[Calculation of DNA condensation, caused by adsorption of ligands].
A method for calculating the curves of DNA transition from linear to condensed state upon binding of condensing ligands has been developed. The character of the transition and ligand concentration necessary for condensation have been shown to be governed by the length of DNA molecule, energy and stoichiometry parameters of DNA-ligand complex (equilibrium constant between linear and condensed form in the absence of ligands, constants for ligand binding to linear and condensed forms, the number of base pairs covered by one ligand, etc.). The results of the calculations indicate that only slight difference in the free energies of these states in free DNA (less than 6 cal/mole(bp) for DNA of 500 bp long) is sufficient for the existence of stable linear state in the absence of ligands (in free DNA) and the formation of stable condensed state upon complexation.


Iron accumulation causes impaired myogenesis correlated with MAPK signaling pathway inhibition by oxidative stress.
Skeletal muscle atrophy is caused by disruption in the homeostatic balance of muscle degeneration and regeneration under various pathophysiological conditions. We have previously reported that iron accumulation induces skeletal muscle atrophy via a ubiquitin ligase-dependent pathway. However, the potential effect of iron accumulation on muscle regeneration remains unclear. To examine the effect of iron accumulation on myogenesis, we used a mouse model with cardiotoxin (CTX)-induced muscle regeneration in vivo and C2C12 mouse myoblast cells in vitro. In mice with iron overload, the skeletal muscles exhibited increased oxidative stress and decreased expression of satellite cell markers. Following CTX-induced muscle injury, these mice also displayed delayed muscle regeneration with a decrease in the size of regenerating myofibers, reduced expression of myoblast differentiation markers, and decreased phosphorylation of MAPK signaling pathways. In vitro, iron overload also suppressed the differentiation of C2C12 myoblast cells but the suppression could be reversed by superoxide scavenging using tempol. Excess iron inhibits myogenesis via oxidative stress, leading to an imbalance in skeletal muscle homeostasis.-Ikeda, Y., Satoh, A., Horinouchi, Y., Hamano, H., Watanabe, H., Imao, M., Imanishi, M., Zamami, Y., Takechi, K., Izawa-Ishizawa, Y., Miyamoto, L., Hirayama, T., Nagasawa, H., Ishizawa, K., Aihara, K.-I., Tsuchiya, K., Tamaki, T. Iron accumulation causes impaired myogenesis correlated with MAPK signaling pathway inhibition by oxidative stress.


[Possible participation of pyrophosphate in ADP and ATP biosyntheses from exogenous adenine by a culture of Corynebacterium species VSTI-301].
The autolyzing culture of Corynebacterium species VSTI-301 producing the synthesis of ATP from exogenous adenine was found to contain enzyme systems, which phosphorylate AMP into ADP and ADP into ATP in the presence of pyrophosphate. The optimal conditions for manifestation of activities of both systems in a cell-free extract were determined. One of the enzymes, i. e. pyrophosphate : ADP phosphotransferase, was isolated and purified 76-fold.


Novel N-substituted 3 alpha-[bis(4'-fluorophenyl)methoxy]tropane analogues: selective ligands for the dopamine transporter.
A series of N-substituted 3 alpha-[bis(4'-fluorophenyl)methoxy]tropane analogues has been prepared that function as dopamine uptake inhibitors. The N-methylated analogue of this series had a significantly higher affinity for the dopamine transporter than the parent compound, N-methyl-3 alpha- (diphenylmethoxy)tropane (benztropine, Cogentin). Yet like the parent compound, it retained high affinity for muscarinic receptors. A series of N-substituted compounds were prepared from nor-3 alpha-[bis(4'-fluorophenyl)methoxy]tropane via acylation followed by hydride reduction of the amide or by direct alkylation. All compounds containing a basic tropane nitrogen displaced [3H]WIN 35,428 at the dopamine transporter (Ki range = 8.5-634 nM) and blocked dopamine uptake (IC50 range = 10-371 nM) in rat caudate putamen, whereas ligands with a nonbasic nitrogen were virtually inactive. None of the compounds demonstrated high binding affinity at norepinephrine or serotonin transporters. Importantly, a separation of binding affinities for the dopamine transporter versus muscarinic m1 receptors was achieved by substitution of the N-methyl group with other N-alkyl or arylalkyl substituents (eg. n-butyl, allyl, benzyl, 3-phenylpropyl, etc.). Additionally, the most potent and selective analogue in this series at the dopamine transporter, N-(4"-phenyl-n-butyl)-3 alpha-[bis(4'-fluorophenyl)methoxy]tropane analogue failed to substitute for cocaine in rats trained to discriminate cocaine from saline. Potentially, new leads toward the development of a pharmacotherapeutic for cocaine abuse and other disorders affecting the dopamine transporter may be discovered.


Isolation and characterization of bacteria capable of tolerating the extreme conditions of clean room environments.
In assessing the bacterial populations present in spacecraft assembly, spacecraft test, and launch preparation facilities, extremophilic bacteria (requiring severe conditions for growth) and extremotolerant bacteria (tolerant to extreme conditions) were isolated. Several cultivation approaches were employed to select for and identify bacteria that not only survive the nutrient-limiting conditions of clean room environments but can also withstand even more inhospitable environmental stresses. Due to their proximity to spacefaring objects, these bacteria pose a considerable risk for forward contamination of extraterrestrial sites. Samples collected from four geographically distinct National Aeronautics and Space Administration clean rooms were challenged with UV-C irradiation, 5% hydrogen peroxide, heat shock, pH extremes (pH 3.0 and 11.0), temperature extremes (4 degrees C to 65 degrees C), and hypersalinity (25% NaCl) prior to and/or during cultivation as a means of selecting for extremotolerant bacteria. Culture-independent approaches were employed to measure viable microbial (ATP-based) and total bacterial (quantitative PCR-based) burdens. Intracellular ATP concentrations suggested a viable microbial presence ranging from below detection limits to 10(6) cells/m(2). However, only 0.1 to 55% of these viable cells were able to grow on defined culture medium. Isolated members of the Bacillaceae family were more physiologically diverse than those reported in previous studies, including thermophiles (Geobacillus), obligate anaerobes (Paenibacillus), and halotolerant, alkalophilic species (Oceanobacillus and Exiguobacterium). Non-spore-forming microbes (alpha- and beta-proteobacteria and actinobacteria) exhibiting tolerance to the selected stresses were also encountered. The multiassay cultivation approach employed herein enhances the current understanding of the physiological diversity of bacteria housed in these clean rooms and leads us to ponder the origin and means of translocation of thermophiles, anaerobes, and halotolerant alkalophiles into these environments.


Osteocalcin has a muscle-protective effect during weight loss in men without metabolic syndrome: a multicenter, prospective, observational study.
Weight reduction often accompanies muscle loss. Existing studies highlight the involvement of osteocalcin (OC) in energy metabolism and its potential to prevent age-related muscle loss. Nevertheless, these studies predominantly involve individuals with hyperglycemia, yielding conflicting research outcomes. This study investigated the protective role of OC against muscle loss during weight reduction in individuals without metabolic syndrome (MetS). We enrolled 130 overweight or obese individuals without MetS in a 4-month high-protein, energy-restricted dietary weight management program conducted at two clinic centers. Body composition and laboratory tests were assessed both before and after weight loss. Correlation and regression analysis were made between the changes in metabolic indicators and muscle mass during weight loss. Following weight loss, there was a decrease in body mass index (BMI), percentage of body fat (PBF), visceral fat area (VFA), fasting insulin (FINS), homeostasis model assessment insulin resistance (HOMA-IR), glycated haemoglobin (HbA1c), and lipid profile, and increase in the percentage of skeletal muscle (PSM) and vitamin D. There was no change in osteocalcin (OC) during the intervention. Correlation analysis of the relative changes in all metabolic indicators revealed a positive correlation between OC and PSM (r=0.383, p=0.002). Multiple linear regression analysis found that OC has a significant protective effect on muscles during weight loss in males after adjusting for confounding factors (β=0.089, p=0.017). High-protein, energy-restricted diets demonstrate efficacy in enhancing metabolic indicators within the weight-loss population. Furthermore, OC exhibits a protective effect on muscle mass during weight reduction in individuals without MetS, with this effect being particularly evident in males.


Hereditary deficiency of C2 in association with linear scleroderma 'en coup de sabre'.
A 32-year-old man suffering from linear frontoparietal scleroderma was found to have low (less than 10% normal) serum classical pathway activity although C1q, C3, C4, C5, and total alternative pathway activity was normal. Addition of purified C2 led to complete restoration of the total hemolytic activity of the classical pathway. The C2 hemolytic assays showed that the patient was not totally deficient in C2. He had about 30% of the normal C2 level. Studies on his available nucleus family members in the Netherlands also showed that the deficiency was inherited; one of the patient's brothers and one of his daughters had half of the normal C2 levels. The C2 deficiency could not be corrected by a three-week regimen of danazol. To the best of our knowledge, this is the first documented case concerning an association of linear frontoparietal scleroderma with C2 deficiency.


Evaluation of modified dried vinasse as an alternative dietary protein source for broilers.
The increase in poultry production and the high cost of soybean led to the search for alternative protein sources. One of these sources is vinasse, a by-product of the baker's yeast industry. Modified dried vinasse (MDV) can be produced for use in poultry nutrition by making some improvements in vinasse. Therefore, the present study aimed to examine the effect of the usage of MDV in broiler diets. A total of 192 daily male Ross 308 chicks were randomly assigned to four groups. MDV was included at the levels of 0%, 2%, 4%, and 6% in the diets for 42-day trial. Linear significant improvements in the final weight, body weight gain, feed efficiency, and digestibility were seen with increasing MDV levels. The use of MDV caused a significant reduction in feed consumption. The relative weight percentages of abdominal fat and serum cholesterol concentration were reduced linearly with increases in MDV levels. MDV inclusion linearly decreased the malondialdehyde concentration, but increased 2,2-diphenyl-1-picrylhydrazyl radical scavenging activity in breast meat significantly. The protein content in breast meat was increased with MDV. Cecal beneficial microorganisms and serum IgG levels were increased linearly with MDV. In conclusion, results suggested that MDV could be a feasible option for alternative protein sources for broilers.


Effect of inositol hexakisphosphate on the spectroscopic properties of the nitric oxide derivative of ferrous naturally glycated human hemoglobin HbA1c.
The effect of inositol hexakisphosphate (IHP) on the spectroscopic (EPR and absorbance) properties of the nitric oxide derivative of ferrous naturally glycated human hemoglobin HbA1c (HbA1cNO) has been investigated quantitatively. The results obtained show that 1) both in the absence and presence of IHP, the EPR and absorbance spectra of HbA1cNO show the same basic characteristics described for the nitrosyl derivative of ferrous HbA0, the nonglycated major component of human hemoglobin (HbA0NO); and 2) HbA1cNO binds IHP with an apparent dissociation equilibrium constant (upsilon = 1.8 x 10(-2) M), which is at least four orders of magnitude higher than that estimated for the polyphosphate interaction with HbA0NO (less than or equal to 3 x 10(-6) M). These data provide further independent evidence that interaction(s) of polyphosphates at the specific cleft between beta-chains along the dyad-axis is sterically hindered in HbA1c by the presence of the two glucose residues covalently bound to the N-termini of beta-chains, this finding being in agreement with the reduced effect of polyanions on HbA1c spectral and ligand-binding properties.


An introduction to tympanometry.
The tympanogram is an objective measure of middle ear effusion or eustachian tube dysfunction. It provides information about the compliance or mobility of the tympanic membrane, the pressure within the middle ear and the volume of the external ear canal. Tympanograms are classified as type A (normal), type B (indicating fluid behind the tympanic membrane) or type C (indicating eustachian tube dysfunction). The objective data obtained by tympanometry are a useful adjunct in the diagnosis and follow-up of middle ear disease.


Mangiferin alleviates hypertension induced by hyperuricemia via increasing nitric oxide releases.
Mangiferin, a natural glucosyl xanthone, was confirmed to be an effective uric acid (UA)- lowering agent with dual action of inhibiting production and promoting excretion of UA. In this study, we aimed to evaluate the effect of mangiferin on alleviating hypertension induced by hyperuricemia. Mangiferin (30, 60, 120 mg/kg) was administered intragastrically to hyperuricemic rats induced by gavage with potassium oxonate (750 mg/kg). Systolic blood pressure (SBP), serum levels of UA, nitric oxide (NO), C-reactionprotein (CRP) and ONOO- were measured. The mRNA and protein levels of endothelial nitric oxide synthase (eNOS), intercellular adhesion molecule-1 (ICAM-1), CRP were also analyzed. Human umbilical vein endothelial cells (HUVECs) were used in vitro studies. Administration of mangiferin significantly decreased the serum urate level and SBP at 8 weeks and last to 12 weeks. Further more, mangiferin could increase the release of NO and decrease the level of CRP in blood. In addition, mangiferin reversed the protein expression of eNOS, CRP, ICAM-1 and ONOO- in aortic segments in hyperuricemic rats. The results in vitro were consistent with the observed results in vivo. Taken together, these data suggested that mangiferin has played an important part in alleviating hypertension induced by hyperuricemia via increasing NO secretion and improving endothelial function.


Mental health needs and accessing specialised healthcare in Mexican children with mental disorders: gender- and diagnosis-dependent differences.
Access describes factors that influence the initial contact or use of services, emphasising both the characteristics of patients and the health resources that influence the use of health services. To compare Mexican boys and girls with mental disorders, with respect to primary diagnosis, symptom onset, and seeking and accessing specialised mental health services (SMHS). Longitudinal data were collected from primary caregiver-reported assessments of 397 child-caretaker dyads (child mean age 12.17 years, range 5-18 years, 63% male) that were obtained in two psychiatric hospitals specialising in child mental healthcare. Student t-tests and χ2-tests were applied to compare boys and girls regarding their diagnosis and variables associated with the seeking of and access to SMHS. Hyperkinetic disorder was the most prevalent diagnosis in boys, whereas depressive disorder and anxiety disorder were most prevalent in girls. The mean age at symptom onset for boys was 7 years, compared with 10 years for girls. Hyperkinetic disorder had the earliest symptom onset (mean 5.9 years), followed by depressive disorder (mean 9.8 years) and anxiety disorder (mean 12 years). Delayed access to SMHS was associated with initially seeking care from a psychologist, whereas quicker access was associated with affiliation with the (now defunct) Popular Insurance, a programme that served low-income and uninsured individuals. Programmes aimed at children's mental health education and early intervention should consider gender- and diagnosis-related differences in symptom onset and trajectory. Access to SMHS might be improved by rapid identification by parents, educators, primary-care physicians and psychologists.


Why might adverse childhood experiences lead to underage drinking among US youth? Findings from an emergency department-based qualitative pilot study.
Research suggests that adverse childhood experiences (e.g., child abuse, interparental violence) predispose youth to early drinking initiation, but specifics about how and why adolescents progress from these exposures to alcohol use are not well understood. This National Institute on Alcohol Abuse and Alcoholism supported study presents data from semistructured interviews with 22 adolescents who reported both initiating drinking ≤18 years old and ≥2 adverse childhood experiences. Data were collected in 2007 as part of a formative research effort for an emergency department-based intervention to reduce adolescent drinking. Findings suggest that prevention initiatives for youth from challenging environments may need to do more than address conformity and social motivations for underage alcohol initiation. Study limitations are noted and future research is suggested.


Sex-specific gene expression in the BXD mouse liver.
Differences in clinical phenotypes between the sexes are well documented and have their roots in differential gene expression. While sex has a major effect on gene expression, transcription is also influenced by complex interactions between individual genetic variation and environmental stimuli. In this study, we sought to understand how genetic variation affects sex-related differences in liver gene expression by performing genetic mapping of genomewide liver mRNA expression data in a genetically defined population of naive male and female mice from C57BL/6J, DBA/2J, B6D2F1, and 37 C57BL/6J x DBA/2J (BXD) recombinant inbred strains. As expected, we found that many genes important to xenobiotic metabolism and other important pathways exhibit sexually dimorphic expression. We also performed gene expression quantitative trait locus mapping in this panel and report that the most significant loci that appear to regulate a larger number of genes than expected by chance are largely sex independent. Importantly, we found that the degree of correlation within gene expression networks differs substantially between the sexes. Finally, we compare our results to a recently released human liver gene expression data set and report on important similarities in sexually dimorphic liver gene expression between mouse and human. This study enhances our understanding of sex differences at the genome level and between species, as well as increasing our knowledge of the molecular underpinnings of sex differences in responses to xenobiotics.


Cytotoxic anticancer candidates from natural resources.
Natural products have been regarded as important sources that could produce potential chemotherapeutic agents. Over 50% of anticancer drugs approved by United States Food and Drug Administration since 1960 were originated from the natural resources, especially from terrestrial plants. Based on cytotoxicity bioassay, over 400 compounds have been isolated from plants, marine organisms and microorganisms from the period of 1996 to 2000. Recently, interest of natural product research has slowly moved to marine organisms. As a result, almost 50% of reported cytotoxic compounds were isolated from marine organisms such as sponges and corals. Also, traditional cytotoxic compounds of acetogenins, alkaloids and terpene skeletons have been reported continuously. In this review, we will present the cytotoxic compounds obtained from natural sources from 1996 to 2000, and the structures and cytotoxic activity of natural compounds isolated from territorial, marine and microorganism resources.


Electron microscopic analysis of mineral deposits in the calcifying epiphyseal growth plate.
Early mineral deposits within calcifying rat epiphyseal growth plates were studied by bright field and selected-area dark field electron microscopy, and X-ray microanalysis. These mineral deposits were prepared in situ by high-pressure freezing, freeze substitution, and low-temperature embedding, and were examined in unstained, stained, and ethyleneglycol tetraacetic acid (EGTA)-treated stained thin sections. On unstained sections mineral rods occur within an amorphous density of calcium and phosphorus (CaP). X-ray microanalysis of stained sections reveals that the location of electron-dense deposits does not always correspond to that of the CaP mineral deposits identified in electron microscopic images. Such an analysis showed a depletion of both Ca and P in stained sections at sites corresponding to high levels of these elements in unstained sections. Staining thus demineralizes early deposition sites of CaP; at the same time lead (Pb) and uranium (U) bind to the organic components of the extracellular matrix formerly associated with Ca and P. This substitution phenomenon alters the overall fine structure of mineral sites by depleting the amorphous density of Ca and P, and by creating isolated rodlike structures that have formerly been interpreted as representing hydroxyapatite (HAP) crystals. Selected-area dark field imaging shows nascent sites of HAP crystals to be associated with the limiting membrane of matrix vesicles, but such crystals were undetectable at these sites with conventional bright field images. Dark field imaging also showed that the typical 30-80 nm crystal rods found in calcified cartilage consist of aggregates of HAP crystals.


[The autopsy in crisis].
In the Western world the autopsy rate is declining at an alarming rate. In the United States of America the rate in some academic hospitals is less than 7% of all hospital deaths. This decline has been documented and deplored in many countries, articles and books. Suggestions on how to resuscitate the autopsy range from mandatory in all hospital deaths to economic bonuses to the doctors obtaining the highest autopsy rate. All in vain, the autopsy decline continues. Pathologists deploring this decline blamed clinical colleagues, new social attitudes, the litigious nature of modern society, but few have questioned a procedure little changed in more than a century. Perhaps the time has come to abandon the "classic" autopsy and rethink the procedure so as to make it useful, alluring and indispensable for the contemporary, concerned clinician.


Regioselective Carbohydrate Oxidations: A Nuclear Magnetic Resonance (NMR) Study on Selectivity, Rate, and Side-Product Formation.
Palladium/neocuproine catalyzed oxidation of glucosides shows an excellent selectivity for the C3-OH, but in mannosides and galactosides, unselective oxidation was initially observed. For further application in more-complex (oligo)saccharides, a better understanding of the reaction, in terms of selectivity and reactivity, is required. Therefore, a panel of different glycosides was synthesized, subjected to palladium/neocuproine catalyzed oxidation and subsequently analyzed by qNMR. Surprisingly, all studied glucosides, mannosides, galactosides, and xylosides show selective oxidation of the C3-OH. However, subsequent reaction of the resulting ketone moiety is the main culprit for side product formation. Measures are reported to suppress these side reactions. The observed differences in reaction rate, glucosides being the most rapidly oxidized, may be exploited for the selective oxidation of complex oligosaccharides.


Genetic and environmental influences on Diagnostic and Statistical Manual of Mental Disorders-Fifth Edition (DSM-5) maladaptive personality traits and their connections with normative personality traits.
The Diagnostic and Statistical Manual for Mental Disorders-Fifth Edition (DSM-5) proposes an alternative model for personality disorders, which includes maladaptive-level personality traits. These traits can be operationalized by the Personality Inventory for the DSM-5 (PID-5). Although there has been extensive research on genetic and environmental influences on normative level personality, the heritability of the DSM-5 traits remains understudied. The present study addresses this gap in the literature by assessing traits indexed by the PID-5 and the International Personality Item Pool NEO (IPIP-NEO) in adult twins (N = 1,812 individuals). Research aims include (a) replicating past findings of the heritability of normative level personality as measured by the IPIP-NEO as a benchmark for studying maladaptive level traits, (b) ascertaining univariate heritability estimates of maladaptive level traits as measured by the PID-5, (c) establishing how much variation in personality pathology can be attributed to the same genetic components affecting variation in normative level personality, and (d) determining residual variance in personality pathology domains after variance attributable to genetic and environmental components of general personality has been removed. Results revealed that PID-5 traits reflect similar levels of heritability to that of IPIP-NEO traits. Further, maladaptive and normative level traits that correlate at the phenotypic level also correlate at the genotypic level, indicating overlapping genetic components contribute to variance in both. Nevertheless, we also found evidence for genetic and environmental components unique to maladaptive level personality traits, not shared with normative level traits. (PsycINFO Database Record


Auditory feedback and memory for music performance: sound evidence for an encoding effect.
Research on the effects of context and task on learning and memory has included approaches that emphasize processes during learning (e.g., Craik & Tulving, 1975) and approaches that emphasize a match of conditions during learning with conditions during a later test of memory (e.g., Morris, Bransford, & Franks, 1977; Proteau, 1992; Tulving & Thomson, 1973). We investigated the effects of auditory context on learning and retrieval in three experiments on memorized music performance (a form of serial recall). Auditory feedback (presence or absence) was manipulated while pianists learned musical pieces from notation and when they later played the pieces from memory. Auditory feedback during learning significantly improved later recall. However, auditory feedback at test did not significantly affect recall, nor was there an interaction between conditions at learning and test. Auditory feedback in music performance appears to be a contextual factor that affects learning but is relatively independent of retrieval conditions.


Complex regulation of prolyl-4-hydroxylases impacts root hair expansion.
Root hairs are single cells that develop by tip growth, a process shared with pollen tubes, axons, and fungal hyphae. However, structural plant cell walls impose constraints to accomplish tip growth. In addition to polysaccharides, plant cell walls are composed of hydroxyproline-rich glycoproteins (HRGPs), which include several groups of O-glycoproteins, including extensins (EXTs). Proline hydroxylation, an early post-translational modification (PTM) of HRGPs catalyzed by prolyl 4-hydroxylases (P4Hs), defines their subsequent O-glycosylation sites. In this work, our genetic analyses prove that P4H5, and to a lesser extent P4H2 and P4H13, are pivotal for root hair tip growth. Second, we demonstrate that P4H5 has in vitro preferred specificity for EXT substrates rather than for other HRGPs. Third, by P4H promoter and protein swapping approaches, we show that P4H2 and P4H13 have interchangeable functions but cannot replace P4H5. These three P4Hs are shown to be targeted to the secretory pathway, where P4H5 forms dimers with P4H2 and P4H13. Finally, we explore the impact of deficient proline hydroxylation on the cell wall architecture. Taken together, our results support a model in which correct peptidyl-proline hydroxylation on EXTs, and possibly in other HRGPs, is required for proper cell wall self-assembly and hence root hair elongation in Arabidopsis thaliana.


Building the foundation of health-related knowledge via near-peer education for children with sickle cell disease.
Health education for children with chronic illnesses (i.e., sickle cell disease [SCD]) has focused on educating adult caregivers with minimal consideration to educating the pediatric patients. We introduce a pediatric-focused educational paradigm, health-related knowledge (HRK), teaching pediatric patients developmentally appropriate general health literacy, and disease-specific knowledge. Using science, technology, engineering, and mathematics (STEM) education concepts, pediatric-specific HRK interactive activities address educational gaps: (a) general STEM education; and (b) general health and disease-specific knowledge to improve clinical outcomes. Total 144 pediatric SCD patients completed HRK activities, revealing overwhelmingly positive feedback (87%). Seventy-five percent of participants in 6th grade and above demonstrated thorough understanding of the STEM/HRK topics taught.


Microencapsulation of bioactives for food applications.
Health issues are an emerging concern to the world population, and therefore the food industry is searching for novel food products containing health-promoting bioactive compounds, with little or no synthetic ingredients. However, there are some challenges in the development of functional foods, particularly in which the direct use of some bioactives is involved. They can show problems of instability, react with other food matrix ingredients or present strong odour and/or flavours. In this context, microencapsulation emerges as a potential approach to overcome these problems and, additionally, to provide controlled or targeted delivery or release. This work intends to contribute to the field of functional food development by performing a comprehensive review on the microencapsulation methods and materials, the bioactives used (extracts and isolated compounds) and the final application development. Although several studies dealing with microencapsulation of bioactives exist, they are mainly focused on the process development and the majority lack proof of concept for final applications. These factors, together with the lack of regulation, in Europe and in the United States, delay the development of new functional foods and, consequently, their market entry. In conclusion, the potential of microencapsulation to protect bioactive compounds ensuring their bioavailability is shown, but further studies are required, considering both its applicability and incentives by regulatory agencies.


Examining Factors Affecting Caregiver Burden: A Comparison of Frontotemporal Dementia and Alzheimer's Disease.
This study was conducted to compare the caregiver burden with regard to Alzheimer's disease (AD) and frontotemporal dementia (FTD) and to determine the factors affecting the caregiver burden of patients with AD and FTD. A comparative descriptive study design was used. The sample consisted of 90 patients with AD and 44 patients with FTD and their caregivers. Sociodemographic questionnaire, Mini-Mental State Examination (MMSE), the Caregiver Burden Inventory (CBI), Neuropsychiatric Inventory (NPI), and Functional Activities Questionnaire (FAQ) were used. Descriptive statistics, t tests, χ2 test, and multinominal regression were used for analysis. No difference was found with subscales and the total score of the CBI, except time dependency scale. The total NPI and FAQ scores correlated significantly, and the MMSE score did not show a significant correlation with the AD and FTD caregiver burden. The presence and frequency of neuropsychological symptoms differ among patients with FTD and AD, and different symptoms affect the caregiver burdens in both groups.


[The hybridization of tetraploid wheat with the octoploid wheat-wild rye amphiploid Elytricum fertile and the chromosome behavior in meiotic MI].
The hybridization and chromosome behaviour regularities at meiotic MI of reciprocal F1 hybrids of tetraploid wheats T. durum and T. turgidum with 56-chromosome incomplete wheat-Elymus amphiploid (IWEA) Elytricum fertile, were investigated. Variation of main indices of the hybridization has been revealed to be determined by variance of such factors as cross direction, genotype peculiarities of wheat strains and their interaction. Elymus sibiricus genome, contained in IWEA karyotype, carries several genes, that can suppress wheat diploidization system. Reduction of homologous chromosome synapsis is not determined by these genes, but is connected with influence of other Elymus sibiricus chromosome factors.


Detecting gender before you know it: How implementation intentions control early gender categorization.
Gender categorization is highly automatic. Studies measuring ERPs during the presentation of male and female faces in a categorization task showed that this categorization is extremely quick (around 130ms, indicated by the N170). We tested whether this automatic process can be controlled by goal intentions and implementation intentions. First, we replicated the N170 modulation on gender-incongruent faces as reported in previous research. This effect was only observed in a task in which faces had to be categorized according to gender, but not in a task that required responding to a visual feature added to the face stimuli (the color of a dot) while gender was irrelevant. Second, it turned out that the N170 modulation on gender-incongruent faces was altered if a goal intention was set that aimed at controlling a gender bias. We interpret this finding as an indicator of nonconscious goal pursuit. The N170 modulation was completely absent when this goal intention was furnished with an implementation intention. In contrast, intentions did not alter brain activity at a later time window (P300), which is associated with more complex and rather conscious processes. In line with previous research, the P300 was modulated by gender incongruency even if individuals were strongly involved in another task, demonstrating the automaticity of gender detection. We interpret our findings as evidence that automatic gender categorization that occurs at a very early processing stage can be effectively controlled by intentions.


Cpipe: a comprehensive computational platform for sequence and structure-based analyses of Cysteine residues.
Due to their chemical plasticity, Cysteine residues (Cys) can serve many different functions. Identification and classification of reactive Cys isn't a trivial job: currently, no available tool exists for an all-round, comprehensive (inclusive of all different functional types) analysis of Cys; herein we present a computational platform called Cp i pe, dedicated to this task: it implements state-of-the art protocols, elaborating and displaying a wealth of information, sufficiently orthogonal to allow a thorough evaluation of all major aspects of Cys reactivity. Cp i pe is implemented in Python and freely available at http://cpipe.explora-biotech.com/cpipe/start.py . All major browsers are supported. email@example.com. Supplementary data are available at Bioinformatics online.


Benign paroxysmal torticollis of infancy: An underdiagnosed condition.
Benign paroxysmal torticollis is probably an under-diagnosed condition of infancy. It is a self-limiting disorder characterised by periods of unusual, sustained posture of the head and neck, during which the head tilts to one side. Episodes are often accompanied by marked autonomic features, irritability, ataxia, apathy and drowsiness. They last several hours to a few days and are often recurring every few weeks. They subside within the pre-school years; however, during later childhood, there is a tendency to develop migraine. Three cases of benign paroxysmal torticollis are presented and are compared with cases in the literature. A telephone survey has been conducted to determine what is the general awareness of paediatricians of this condition in Cyprus. Eighty-two paediatricians were randomly selected out of 235 paediatricians. All of them agreed to participate. Our cases revealed that benign paroxysmal torticollis may coexist with other problems during infancy. The telephone survey showed that only two out of eighty-two (2.4%) of the paediatricians are aware of the condition, and none of them was confident regarding the management. Our telephone survey clearly shows that Cypriot paediatricians are not familiar with benign paroxysmal torticollis in infancy which is a benign, self-limiting disorder. It is essential to recognise the condition and to reassure parents of its benign course and not to be misdiagnosed for other disorders, such as epileptic seizures. We have shown again that benign paroxysmal torticollis in infancy may coexist with motor delay and hearing problems.


Estimates of smoking-attributable deaths at ages 15-54, motherless or fatherless youths, and resulting Social Security costs in the United States in 1994.
Deaths of parents often harm their children, taxpayers, and society, for decades. So we estimated the smoking-attributable (SA) counts and percentages (SA%) of U.S. 1994 deaths at child-rearing ages; youths (ages <18) left motherless or fatherless; and resulting Social Security Survivors Insurance taxes. U.S. 1994 age/sex/education-specific total and SA death counts were estimated using death certificate data and standard CDC SAMMEC methods (with added injury mortality), respectively. We separately summed (a) total and (b) SA age/sex/education-specific death counts times their average number of youths per adult (cumulative fertility, adjusted for infant mortality). We then multiplied the SA and total bereft youth counts by their average duration of Survivors Insurance, and calculated the SA cost of youth Survivors Insurance. In 1994, smoking caused an estimated 44,000 male and 19,000 female U.S. deaths at ages 15-54, leaving 31,000 fatherless and 12,000 motherless youths. On December 31, 1994, the SA prevalences [count (SA%)] of fatherless or motherless youths were an estimated 220,000 (17%) and 86,000 (16%), respectively. Resulting Survivors Insurance costs were about $1.4 (sensitivity range: $0.58-3.7) billion in 1994. Smoking causes many U.S. deaths at ages 15-54, youth bereavements, and Survivors Insurance costs. Reductions in smoking may greatly reduce those deaths, bereavements, and taxpayer and societal costs.


Finding extraterrestrial sites for thermophiles.
Virtually our entire knowledge of the universe comes from two sorts of measurement of the electromagnetic radiation from the stars and galaxies within it; either their flux through relatively wide bandpasses (photometry), or measurements of the shape and wavelength of relatively narrow lines via spectroscopy. These techniques are now being used to discover planets outside our solar system, and perhaps in the next 10 years will begin to characterize them. If a serious search is to be made for extraterrestrial thermophiles, we need predictions for the effects of thermophiles on their host planets that are observable with these techniques. In this paper I shall outline what sorts of observation are likely to be used in the next 15 years for extra-solar planet work. All of the journal articles quoted here can be found through http://adsabs.harvard.edu/abstract_service.html, and often also accessed as preprints at http://uk.arxiv.org/form/astro%20ph?MULTI=form%20+/-%20interface.


Global properties of the metabolic map of Escherichia coli.
The EcoCyc database characterizes the known network of Escherichia coli small-molecule metabolism. Here we present a computational analysis of the global properties of that network, which consists of 744 reactions that are catalyzed by 607 enzymes. The reactions are organized into 131 pathways. Of the metabolic enzymes, 100 are multifunctional, and 68 of the reactions are catalyzed by >1 enzyme. The network contains 791 chemical substrates. Other properties considered by the analysis include the distribution of enzyme subunit organization, and the distribution of modulators of enzyme activity and of enzyme cofactors. The dimensions chosen for this analysis can be employed for comparative functional analysis of complete genomes.


Functionality of Sugars in Foods and Health.
Overweight and obesity are global health problems that affect more than 1.9 billion adults who are overweight, and of these 600 million are obese. In the United States, these problems affect 60% of the population. Critical to these statistics is the association with increased risk of cardiovascular disease, type 2 diabetes, and metabolic syndrome among other noncommunicable diseases. Many factors, including sugars, have been charged as potential causes. However, obesity and overweight and their attendant health problems continue to increase despite the fact that there is a decline in the consumption of sugars. Sugars vary in their types and structure. From a food science perspective, sugars present an array of attributes that extend beyond taste, flavor, color, and texture to aspects such as structure and shelf-life of foods. From a public health perspective, there is considerable controversy about the effect of sugar relative to satiety, digestion, and noncommunicable diseases. This comprehensive overview from experts in food science, nutrition and health, sensory science, and biochemistry describes the technical and functional roles of sugar in food production, provides a balanced evidence-based assessment of the literature and addresses many prevalent health issues commonly ascribed to sugar by the media, consumer groups, international scientific organizations, and policy makers. The preponderance of the evidence indicates that sugar as such does not contribute to adverse health outcomes when consumed under isocaloric conditions. The evidence generally indicates, as noted by the 2010 Dietary Guidelines Advisory Committee, that sugar, like any other caloric macronutrient, such as protein and fat, when consumed in excess leads to conditions such as obesity and related comorbidities. More recently, the 2015-2020 Dietary Guidelines for Americans recommended limiting dietary sugar to 10% of total energy in an effort to reduced the risk of these noncommunicable diseases.


Madagascarhinus, a new genus of the family Siphonorhinidae with two new species from Madagascar (Diplopoda, Siphonophorida).
Millipedes of the family Siphonorhinidae Cook, 1895, famous for including the leggiest animal on this planet until recently, with up to 750 legs, show a disjunct distribution in California, South Africa and South-East Asia (from India to the Indonesian Islands of Java and Flores). Here I formally describe the first members of the family from Madagascar, Madagascarhinus madagascariensis n. gen., n. sp. and Madagascarhinus andasibensis n. gen., n. sp., from degraded central highland rainforests. Both species of Madagascarhinus n. gen. are relatively short (61 or 63 tergites), setose, pale and slender, and differ from the other known five genera of the family in numerous characters of the antennae, head, and tergites.


[SUCCESSFUL TREATMENT OF ACUTE PULMONARY ABSCESS IN AN ELDERLY PATIENT].
This paper describes successful application of nebulizer inhalation therapy with the antibacterial drug tobramycin in the combined treatment of acute pulmonary abscess caused by Pseudomonas aeruginosa in an elderly woman. Possibilities of modern antibiotic therapy of pulmonary abscess are discussed along with prospects for its further development.


Structure of human heat-shock transcription factor 1 in complex with DNA.
Heat-shock transcription factor 1 (HSF1) has a central role in mediating the protective response to protein conformational stresses in eukaryotes. HSF1 consists of an N-terminal DNA-binding domain (DBD), a coiled-coil oligomerization domain, a regulatory domain and a transactivation domain. Upon stress, HSF1 trimerizes via its coiled-coil domain and binds to the promoters of heat shock protein-encoding genes. Here, we present cocrystal structures of the human HSF1 DBD in complex with cognate DNA. A comparative analysis of the HSF1 paralog Skn7 from Chaetomium thermophilum showed that single amino acid changes in the DBD can switch DNA binding specificity, thus revealing the structural basis for the interaction of HSF1 with cognate DNA. We used a crystal structure of the coiled-coil domain of C. thermophilum Skn7 to develop a model of the active human HSF1 trimer in which HSF1 embraces the heat-shock-element DNA.


One-stoma carinoplasty: right upper sleeve lobectomy with hemicarinectomy for resection of right-tracheobronchial-angle tumors.
Tracheobronchial-angle tumors involve the right main bronchus, the right upper lobar bronchus, and the lateral wall of the lower trachea. Resecting these tumors is one of the most complex procedures in thoracic surgery. In cases of high-caliber mismatch, the selection of a suitable anastomotic technique can be challenging. We found that our use of a one-stoma carinoplasty technique overcame high-caliber mismatch after the resection of these tumors. From 2009 through 2012, 8 men (mean age, 59 ± 6.2 yr; range, 46-66 yr) underwent complete resection of non-small-cell right-tracheobronchial-angle tumors at our institution. In every case, right upper sleeve lobectomy, wedge carinal resection, and one-stoma carinoplasty were applied. After tumor resection, one patient with hemoptysis and bronchopleural fistula underwent a completion pneumonectomy and died 10 days postoperatively. Bronchoscopy was necessary in 2 patients who had atelectasis in the contralateral lung. At a mean follow-up duration of 19.43 ± 8.4 months (range, 0.2-27.1 mo), 6 patients were alive and free of disease. We conclude that our one-stoma carinoplasty technique enables the resection of tumors at the right tracheobronchial angle, with acceptable morbidity and mortality rates. This method saves the unaffected part of the ipsilateral lung and can overcome high-caliber mismatch. Because of these and other advantages, we suggest that using our method first might preclude having to perform a right carinal sleeve pneumonectomy or using Barclay's method.


Hemorrhage and culture: management in the developing world and cultural implications for nursing care.
In the industrialized world, technological resources and skilled personnel characterize the response to a hemorrhagic crisis. Such an efficient use of supplied technology stands in stark contrast to the responses toward a similar crisis when encountered in a developing country. In fact, attempting to manage a hemorrhage in a developing country may pose entanglements with economic, political, cultural, environmental, and medical obstacles. The uniqueness of this task and its challenges to the health professional are presented to provide nurses in advanced societies with a basic understanding of principles involved in managing hemorrhage in less-than-ideal circumstances. In addition, cultural care considerations are briefly described as they relate to the nursing role in the developing world.


Whole-exome sequencing for the identification of susceptibility genes of Kashin-Beck disease.
To identify and investigate the susceptibility genes of Kashin-Beck disease (KBD) in Chinese population. Whole-exome capturing and sequencing technology was used for the detection of genetic variations in 19 individuals from six families with high incidence of KBD. A total of 44 polymorphisms from 41 genes were genotyped from a total of 144 cases and 144 controls by using MassARRAY under the standard protocol from Sequenom. Association was applied on the data by using PLINK1.07. In the sequencing stage, each sample showed approximately 70-fold coverage, thus covering more than 99% of the target regions. Among the single nucleotide polymorphisms (SNPs) used in the transmission disequilibrium test, 108 had a p-value of <0.01, whereas 1056 had a p-value of <0.05. Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway analysis indicates that these SNPs focus on three major pathways: regulation of actin cytoskeleton, focal adhesion, and metabolic pathways. In the validation stage, single locus effects revealed that two of these polymorphisms (rs7745040 and rs9275295) in the human leukocyte antigen (HLA)-DRB1 gene and one polymorphism (rs9473132) in CD2-associated protein (CD2AP) gene have a significant statistical association with KBD. HLA-DRB1 and CD2AP gene were identified to be among the susceptibility genes of KBD, thus supporting the role of the autoimmune response in KBD and the possibility of shared etiology between osteoarthritis, rheumatoid arthritis, and KBD.


A marked diurnal rhythm of melatonin ML1A receptor mRNA expression in the suprachiasmatic nucleus.
Melatonin (ML1A) receptor binding in the suprachiasmatic nucleus (SCN) exhibits a diurnal rhythm, with significant increases during the daytime. In order to determine whether the diurnal variation in binding is reflected by a cycling of melatonin ML1A receptor mRNA levels, we utilized a semiquantitative reverse transcriptase-polymerase chain reaction procedure to examine receptor expression throughout the light-dark cycle. Here we report the first evidence of a significant diurnal variation in ML1A receptor mRNA levels within the SCN. Furthermore, this mRNA expression occurs approximately 3 h prior to, but is tightly correlated to the diurnal rhythm in high-affinity melatonin binding in the SCN.


Attachment security and parenting quality predict children's problem-solving, attributions, and loneliness with peers.
The influence of early relational experience on later social understanding has evoked rich theoretical discussion but relatively little empirical inquiry. Enlisting data from the NICHD Study of Early Child Care and Youth Development, measures of the security of attachment in infancy, toddlerhood, and early childhood, together with measures of parenting quality (maternal sensitivity and depressive symptoms) gathered longitudinally throughout infancy and early childhood, were used to predict differences in children's thoughts and feelings about peers (i.e., social problem solving, negative attributional biases, aggressive solutions to ambiguous social situations, and self-reported loneliness) when children were 54 months and in first grade. Relational experiences, especially before 36 months, were significantly predictive of later peer-related representations. Attachment security at 24 and 36 months was associated with enhanced social problem-solving skills and less loneliness, but security of attachment at 15 months was nonpredictive. Early maternal sensitivity was positively associated with later social problem-solving and negatively with aggressive responses, and early maternal depressive symptoms were positively associated with children's negative attributions. Concurrent parenting quality was also associated with children's thoughts and feelings about peers, but less consistently. These findings shed new light on how early relational experiences may contribute to social information processing with peers at the end of the preschool years, and that the timing of relational influences may be crucial.


Clinical development of CAR T cells-challenges and opportunities in translating innovative treatment concepts.
Chimeric antigen receptor (CAR) T cell therapy, together with checkpoint inhibition, has been celebrated as a breakthrough technology due to the substantial benefit observed in clinical trials with patients suffering from relapsed or refractory B-cell malignancies. In this review, we provide a comprehensive overview of the clinical trials performed so far worldwide and analyze parameters such as targeted antigen and indication, CAR molecular design, CAR T cell manufacturing, anti-tumor activities, and related toxicities. More than 200 CAR T cell clinical trials have been initiated so far, most of which aim to treat lymphoma or leukemia patients using CD19-specific CARs. An increasing number of studies address solid tumors as well. Notably, not all clinical trials conducted so far have shown promising results. Indeed, in a few patients CAR T cell therapy resulted in severe adverse events with fatal outcome. Of note, less than 10% of the ongoing CAR T cell clinical trials are performed in Europe. Taking lead from our analysis, we discuss the problems and general hurdles preventing efficient clinical development of CAR T cells as well as opportunities, with a special focus on the European stage.


Saline versus balanced crystalloids for intravenous fluid therapy in the emergency department: study protocol for a cluster-randomized, multiple-crossover trial.
Prior studies in critically ill patients suggest the supra-physiologic chloride concentration of 0.9% ("normal") saline may be associated with higher risk of renal failure and death compared to physiologically balanced crystalloids. However, the comparative effects of 0.9% saline and balanced fluids are largely unexamined among patients outside the intensive care unit, who represent the vast majority of patients treated with intravenous fluids. This study, entitled Saline Against Lactated Ringer's or Plasma-Lyte in the Emergency Department (SALT-ED), is a pragmatic, cluster, multiple-crossover trial at a single institution evaluating clinical outcomes of adults treated with 0.9% saline versus balanced crystalloids for intravenous fluid resuscitation in the emergency department. All adults treated in the study emergency department receiving at least 500 mL of isotonic crystalloid solution during usual clinical care and subsequently hospitalized outside the intensive care unit are included. Treatment allocation of 0.9% saline versus balanced crystalloids is assigned by calendar month, with study patients treated during the same month assigned to the same fluid type. The first month (January 2016) was randomly assigned to balanced crystalloids, with each subsequent month alternating between 0.9% saline and balanced crystalloids. For balanced crystalloid treatment, clinicians can choose either Lactated Ringer's or Plasma-Lyte A©. The study period is set at 16 months, which will result in an anticipated estimated sample size of 15,000 patients. The primary outcome is hospital-free days to day 28, defined as the number of days alive and out of the hospital from the index emergency department visit until 28 days later. Major secondary outcomes include proportion of patients who develop acute kidney injury by creatinine measurements; major adverse kidney events by hospital discharge or day 30 (MAKE30), which is a composite outcome of death, new renal replacement therapy, and persistent creatinine elevation >200% of baseline; and in-hospital mortality. This ongoing pragmatic trial will provide the most comprehensive evaluation to date of clinical outcomes associated with 0.9% saline compared to physiologically balanced fluids in patients outside the intensive care unit. ClinicalTrials.gov, NCT02614040 . Registered on 18 November 2015.


Molecular Diffusion in Nanoreactors' Pore Channel System: Measurement Techniques, Structural Regulation, and Catalytic Effects.
Nanoreactors, as a new class of materials with highly enriched and ordered pore channel structures, can achieve special catalytic effects by precisely identifying and controlling the molecular diffusion behavior within the ordered pore channel system. Nanoreactors-driven molecular diffusion within the ordered pore channels can be highly dependent on the local microenvironment in the nanoreactors' pore channel system. Although the diffusion process of molecules within the ordered pore channels of nanoreactors is crucial for the regulation of catalytic behaviors, it has not yet been as clearly elucidated as it deserves to be in this study. In this review, fundamental theory and measurement techniques for molecular diffusion in the pore channel system of nanoreactors are presented, structural regulation strategies of pore channel parameters for controlling molecular diffusion are discussed, and the effects of molecular diffusion in the pore channel system on catalytic reactivity and selectivity are further analyzed. This article attempts to further develop the underlying theory of molecular diffusion within the theoretical framework of nanoreactor-driven catalysis, and the proposed perspectives may contribute to the rational design of advanced catalytic materials and the precise control of complex catalytic kinetics.


Tetrazine-TCO Ligation: A Potential Simple Approach to Improve Tumor Uptake through Enhanced Blood Circulation.
Targeted imaging via peptides has been extensively investigated for both diagnostic and therapeutic applications. However, peptides can be cleared out from the blood circulation quickly, leading to only moderate to low accumulation in regions of interest. Previously, 18F-sTCO-DiPhTz-RGDyK demonstrated relatively high blood retention with increased tumor uptake at the late time point (5.3 ± 0.4 and 8.9 ± 0.5%ID/g tumor uptake at 1 h p.i. and 4 h p.i., respectively). In this study, we aim to develop a novel platform based on TCO/tetrazine ligation that could be used not only to label the peptides with F-18 for PET but also to lead to increased or persistent tumor uptake potentially due to enhanced blood circulation of the labeled peptides. We first constructed systems containing different combinations of TCOs/tetrazines and found that the tetrazine moiety played a more important role to facilitate the enhanced blood circulation compared with TCO moiety. Four clinically relevant peptides including NT20.3, RGD, BBN, and exendin-4 were then evaluated, and the increased tumor uptake at a late time point was demonstrated by the combination of 18F-sTCO-DiPhTz system to NT20.3, RGD, and exendin-4. The plasma binding components of the PET agents were investigated by electrophoresis and autoradiography and indicated that transferrin and hemopexin could be the major proteins in blood plasma for binding with 18F-sTCO-DiPhTz conjugates. In summary, we have discovered a TCO/tetrazine system that could not only be used for PET probe construction but also potentially improve the tumor uptake and retention of fast-clearing peptides. Although additional binding experiments are still needed for some of the constructs, the promising preliminary result suggested that this strategy may be used to convert fast-clearing bioligands into relatively long circulating agents with enhanced tumor uptake/retention for either imaging or therapy applications.


Crisis management briefings (CMB): large group crisis intervention in response to terrorism, disasters, and violence.
A single act of violence or terrorism can adversely affect thousands of people. Such acts will invariably engender a psychological morbidity that will far surpass any physical morbidity. Heretofore, efforts in primary and secondary prevention have focused largely upon the physical consequences of these incidents, rather than their psychological consequences. This paper describes a practical group psychological crisis intervention, the "crisis management briefing" (CMB), that may be used with large groups of individuals in the wake of terrorism, violence, disasters, and other crises. This intervention, which is one component of the Critical Incident Stress Management (CISM) crisis intervention system, is designed to mitigate the effects of these crises and requires anywhere from 45 to 75 minutes to implement. The CBM may be employed with groups ranging from 10 to 300 individuals at one time.


Investigation of the allergenicity alterations of shrimp tropomyosin as glycated by glucose and maltotriose containing advanced glycation end products.
Tropomyosin (TM) is the major allergen in shrimp that is known to be the primary trigger for shrimp-induced food allergy. Our previous reports suggest that glycation could reduce the allergenicity of TM and the reduction of allergenicity is largely dependent on the sources of saccharides. This investigation aimed to investigate the glycation of TM by glucose and maltotriose as well as the effects of glycation on the allergenicity of TM. Compared to TM, the IgG-binding capacity and IgE-binding capacity of tropomyosin glycated by glucose (TM-G) was greatly reduced with a longer glycation time, the release of allergic mediators from RBL-2H3 mast cells was reduced in a time-dependent manner, and weaker allergic reactions were induced in BALB/c mice. Conversely, tropomyosin glycated by maltotriose (TM-MTS) exhibited a stronger allergenicity after 48 hours of glycation due to the generation of neoallergens that were derived from the advanced glycation end products (AGEs). In conclusion, glucose could be used to desensitize the shrimp TM-induced food allergy via glycation, which could significantly reduce the allergenicity and alleviate allergic symptoms. This work could provide a novel approach to reduce the allergenicity of shrimp tropomyosin and prevent the shrimp tropomyosin-induced food allergy.


A Mathematical Analysis of HDV Genotypes: From Molecules to Cells.
Hepatitis D virus (HDV) is classified according to eight genotypes. The various genotypes are included in the HDVdb database, where each HDV sequence is specified by its genotype. In this contribution, a mathematical analysis is performed on RNA sequences in HDVdb. The RNA folding predicted structures of the Genbank HDV genome sequences in HDVdb are classified according to their coarse-grain tree-graph representation. The analysis allows discarding in a simple and efficient way the vast majority of the sequences that exhibit a rod-like structure, which is important for the virus replication, to attempt to discover other biological functions by structure consideration. After the filtering, there remain only a small number of sequences that can be checked for their additional stem-loops besides the main one that is known to be responsible for virus replication. It is found that a few sequences contain an additional stem-loop that is responsible for RNA editing or other possible functions. These few sequences are grouped into two main classes, one that is well-known experimentally belonging to genotype 3 for patients from South America associated with RNA editing, and the other that is not known at present belonging to genotype 7 for patients from Cameroon. The possibility that another function besides virus replication reminiscent of the editing mechanism in HDV genotype 3 exists in HDV genotype 7 has not been explored before and is predicted by eigenvalue analysis. Finally, when comparing native and shuffled sequences, it is shown that HDV sequences belonging to all genotypes are accentuated in their mutational robustness and thermodynamic stability as compared to other viruses that were subjected to such an analysis.


Clinical value of radionuclide shuntography by qualitative methods in hydrocephalic adult patients with suspected ventriculoperitoneal shunt malfunction.
To determine the clinical value of radionuclide shuntography in the evaluation of adult hydrocephalic patients with suspected ventriculoperitoneal (V-P) shunt malfunction. All adult patients who underwent Tc-99m diethylenetriamine pentaacetic acid shuntographic scans at Far Eastern Memorial Hospital between August 2005 and December 2015 were included. Shuntographic results were visually evaluated in a simple qualitative manner: prompt flow that reached the peritoneum on 30-minute early images and diffuse peritoneal tracer distribution on 2-hour delayed images were interpreted as nonobstructive shunt flow. Partial dysfunction was diagnosed as scintigraphic findings between no obstruction and complete obstruction (where complete malfunction indicated no peritoneal distribution on delayed images). The results were correlated with the clinical outcomes and surgical results within 30 days. Diagnostic sensitivity (Se), specificity (Sp), positive predictive value (PPV), negative predictive value (NPV), and overall accuracy were also calculated. A total of 93 scans in 69 patients with suspected V-P shunt malfunction were analyzed. Sixty-two scans were interpreted as abnormal, including complete (n = 26, 41.9) distal obstruction, partial (n = 35, 56.5) distal dysfunction, and miscellaneous (n = 1, 1.6, cerebrospinal fluid leak). The Se and Sp were 83.0% and 55.0%, respectively, and PPV, NPV, and accuracy were all 71.0%. Twenty-five patients (28 scans) underwent surgical revision, and the results were highly concordant with the imaging findings (Se, 92.0%; Sp, 100.0%; PPV, 100.0%; NPV, 60.0%; and accuracy, 92.9%). Radionuclide shuntography provides useful information in adult patients with V-P shunt malfunction and could be used to guide further surgical intervention.


Cancer immunology: the search for specificity--G. H. A. Clowes Memorial lecture.
The major focus of cancer immunology has shifted away from arguments about the validity of the immunosurveillance theory of cancer to the more basic question of tumor-specific antigens. Despite vast effort aimed at demonstrating such antigens, their existence in the generality of cancer remains unproven. Serological analysis of three tumor types, mouse leukemia, mouse sarcoma, and human malignant melanoma, has received most attention, and a rudimentary classification of the surface antigens expressed by these tumors has begun to emerge. The prime candidates for antigens that can be considered tumor specific are the few instances of Class 1 antigens that have now been serologically defined on mouse and human tumors. These antigens show an absolute restriction to individual tumors, not being demonstrable on any other normal or malignant cell type. Biochemical and genetic characterization of Class 1 antigens represents an essential next step in evaluating the significance of these antigens. The surprising features of the Thymus Leukemia (TL) antigens of the mouse provide insight into the genetic origin of another key class of tumor antigens, in this case antigens with characteristic properties of both differentiation antigens and tumor-specific antigens. In normal mice, TL antigens are restricted to cells in the thymus, and strains differ with regard to expression versus nonexpression of TL antigens. Genetic information for TL is universal in the mouse, however, as leukemias developing in mice that normally lack TL are found to express TL. What is clear from the past two decades of research in cancer immunology is that a far more detailed knowledge of surface antigens of tumor cells will be necessary before we can begin to assess the possibility of immunological control of cancer.


Cloning, sequencing, characterisation and implications for vaccine design of the novel dihydrolipoyl acetyltransferase of Neisseria meningitidis.
A lambdaZap-II expression library of Neisseria meningitidis was screened with a rabbit polyclonal antiserum (R-70) raised against c. 70-kDa proteins purified from outer membrane vesicles by elution from preparative SDS-polyacrylamide gels. Selected clones were isolated, further purified, and their recombinant pBluescript SKII plasmids were excised. The cloned DNA insert was sequenced from positive clones and analysed. Four open reading frames (ORFs) were identified, three of which showed a high degree of homology with the pyruvate dehydrogenase (E1p), dihydrolipoyl acetyltransferase (E2p) and dihydrolipoyl dehydrogenase (E3) components of the pyruvate dehydrogenase complex (PDHC) of a number of prokaryotic and eukaryotic species. Sequence analysis indicated that the meningococcal E2p (Men-E2p) contains two N-terminal lipoyl domains, an E1/E3 binding domain and a catalytic domain. The domains are separated by hinge regions rich in alanine, proline and charged residues. Another lipoyl domain with high sequence similarity to the Men-E2p lipoyl domain was found at the N-terminal of the E3 component. A further ORF, coding for a 16.5-kDa protein, was found between the ORFs encoding the E2p and E3 components. The identity and functional characteristics of the expressed and purified heterologous Men-E2p were confirmed as dihydrolipoyl acetyltransferase by immunological and biochemical assays. N-terminal amino-acid analysis confirmed the sequence of the DNA-derived mature protein. Purified Men-E2p reacted with monospecific antisera raised against the whole E2p molecule and against the lipoyl domain of the Azotobacter vinelandii E2p. Conversely, rabbit antiserum raised against Men-E2p reacted with protein extracts of A. vinelandii, Escherichia coli and N. gonorrhoeae and with the lipoyl and catalytic domains of E2p obtained by limited proteolysis. In contrast, the original R-70 antiserum reacted almost exclusively with the lipoyl domain, indicating the strong immunogenicity of this domain. Antibodies to Men-E2p were detected in patients and animals (rabbits and mice) infected with homologous or heterologous meningococci or other neisserial species. These results have important implications for the understanding of PDHC and the design of future outer membrane vesicle-based vaccines.


A quantitative bioassay for erythropoietin using mouse fetal liver cells.
The conditions under which mouse fetal liver cells in vitro are most sensitive to erythropoietin have been investigated with the object of establishing a rapid and sensitive bioassay for this hormone. Fetal liver age and incubation times are shown to be relatively unimportant. Of the commercially available media studied, Eagles Minimal Essential Medium plus 5 percent Fetal Calf Serum is superior to other media used to study erythropoiesis in mouse fetal liver cells. The number of cells per 1 ml culture is important since some evidence was obtained for cell cooperation occurring above 10-6 cells per culture. To minimize this possibility 5 x 10-5 cells are used. If (59Fe) ferric citrate is used to assess heme synthesis, no significant advantage is observed by prior binding of the isotope to mouse serum transferrin. Butan-2-one is preferred to cyclohexanone for extracting heme. Using the conditions described in this report the mouse fetal liver cell assay for erythropoietin is capable of detecting erythropoietin concentrations as low as 0.001 unit culture. Preliminary results using normal human sera show that it is sufficiently sensitive to detect erythropoietin over a range of serum concentrations. This allows a full dose-response relationship to the sera to be determined and, by a comparison with an erythropoietin standard, detailed quantitative results can be obtained. Therefore the technique seems to fulfill the need for a rapid and sensitive erythropoietin bioassay for routine clinical use.


Parasites associated with pork and pork products.
Three parasites pose a public health risk from the ingestion of raw or undercooked pork, namely: Trichinella spiralis, Taenia solium and Toxoplasma gondii. Inspection procedures, when practised according to prescribed methods, are effective in eliminating the majority of risks from T. spiralis and T. solium. No suitable methods for the post-slaughter detection of T. gondii are available. All three parasites are inactivated by various methods of cooking, freezing and curing; some information is also available on inactivation by irradiation. Good production practices, including a high level of sanitation, rodent and cat control on farms, can prevent opportunities for exposure of pigs to these parasites. Alternatively, meat inspection, proper commercial processing and adherence to guidelines for in-home preparation of meat are effective methods for reduction of risks for human exposure.


Epidermal growth factor receptors on corneal endothelium.
If a growth factor could bind to and stimulate human endothelial healing, corneal disease could be minimized. To this end, primary cultures of feline and human corneal endothelium were tested in receptor binding assays for radiolabeled epidermal growth factor (EGF). Both of these cells bound ten times as much 125I-EGF as did the negative control cell lines. The time course of association of 125I-EGF to cat corneal endothelium was found to be complete after approximately 120 minutes at 22 degrees C. The 125I-EGF was shown not to dissociate greatly when fresh binding buffer was added to endothelial cultures that had bound the radiolabeled peptide. The pH optimum for binding was determined to be approximately 6.4. The receptor number per cell and the affinity constant for binding were determined to be 40,000 receptors per cell and 1.1 x 10(9) L/mole, respectively, using a Scatchard plot. Parallel cultures of human fetal corneal endothelium grew in vitro only when the growth medium was supplemented with low concentrations of EGF. These studies provide evidence that EGF is specifically bound to the corneal endothelium.


Respiratory depression produced by diazepam in cats: effect of anaesthesia.
Diazepam (Valium, Roche; 0.37 mg/kg was given by slow injection into the left femoral vein and flushed in with 0.9 % saline. Within 3 min following the i.v. injection of diazepam spontaneous respiration ceased in rats anaesthetized with chloralose; mean arterial pressure fell from a control level of 99.4 (+/- 28.3) mmHg to 32.5 (+/- 13.44) mmHg. If artificial ventilation was initiated immediately upon cessation of respiration, the animal recovered. Cats anesthetized with ketamine (Ketaset, Roger; 44 mg/kg i.m.) showed no respiratory depression following i.v. diazepam injection.


Depression after status epilepticus: behavioural and biochemical deficits and effects of fluoxetine.
Depression represents one of the most common comorbidities in patients with epilepsy. However, the mechanisms of depression in epilepsy patients are poorly understood. Establishment of animal models of this comorbidity is critical for both understanding the mechanisms of the condition, and for preclinical development of effective therapies. The current study examined whether a commonly used animal model of temporal lobe epilepsy (TLE) is characterized by behavioural and biochemical alterations involved in depression. Male Wistar rats were subjected to LiCl and pilocarpine status epilepticus (SE). The development of chronic epileptic state was confirmed by the presence of spontaneous seizures and by enhanced brain excitability. Post-SE animals exhibited increase in immobility time under conditions of forced swim test (FST) which was indicative of despair-like state, and loss of taste preference in saccharin solution consumption test which pointed to the symptomatic equivalence of anhedonia. Biochemical studies revealed compromised serotonergic transmission in the raphe-hippocampal serotonergic pathway: decrease of serotonin (5-HT) concentration and turnover in the hippocampus, measured by high performance liquid chromatography, and decrease of 5-HT release from the hippocampus in response to raphe stimulation, measured by fast cyclic voltammetry. Administration of fluoxetine (FLX, 20 mg/kg/day for 10 days) to naive animals significantly shortened immobility time under conditions of FST, and inhibited 5-HT turnover in the hippocampus. In post-SE rats FLX treatment led to a further decrease of hippocampal 5-HT turnover; however, performance in FST was not improved. At the same time, FLX reversed SE-induced increase in brain excitability. In summary, our studies provide initial evidence that post-SE model of TLE might serve as a model of the comorbidity of epilepsy and depression. The finding that behavioural equivalents of depression were resistant to an antidepressant medication suggested that depression in epilepsy might have distinct underlying mechanisms beyond alterations in serotonergic pathways.


[Preoperative thrombocytopenia with a postoperative diagnosis of thrombotic thrombocytopenic purpura].
A 64-year-old woman came to the emergency room complaining of vomiting and abdominal pain; appendicitis was suspected and surgery ordered. A blood work up showed a significantly low platelet count (39,000/microliter) and 6 units were transfused before surgery. The only observations during surgery were ileitis and Meckel's diverticulum. Thrombocytopenia persisted over the first 48 hours after surgery in spite of another transfusion of platelets, with worsening awareness and acute renal failure. After diagnosis of thrombotic thrombocytopenic purpura (TTP), the patient was admitted to the intensive care unit and treatment with fresh plasma and corticoids was started. Two weeks later, after complex evolution and ten sessions of plasmapheresis, the patient was transferred to the hematology ward. TTP must be considered a medical emergency. Platelet transfusions are contraindicated, as they can cause serious clinical deterioration. A low platelet count before surgery should lead to differential diagnosis to determine the cause, with the aim of judging whether platelet transfusion is warranted or not. In some etiological processes, such as in the case we report, platelet transfusion may be life-threatening; corrective measures must be taken early in the process and such transfusion avoided.


Lubricant effects on low Dk and silicone hydrogel lens comfort.
To investigate the influence of three lubricants of varying viscosity, on postinsertion and 6 h comfort with contact lens wear. Comfort and associated symptoms of dryness were assessed in 15 experienced contact lens wearers. Subjects wore a low Dk lens in one eye and a silicone hydrogel in the other and participated in four separate trials involving no lubricant (baseline), saline, and two commercially available lubricants of differing viscosity. The in-eye lubricants were used immediately following lens insertion and every 2 h postinsertion for a 6 h wear period. Postlens insertion comfort was significantly better for both lens types when lubricants or saline were used compared with no lubricant use. After 6 h lens wear, comfort was influenced by lens type and not by in-eye lubricant or saline use. Also after 6 h lens wear, less dryness sensation was reported for silicone hydrogel lenses when using lubricants but not saline. Although lubricant use does help reduce dryness symptoms with silicone hydrogel lens wear, there appears to be minimal longer-term benefit to comfort. Furthermore, increased lubricant viscosity did not lead to improved longer-term comfort.


The Role of Hindu Mandirs in Addressing Intimate Partner Violence Among South Asian American Communities.
There is a growing body of literature that documents high rates of intimate partner violence within South Asian American communities, indicating a critical need for research that can respond directly to this issue. From a socioecological perspective, Hindu temples can influence members' behaviors at multiple levels of change and thus may be important sites of collaboration for the prevention of intimate partner violence. Through in-depth qualitative interviews with South Asian families, temple leaders, and community stakeholders, this study indicates that Hindu temples have tremendous capacity to significantly impact intimate partner violence within South Asian American communities.


Healthy sleep score changes and incident cardiovascular disease in European prospective community-based cohorts.
Evidence on the link between sleep patterns and cardiovascular diseases (CVDs) in the community essentially relies on studies that investigated one single sleep pattern at one point in time. This study examined the joint effect of five sleep patterns at two time points with incident CVD events. By combining the data from two prospective studies, the Paris Prospective Study III (Paris, France) and the CoLaus|PsyCoLaus study (Lausanne, Switzerland), a healthy sleep score (HSS, range 0-5) combining five sleep patterns (early chronotype, sleep duration of 7-8 h/day, never/rarely insomnia, no sleep apnoea, and no excessive daytime sleepiness) was calculated at baseline and follow-up. The study sample included 11 347 CVD-free participants aged 53-64 years (44.6% women). During a median follow-up of 8.9 years [interquartile range (IQR): 8.0-10.0], 499 first CVD events occurred (339 coronary heart disease (CHD) and 175 stroke). In multivariate Cox analysis, the risk of CVD decreased by 18% [hazard ratio (HR) 0.82, 95% confidence interval (CI) 0.76-0.89] per one-point increment in the HSS. After a median follow-up of 6.0 years (IQR: 4.0-8.0) after the second follow-up, 262 first CVD events occurred including 194 CHD and 72 stroke. After adjusting for baseline HSS and covariates, the risk of CVD decreased by 16% (HR 0.84, 95% CI 0.73-0.97) per unit higher in the follow-up HSS over 2-5 years. Higher HSS and HSS improvement over time are associated with a lower risk of CHD and stroke in the community.


Identification of donor factors predisposing to high discard rates of cadaver kidneys and increased graft loss within one year posttransplantation--SEOPF 1977-1982. South-Eastern Organ Procurement Foundation.
From 1977 to 1982, the South-Eastern Organ Procurement Foundation (SEOPF) conducted a prospective study to determine the fate of all cadaver kidneys retrieved by member institutions. During the study period, 6152 kidneys were retrieved, 1264 being discarded. Donor factors predisposing to wastage included AB and A blood groups, donor age greater than 30, hospitalization greater than 3 days, serum creatinine greater than 2.0 mg%, average systolic blood pressure less than 80, last-hour urine output less than 100 ml, proteinuria, heart not beating at time of nephrectomy, and kidneys not removed en bloc. Donor factors affecting graft survival rate at one year include age, length of hospitalization, last-hour urine output, and changing serum creatinine. The data suggest that certain donor kidneys are less likely than others to be transplanted depending on donor characteristics and retrieval practices. Furthermore, some of these factors have a negative impact on long-term success when kidneys are transplanted.


Low molecular weight heparin-based reduction-sensitive nanoparticles for antitumor and anti-metastasis of orthotopic breast cancer.
Tumor metastasis has become a major obstacle for the clinical treatment of malignant breast cancer. Thus, a delivery system capable of both antitumor and anti-metastasis efficacy is desired. In this work, a low molecular weight heparin (LMWH)-based reduction-sensitive delivery system was developed, aiming to combine the properties of both the antitumor drug and active excipients to achieve a synergistic antitumor and anti-metastatic efficiency as well as resolving the potential adverse effects of both doxorubicin and LMWH. That is, the efficiency of DOX could be enhanced and its toxicity could be lowered. Meanwhile, the biological properties of LMWH could be strengthened and its bleeding risk could also be alleviated. Briefly, drug-loaded crosslinked nanoparticles (DOX/cLLHC2) had a longer blood circulation time and exhibited a rapid reduction-triggered release of DOX. The in vitro assays revealed that DOX/cLLHC2 exhibited a higher cellular uptake and cytotoxicity compared to free DOX. Meanwhile, for the existence of LMWH, DOX/cLLHC2 inhibited cell migration and invasion, as well as effectively inhibited the tube-like formation of human umbilical vein endothelial cells. DOX/cLLHC2 possessed a superior tumor accumulation compared to lipoic acid unmodified nanoparticles and free DOX. Also, DOX/cLLHC2 exhibited encouraging antitumor and anti-metastasis efficiency in an orthotopic breast cancer model. Overall, DOX/cLLHC2 could exert antitumor, anti-metastasis, and anti-angiogenesis efficacy simultaneously as well as having lower systemic toxicity, which makes it suitable for the therapy of metastatic breast carcinoma.


Acute air pollution exposure and NICU admission: a case-crossover analysis.
Neonatal intensive care unit (NICU) admission rates have increased over time. Air pollution is associated with adverse pregnancy outcomes, but the relationship between prenatal air pollution exposure and NICU admission has not been investigated. In the Consortium on Safe Labor (2002-2008), 27,189 singletons were admitted to the NICU. Modified Community Multiscale Air Quality models estimated exposures for criteria air pollutants and constituents of particles less than or equal to 2.5 microns (PM2.5). Case-crossover analyses calculated odds ratios and 95% confidence intervals for interquartile range increases in pollutant exposure, comparing exposures during the week of delivery to control periods before and after delivery. In models that adjusted for PM2.5, exposure to PM2.5 constituents during the week before delivery was significantly associated with increased odds of NICU admission: elemental carbon (35%), ammonium ions (37%), nitrate compounds (16%), organic compounds (147%), and sulfate compounds (35%). Odds were also significantly increased by day of and day before delivery exposures to carbon monoxide (4%-5%), nitrogen dioxide (13%), nitrogen oxides (4%-8%), particles less than or equal to 10 microns (2%), particles less than or equal to 2.5 microns (2%), and sulfur dioxide (3%-6%). No associations were observed for ozone. Acute exposures to PM2.5 constituents and several traffic-related pollutants during the week before delivery, the day of delivery, and day before delivery appear to increase the odds of NICU admissions. These novel associations suggest infants exposed in utero to common air pollutants may require additional care during the newborn hospital admission.


Word-finding difficulties confound performance on verbal cognitive measures in adults with intractable left temporal lobe epilepsy.
This study sought to determine if word-finding difficulties (WFDs), which are common in adults with dominant temporal lobe epilepsy (TLE), are related to performance on verbal cognitive measures, including memory. One hundred six individuals with left TLE and pathologically confirmed mesial temporal sclerosis completed comprehensive preoperative neuropsychological evaluations. Patients were divided into two groups based on the degree of benefit received from phonemic cueing on a confrontation naming task. Cognitive performance was then compared between patients with greater and fewer WFDs. Patients with greater WFDs demonstrated poorer performance on many verbal cognitive measures compared to those with fewer WFDs. In contrast, there were no significant differences between groups on any of the nonverbal cognitive measures. Chi-square analyses indicated that below average verbal memory performance occurred at a significantly higher rate for patients with greater WFDs (42-46%) as compared to patients with fewer WFDs (18-24%). Results showed that WFDs confound performance on verbal cognitive measures in adult patients with left TLE, particularly on measures with high demands for lexical retrieval. This suggests that when patients have word-retrieval difficulties, measures of verbal memory and verbal intelligence may be underestimated and potentially lead to misinterpretation of test performance and misinformation regarding risk of declines after surgical resection.


Toward Automation of the Supine Pressor Test for Preeclampsia.
Preeclampsia leads to increased risk of morbidity and mortality for both mother and fetus. Most previous studies have largely neglected mechanical compression of the left renal vein by the gravid uterus as a potential mechanism. In this study, we first used a murine model to investigate the pathophysiology of left renal vein constriction. The results indicate that prolonged renal vein stenosis after 14 days can cause renal necrosis and an increase in blood pressure (BP) of roughly 30 mmHg. The second part of this study aimed to automate a diagnostic tool, known as the supine pressor test (SPT), to enable pregnant women to assess their preeclampsia development risk. A positive SPT has been previously defined as an increase of at least 20 mmHg in diastolic BP when switching between left lateral recumbent and supine positions. The results from this study established a baseline BP increase between the two body positions in nonpregnant women and demonstrated the feasibility of an autonomous SPT in pregnant women. Our results demonstrate that there is a baseline increase in BP of roughly 10-14 mmHg and that pregnant women can autonomously perform the SPT. Overall, this work in both rodents and humans suggests that (1) stenosis of the left renal vein in mice leads to elevation in BP and acute renal failure, (2) nonpregnant women experience a baseline increase in BP when they shift from left lateral recumbent to supine position, and (3) the SPT can be automated and used autonomously.


Adult idiopathic jejuno-ileal intussusception.
This 67-year-old woman, with numerous previous abdominal operations, presented to her general practitioner 3 years ago with generalised abdominal pain and diarrhoea. With unremarkable haematology tests and a CT scan at that time she was given the diagnosis of irritable bowel syndrome. During the next 3 years her symptoms continued intermittently and now associated with vomiting and weight loss. This time both a barium follow-through followed by a CT scan demonstrated a small bowel intussusception. A laparotomy was done but surprisingly no intussusception was found, only a single adhesional band which was divided. She was discharged 5-days postoperative but re-admitted 3 days later with abdominal discomfort, bloating and vomiting. A repeat CT scan again showed the presence of a small bowel intussusception and a second laparotomy was performed, this time demonstrating a jejuno-ileal intussusception which was reduced and resected with primary anastomosis. Her postoperative course was without incidents.


Effects of photoperiod on the ultrastructure of Leydig cells in rat.
The aim of this study was to examine effects of photoperiod on the ultrastructure of Leydig cells in rat. For this purpose, 21 male Wistar rats were used. Animals were divided into three groups: Control rats in group I were kept under 12 hrs light: 12 hrs dark conditions (12L: 12D) for 10 weeks. Animals in group II were exposed to long photoperiods (18L: 6D), while rats in group III were exposed to short photoperiods (6L:18D) for 10 weeks. At the end of the experiment, all animals were killed by decapitation and blood samples were obtained. Serum testosterone levels were determined with the use of a chemiluminescent enzyme immunoassay. The testes of all rats were removed and weighed, then processed for light and electron microscopy. For morphometric comparison, diameters of seminiferous tubules in each group were measured. In rats exposed to long photoperiods, testicular weights, diameters of seminiferous tubules and serum testosterone levels were significantly increased as compared to those in control rats, whereas exposure of rats to short photoperiods resulted in a significant decrease of testicular weights, diameters of seminiferous tubules and serum testosterone levels as compared to those in control rats and rats maintained in long photoperiods. The amount of mitochondria and cytoplasmic secretory granules were increased in the cytoplasm of Leydig cells of rats exposed to long photoperiods. Furthermore, an increase in extensiveness of rough endoplasmic reticulum in the cell cytoplasm was noticed in this group, whereas a decrease in mitochondria and cytoplasmic secretory granules of the Leydig cell cytoplasm was seen in rats exposed to short photoperiods. The results of our study indicate that testicular functions increase after exposure to long photoperiods and decrease after exposure to short photoperiods.


Natural acidification changes the timing and rate of succession, alters community structure, and increases homogeneity in marine biofouling communities.
Ocean acidification may have far-reaching consequences for marine community and ecosystem dynamics, but its full impacts remain poorly understood due to the difficulty of manipulating pCO2 at the ecosystem level to mimic realistic fluctuations that occur on a number of different timescales. It is especially unclear how quickly communities at various stages of development respond to intermediate-scale pCO2 change and, if high pCO2 is relieved mid-succession, whether past acidification effects persist, are reversed by alleviation of pCO2 stress, or are worsened by departures from prior high pCO2 conditions to which organisms had acclimatized. Here, we used reciprocal transplant experiments along a shallow water volcanic pCO2 gradient to assess the importance of the timing and duration of high pCO2 exposure (i.e., discrete events at different stages of successional development vs. continuous exposure) on patterns of colonization and succession in a benthic fouling community. We show that succession at the acidified site was initially delayed (less community change by 8 weeks) but then caught up over the next 4 weeks. These changes in succession led to homogenization of communities maintained in or transplanted to acidified conditions, and altered community structure in ways that reflected both short- and longer-term acidification history. These community shifts are likely a result of interspecific variability in response to increased pCO2 and changes in species interactions. High pCO2 altered biofilm development, allowing serpulids to do best at the acidified site by the end of the experiment, although early (pretransplant) negative effects of pCO2 on recruitment of these worms were still detectable. The ascidians Diplosoma sp. and Botryllus sp. settled later and were more tolerant to acidification. Overall, transient and persistent acidification-driven changes in the biofouling community, via both past and more recent exposure, could have important implications for ecosystem function and food web dynamics.


Evaluation of a Longitudinal Family Stress Model in a Population-Based Cohort.
The Family Stress Model (FSM) is an influential family process model that posits that socioeconomic disadvantage impacts child outcomes via its effects on parents. Existing evaluations of the FSM are constrained by limited measures of socioeconomic disadvantage, cross-sectional research designs, and reliance on non-population-based samples. The current study tested the FSM in a subsample of the Fragile Families and Child Wellbeing Study (N = 2,918), a large population-based study of children followed from birth through age 9. We employed a longitudinal framework and used measures of socioeconomic disadvantage beyond economic resources. Although the hypothesized FSM pathways were identified in the longitudinal model (e.g., economic pressure at age 1 was associated with maternal distress at age 3, maternal distress at age 3 was associated with parenting behaviors at age 5), the effects of socioeconomic disadvantage at childbirth on youth socioemotional outcomes at age 9 did not operate through all of the hypothesized mediators. In longitudinal change models that accounted for the stability in constructs, multiple indicators of socioeconomic disadvantage at childbirth were indirectly associated with youth externalizing behaviors at age 9 via either economic pressure at age 1 or changes in maternal warmth from ages 3 to 5. Greater economic pressure at age 1, increases in maternal distress from ages 1 to 3, and decreases/increases in maternal warmth/harshness from ages 3 to 5 were also directly associated with increases in externalizing behaviors from ages 5 to 9. Results provide partial support for the FSM across the first decade of life.


[The physician as expert witness. Aspects of an ambivalent role exemplified by expert testimony for legal health insurance].
This article provides a broad survey of the difficulties confronting the physician in his role as a specialist in the Health Insurance Medical Service, assessing claims relating to the state medical insurance system. These problems can be divided into the three following categories. Firstly, problems on a personal level relating to the interaction of the different people involved, albeit within the given institutional framework. Secondly, problems involving matters of principle in reconciling diagnosis, the patient's subjective assessment of his condition and legal criteria. Thirdly, problems arising from the pressure created by socio-cultural developments which influence both the patient and the specialist physician in his assessment.


Surface display of a redox enzyme and its site-specific wiring to gold electrodes.
The generation of a current through interaction between bacteria and electrodes has been explored by various methods. We demonstrate the attachment of living bacteria through a surface displayed redox enzyme, alcohol dehydrogenase II. The unnatural amino acid para-azido-L-phenylalanine was incorporated into a specific site of the displayed enzyme, facilitating electron transfer between the enzyme and an electrode. In order to attach the bacteria carrying the surface displayed enzyme to a surface, a linker containing an alkyne and a thiol moiety on opposite ends was synthesized and attached to the dehydrogenase site specifically through a copper(I)-catalyzed azide-alkyne cycloaddition reaction. Using this approach we were able to covalently link bacteria to gold-coated surfaces and to gold nanoparticles, while maintaining viability and catalytic activity. We show the performance of a biofuel cell using these modified bacteria at the anode, which resulted in site-specific dependent fuel cell performance for at least a week. This is the first example of site-specific attachment of a true living biohybrid to inorganic material.