Scaling trace organic contaminant adsorption capacity by granular activated carbon.
The role of particle size on the reduction of granular activated carbon (GAC) adsorption capacity for trace organic contaminants by dissolved organic matter (DOM) is examined and applied to performance scale-up. The adsorption capacity reduction, termed fouling, must be scalable in order to use bench scale tests, such as the rapid small-scale column test (RSSCT) to predict full-scale breakthrough. Equilibrium adsorption capacity tests with GAC preloaded with DOM and RSSCT breakthrough curves at three different GAC particle sizes indicate that GAC adsorption capacity is dependent on GAC particle size when DOM is present. Thus, the RSSCT cannot be expected to match full-scale results regardless of which RSSCT design approach is used (constant or proportional diffusivity), unless a scaling factor is applied to the results. Proportional diffusivity RSSCT breakthrough curves demonstrate that surface concentration of DOM is not a good measure of fouling. It is hypothesized that pore blockage is the mechanism responsible for the dependence on particle size. As GAC particle size increases, the microporous surface area behind a constricted pore also increases. The result is lower adsorption capacity per mass of adsorbent in the larger GAC particles. A scaling methodology for equilibrium and breakthrough data is presented that accounts for the dependence of NOM preloading effects on GAC particle diameter.


Host genetic background determines whether IL-18 deficiency results in increased susceptibility or resistance to murine Leishmania major infection.
Interleukin-18 (IL-18) plays an important role in innate and acquired immunity. IL-18 gene deficient (IL-18-/-) mice of the 129 x CD1 strain were reported to be more susceptible to Leishmania major infection than the wild-type mice. In contrast IL-18-/- mice of the C57BL/6 background were found to be as resistant as the wild-type (WT) mice. To resolve this discrepancy, IL-18 gene deficiency was introduced by backcrossing on to the highly susceptible BALB/c, or the moderately resistant DBA/1 backgrounds. Here we have demonstrated that BALB/c IL-18-/- mice were more resistant to L. major infection than WT BALB/c mice, whereas DBA/1 IL-18-/- mice were markedly more susceptible than their WT littermates. BALB/c IL-18-/- mice produced less IFNgamma and IL-4, whereas DBA/1 IL-18ko mice produced more IFNgamma and IL-4 than their respective WT controls. These result clearly demonstrate that the role of IL-18 in resistance or susceptibility to L. major is determined by host genetic background.


[A case-control study on risk factors of type 2 diabetes mellitus related chronic complications in Baoding city].
To recognize the main risk factors and to provide evidence for prevention and intervention of type 2 diabetes chronic complications. A hospital-based frequency matched case-control study including 200 type 2 diabetes mellitus (T2DM) chronic complications cases and 200 controls without T2DM chronic complications was carried out in Baoding city. Relationships between factors and T2DM chronic complications were analyzed by non-conditional uni-variate and multivariate logistic regression methodologies. High C-reactive protein (CRP) (OR = 5.568), dyslipidemia (OR = 4.400), high blood urea nitrogen (BUN) (OR = 4.399), high low density lipoprotein-cholesterol (LDL-C) (OR = 3.594), time of hospitalization (OR = 2.612), grease food intake before developing DM (OR = 2.300), high HbA1c% (OR = 1.747), lack of exercise after the development of DM (OR = 1.672), duration of DM (OR = 1.509), mental stress (OR = 1.427), high-quality sleep (OR = 0.606), well control of blood glucose (OR = 0.517), well control of blood fat (OR = 0.299), insulin injections (OR = 0.155) etc. were all significantly associated with T2DM chronic complications. The main risk factors of T2DM chronic complications seemed to be related to high CRP, dyslipidemia, high BUN and high LDL-C. The main protective factors were insulin injections, well control of blood fat and blood glucose, good-quality of sleep, while the unique risk factors of cardiovascular disease seemed to be high LDL-C and mental stress. The unique risk factors of neuropathy were lack of exercise after developing DM and the amount of sweet food intake. The duration of DM appeared to be the common risk factor and the common protective factor on those three complications was insulin injection.


Effects of Cetylpyridinium Chloride on Phase and Rheological Behavior of the Diluted C(12)E(4)/Benzyl Alcohol/Water System.
The influence of a small amount of cetylpyridinium chloride on the phase diagram of the diluted C(12)E(4)/benzyl alcohol/water system is studied. The presence of the ionic surfactant results in the stabilization of the vesicles in relation to the open bilayers. The bilayer structures are less sensitive to shear effects than for the system without cationic surfactant. Moreover, the formation of the mixed micelle phase is also favored. The transition from spherical to rod micelles has been detected from viscosity measurements. The micelles located close to the two-phase region (at the lower amount of cationic surfactant) are the largest and most flexible micelles. Copyright 2000 Academic Press.


[The infection and molecular characteristics of Vibrio parahaemolyticus isolated from intestinal outpatient in two sentinel hospitals in Shanghai, 2010-2012].
To analyze virulence genes and molecular characteristics of Vibrio parahaemolyticus isolated from sporadic cases with diarrhea in tow sentinel hospitals of Shanghai, 2010-2012. A total of 2 729 stool samples were collected from two surveillance sentinel hospitals in Shanghai 2010-2012. Vibrio parahaemolyticus strains were isolated and identified from diarrhea out patients using TCBS agar plates and biochemical reactions. Thermostable direct hemolysingene (tdh), thermostable-related hemolysin gene (trh), hemolysin gene (tlh) were detected by multiplex PCR method. Isolates were analyzed by PFGE and MLST. The PFGE profiles were analyzed using BioNumerics software. A total of 30 clinical Vibrio parahaemolyticus strains isolated from 2 729 stool samples. The anually Vibrio parahaemolyticus isolation rate during 2010 to 2012 were 1.1%(11/973), 1.0%(11/1 120) and 1.3%(8/636) respectively. The PCR positive rates of virulence genes tlh, tdh and trh were 100%, 97% and 0 respectively. The Vibrio parahaemolyticus strains were divided into 13 PFGE types (P1-P13)and 3 ST types (ST-189, ST-799, ST-3). Among 13 PFGE types, P4 was the main PFGE type, accounting for 30%(9/30). P9, P10 were accounting for 12% (4/30) respectively, P1, P2, P12, P13 were accounting for 7%(2/30) respectively, the others types were 3%(1/30) respectively. MLST analysis results showed there are three ST types, ST3 was 84%(25/30), ST189 and ST799 were accounting for 13% (4/30) and 3% (1/30) respectively. The infection rate of Vibrio parahaemolyticus was not very high from 2010-2012 in Shanghai, all strains were positive for tlh and negative for trh. ST3 was the major type of Vibrio parahaemolyticus.


Histological markers in nasal mucosa of patients with Alzheimer's disease.
Neuropathological changes such as dystrophic neurites and the presence of abnormal tau protein in the olfactory system, including primary sensory cells and nerve fibres have previously been demonstrated in nasal mucosa tissue of patients with Alzheimer's disease (AD). These changes were detected in autopsy-derived material from histopathologically confirmed AD cases as well as in biopsy tissue from clinical severely ill AD patients. To investigate the potential usefulness for the early diagnosis of AD, we obtained biopsy tissue from olfactory mucosa from 5 clinically mild to moderate AD patients and stained for the presence of tau or beta-amyloid by immunocytochemistry using a panel of specific antibodies. No positive staining was found in any of the cases. For comparison, post-mortem olfactory tissue from AD patients with severe neuropathological changes (widespread neurofibrillary tangles and amyloid in the brain) was investigated. In these severe cases, tau immunoreactivity was found in fine nerve fibres in the lamina propria and in a few olfactory epithelial cells. These results are consistent with other reports showing that cytoskeletal changes and tau pathology in the olfactory epithelium are not primary (or specific) features of AD and may occur predominantly in late stages of the disease.


Atomoxetine for the treatment of attention-deficit/hyperactivity disorder in children and adolescents with bipolar disorders.
Children and adolescents with bipolar disorder (BD) have a high incidence of comorbid attention-deficit/hyperactivity disorder (ADHD). In this paper, we report a consecutive case series on 7 patients with pediatric BD and ADHD who were treated with atomoxetine-and all but one were also treated in conjunction with mood stabilizers. All patients were outpatients at the Stanford Pediatric Bipolar Disorders Clinic. Information on patients was collected in a retrospective chart review. All but 1 patient demonstrated significant improvement in symptoms of ADHD. No patients had episodes of hypomania or mania during the treatment period. Adverse effects of atomoxetine treatment included sedation, nausea, and decreased appetite. These cases suggest that atomoxetine may be a safe and effective treatment for ADHD in conjunction with mood stabilizers in children with BD.


Clinical features and management of pseudoaneurysmal bleeding after pancreatoduodenectomy.
A ruptured pseudoaneurysm is the most serious and life-threatening cause of postpancreatoduodenectomy (PD) hemorrhages. We have evaluated the clinical course and management of pseudoaneurysms after PD. Of 586 patients who underwent PD for periampullary tumors in Asan Medical Center between March 2003 and March 2011, 27 experienced pseudoaneurysmal bleeding. Bleeding developed at a median of 21 days (range, 8 to 45 days) after surgery, including 9 patients who developed bleeding more than 4 weeks after surgery. Before development of bleeding, 26 patients showed pancreatic fistula. Bleeding was developed from the gastroduodenal artery stump in 12 patients, the common hepatic artery in eight, the proper hepatic artery in five, and the left hepatic artery in two. Of the angiographic group, 21 patients underwent with microcoil embolization, four underwent stent insertion, and one experienced technical failure. Only one patient required emergent laparotomy without angiography. Of 25 patients with angiographic procedures, all patients achieved hemostasis. The mortality rate was 22.2 per cent (6 patients). Delayed hemorrhage after PD is closely associated with pancreatic fistula and carried a significantly higher mortality rate. The patients with pancreatic fistula should be carefully monitored, even more than 4 weeks after surgery. Selective microcoil embolization or stent graft is effective for pseudoaneurysmal bleeding.


Bluetongue virus RNA detection by RT-qPCR in blood samples of sheep vaccinated with a commercially available inactivated BTV-8 vaccine.
In 2008, a country-wide bluetongue virus 8 (BTV-8) vaccination campaign has been initiated in Austria, using a single commercial inactivated BTV-8 vaccine. Based on preliminary data, we hypothesised that vaccine-derived BTV RNA is transiently detectable by reverse transcription quantitative real-time PCR (RT-qPCR) in the blood of vaccinated animals. Thus BTV-8 vaccine was administered to five BTV-naïve adult sheep and blood samples were taken at various time-points post-vaccination. BTV RNA was detectable by several RT-qPCR methods in all five animals, mainly within the first 9 days post-vaccination. These results show that RT-qPCR based testing for BTV-infection may be influenced by vaccination with certain inactivated BTV-8 vaccines.


Spinal cord stimulation attenuates visceromotor reflexes in a rat model of post-inflammatory colonic hypersensitivity.
Spinal cord stimulation (SCS) has been found to relieve neuropathic and ischemic pain clinically and to attenuate a nociceptive reflex in an animal model of acute colonic hypersensitivity. The goal of the present study was to determine the effect of SCS in a rat model of post-inflammatory colonic hypersensitivity. Acute inflammation was induced in rats by a single enema of trinitrobenzenesulfonic acid (TNBS) (50 mg/kg, 0.5 ml, 25% EtOH). Control rats received a single saline enema. A visceromotor behavioral response (VMR), induced by innocuous colorectal distention (30 mm Hg, 10 min) was used to quantify the level of colonic sensitivity on day 3 and 30 post-enema. Prior to VMR testing, under general anesthesia, an electrode (cathode) was placed epidurally on the dorsal surface of the spinal cord at L1 with a paravertebral anode plate. Three to 7 days after implantation of the SCS electrode, the effect of SCS (50 Hz, 0.2 ms, amplitude 90% of motor threshold for 30 min) on colonic sensitivity was determined. On day 30, rats that had received a single TNBS enema were hypersensitive to innocuous colonic distention when compared to rats that received a saline enema (VMR/10 min: TNBS: 17.2+/-0.8 vs. Saline: 9.6+/-1.1, p<0.01). Spinal cord stimulation significantly reduced the VMR in the TNBS-enema group to a value that resembled the saline-enema group (VMR/10 min: TNBS: 11.2+/-1.2 vs. Saline: 10.0+/-1.0). This study provides the first evidence that SCS might be a potential therapeutic for the treatment of abdominal pain observed in patients with post-inflammatory irritable bowel syndrome.


Influence of intermolecular N-H...pi interactions on molecular packing and field-effect performance of organic semiconductors.
Charge transport in organic semiconductors is strongly dependent on their molecular packing modes in the solid state. Therefore, understanding the relationship between molecular packing and charge transport is imperative, both experimentally and theoretically. However, so far, the fundamental effects of solid-state packing and molecular interactions (e.g. N-H...pi) on charge transport need further elucidation. Herein, indolo[3,2-b]carbazole (ICZ) and a derivative thereof are used as examples to approach this scientific target. An interesting insight obtained thereby is that N-H...pi interactions among ICZ molecules facilitate charge transport for higher mobility. Subtle changes in the of N-H...pi interactions can significantly influence both the molecular packing and the charge-transport properties. Therefore, a method for exploiting intermolecular N-H...pi interactions would yield novel molecular systems with designable characteristics.


The effect of young children's faeces disposal practices on child growth: evidence from 34 countries.
To characterize the relationship between child faeces disposal and child growth in low- and middle-income countries. We analysed caregiver responses and anthropometric data from Demographic and Health Surveys (2005-2014) for 202 614 children under five and 82 949 children under two to examine the association between child faeces disposal and child growth. Child faeces disposal in an improved toilet was associated with reduced stunting for children under five [adjusted prevalence ratio (aPR) = 0.90, 95% confidence interval (CI) 0.89-0.92] and a 0.12 increase in height-for-age z-score (HAZ; 95% CI: 0.10-0.15) among all households. Among households with improved sanitation access, practicing improved child faeces disposal was still associated with a decrease in stunting (aPR = 0.94, 95% CI: 0.91-0.96) and a 0.09 increase in HAZ (95% CI: 0.06-0.13). Improved child faeces disposal was also associated with reductions in underweight and wasting, and an increase in weight-for-age z-score (WAZ), but not an increase in weight-for-height z-score (WHZ). Community coverage level of improved child faeces disposal was also associated with stunting, with 75-100% coverage associated with the greatest reduction in stunting. Child faeces disposal in an unimproved toilet was associated with reductions in underweight and wasting, but not stunting. Improved child faeces disposal practices could achieve greater reductions in child undernutrition than improving toilet access alone. Additionally, the common classification of child faeces disposal as 'safe' regardless of the type of toilet used for disposal may underestimate the benefits of disposal in an improved toilet and overestimate the benefits of disposal in an unimproved toilet.


[Microbiology of urinary tract infections in ambulatory patients. Therapeutic options in times of high antibiotic resistance].
To determine the antibiotic resistance of urinary pathogens in ambulatory patients from Mexico City, in order to infer therapeutic options in environments of high resistance. Cross sectional survey performed between July 2006, and January 2007, in patients > or =3 year-old from a private institution. Cultured organisms were identified with a commercial biochemical system. For common antibiotics, susceptibility was performed by broth microdilution with a commercial system; for fosfomycin tromethamine, the disk diffusion test was performed. From 1685 urine specimens, 257 (15.3%) yielded a positive culture; 215 (83.7%) from women and 42 (16.3%) from men. Global resistance was the following: ampicillin, 68.4%; co-amoxiclav, 19.5%; ciprofloxacin, 36.3%; cephalothin, 64.7%; ceftriaxone, 12.2%; cefuroxime, 18.7%; nitrofurantoin, 19%; trimethoprim-sulphamethoxazol, 53.4%; gentamicin, 18.9%; and fosfomycin tromethamine, 0.8%. Escherichia coli was the main pathogen, with 203 (79%) isolations; its specific resistance was similar to the global one, and its production of extended-spectrum beta-lactamases (ESBLs) was 9.4%. The high resistance rate found is alarming; we have few options for the initial treatment of urinary tract infections in ambulatory patients. To control the problem, health authorities must regulate the indiscriminate use of antibiotics.


Synthesis and evaluation of new coumarin derivatives as potential atypical antipsychotics.
In this paper, we report the synthesis of novel, potential antipsychotic coumarin derivatives combining potent dopamine D₂, D₃ and serotonin 5-HT(1A), 5-HT(2A) receptors properties. We describe the structure activity relationship that leads us to the promising derivative: 7-(4-(4-(6-fluorobenzo[d]isoxazol-3-yl)piperidin-1-yl)butoxy)-6-methyl-2,3-dihydrocyclopenta[c]chromen-4(1H)-one 27. The unique pharmacological features of compound 27 are a high affinity for dopamine D₂, D₃ and serotonin 5-HT(1A), 5-HT(2A) receptors, together with a low affinity for H₁ receptor (to reduce the risk of obesity under chronic treatment). In animal models, compound 27 inhibited apomorphine-induced climbing and MK-801-induced hyperactivity without observable catalepsy at the highest dose tested. In particular, compound 27 was more potent than clozapine.


Catalytic asymmetric vinylogous mannich reaction of N-(2-thienyl)sulfonylimines.
Both cyclic and acyclic silyl dienol ethers participate efficiently in the asymmetric vinylogous Mannich reaction of N-2-thienylsulfonylimines catalyzed by copper(I) complexes of Fesulphos ligands. This procedure displays wide imine and nucleophile versatility, high enantiocontrol, and complete gamma-regioselectivity in most cases examined. The mild sulfonamide deprotection allows the resulting products to be readily transformed into optically active delta-lactams or 5-hydroxy-2-piperidone derivatives.


The role of magnetic resonance imaging in problematic gynecologic diagnoses.
MRI is a modality that provides excellent anatomic detail, especially of soft tissue and bone. Comparison of T1-weighted and T2-weighted images offers significant diagnostic information of pelvic pathology. In five problematic gynecologic cases, magnetic resonance imaging (MRI) provided key information for optimal treatment planning or a definitive diagnosis for the gynecologist.


[A Case of Gastric Carcinoid Associated with Hypergastrinemia Treated with LATG].
A 67-year-old man had a gastric polyp diagnosed on screening. Atrophic changes in the upper gastric mucosa were seen on upper gastrointestinal endoscopy. In addition, endoscopy revealed in the middle area of the stomach wall a 10 mm polyp that was diagnosed as a carcinoid tumor through biopsy. Blood serum gastrin was elevated at 2,800 pg/mL.We diagnosed a Rindi Type 1 gastric carcinoid. The patient was planned to be treated with surgical laparoscopy assisted distal gastrectomy (LADG); however, the procedure was changed to intraoperative laparoscopy assisted total gastrectomy (LATG). Chromogranin-positive tumor pathological findings in the mucous membrane submucosa and in the muscularis mucosae endocrine cell micronest (ECM) were widespread. There was no obvious vascular invasion. After the surgery, the serum gastrin level normalized and the patient remains alive.


Structural relationship of streptavidin to the calycin protein superfamily.
Streptavidin is a binding protein, from the bacteria Streptomyces avidinii, with remarkable affinity for the vitamin biotin. The lipocalins and the fatty acid-binding proteins (FABPs), are two other protein families which also act by binding small hydrophobic molecules. Within a similar overall folding pattern (a beta-barrel with a repeated +1 topology), large parts of the lipocalin, FABP, and streptavidin molecules can be structurally equivalenced. The first structurally conserved region within the three-dimensional alignment, or common core, characteristic of the three groups corresponds to an unusual structural feature (a short 3(10) helix leading into a beta-strand, the first of the barrel), conserved in both its conformation and its location within their folds, which also displays characteristic sequence conservation. These similarities of structure and sequence suggest that all three families form part of a larger group: the calycin structural superfamily.


Novel susceptibility genes associated with diabetic cataract in a Taiwanese population.
To identify genetic variants that predispose to type 2 diabetes (T2D) with cataract. Genome-wide association study (GWAS) of T2D patients with cataract, as graded by Lens Opacities Classification System (LOCS). A total of 109 T2D patients with cataract score equal to or above 10 designated as the study group, 649 T2D patients with cataract score equal to or below 3 as the control group. Single nucleotide polymorphisms (SNPs) with p-values < 10(-5) were considered to be putatively associated with the diabetic cataract. Fifteen SNPs were found to be putatively associated with diabetic cataract. These variants were located near the following genes: PPARD, CCDC102A, GBA3, NEDD9, GABRR1/2, RPS6KA2, tcag7.1163, TAC1, GALNTL1 and KIAA1671. We defined haplotype 1 to haplotype 4 from the alternative alleles of related polymorphisms. Distribution of haplotype 2 on chromosome 4 and haplotype 4 on chromosome 7 revealed significant differences (OR = 1.86 and 1.69, respectively; 95% confidence interval were 1.26-2.76 and 1.23-2.31, respectively). The 15 loci coded on chromosomes 4, 6, 7, 14, 16 and 22 were associated with diabetic cataract. Gene functions are either with mechanisms of regulating blood sugar or formation of cataract. High linkage disequilibrium appeared on chromosome 4p15.31 and chromosome 7q21.3.


Double Carbon Nano Coating of LiFePO4 Cathode Material for High Performance of Lithium Ion Batteries.
Double carbon-coated LiFePO4 (D-LiFePO4/C) composite with sphere-like structure was synthesized through combination of co-precipitation and solid-state methods. Cetyl-trimethyl-ammonium bromide (CTAB) and citric acid served as two kinds of carbon sources in sequence. SEM images demonstrated that double carbon coating had certain influence on the morphology. The thickness of carbon coating on D-LiFePO4/C was about 1.7 nm and the content of carbon was 2.48 wt%, according to HRTEM and TG analysis. The electrochemical impedance spectroscopy analysis indicated that the D-LiFePO4/C composite presented the charge-transfer resistance of 68 Ω and Li ion diffusion coefficient of 2.68 x 10(-13) cm2 S(-1), while the single carbon-coated LiFePO4 (S-LiFePO4/C) exhibited 135.5Ω and 4.03 x 10(-14) cm2 S(-1). Especially, the prepared D-LiFePO4/C electrode showed discharge capacities of 102.9 (10C) and 87.1 (20C) mA h g(-1), respectively, with almost no capacity lost after 400 cycles at 10C, which were much better than those of S-LiFePO4/C composite.


Role of the ubiquitin-proteasome in protein quality control and signaling: implication in the pathogenesis of eye diseases.
The ubiquitin-proteasome pathway (UPP) plays important roles in many cellular functions, such as protein quality control, cell cycle control, and signal transduction. The selective degradation of aberrant proteins by the UPP is essential for the timely removal of potential cytotoxic damaged or otherwise abnormal proteins. Conversely, accumulation of the cytotoxic abnormal proteins in eye tissues is etiologically associated with many age-related eye diseases such as retina degeneration, cataract, and certain types of glaucoma. Age- or stress-induced impairment or overburdening of the UPP appears to contribute to the accumulation of abnormal proteins in eye tissues. Cell cycle and signal transduction are regulated by the conditional UPP-dependent degradation of the regulators of these processes. Impairment or overburdening of the UPP could also result in dysregulation of cell cycle control and signal transduction. The consequences of the improper cell cycle and signal transduction include defects in ocular development, wound healing, angiogenesis, or inflammatory responses. Methods that enhance or preserve UPP function or reduce its burden may be useful strategies for preventing age-related eye diseases.


[Structural equation model for the health behaviors of university students in Korea].
A structural equation model was analysed to explore the determinants of health behaviors of university students in Korea. Nine hundred sixty nine university students were selected by random cluster sampling from five universities located in the central area of Korea. The data was collected by questionnaires about demographic characteristics, stressful life events, perceived social support, perceived health status and health behaviors. 1. Gender showed indirect effect on health behaviors. 2. Living together with(out) family had a direct effect on health behaviors: students living with family showed more positive health behaviors. 3. Stressful life events had an indirect effect on health behaviors via perceived health status; a higher score of stressful life events was the predictor for negative health behaviors. 4. A higher score of perceived health status predicted positive health behaviors. Each university should be encouraged to develop a health behavior control program and health promotion program for their own university students. It would be more effective to develop health programs separately according to the demographic or social characteristics of the students. It is also necessary for the Ministry of Education to reform the School Health Act and school health policy to strengthen a health promotion program for university students. In conclusion, following studies should identify and promote the validity and reliability of perceived health status and health behaviors measurements.


Effects of bisoprolol treatment for chronic heart failure initiated and followed up by primary care physicians.
Primary care physicians prescribe beta-blockers for chronic heart failure infrequently. The aims of the study were to assess the effects of beta-blocker treatment in out-clinic patients with regard to NYHA class and frequency of adverse events. Beta-blocker treatment was initiated and followed up by primary care physicians. Chronic heart failure patients already treated with ACE-inhibitors and diuretics were included. The 24-week follow-up consisted of a titration phase followed by a maintenance phase. The patients received the beta-blocker bisoprolol with an initial dose of 1.25 mg and a maximal dose of 10 mg. NYHA class II, III and IV had 174, 146, and one patient, respectively. Treatment duration lasted 189+/-73 days with a maximal bisoprolol dose of 7.2+/-3.2 mg. Sixty-one percent of the patients tolerated at least 7.5 mg bisoprolol. The NYHA class improved from 2.4+/-0.5 at baseline to 1.8+/-0.6 at week 24 (P<0.001). At final assessment, 74% of the patients showed an improvement. The number of permanent treatment withdrawals was 57 (17%). Death occurred in six patients and hospitalisation in 38 patients. Bisoprolol treatment in patients with chronic heart failure was effectively and safely carried out by primary care physicians.


Associations of gestational glycemia and prepregnancy adiposity with offspring growth and adiposity in an Asian population.
Maternal obesity and hyperglycemia increase risk of obesity and diabetes in offspring later in life. We examined the relation between gestational glycemia and prepregnancy body mass index (ppBMI) with offspring growth in an Asian mother-offspring cohort. Pregnant mothers undertook a 75-g 2-h oral-glucose-tolerance test at 26-28 wk of gestation. In 937 singleton offspring, ≤9 serial measurements of weight and length were obtained from birth until 36 mo of age. Gestational fasting plasma glucose (FPG) was positively associated with birth weight (B: 0.17; 95% CI: 0.10, 0.24; P < 0.001) and birth BMI (B: 0.15; 95% CI: 0.06, 0.40; P = 0.001) but not at ≥3 mo of age. In contrast, maternal ppBMI was positively associated with birth variables and conditional growth in weight and BMI in the first 36 mo of life. However, gestational FPG and prepregnancy obesity status interacted significantly for the association with offspring growth and overweight status in the first 36 mo of life (P-interaction < 0.01). In nonobese mothers, each unit increase in gestational FPG was associated with increased offspring weight (B: 0.08; 95% CI: 0.008, 0.16; P = 0.03) and BMI (B: 0.08; 95% CI: 0.003, 0.15; P = 0.04) as well as increased risk of overweight in the first 36 mo of life (OR: 1.36; 95% CI: 1.10, 1.68). However, in obese mothers, each unit increase in gestational FPG was associated with decreased offspring weight (B: -0.01; 95% CI: -0.02, -0.003) and BMI (B: -0.008; 95% CI: -0.01, -0.002) velocity (P < 0.01 for both) and decreased risk of overweight (OR: 0.59; 95% CI: 0.41, 0.86) in the first 36 mo of life. Prepregnancy adiposity was associated with offspring growth in early childhood. Although pooled analyses showed no demonstrable difference by 3 mo of age, there were contrasting and opposite associations of gestational glycemia with weight and BMI in the first 36 mo of life in offspring of nonobese and obese mothers separately. This study was registered at clinicaltrials.gov as NCT01174875.


Anti-proliferative and antibacterial in vitro evaluation of the polyurethane nanostructures incorporating pentacyclic triterpenes.
Oleanolic and ursolic acids are antitumor and antibacterial agents which are extensively studied. Their major disadvantage is the poor water solubility which limits their applications. Oleanolic and ursolic acid were encapsulated into polyurethane nanostructures that act as drug carriers. In order to evaluate the effectiveness of the particles, anti-microbial and anti-proliferative activity compared to un-encapsulated active compounds was tested. Using an interfacial polycondensation technique, combined with spontaneous emulsification, structures with nanoscale dimensions were obtained. Scanning electron microscopy, differential scanning calorimetry and X-ray assays confirmed the encapsulation process. Concentrations of 10 and 30 μM particles and un-encapsulated compounds were tested by MTT viability assay for several breast cancer lines, with an exposure time of 72 h. For the antibacterial studies, the dilution method with MIC determination was used. Ursolic acid had an excellent inhibitory effect with IC50 value of 2.47, 1.20, 1.26 and 1.34 μM on MCF7, T47D, MDA-MB-231 and MDA-MB-361, respectively. Oleanolic acid did not show anti-proliferative activity. The pure compounds showed their antibacterial activity only against Bacillus species and Candida albicans, but MIC values were too high to be considered efficient antimicrobial agents (2280 and 4570 μg mL - 1, respectively). Polyurethane nanoparticles which incorporated the agents did not show any biological activity. Although the active compounds did not fully exert their anti-proliferative activity following encapsulation inside polymeric nanoparticles, in vivo evaluation is needed in order to obtain an exhaustive conclusion, as the active compounds could be released as a result of metabolic activity.


How to simulate affinities for host-guest systems lacking binding mode information: application to the liquid chromatographic separation of hexabromocyclododecane stereoisomers.
A novel approach for the simulation of host-guest systems by systematically scanning the host molecule's orientations within the guest cavity is presented along with a thermodynamic strategy for determining preferential binding modes and corresponding optimal interaction energies between host and guest molecules. By way of example, the elution order of hexabromocyclododecane stereoisomers from high performance liquid chromatography separation on a permethylated β-cyclcodextrin stationary phase has been computed using classical molecular dynamics simulations with the explicit solvents water and acetonitrile. Comparison of estimated with experimental separation data reveals remarkable squared coefficients of correlation with R(2) = 0.87 and a very high correlation R(LOO2) = 0.72 using the leave-one-out cross-validation method and water as solvent. In particular, the approach presented shapes up as very robust in terms of the evaluated time range under consideration, reflecting well thermodynamic equilibria. These and further observations correlating with experimental results suggest the suitability of the underlying force fields and our multi-mode approach for the estimation of relative binding affinities for host-guest systems with unknown binding modes.


Discovery of Novel Potent Muscarinic M3 Receptor Antagonists with Proper Plasma Stability by Structural Recombination of Marketed M3 Antagonists.
The marketed long-acting M3 antagonists for treatment of chronic obstructive pulmonary disease have inappropriate plasma stability (either overstable or excessively unstable), which causes substantial systemic exposure or poor patient compliance. To discover novel M3 antagonists with proper plasma stability, we synthesized and biologically evaluated a series of chiral quaternary ammonium salts of pyrrolidinol esters, which were designed by structural recombination of the marketed M3 antagonists. As a result, two novel potent M3 antagonists, (R/S)-3-[2-hydroxy-2,2-di(thiophen-2-yl)acetoxy]-1,1-dimethylpyrrolidinium bromides (1 a: Ki =0.16 nm, IC50 =0.38 nm, t1/2 =9.34 min; 1 b: Ki =0.32 nm, IC50 =1.01 nm, t1/2 =19.2 min) with proper plasma stability were identified, which (particularly 1 a) hold great promise as clinical drug candidates to overcome the drawbacks caused by the inappropriate stability of the currently marketed M3 antagonists. In addition, structure-activity relationship studies revealed that the R configuration of the pyrrolidinyl C3 atom was clearly better than the S configuration.


Stress management in the difficult patient encounter.
Patient care and management can present a significant source of stress for the practicing dentist. This article presents the various facets and underpinnings of stress, followed by an overview of the physiologic phenomena attending the classic stress response, with an examination of the interplay between the psychologic components of stress and its influences on the development or exacerbation of somatic disorders. In addition, the characteristics that can be attributed to the patient and the practitioner that give rise to difficult encounters are explored, with an eye toward proper professional management. Further, the motivations of select patient personae are examined, including discussions regarding the angry patient, the anxious or demanding patient, and the noncompliant and addicted patient. The article offers suggestions for management of such patients, with short- and long-term stress management techniques.


Differentiation of germination characteristics in Scutellaria rubropunctata (Lamiaceae) associated with adaptation to rheophytic habitats in the subtropical Ryukyu Islands of Japan.
Seed germination characteristics of a facultative rheophyte Scutellaria rubropunctata, a perennial skullcap endemic to the subtropical Ryukyu Islands of Japan, were investigated at temperatures of 15 °C, 20 °C, 25 °C, and 30 °C. The rheophytic type of S. rubropunctata showed relatively simultaneous germination times and reached high germination rates under all temperatures tested. This characteristic may allow it to establish quickly without being influenced by temperature, giving a survival advantage in rheophytic habitats by avoiding seeds being washed away by the rising water. In contrast, the final germination rate of the terrestrial type of S. rubropunctata, as well as that of the congener S. indica var. parvifolia, was highest at 15 °C and declined drastically at 30 °C. Seeds of both of these plants that remained ungerminated at higher temperatures germinated soon after the temperature was changed to 15 °C, indicating that the germination suppression was a state of enforced dormancy that was released after transfer to the optimal temperature. These characteristics suggest an asynchronous germination which is thought to reduce the risk of disturbance in fluctuating environments. Our study may be the first to demonstrate the differentiation of seed germination characteristics in relation to adaptations to a rheophytic habitat. Because rheophytes occupy such a harsh environment under strong selective pressure, the adaptive differentiation of seed germination characteristics may occur in many other rheophytes.


Experimental brain ischemia: neuron-specific enolase level in cerebrospinal fluid as an index of neuronal damage.
Levels of neuron-specific enolase (NSE) were measured in rat CSF following occlusion of the four major arteries to the brain for 10, 20, or 30 min. In the CSF of rats submitted to 30 min of total ischemia, an up to nine-fold increase of NSE level occurred within the first few hours and then slowly diminished. Significant levels were seen for as long as 8 days. Histological observations 3 days after ischemia showed neuronal loss as well as neuronal damage in several forebrain regions such as hippocampus, striatum, and thalamus. Ischemia was followed by transient decreases in exploration behavior and neurological states that were no longer visible 24 h later. After 10 or 20 min ischemia, NSE levels were increased to a lesser degree and fewer damaged neurons were observed. The positive correlation between duration of ischemia and amount of NSE release in CSF indicates that the measurement of NSE in the CSF is a sensitive and reliable index of neuronal lesions.


Rapid cervicovaginal smear screening: method of quality control and assessing individual cytotechnologist performance.
To validate the method of rapid screening (RS) in the detection of cervical lesions and false-negative results as well as in quality control of cytotechnologist performance. The RS method was validated on Papanicolaou-stained and initially conventionally analysed vaginal, cervical and endocervical (VCE) smears collected in an opportunistic programme for the detection of cervical carcinoma. The study included 3680 VCE smears from the Department of Gynaecologic Cytology, University Department of Gynaecology and Obstetrics, Zagreb University Hospital Center, Zagreb and from the Department of Clinical Cytology, Osijek University Hospital, Osijek. Histologically verified abnormal findings accounted for 10% of the study samples. Thirteen cytotechnologists, with no previous experience in RS, performed the test. Each slide was examined using the 'step' technique for 1.5 minutes, the findings were classified as negative or abnormal, and the abnormal ones were also classified according to differential cytological diagnosis. The results were compared with those obtained on initial screening. Abnormal findings from a group of initially negative findings were reanalysed using conventional methods to make definitive cytological diagnosis. RS yielded a sensitivity of 83.7%, specificity of 93.7%, positive predictive value of 62.4%, negative predictive value of 97.9% and diagnostic accuracy of 92.6%. Relative to the initial abnormal differential cytological diagnosis, the diagnostic value of RS increased with lesion severity [54.8%, 68.0% and 91.3% for cervical intraepithelial neoplasia (CIN) I, CIN II and CIN III respectively]. RS detected 38 additional positive findings; 94.2% of these were atypical squamous cells of undetermined significance (ASCUS)/abnormal glandular cells undetermined significance (AGUS) and CIN I. The rate of additional positive findings was 1.14% (38/3135). The false-negative rate of initial screening was 9.4% (38/406), and individual cytotechnologist sensitivity was 60.0-100.0%. RS could be introduced as an efficient method of quality control to improve the sensitivity of cytological screening as well as for quality control of cytotechnologist performance.


Revelation of Brugada electrocardiographic pattern during a febrile state.
The prevalence of the Brugada-type ECG and its natural history are still unclear. The Brugada syndrome is usually identified by a characteristic Brugada-type ECG that consists of ST elevation of a coved type in the precordial leads V1 to V3 and ventricular fibrillation that can lead to sudden cardiac death, although affected individuals may have a normal ECG. Mutations in the cardiac sodium channel gene SCN5A, which encodes the alpha-subunit of the human cardiac voltage-dependent Na+ channel (Na(v)1.5), are identified in 15-30% of patients with Brugada syndrome. Most SCN5A mutations lead to a 'loss-of-function' phenotype, reducing the Na+ current during the early phases of the action potential. Several nongenetic factors have been mentioned in the literature as possible inductors of the ECG pattern resembling Brugada syndrome. As such, a Brugada-type ECG may appear in some patients during febrile states and in those who are under the influence of cocaine and pharmaceutical drugs that have a sodium channel-blocking effect. It has been also reported that chest pain and ST elevation Brugada pattern occur during febrile states. We present a case of revelation of Brugada pattern in a 61-year-old Italian man complaining of pain in the left hipocondrium during a febrile state. Also this report confirms that Brugada pattern should be considered as one of differential diagnoses when we examine the patients during a febrile state.


[Accumulation and precipitation of Mn2+ by the cells of Oscillatoria terebriformis].
The cyanobacterium Oscillatoria terebriformis was shown to exhibit resistance to high manganese concentrations, remaining viable at 2.5 mM MnCl2 in the medium. Cyanobacterial cells were capable of considerable manganese consumption from the medium. Dynamics of Mn sorption by the cells was the same in all experimental variants, independent on the manganese concentration. Manganese concentration in the biomass peaked after 2-3 days and depended on Mn2+ concentration in the medium and on the amount of biomass introduced. In the case of O. terebriformis, manganese removed from the medium may be subdivided into Mn absorbed by the cell, Mn bound to the cell wall, Mn absorbed by the glycocalix, and chemically precipitated Mn. Of the total 21.25 ± 1.0 mg of consumed manganese, biological absorption and chemical precipitation were responsible for 11.78 ± 0.98 and 9.2 ± 0.8 mg, respectively. In the presence of cyanobacteria, Mn removal from the medium was 2.28 times higher than in the control. This process depended considerably on Mn sorption by exopolysaccharides. At 1.3 mM Mn2+, a lamellar mat was formed with interlayers of manganese carbonate.


Interbody fusion cage design using integrated global layout and local microstructure topology optimization.
An approach combining global layout and local microstructure topology optimization was used to create a new interbody fusion cage design that concurrently enhanced stability, biofactor delivery, and mechanical tissue stimulation for improved arthrodesis. To develop a new interbody fusion cage design by topology optimization with porous internal architecture. To compare the performance of this new design to conventional threaded cage designs regarding early stability and long-term stress shielding effects on ingrown bone. Conventional interbody cage designs mainly fall into categories of cylindrical or rectangular shell shapes. The designs contribute to rigid stability and maintain disc height for successful arthrodesis but may also suffer mechanically mediated failures of dislocation or subsidence, as well as the possibility of bone resorption. The new optimization approach created a cage having designed microstructure that achieved desired mechanical performance while providing interconnected channels for biofactor delivery. The topology optimization algorithm determines the material layout under desirable volume fraction (50%) and displacement constraints favorable to bone formation. A local microstructural topology optimization method was used to generate periodic microstructures for porous isotropic materials. Final topology was generated by the integration of the two-scaled structures according to segmented regions and the corresponding material density. Image-base finite element analysis was used to compare the mechanical performance of the topology-optimized cage and conventional threaded cage. The final design can be fabricated by a variety of Solid Free-Form systems directly from the image output. The new design exhibited a narrower, more uniform displacement range than the threaded cage design and lower stress at the cage-vertebra interface, suggesting a reduced risk of subsidence. Strain energy density analysis also indicated that a higher portion of total strain energy density was transferred into the new bone region inside the new designed cage, indicating a reduced risk of stress shielding. The new design approach using integrated topology optimization demonstrated comparable or better stability by limited displacement and reduced localized deformation related to the risk of subsidence. Less shielding of newly formed bone was predicted inside the new designed cage. Using the present approach, it is also possible to tailor cage design for specific materials, either titanium or polymer, that can attain the desired balance between stability, reduced stress shielding, and porosity for biofactor delivery.


Relationship of changes in diaphragmatic muscle blood flow to muscle contractile activity.
The effect of increases in diaphragmatic muscle contractile activity on diaphragm blood flow remains unclear. The present study examined the effect of electrically induced isometric diaphragmatic muscle contractions on diaphragmatic blood flow. Studies were performed on diaphragmatic muscle strips prepared in anesthetized mechanically ventilated dogs. Diaphragmatic contractile activity was quantitated as the tension-time index (TTI) (i.e., the product of tension magnitude and duration). Blood flow to the strip (Qdi) was measured from the volume of the phrenic venous effluent using a drop counter. The separate effects on Qdi of 30-s periods of continuous and rhythmic contractions were examined. Qdi increased with increases in TTI and peaked at a TTI of 20-30% of maximum after which Qdi fell progressively with further increases in TTI. At levels of TTI greater than 30%, the pattern of muscle contraction significantly affected blood flow. Qdi was significantly lower during activity and the postcontraction hyperemia significantly greater at a given TTI when contractions were continuous than when contractions were intermittent. Above a TTI of 30%, Qdi during contraction decreased linearly with increases in duty cycle and curvilinearly with increases in tension. We conclude that during isometric diaphragmatic contractions, diaphragmatic blood flow may become mechanically impeded, and the magnitude of the impediment in blood flow depends on the pattern of diaphragmatic contractions. With increases in contractile activity above a critical level, changes in duty cycle exert progressively greater effects on diaphragmatic blood flow than changes in muscle tension.


Tension pneumocephalus secondary to non-invasive mechanical ventilation in a patient with severe traumatic brain injury.
The presence of air inside intracranial cavity is a rare entity known as pneumocephalus and in most cases doesńt present any clinical repercussion except in case of elevated intracranial pressure that can lead to a decreasing level of consciousness, coma and even death. We present a rare case of a young male, without medical precedents of interest, hospitalized in an intensive care unit for vigilance after a traffic accident with asymptomatic crane encephalic trauma and cranial computerized tomography without meaningful findings. During the intensive care unit stay positive pressure is applied in airway with non-invasive mechanical ventilation that produces air entrance in cranial cavity (pneumocephalus) causing neurological deterioration and necessity of urgent surgery.


Increased leptin production in vivo and insulin cleavage by the omental adipose tissue of morbidly obese patients.
The aim of this investigation was to assess the insulin cleavage capacity in obese humans. Increased insulin degradation by visceral adipose tissue has previously been demonstrated in obese rats and could be interpreted as a physiological response to hyperinsulinaemia. The recent characterization of leptin receptors in pancreatic beta cells, liver and muscle suggests that leptin may influence insulin function and metabolism. Our study focuses on the possible relationship between leptin secretion and adipose tissue insulin-degrading capacity. Insulin and leptin were measured in arterial blood and in the epiploic vein of morbidly obese (n = 7) and non-obese patients (n = 7) who were undergoing abdominal surgery. Arteriovenous insulin difference (AV insulin) was considered an in vivo marker of insulin degradation by the omental fat tissue. Statistical comparison between venous and arterial leptin was used to assess endogenous leptin production. Insulin was measured using an oligoclonal IRMA and leptin levels were determined by using a specific radioimmunoassay. Morbidly obese patients were hyperinsulinaemic compared to non-obese patients according to arterial insulin levels (P = 0.049) but not to venous levels. Insulin cleavage capacity, nil in the control group, was clearly significant in the morbidly obese patients (P = 0.001). In the morbidly obese group, leptin levels in venous epiploic samples were significantly higher (P = 0.028) than in the arterial samples, confirming in situ the synthesis of leptin by human white adipose tissue. We also observed a correlation between insulin arterial levels and venous leptin concentrations (P = 0.009) which supports the chronic leptinogenic effect of insulin suggested in previous works. Finally, our results show that venous leptin levels are correlated with the extent of insulin cleavage by omental tissue (P = 0.033). Morbidly obese patients have a higher white adipose tissue insulin cleavage capacity, which could partially diminish hyperinsulinaemia-derived adverse effects. High leptin production, a consequence of high insulin levels, may act as a signal to the insulin-degrading tissues in order to lower insulinaemia.


[Application of ultrafast 3D-CT in cervical spine injury].
The authors investigated the usefulness of the ultrafast three-dimensional computed tomography (UF-3D-CT) in cervical spine injury. At Osaka City General Hospital, between April 1995 and March 1998, the authors examined 38 patients with cervical spine injury using UF-3D-CT. The ultrafast CT reduces scanning time. There were no complications associated with the examination. We examined 12 patients with vertebral body fracture, 11 patients with lamina fracture, 8 cases with subluxation including locking facet, 2 patients with atlanto-axial dislocation and 8 patients without bony abnormality. Results suggested that UF-3D-CT was very useful for helping us to understand the bony deformity and the relationship between the bone and the important vessels. UF-3D-CT is very useful for preoperative evaluation and pathophysiological evaluation in cervical spin injury.


Impact of availability on gambling: a longitudinal study.
Legalized gambling opportunities have markedly increased in most industrialized countries. While most authors agree that the rate of pathological gamblers is related to the accessibility of gambling activities, no published studies have yet empirically estimated the impact of the introduction of new gambling activities within a longitudinal study. Thus, we evaluate the impact of the opening of a casino on gambling activities among nearby inhabitants. A random sample of 457 respondents from the Hull area (experimental group) and 423 respondents from the Quebec City area (control group) completed the South Oaks Gambling Screen and related questions, both before the opening of the Casino de Hull and 1 year later. Within each household contacted, a resident was randomly chosen by selecting the adult whose birthday was next. The experimental group exposed to the new casino showed a significant increase in 1) gambling on casino games, 2) the maximum amount of money lost in 1 day on gambling, 3) reluctance toward the opening of a local casino, and 4) the number of participants who reported knowing a person who has developed a gambling problem in the last 12 months. The impact of legalized gambling is discussed in relation to the availability of gambling.


Impaired postprandial response of active ghrelin and prolonged suppression of hunger sensation in the elderly.
The role of the orexigenic hormone ghrelin is of major interest in the altered appetite regulation of the elderly. Basal and postprandial levels of active and total ghrelin were measured in 15 younger (mean age 35.4 years) and 19 older (80.7 years) participants following a carbohydrate-rich test meal. Our results showed that older participants felt postprandially less hungry and more full. Although basal levels were not significantly different, active and total ghrelin levels declined postprandially only in the younger study participants. Highly significant differences between the two age groups were shown for the changes of the area under the curve for active ghrelin (p = .024). Our study demonstrates for the first time that differences in hunger and satiety sensations in relation to age are paralleled by a substantially different response of acylated and total ghrelin, that is, the absence of a postprandial decline in ghrelin levels.


CE-SDS method development, validation, and best practice-An overview.
CE-SDS has been implemented in the biopharmaceutical industry and is being used for the characterization of therapeutic proteins in most Biological License Applications currently submitted. An overview is presented on the separation mechanism, methodology, and good working practices/best practices. The CE-SDS platform method development and validation are discussed and typical scientifically and regulatory issues and troubleshooting situations are highlighted.


[Medico-psychological base and trend documentation in a residential facility for rehabilitation of the handicapped].
The article presents the system for medical-psychological base and trend documentation developed between 1977 and 1980 at Rotenburger Anstalten der Inneren Mission (Home Mission). A practicable system from the user angle, it is operated on a mediumsized data processing unit. Being a pure dialogue system with programme generators, it is easy to handle and flexible in its possible applications, several of which are illustrated by examples from the rehabilitative field. As the various characteristics used can easily be attributed with other contents, and as the data base can moreover be expanded, the documentation system could also be used by comparable facilities that have the necessary electronic data processing equipment at their disposal.


Optical design of a crossed Czerny-Turner spectrometer with a linear array photomultiplier tube.
Conventional Czerny-Turner spectrometers exhibit keystone distortion due to astigmatism, which affects their performance when a linear array photomultiplier tube (LaPMT) is used as the detector. We propose a novel optical design of a crossed Czerny-Turner spectrometer with a 32-channel LaPMT detector. We use convergent illumination of the grating to modify the astigmatism of the off-axis spherical mirrors, and the image spot radius at the central wavelength in the sagittal plane is matched with the width of the LaPMT. A first-order equation is derived for the elimination of the broadband keystone distortion. After optimization, the image size over the entire bandwidth matches well with the LaPMT size, which is consistent with the theory, and the spectral resolution is ∼4 nm per channel.


Fibroproliferative phase of ARDS. Clinical findings and effects of corticosteroids.
Most patients with adult respiratory distress syndrome (ARDS) survive the initial insult which caused respiratory failure only to succumb later to sepsis caused by nosocomial pneumonia or to pulmonary fibrosis. Clinical criteria and analysis of the tracheal aspirate are notoriously inadequate for establishing a diagnosis of ventilator-associated pneumonia. We implemented a comprehensive diagnostic protocol to determine the cause of sepsis in ARDS patients who had been ventilated for more than three days and who had no bronchoscopic evidence of pneumonia. Nine patients with late ARDS who had fever (89 percent), leukocytosis (89 percent), a new localized infiltrate (78 percent), purulent tracheal secretions (89 percent), low systemic vascular resistance (50 percent), and marked uptake of gallium in the lungs (100 percent) had no source of infection identified. Open-lung biopsy specimens from seven patients showed the fibroproliferative phase of diffuse alveolar damage and confirmed absence of pneumonia. Treatment with prolonged high doses of corticosteroids was associated with a marked and rapid improvement in lung injury score (p less than 0.003 at five days). Our findings indicate that the fibroproliferative process occurring in the lungs of patients with late ARDS gives rise to clinical manifestations identical to those of pneumonia and is potentially responsive to steroid treatment.


A practical approach to the child with abnormal liver tests.
The presence of elevated aminotransferases on routine blood tests can reveal liver diseases of various severities. In children, etiologies are more numerous and complex than those usually considered in adults. Information derived from family and personal history, physical examination and basic laboratory data are necessary to reach a timely and correct diagnosis. A stepwise approach is proposed to guide the timing of more specific investigations that are often required.


Variability in TRBV haplotype frequency and composition in Caucasian, African American, Western African and Chinese populations.
The polymorphic T-cell receptor Vbeta (TRBV) genes encode much of the variable region of the T-cell receptor beta chain. Analysis of allele frequencies of three closely linked polymorphic TRBV genes, TRBV7-3, TRBV9 and TRBV6-4, was undertaken in several populations. The frequencies of these alleles are not significantly different in populations of Caucasians, African Americans and Western Africans. However, Chinese population is extremely homogenous at all three loci. The current study identifies the existence of haplotypic relationships between alleles of these genes in the Caucasian population. The ORF allele TRBV7-3*A3 is found exclusively on chromosomes bearing TRBV9*A2 and TRBV6-4*A2 in this cohort. In contrast, TRBV7-3*A1 and the null allele TRBV7-3*A2 are associated only with TRBV9*A1 and TRBV6-4*A1. This pattern of linkage disequilibrium (LD) is altered in the African American and Western African populations. In these cohorts, there is a marked reduction in LD between alleles of TRBV7-3 and TRBV9. This study is consistent with previous population genetic studies wherein African-derived samples have a greater level of genetic diversity compared to Caucasians. These data also demonstrate that patterns of LD are not consistent across the entire TRBV locus.


Down-regulation of miR-664 in cervical cancer is associated with lower overall survival.
The aim of our study was to explore the clinicopathologic and prognostic significance of microRNA-664 expression in human cervical cancer. qRT-PCR was used to determine the expression of miR-664 in cervical cancer tissues. The relationship between miR-664 expression levels in cervical cancer tissues and clinicopathological characteristics was estimated respectively. The survival curves of the patients were determined using the Kaplan-Meier method. Univariate and multivariate Cox regression analyses were performed. The expression of miR-664 is downregulated in human cervical cancer tissues when compared to the corresponding noncancerous tissues (p < 0.01). Low miR-664 expression was significantly associated with lymphatic invasion (p = 0.000), distant metastasis (p < 0.000), FIGO stage (p = 0.001), and histological grade (p = 0.008). Kaplan-Meier analysis demonstrated that low levels of miR-664 expression were associated with poorer overall survival (p < 0.001). In the multivariate analysis, low miR-664 expression was an independent prognostic factor for OS (p = 0.005). MiR-664 may be a promising biomarker for the detection and prognosis evaluation of cervical cancer.


Evidence for universality and cultural variation of differential emotion response patterning.
The major controversy concerning psychobiological universality of differential emotion patterning versus cultural relativity of emotional experience is briefly reviewed. Data from a series of cross-cultural questionnaire studies in 37 countries on 5 continents are reported and used to evaluate the respective claims of the proponents in the debate. Results show highly significant main effects and strong effect sizes for the response differences across 7 major emotions (joy, fear, anger, sadness, disgust, shame, and guilt). Profiles of cross-culturally stable differences among the emotions with respect to subjective feeling, physiological symptoms, and expressive behavior are also reported. The empirical evidence is interpreted as supporting theories that postulate both a high degree of universality of differential emotion patterning and important cultural differences in emotion elicitation, regulation, symbolic representation, and social sharing.


Characterization of chitin and its hydrolysis to GlcNAc and GlcN.
Proton NMR spectra of chitin dissolved in concentrated and deuterated hydrochloric acid (DCl) were found to be a simple and powerful method for identifying chitin from samples of biological origin. During the first hour after dissolving chitin in concentrated DCl (25 degrees C), insignificant de-N-acetylation occurred, meaning that the fraction of acetylated units (FA) of chitin could be determined. FA of demineralized shrimp shell samples treated with 1 M NaOH at 95 degrees C for 1-24 h were determined and were found to decrease linearly with time from 0.96 to 0.91 during the treatment with NaOH. Extrapolation to zero time suggested that chitin from shrimp shells has a FA of 0.96, that is, contains a small but significant fraction of de-N-acetylated units. Proton NMR spectra of chitin ( FA = 0.96) dissolved in concentrated DCl were obtained as a function of time until the samples were almost quantitatively hydrolyzed to the monomer glucosamine (GlcN). The initial phase of the reaction involves mainly depolymerization of the chitin chains, resulting in that almost 90% (molar fraction) of the chitin is converted to the monomer N-acetyl-glucosamine (GlcNAc).Thus, effective conversion of chitin to GlcNAc in concentrated acid is reported for the first time. GlcNAc is then further de-N-acetylated to GlcN. A new theoretical model was developed to simulate the experimental data of the kinetics of hydrolysis of chitin in concentrated acid. The model uses three different rate constants; two for the hydrolysis of the glycosidic linkages following an N-acetylated or a de-N-acetylated sugar unit and one for the de-N-acetylation reaction. The three rate constants were estimated by fitting model data to experimental results. The rate of hydrolysis of a glycosidic linkage following an N-acetylated unit was found to be 54 times higher as compared to the rate of de-N-acetylation and 115 times higher than the rate of hydrolysis of a glycosidic linkage following a de-N-acetylated unit. Two chitin samples with different F A values (0.96 and 0.70) were incubated in concentrated DCl until the samples were converted to the maximum yield of GlcNAc and the oligomer composition analyzed, showing that the maximum yield of GlcNAc was much higher when prepared from the chitin with the highest F A value.


Patterns of upper aero-digestive tract cancers in Kamrup Urban District of Assam: a retrospective study.
The incidence of upper aero-digestive tract (UADT) cancers, including C00-C14, C30-C32, C15 and C16, is increasing rapidly in Kamrup Urban District (KUD) of Assam, North East (NE) India. According to the NCRP (2013) report 37.6% of all cancers in both sexes are UADT cancers in the NE region, accounting for 53.3% in males and about 27.5% in females of the total cases A retrospective study was conducted for patient information from the period of 2008-2011. Age-standardized or age-adjusted rates (ASR or AAR) (per 100,000 person-years) were calculated using the World Standard Population as proposed by Segi and modified by Doll et al. The registry population area at risk was estimated using the 1991 and 2001 census population by sex, as well as the growth rate during that interval using the difference distribution method. There were 5,638 cases registered during the last four years of the study (2008-2011) accounting for 56.7% (3,198/5,638) of the total in males and 43.3% (2,440/5,638) in females. The male: female ratio was 1.31: 1.00. The overall age adjusted rates (AAR) were 179.4 and 153.8 per 100 000 males and females respectively. Cancer of the oesophagus was most common in both sexes, with most appreciable gender variation for tongue and hypopharynx, presumably reflecting differential exposure to risk factors.


Diterpenoids from Euphorbia paralias.
Two segatane diterpenoids containing a bicyclic [4,3,1] ring system were isolated, together with 11 known diterpenoids, four segetanes, five jatrophanes and two paralianes, from the aerial parts of Euphorbia paralias. The structures of the new compounds were established by spectroscopic means, including by 2D NMR and CD spectroscopic analyses. The antifeedant and antiviral activities of the isolated compounds are also described.


Further studies on irreversible inhibition of dopamine-beta-hydroxylase by cysteine.
In the process of studying the inhibition of dopamine-beta-hydroxylase by cysteine, we observed an interesting relationship between cysteine and catalase. This suggests that two different patterns of the inhibition of dopamine-beta-hydroxylase exist; the one is reversible inhibition, the other is irreversible inhibition. In the present experiments, we have particularly investigated the irreversible inhibition of dopamine-beta-hydroxylase by cysteine, and the following conclusions were drawn: (a) The rate of the inhibitory effect of cysteine pretreatment on dopamine-beta-hydroxylase is independent of a function of the temperature, while at temperature above 20 degrees C the extent of the reversibility of cysteine inhibition by N-ethylmaleimide is temperature dependent. (b) The rate of inhibitory effect is dependent on the time of cysteine pretreatment at 37 degrees C, and the ability of N-ethylmaleimide to reverse the cystine-induced inhibition is gradually diminished by increasing the time of cysteine pretreatment. (c) The inhibitory effect of cysteine pretreatment (37 degrees C, 10 min) is not reversed by the addition of Cu++. (d) In the presence of higher concentrations of catalase, the cystein-induced inhibition is recovered after the addition of equimolar concentration of N-ethylmaleimide. (e) Both inhibitions of cysteine on dopamine-beta-hydroxylase with and without pretreatment were the noncompetitive type to the substrate, tyramine.


In vitro comparison of disk diffusion and agar dilution antibiotic susceptibility test methods for Neisseria gonorrhoeae.
At present, most Neisseria gonorrhoeae testing is done with beta-lactamase and agar dilution tests with common therapeutic agents. Generally, in bacteriological diagnosis laboratories in Argentina, study of antibiotic susceptibility of N. gonorrhoeae is based on beta-lactamase determination and agar dilution method with common therapeutic agents. The National Committee for Clinical Laboratory Standards (NCCLS) has recently described a disk diffusion test that produces results comparable to the reference agar dilution method for antibiotic susceptibility of N. gonorrhoeae, using a dispersion diagram for analyzing the correlation between both techniques. We obtained 57 gonococcal isolates from patients attending a clinic for sexually transmitted diseases in Tucumán, Argentina. Antibiotic susceptibility tests using agar dilution and disk diffusion techniques were compared. The established NCCLS interpretive criteria for both susceptibility methods appeared to be applicable to domestic gonococcal strains. The correlation between the MIC's and the zones of inhibition was studied for penicillin, ampicillin, cefoxitin, spectinomycin, cefotaxime, cephaloridine, cephalexin, tetracycline, norfloxacin and kanamycin. Dispersion diagrams showed a high correlation between both methods.


Localization of actin-related sequences by in situ hybridization to R-banded human chromosomes.
Using a cytoplasmic actin cDNA probe we have localized a number of actin sequences in the human genome using a novel in situ hybridization technique. Metaphase chromosomes treated to produce R-bands were directly annealed with 125I-labeled actin probe. Under these conditions many regions of the genome were apparently denatured enough to be capable of hybridizing with the probe. Most of the actin sites detected in prior experiments using chromosome preparations, which had been completely denatured, were recognized in this experiment. The major advantage of this method over standard in situ hybridization techniques is the marked increase in the resolution of subregional localization.


An audit of diabetes care at 3 centres in Alexandria.
Selected indicators for structure, process and outcome of care were used to audit diabetes care in 3 centres in Alexandria. Structure was poor: main problems included absence of appointment and recall system, deficiencies in laboratory resources and lack of educational material. Process of care was poor for 69.2% of patients: deficiencies included absence of essential information in records and missing some essential clinical examinations. Degree of control was poor for 49.2% of patients and only 30.6% had no complications. Compliance to appointment was good for about 80% of patients. Better outcome (fewer complications and higher compliance) was significantly associated with poor process of care. This cannot, however, be considered a valid predictor of outcome as good care might be initiated by the presence of complications.


[A case of direct carotid cavernous fistula, whom three-dimensional computed tomographic angiography was helpful for decision making of selective coil embolization].
We reported the case of an 84-year-old female suffering from chemosis and exophthalmos. Carotid arteriograms revealed a direct carotid-cavernous fistula (CCF) but could not clearly show the fistula point because of its high-flow nature. We then performed three-dimensional computed tomographic angiography (3D-CTA) using a multi detector-row CT (MDCT) scanner. Multi-planar reformatted CT images distinctly revealed a right carotid aneurysm at the cavernous portion and a shunting point between the aneurysm and the cavernous sinus. Based on this information, we opted to performa transvenous coil embolization to treat this patient. Successful selective coil embolization was performed at the fistulous point was done with a smaller number of coils than ordinarily required in sinus packing. Performing 3D-CTA by using a MDCT was helpful in decision making for the selective coil embolization to treat direct CCF.


Unusual case of pulmonary renal syndrome with autopsy findings.
Scleroderma renal crises (SRC) is a serious complication of systemic sclerosis whose prognosis remains serious despite management with angiotensin-converting enzyme inhibitors, antihypertensives and dialysis. Pulmonary renal syndrome (PRS), characterised by diffuse alveolar hemorrhage (DAH) and SRC, is rare and carries a grave prognosis. This case report discusses the clinicopathological features of a 43-year-old male presenting with severe hypertension and rapidly progressive renal failure who subsequently developed DAH and died. The clinical course, exhaustive investigative work-up and autopsy findings led to a diagnosis of diffuse systemic sclerosis with PRS subcategorized into PRS with thrombotic microangiopathy. The index case came without a prior diagnosis of systemic sclerosis, thereby posing a serious diagnostic challenge and management issues.


Melanoma genetics.
Approximately 10% of melanoma cases report a relative affected with melanoma, and a positive family history is associated with an increased risk of developing melanoma. Although the majority of genetic alterations associated with melanoma development are somatic, the underlying presence of heritable melanoma risk genes is an important component of disease occurrence. Susceptibility for some families is due to mutation in one of the known high penetrance melanoma predisposition genes: CDKN2A, CDK4, BAP1, POT1, ACD, TERF2IP and TERT. However, despite such mutations being implicated in a combined total of approximately 50% of familial melanoma cases, the underlying genetic basis is unexplained for the remainder of high-density melanoma families. Aside from the possibility of extremely rare mutations in a few additional high penetrance genes yet to be discovered, this suggests a likely polygenic component to susceptibility, and a unique level of personal melanoma risk influenced by multiple low-risk alleles and genetic modifiers. In addition to conferring a risk of cutaneous melanoma, some 'melanoma' predisposition genes have been linked to other cancers, with cancer clustering observed in melanoma families at rates greater than expected by chance. The most extensively documented association is between CDKN2A germ line mutations and pancreatic cancer, and a cancer syndrome including cutaneous melanoma, uveal melanoma and mesothelioma has been proposed for BAP1 germ line mutations. Other medium to high penetrance melanoma predisposition genes have been associated with renal cell carcinoma (MITF, BAP1) and glioma (POT1). These associations between melanoma and other cancers hint at the possibility of common pathways for oncogenesis, and better knowledge of these pathways may improve understanding of the genetic basis underpinning familial melanoma. It is likely that 'melanoma' risk genes will impact on mutation screening and genetic counselling not only for melanoma but also a range of other cancers.


Biowaiver monographs for immediate release solid oral dosage forms: amodiaquine hydrochloride.
The present monograph reviews data relevant to applying the biowaiver procedure for the approval of immediate release (IR) multisource solid dosage forms containing amodiaquine hydrochloride (ADQ) as the single active pharmaceutical ingredient (API). Both biopharmaceutical and clinical data of ADQ were assessed. Solubility studies revealed that ADQ meets the "highly soluble" criteria according to World Health Organization (WHO) and European Medicines Agency (EMA) but fails to comply with the United States Food and Drug Administration (US FDA) specifications. Although metabolism hints at high permeability, available permeability data are too scanty to classify ADQ inequivocably as a Class I drug substance. According to WHO and EMA guidances, ADQ would be conservatively categorized as a Class III drug, whereas according to the US FDA specifications, it would fall into Class IV. ADQ has a wide therapeutic index. Furthermore, no cases of bioinequivalent products have been reported in the open literature. As risks associated with biowaiving appear minimal and requirements for "highly soluble" API are met in the WHO and EMA jurisdictions, the biowaiver procedure can be recommended for bioequivalence (BE) testing of multisource IR products containing ADQ as the only API, provided the test product contains excipients used in ADQ products approved in International Conference of Harmonisation and associated countries, and in similar amounts. Furthermore, both comparator and test should conform to "very rapidly dissolving" product criteria (≥85% dissolution of the API in 15 min at pH 1.2, 4.5, and 6.8) and the labeling should specify that the product not be coadministered with high-fat meals. If the comparator and/or test product fails to meet these criteria, BE needs to be established by pharmacokinetic studies in humans.


Insights into B-type RR members as signaling partners acting downstream of HPt partners of HK1 in the osmotic stress response in Populus.
The B-type response regulators (B-type RRs), final elements of a signaling pathway called "histidine/aspartate phosphorelay system" in plants, are devoted to the regulation of response genes through a transcription factor activity. Signal transduction consists in the transfer of a phosphoryl group from a transmembrane histidine kinase (HK) which recognizes a given stimulus to nuclear RRs via cytosolic shuttle phosphotransfer proteins (HPts). In Arabidopsis, the receptors HK are to date the major characterized candidates to be responsible for initiation of osmotic stress responses. However, little information is available concerning the signaling partners acting downstream of HKs. In Populus, three HPts and five B-type RRs were previously identified as interacting partners of HK1, the Arabidopsis AHK1 homolog. Here, we report the isolation of RR18, a member of the B-type RR family, which shares high sequence similarities with ARR18 characterized to act in the osmosensing signaling pathway in Arabidopsis, from poplar cuttings subjected to osmotic stress conditions. By using yeast and in planta interaction assays, RR18 was further identified as acting downstream of HK1 and its three preferential HPt partners. Besides, our results are in favor of a possible involvement of both RR18 and RR13, the main expressed poplar B-type RR, in the osmotic signaling pathway. Nonetheless, different behaviors of these two B-type RRs in this pathway need to be noted, with one RR, RR13, acting in an early phase, mainly in roots of poplar cuttings, and the other one, RR18, acting in a late phase, mainly in leaves to supply an adequate response.


Regulation of renal Na(+),K(+)-ATPase and ouabain-sensitive H(+),K(+)-ATPase by the cyclic AMP-protein kinase A signal transduction pathway.
We investigated the effect of the cyclic AMP-protein kinase A (PKA) signalling pathway on renal Na(+),K(+)-ATPase and ouabain-sensitive H(+),K(+)-ATPase. Male Wistar rats were anaesthetized and catheter was inserted through the femoral artery into the abdominal aorta proximally to the renal arteries for infusion of the investigated substances. Na(+),K(+)-ATPase activity was measured in the presence of Sch 28080 to block ouabain-sensitive H(+),K(+)-ATPase and improve specificity of the assay. Dibutyryl-cyclic AMP (db-cAMP) administered at a dose of 10(-7) mol/kg per min and 10(-6) mol/kg per min increased Na(+),K(+)-ATPase activity in the renal cortex by 34% and 42%, respectively, and decreased it in the renal medulla by 30% and 44%, respectively. db-cAMP infused at 10(-6) mol/kg per min increased the activity of cortical ouabain-sensitive H(+),K(+)-ATPase by 33%, and medullary ouabain-sensitive H(+),K(+)-ATPase by 30%. All the effects of db-cAMP were abolished by a specific inhibitor of protein kinase A, KT 5720. The stimulatory effect on ouabain-sensitive H(+),K(+)-ATPase and on cortical Na(+),K(+)-ATPase was also abolished by brefeldin A which inhibits the insertion of proteins into the plasma membranes, whereas the inhibitory effect on medullary Na(+),K(+)-ATPase was partially attenuated by 17-octadecynoic acid, an inhibitor of cytochrome p450-dependent arachidonate metabolism. We conclude that the cAMP-PKA pathway stimulates Na(+),K(+)-ATPase in the renal cortex as well as ouabain-sensitive H(+),K(+)-ATPase in the cortex and medulla by a mechanism requiring insertion of proteins into the plasma membrane. In contrast, medullary Na(+),K(+)-ATPase is inhibited by cAMP through a mechanism involving cytochrome p450-dependent arachidonate metabolites.


Phenotypic and genetic divergence among harbour porpoise populations associated with habitat regions in the North Sea and adjacent seas.
Determining the mechanisms that generate population structure is essential to the understanding of speciation and the evolution of biodiversity. Here, we investigate a geographical range that transects two habitat gradients, the North Sea to North Atlantic transition, and the temperate to subpolar regions. We studied the harbour porpoise (Phocoena phocoena), a small odontocete inhabiting both subpolar and temperate waters. To assess differentiation among putative populations, we measured morphological variation at cranial traits (N = 462 individuals) and variation at eight microsatellite loci for 338 of the same individuals from Norwegian, British and Danish waters. Significant morphological differentiation reflected the size of the buccal cavity. Porpoises forage in relatively shallow waters preying mainly on benthic species in British and Danish waters, and on mesopelagic and pelagic fish off the coast of Norway. We suggest that the observed differentiation may be explained by resource specialization and either adaptation or developmental responses to different local habitats.


Hypoglycemia associated with carcinoid tumors. A case report and review of the literature.
The authors report a 73-year-old man with a jejunal carcinoid tumor and spontaneous hypoglycemia. Plasma insulin was suppressed (insulin/glucose ratio, 0.2), and nonsuppressible insulin-like proteins (NSILP) were elevated. Seven other patients with carcinoid or related tumors associated with hypoglycemia were found in the literature. Nonsuppressible insulin-like proteins were not measured in these patients.


"A life of living death": the experiences of people living with chronic low back pain in rural Nigeria.
This study explored the experiences of people living with non-specific chronic low back pain (CLBP) in a rural Nigerian community. Qualitative in-depth semi-structured face-to-face interviews were conducted with purposively sampled participants until data saturation. Questions explored back pain beliefs, coping/management strategies and daily activities. Thematic analysis of transcripts was performed using the Framework approach. Themes showed that back pain beliefs were related to manual labour/deprivation, infection/degeneration, spiritual/cultural beliefs and rural-urban divide. These beliefs impacted on gender roles resulting in adaptive or maladaptive coping. Adaptive coping was facilitated by positive beliefs, such as not regarding CLBP as an illness, whereas viewing CLBP as illness stimulated maladaptive coping strategies. Spirituality was associated with both adaptive and maladaptive coping. Maladaptive coping strategies led to dissatisfaction with health care in this community. CLBP-related disability in rural Nigeria is strongly influenced by beliefs that facilitate coping strategies that either enhance or inhibit recovery. Interventions should therefore target maladaptive beliefs while emphasizing behavioural modification. Implications for Rehabilitation Non-specific chronic low back pain (CLBP) is highly prevalent and responsible for much pain and disability in rural Nigeria. No qualitative study has investigated the experiences of people living with CLBP in rural Nigeria or any other rural African context. Qualitative study of peoples' experiences of living with CLBP in rural Nigeria has the potential of exposing complex socio-cultural and psychological factors associated with CLBP which has potential implications for designing effective interventions. The results of this study may inform the development of complex interventions for reducing the disability associated with CLBP in rural Nigeria and other rural African contexts.


Management of skin loss in meningococcal infection.
The case of a 17-month-old girl with fulminant meningococcemia is presented to illustrate the protean and fulminant course of the disease. Special attention is given to the meningococcal skin manifestation, with guidelines for its treatment.


Expression of GluR6/7 subunits of kainate receptors in rat adenohypophysis.
We have previously demonstrated the presence of unidentified [3H]glutamate (Glu) binding sites with stereo-selectivity, high affinity and saturability in rat peripheral excitable tissues such as the pituitary (Yoneda, Y., Ogita, K., 1986a. [3H]Glutamate binding sites in the rat pituitary. Neurosci. Res. 3, 430--435) and adrenal (Yoneda, Y., Ogita, K., 1986b. Localization of [3H]glutamate binding sites in rat adrenal medulla. Brain Res. 383, 387--391, 1986). In this study, peripheral binding sites were further evaluated for the ionotropic Glu receptor subtype insensitive to N-methyl-D-aspartate by using reverse transcription polymerase chain reaction (RT-PCR) and Western blotting, in addition to receptor binding using radiolabeled ligands other than [3H]Glu. Binding of [3H]kainate (KA) and [3H]DL-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate was detected in membrane preparations obtained from the rat pituitary and adrenal irrespective of prior treatment with Triton X-100. An RT-PCR analysis revealed constitutive expression of mRNA for GluR1, GluR3, GluR5, KA1 and KA2 subunits in the rat adrenal and pituitary, as well as the brain and retina. The pituitary also expressed mRNA for GluR2, GluR4, GluR6 and GluR7 subunits in contrast to the adrenal. Under our experimental conditions employed, however, Western blotting assays failed to confirm the expression of receptor proteins for GluR1, GluR2/3 and GluR4 subunits in the adrenal cortex, adrenal medulla, adenohypophysis and neurohypophysis. Immunoreactive GluR6/7 subunits were only detectable in the adenohypophysis, but not in the adrenal cortex, adrenal medulla and neurohypophysis. An intraperitoneal injection of KA doubled DNA binding activity of the nuclear transcription factor activator protein-1 in the rat pituitary, with concomitant more potent potentiation of that in the hippocampus. These results suggest that GluR6/7 subunits of KA receptors may be constitutively expressed with responsiveness to the systemic administration of an agonist at least in the rat adenohypophysis.


Effects of polyphosphate additives on the pH of processed chicken exudates and the survival of Campylobacter.
Campylobacter spp. are nutritionally fastidious organisms that are sensitive to normal atmospheric oxygen levels and lack homologues of common cold shock genes. At first glance, these bacteria seem ill equipped to persist within food products under processing and storage conditions; however, they survive in numbers sufficient to cause the largest number of foodborne bacterial disease annually. A mechanism proposed to play a role in Campylobacter survival is the addition of polyphosphate-containing marinades during poultry processing. Campylobacter jejuni and Campylobacter coli strains incubated in chicken exudates collected from poultry treated with a marinade demonstrated considerable survival advantages (1 to 4 log CFU/ml) over the same strains incubated in chicken exudate from untreated birds. Polyphosphates, which constitute a large portion of the commercial poultry marinades, were shown to account for a majority of the observed influence of the marinades on Campylobacter survival. When six different food grade polyphosphates (disodium pyrophosphate, tetrasodium pyrophosphate, pentasodium triphosphate, sodium polyphosphate, monosodium phosphate, and trisodium phosphate) were utilized to compare the survival of Campylobacter strains in chicken exudate, significant differences were observed with regard to Campylobacter survival between the different polyphosphates. It was then determined that the addition of polyphosphates to chicken exudate increased the pH of the exudate, with the more sodiated polyphosphates increasing the pH to a greater degree than the less sodiated polyphosphates. It was confirmed that the change in pH mediated by polyphosphates is responsible for the observed increases in Campylobacter survival.


How do homozygous parents affect TDT as a test for association?
The traditional transmission disequilibrium test (TDT) (Spielman et al., 1993) is a powerful test for association only in the presence of linkage. Since allele transmissions from homozygous parents do not carry any information on linkage, the TDT statistic uses data only on heterozygous parents. However, homozygous parents carry information on association between alleles at a marker locus and a disease locus. In this article, we explore whether inclusion of homozygous parents increases the power to detect association. The resultant test statistic follows a chi(2) distribution with 2 degrees of freedom. Monte-Carlo simulations are included to compare the performance of this test with the traditional TDT under different disease models.


Efficacy and Safety of Platelet Glycoprotein Receptor Blockade in Aged and Comorbid Mice With Acute Experimental Stroke.
Despite the medical and socioeconomic effect of ischemic stroke and extensive preclinical research, treatment options for ischemic stroke are limited. We recently identified and characterized essential steps of thrombus formation in stroke and demonstrated that inhibition of the platelet glycoprotein (GP) receptors Ib and VI, but not IIb/IIIa, protects young and healthy mice from ischemic neurodegeneration. Whether these findings translate to the clinic remains unclear. Considering that the typical stroke patient is elderly with comorbidity, we aimed to analyze the efficacy and safety of novel preclinical antithrombotics in adult and comorbid mice with acute experimental stroke. We subjected adult, healthy, atherosclerotic (Ldlr(-/-)), diabetic (streptozotocin treated), and hypertensive (RenTgMK) mice to a 60-minute transient middle cerebral artery occlusion. Animals were pretreated with anti-GPVI antibodies or treated 1 hour after stroke induction with anti-GPIb or anti-GPIIb/IIIa antigen-binding fragments, respectively. Isotype treatment served as control. Twenty-four hours after transient middle cerebral artery occlusion, we visually assessed the intracerebral hemorrhage rate and measured infarct volumes (using 2,3,5-triphenyltetrazolium chloride-stained brain slices) and functional outcome (using Bederson and grip-test scores). GPIb and GPVI inhibition protected the mice from ischemic stroke without increasing bleeding complications. In contrast, GPIIb/IIIa inhibition was not protective but increased the intracerebral hemorrhage rate. Inhibition of early steps of thrombus formation protects adult and comorbid mice from ischemic stroke. The use of clinically meaningful mouse strains might improve the translation of preclinical stroke research to the clinic.


Adherence to the Mediterranean diet and risk of stroke and stroke subtypes.
Several meta-analyses including a small number of cohorts showed inverse associations between the Mediterranean Diet (MedDiet) and risk of stroke. However, it remains unclear whether such a relation varies by region of the study population or by major subtypes of stroke. We searched PubMed and EMBASE databases for relevant studies and we further included unpublished results from the Singapore Chinese Health Study (N = 57,078) and the Seguimiento Universidad de Navarra (SUN) study (N = 12,670). We used a random-effects model to calculate summary relative risk (RR) with 95% confidence intervals (CI) of stroke for each 4-point increment of the MedDiet score, roughly corresponding to the difference between extreme quintiles of the MedDiet score among participants of the included studies. The final analyses included 20 prospective cohort studies involving 682,149 participants and 16,739 stroke cases. The summary RRs for each 4-point increment of the MedDiet score were 0.84 (95% CI 0.81-0.88; I2 = 11.5%) for all combined, 0.76 (95% CI 0.65-0.89) for studies in Mediterranean populations and 0.86 (95% CI 0.83-0.89) for those in non-Mediterranean populations. Lower risk of stroke associated with higher MedDiet score also was observed in the analyses stratified by study population and methodological characteristics including study risk of bias, version of the MedDiet index, and definition of moderate alcohol consumption. The MedDiet was similarly associated with lower risk of ischemic stroke (RR 0.86, 95% CI 0.81-0.91; nine studies) and hemorrhagic stroke (RR 0.83, 95% CI 0.74-0.93; eight studies). Our meta-analysis suggests that adhering to the Mediterranean diet was associated with lower risk of stroke in both Mediterranean and non-Mediterranean populations, and for both ischemic stroke and hemorrhagic stroke risk.


Efficacy and safety of sitagliptin as add-on therapy on glycemic control and blood glucose fluctuation in Japanese type 2 diabetes subjects ongoing with multiple daily insulin injections therapy.
To assess the efficacy and safety of adding sitagliptin, an oral dipeptidyl peptidase-4 inhibitor, in subjects with type 2 diabetes inadequately controlled with multiple daily insulin injections therapy (MDI). HbA1c, 1,5-anhydroglucitol (1,5-AG), body mass index (BMI), insulin doses, six-point self-measured plasma glucose (SMPG) profiles were assessed before, after 12 weeks, and after 24 weeks of MDI with 50 mg/day of sitagliptin in 40 subjects with type 2 diabetes. Safety endpoints included hypoglycemia and any adverse events. HbA1c significantly decreased during the first 12 weeks ( -0.64±0.60%), and was sustained over 24 weeks ( -0.69±0.85%). 1,5-AG increased significantly from 7.5±4.5 μg/mL at baseline to 9.6±5.5 μg/mL after 24 weeks. The bolus insulin dose at 12 weeks was decreased, and the mean plasma glucose, the SD of daily glucose, M-value, and the mean amplitude of glycemic excursions (MAGE) also decreased significantly as compared with baseline values. BMI and frequency of hypoglycemia were not changed significantly. Univariate linear regression analyses revealed that % change in HbA1c was significantly associated with BMI, and % changes in the indexes of glycemic instability (SD of daily glucose and MAGE) were significantly associated with age. In conclusion, adding sitagliptin to MDI significantly improved glycemic control and decreased the daily glucose fluctuation in subjects with type 2 diabetes inadequately controlled with MDI, without weight gain or an increase in the incidence of hypoglycemia. This trial was registered with UMIN (no. UMIN000010157).


Effects of celecoxib on voltage-gated calcium channel currents in rat pheochromocytoma (PC12) cells.
Cyclooxygenase-2 (COX-2) plays crucial roles in the development and invasion of tumors. Celecoxib, a selective COX-2 inhibitor, has been shown to be chemopreventive against cancer. However, to date, the mechanisms of these effects remain unclear. In this study, we investigate the effects of celecoxib on voltage-gated calcium channel (VGCC) currents in undifferentiated pheochromocytoma (PC12) cells using whole-cell patch clamp. Our results showed that celecoxib, instead of rofecoxib or NS-398, another selective COX-2 inhibitor, reversibly inhibited the current density of VGCC in a concentration-dependent manner, but had no apparent effects on the cells treated with nifedipine (1 microM), an L-type calcium channel blocker. Upon pre-incubation of PC12 cells with omega-conotoxia GVIA (1 microM), an N-type calcium channel blocker, omega-agatoxin IVA (1microM), a P/Q-type calcium channel blocker, or SNX-482 (1microM), a R-type calcium channel blocker, celecoxib (1microM) inhibited the currents by 36%, 28%, and 25%, respectively. Celecoxib up-shifted the current-voltage (I-V), and hyperpolarizedly shifted the inactivation curve, but did not markedly affect the activation curve. Intracellular application of H89, a protein kinase A inhibitor, failed to affect the celecoxib's VGCC currents inhibition. Taken together, our present results suggested that celecoxib inhibited L-type calcium channels in PC12 cells via a COX-2 independent pathway, which might be responsible for its clinical effects including anti-tumor.


A Block-matching based technique for the analysis of 2D gel images.
Research at protein level is a useful practice in personalized medicine. More specifically, 2D gel images obtained after electrophoresis process can lead to an accurate diagnosis. Several computational approaches try to help the clinicians to establish the correspondence between pairs of proteins of multiple 2D gel images. Most of them perform the alignment of a patient image referred to a reference image. In this work, an approach based on block-matching techniques is developed. Its main characteristic is that it does not need to perform the whole alignment between two images considering each protein separately. A comparison with other published methods is presented. It can be concluded that this method works over broad range of proteomic images, although they have a high level of difficulty.