Subjective well-being and quality of life under atypical antipsychotic treatment.
The increasing interest in subjective well-being and quality of life of schizophrenic patients represents a conceptual shift in therapeutic outcome criteria. Symptom reduction alone was the most essential outcome parameter for a long time; with the development of atypical antipsychotics more ambitious success criteria, including the patients' perspective, are considered today. While effects on (positive) psychopathology do not differ markedly between typical and atypical antipsychotics, the lack of motor symptoms, the improvement of negative, affective and cognitive symptoms, and particularly the better subjective well-being as well as quality of life are major advantages for the new antipsychotic drugs. Quality of life assessment is a new methodological approach to differentiate therapeutic effects and to give more consideration to the patient's perspective. A number of disease-specific or generic scales have been used to measure quality of life of schizophrenic patients under neuroleptic treatment. There is strong evidence by seven controlled and eight open trials that in comparison to typical neuroleptics, atypicals increase the quality of life significantly, and the difference is of major clinical relevance in many patients. This review describes the development of quality of life research in schizophrenic patients, and summarises the methodological problems and the numerous clinical trials. Furthermore, the benefit of introducing atypical antipsychotics early in the course of illness and their particular benefit in combination with rehabilitative non-pharmacological treatment is discussed.


Threat of death and autobiographical memory: a study of passengers from Flight AT236.
We investigated autobiographical memory in a group of passengers onboard a trans-Atlantic flight that nearly ditched at sea. The consistency of traumatic exposure across passengers, some of whom developed post-traumatic stress disorder (PTSD), provided a unique opportunity to assess verified memory for life-threatening trauma. Using the Autobiographical Interview, which separates episodic from non-episodic details, passengers and healthy controls (HCs) recalled three events: the airline disaster (or a highly negative event for HCs), the September 11, 2001 attacks, and a non-emotional event. All passengers showed robust mnemonic enhancement for episodic details of the airline disaster. Although neither richness nor accuracy of traumatic recollection was related to PTSD, production of non-episodic details for traumatic and non-traumatic events was elevated in PTSD passengers. These findings indicate a robust mnemonic enhancement for trauma that is not specific to PTSD. Rather, PTSD is associated with altered cognitive control operations that affect autobiographical memory in general.


The prevalence of naturally occurring antibodies to human syncytial virus in East African populations.
A seroepidemiological study of naturally occurring antibodies to the human syncytial virus has been carried out by means of an indirect immunofluorescence test on 639 East Africans, consisting of 493 normal Ugandans, 66 Kenyan patients with nasopharyngeal carcinoma (NPC), and 80 Kenyan and Tanzanian patients with various other tumours or non-cancerous conditions. It was found that 3.4% of the normal individuals had antibodies to the virus and serial serum samples were available from 14 of these, permitting the study of antibody class in seroconversion and antibody persistence. As in an earlier survey, a significantly higher incidence of antibodies was found amongst NPC patients. Blocking and indirect immunofluorescence test with simian foamy viruses (SFV) showed some cross-reactivity between SFV 6 and the human syncytial virus, but not identity. The results are discussed in relation to the very real occurrence of natural infection by human syncytial virus in certain geographical regions.


Cell death in weaver mouse cerebellum.
Mice with the weaver mutation exhibit an uneven weave to their gait, ataxia, mild locomotor hyperactivity and, occasionally, tonic-clonic seizures. A single amino acid mutation in a G-protein coupled, inwardly rectifying K+ channel, GIRK2, gives rise to the symptoms seen in the weaver mice. Two areas of the brain are primarily affected. Cerebellar granule cell neurons die soon after birth and dopaminergic neurons are severely depleted in the substantia nigra. In this article we review recent studies of wild-type and mutant GIRK channels found in native cells or introduced into expression systems. We also review two models that explain some of the details leading to the neuronal cell death observed in weaver mice.


Protein chip and bioinformatic analyses of differentially expressed proteins involved in the effect of hydrogen-rich water on myocardial ischemia-reperfusion injury.
Background: The differentially expressed proteins (DEPs) involved in the effect of hydrogen-rich water on myocardial ischemia reperfusion injury (MIRI) and their biological processes and signaling pathway were analyzed. Methods: 20 Wistar rats were randomly and equally divided into a control and a hydrogen-rich group. Hearts were removed and fixed in a Langendorff device. The control group was perfused with K-R solution, and the hydrogen-rich water group was perfused with K-R solution + hydrogen-rich water. Protein was extracted from the ventricular tissues, and GSR-CAA-67 was used to identify the DEPs between two groups. DEPs were analyzed through bioinformatic methods. Results: Compared with the control group, in the treatment group, the expression of 25 proteins was obviously decreased (P<0.05). For the DEPs, 359 biological processes, including the regulation of signaling pathways, immune reaction and formation of cardiovascular endothelial cells, were selected by GO enrichment analysis. Five signaling pathways were selected by KEGG pathway enrichment analysis. Conclusions: 25 proteins that are involved in hydrogen-water reducing MIRI were selected by high-throughput GSR-CAA-67. The biological processes and metabolic pathways involved in the DEPs were summarized, providing theoretical evidence for the clinical application of hydrogen-rich water.


Induction and maintenance of the neuronal cholinergic phenotype in the central nervous system by BMP-9.
Bone morphogenetic proteins (BMPs) have multiple functions in the developing nervous system. A member of this family, BMP-9, was found to be highly expressed in the embryonic mouse septum and spinal cord, indicating a possible role in regulating the cholinergic phenotype. In cultured neurons, BMP-9 directly induced the expression of the cholinergic gene locus encoding choline acetyltransferase and the vesicular acetylcholine transporter and up-regulated acetylcholine synthesis. The effect was reversed upon withdrawal of BMP-9. Intracerebroventricular injection of BMP-9 increased acetylcholine levels in vivo. Although certain other BMPs also up-regulated the cholinergic phenotype in vitro, they were less effective than BMP-9. These data indicate that BMP-9 is a differentiating factor for cholinergic central nervous system neurons.


Effect of gentamicin on glomerular ultrastructure.
Previous micropuncture experiments have shown that gentamicin reduces the glomerular Kf even at low doses. Light and transmission electron microscopy have failed to provide evidence of structural alterations to explain the observed decreases in Kf. To elucidate and effects of gentamicin on glomerular ultrastructure, we used both scanning and transmission electron microscopy to study the glomeruli of rats given gentamicin at 4 and 40 mg/kg/day for 10 days, as well as 20 mg/kg/day for 4 weeks. Observations were also made during recovery from gentamicin-induced renal injury. Scanning and transmission electron microscopy revealed that gentamicin induced striking reductions in endothelial fenestral diameter, density, and area. These changes were not appreciated by light microscopy. By quantitative measurements, the reductions in endothelial fenestral area were found to be parallel to the previously observed reduction in Kf. During recovery, the morphological alterations improved pari passu with functional recovery. Contrary to observations in other models of acute renal failure, gentamicin-induced glomerular injury was unique in that the visceral epithelial surface was not affected. The mechanisms by which gentamicin induces alterations in glomerular ultrastructure remain to be defined.


Chlordecone, a mixed pregnane X receptor (PXR) and estrogen receptor alpha (ERalpha) agonist, alters cholesterol homeostasis and lipoprotein metabolism in C57BL/6 mice.
Chlordecone (CD) is one of many banned organochlorine (OC) insecticides that are widespread persistent organic pollutants. OC insecticides alter lipid homeostasis in rodents at doses that are not neurotoxic or carcinogenic. Pretreatment of mice or rats with CD altered tissue distribution of a subsequent dose of [(14)C]CD or [(14)C]cholesterol (CH). Nuclear receptors regulate expression of genes important in the homeostasis of CH and other lipids. In this study, we report that CD suppresses in vitro reporter systems for human liver X receptors (LXRs) and activates those for human farnesoid X receptor (FXR), pregnane X receptor (PXR) and estrogen receptor alpha (ERalpha) in a concentration-dependent manner (0-50 muM). Consistent with human PXR activation in vitro, three days after a single dose of CD (15 mg/kg) hepatic microsomal CYP3A11 protein increases in C57BL/6 mice. CD decreases hepatic CH ester content without altering total CH concentration. Apolipoprotein A-I (apoA-I) contents of hepatic lipoprotein-rich and microsomal fractions of CD-treated mice are higher than controls. There is a significant reduction in non-high density lipoprotein CH but not apolipoprotein B-48/100 (apoB-48/100) in plasma from CD-treated mice after a 4 h fast. At 14 days after 15 mg CD/kg apoA-I and apoB-100 proteins but not CYP3A11 protein in hepatic microsomes are similar to controls. This work indicates that altered CH homeostasis is a mode of OC insecticide action of relevance after a single dose. This at least partially explains altered CH tissue distribution in CD-pretreated mice.


Blood flow response to cryosurgery on basal cell carcinomas.
Cryosurgery with liquid nitrogen is commonly used to treat benign and malignant skin tumours. One of the crucial factors which influences the freezing and thawing rate of the target cells is the response of the microcirculation to cold stimulus. In our experiment, laser Doppler flowmetry was used to monitor blood flow during cryosurgical treatment of basal cell carcinomas. Outside the frozen tissue hemisphere, blood flow, as measured by laser Doppler flowmetry, increased almost instantaneously and remained on a high level during thawing. Baseline blood flow at the contralateral anatomical site remained stable. Pharmacological or physical modification of the cutaneous microcirculation before therapy may influence freezing and thawing times, and therefore the outcome with regard to healing, cosmetic appearance and the recurrence rate of basal cell carcinomas.


Access to Certified Burn Centers in the United States: The Geospatial and Transport Cost of Transfer.
Specialized burn centers are critical in minimizing burn-associated morbidity and mortality. However, American Burn Association (ABA)-verified burn centers are unequally distributed across the U.S., and fewer centers are available for pediatric patients relative to adults. The economic burden of transport to these centers contributes significantly to the high cost of burn care. This study quantifies inequitable burn care access in the contiguous U.S. due to age group and location as a function of physical proximity to a verified burn center and transportation cost. County-level distances to the nearest verified adult or pediatric burn center were determined and mapped. Distance calculations for each population were combined with transport cost data (2022 CMS Ambulance Fee Schedules) to estimate transportation costs for each population (adult versus pediatric, urban versus rural). Pediatric patients reside 30.5 miles further than adults from the nearest center, significantly increasing transportation costs. Ground and Air transport costs also increased for rural versus urban patients. Notably, rural patients face almost double the cost of air transport. While physical proximity to burn care appears to differ only modestly across age and region, this marginal increase in distance is associated with significant economic impact. This study highlights physical and economic barriers to burn care access faced by rural and pediatric patients and underscores the critical need to improve equity in burn care access.. Future studies should expand on this report's findings to more fully characterize additional costs associated with inequitable burn care access.


Comparative analysis of the genomes of cyanobacteria and plants.
Chloroplast genome originates from the genome of ancestral cyanobacterial endosymbiont. The comparison of the genomes of cyanobacteria and plants has been made possible by the advance in genome sequencing. I report here current results of our computational efforts to compare the genomes of cyanobacteria and plants and to trace the process of evolution of cyanobacteria, chloroplasts and plants. Cyanobacteria form a clearly defined monophyletic clade with reasonable level of diversity and are ideal for testing various approaches of genome comparison. Analysis of short sequence features such as genome signature was found to be useful in characterizing cyanobacterial genomes. Comparison of genome contents was performed by homology grouping of predicted protein coding sequences, rather than orthologue-based comparison, to minimize effects of multi-domain proteins and large protein families, both of which are important in cyanobacterial genomes. Comparison of the genomes of six species of cyanobacteria suggests that there are a number of species-specific additions of protein genes, and this information is useful in reconstructing phylogenetic relationship. The homology groups in cyanobacteria were used as a reference to compare plants and non-photosynthetic organisms. The results suggest that 238 groups that are common to all organisms analyzed may define a minimal set of gene groups. In addition, only 80 groups are identified as the gene groups that could not have been acquired by plants without cyanobacterial endosymbiosis. Further study is needed to identify plant genes of cyanobacterial origin.


Association between occupational exposure and Dupuytren's contracture using a job-exposure matrix and self-reported exposure in the CONSTANCES cohort.
Although several studies highlighted an association between occupational exposure and Dupuytren's contracture (DC), they were often limited by the highly selected population. We aimed to study this association using a job-exposure matrix (JEM) and self-reported exposure in a large cohort. From CONSTANCES, a French population-based prospective cohort, we retrieved sex, age, social position, alcohol/tobacco intake and diabetes. Lifetime exposures were assessed by two different methods: with the biomechanical JEM 'JEM Constances', we assessed exposure to vibration and/or forearm rotation for participants whose work history was available, and from a self-administered questionnaire, we retrieved self-reported exposure to arduous work and/or carrying heavy loads. Surgery for DC was collected from the French Health Administrative database from 2009 to 2016. Multivariate logistic regression models adjusted for confounders were built to assess association between surgery for DC and occupational exposures. Work history was retrieved for 23 795 subjects among whom 98 underwent surgery for DC. Adjusted OR (aOR) was 2.08 (1.03-4.2) for being ever exposed to vibration and/or forearm rotation for subjects <60 years and 1.20 (0.69-2.08) for subjects ≥60 years. Data for self-reported exposure were available for 81 801 participants among whom 367 underwent surgery for DC. aOR for being exposed more than 20 years to arduous work and/or carrying heavy loads was 2.01 (1.32-3.04) for subjects <60 years and 1.04 (0.7-1.54) for subjects ≥60. Manual work is associated with surgery for DC among younger subjects. Monitoring exposed workers is important to prevent future functional limitations.


Larval descriptions of the family Porcellanidae: A worldwide annotated compilation of the literature (Crustacea, Decapoda).
For most of the family Porcellanidae, which comprises 283 species, larval development remains to be described. Full development has been only described for 52 species, while part of the larval cycle has been described for 45 species. The importance of knowing the complete larval development of a species goes beyond allowing the identification of larval specimens collected in the plankton. Morphological larval data also constitute a support to cladistic techniques used in the establishment of the phylogenetic status (see Hiller et al. 2006, Marco-Herrero et al. 2013). Nevertheless, the literature on the larval development of this family is old and widely dispersed and in many cases it is difficult to collect the available information on a particular taxon. Towards the aim of facilitating future research, all information available on the larval development of porcellanids has been compiled. Following the taxonomic checklist of Porcellanidae proposed by Osawa and McLaughlin (2010), a checklist has been prepared that reflects the current knowledge about larval development of the group including larval stages and the method used to obtain the larvae, together with references. Those species for which the recognised names have been changed according to Osawa and McLaughlin (2010) are indicated.


Endocrine disruption in wild populations of chub (Leuciscus cephalus) in contaminated French streams.
The aim of this study was to assess endocrine disruptive effects in wild population of fish in five French rivers selected to represent different pollution contexts at two seasons (summer and fall). For that purpose, a panel of biometrical parameters (length, weight, and gonado-somatic index: GSI) and biochemical (ethoxyresorufin-O-deethylase: EROD, vitellogenin: VTG, and brain aromatase) and histological biomarkers (gonads histology) were used in chub (Leuciscus cephalus), a common cyprinid fish species. In fish from the reference site, EROD activity and VTG levels were low at the two seasons. Brain aromatase activities (AAs) were similar to other species and increased with increasing GSI and gonad maturation. Among the four contaminated sites, the Jalle d'Eysines River was the most impacted site. At this site, fish were exposed to estrogenic substances as demonstrated by the VTG induction in males and the arrest of development of the gonads that led to lower brain AA compared to fish from the reference site. In fish from other contaminated sites, EROD activity was induced as compared to fish from the reference site and some males had elevated concentrations of VTG. Moreover, the presence of aromatase-inhibiting compounds was demonstrated in the sediments of three contaminated sites, even if the precise nature of contaminants is not known. This study provides new data concerning endocrine disruption in wild fish populations inhabiting French rivers and demonstrates that measurements of in vivo and in vitro aromatase could be used as biomarkers of endocrine disruption in field studies.


Towards cross-Canada monitoring of the unregulated street drug supply.
The well-being of people who use drugs (PWUD) continues to be threatened by substances of unknown type or quantity in the unregulated street drug supply. Current efforts to monitor the drug supply are limited in population reach and comparability. This restricts capacity to identify and develop measures that safeguard the health of PWUD. This study describes the development of a low-barrier system for monitoring the contents of drugs in the unregulated street supply. Early results for pilot sites are presented and compared across regions. The drug content monitoring system integrates a low-barrier survey and broad spectrum urine toxicology screening to compare substances expected to be consumed and those actually in the drug supply. The system prototype was developed by harm reduction pilot projects in British Columbia (BC) and Montreal with participation of PWUD. Data were collected from harm reduction supply distribution site clients in BC, Edmonton and Montreal between May 2018-March 2019. Survey and urine toxicology data were linked via anonymous codes and analyzed descriptively by region for trends in self-reported and detected use. The sample consisted of 878 participants from 40 sites across 3 regions. Reported use of substances, their detection, and concordance between the two varied across regions. Methamphetamine use was reported and detected most frequently in BC (reported: 62.8%; detected: 72.2%) and Edmonton (58.3%; 68.8%). In Montreal, high concordance was also observed between reported (74.5%) and detected (86.5%) cocaine/crack use. Among those with fentanyl detected, the percentage of participants who used fentanyl unintentionally ranged from 36.1% in BC, 78.6% in Edmonton and 90.9% in Montreal. This study is the first to describe a feasible, scalable monitoring system for the unregulated drug supply that can contrast expected and actual drug use and compare trends across regions. The system used principles of flexibility, capacity-building and community participation in its design. Results are well-suited to meet the needs of PWUD and inform the local harm reduction services they rely on. Further standardization of the survey tool and knowledge mobilization is needed to expand the system to new jurisdictions.


Detection of Neisseria meningitidis in cerebrospinal fluid samples from suspicious cases of meningococcal meningitis using polymerase chain reaction and counterimmunoelectrophoresis.
Rapid diagnosis of meningococcal disease followed by an early treatment is essential. However, blood or cerebrospinal fluid cultures may not be successful because antibiotic treatment is often started before proper specimens are collected and because bacteria may die during transportation to the laboratory. Improvements in antibiotic therapy for specific microorganisms will require the use of more than one method for immunodiagnosis. In this study a collection of cerebrospinal fluid samples from Brazilian patients was analyzed. Gram stains, culture, counterimmunoelectrophoresis and clinical evaluations for meningococcal diseases were available. The sensitivity of nested PCR (nPCR) was 73% for cerebrospinal fluid of clinically suspected cases, whereas both sensitivity and specificity were 100% when subtypes of Brazilian epidemic strains (P1.7, P1.9 and P1.15) isolated from the samples were used.


Quantitative analysis of deconvolved X-ray absorption near-edge structure spectra: a tool to push the limits of the X-ray absorption spectroscopy technique.
A deconvolution procedure has been applied to K-edge X-ray absorption near-edge structure (XANES) spectra of lanthanoid-containing solid systems, namely, hexakis(dmpu)praseodymium(III) and -gadolinium(III) iodide. The K-edges of lanthanoids cover the energy range 38 (La)-65 (Lu) keV, and the large widths of the core-hole states lead to broadening of spectral features, reducing the content of structural information that can be extracted from the raw X-ray absorption spectra. Here, we demonstrate that deconvolution procedures allow one to remove most of the instrumental and core-hole lifetime broadening in the K-edge XANES spectra of lanthanoid compounds, highlighting structural features that are lost in the raw data. We show that quantitative analysis of the deconvolved K-edge XANES spectra can be profitably used to gain a complete local structural characterization of lanthanoid-containing systems not only for the nearest neighbor atoms but also for higher-distance coordination shells.


Application of TaqMan low-density arrays for simultaneous detection of multiple respiratory pathogens.
The large and growing number of viral and bacterial pathogens responsible for respiratory infections poses a challenge for laboratories seeking to provide rapid and comprehensive pathogen identification. We evaluated a novel application of the TaqMan low-density array (TLDA) cards for real-time PCR detection of 21 respiratory-pathogen targets. The performance of the TLDA was compared to that of individual real-time PCR (IRTP) assays with the same primers and probes using (i) nucleic acids extracted from the 21 pathogen strains and 66 closely related viruses and bacteria and (ii) 292 clinical respiratory specimens. With spiked samples, TLDA cards were about 10-fold less sensitive than IRTP assays. By using 292 clinical specimens to generate 2,238 paired individual assays, the TLDA card exhibited 89% sensitivity (95% confidence interval [CI], 86 to 92%; range per target, 47 to 100%) and 98% specificity (95% CI, 97 to 99%; range per target, 85 to 100%) overall compared to IRTP assays as the gold standard with a threshold cycle (C(T)) cutoff of 43. The TLDA card approach offers promise for rapid and simultaneous identification of multiple respiratory pathogens for outbreak investigations and disease surveillance.


Effect of DNA repair deficiencies on the cytotoxicity of drugs used in cancer therapy - a review.
Tumor cells often have defects in DNA repair pathways that make them vulnerable to specific DNA-damaging anticancer agents. The identification of DNA repair defects in tumor cells and the evaluation of their influence on the cytotoxicity of anticancer drugs are active areas of scientific investigation that may help rationalize and improve cancer chemotherapy. This article reviews the available data on the influence of defects in proteins involved in the major DNA repair pathways (i.e., homologous recombination, non-homologous end joining, base excision repair, nucleotide excision repair, mismatch repair, Fanconi anemia repair, translesion synthesis and direct reversal repair) on the cytotoxicity of the FDA-approved anticancer drugs. It is shown that specific deficiencies in these DNA repair pathways alter the cytotoxicity of 60 anticancer drugs, including classical DNA-targeting drugs (e.g., alkylating agents, cytotoxic antibiotics, DNA topoisomerase inhibitors and antimetabolites) and other drugs whose primary pharmacological target is not the DNA (e.g., antimitotic agents, hormonal and targeted therapies). This information may help predict response to anticancer drugs in patients with tumors having specific DNA repair defects.


A Novel Miniaturized Biosensor for Monitoring Atlantic Salmon Swimming Activity and Respiratory Frequency.
The advanced development of sensor technologies has led to the emergence of fish biosensors that are currently used for research and commercial purposes. AEFishBIT is a miniaturized biosensor attached to fish operculum that measures physical activity and respiration frequencies. In this study, we determined the effect of the tagging method and evaluated the use of this biosensor to monitor post-smolt Atlantic salmon in a tank-based system. The use of piercing fish tag had a negative impact on the gills and operculum, unlike the identical protocols used in gilthead sea bream and European sea bass. In contrast, a surgical thread did not show any apparent tissue damage. Two data recording schedules were considered to monitor immediate early reaction to fish handling and light regime changes (records every 15 min over 2 days) or adaptation to new light conditions (records every 30 min over 4 days). Data showed stabilization of physical activity 8 h post-tagging, with different steady states for the activity/respiratory ratio after changes in light intensity that reflected a different time course adaptation to new light conditions. High correlations were observed between AEFishBIT and video recording data. These findings supported the use of AEFishBIT as a promising tool for smart sensing of Atlantic salmon.


Faecal peritonitis in the rat. An experimental model for evaluation of surgical and adjuvant therapies.
Wistar rats were equipped with two central venous catheters used for parenteral nutrition/antibiotics and blood sampling. The rats were conditioned in special cages and given a meat pellet diet to achieve a bowel flora more similar to man. When the animals after two weeks were adjusted to life in cages, meat pellets and indwelling non-functioning venous catheters, peritonitis was induced with a standardized 3 mm caecal perforation without any ligation or devascularization. Within few hours the animals were severe septic and blood cultures were positive in all with a mixed flora of gram-negative coliforms and anaerobic bacteroides. Important occurrence of circulating endotoxin was detected and found to increase gradually till death. Without any treatment this form of septic peritonitis gave a 100% mortality. Total parenteral nutrition (TPN) reduced mortality to 50%. Substitution of TPN with a simple saline/glucose solution gave the same survival rate demonstrating the importance of fluid supply and crystalloids during the early phase of septicaemia. Intravenously given antimicrobial agents active against anaerobes (tinidazole) and aerobes (cefotaxim) will in combination reduce mortality to less than 15%. The lethal effect of a 3 mm caecal perforation was almost abolished when TPN was added to this combination of antimicrobial agents. Continuous peritoneal irrigation did not increase survival rate.


Ultrasound assessment of the motion patterns of human flexor digitorum superficialis and profundus tendons with speckle tracking.
The purposes of our study were to correlate ultrasonographically measured and joint angle estimated excursions of the flexor digitorum superficialis (FDS) and flexor digitorum profundus (FDP) tendons of the hand and to estimate the relative motion of FDS and FDP while gripping cylinders of standard diameter in normal human subjects. Thirty wrists from 15 human subjects were imaged with an ultrasound scanner. Speckle tracking was used to measure the excursion of the FDS and FDP tendons. The tendon excursions necessary to grip three differently sized acrylic tubes were measured and correlated with the corresponding finger joint angles. The FDP/FDS excursion ratio was calculated. The Pearson's correlation coefficient between the FDS excursion and MP + PIP joint angle was 0.61. The Pearson's correlation coefficient between the FDP + FDS excursion and the DIP + PIP + MP joint angle was 0.67. The FDP/FDS excursion ratio was smaller for larger excursions (gripping a smaller diameter tube) and larger for small excursions (gripping a larger diameter tube, P < 0.01). These data suggest that speckle tracking may be a useful method to discriminate the relative motion of flexor tendons, which in turn may be relevant in evaluating tendon function, for example after tendon injury.


[Analysis of Single Particle Aging and Mixing State at an Agriculture Site (Quzhou) in the North China Plain in Summer Using a Single Particle Aerosol Mass Spectrometer].
To characterize the size distribution and chemical ompsitins f abiet prtices t a agicuturesit intheNorh o Chinese Plain, a single particle aerosol mass spectrometer (SPAMS) was deployed from June 30 to July 8, 2013. A total of 230,152 particles in the size range of 0.2-2.0 pm were chemically analyzed with both positive and negative ion spectra. The results revealed that aerosol could he classified into eight dominant groups, including elemental carbon (EC, 55.5%), organic carbon (OC, 10.7%), alkalis (Na-K, 17.4%), other metals (1.7%), Fe-rich (6.3%), Pb-rich (3.1%), dust (4.8%), and other (0.8%). The observed eight types of particles contained secondary components such as 46NO2-, 62NO3-, 96SO3-, 96SO4-, 97HSO4-, showing that they probably went through different aging processes. The analysis of particle size distribution showed that 700-800 nm was the peak value of all particles, and that dust and Fe particles were mainly in the coarse size range. EC particles subtype group research revealed EC particles tended to be aging with the above mentioned secondary ions and eventually led to a particle type conversion from EC to the less aging ECN and the more serious aging ECS, the diurnal variation of which was obviously negatively correlated, and there was a possibility of forming OC/EC mixture with the adsorption of secondary organic matter on EC surface.


The mediating effect of psychological resilience between social support and anxiety/depression in people living with HIV/AIDS-a study from China.
Objective To understand the relationship between psychological resilience in social support and anxiety/depression in people living with HIV/AIDS and to verify whether there is a mediating effect. Methods The questionnaire was administered to 161 people living with HIV/AIDS in a hospital. The questionnaire contained a general questionnaire, the Hospital Anxiety and Depression Scale (HADS), the Psychological Resilience Inventory (CD-RICS), and the Social Collaborative Support Scale (PSSS), and Pearson correlation analyses were used to explore the correlation between the factors and anxiety/depression, stratified linear regression analyses were used to validate the mediation model, and the bootstrap method was used to test for mediating effects. Results Anxiety was negatively correlated with psychological resilience and social support (r=-0.232, P < 0.01; r=-0.293, P < 0.01); depression was negatively correlated with psychological resilience and social support (r=-0.382, P < 0.01; r=-0.482, P < 0.01); there was a mediation effect model of social support between psychological resilience and anxiety/depression; psychological resilience played a fully mediating role in social support and anxiety/depression, with an effect contribution of 68.42%/59.34% and a 95% CI(-0.256~-0.036)/(-0.341 to~-0.106). Conclusion Psychological resilience plays a complete mediating effect between social support and anxiety/depression. It is recommended that more channels of social support be provided to patients with HIV/AIDS, thereby enhancing their psychological resilience and reducing anxiety/depression levels.


Grip strength and grip endurance in physical therapy students.
A hand-grip dynamometer was used to test the maximal grip strength and endurance index of 15 male and 15 female physical therapy students. The results showed that there was no apparent correlation between maximal grip strength and endurance index in the male subjects, but there was a tendency for endurance index to decrease as maximal grip strength increases in the female subjects. Maximal grip strength and body weight were positively correlated in both the males and the females. There was no significant difference in endurance index between the males and the females.


Sulfated oligosaccharides: new targets for drug development?
Sulfated oligosaccharides display an important role in biological processes. They bind proteins through interactions mediated by highly specific sequences (heparin - antithrombin, heparan sulfate - growth factors / herpes simplex virus) or by electrostatic interaction between sulfate groups and cationic sites of proteins. Sulfated oligosaccharides are involved in biological events as protein localisation at cell surfaces, the control of proteolysis, the modulation of the angiogenesis and metastasis of tumours, the oligomerisation of cell growth factors. Sulfated residues have been recently found in glycoproteins, as GlcNAc or Mannose in N-glycosidic chains of different sources: gp120 of HIV, the envelope glycoprotein of influenza virus, the cysteine protease of Trypanosoma cruzi. This paper reviews recent findings concerning the implication of sulfated sugars in carbohydrate - protein interactions, from glycosaminoglycans to glycosidic chains in proteins, and their potential application as new targets for drugs/vaccines/diagnosis developments will be discussed. New approaches for their detection and analysis (ESI-MS, MALDI, Molecular Imprinting) are presented.


[Radio-ecological and genetic assessment of late consequences of Totsk nuclear explosion].
Radio-ecological and cytogenetic assessments were made in the vicinity of Totsk nuclear explosion in the Orenburg Region. Increased contents of radioactive isotopes Cs and Pu were detected in the soil. A comparative cytogenetic analysis indicated that the population continued to be exposed to radioactive agents.


[Nursing consultation: analysis of actions in programs for arterial hypertension, in Fortaleza].
The nurses' performance in a hypertension and diabetes programs has been important, once its approach is not only directed to illness, but also to the patient as a whole. Therefore, the nursing consultation is a unique moment of this approach. This is a descriptive study aiming at searching the activities performed in the nursing consultations that are performed within Hypertension Programs in the city of Fortaleza, State of Ceará, Brazil. The data were gathered from March to May 1999, with 14 nurses, who work in these services. Data were analyzed according to Bardin's content analysis as well as the categorical analysis. The results showed that the nursing consultation is still based on the traditional curative medical model. The activities performed by nurses are restricted to anamnesis, brief physical examination and diet orientations, medications, walks and use of infusions. In the consultations, individual care prevails, without considering family and group approaches.


The impact of health insurance market reforms on market competition.
To assess the impact of state and federal health insurance market reforms on the nature and extent of market competition. Qualitative, comparative case studies in 7 states. Two rounds of in-depth interviews were conducted with over 100 key informants from the insurance industry. In each state, these sources included 2 to 4 regulators, 5 to 6 independent agents, and several sources at each of 4 to 5 of the top insurers. Extensive documentary data relating to market activity were also collected. These multiple sources of information and data were analyzed with both qualitative and quantitative techniques. (1) Small-group health insurance markets are highly competitive, both in price and in product innovation and diversity. (2) In some of the more heavily regulated states, there is very little competition in less-populated areas, especially for indemnity insurance. (3) The rapid growth of managed care in the small-group market may have been precipitated by these reforms. (4) Standardized benefit plans have not achieved their objectives. (5) Competitive forces still focus to a considerable extent on risk selection techniques. Small-group market reforms have not harmed market competition and may have improved competition in several respects. However, these reforms do not alter the fundamental orientation of competitive insurance markets, which is to focus on risk selection factors and techniques to the extent feasible.


Impact of low-dose irradiation and in vivo T-cell depletion on hematopoietic stem cell transplantation for non-malignant diseases using fludarabine-based reduced-intensity conditioning.
Reduced-intensity conditioning is widely used with hematopoietic stem cell transplantation for non-malignant diseases: however, the optimal conditioning to ensure stable engraftment has not been established. In this study, we retrospectively compared the impact of low-dose (1-6 Gy) irradiation and in vivo T-cell depletion on the clinical outcome of 523 patients with non-malignant disease who underwent a first allogeneic hematopoietic stem cell transplantation using fludarabine-based reduced-intensity conditioning. Use of low-dose irradiation, but not of anti-thymocyte globulin/anti-lymphocyte globulin, showed a beneficial effect on overall survival (adjusted hazard ratio: 0.56; 95% confidence interval: 0.35-0.91, P = 0.018). Furthermore, use of low-dose irradiation was strongly associated with lower transplant-related mortality (adjusted hazard ratio: 0.55; 95% confidence interval: 0.32-0.96, P = 0.034). The addition of low-dose irradiation to the conditioning regimen was beneficial, at least to the short-term clinical outcome. A large prospective study with long-term follow-up is now required to extend these findings and establish the optimal hematopoietic stem cell transplant conditioning for patients with at least some subgroups of non-malignant diseases.


CD8+ cell lines isolated from HIV-1-infected children have potent soluble HIV-1 inhibitory activity that differs from beta-chemokines.
CD8+ cells from human immunodeficiency virus type 1 (HIV-1) infected individuals have been shown to suppress HIV-1 replication both through a major histocompatibility complex (MHC)-restricted cytolytic pathway as well as through a noncytolytic pathway mediated through soluble factors. To characterize this soluble activity and its potential role in disease progression further, we studied the HIV-1 inhibition by supernatants derived from herpesvirus saimiri-transformed CD8+ cells isolated from infected children. Three of the six CD8+ cell lines derived had a phenotype consistent with an unusual natural killer (NK) cells phenotype with low CD3, high CD56, and low CD16. Supernatants from some of the cell lines derived from children with rapid progression as well as long-term nonprogressors exhibited broad HIV-1-inhibitory activity in primary CD4+ cells as well as in primary macrophages. In contrast to a cocktail of beta-chemokines, the supernatants inhibited T-tropic as well as M-tropic viruses, efficiently inhibited infection in primary macrophages, and inhibited HIV-1 activation in the chronically infected U1 cell line. The HIV-1-inhibitory activity was heat stable and active over a broad pH range. Fractionation of the supernatant by size and ion exchange chromatography demonstrated activity in the complete absence of RANTES as well as interferons-alpha, beta, and gamma and in a size range of less than 10 kD and greater than 3 kD. CD8+ cell supernatants contain additional unidentified factors that have anti-HIV activity to account for this broad phenomenon.


Discordant non-invasive prenatal testing (NIPT) - a systematic review.
With a high sensitivity and specificity, non-invasive prenatal testing (NIPT) is an incomparable screening test for fetal aneuploidy. However, the method is rather newly introduced, and experiences with discordant results are few. We did a systematic review of literature reporting details of false positive and false negative NIPT results. Discordant sex chromosome results were not included. We identified 22 studies reporting case details. In total, 206 discordant cases were included, of which 88% were false positive and 12% false negative. Details on maternal age, gestational age, platform/company, Z-score, fetal fraction, results and explanation were specified. The main reasons for discordant results were confined placental mosaicism, maternal copy number variation, vanished twin, maternal cancer and true fetal mosaicism. A very high percentage of cases (67%) were reported with no obvious biological or technical explanation for the discordant result. The included cases represent only a minor part of the true number of false positive or false negative NIPT cases identified in fetal medicine clinics around the world. To ensure knowledge exchange and transparency of NIPT between laboratories, we suggest a systematic recording of discordant NIPT results, as well as a quality assurance by external quality control and accreditation. © 2017 John Wiley & Sons, Ltd.


Shared Selective Pressures on Fungal and Human Metabolic Pathways Lead to Divergent yet Analogous Genetic Responses.
Reduced metabolic efficiency, toxic intermediate accumulation, and deficits of molecular building blocks, which all stem from disruptions of flux through metabolic pathways, reduce organismal fitness. Although these represent shared selection pressures across organisms, the genetic signatures of the responses to them may differ. In fungi, a frequently observed signature is the physical linkage of genes from the same metabolic pathway. In contrast, human metabolic genes are rarely tightly linked; rather, they tend to show tissue-specific coexpression. We hypothesized that the physical linkage of fungal metabolic genes and the tissue-specific coexpression of human metabolic genes are divergent yet analogous responses to the range of selective pressures imposed by disruptions of flux. To test this, we examined the degree to which the human homologs of physically linked metabolic genes in fungi (fungal linked homologs or FLOs) are coexpressed across six human tissues. We found that FLOs are significantly more correlated in their expression profiles across human tissues than other metabolic genes. We obtained similar results in analyses of the same six tissues from chimps, gorillas, orangutans, and macaques. We suggest that when selective pressures remain stable across large evolutionary distances, evidence of selection in a given evolutionary lineage can become a highly reliable predictor of the signature of selection in another, even though the specific adaptive response in each lineage is markedly different.


Fabrication of a Nanosized g-C3N4-Loaded Cellulose Microfiber Bundle to Induce Highly Efficient Water Treatment via Photodegradation .
Graphite carbon nitride (g-C3N4) with a suitable structure and strong amine activity is designed and prepared to serve as a hydrogen bond donor for the microfibrilization of corncob cellulose to form a cellulose microfiber (CMF) bundle. Simultaneously, well-dispersed nanosized g-C3N4 is loaded into the bundle to form a photocatalyst for efficient photodegradation of rhodamine B (Rh B) in water. Under the optimal preparation conditions at 165 °C, 10 min, and 0.08 mol/L H2SO4, the yield of g-C3N4-functionalized cellulose microfibers (CMF-g-C3N4) reaches to the highest over 70%. The catalytic rate of CMF-g-C3N4 is 3.3 times larger than that of pure g-C3N4. The degradation rate of Rh B is maintained at over 90% in 10 cycles of photocatalytic degradation. The obtained CMF-g-C3N4 also has good thermal stability and mechanical properties. This research suggests a particularly simple way to transform cellulose into a highly efficient photocatalyst for water treatment.


Management of scrotal gangrene.
Sixteen cases of scrotal gangrene are presented. The aetiology, environmental factors and pattern of clinical presentation are described. A total reconstruction of the scrotal sac in all cases as practised in Ife is described. It is advocated that surgeons in the tropics should, in spite of various constraints, try to salvage any infected testis before considering orchidectomy. Infective gangrene of the scrotum is considered a more suitable diagnostic label than Fournier's gangrene.


Protection against cisplatin-induced toxicities by N-acetylcysteine and sodium thiosulfate as assessed at the molecular, cellular, and in vivo levels.
Cisplatin (CDDP) is a common, highly toxic chemotherapeutic agent. This study investigates chemoprotective effects of N-acetylcysteine (NAC) and sodium thiosulfate (STS) on in vitro and in vivo CDDP toxicities. For ototoxicity studies, CDDP (6 mg/kg) was administered to rats via a retrograde carotid artery infusion. Auditory brainstem response thresholds at 4 to 20 kHz were tested before and 7 days post-treatment. STS (8 g/m(2) i.v.) was administered at 4, 8, or 12 h after CDDP. For nephrotoxicity studies, rats were treated with CDDP intraperitoneally (10 mg/kg) before or after NAC (400 mg/kg) or STS (8 g/m(2)), and blood urea nitrogen (BUN) and creatinine concentrations were measured after 3 days. In vitro cytotoxicity and chemoprotection in human tumor cell lines were assessed by cell viability and immunoblotting assays. Rats treated with STS 4 h after CDDP exhibited no hearing change. The STS 8-h group had less otoprotection, whereas 12-h rats had ototoxicity. CDDP induced high BUN and creatinine, corresponding to renal tubule toxicities. All NAC-treated animals showed normal BUN and reduced creatinine levels compared with CDDP alone and no histopathological evidence of nephrotoxicity. Delayed STS treatment was not consistently protective against nephrotoxicity. STS administration fully protected against the in vitro cytotoxic and apoptotic effects of CDDP if added within 2 h of CDDP, but chemoprotection decreased if STS administration was 4 h, and was minimal by 6 h, after CDDP. Thus, the chemoprotection route and timing of administration can be manipulated to maintain CDDP antitumor efficacy while protecting against toxicities.


[Measurement of the Fowler dead space in patients with pulmonary emphysema using C18O2].
In patients with lung emphysema, changes in lung volumes as well as changes in airway resistance are well known. The change in airway resistance is caused by obstruction of central airways, which is supposed to reduce the respiratory dead space. Until now, it was not possible to measure the respiratory dead space in patients with lung emphysema using the method of Fowler [2], because in this method distinction of the three phases of an inert gas expirogram is essential. While this distinction is easy in healthy subjects (fig. 1; expirogram 3), the separation of the three phases in patients with lung emphysema is not possible due to gradual transition of phase II into phase III in these patients (fig. 1; expirogram 2). The use of C18O2 as tracer gas allows to separate phase II and phase III even if the patients have severe emphysema (fig. 1; expirogram 1). CO2 labeled with the stable oxygen isotope 18O (C18O2) is completely taken up in the gas exchanging region of the lung, but not from the conducting airways. Therefore C18O2 is only expired from the dead space of the lung, but not from the alveolar region. Hence, C18O2 allows exact measurement of the respiratory dead space in patients with lung emphysema. 21 healthy nonsmoking subjects and 29 patients with clinical signs of lung emphysema participated in this study. There was a good correlation between respiratory dead space, measured by the use of Ar-gas and C18O2-gas in healthy subjects (fig. 2). This indicates, that the use of C18O2 is a valid method to measure the functional dead space. As expected, there was also a correlation between the airway resistance and respiratory dead space in patients with lung emphysema (fig. 3), but not in healty subjects. There was no significant difference of the mean values of the respiratory dead space between these two groups (223 +/- 43 ml in healthy subjects vs. 227 +/- 52 ml in patients), even though there were large differences in airway resistance (0.20 +/- 0.10 kPa/l/s vs. 0.49 +/- 0.27 kPa/l/s). This may be due to a loss of alveolar function in the area of the terminal bronchioli, which is typical for emphysematous patients. This entails a shift of functional dead space towards lung periphery and therefore causes an increase of the volume of functional dead space. But this enlargement may be compensated by the volume reduction, caused by the airway obstruction. Hence, these two oppositional mechanisms may result in only minimal change of dead space volume.


Bean ribonuclease-like pathogenesis-related protein genes (Ypr10) display complex patterns of developmental, dark-induced and exogenous-stimulus-dependent expression.
The intracellular pathogenesis-related (PR) proteins of common bean (Phaseolus vulgaris L.) are encoded by a highly polymorphic family of at least 20 genes. One member, the Ypr10*c gene, has been isolated and characterised. The deduced amino acid sequence of the encoded protein, PR-10, exhibits similarities to tree-pollen allergens, to food allergens from celery and apple and to ginseng ribonuclease peptide sequences. We show by RNA blot analysis that the Ypr10 gene family, including Ypr10*c, is strongly expressed in bean roots. In leaves Ypr10 transcript levels are low in young and mature stages but are elevated during senescence and in diseased states. Dark treatment of leaves causes strong induction of Ypr10 transcripts, which is reversible by light, and diurnal rhythms of transcript accumulation during the night are observed. Ypr10 genes are responsive to external stimuli related to pathogen-defence such as glutathione or salicylic acid. Transcriptional activity of a Ypr10*c promoter-beta-glucuronidase fusion gene in transgenic tobacco was observed in roots, in developing xylem and phloem of stems, and in the blade of senescent leaves, with highest levels at the onset of senescence. The most striking characteristic of developmental expression was the specific localisation of beta-glucuronidase activity in the transmitting tract of styles in flowers at anthesis. Feeding of various pathogen-related and stress-related stimuli to young tobacco leaves led to accumulation of GUS activity in leaf blades. We identify considerable spatio-temporal similarities between reported expression patterns of Ypr10 genes and ribonuclease genes, which, together with the significant sequence similarity to the ginseng ribonuclease, support the hypothesis of a ribonuclease function for PR-10 proteins and allow the prediction of possible biological roles.


Comparative absorption of theophylline from theophylline-guaifenesin tablets and liquid and from a reference theophylline liquid.
This single-dose, three-way crossover study in 18 healthy adults compared the oral absorption of theophylline from a theophylline-guaifenesin tablet and from a theophylline-guaifenesin liquid with absorption from a theophylline liquid. Each dose form contained 500 mg theophylline and, when indicated, 400 mg guaifenesin. The extents of theophylline absorption from the formulations were within 10% of each other. The absolute differences in the areas under the curve among the formulations were small and, although significantly higher statistically for the theophylline-guaifenesin tablet, are without therapeutic consequence. The theophylline plasma level curves from each of the three formulations were similar. Comparable theophylline absorption and elimination characteristics were seen.


Association of Dynapenia, Sarcopenia, and Cognitive Impairment Among Community-Dwelling Older Taiwanese.
A decline in physical and/or cognitive function is a common feature of aging, and frailty has been shown to be associated with cognitive impairment and dementia. This study aimed to evaluate the association between dynapenia, sarcopenia, and cognitive impairment among community-dwelling older people in Taiwan. Data from the I-Lan Longitudinal Aging Study (ILAS) were retrieved for study. Global cognitive function was assessed by Mini-Mental State Examination (MMSE), whereas the Chinese Version Verbal Learning Test, Boston Naming Test, Verbal Fluency Test, Taylor Complex Figure Test, Digits Backward Test, and Clock Drawing Test were used to assess different domains of cognitive function. Association between sarcopenia and global cognitive function as well as all different dimensions of cognitive function were evaluated. Data from 731 elderly participants (mean age 73.4 ± 5.4 years, 53.8% males) were used for study analysis. The overall prevalence of sarcopenia was 6.8%, which was significantly higher in men (9.3% versus 4.1%, p < 0.05). The mean MMSE score was 23.4 ± 4.4 for all participants, and 10.3% of the study participants were cognitively impaired. Sarcopenia was not significantly associated with global cognitive function (odds ratio [OR] = 1.55, p = 0.317), but global cognitive impairment was significantly associated with low physical performance (OR = 2.31, p = 0.003) and low muscle strength (OR = 2.59, p = 0.011). Nonetheless, sarcopenia was significantly associated with impairment in the verbal fluency test (OR = 3.96, p = 0.006) after adjustment for potential confounders. Dynapenia was significantly associated with cognitive impairment in multiple dimensions and global cognitive function, but sarcopenia was only associated with an impaired verbal fluency test. Reduced muscle strength and/or physical performance related to non-muscle etiology were strongly associated with cognitive impairment. More longitudinal studies are needed.


A Cross-sectional, Descriptive Study of Medication Use Among Persons With a Gastrointestinal Stoma.
Research on the use of medications in people with intestinal stomas is lacking, creating gaps in knowledge of pharmacoepidemiology in these patients. A cross-sectional, descriptive study was conducted over a period of 4 months in Divinópolis, Brazil to describe the profile of medication use among people enrolled in the Health Support Service for People with Stoma - Level II (SSPS II) of a municipality in the state of Minas Gerais, Brazil. All patients from SSPS II with a colostomy or ileostomy were invited by phone to participate; those with incomplete registration data and/or who were <18 years old, hospitalized for any reason, or had their stoma reversed were excluded from participation. During home interviews, researchers obtained sociodemographic profiles (age, gender, education, occupation, and family income) and information on comorbidities, medication use, adherence to medication protocols (per the Morisky Green Levine test), polypharmacy, and adult/pharmaceutical care (medication description and indication, expiration date, self-medication). Drug storage was assessed by visual evaluation. The information was entered onto individual data sheets, numbered to ensure patient anonymity. The data then were entered into and analyzed using SSPS II statistical software using frequency measurements, measures of central tendency, and dispersion of demographic variables, health conditions, and medicine use. The study population included 59 persons (average age 66.9 ± 13.27 years), 36 (61.0%) women, 38 (64.4%) with an incomplete/primary level education, and 44 (74.5%) retired. Forty-nine (49) patients had a colostomy and 10 had an ileostomy; cancer was the main reason for stoma creation (61.1%). Half of the survey participants reported having 1 or 2 comorbidities (average 2.3); the most prevalent (52) was circulatory system disease among which hypertension (38, 64.4%) was most common. Analysis of the pharmacotherapeutic profile (prescribed and used) showed 89.8% of the study population used medication, and 52.8% were prescribed >5 medications (polypharmacy). Low and medium level adherence with prescriptions was noted (37.7%); 39.6% reported receiving no guidance on the use of the medication associated with their condition. Improper storage was observed in 33.9% of participants. In this population, persons with a stoma had complex pharmacotherapy, a high rate of polypharmacy, and deficiency in guidance on the use of medication. Further research into determining whether investments in both inclusion of a pharmacist on the team and more pharmacoepidemiological studies would improve patient care and medication safety in patients with a stoma is warranted.


Refinement of conformational preferences of Leu enkephalin and Tyr-Gly-Gly-Phe by 15N n.m.r.: chemical shifts and vicinal coupling constants.
15N labeled Tyr-*Gly-*Gly-*Phe (I) and Tyr-*Gly-*Gly-*Phe-*Leu or Leu-enkephalin (II) are taken as models to test the ability of 15N n.m.r. as conformational probe for peptide analysis. Analysis of the 3J 15N-1H alpha constants using a Karplus relationship permits the proposal of a 2-5 beta II' type turn for Leu-enkephalin, instead of the previously proposed 2-5 beta I bend. In the two peptides, side-chain populations for Phe and Leu residues are computed, without any assignment assumption, by an optimization procedure taking into account all the available vicinal coupling constants (3J H alpha H beta, 3J 13CO-H beta, 3J 15H-H beta). Our results confirm the upfield shift of the beta ProR proton relatively to the beta ProS for the beta CH2 group of Phe residue in Me2SO solution. In both peptides (I) and (II), the tg- rotamer is the most populated for residue Phe4, whereas in (II) only this rotamer is present for the Leu5 side-chain. This feature indicates that the hydrophobic group lies opposite to the N-terminal Tyr residue, a feature not found for the methionine side-chain in Met-enkephalin.


State of the art treatment options for Pakistan's opioid, alcohol and methamphetamine crisis.
The literature review was planned to discuss the extent of opioid, alcohol and methamphetamine use disorder in Pakistan, the neurobiology of opioids, alcohol and methamphetamine, the importance of medication-assisted treatment and recommendations for Pakistan. A PubMed literature search was conducted and newspaper articles were also reviewed. In per capita terms, Pakistan is reported to be the most heroin-addicted country in the world. Pakistan has a significant alcohol abuse issue as well. The newest epidemic is that of crystal methamphetamine or "ice" which is consuming the youth and urban elite. There are long-term structural and functional changes in the opioid-addicted brain and factors that influence the vulnerability to addiction. The genesis of Pakistan's opioid epidemic is critical to understand as the country became victim to the proximity to, and politics of, Iran and Afghanistan. There is poor resource allocation for the treatment of substance use disorder, especially in comparison to what is spent on counter-terrorism. Addiction has had a devastating effect on children and the youth of Pakistan. It is vital to recognise addiction as a chronic disease comparable to diabetes, hypertension and asthma; and not a personal weakness. Medication-assisted treatment includes using buprenorphine-naloxone and naltrexone for opioid use disorder, injectable naltrexone for alcohol use disorder, and mirtazapine and bupropion for amphetamine use disorder. Coordination between the healthcare system, the Anti-Narcotics Force, the pharmaceutical industry and parliament is important. A university-affiliated addiction centre should be developed so it can provide guidance with research and treatment. Buprenorphine-naloxone and injectable naltrexone are urgently needed at an institutional level for the treatment of opioid and alcohol use disorder.


Point shear wave elastography method for assessing liver stiffness.
To estimate the validity of the point shear-wave elastography method by evaluating its reproducibility and accuracy for assessing liver stiffness. This was a single-center, cross-sectional study. Consecutive patients with chronic viral hepatitis scheduled for liver biopsy (LB) (Group 1) and healthy volunteers (Group 2) were studied. In each subject 10 consecutive point shear-wave elastography (PSWE) measurements were performed using the iU22 ultrasound system (Philips Medical Systems, Bothell, WA, United States). Patients in Group 1 underwent PSWE, transient elastography (TE) using FibroScan (Echosens, Paris, France) and ultrasound-assisted LB. For the assessment of PSWE reproducibility two expert raters (rater 1 and rater 2) independently performed the examinations. The performance of PSWE was compared to that of TE using LB as a reference standard. Fibrosis was staged according to the METAVIR scoring system. Receiver operating characteristic curve analyses were performed to calculate the area under the receiver operating characteristic curve (AUC) for F ≥ 2, F ≥ 3 and F = 4. The intraobserver and interobserver reproducibility of PSWE were assessed by calculating Lin's concordance correlation coefficient. To assess the performance of PSWE, 134 consecutive patients in Group 1 were studied. The median values of PSWE and TE (in kilopascals) were 4.7 (IQR = 3.8-5.4) and 5.5 (IQR = 4.7-6.5), respectively, in patients at the F0-F1 stage and 3.5 (IQR = 3.2-4.0) and 4.4 (IQR = 3.5-4.9), respectively, in the healthy volunteers in Group 2 (P < 10(-5)). In the univariate analysis, the PSWE and TE values showed a high correlation with the fibrosis stage; low correlations with the degree of necroinflammation, aspartate aminotransferase and gamma-glutamyl transferase (GGT); and a moderate negative correlation with the platelet count. A multiple regression analysis confirmed the correlations of both PSWE and TE with fibrosis stage and GGT but not with any other variables. The following AUC values were found: 0.80 (0.71-0.87) for PSWE and 0.82 (0.73-0.89) for TE (P = 0.42); 0.88 (0.80-0.94) for PSWE and 0.95 (0.88-0.98) for TE (P = 0.06); and 0.95 (0.89-0.99) for PSWE and 0.92 (0.85-0.97) for TE (P = 0.30) for F ≥ 2, F ≥ 3 and F = 4, respectively. To assess PSWE reproducibility, 116 subjects were studied, including 47 consecutive patients scheduled for LB (Group 1) and 69 consecutive healthy volunteers (Group 2). The intraobserver agreement ranged from 0.83 (95%CI: 0.79-0.88) to 0.96 (95%CI: 0.95-0.97) for rater 1 and from 0.84 (95%CI: 0.79-0.88) to 0.96 (95%CI: 0.95-0.97) for rater 2. The interobserver agreement yielded values from 0.83 (95%CI: 0.78-0.88) to 0.93 (95%CI: 0.91-0.95). PSWE is a reproducible method for assessing liver stiffness, and it compares with TE. Compared with patients with nonsignificant fibrosis, healthy volunteers showed significantly lower values.


Plasmid DNA molecules complexed with cationic liposomes are protected from degradation by nucleases and shearing by aerosolisation.
The cationic liposome DOTAP was complexed with plasmid DNA encoding beta-galactosidase in various ratios. As the concentration of DOTAP increased, the DNA became increasingly refractory to staining with ethidium bromide, presumably because the DNA was becoming condensed and being encapsulated by the liposomes. Transfection by DNA-DOTAP complexes at all ratios tested was unaffected by treatment of the complexes with DNase I. This finding has relevance to clinical trials for gene therapy of cystic fibrosis, in which patients are normally removed from treatment with DNase before receiving administration of DNA. We additionally tested the effect of aerosolisation of the liposome-DNA complex and of the DNA alone on the efficiency of in vitro transfection. Aerosolised DNA complexed with fresh DOTAP led to much lower reporter gene expression in Cos 7 cells than non-aerosolised complex, since aerosolisation appeared to destroy almost all of the plasmid. However, complexing the plasmid before passage through the nebuliser did protect most of the DNA from degradation, as reflected in the levels of transfection obtained. These findings contribute towards an overall understanding of both how DNA-cationic liposome complexes are formed and their fate following administration in vivo.


Water availability and quality in the Gulf Cooperation Council countries: implications for public health.
Environmental problems and their potential impacts on public health vary in scale and time depending on the level and nature of pollutants. Although water is regarded as the source of all kinds of life on earth, it also acts as an efficient carrier of pollutants. Contamination of drinking water, agricultural water, or recreational water by infectious pathogens, chemical pollutants, or others can have significant impacts on public health. During the past few decades, waterborne diseases continued to spread and the health risks continued to increase. The correlation between water resources and public health is more evident in arid regions. This article discusses the availability of water resources in the Gulf Cooperation Council countries and elaborates on the possible impacts of water resources on public health. It emphasizes the importance of preservation of water quality and prevention of waterborne diseases, which could be achieved through a coordinated effort from diverse groups and disciplines.


Tetrahydroindenoindole inhibits the progression of diabetes in mice.
Diabetes is characterized by elevated fasting blood glucose (FBG) resulting from improper insulin regulation and/or insulin resistance. Herein we used female C57BL/6J mouse models for type 1 diabetes (streptozotocin [STZ] treatment) and type 2 diabetes (high-fat diet) to examine the ability of 4b,5,9b,10-tetrahydroindeno[1,2-b]indole (THII) to intervene in the progression of diabetes. THII (100 microM in drinking water) significantly diminished and partially reversed the increase in FBG levels produced by STZ. After 10 weeks on a high-fat diet, mice had normal FBG levels, but exhibited fasting hyperinsulemia and loss of glucose tolerance. THII significantly diminished these changes in glucose and insulin. In isolated liver mitochondria, THII inhibited succinate-dependent H(2)O(2) production, while in white adipose tissue, THII inhibited NADPH oxidase-mediated H(2)O(2) production and lipid peroxidation. Without intervention, such oxidative processes might otherwise promote diabetogenesis via inflammatory pathways. THII also increased O(2) consumption and lowered respiratory quotient (CO(2) produced/O(2) consumed) in vivo, indicating a greater utilization of fat for metabolic fuel. Increased metabolic utilization of fat correlated with a decrease in the rate of body weight gain in THII-treated mice fed the high-fat diet. We conclude that THII may retard the progression of diabetes via multiple pathways, including the inhibition of oxidative and inflammatory pathways.


Residual calcium ions depress activation of calcium-dependent current.
Calcium ions enter and accumulate during depolarization of some cells, activating a potassium current, IK(Ca), that depends on the cytoplasmic concentration of calcium ions, [Ca]i. However, elevation of [Ca]i can depress IK(Ca) elicited by a subsequent membrane depolarization. The depression of IK(Ca) is ascribed here to a [Ca]i-mediated inactivation of the voltage-gated calcium conductance, which causes a net reduction in calcium ions available for the activation of IK(Ca). This suggests that other processes dependent on gated calcium entry may also be depressed by small background elevations in cytosolic free calcium ions.


Creating a connected community: lessons learned from the Western new york beacon community.
Secure exchange of clinical data among providers has the potential to improve quality, safety, efficiency, and reduce duplication. Many communities are experiencing challenges in building effective health information exchanges (HIEs). Previous studies have focused on financial and technical issues regarding HIE development. This paper describes the Western New York (WNY) HIE growth and lessons learned about accelerating progress to become a highly connected community. HEALTHeLINK, with funding from the Office of the National Coordinator for Health Information Technology (ONC) under the Beacon Community Program, expanded HIE usage in eight counties. The communitywide transformation process used three main drivers: (1) a communitywide Electronic Health Record (EHR) adoption program; (2) clinical transformation partners; and (3) HIE outreach and infrastructure development. ONC Beacon Community funding allowed WNY to achieve a new level in the use of interoperable HIE. Electronic delivery of results into the EHR expanded from 23 practices in 2010 to 222 practices in 2013, a tenfold increase. There were more than 12.5 million results delivered electronically (HL7 messages) to 222 practices' EHRs via the HIE in 2013. Use of a secure portal and Virtual Health Record (VHR) to access reports (those not delivered directly to the EHR) also increased significantly, from 13,344 report views in 2010 to over 600,000 in 2013. The WNY Beacon successfully expanded the sharing of clinical information among different sources of data and providers, creating a highly connected community to improve the quality and continuity of care. Technical, organizational, and community lessons described in this paper should prove beneficial to others as they pursue efforts to create connected communities.


Paget's disease of the breast. A subtle clinical presentation.
Paget's disease of the breast often presents with an underlying palpable breast mass. However, the absence of an underlying mass at the time of diagnosis is associated with improved survival rates. A case is presented emphasizing the importance of careful clinical and biopsy examination when the disorder presents with subtle clinical findings.


Daily life activity routine discovery in hemiparetic rehabilitation patients using topic models.
Monitoring natural behavior and activity routines of hemiparetic rehabilitation patients across the day can provide valuable progress information for therapists and patients and contribute to an optimized rehabilitation process. In particular, continuous patient monitoring could add type, frequency and duration of daily life activity routines and hence complement standard clinical scores that are assessed for particular tasks only. Machine learning methods have been applied to infer activity routines from sensor data. However, supervised methods require activity annotations to build recognition models and thus require extensive patient supervision. Discovery methods, including topic models could provide patient routine information and deal with variability in activity and movement performance across patients. Topic models have been used to discover characteristic activity routine patterns of healthy individuals using activity primitives recognized from supervised sensor data. Yet, the applicability of topic models for hemiparetic rehabilitation patients and techniques to derive activity primitives without supervision needs to be addressed. We investigate, 1) whether a topic model-based activity routine discovery framework can infer activity routines of rehabilitation patients from wearable motion sensor data. 2) We compare the performance of our topic model-based activity routine discovery using rule-based and clustering-based activity vocabulary. We analyze the activity routine discovery in a dataset recorded with 11 hemiparetic rehabilitation patients during up to ten full recording days per individual in an ambulatory daycare rehabilitation center using wearable motion sensors attached to both wrists and the non-affected thigh. We introduce and compare rule-based and clustering-based activity vocabulary to process statistical and frequency acceleration features to activity words. Activity words were used for activity routine pattern discovery using topic models based on Latent Dirichlet Allocation. Discovered activity routine patterns were then mapped to six categorized activity routines. Using the rule-based approach, activity routines could be discovered with an average accuracy of 76% across all patients. The rule-based approach outperformed clustering by 10% and showed less confusions for predicted activity routines. Topic models are suitable to discover daily life activity routines in hemiparetic rehabilitation patients without trained classifiers and activity annotations. Activity routines show characteristic patterns regarding activity primitives including body and extremity postures and movement. A patient-independent rule set can be derived. Including expert knowledge supports successful activity routine discovery over completely data-driven clustering.


Comparison of ultrasonography, computed tomography and 99mTc liver scan in diagnosis of Budd-Chiari syndrome.
Ultrasonography, computed tomography and 99mTc liver scanning are all useful in diagnosis of patients with the Budd-Chiari syndrome. In a study to determine their comparative value characteristic findings were recorded in all nine patients at ultrasonography and in seven patients at computed tomography. In contrast 99mTc liver scan showed a characteristic pattern in only one of eight patients. In our experience intrahepatic venous abnormalities were seen better at ultrasonography than at computed tomography. In addition, abnormality in the direction of blood flow could be detected by pulsed Doppler examination. Ultrasonography is relatively inexpensive, readily accessible, does not require administration of radiation or contrast agents and therefore should be the primary non-invasive investigation of patients with Budd-Chiari syndrome, or those at risk of developing it.


Enzymic sulphation of p-nitrophenol and steroids by larval gut tissues of the southern armyworm (Prodenia evidania Cramer).
1. An enzyme system that catalyses the sulphation of p-nitrophenol, cholesterol, alpha-ecdysone, beta-sitosterol, dehydroepiandrosterone, oestrone and four other steroids of plant and insect origin was obtained from the soluble fraction of southern-armyworm gut tissues. 2. The enzyme system required ATP and inorganic sulphate, and activity was slightly enhanced in the presence of GSH. 3. The properties of this enzyme system with respect to pH, temperature, substrate and protein concentrations and various cofactors and reagents were studied. At -23 degrees C the enzyme preparation could be stored for 2 weeks without drastic loss of activity. At the end of storage for 1 month the loss of activity was approx. 21%. 4. The possible involvement of this enzyme system in insect endocrine control is discussed.


FFA4/GPR120: Pharmacology and Therapeutic Opportunities.
Free Fatty Acid receptor 4 (FFA4), also known as GPR120, is a G-protein-coupled receptor (GPCR) responsive to long-chain fatty acids that is attracting considerable attention as a potential novel therapeutic target for the treatment of type 2 diabetes mellitus (T2DM). Although no clinical studies have yet been initiated to assess efficacy in this indication, a significant number of primary publications and patents have highlighted the ability of agonists with potency at FFA4 to improve glucose disposition and enhance insulin sensitivity in animal models. However, the distribution pattern of the receptor suggests that targeting FFA4 may also be useful in other conditions, ranging from cancer to lung function. Here, we discuss and contextualise the basis for these ideas and the results to support these conclusions.


A temporal analysis of antioxidative defense responses in the phloem of Picea abies after attack by Ips typographus.
The temporal gradation of antioxidants was investigated on the phloem tissue of Norway spruce [Picea abies (L.) Karst.] in response to weather conditions and colonization levels of Ips typographus L. (Col., Scolytidae). Two weeks after pheromone dispensers were placed on trees, the initial reaction of Norway spruce to bark beetle attack resulted in moderately lowered levels of total glutathione (tGSH) and total cysteine. Likewise, the total ascorbic acid dropped slightly below the control levels, whereas the concentration of dehydroascorbic acid increased in comparison to the first sampling date. This transient degradation and oxidation of the glutathione and ascorbate system was accompanied by moderately increased concentrations of total phenolics. One month later, the shift in antioxidant balance after moderate attack differed quantitatively from the reaction after massive attack. An intensification of antioxidant defense occurred within moderately affected bark. Total cysteine and tGSH contents were markedly raised, whereas the concentrations of total ascorbic acid and total phenolics were slightly increased by moderate attack. On the other hand, massive bark beetle colonization caused a strong decrease in tGSH and total phenolics, whereas total cysteine and total ascorbic acid values remained at control level. Dependent upon the intensity and the success of the attack, a progressive degradation of antioxidants was determined at later sampling dates, which was accompanied by an obvious oxidation of the ascorbate and glutathione pools. With an unsuccessful defense upon massive attack, the thiols and total phenolics did not reach a new steady state, but deteriorated until the end of the brood beetles' development. In contrast, the dynamic antioxidative response within the moderately affected trees indicated an acclimation stage in the middle of July. It was characterized by a higher accumulation of tGSH, total ascorbic acid and total phenolics as well as a more reduced redox state of glutathione. A sequence of changes in the endogenous levels of antioxidant defense molecules in the bark beetle-affected Norway spruce showed consistency with the general ecophysiological stress-response concept, and provided important avenues for evaluating the role and effectiveness of antioxidants in systemic acquired resistance against the complex interactive effects of bark beetle attack and environmental factors.


[Prevalence and cause of dental loss in children and adolescents].
The author analyzes statistical data of examinations of the oral cavity and teeth and of sociological interviews of 739 schoolchildren of a Moscow school, carried out in March, 1997. Loss of teeth has been recorded; the data characterize the maxillodental status and dental health. Relationship between dental loss and such factors as sex, age, place of lost teeth (functional orientation in the maxilla and mandible), etc., has been established. The author emphasizes the need in regular check-ups of the oral cavity and teeth in various age groups of children and adolescents both in girls and boys and considers that both dentists and endocrinologists should take part in these check-ups.


Synthesis and Organization of Gold-Peptide Nanoparticles for Catalytic Activities.
A significant development in the synthesis strategies of metal-peptide composites and their applications in biomedical and bio-catalysis has been reported. However, the random aggregation of gold nanoparticles provides the opportunity to find alternative fabrication strategies of gold-peptide composite nanomaterials. In this study, we used a facile strategy to synthesize the gold nanoparticles via a green and simple approach where they show self-alignment on the assembled nanofibers of ultrashort oligopeptides as a composite material. A photochemical reduction method is used, which does not require any external chemical reagents for the reduction of gold ions, and resultantly makes the gold nanoparticles of size ca. 5 nm under mild UV light exposure. The specific arrangement of gold nanoparticles on the peptide nanofibers may indicate the electrostatic interactions of two components and the interactions with the amino group of the peptide building block. Furthermore, the gold-peptide nanoparticle composites show the ability as a catalyst to degradation of environmental pollutant p-nitrophenol to p-aminophenol, and the reaction rate constant for catalysis is calculated as 0.057 min-1 at a 50-fold dilute sample of 2 mg/mL and 0.72 mM gold concentration in the composites. This colloidal strategy would help researchers to fabricate the metalized bioorganic composites for various biomedical and bio-catalysis applications.


Anti-inflammatory IL-10 administration rescues depression-associated learning and memory deficits in mice.
Major depressive disorder is a widespread mood disorder. One of the most debilitating symptoms patients often experience is cognitive impairment. Recent findings suggest that inflammation is associated with depression and impaired cognition. Pro-inflammatory cytokines are elevated in the blood of depressed patients and impair learning and memory processes, suggesting that an anti-inflammatory approach might be beneficial for both depression and cognition. We subjected mice to the learned helplessness paradigm and evaluated novel object recognition and spatial memory. Mice were treated with IL-10 intranasally or/and microglia cells were depleted using PLX5622. Statistical differences were tested using ANOVA or t tests. We first established a mouse model of depression in which learning and memory are impaired. We found that learned helplessness (LH) impairs novel object recognition (NOR) and spatial working memory. LH mice also exhibit reduced hippocampal dendritic spine density and increased microglial activation compared to non-shocked (NS) mice or mice that were subjected to the learned helpless paradigm but did not exhibit learned helplessness (non-learned helpless or NLH). These effects are mediated by microglia, as treatment with PLX5622, which depletes microglia, restores learning and memory and hippocampal dendritic spine density in LH mice. However, PLX5622 also impairs learning and memory and reduces hippocampal dendritic spine density in NLH mice, suggesting that microglia in NLH mice produce molecules that promote learning and memory. We found that microglial interleukin (IL)-10 levels are reduced in LH mice, and IL-10 administration is sufficient to restore NOR, spatial working memory, and hippocampal dendritic spine density in LH mice, and in NLH mice treated with PLX5622 consistent with a pro-cognitive role for IL-10. Altogether these data demonstrate the critical role of IL-10 in promoting learning and memory after learned helplessness.


Interferon-gamma-responsive neuronal sites in the normal rat brain: receptor protein distribution and cell activation revealed by Fos induction.
Constitutive expression of the interferon-gamma receptor protein (IFN-gammaR), and the distribution of cells in which Fos, a marker of cell activation, is induced by intracerebroventricular administration of IFN-gamma, were studied in the rat brain by immunohistochemistry. IFN-gammaR immunopositivity was found in neuronal elements, which exhibited a selective distribution being concentrated in the piriform and entorhinal cortex, midline thalamus and medial hypothalamic structures, brainstem nociceptive relays (including the periaqueductal gray, the parabrachial nuclei and the caudal part of the spinal trigeminal nuclei), and circumventricular organs such as the median eminence and area postrema. IFN-gamma-induced Fos expression mostly corresponded to neuronal sites of receptor distribution. Because of its topographical distribution, it is suggested that activation of the IFN-gammaR in neurons may play a role to limit spread of infections in the brain and, in concert with other proinflammatory cytokines, to modulate adaptive responses to an antigen challenge mediated by the central nervous system.


Factors associated with neurocognitive test performance at baseline: a substudy of the INSIGHT Strategic Timing of AntiRetroviral Treatment (START) trial.
We describe neuropsychological test performance (NP) in antiretroviral treatment (ART)-naïve HIV-positive individuals with CD4 cell counts above 500 cells/μL. In a neurology substudy of the International Network for Strategic Initiatives in Global HIV Trials (INSIGHT) Strategic Timing of AntiRetroviral Treatment (START) study, eight neurocognitive tests were administered. The primary measure of NP was the quantitative NP z-score (QNPZ-8), the average of the z-scores for the eight tests. Associations of baseline factors with QNPZ-8 scores were assessed by multiple regression. Mild neurocognitive impairment (NCI) was defined as z-scores < -1 in at least two of six cognitive domains. A total of 608 participants had a median age of 34 years; 11% were women and 15% were black; the median time since HIV diagnosis was 0.9 years; the median CD4 cell count was 633 cells/μL; 19.9% had mild NCI. Better NP was independently associated with younger age, being white, higher body mass index (0.10 per 10 kg/m(2) higher), and higher haematocrit percentage (0.19 per 10% higher). Worse NP was associated with longer time since HIV diagnosis (-0.17 per 10 years), diabetes (-0.29) and higher Framingham risk score (-0.15 per 10 points higher). QNPZ-8 scores differed significantly between geographical locations, with the lowest scores in Brazil and Argentina/Chile. This is the largest study of NP in ART-naïve HIV-positive adults with CD4 counts > 500 cells/μL. Demographic factors and diabetes were most strongly associated with NP. Unmeasured educational/sociocultural factors may explain geographical differences. Poorer NP was independently associated with longer time since HIV diagnosis, suggesting that untreated HIV infection might deleteriously affect NP, but the effect was small.


Reduction of benzaldehyde catalyzed by papain-based semisynthetic enzymes.
Some features of native enzyme's active site were used to conjunction with a chemical reagent or modifying group, which would generate new functionality different from the natural enzyme. In order to obtain an efficient catalyst, we have designed four different molecular size N-derivatives of modifiers and introduced them into the active site of papain to obtain new semisynthetic enzymes, which were used as catalyst in reduction of benzaldehyde to yield benzyl alcohol respectively, and the reactions carried out with recycling agent in 0.1 M phosphate buffer pH 6.5 at 37 degrees C. The results had shown that a longer N-derivative of semisynthetic enzyme had higher catalytic activity. Furthermore, we propose a plausible model for the catalytic mechanism in the semisynthetic enzymes system.


Ankyrin-bound fatty acid turns over rapidly at the erythrocyte plasma membrane.
The membrane skeletal protein ankyrin was shown to be continuously acylated and deacylated with long-chain fatty acids in mature erythrocytes. At least a fraction of the lipid bound to ankyrin turned over rapidly (half-life, approximately 50 min) compared with the polypeptide backbone, which was stable throughout the erythrocyte life. This indicates a regulatory significance of the fatty acid modification for the function of ankyrin.


Beta carbonic anhydrases: novel targets for pesticides and anti-parasitic agents in agriculture and livestock husbandry.
The genomes of many insect and parasite species contain beta carbonic anhydrase (β-CA) protein coding sequences. The lack of β-CA proteins in mammals makes them interesting target proteins for inhibition in treatment of some infectious diseases and pests. Many insects and parasites represent important pests for agriculture and cause enormous economic damage worldwide. Meanwhile, pollution of the environment by old pesticides, emergence of strains resistant to them, and their off-target effects are major challenges for agriculture and society. In this study, we analyzed a multiple sequence alignment of 31 β-CAs from insects, some parasites, and selected plant species relevant to agriculture and livestock husbandry. Using bioinformatics tools a phylogenetic tree was generated and the subcellular localizations and antigenic sites of each protein were predicted. Structural models for β-CAs of Ancylostoma caninum, Ascaris suum, Trichinella spiralis, and Entamoeba histolytica, were built using Pisum sativum and Mycobacterium tuberculosis β-CAs as templates. Six β-CAs of insects and parasites and six β-CAs of plants are predicted to be mitochondrial and chloroplastic, respectively, and thus may be involved in important metabolic functions. All 31 sequences showed the presence of the highly conserved β-CA active site sequence motifs, CXDXR and HXXC (C: cysteine, D: aspartic acid, R: arginine, H: histidine, X: any residue). We discovered that these two motifs are more antigenic than others. Homology models suggested that these motifs are mostly buried and thus not well accessible for recognition by antibodies. The predicted mitochondrial localization of several β-CAs and hidden antigenic epitopes within the protein molecule, suggest that they may not be considered major targets for vaccines. Instead, they are promising candidate enzymes for small-molecule inhibitors which can easily penetrate the cell membrane. Based on current knowledge, we conclude that β-CAs are potential targets for development of small molecule pesticides or anti-parasitic agents with minimal side effects on vertebrates.


Infancy-onset dietary counseling of low-saturated-fat diet improves insulin sensitivity in healthy adolescents 15-20 years of age: the Special Turku Coronary Risk Factor Intervention Project (STRIP) study.
We reported previously that low-saturated-fat dietary counseling started in infancy improves insulin sensitivity in healthy children 9 years of age. The aim of this study was to evaluate the effect of lifelong dietary counseling on insulin sensitivity in healthy adolescents between 15 and 20 years of age. In addition, we examined dietary fiber intake and the polyunsaturated fatty acid (PUFA)+monounsaturated (MUFA)-to-saturated fatty acid (SFA) ratio in the intervention and control adolescents and the association of these dietary factors with homeostasis model of insulin resistance (HOMA-IR). The study comprised adolescents participating in the randomized, controlled Special Turku Coronary Risk Factor Intervention Project (STRIP) study, which aims to guide the study participants toward a diet beneficial for cardiovascular health. HOMA-IR was assessed annually between 15 and 20 years of age (n=518; intervention, n=245; control, n=273), along with diet, BMI, pubertal status, serum cotinine concentrations, and physical activity. Dietary counseling was given biannually during the follow-up. HOMA-IR was lower (7.5% on average) in the intervention group than in the control group between 15 and 20 years of age (P=0.0051). The intervention effect was similar in girls and boys. The PUFA+MUFA-to-SFA ratio was higher (P<0.0001) and the dietary fiber (g/MJ) intake was higher (P=0.0058) in the intervention group compared with the control group. There was no association between the PUFA+MUFA-to-/SFA ratio and HOMA-IR, whereas dietary fiber intake (g/MJ) was associated with HOMA-IR in girls (P<0.0001). Dietary counseling initiated in infancy and maintained until 20 years of age was associated with improved insulin sensitivity in adolescents.


School response to self-injury: Concerns of mental health staff and parents.
Nonsuicidal self-injury (NSSI) among adolescents poses a significant problem for schools, adolescents, and their families. However, appropriate guidelines for addressing NSSI, including when to disclose the behavior to parents, are currently lacking. The present study aimed to understand how school mental health staff and parents of secondary school students view NSSI to determine how parent-school communication about NSSI, and responses to NSSI, can be improved. Nineteen school mental health staff participated in interviews and 10 parents of adolescents with a history of NSSI completed open-ended questionnaire items. Staff identified that sector-wide NSSI policy and education for teachers and principals would help them feel more supported and improve consistency in addressing NSSI between and within schools. In contrast, parents wanted more support directed at them rather than solely their adolescent. Implications for policy and parental support provided by the school are discussed. (PsycINFO Database Record


Semantic Integrative Digital Pathology: Insights into Microsemiological Semantics and Image Analysis Scalability.
Being able to provide a traceable and dynamic second opinion has become an ethical priority for patients and health care professionals in modern computer-aided medicine. In this perspective, a semantic cognitive virtual microscopy approach has been recently initiated, the MICO project, by focusing on cognitive digital pathology. This approach supports the elaboration of pathology-compliant daily protocols dedicated to breast cancer grading, in particular mitotic counts and nuclear atypia. A proof of concept has thus been elaborated, and an extension of these approaches is now underway in a collaborative digital pathology framework, the FlexMIm project. As important milestones on the way to routine digital pathology, a series of pioneer international benchmarking initiatives have been launched for mitosis detection (MITOS), nuclear atypia grading (MITOS-ATYPIA) and glandular structure detection (GlaS), some of the fundamental grading components in diagnosis and prognosis. These initiatives allow envisaging a consolidated validation referential database for digital pathology in the very near future. This reference database will need coordinated efforts from all major teams working in this area worldwide, and it will certainly represent a critical bottleneck for the acceptance of all future imaging modules in clinical practice. In line with recent advances in molecular imaging and genetics, keeping the microscopic modality at the core of future digital systems in pathology is fundamental to insure the acceptance of these new technologies, as well as for a deeper systemic, structured comprehension of the pathologies. After all, at the scale of routine whole-slide imaging (WSI; ∼0.22 µm/pixel), the microscopic image represents a structured 'genomic cluster', enabling a naturally structured support for integrative digital pathology approaches. In order to accelerate and structure the integration of this heterogeneous information, a major effort is and will continue to be devoted to morphological microsemiology (microscopic morphology semantics). Besides insuring the traceability of the results (second opinion) and supporting the orchestration of high-content image analysis modules, the role of semantics will be crucial for the correlation between digital pathology and noninvasive medical imaging modalities. In addition, semantics has an important role in modelling the links between traditional microscopy and recent label-free technologies. The massive amount of visual data is challenging and represents a characteristic intrinsic to digital pathology. The design of an operational integrative microscopy framework needs to focus on scalable multiscale imaging formalism. In this sense, we prospectively consider some of the most recent scalable methodologies adapted to digital pathology as marked point processes for nuclear atypia and point-set mathematical morphology for architecture grading. To orchestrate this scalable framework, semantics-based WSI management (analysis, exploration, indexing, retrieval and report generation support) represents an important means towards approaches to integrating big data into biomedicine. This insight reflects our vision through an instantiation of essential bricks of this type of architecture. The generic approach introduced here is applicable to a number of challenges related to molecular imaging, high-content image management and, more generally, bioinformatics.