for BC risks by MHT, in particular EPT, have been increasing in recent years. Given the widespread use of MHT, and often long duration, more detailed knowledge about differential BC risks of both estrogens and progestins are necessary to minimize BC risk in symptomatic women who consider MHT.


Quantitative uptake studies of 131I-labeled (E)-5-(2-iodovinyl)-2'-deoxyuridine in herpes simplex virus-infected cells in vitro.
We have synthesized a 131I-radiolabeled antiviral compound (E)-5-(2-iodovinyl)-2'-deoxyuridine (IVdU) and shown that this agent was selectively trapped within rabbit kidney cells, infected in vitro by thymidine kinase-positive (TK+) herpes simplex virus (HSV). The uptake of 131I-labeled IVdU was specific, as it was not concentrated within either HSV (TK-) or mock-infected cells. In certain conditions, over 40% of the radiolabel was selectively trapped within HSV (TK+)-infected cells. This was a 20- to 30-fold increase over the uptake of 131I-labeled IVdU by HSV (TK-) or mock-infected cells. The uptake of 131I-labeled IVdU varied directly with (i) the dose of the virus used to infect the rabbit kidney cells; (ii) the concentration of radiolabeled IVdU added to the system; and (iii) the time of exposure of IVdU to infected cells. The ability of this agent to be trapped within HSV (TK+)-infected cells merits further evaluation in animal models as it has potential as a noninvasive, herpes-specific diagnostic test, in particular for HSV encephalitis.


Improved methodology for field validation of industrial hygiene monitoring methods.
During the development and validation of industrial hygiene monitoring methods in the laboratory, various parameters of collection, storage, and analysis are studied. It is not feasible, however, to study all the environmental variables in the laboratory, so field validation is necessary to detect problems which are specific to the actual work site. A statistical procedure to evaluate the field validation experiment is described together with the methodology necessary to perform these experiments and the equipment to facilitate these experiments. These procedures are demonstrated in an experiment measuring acrylonitrile in the workplace.


Artisanal Sonoran cheese (Cocido cheese): an exploration of its production process, chemical composition and microbiological quality.
The objective of this study was to explore and document the production process of artisanal Cocido cheese and to determine its chemical composition and microbiological quality, considering samples from six dairies and four retailers. Cocido cheese is a semi-hard (506-555 g kg-1 of moisture), medium fat (178.3-219.1 g kg-1 ), pasta filata-type cheese made from raw whole cow's milk. The production process is not standardized and therefore the chemical and microbiological components of the sampled cheeses varied. Indicator microorganisms significantly decreased (P < 0.05) during the processing of Cocido cheese. Salmonella spp. were not found during the production process, and both Listeria monocytogenes and staphylococcal enterotoxin were absent in the final cheeses. This study provides more information on one of the most popular artisanal cheeses with high cultural value and economic impact in northwestern Mexico. In view of the foregoing, good manufacturing practices need to be implemented for the manufacture of Cocido cheese. Also, it is of utmost importance to make sure that the heat treatment applied for cooking the curd ensures a phosphatase-negative test, otherwise it would be necessary to pasteurize milk. Nevertheless, since Cocido cheese is a non-ripened, high-moisture product, it is a highly perishable product that could present a health risk if not properly handled. © 2017 Society of Chemical Industry.


Maximizing slow-light enhancement in one-dimensional photonic crystal ring resonators.
Photonic crystal ring resonators (PhCRR) combine the features of ring resonators with the slow-light effects present in photonic crystal waveguides, resulting in better mode confinement and increased light-matter interaction. When the resonator modes are near the photonic band edge, this enhancement is maximized. However, for this to be useful it is necessary to design the resonator so that these modes are at a desired wavelength. We introduce a design prescription, based on a theoretical analysis of the mode spectrum of PhCRRs, that maximizes these effects at a given wavelength. We test the procedure using numerical simulations, finding a good agreement between the design objectives and the simulated mode structures. We also consider the effects of disorder on the device.


Carbohydrate moieties in recombinant human thyroid peroxidase: role in recognition by antithyroid peroxidase antibodies in Hashimoto's thyroiditis.
We studied the oligosaccharide moieties of recombinant human thyroid peroxidase (hTPO) expressed in Chinese hamster ovary (CHO) cells, and the role of these glycans in hTPO antigenicity in Hashimoto's thyroiditis. To determine whether hTPO carbohydrate moieties were N-linked, O-linked, or both, and to obtain information about the characteristics of the carbohydrate component(s), we digested hTPO with deglycosylating enzymes of varying specificity. Proteins in CHO-TPO cells were labeled with [35S]methionine, and hTPO was immunoprecipitated with anti-hTPO antibodies present in Hashimoto's thyroiditis serum. Digestion with endoglycosidase (endo) F, which removes both complex and polymannose N-linked glycans, increased the electrophoretic mobility of the hTPO doublet from approximately 115 kD and 110 kD to 110 kD and 105 kD. Endo H, which acts similarly to endo F, but only on polymannose, and not complex, glycans, had a similar effect. In contrast, O-glycanase and neuraminidase, which remove O-linked glycans and terminal neuraminic acid, respectively, did not alter the mobility of radiolabeled hTPO. Radiolabeled recombinant hTPO was retained by concanavalin A, but not by wheat germ agglutinin, Ricinus communis agglutinin 1, peanut agglutinin and Ulex europaeus lectins. To determine whether or not the glycan moieties in hTPO play a role in the disease-associated epitopes in Hashimoto's thyroiditis, radiolabeled recombinant hTPO was immunoprecipitated after digestion with N-glycanase. Removal of the N-linked carbohydrate chains with endo F and endo H did not prevent antibody binding. In summary, the present data indicate that: i) hTPO expressed in CHO cells contains N-linked, but not O-linked glycan moieties; ii) the N-linked carbohydrate is primarily of the polymannose variety; and, iii) the glycan moieties do not contribute to the hTPO epitopes in Hashimoto's thyroiditis.


Ambient assisted living for frail people through human activity recognition: state-of-the-art, challenges and future directions.
Ambient Assisted Living is a concept that focuses on using technology to support and enhance the quality of life and well-being of frail or elderly individuals in both indoor and outdoor environments. It aims at empowering individuals to maintain their independence and autonomy while ensuring their safety and providing assistance when needed. Human Activity Recognition is widely regarded as the most popular methodology within the field of Ambient Assisted Living. Human Activity Recognition involves automatically detecting and classifying the activities performed by individuals using sensor-based systems. Researchers have employed various methodologies, utilizing wearable and/or non-wearable sensors, and employing algorithms ranging from simple threshold-based techniques to more advanced deep learning approaches. In this review, literature from the past decade is critically examined, specifically exploring the technological aspects of Human Activity Recognition in Ambient Assisted Living. An exhaustive analysis of the methodologies adopted, highlighting their strengths and weaknesses is provided. Finally, challenges encountered in the field of Human Activity Recognition for Ambient Assisted Living are thoroughly discussed. These challenges encompass issues related to data collection, model training, real-time performance, generalizability, and user acceptance. Miniaturization, unobtrusiveness, energy harvesting and communication efficiency will be the crucial factors for new wearable solutions.


A study with cumulative doses of formoterol and salbutamol in children with asthma.
In a double-blind, cross-over study, 9 children (7-13 yrs old) with stable, moderate asthma inhaled formoterol (6, 18 and 54 micrograms) and salbutamol (100, 300 and 900 micrograms) at hourly intervals, in order to compare the peak effect of cumulative doses of the two drugs. One hour after the last dose, 1 mg salbutamol was inhaled to ensure that maximum bronchodilatation was obtained. The forced expiratory volume in one second (FEV1), peak expiratory flow rate (PEFR), forced vital capacity (FVC), pulse rate, blood pressure and tremor were measured regularly after each dose and the PEFR 5, 7, 9 and 20 h after the last dose. The first dose of each drug improved the FEV1, PEFR and FVC substantially while the following doses only gave minor improvement. The final addition of 1 mg salbutamol produced no further improvement. No statistically significant difference in bronchodilating effect was seen between the two drugs at any point in time. Side-effects were minimal. Our data indicate that doses of 6-24 micrograms formoterol can be recommended for school children. For most patients with mild to moderate bronchial asthma higher doses will not add much to the bronchodilating effect.


[Osteoporosis-profile--a bad examination?].
A so-called osteoporosis-profile has become increasingly popular among Danish doctors. Future bone loss in peri- and postmenopausal women is estimated by means of an algorithm comprising serum osteocalcin and alkaline phosphatases as markers of bone formation and urinary calcium and hydroxyproline excretions, corrected for creatinine, as markers of bone resorption. The osteoporosis-profile, performed by Medi-Lab, was tested in six females aged 46-56 years. Three different diets were used on three successive week-ends, each ending with a collagen-free supper and an overnight fast. Individual changes in estimated bone loss of up to 200-300% were found, demonstrating that the test was useless in a single person.


Clinically relevant connectivity features define three subtypes of Parkinson's disease patients.
Parkinson's disease (PD) is characterized by complex clinical symptoms, including classic motor and nonmotor disturbances. Patients with PD vary in clinical manifestations and prognosis, which point to the existence of subtypes. This study aimed to find the fiber connectivity correlations with several crucial clinical symptoms and identify PD subtypes using unsupervised clustering analysis. One hundred and thirty-four PD patients and 77 normal controls were enrolled. Canonical correlation analysis (CCA) was performed to define the clinically relevant connectivity features, which were then used in the hierarchical clustering analysis to identify the distinct subtypes of PD patients. Multimodal neuroimaging analyses were further used to explore the neurophysiological basis of these subtypes. The methodology was validated in an independent data set. CCA revealed two significant clinically relevant patterns (motor-related pattern and depression-related pattern; r = .94, p < .001 and r = .926, p = .001, respectively) among PD patients, and hierarchical clustering analysis identified three neurophysiological subtypes ("mild" subtype, "severe depression-dominant" subtype and "severe motor-dominant" subtype). Multimodal neuroimaging analyses suggested that the patients in the "severe depression-dominant" subtype exhibited widespread disruptions both in function and structure, while the other two subtypes exhibited relatively mild abnormalities in brain function. In the independent validation, three similar subtypes were identified. In conclusion, we revealed heterogeneous subtypes of PD patients according to their distinct clinically relevant connectivity features. Importantly, depression symptoms have a considerable impact on brain damage in patients with PD.


Purification and characterization of rat-liver cytosolic epoxide hydrolase.
Rat liver cytosolic epoxide hydrolase has been purified and characterized. The enzyme was purified from tiadenol-induced rat liver 540-fold with respect to trans-stilbene oxide as a substrate. Similar purification was obtained with the substrates trans-beta-ethyl styrene oxide and styrene 7,8-oxide, the specific activities decreasing in the order trans-beta-ethyl styrene oxide greater than styrene 7,8-oxide greater than trans-stilbene oxide. The enzyme exerts highest activity at pH 7.4 Km and Vmax of the pure enzyme for trans-stilbene oxide were 1.7 microM and 205 nmol x min-1 x mg protein-1 respectively. With trans-stilbene oxide as a substrate, the inhibition by organic solvents (2.5% by vol.) increased in the order ethanol less than methanol less than acetone less than isopropanol = N,N-dimethyl formamide less than acetonitrile less than tetrahydrofuran. The native enzyme, with a molecular mass of 120 kDa, consists of two 61-kDa subunits. Digestion of rat liver cytosolic and microsomal epoxide hydrolase by three proteases resulted in markedly different peptide maps. Western-blot analysis with antiserum against rat liver cytosolic epoxide hydrolase revealed a single band with the purified enzyme, and with liver cytosol from control and clofibrate-induced rats. No cross-reactivity was observed with purified rat microsomal epoxide hydrolase or microsomes. A positive reaction at the same molecular mass was obtained with liver cytosol of mouse, guinea pig, Syrian hamster and New Zealand white rabbit but not with that of green monkey.


Non-classical monocytes are biased progenitors of wound healing macrophages during soft tissue injury.
Successful tissue repair requires the activities of myeloid cells such as monocytes and macrophages that guide the progression of inflammation and healing outcome. Immunoregenerative materials leverage the function of endogenous immune cells to orchestrate complex mechanisms of repair; however, a deeper understanding of innate immune cell function in inflamed tissues and their subsequent interactions with implanted materials is necessary to guide the design of these materials. Blood monocytes exist in two primary subpopulations, characterized as classical inflammatory or non-classical. While classical monocytes extravasate into inflamed tissue and give rise to macrophages or dendritic cells, the recruitment kinetics and functional role of non-classical monocytes remains unclear. Here, we demonstrate that circulating non-classical monocytes are directly recruited to polymer films within skin injuries, where they home to a perivascular niche and generate alternatively activated, wound healing macrophages. Selective labeling of blood monocyte subsets indicates that non-classical monocytes are biased progenitors of alternatively activated macrophages. On-site delivery of the immunomodulatory small molecule FTY720 recruits S1PR3-expressing non-classical monocytes that support vascular remodeling after injury. These results elucidate a previously unknown role for blood-derived non-classical monocytes as contributors to alternatively activated macrophages, highlighting them as key regulators of inflammatory response and regenerative outcome.


Pontine respiratory-modulated activity before and after vagotomy in decerebrate cats.
The dorsolateral (DL) pons modulates the respiratory pattern. With the prevention of lung inflation during central inspiratory phase (no-inflation (no-I or delayed-I) tests), DL pontine neuronal activity increased the strength and consistency of its respiratory modulation, properties measured statistically by the eta(2) value. This increase could result from enhanced respiratory-modulated drive arising from the medulla normally gated by vagal activity. We hypothesized that DL pontine activity during delayed-I tests would be comparable to that following vagotomy. Ensemble recordings of neuronal activity were obtained before and after vagotomy and during delayed-I tests in decerebrate, paralysed and ventilated cats. In general, changes in activity pattern during the delayed-I tests were similar to those after vagotomy, with the exception of firing-rate differences at the inspiratory-expiratory phase transition. Even activity that was respiratory-modulated with the vagi intact became more modulated while withholding lung inflation and following vagotomy. Furthermore, we recorded activity that was excited by lung inflation as well as changes that persisted past the stimulus cycle. Computer simulations of a recurrent inhibitory neural network model account not only for enhanced respiratory modulation with vagotomy but also the varied activities observed with the vagi intact. We conclude that (a) DL pontine neurones receive both vagal-dependent excitatory inputs and central respiratory drive; (b) even though changes in pontine activity are transient, they can persist after no-I tests whether or not changes in the respiratory pattern occur in the subsequent cycles; and (c) models of respiratory control should depict a recurrent inhibitory circuitry, which can act to maintain the stability and provide plasticity to the respiratory pattern.


Efficient graphite ring heater suitable for diamond-anvil cells to 1300 K.
In order to generate homogeneous high temperatures at high pressures, a ring-shaped graphite heater has been developed to resistively heat diamond-anvil cell (DAC) samples up to 1300 K. By putting the heater in direct contact with the diamond anvils, this graphite heater design features the following advantages: (1) efficient heating: sample can be heated to 1300 K while the DAC body temperature remains less than 800 K, eliminating the requirement of a special alloy for the DAC; (2) compact design: the sample can be analyzed with in situ measurements, e.g., x-ray, optical, and electrical probes are possible. In particular, the side access of the heater allows for radial x-ray diffraction (XRD) measurements in addition to traditional axial XRD.


Fibrinogen geneva II: a new congenitally abnormal fibrinogen alpha chain (Gly17Asp) with a review of similar mutations resulting in abnormal knob A.
Congenital dysfibrinogenemias are characterized by biosynthesis of a structurally abnormal fibrinogen molecule that exhibits reduced functional levels compared with the level of fibrinogen antigen. To date a large number of mutations have been identified in patients with dysfibrinogenemia. Mutations occurring at the thrombin cleavage site (Arg16-Gly17 in the mature alpha-chain) at the amino-terminal end of the fibrinogen alpha chain are a common cause of the disease. These mutations causing abnormal fibrin polymerization are associated with different phenotypes. Here, we report the identification of a novel heterozygous missense mutation of Glycine 17 (Gly17Asp) in a female patient with mild bleeding manifestations, and compare it with other previously reported mutations also resulting in abnormal knob A.


The Effect of GLUT1 and HIF-1α Expressions on Glucose Uptake and Patient Survival in Non-Small-Cell Lung Carcinoma.
Lung cancer is the second-most-common cancer while being the leading cause of cancer deaths worldwide. It has been found that glucose transporter 1 (GLUT1) and hypoxia-inducible factor 1α (HIF-1α) are overexpressed in various malignancies and that they correlate with the maximum standard uptake values (SUVmax) on 18F-fluorodeoxyglucose-positron emission tomography/computed tomography (18F-FDG PET/CT) and poor prognosis. In this study, we aim to evaluate the relationship between the SUVmax, GLUT1, and HIF-1α expression with primary tumor size, histological type, lymph node metastases, and patient survival. Of the 48 patients with non-small-cell lung cancer, those with squamous cell carcinomas (SCCs) had significantly higher GLUT1 and HIF-1α immunohistochemical expressions in comparison to adenocarcinomas (ACs), while there was no statistically significant difference in FDG accumulation between them. No significant correlation was noted between either GLUT1 or HIF-1α protein expression and FDG uptake and overall survival. However, an analysis of tumor transcriptomics showed a significant difference in overall survival depending on mRNA expression; patients with SCC and high HIF-1α levels survived longer compared to those with low HIF-1α levels, while patients with AC and low GLUT1 levels had a higher average survival time than those with high GLUT1 levels. Further studies are needed to determine the prognostic value of the expression of these factors depending on the histologic type.


Targeting the NLRP3 inflammasome and associated cytokines in scleroderma associated interstitial lung disease.
SSc-ILD (scleroderma associated interstitial lung disease) is a complex rheumatic disease characterized in part by immune dysregulation leading to the progressive fibrotic replacement of normal lung architecture. Because improved treatment options are sorely needed, additional study of the fibroproliferative mechanisms mediating this disease has the potential to accelerate development of novel therapies. The contribution of innate immunity is an emerging area of investigation in SSc-ILD as recent work has demonstrated the mechanistic and clinical significance of the NLRP3 inflammasome and its associated cytokines of TNFα (tumor necrosis factor alpha), IL-1β (interleukin-1 beta), and IL-18 in this disease. In this review, we will highlight novel pathophysiologic insights afforded by these studies and the potential of leveraging this complex biology for clinical benefit.


Incidence assessment of rotavirus and adenovirus associated acute gastroenteritis cases in early childhood.
This study was undertaken to give an insight into the incidence of acute gastroenteritis cases of rotaviral/adenoviral aetiology in patients presenting to the emergency room of an inner-city government teaching hospital. Group A rotavirus and adenovirus serotype 40-41 antigen results were obtained via immunochromatography. In 2007, there were 1543 patients with gastroenteritis between 0-5 years of age whose stool samples were tested for rota and adenovirus, of whom 386 (25%) had positive stool samples for rotavirus, and 133 (8.6%) for adenovirus serotype 40-41. The majority of rotavirus (74.6%) and adenovirus (73%) cases were between 0-2 years of age. The peak season for rotavirus gastroenteritis was January (44%) and February (50.6%), whereas July (9.7%) and August (9%) were months of low incidence. For enteric adenoviral infections summer was the peak season, with August (20.9%) and July (17.3%) being the foremost months. Among the viral gastroenteritis cases, rotavirus infections were in the majority. A seasonal trend emerges for viral gastroenteritis: Rota virus infections are most frequently seen in winter whereas adenoviral infections prefer summer months. Both viruses mostly affect children up to 2 years.


Gastric MUC5AC and MUC6 are large oligomeric mucins that differ in size, glycosylation and tissue distribution.
Gastric MUC5AC and MUC6 mucins were studied using polyclonal antibodies. Immunohistochemistry showed MUC5AC to originate from the surface epithelium, whereas MUC6 was produced by the glands. Mucins from the surface epithelium or glands of corpus and antrum were purified using CsCl/4M guanidinium chloride density-gradient centrifugation. MUC5AC appeared as two distinct populations at 1.4 and 1.3 g/ml, whereas MUC6, which was enriched in the gland tissue, appeared at 1.45 g/ml. Reactivity with antibodies against the Le(b) structure (where Le represents the Lewis antigen) followed the MUC5AC distribution, whereas antibodies against the Le(y) structure and reactivity with the GlcNAc-selective Solanum tuberosum lectin coincided with MUC6, suggesting that the two mucins are glycosylated differently. Rate-zonal centrifugation of whole mucins and reduced subunits showed that both gastric MUC5AC and MUC6 are oligomeric glycoproteins composed of disulphide-bond linked subunits and that oligomeric MUC5AC was apparently smaller than MUC6. A heterogeneous population of 'low-density' MUC5AC mucins, which were smaller than the 'high-density' ones both before and after reduction, reacted with an antibody against a variable number tandem repeat sequence within MUC5AC, suggesting that they represent precursor forms of this mucin. Following ion-exchange HPLC, both MUC5AC and MUC6 appeared as several distinct populations, probably corresponding to 'glycoforms' of the mucins, the most highly charged of which were found in the gland tissue.


Discrimination of crude and processed rhubarb products using a chemometric approach based on ultra fast liquid chromatography with ion trap/time-of-flight mass spectrometry.
Crude rhubarb subjected to different processing procedures will produce different therapeutic effects that are possibly due to processing-induced variation in chemical composition. In this study, a chemometric approach based on ultra fast liquid chromatography with ion trap/time-of-flight mass spectrometry was established to systematically investigate the chemical variations of rhubarb induced by different processing methods. The approach was validated based on pooled quality-control samples from two perspectives: the individual properties of variables and the bulk properties of samples. Orthogonal partial least squares discriminant analysis was introduced to compare the differences between crude and processed rhubarb products. A total of 20 significantly different markers were screened out and unambiguously/tentatively characterized. This research proved that a chemometric method based on ultra fast liquid chromatography with ion trap/time-of-flight mass spectrometry can comprehensively analyze the chemical variation of herbal medicine and provide evidence for a deeper understanding of the pharmacological activities of processed rhubarb products.


The alternative life of RNA-sequencing meets single molecule approaches.
The central dogma of RNA processing has started to totter. Single genes produce a variety of mRNA isoforms by mRNA modification, alternative polyadenylation (APA), and splicing. Different isoforms, even those that code for the identical protein, may differ in function or spatiotemporal expression. One option of how this can be achieved is by the selective recruitment of trans-acting factors to the 3'-untranslated region of a given isoform. Recent innovations in high-throughput RNA-sequencing methods allow deep insight into global RNA regulation, whereas novel imaging-based technologies enable researchers to explore single RNA molecules during different stages of development, in different tissues and different compartments of the cell. Resolving the dynamic function of ribonucleoprotein particles in splicing, APA, or RNA modification will enable us to understand their contribution to pathological conditions.


Pseudodeficiencies of arylsulfatase A and galactocerebrosidase activities.
Pseudodeficiency is defined as the in vitro measurement of low activity (usually under 15% of the normal mean for controls) of an enzyme in a healthy person. They may be hard to distinguish from presymptomatic people who will present with adult-onset clinical disease. The finding of healthy people with low arylsulfatase A and galactocerebrosidase activities is well documented. This confuses the laboratory doing testing and the clinician providing the sample. Therefore confirmation of a diagnosis of metachromatic leukodystrophy and Krabbe disease, as well as accurate identification of carriers, requires additional testing including 14C-sulfatide loading in cultured skin fibroblasts, examination of urine for excretion of undegraded lipids, examination of enzyme levels in additional family members including grandparents, and molecular analysis of DNA samples for known mutations.


[Related substitutions in the small segment of Old World hantavirus genome].
Whether there were related nucleotide substitutions in the S-segments of the genome of Tula, Puumala, Hantaan, Dorava/Belgrad, and Seoul viruses was studied. The significance of the correlations found in nucleotide substitutions was estimated by the level of mutual information. The majority of the correlated changes were synonymous substitutions. The correlations were mostly restricted to non-synonymous substitutions sites: Tula 258 (a.a.) and Dobrava/Belgrad (56 a.a.). In the genome of Puumala, both synonymous (204, 215, and 254 a.a.) and non-synonymous (304 a.a.) changes occurred. For Hantaan virus, the related correlations were less frequent. For Seoul virus, such correlations were not revealed. Hence, for some viruses, the selection of mutation proceeded as related at several positions in a segment. The evolution of virus sequences may depend on the number of available correlations of nucleotide substitutions in the segment.


Transthoracic intracardiac catheters in pediatric cardiac patients: A single-center experience.
Transthoracic intracardiac catheters are frequently inserted in children during congenital heart surgery for monitoring and vascular access purposes. Their use entails a small potential risk. We aimed to evaluate both catheter-associated morbidities related to maintenance and removal of transthoracic intracardiac catheters in pediatric cardiac patients, and predictors for catheter-associated adverse events. Single-center retrospective cohort study of prospectively collected data of children aged 0-14 years receiving a transthoracic intracardiac catheter inserted in the operating room during 7 consecutive years at the University Children's Hospital Zurich. A total of 115 transthoracic intracardiac catheters were placed in 112 patients: 45 right atrial, 68 left atrial, and 2 pulmonary artery catheters. Five catheters (4.3%) had to be removed due to catheter-associated adverse events (infection, 2; nonfunction, 2; and leakage 1). After catheter removal, 19% of patients suffered adverse events, these were minor in 16 (14%) and serious in 6 (5.1%) (symptomatic bleeding in four (3.5%) patients, pericardial tamponade leading to death in one (0.8%), and tension pneumothorax in one (0.8%)). Catheter position in the right atrium and the need for platelet transfusion prior to removal were risk factors for adverse events. Transthoracic intracardiac catheters are useful in the management of specific patient groups with complex congenital heart defects. Adverse events do occur; most of them do not require intervention. The insertion technique plays an important role in avoiding adverse events. Strict guidelines for the use and removal of transthoracic intracardiac catheters are required. Low platelet count should delay catheter removal. The wealth of information and therapeutic options offered by these catheters appear to outweigh the associated potential adverse events in this specific patient group.


Study of the physical properties of whey protein isolate and gelatin composite films.
The relationships between the microstructural and physical properties of the whey protein isolate and gelatin (WPI/gelatin) composite films were investigated in the present work. Through the electrostatic effects at pH 8, WPI and gelatin molecules could form compact aggregates in solution, where a remarkable shrinkage of the gelatin molecules was observed, when the WPI/gelatin mass ratio was close to 50W:50G. FT-IR analysis indicated that hydrogen bonding also involved the aggregation and film-forming process. The melting temperature of the 50W:50G composite film increased by 9 degrees C compared with the single component films. However, this aggregation process also made the film network microstructure discontinuous, and led to a decline of the puncture strength of the film near 50W:50G; in contrast, the deformation and water vapor permeability of the composite films increased with the gelatin content, while the moisture content and solubility did not show significant variations.


Histiocytic lymphoma and malignant angioendotheliomatosis: one disease or two?
The case history of a patient with diffuse histiocytic lymphoma and skin lesions characteristic of malignant angioendotheliomatosis is reported. The patient initially responded to aggressive chemotherapy but quickly had a relapse, CNS disease developed, and the patient died one year after diagnosis. Microscopic, ultrastructural, and surface membrane studies showed that the intravascular tumor cells were not of endothelial origin. The morphologic similarity of the malignant intravascular cells and peripheral blood cells, as well as the demonstration of surface membrane immunoglobulin on malignant blood cells suggested that, in some cases, unusual features of malignant lymphoma may be confused with malignant angioendotheliomatosis.


Somatostatin (SRIF) prevents natural motoneuron cell death in embryonic chick spinal cord.
Natural motoneuron cell death is a developmental process that effects the loss of about 50% of the cells in the lateral motor column of the spinal cord. The present study demonstrates that the systemic treatment of developing chick embryos with somatostatin (somatotropin release-inhibiting factor, SRIF) during the period of natural motoneuron cell death resulted in a 13-22% increase in the number of surviving motoneurons, suggesting that SRIF may be an endogenous contributor to motoneuron survival during normal development. It is hypothesized that SRIF may act, through its ability to reduce intraneuronal calcium, as an endogenous antagonist of neuronal death both during development and in the course of adult neurodegenerative diseases.


Global low back pain prevalence and years lived with disability from 1990 to 2017: estimates from the Global Burden of Disease Study 2017.
Low back pain (LBP) is a common musculoskeletal problem globally. Updating the prevalence and burden of LBP is important for researchers and policy makers. This paper presents, compares and contextualizes the global prevalence and years lived with disability (YLDs) of LBP by age, sex and region, from 1990 to 2017. Data were extracted from the GBD (the Global Burden of Disease, Injuries, and Risk Factors Study) 2017 Study. Age, sex and region-specific analyses were conducted to estimate the global prevalence and YLDs of LBP, with the uncertainty intervals (UIs). The age-standardized point prevalence of LBP was 8.20% (95% UI: 7.31-9.10%) in 1990 and decreased slightly to 7.50% (95% UI: 6.75-8.27%) in 2017. The prevalent numbers of people with LBP at any one point in time in 1990 was 377.5 million, and this increased to 577.0 million in 2017. Age-standardized prevalence of LBP was higher in females than males. LBP prevalence increased with age, and peaked around the ages of 80 to 89 years, and then decreased slightly. Global YLDs were 42.5 million (95% UI: 30.2 million-57.2 million) in 1990 and increased by 52.7% to 64.9 million (95% UI: 46.5 million-87.4 million) in 2017. YLDs were also higher in females than males and increased initially with age; they peaked at 35-39 years of age in 1990, before decreasing, whereas in 2017, they peaked at 45-49 years of age, before decreasing. Western Europe had the highest number of LBP YLDs. Globally, LBP is the leading global cause of YLDs. Greater attention is urgently needed to mitigate this increasing burden and the impact it is having on health and social systems.


Cancer and the environment.
The evidence that problems in the environment are causing cancer is reviewed. Although there is concern that our environment is deteriorating, there is little evidence that this is leading to an increased cancer burden as, although rates in the elderly have been increasing, rates in younger people are declining. It is estimated that only about 5% of cancers are due to environmental factors and more than half of these are due to the geophysical properties of the environment, rather than man-made pollutants. Hazards to which people are exposed at work do contribute to increased cancer rates. Once such a hazard is identified then legislation is used to limit, or eliminate, exposure to it, both at work and in the environment. This paper describes certain specific hazards, but concludes that the largest contribution to cancer prevention would be a reduction in smoking rather than any environmental measure.


Serum lidocaine concentrations following subcutaneous administration.
Serum lidocaine concentrations were determined following subcutaneous administration for local anesthesia in the management of lacerations in the emergency room setting. Thirty patients received doses of lidocaine hydrochloride 1% solution ranging from 10 to 300 mg. Venous blood samples were drawn 15, 30, 45, and 60 minutes after lidocaine administration. Serum lidocaine determinations were made using an immunoassay system and verified by gas chromatography. There was no evidence of lidocaine absorption from the subcutaneous injection sites. There were no detectable concentrations of lidocaine in any of the patient blood samples. The absorption characteristics of subcutaneously administered lidocaine appear to be altered in traumatized tissue.


Role of Feedback during Evaluation in Improving Emergency Medicine Residents' Skills; an Experimental Study.
Evaluation of students' learning in clinical education system is one of the most important and challenging issues that facilities in this field have been facing. The present study aimed to evaluate the role of feedback during evaluation in increasing emergency medicine residents' clinical skills. The present experimental study was performed on all second year emergency medicine residents of two educational hospitals, Tehran, Iran, with switching replications design and before-after method. They were randomly allocated to two groups (with or without feedback) and evaluated three times regarding chest ultrasonography for trauma patients, using direct observation of procedural skills (DOPS) and valid and reliable checklist. Data were analyzed using SPSS 20. 30 emergency medicine residents with the mean age of 36.63 ± 30.30 years were allocated to two equal groups (56.7% male). Studied groups were similar regarding the baseline characteristics. In both groups, obtained scores showed a significant increase from the first to the third evaluation (p < 0.001). Mean scores of first and second evaluations were 10.24 ± 0.77, 17.73 ± 0.46 in feedback receivers and 9.73 ± 0.77 and 12.13 ± 0.47 in others (p < 0.001). Mean third score after switching groups were 18.53 ± 0.22 in feedback receivers and 18.99 ± 0.22 in others (p = 0.213). Based on the findings of the present study, giving feedback after evaluating the second year emergency medicine residents regarding chest ultrasonography for trauma patients, led to a significant improvement in their scores in future evaluations and consequently their skill.


Evaluation of Long-Term Quality of Life Using the Foot and Ankle Outcome Score (FAOS) Questionnaire in Patients Treated by Minimally Invasive Reduction and Percutaneous Stabilization of Intra-Articular Calcaneal Fractures.
BACKGROUND Treatment of displaced intra-articular calcaneal fractures is controversial. Choosing the optimal surgical technique is very important for patient quality of life and activity. In this study, we asked the question: "What is the long-term quality of life of patients after intra-articular calcaneal fractures treated by minimally invasive reduction and percutaneous stabilization (MIRPS)?". MATERIAL AND METHODS We included 51 patients - 45 males (88%) and 6 females (12%) - who underwent MIRPS of intra-articular calcaneal fractures. The males were ages 22-63 years, with a mean age of 46 years, while the females were aged 31-63, with a mean age of 47 years. The FAOS (Foot and Ankle Outcome Score) survey was used. RESULTS Women's FAOS scores were 72-95%, with a mean of 82%, and varied according to type of fracture, surgery method used, and comorbid fractures. Men's FAOS scores were 50-95%, with a mean of 84%, and varied according to type of fracture, surgery method used, and comorbid fractures. CONCLUSIONS According to set criteria regarding the FAOS scale, mainly good and very good results were observed in patients treated surgically for intra-articular calcaneus fractures using MIRPS. Westhues' method scored a significantly higher foot rating than W-R (Westhues'-Rąpała method). Patients with TTF (tongue-type fracture) scored higher in the FAOS than patients treated with JDTF (joint depression-type fracture). In other cases, no significant differences were observed.


Case report of Lewy body disease mimicking Creutzfeldt-Jakob disease in a 44-year-old man.
Few patients are reported with dementia with Lewy bodies before fifty years-old, which may partly reflect the difficulty of accurate diagnosis in young population. We report the case of a 44-year-old male with pathologically confirmed sporadic dementia with Lewy bodies, who did not fulfil the revised clinical criteria for this disease. We document this atypical case with clinical and cognitive evaluation, imaging, biochemistry, genetics and pathology investigations. Creutzfeldt-Jakob disease was first suspected in this patient with no previous medical history, who developed acute and rapid cognitive impairment, L-dopa-non-responsive parkinsonism, and delusion. Positive 14-3-3 protein was initially detected in cerebrospinal fluid and until the late stages of the disease. Severe atrophy with no diffusion hypersignal was found on structural MRI as well as an extensive hypometabolism on (18)F-FDG-PET, in comparison to age-matched healthy volunteers. Genetic investigation found no alpha-synuclein gene mutation. The patient died within 5 years, and post-mortem examination found numerous Lewy bodies and Lewy neurites consistent with pure Lewy body disease. This comprehensively described case illustrates that dementia with Lewy bodies can occur in young patients with atypical clinical presentation. Biochemistry and neuroimaging investigations can sometimes be insufficient to allow accurate diagnostic. More specific markers to support such diagnosis are needed.


Granular cell tumor of the esophagus: a study of seven cases diagnosed by histologic examination of endoscopic biopsies.
Among the benign tumors of the esophagus, the discovery of a granular cell tumor is exceptional. Although endoscopy permits recognition of this tumor and supports its benign nature, only histologic examination of the endoscopic biopsy specimen permits one to determine its precise nature. The endoscopic appearance of esophageal granular cell tumor ranges from a plaque-like thickening of the mucosa to a polypoid mass. We describe here seven cases of granular cell tumor of the esophagus diagnosed by histologic examination of endoscopic biopsy specimens. We believe the actual incidence of this tumor in this location might be greater if every esophagus were given as much attention at endoscopic examination and at autopsy.


Antibiotic resistance and mecA characterization of coagulase-negative staphylococci isolated from three hotels in London, UK.
Antibiotic resistance in bacteria isolated from non-healthcare environments, is a potential problem to public health. In our survey a total of 71 coagulase negative staphylococci (CNS) belonging to 11 different species were isolated from three large hotels in London, UK. The most prevalent species was Staphylococcus haemolyticus, with S. hominis, S. warneri, S. cohnii, and Staphylococcus epidermidis commonly detected. Antimicrobial susceptibilities and carriage of the mecA gene were determined for all of these isolates. Most (85.9%) staphylococci were resistant to multiple antibiotics with all displaying increased susceptibility toward penicillin, fusidic acid, erythromycin, and cefepime. Twenty-one (29.5%) of the isolates were mecA positive, however MIC values to oxacillin, normally associated with the carriage of mecA, varied widely in this group (from 0.06 to 256 mg/L). Fifteen of the twenty-one mecA positive isolates carried SCCmec of these seven were type V, one type I, one type II, and one type IV. Additionally, five of these 15 isolates carried a previously unreported type, 1A, which involves an association between class A mec complex and ccr type 1. The remaining six of the 21 isolates were non-typeable and carried a combination of class A mec complex and ccrC. In addition to this, we also report on new MLST types which were assigned for five S. epidermidis isolates. Four out of these five isolates had MICs between 0.06 and 256 mg/L to oxacillin and would be regarded as clinically susceptible but one isolate had a high oxacillin MIC of 256 mg/L. We demonstrated widespread multiple drug resistance among different staphylococcal species isolated from non-healthcare environments highlighting the potential for these species to act as a reservoir for methicillin and other forms of drug resistance.


Mortality study of employees at a chemical manufacturing plant using administrative databases.
This study investigated mortality in a cohort of 1,988 male workers at a chemical manufacturing plant (1981-2011) and evaluated the quality of the results obtained using administrative databases. Information about the workers was obtained from the archives of the Italian National Institute for Social Insurance. Vital status and causes of death were ascertained through record linkage with electronic archives and follow-up mailing. Regional reference rates were used to calculate standardized mortality ratios (SMRs) and 90% confidence intervals (CI). The analysis showed increased SMR for selected cancers of a priori interest: respiratory system (SMR: 126.8; 90%CI: 105-152), pleura (330.5; 90%CI 164-596), and non-Hodgkin lymphoma (196.1; 90%CI 102-342). The results indicate an effect of hazardous exposures among workers in this chemical manufacturing plant. Using administrative databases to construct historical cohorts is an efficient method in time and resources, for estimating the risk of mortality and generating hypotheses. Am. J. Ind. Med. 59:866-876, 2016. © 2016 Wiley Periodicals, Inc.


Isoform-selective physical coupling of TRPC3 channels to IP3 receptors in smooth muscle cells regulates arterial contractility.
Inositol 1,4,5-trisphosphate (IP(3))-induced vasoconstriction can occur independently of intracellular Ca(2+) release and via IP(3) receptor (IP(3)R) and canonical transient receptor potential (TRPC) channel activation, but functional signaling mechanisms mediating this effect are unclear. Study mechanisms by which IP(3)Rs stimulate TRPC channels in myocytes of resistance-size cerebral arteries. Immunofluorescence resonance energy transfer (immuno-FRET) microscopy using isoform-selective antibodies indicated that endogenous type 1 IP(3)Rs (IP(3)R1) are in close spatial proximity to TRPC3, but distant from TRPC6 or TRPM4 channels in arterial myocytes. Endothelin-1 (ET-1), a phospholipase C-coupled receptor agonist, elevated immuno-FRET between IP(3)R1 and TRPC3, but not between IP(3)R1 and TRPC6 or TRPM4. TRPC3, but not TRPC6, coimmunoprecipitated with IP(3)R1. TRPC3 and TRPC6 antibodies selectively inhibited recombinant channels, but only the TRPC3 antibody blocked IP(3)-induced nonselective cation current (I(Cat)) in myocytes. TRPC3 knockdown attenuated immuno-FRET between IP(3)R1 and TRPC3, IP(3)-induced I(Cat) activation, and ET-1 and IP(3)-induced vasoconstriction, whereas TRPC6 channel knockdown had no effect. ET-1 did not alter total or plasma membrane-localized TRPC3, as determined using surface biotinylation. RT-PCR demonstrated that C-terminal calmodulin and IP(3)R binding (CIRB) domains are present in myocyte TRPC3 and TRPC6 channels. A peptide corresponding to the IP(3)R N-terminal region that can interact with TRPC channels activated I(Cat). A TRPC3 CIRB domain peptide attenuated IP(3)- and ET-1-induced I(Cat) activation and vasoconstriction. IP(3) stimulates direct coupling between IP(3)R1 and membrane-resident TRPC3 channels in arterial myocytes, leading to I(Cat) activation and vasoconstriction. Close spatial proximity between IP(3)R1 and TRPC3 establishes this isoform-selective functional interaction.


Development of a screening algorithm for Alzheimer's disease using categorical verbal fluency.
We developed a weighted composite score of the categorical verbal fluency test (CVFT) that can more easily and widely screen Alzheimer's disease (AD) than the mini-mental status examination (MMSE). We administered the CVFT using animal category and MMSE to 423 community-dwelling mild probable AD patients and their age- and gender-matched cognitively normal controls. To enhance the diagnostic accuracy for AD of the CVFT, we obtained a weighted composite score from subindex scores of the CVFT using a logistic regression model: logit (case) = 1.160+0.474× gender +0.003× age +0.226× education level - 0.089× first-half score - 0.516× switching score -0.303× clustering score +0.534× perseveration score. The area under the receiver operating curve (AUC) for AD of this composite score AD was 0.903 (95% CI = 0.883 - 0.923), and was larger than that of the age-, gender- and education-adjusted total score of the CVFT (p<0.001). In 100 bootstrapped re-samples, the composite score consistently showed better diagnostic accuracy, sensitivity and specificity for AD than the total score. Although AUC for AD of the CVFT composite score was slightly smaller than that of the MMSE (0.930, p = 0.006), the CVFT composite score may be a good alternative to the MMSE for screening AD since it is much briefer, cheaper, and more easily applicable over phone or internet than the MMSE.


Experienced radio-guided surgery teams can successfully perform minimally invasive radio-guided parathyroidectomy without intraoperative parathyroid hormone assays.
Minimally invasive parathyroidectomy is an accepted treatment option for primary hyperparathyroidism. The need for intraoperative parathyroid hormone assays (iPTH) to confirm adenoma removal remains controversial. We studied minimally invasive radio-guided parathyroidectomy (MIRP) performed using preoperative sestamibi localization studies, intraoperative gamma detection probe, and the selective use of frozen section pathology without the use of iPTH. This is a single institution review of patients with primary hyperparathyroidism treated with MIRP by surgeons experienced in radio-guided surgery between October 1, 1998 and July 15, 2005. Information was obtained by reviewing computer medical records as well as contacting primary care physicians. Factors evaluated included laboratory values, pathology results, and evidence of recurrence. One hundred forty patients were included with a median preoperative calcium level of 11.3 mg/dL (range, 9.6-17) and a PTH level of 147 pg/mL (range, 19-5042). The median postoperative calcium level was 9.3 mg/dL. All patients were initially eucalcemic postoperatively except for one who had normal parathyroid levels. However, five (4%) patients required re-exploration for various reasons. Of the failures, one was secondary to the development of secondary hyperparathyroidism, and therefore would not have benefited from iPTH, one had thyroid tissue removed at the first operation, and three developed evidence of a second adenoma. One of these three patients had a drop in PTH level from 1558 pg/mL preoperatively to 64 pg/mL on postoperative Day 1, indicating that iPTH would not have prevented this failure. Thus, only three (2.1%) patients could have potentially benefited from the use of iPTH. MIRP was successful in 96 per cent of patients using a combination of preoperative sestamibi scans, intraoperative localization with a gamma probe, and the selective use of frozen pathology. This correlates with reported success rates of 95 per cent to 100 per cent using iPTH. We conclude that minimally invasive parathyroidectomy can be successfully performed without using iPTH assays.


Emerging strategies for RNA interference (RNAi) applications in insects.
RNA interference (RNAi) in insects is a gene regulatory process that also plays a vital role in the maintenance and in the regulation of host defenses against invading viruses. Small RNAs determine the specificity of the RNAi through precise recognition of their targets. These small RNAs in insects comprise small interfering RNAs (siRNAs), micro RNAs (miRNAs) and Piwi interacting RNAs (piRNAs) of various lengths. In this review, we have explored different forms of the RNAi inducers that are presently in use, and their applications for an effective and efficient fundamental and practical RNAi research with insects. Further, we reviewed trends in next generation sequencing (NGS) technologies and their importance for insect RNAi, including the identification of novel insect targets as well as insect viruses. Here we also describe a rapidly emerging trend of using plant viruses to deliver the RNAi inducer molecules into insects for an efficient RNAi response.


Higd-1a interacts with Opa1 and is required for the morphological and functional integrity of mitochondria.
The activity and morphology of mitochondria are maintained by dynamic fusion and fission processes regulated by a group of proteins residing in, or attached to, their inner and outer membranes. Hypoxia-induced gene domain protein-1a (Higd-1a)/HIMP1-a/HIG1, a mitochondrial inner membrane protein, plays a role in cell survival under hypoxic conditions. In the present study, we showed that Higd-1a depletion resulted in mitochondrial fission, depletion of mtDNA, disorganization of cristae, and growth retardation. We demonstrated that Higd-1a functions by specifically binding to Optic atrophy 1 (Opa1), a key element in fusion of the inner membrane. In the absence of Higd-1a, Opa1 was cleaved, resulting in the loss of its long isoforms and accumulation of small soluble forms. The small forms of Opa1 do not interact with Higd-1a, suggesting that a part of Opa1 in or proximal to the membrane is required for that interaction. Opa1 cleavage, mitochondrial fission, and cell death induced by dissipation of the mitochondrial membrane potential were significantly inhibited by ectopic expression of Higd-1a. Furthermore, growth inhibition due to Higd-1a depletion could be overcome by overexpression of a noncleavable form of Opa1. Collectively, our observations demonstrate that Higd-1a inhibits Opa1 cleavage and is required for mitochondrial fusion by virtue of its interaction with Opa1.


Caspase-9-induced mitochondrial disruption through cleavage of anti-apoptotic BCL-2 family members.
Mitochondrial disruption during apoptosis results in the release of cytochrome c that forms apoptosomes with Apaf-1 and caspase-9. Activation of caspase-9 by dimerization in apoptosomes then triggers a caspase signaling cascade. In addition, other apoptosis signaling molecules released from the mitochondrion, such as apoptosis-inducing factor and endonuclease G, may induce caspase-9-independent apoptosis. To determine the signaling events induced by caspase-9, we used chemically induced dimerization for specific activation of caspase-9. We observed that caspase-9 dimerization resulted in the loss of mitochondrial membrane potential and the cleavage of anti-apoptotic Bcl-2, Bcl-xL, and Mcl-1. Moreover, cleavage-resistant Bcl-2, Bcl-xL, or Mcl-1 potently inhibited caspase-9-dependent loss of mitochondrial membrane potential and the release of cytochrome c. Our data suggest that a caspase-9 signaling cascade induces feedback disruption of the mitochondrion through cleavage of anti-apoptotic Bcl-2, Bcl-xL, and Mcl-1.


Isolation of NF-E2-related factor 2 (Nrf2), a NF-E2-like basic leucine zipper transcriptional activator that binds to the tandem NF-E2/AP1 repeat of the beta-globin locus control region.
Hypersensitive site 2 located in the beta-globin locus control region confers high levels of expression to the genes of the beta-globin cluster. A tandem repeat of the consensus sequence for the transcription factors AP1 and NF-E2 (activating protein 1 and nuclear factor erythroid 2, respectively) is present within hypersensitive site 2 and is absolutely required for strong enhancer activity. This sequence binds, in vitro and in vivo, to ubiquitous proteins of the AP1 family and to the recently cloned erythroid-specific transcription factor NF-E2. Using the tandem repeat as a recognition site probe to screen a lambda gt11 cDNA expression library from K562 cells, we isolated several DNA binding proteins. Here, we report the characterization of one of the clones isolated. The gene, which we named Nrf2 (NF-E2-related factor 2), is encoded within a 2.2-kb transcript and predicts a 66-kDa protein with a basic leucine zipper DNA binding domain highly homologous to that of NF-E2. Although Nrf2 is expressed ubiquitously, a role of this protein in mediating enhancer activity of hypersensitive site 2 in erythroid cells cannot be excluded. In this respect, Nrf2 contains a powerful acidic activation domain that may participate in the transcriptional stimulation of beta-globin genes.


Inhibition of topoisomerase I by anthracycline antibiotics: evidence for general inhibition of topoisomerase I by DNA-binding agents.
Inhibition of eukaryotic topoisomerase I by daunomycin and structurally modified daunomycin analogues is demonstrated. These studies suggest that binding of the drug to DNA, at low ratios of drug to base pairs of DNA, is sufficient for inhibition that is nonspecific, i.e., inhibition that does not involve the trapping of covalent DNA-topoisomerase I cleavable complexes. Inhibition of numerous DNA-processing enzymes by DNA-binding agents is also implicated.


Sperm competition as an under-appreciated factor in domestication.
Humans created an environment that increased selective pressures on subgroups of those species that became domestic. We propose that the domestication process may in some cases have been facilitated by changes in mating behaviour and resultant sperm competition. By adapting to sperm competition, proto-domestic animals could potentially have outcompeted their wild counterparts in human-constructed niches. This could have contributed to the restriction of gene flow between the proto-domesticates and their wild counterparts, thereby promoting the fixation of other domestication characteristics. Further to this novel perspective for domestication, we emphasize the general potential of postcopulatory sexual selection in the restriction of gene flow between populations, and urge more studies.