Characterization of human serum albumin's interactions with safranal and crocin using multi-spectroscopic and molecular docking techniques.
Interaction mechanisms of human serum albumin (HSA) with safranal and crocin were studied using UV-Vis absorption, fluorescence quenching and circular dichroism (CD) spectroscopies as well as molecular docking techniques. Changes in absorbance and fluorescence of HSA upon interactions with both compounds were attributed to their binding to amino acid chromophores located in subdomains IIA and IIIA. Fluorescence secondary inner filter effect was excluded using 278 nm and 340 nm as the wavelengths of HSA's excitation and fluorescence while safranal and crocin absorbed at 320 nm and 445 nm, respectively. Stern-Volmer model revealed a static quenching mechanism involve the formation of non-fluorescent ground state complexes. Stern-Volmer, Hill, Benesi-Hilbrand and Scatchard models gave apparent binding constants ranged in 4.25 × 103 - 2.15 × 105 for safranal and 7.67 × 103 - 4.23 × 105 L mol-1 for crocin. CD measurements indicated that 13 folds of safranal and crocin unfolded the α-helix structure of HSA by 7.47-21.20%. In-silico molecular docking revealed selective exothermic binding of safranal on eight binding sites with binding energies ranged in -3.969 to -6.6.913 kcal/mol. Crocin exothermally bound to a new large pocket located on subdomain IIA (sudlow 1) with binding energy of -12.922 kcal/mol. These results confirmed the formation of HSA stable complexes with safranal and crocin and contributed to our understanding for their binding characteristics (affinities, sites, modes, forces … etc.) and structural changes upon interactions. They also proved that HSA can solubilize and transport both compounds in blood to target tissues. The results are of high importance in determining the pharmacological properties of the two phytochemical compounds and for their future developments as anticancer, antispasmodic, antidepressant or aphrodisiac therapeutic agents.


Phosphorus utilization and characterization of excreta from swine fed diets containing a variety of cereal grains balanced for total phosphorus.
Intrinsic phytase in swine feeds may increase phytate utilization and alter the solubility of the excreted P. The objective of this experiment was to quantify changes in fecal P composition from swine fed a variety of cereal grains containing a range of phytate concentrations and endogenous phytase activities. Twenty-five crossbred barrows (89.3 +/- 6.8 kg) were fed 1 of 5 dietary treatments that were based on wheat, corn, barley, low-phytate barley, or high-fat-low-lignin oats. Experimental diets were formulated to contain 75% of the test grain and were fed for a 7-d acclimation period followed by a 3-d fecal collection period. Total-tract apparent digestibility coefficients were determined for DM, P, and phytate using an indicator method. Fecal P was characterized using solution-state (31)P nuclear magnetic resonance spectroscopy. Water-soluble P (WSP) and WSP-to-total P (TP) ratio were determined in the feces. Apparent total-tract digestibility coefficients for P and phytate ranged from 0.33 (barley) to 0.45 (low-phytate barley) and from 0.20 (corn) to 0.79 (oats), respectively. The majority of P excreted in the feces was in the form of phosphate (>47% of TP), and phytate degradation was not related to the endogenous phytase activity in the diet. There was a positive linear relationship between dietary NDF and apparent total-tract phytate digestibility (r(2) = 0.82; P = 0.03), indicating that greater dietary fiber content may enhance microbial breakdown of phytate in the hindgut. There was a negative relationship between the fecal WSP-to-TP ratio and the percentage of TP that was in the form of phytate in the feces. In summary, our results indicate that the majority of P in the feces of pigs fed diets based on cereal grains is present in the form of phosphate and relatively small amounts of phytate were contained in the excreta. The exception to this was the corn diet, for which 45% of the total fecal P was in the form of phytate. Hydrolysis of phytate in the gut did not appear to be related to the content of either phytate or phytase in the grain, but was related to dietary fiber concentration.


Differential effects of caerulein and bombesin on the ethanol intake in the rat.
Male Wistar rats were allowed to drink either water or water mixed with ethyl alcohol (4%, 8% and 12%) as part of a water-deprived procedure. The decapeptide caerulein (1, 3 and 6 micrograms/kg i.p.), a cholecystokinin analog, decreased the intake of ethanol while the consumption of tap water remained unchanged in a choice paradigm. The addition of quinine (a bitter substance) in drinking bottles did not significantly modify the fluid consumption while the i.p. injection of caerulein produced a significant decrease in the consumption of the saccharin containing bottle. The i.p. administration of bombesin (10 and 20 micrograms/kg) failed to modify the intake of water or ethanol solution in water-deprived animals. Interpretations are given in terms of the action of the cholecystokinin analog on differences in the taste intensity induced by the beverage or in terms of a direct consequence of the caerulein-induced decreased gastric emptying effect leading to an accumulation of ethanol in the gut.


Staphylococcus epidermidis with intermediate resistance to vancomycin: elusive phenotype or laboratory artifact?
The recent and troubling isolation of Staphylococcus aureus and coagulase-negative staphylococci that have increased resistance to glycopeptide antibiotics has prompted the use of aggressive surveillance measures in the clinical microbiology laboratory to aid in the recognition of these strains. Despite increasing awareness, the confirmation of glycopeptide resistance among staphylococci can be problematic; we present a case of catheter-associated peritonitis caused by Staphylococcus epidermidis to illustrate the dilemma.


Human Bertiella studeri in Spain, probably of African origin.
A mature tapeworm and gravid proglottids of Bertiella studeri were reported from the stools of a 33-year-old pregnant Spanish woman. The patient had spent the six months preceding this discovery in Kenya. The evidence suggests a case of parasitism imported to Spain from the African continent. The patient presented no symptoms related to the parasite and the discovery in stools of a number of active, white structures led her to collect them. A morphologic and morphometric description of the material obtained is presented. Mebendazole failed to remove the parasite but niclosamide was effective.


Contact alters cAMP metabolism in aggregation-competent Dictyostelium amoebae.
cAMP and cell-cell contact are involved in the coordination of differentiation and morphogenesis in Dictyostelium discoideum. The experiments described in this paper establish a relationship between cAMP and cell-cell contact. Contact between Enterobacter aerogenes and aggregation-competent Dictyostelium amoebae and contact between Dictyostelium amoebae themselves results in the transient secretion of cAMP and an alteration in the amount of cAMP secreted in response to subsequent stimulation by cAMP, i.e., an alteration in magnitude of a cAMP relay response. The subsequent cAMP relay response can be enhanced or diminished depending upon the number of contacts formed and the concentration of cAMP present at the time of contact. Latex beads are capable of evoking cAMP secretion. However, the bead/amoebal contact is unable to alter the magnitude of a subsequent response to cAMP. This suggests that a nonspecific interaction via cell-cell contact elicits transient cAMP secretion in aggregation-competent Dictyostelium amoebae. The two responses to cell-cell contact are distinct from each other and distinct from the cAMP relay response. 1) The dose-response curves for the responses to Enterobacter contact are clearly different. 2) Contact with latex beads can elicit cAMP secretion but not alter the magnitude of a subsequent cAMP relay response. 3) The temperature dependences of the contact-induced responses and the cAMP relay response show that only the contact-induced cAMP secretion is inhibited at 12 and 15 degrees C, while only the cAMP relay response is inhibited at 28 degrees C. A 4-second application of cAMP at the time that contact is initiated enhances both contact-induced responses. Whether the relationship between these two developmental regulators is important for the regulation of Dictyostelium development has yet to be established.


Exploring and targeting saccades dissociated by saccadic adaptation.
Saccadic adaptation maintains saccade accuracy and has been studied with targeting saccades, i.e. saccades that bring the gaze to a target, with the classical intra-saccadic step procedure in which the target systematically jumps to a new position during saccade execution. Post-saccadic visual feedback about the error between target position and the saccade landing position is crucial to establish and maintain adaptation. However, recent research focusing on two-saccade sequences has shown that exploring saccades, i.e. saccades that explore an object, resists this classical intra-saccadic step procedure but can be adapted by systematically changing the main parameter used for their coding: stimulus size. Here, we adapted an exploring saccade and a targeting saccade in two separate experiments, using the appropriate adaptation procedure, and we tested whether the adaptation induced on one saccade type transferred to the other. We showed that whereas classical targeting saccade adaptation does not transfer to exploring saccades, the reciprocal transfer (i.e., from exploring to targeting saccades) occurred when targeting saccades aimed for a spatially extended stimulus, but not when they aimed for an isolated target. These results show that, in addition to position errors, size errors can drive adaptation, and confirm that exploring vs. targeting a stimulus leads to two different motor planning modes.


Excellent population research prize to be awarded.
In order to promote the development of population science in China, mobilize the initiativeness of demographers and more effectively serve the purpose of controlling population growth and improving the quality of human resources, the Population Association of China has sponsored an Excellent Population Research Award to encourage the demographers with outstanding achievements within the term (January 1991-June 30, 1993) of the Association. All the research staff and family planning workers with the membership of the Population Association of China as well as research institutes with notable achievements are eligible to the application for the award. The research achievements include monographs (or teaching materials), papers, survey reports, translated works, dictionaries or reference books, and softwares. For each category, 2 classes of prizes have been set, and winners are to be awarded with diplomas and money. The evaluation work will be started in September and October and concluded by the end of November 1993.


Strategy for the control of drug-induced liver injury due to investigational treatments/drugs for COVID-19.
Investigational treatments/drugs for coronavirus disease 2019 (COVID-19) have been applied, with repurposed or newly developed drugs, and their effectiveness has been evaluated. Some of these drugs may be hepatotoxic, and each monotherapy or combination therapy may increase the risk of drug-induced liver injury (DILI). We should aim to control dysregulation of liver function, as well as the progression of COVID-19, as much as possible. We discussed the potential risks of investigational treatments/drugs and promising drugs for both COVID-19 and DILI due to investigational treatments/drugs.


Hydroxycinnamoyl-CoA:Putrescine Hydroxycinnamoyltransferase in Tobacco Cell Cultures with High and Low Levels of Caffeoylputrescine.
A new hydroxycinnamoyl-CoA:putrescine hydroxycinnamoyltransferase (PHT) was detected in two variant lines of Nicotiana tabacum L. (TX1, TX4) accumulating markedly different levels of caffeoylputrescine. The enzyme accepted only the aliphatic diamines putrescine, cadaverine and 1,3-diaminopropane at a ratio of 100:33:8. Caffeoyl- and feruloyl-CoAs were the best acyl donors. The apparent K(m)-values for caffeoyl-CoA and putrescine were near 3 and 10 micromolar, respectively, at the pH-optimum of 10.0. PHT activity was quite similar in low producing TX1 and high producing TX4 cells, while some other biosynthetic enzymes (phenylalanine ammonia-lyase, ornithine decarboxylase) were greatly enhanced in TX4 cells, suggesting that PHT does not catalyze the rate-limiting step in hydroxycinnamoylputrescine formation.


Teachers' beliefs about mental health needs in inner city elementary schools.
To survey teachers' beliefs about mental health service needs in inner city elementary schools. A total of 119 teachers from six elementary schools in a major city in the midwestern United States were surveyed to assess their beliefs about the major mental health problems facing their schools, the major barriers to surmounting those problems, their preferences for mental health topics for in-service education, and their education, experience, knowledge, attitudes, and self-efficacy pertaining to mental health issues. Disruptive behavior was endorsed by approximately 50% of teachers as the largest mental health problem facing their schools, and lack of information/training was endorsed as the greatest barrier to surmounting mental health problems. The highest-rated topics for in-service education were disruptive behavior disorders and implementing behavior plans. Although most teachers had taught students with mental health problems, most had had little education in mental health and little consultation with mental health professionals. Correspondingly, teachers' knowledge about mental health issues was limited, and they did not feel confident about their ability to manage mental health problems in their classrooms. Teachers would benefit from education, training, and consultation from mental health professionals if they serve as effective gatekeepers to mental health services.


[Verification of two methods of indirectly estimating mortality].
"This paper examines two methods of indirectly estimating mortality: the Bourgeois-Pichat method (estimation of life expectancy at birth), and the Bourbeau and Legare method.... This last method consists of estimating various past mortality measures, for a given population, by examining these same measures as they were observed in certain other populations, during the period in question." These methods are applied to Norwegian data for 1826-1976. The results are then compared with data observed during the same period. The findings are used to evaluate the two methods and assess their advantages and disadvantages. However, the emphasis is on the Bourbeau and Legare method. (summary in ENG, SPA)


Thrombopoietin levels in patients with primary and reactive thrombocytosis.
Human c-mpl ligand or thrombopoietin (TPO) has been proved to be a critical cytokine in the physiological regulation of thrombopoiesis. Previous evidence suggested that TPO production is constitutive and TPO plasma levels are regulated by the platelet-megakaryocyte mass through c-mpl receptor-mediated uptake and metabolism. To evaluate whether this mechanism of TPO level regulation is also operative in subjects with an elevated platelet count, we evaluated serum TPO in 32 patients with thrombocytosis due to essential thrombocythaemia (ET) or polycythaemia vera (PV) and in 70 subjects with reactive thrombocytosis; 32 healthy subjects were also studied. TPO levels were significantly higher in the ET and PV groups (median 246.2 pg/ml, range 93.5-4596) and reactive thrombocytosis patients (median 287 pg/ml, range 82.7-1960.0) than in normal subjects (median 156.7 pg/ml, range 62.2-352.7). No significant difference was found between the two groups of patients, indicating that serum TPO levels cannot differentiate between primary and reactive thrombocytosis. No significant correlation was found between platelet count and TPO levels in either ET-PV or reactive thrombocytosis, whereas a trend toward a correlation between acute-phase reactants and TPO was observed in patients with reactive thrombocytosis. These results indicate that TPO clearance by platelets-megakaryocytes is not fully operative or is not the only mechanism of TPO level regulation in primitive and reactive thrombocytosis.


Sub-10 nm Aggregation-Induced Emission Quantum Dots Assembled by Microfluidics for Enhanced Tumor Targeting and Reduced Retention in the Liver.
A robust platform is developed to assemble sub-10 nm organic aggregation-induced emission (AIE) particles using four different AIE luminogens (AIEgens) with emissions from green to the second near-infrared window (NIR-II). They are called AIE quantum dots (QDs) to distinguish from typical AIE dots which are larger than 25 nm. Compared with AIE dots that are larger than 25 nm, AIE QDs allow more efficient cellular uptake and imaging without surface modification of any membrane-penetrating peptides or other targeting molecules. NIR-II AIEgens, which have nearly no background fluorescence from organisms, are used to demonstrate that AIE QDs can achieve high contrast at the tumor as small as 80 mm3 and evade the liver more efficiently than AIE dots. AIE QDs hold a good promise for sensitive and precise diagnosis of the latent solid tumor in clinical medicine with much lower off-targeting to the liver than AIE dots.


Patterns of Physical Activity and Associated Factors in Cubans Aged 15-69 Years.
INTRODUCTION Systematic measurement of population physical activity levels is an important component of public health surveillance. OBJECTIVES Describe patterns of physical activity in the Cuban population aged 15-69 years and identify factors associated with regular physical activity. METHODS A descriptive cross-sectional study was conducted using a complex sampling design, representative of urban and rural areas, sex and age groups, including 7915 individuals. The International Physical Activity Questionnaire (short format) was applied. The population was classified as active, irregularly active and sedentary, according to sex, age, marital status, education, skin color, employment and perception of health risk related to physical inactivity or overweight. Percentages, odds ratios (OR) and 95% confidence intervals (CI) were calculated and a multinomial regression model was fitted with active persons as the reference category. RESULTS Approximately 71% of the population self-classified as active, 23% as sedentary and 5.9% as irregularly active. Women had a higher probability of being sedentary (OR 2.51, CI 2.12-2.98) and irregularly active (OR 2.56, CI 95% 1.87-3.49). The probability of being sedentary increased with age (OR 1.19, CI 1.12-1.26), and also with the condition of being a homemaker, retired, or unemployed. Perceiving overweight as a high risk to health reduced likelihood of inactivity (OR 0.49, CI 0.29-0.83). CONCLUSIONS Some 7 of 10 Cubans are physically active. The groups with the highest probability of inactivity and irregular activity and associated factors have been identified through national application (for the first time) of the International Physical Activity Questionnaire. The results should be taken into account for implementation of specialized strategies to promote systematic physical activity. KEYWORDS Physical activity, physical exercise, sedentary lifestyle, health behavior, risk factors, chronic disease, women's health, surveillance, Cuba.


Induction of intestinal stem cells by R-spondin 1 and Slit2 augments chemoradioprotection.
Cancer research has been rightly and successfully focused on prevention, early detection, and identification of specific molecular targets that distinguish the malignant cells from the neighbouring benign cells. However, reducing lethal tissue injury caused by intensive chemoradiotherapy during treatment of late-stage metastatic cancers remains a key clinical challenge. Here we tested whether the induction of adult stem cells could repair chemoradiation-induced tissue injury and prolong overall survival in mice. We found that intestinal stem cells (ISCs) expressed Slit2 and its single-span transmembrane cell-surface receptor roundabout 1 (Robo1). Partial genetic deletion of Robo1 decreased ISC numbers and caused villus hypotrophy, whereas a Slit2 transgene increased ISC numbers and triggered villus hypertrophy. During lethal dosages of chemoradiation, administering a short pulse of R-spondin 1 (Rspo1; a Wnt agonist) plus Slit2 reduced ISC loss, mitigated gut impairment and protected animals from death, without concomitantly decreasing tumour sensitivity to chemotherapy. Therefore Rspo1 and Slit2 may act as therapeutic adjuvants to enhance host tolerance to aggressive chemoradiotherapy for eradicating metastatic cancers.


Fique Fabric: A Promising Reinforcement for Polymer Composites.
A relatively unknown natural fiber extracted from the leaves of the fique plant, native of the South American Andes, has recently shown potential as reinforcement of polymer composites for engineering applications. Preliminary investigations indicated a promising substitute for synthetic fibers, competing with other well-known natural fibers. The fabric made from fique fibers have not yet been investigated as possible composite reinforcement. Therefore, in the present work a more thorough characterization of fique fabric as a reinforcement of composites with a polyester matrix was performed. Thermal mechanical properties of fique fabric composites were determined by dynamic mechanical analysis (DMA). The ballistic performance of plain woven fique fabric-reinforced polyester matrix composites was investigated as a second layer in a multilayered armor system (MAS). The results revealed a sensible improvement in thermal dynamic mechanical behavior. Both viscoelastic stiffness and glass transition temperature were increased with the amount of incorporated fique fabric. In terms of ballistic results, the fique fabric composites present a performance similar to that of the much stronger KevlarTM as an MAS second layer with the same thickness. A cost analysis indicated that armor vests with fique fabric composites as an MAS second layer would be 13 times less expensive than a similar creation made with Kevlar™.


Clinical profiles and risk factors of 7-day and 30-day mortality among 160 pediatric patients with hemophagocytic lymphohistiocytosis.
Hemophagocytic lymphohistiocytosis (HLH) is a relatively rare and life-threatening disorder. Early mortality remains significantly high among patients with HLH. Our aim was to investigate clinical features and risk factors associated with 7-day and 30-day mortality among pediatric HLH patients. We retrospectively collected medical records of patients with discharge diagnosis of HLH between August 2014 and October 2018 from a tertiary children's hospital in China. The main outcome measures were the 7-day and 30-day outcome after hospital admission. The associations between symptoms, concomitant diagnoses, laboratory test results, and the risk of 7-day and 30-day mortality were examined. Among 160 pediatric HLH patients, 18 (11.3%) patients were deceased within 7 days after admission, and 46 (28.8%) patients were deceased within 30 days. The identified strong risk factors (OR > 10 and p < 0.05) for 30-day mortality were myocardial damage, severe pneumonia, respiratory failure, coagulopathy, gastrointestinal disorder, and multiple organ dysfunction syndrome (MODS). Factors strongly associated with 7-day mortality were sepsis, myocardial damage, shock, and respiratory failure. All patients deceased within 7 days developed hepatic dysfunction, coagulopathy, and MODS. The identified risk factors could help to stratify patients with high risk of early death, and need to be considered in the development of treatment protocols. As early mortality of HLH remains high, studies are needed to investigate how to initiate adequate HLH-directed treatment strategies for patients at higher risk of early death.


Unbiased Screens Show CD8+ T Cells of COVID-19 Patients Recognize Shared Epitopes in SARS-CoV-2 that Largely Reside outside the Spike Protein.
Developing effective strategies to prevent or treat coronavirus disease 2019 (COVID-19) requires understanding the natural immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We used an unbiased, genome-wide screening technology to determine the precise peptide sequences in SARS-CoV-2 that are recognized by the memory CD8+ T cells of COVID-19 patients. In total, we identified 3-8 epitopes for each of the 6 most prevalent human leukocyte antigen (HLA) types. These epitopes were broadly shared across patients and located in regions of the virus that are not subject to mutational variation. Notably, only 3 of the 29 shared epitopes were located in the spike protein, whereas most epitopes were located in ORF1ab or the nucleocapsid protein. We also found that CD8+ T cells generally do not cross-react with epitopes in the four seasonal coronaviruses that cause the common cold. Overall, these findings can inform development of next-generation vaccines that better recapitulate natural CD8+ T cell immunity to SARS-CoV-2.


Computed radiography in musculoskeletal imaging: state of the art.
Computed radiography is a 2K x 2K x 10 bit digital radiographic system that replaces the film-screen combination with a photo-stimulable phosphor plate. The advantages of this relatively new technology include linear detector response, improved detector efficiency, and digital processing capabilities. Musculoskeletal applications benefit significantly from these attributes, which result clinically in the ability to reduce both radiation dose and number of exposures. Studies of observers' performance have shown no statistically significant difference in diagnostic accuracy between film-screen and computed radiographic musculoskeletal images. Computed radiography is particularly useful in the evaluation of the musculoskeletal system in traumatized patients with portable radiographs, spine radiographs, scoliosis studies, and depiction of soft-tissue abnormalities. Limitations include change in image format and size, high cost, decreased spatial resolution, restricted throughput, increased perception of noise, and new artifacts that must be recognized. Spatial resolution limitations of computed radiography in identification of fine detail information can be improved by using magnification techniques. Radiation dose reduction with an exposure decrease of 25-50% can be achieved without loss of diagnostic accuracy, although this depends on the examination and the abnormality. An interactive workstation is important in the use of a computed radiographic system with capabilities to adjust display parameters to best depict images and disease. We conclude that computed radiography is an alternative to film-screen radiography without significant differences in diagnostic quality in the evaluation of musculoskeletal images.


Accuracy of estimation of time-intervals in psychogeriatric outpatients.
Accuracy of estimation of time-intervals has received marginal attention in psychogeriatrics. We examined presumed differences in this time measure in participants with dementia (PWD) versus participants without dementia (PWoutD), further subdivided into specific diagnoses and performance subgroups. We also studied its demographic, clinical, and cognitive correlates and predictors. A diagnostic role was hypothesized. Forty-three individuals (27 PWD: 16 dementia of the Alzheimer's type (DAT), 11 vascular dementia (VaD); 16 PWoutD: 10 major depressive disorder (MDD), 6 normal) were interviewed with the Cambridge Examination for Mental Disorders of the Elderly - Revised (CAMDEX-R) that permits the registration of this time measure. Demographic, clinical, and cognitive data were obtained. Neither absolute accuracy of estimation of duration of interview nor its transformed logarithm were significantly different between PWD and PWoutD, or between DAT and VaD participants. MDD participants performed significantly poorer than normal and did not differ from PWD, and the PWD relatively better performing subgroup. The logarithm of absolute accuracy of estimation correlated with some clinical and cognitive variables. Only a measure of depression and of impaired judgment could significantly predict it. The absolute accuracy of estimation of time-intervals did not differ between the major groups and the main diagnoses subgroups. It was associated with a variety of clinical and cognitive measures, and was predicted by the composite constructs of depression and impaired judgment. The diagnostic value of this measure in the psychogeriatric clinic is questionable, and limited to "worried" well individuals.


Short amyloid-beta (Abeta) immunogens reduce cerebral Abeta load and learning deficits in an Alzheimer's disease mouse model in the absence of an Abeta-specific cellular immune response.
Amyloid-beta (Abeta) immunotherapy lowers cerebral Abeta and improves cognition in mouse models of Alzheimer's disease (AD). A clinical trial using active immunization with Abeta1-42 was suspended after approximately 6% of patients developed meningoencephalitis, possibly because of a T-cell reaction against Abeta. Nevertheless, beneficial effects were reported in antibody responders. Consequently, alternatives are required for a safer vaccine. The Abeta1-15 sequence contains the antibody epitope(s) but lacks the T-cell reactive sites of full-length Abeta1-42. Therefore, we tested four alternative peptide immunogens encompassing either a tandem repeat of two lysine-linked Abeta1-15 sequences (2xAbeta1-15) or the Abeta1-15 sequence synthesized to a cross-species active T1 T-helper-cell epitope (T1-Abeta1-15) and each with the addition of a three-amino-acid RGD (Arg-Gly-Asp) motif (R-2xAbeta1-15; T1-R-Abeta1-15). High anti-Abeta antibody titers were observed in wild-type mice after intranasal immunization with R-2xAbeta1-15 or 2xAbeta1-15 plus mutant Escherichia coli heat-labile enterotoxin LT(R192G) adjuvant. Moderate antibody levels were induced after immunization with T1-R-Abeta1-15 or T1-Abeta1-15 plus LT(R192G). Restimulation of splenocytes with the corresponding immunogens resulted in moderate proliferative responses, whereas proliferation was absent after restimulation with full-length Abeta or Abeta1-15. Immunization of human amyloid precursor protein, familial AD (hAPP(FAD)) mice with R-2xAbeta1-15 or 2xAbeta1-15 resulted in high anti-Abeta titers of noninflammatory T-helper 2 isotypes (IgG1 and IgG2b), a lack of splenocyte proliferation against full-length Abeta, significantly reduced Abeta plaque load, and lower cerebral Abeta levels. In addition, 2xAbeta1-15-immunized hAPP(FAD) animals showed improved acquisition of memory compared with vehicle controls in a reference-memory Morris water-maze behavior test that approximately correlated with anti-Abeta titers. Thus, our novel immunogens show promise for future AD vaccines.


Nuclear and Fluorescent Labeled PD-1-Liposome-DOX-64Cu/IRDye800CW Allows Improved Breast Tumor Targeted Imaging and Therapy.
The overexpression of programmed cell death-1 (PD-1) in tumors as breast cancer makes it a possible target for cancer imaging and therapy. Advances in molecular imaging, including radionuclide imaging and near-infrared fluorescence (NIRF) imaging, enable the detection of tumors with high sensitivity. In this study, we aim to develop a novel PD-1 antibody targeted positron emission tomography (PET) and NIRF labeled liposome loaded with doxorubicin (DOX) and evaluate its application for in vivo cancer imaging and therapy. IRDye800CW and 64Cu were conjugated to liposomes with PD-1 antibody labeling, and DOX was inside the liposomes to form theranostic nanoparticles. The 4T1 tumors were successfully visualized with PD-1-Liposome-DOX-64Cu/IRDye800CW using NIRF/PET imaging. The bioluminescent imaging (BLI) results showed that tumor growth was significantly inhibited in the PD-1-Liposome-DOX-treated group than the IgG control. Our results highlight the potential of using dual-labeled theranostic PD-1 mAb-targeted Liposome-DOX-64Cu/IRDye800CW for the management of breast tumor.


miR-147b-mediated TCA cycle dysfunction and pseudohypoxia initiate drug tolerance to EGFR inhibitors in lung adenocarcinoma.
Drug-tolerance is an acute defense response prior to a fully drug-resistant state and tumor relapse, however there are few therapeutic agents targeting drug-tolerance in the clinic. Here we show that miR-147b initiates a reversible tolerant-state to the EGFR inhibitor osimertinib in non-small cell lung cancer. With miRNA-seq analysis we find that miR-147b is the most upregulated microRNA in osimertinib-tolerant and EGFR mutated lung cancer cells. Whole transcriptome analysis of single-cell derived clones reveals a link between osimertinib-tolerance and pseudohypoxia responses irrespective of oxygen levels. Further metabolomics and genetic studies demonstrate that osimertinib-tolerance is driven by miR-147b repression of VHL and succinate dehydrogenase linked to the tricarboxylic acid cycle and pseudohypoxia pathways. Finally, pretreatment with a miR-147b inhibitor delays osimertinib-associated drug tolerance in patient-derived three-dimensional (3D) structures. This link between miR-147b and tricarboxylic acid cycle may provide promising targets for preventing tumor relapse.


Nightly and seasonal movements, seasonal home range, and focal location photo-monitoring of urban striped skunks (Mephitis mephitis): implications for rabies transmission.
We followed radio-collared striped skunks (Mephitis mephitis) from January 2004-December 2005 in two urban areas of Flagstaff, Arizona, USA to determine seasonal patterns of movement and home-range size. We also used automated cameras to determine the potential for inter- and intraspecific interaction at skunks' diurnal resting sites and nocturnal focal locations. We found no difference between sexes in nightly rates of travel or in size of seasonal home range. Nightly rates of travel were greatest in the postbreeding months (May-July) and smallest from November to February, consistent with larger home ranges (95% kernel estimates) from March-August and smaller home ranges from September-February. Sixty-three percent of monitored males and 38% of monitored females crossed the urban-wildland interface, in at least one direction on at least one night, and some remained outside the urban area for days or weeks, indicating that skunks could act as vectors of disease across the urban-wildland interface. We recorded co-occurrence of skunks with domestic cats (Felis domesticus), raccoons (Procyon lotor), gray foxes (Urocyon cinereoargenteus), and other skunks at focal locations and diurnal retreats used by skunks, suggesting these areas are potential sites for both inter- and intraspecific rabies transmission and could be targeted by wildlife managers during trapping or vaccination programs.


Murine T lymphocyte specificity for African trypanosomes. II. Suppression of the T lymphocyte proliferative response to Trypanosoma brucei by systemic trypanosome infection.
Previously, we described a system allowing the study of murine T cell-dependent proliferative responses to Trypanosoma brucei antigens. It was observed that T. brucei-specific T cells could be demonstrated in the regional lymph nodes of primed mice for only 2 to 3 weeks following priming. The results of the present study indicate that this inability to demonstrate a long-lived memory response is due to an immunosuppressive effect of the resulting T. brucei infection. The exact mechanism of the suppression is not known, and appears to function in the absence of demonstrable suppressor cells. Since the T cell responses are strictly dependent on the presence of macrophages, we have investigated whether the loss in responsiveness is due to a defect in the T cell population, or to a loss of macrophage function. Our results show that T cells taken from mice 3 weeks after priming with T. brucei are unable to mount a proliferative response in the presence of a normal macrophage population, and conversely that macrophages taken 3 weeks after infection with T. brucei are unable to elicit a normal proliferative response using a competent primed T cell population. Thus these results indicate that both populations are affected by the parasite infection.


A computational study of the role of mitochondrial organization on cardiac bioenergetics.
All cells in the body have a specific shape and internal organization which is specific to that cell's function. Heart cells are rod-shaped, and contain arrays of contractile protines (myofibrils) and mitochondria (organelles that produce energy) that are aligned along the length of the rod. This arrangement is presumed to allow the cell to generate maximal contractile force for each heartbeat and for energy metabolites to be readily available to generate this force. Heart disease phenotypes, such as diabetic cardiomyopathy and heart failure, exhibit altered organization of mitochondria. However, physiological and computational studies have predominantly investigated the effect of the biochemical changes that accompany the disease alone, such as reduced rates of ATP production by mitochondria. We present a modeling study that examines the effect of mitochondrial organization on energy metabolite distribution during the heartbeat. A 2D micrograph of the cell cross-section was selected from a 3D image stack of structural data of a cardiac cell. The image was used to generate a 2D finite element model, on which mitochondrial oxidative phosphorylation and energy metabolite diffusion was modelled. Results illustrate that mitochondrial density can induce heterogeneity in the distribution of metabolites across the cell area. We discuss the implications of these findings and avenues for future, more indepth studies.


Draft Genome Sequence of the Ionic Liquid-Tolerant Bacterium Bacillus amyloliquefaciens CMW1.
Here, we report the draft genome sequence of an ionic liquid-tolerant bacterium, Bacillus amyloliquefaciens CMW1, which is newly isolated from a Japanese fermented soybean paste. The genome sequence will allow for a characterization of the molecular mechanism of its ionic liquid tolerance.


Altered ex vivo expression of caspase 8, caspase 9, and Bcl-2 is associated with T-cell hyporeactivity in patients with paracoccidioidomycosis.
To better understand the T-cell hyporesponsiveness of patients with paracoccidioidomycosis, we tested the hypothesis that the T cells were committed to apoptosis. We show here that T cells of patients with paracoccidioidomycosis overexpress caspase 9 and caspase 8 but express low Bcl-2 levels and that interleukin-2 was unable to revert the hyporesponsiveness. These data suggest that the T cells would in vivo be driven to a tolerant state and apoptosis.


An update on diagnosis and therapy of metabolic myopathies.
Metabolic myopathies are a heterogeneous group of disorders characterized by inherited defects of enzymatic pathways involved in muscle fiber energetics. Diagnosing metabolic myopathies requires a thoroughly taken individual and family history, a meticulous neurologic exam, exercise tests, blood and urine tests, needle-electromyography, nerve-conduction studies, muscle biopsy, targeted genetic tests, or next-generation sequencing. There is limited evidence from the literature to guide treatment of metabolic myopathies. Treatment is largely limited to non-invasive/invasive symptomatic measures. However, promising results have been achieved with enzyme replacement therapy in Pompe disease (GSD-II). Primary coenzyme-Q deficiency responds favorably to coenzyme-Q supplementation. MNGIE responds to allogeneic hematopoietic stem cell transplantation, orthotopic liver transplantation, and carrier erythrocyte entrapped thymidine phosphorylase enzyme therapy. MADD may respond to riboflavin. Areas covered: This review aims to summarize and discuss recent findings and new insights concerning diagnosis and treatment of metabolic myopathies. Expert commentary: Except for GSD-II, coenzyme-Q deficiency, and MNGIE, treatment of metabolic myopathies is usually palliative and supportive (non-invasive or invasive). Non-invasive symptomatic treatment includes physiotherapy, diet, administration of drugs, conservative orthopedic measures, and respiratory non-invasive support. Important is the avoidance of triggers for episodic forms of fatty acid oxidation disorders. Invasive measures include orthopedic surgery and invasive mechanical ventilation.


Cell proliferation kinetics in the marginal mucosa of gastric ulcer evaluated by immunostaining of DNA polymerase alpha.
We studied the proliferative ability of the marginal mucosal cells surrounding the ulcer in the healing processes of gastric ulcers. We obtained a labeling index (LI) at the neck and generative zone of gastric pit using a monoclonal antibody against DNA polymerase alpha for tractable and intractable gastric ulcers located at the fundic mucosa during each endoscopic stage. The LI during the healing stage was higher than that during the active stage in both the tractable and intractable cases. However, in each stage, the LI of the tractable gastric ulcers was higher than that of their intractable counterparts. Finally, we analyzed the LI in tractable gastric ulcers after setting two groups: one treated with anti-ulcer drugs and the other untreated. There were no significant differences between these two groups. We believe that investigation of proliferative abilities in the marginal mucosa of gastric ulcers is important to understand the nature of gastric ulcers and to assess therapeutic efficacy.


[Glutamate receptors and transporters in the brain and peripheral tissues].
Functional diversity of glutamate receptors in the central nervous system (CNS) is a consequence of their considerable molecular diversity. The family of glutamate receptors including their subunits consists of more than 25 proteins. It is the result of gene expression as well as extensive post-transcriptional modifications. Evidence is increasing that glutamate receptors are localised not only in the CNS, but also in the peripheral tissues. Whereas characteristics and physiological significance of peripheral glutamate receptors are little understood, there are studies indicating their role in hormone secretion, neuromuscular functions, sensory transmission and paracrine signalization. In addition, peripheral glutamate receptors may participate in mediating of excitatory amino acids toxicity. A special attention is paid to glutamate receptors localised in the heart and adrenals, as these receptors may be involved in the maintenance of homeostatic mechanisms under pathological or stress conditions.


[Fatal chronic oxalosis after sublethal ethylene glycol poisoning].
A 36-year-old man known as chronic alcohol abuser presently suffered from arthralgia and showed bilateral petriefied kidneys by sonography and computed tomography. Because of an unclear renal failure a kidney biopsy was performed and presented typical chronic renal oxalosis with massive oxalate crystal deposits, tubular atrophy and interstitital fibrosis. Since the man had never shown signs of hyperoxaluria in his life before, a secondary oxalosis was supposed. The subsequently prompted exploration established a three to four times abuse of rocket fuel with cola lemonade 12 years before during the patient's army time as a marine soldier. Such fuels contain ethylene glycol (glysantin) as antifreeze commonly known to cause in toxic doses acute renal tubular necrosis with hyperoxaluria. The presented case, however, suggests a rare sublethal ethylene glycol poisoning with initial renal tubular damage, oxalate crystal deposition and subsequent chronic interstitial oxalate nephritis with tubular atrophy, interstitial fibrosis and chronic renal failure. Undergoing chronic hemodialysis, the patient died 5 months after the kidney biopsy diagnosis by acute heart failure. At autopsy, progressed chronic renal oxalosis could be confirmed. Decompensated oxalate cardiomyopathy with disseminated myocardial oxalate crystal deposits caused acute heart failure promoted by myocardial hypertrophy in renal hypertension.


Activity of a platelet protein kinase that phosphorylates fibrinogen and histone in Argentine hemorrhagic fever.
The activity of a platelet protein kinase that phosphorylates the alpha-chain of fibrinogen and the exogenous substrate histone was evaluated in 28 patients with Argentine hemorrhagic fever, grouped into: 13 mild, 6 moderate and 9 severe clinical forms. Blood samples were obtained before treatment with immune plasma, 4 days later and at recovery. Exogenous histone and fibrinogen phosphorylation were assayed with 25 Ci/mmol (gamma-32P)-ATP. Platelet counts and interferon (IFN) activity were performed simultaneously. Histone phosphorylation was found below normal in all patients during the acute phase of illness. This reduction was coincident with the lowest platelet count and the highest IFN titers. Fibrinogen phosphorylation was similarly reduced. Histone and fibrinogen phosphorylation were still low after 4 days of treatment, when IFN levels were almost undetectable. The low level of phosphorylation was not simply due to the reduced number of platelets and may be another evidence of a platelet abnormality in patients with Argentine hemorrhagic fever.


Antagonizing Sec62 function in intracellular Ca2+ homeostasis represents a novel therapeutic strategy for head and neck cancer.
Various cancer types including head and neck squamous cell carcinomas (HNSCC) show a frequent amplification of chromosomal region 3q26 that encodes, among others, for the SEC62 gene. Located in the ER membrane, this translocation protein is known to play a critical role as a potential driver oncogene in cancer development. High SEC62 expression levels were observed in various cancer entities and were associated with a poor outcome and increased metastatic burden. Because of its intracellular localization the SEC62 protein is poorly accessible for therapeutic antibodies, therefore a functional SEC62 knockdown represents the most promising mechanism of a potential antineoplastic targeted therapy. By stimulating the Ca2+ efflux from the ER lumen and thereby increasing cellular stress levels, a functional inhibition of SEC62 bears the potential to limit tumor growth and metastasis formation. In this study, two potential anti-metastatic and -proliferative agents that counteract SEC62 function were investigated in functional in vitro assays by utilizing an immortalized human hypopharyngeal cancer cell line as well as a newly established orthotopic murine in vivo model. Additionally, a CRISPR/Cas9 based SEC62 knockout HNSCC cell line was generated and functionally characterized for its relevance in HNSCC cell proliferation and migration as well as sensitivity to SEC62 targeted therapy in vitro.


Dental infections increase the likelihood of hospital admissions among adult patients with sickle cell disease.
To determine if dental infections increase the likelihood of hospital admission among adult patients with sickle cell disease (SCD). Cross-sectional analysis of data from the Nationwide Emergency Department Sample (NEDS) pooled for the years 2006 through 2008. Prevalence ratios (PR) for the effects of interest were estimated using Poisson regression with robust estimates of the variance. Adults, aged 18 and over, diagnosed with SCD using ICD-9-CM codes excluding participants discharged with a code for sickle cell trait. Emergency department (ED) visit disposition, dichotomised to represent whether or not the ED visit ended in admission versus being treated and released. Among patients having a sickle cell crisis, those with dental infections were 72% more likely to be admitted compared to those not having dental infections (PR = 1.72, 95% CI 1.58-1.87). No association was observed among adult SCD patients not having a sickle crisis event. Based on preliminary data from this analysis, prevention of dental infection among patients with SCD could result in an estimated cost saving of $2.5 million dollars per year. Having a dental infection complicated by a sickle cell crisis significantly increases the likelihood of hospital admission among adult SCD patients presenting to the ED.


Clinico-pathologic factors associated with the occurrence of early and late metastatic spread in a cohort of breast cancer patients.
Distant metastatic spread in breast cancer patients is a complex phenomenon involving several prognostic factors. We focused our analysis on early metastatic breast cancer (EMBC) (occurring during the first 36 months) versus late metastatic breast cancer (LMBC) (occurring beyond 3 years) in order to ascertain their possible differential predictive factors. diagnostic, surgical, and follow-up data were assessed for consecutive patients with breast cancer undergoing surgery between 1997 and 2019. We analysed the predictive factors for distant metastasis using both univariate and multivariate analysis. The median follow-up for this cohort of 2708 patients was 89 months. The median metastasis-free interval (FMI) for metastasis patients was 38 months (17 months for EMBC group and 76 months for LMBC group). Distant metastases developed in 12.9% (350/2708); 48% (168/350) of them as EMBC and 52% (182/350) as LMBC. Loco-regional recurrence and nodal extracapsular extension were the only common predictors for both. EMBC and LMBC appeared as two separate conditions, with a different outcome. In the EMBC group, tumour proliferation related factors were significant (histological grade, tumour size, body mass index), whereas for LMBC, other slow-acting factors seemed to be involved (screening program, tumour burden, bilateral tumour).


Analysis of testosterone pulsatility in women with ovulatory menstrual cycles.
To evaluate the pattern of the pulsatile secretion of testosterone in normal menstrual cycle. Eight healthy women with ovulatory menstrual cycles were enrolled. Blood samples were collected at ten-minute intervals for six hours, starting between 7 and 8 am, after a ten-hour fasting, in three phases: mid-follicular (Day 7), late follicular (Day 12) and mid-luteal phase (Day 21). Samples were assayed for testosterone, LH and the baseline also for SHBG. Testosterone pulse frequency, mean amplitude pulse, percentage of increment in pulse amplitude, mean duration of pulses and pulse interval were similar in the three phases. LH pulsatility was statistically different among the three phases (p < 0.001) representing normal ovulatory cycles. These data increase the knowledge about the testosterone secretion profile in the human menstrual cycle and can be used as a contribution to clinical investigation in both hyperandrogenism and androgen insufficiency syndrome.


Home range size and choice of management strategy for lynx in Scandinavia.
Annual and seasonal home ranges were calculated for 47 Eurasian lynx in four Scandinavian study sites (two in Sweden and two in Norway). The observed home ranges were the largest reported for the species, with study site averages ranging from 600 to 1,400 km2 for resident males and from 300 to 800 km2 for resident females. When home range sizes were compared to the size of protected areas (national parks and nature reserves) in Scandinavia, it was concluded that very few protected areas contained sufficient forest to provide space for more than a few individuals. As a direct consequence of this, most lynx need to be conserved in the multiuse semi-natural forest habitats that cover large areas in Scandinavia. This conservation strategy leads to a number of conflicts with some land uses (sheep and semidomestic reindeer herding, and roe deer hunters), but not all (forestry and moose harvest). Accordingly research must be aimed at understanding the ecology of these conflicts, and finding solutions.


Corticostriatothalamic reward prediction error signals and executive control in late-life depression.
Altered corticostriatothalamic encoding of reinforcement is a core feature of depression. Here we examine reinforcement learning in late-life depression in the theoretical framework of the vascular depression hypothesis. This hypothesis attributes the co-occurrence of late-life depression and poor executive control to prefrontal/cingulate disconnection by vascular lesions. Our fMRI study compared 31 patients aged ⩾60 years with major depression to 16 controls. Using a computational model, we estimated neural and behavioral responses to reinforcement in an uncertain, changing environment (probabilistic reversal learning). Poor executive control and depression each explained distinct variance in corticostriatothalamic response to unexpected rewards. Depression, but not poor executive control, predicted disrupted functional connectivity between the striatum and prefrontal cortex. White-matter hyperintensities predicted diminished corticostriatothalamic responses to reinforcement, but did not mediate effects of depression or executive control. In two independent samples, poor executive control predicted a failure to persist with rewarded actions, an effect distinct from depressive oversensitivity to punishment. The findings were unchanged in a subsample of participants with vascular disease. Results were robust to effects of confounders including psychiatric comorbidities, physical illness, depressive severity, and psychotropic exposure. Contrary to the predictions of the vascular depression hypothesis, altered encoding of rewards in late-life depression is dissociable from impaired contingency learning associated with poor executive control. Functional connectivity and behavioral analyses point to a disruption of ascending mesostriatocortical reward signals in late-life depression and a failure of cortical contingency encoding in elderly with poor executive control.


Gas-phase intramolecular phosphate shift in phosphotyrosine-containing peptide monoanions.
Phosphotyrosine-containing peptide monoanions [M-H](-) exhibit extensive neutral loss of phosphoric acid (98 Da) upon quadrupole time-of-flight and ion-trap collision-induced dissociation (CID). In contrast, a neutral loss of metaphosphoric acid HPO(3) (80 Da) is negligible from the deprotonated phosphotyrosine peptides. The efficient H(3)PO(4) release is unexpected, given the structure of phosphotyrosine. Our study reveals that the abundant [M-H-98](-) product ions of pTyr-peptides are not a result of consecutive losses of HPO(3) and H(2)O but, rather, are induced by an intramolecular interaction of the phosphotyrosine phosphate with deprotonated peptide functions such as hydroxyl, carboxyl, and to a small extent, amide. As a result, an internal phosphotyrosine phosphate shift occurs, and the obtained phosphorylated functionalities undergo elimination of H(3)PO(4) to give rise to the [M-H-98](-) fragments. The mechanism proposed for the phosphoric acid neutral loss is based on extensive CID studies of Ala-substituted model phosphorylated peptides and oxygen-18 labeling. The proposed mechanistic pathway explains the fact that the pTyr phosphate transfer and the subsequent H(3)PO(4) neutral loss are not observed for multiply charged anions of pTyr-peptides. Monoanions of pSer-containing peptides undergo the intramolecular phosphate shift as well, although its efficiency is much lower compared to the aromatic phosphorylation sites. These observations facilitate correct identification of pSer-, pThr-, and pTyr-peptides in CID studies. This work demonstrates that the established phosphate-specific neutral loss fragmentation rules of protonated pTyr-peptides cannot be applied to the CID spectra of their [M-H](-) ions.


Design and acceptability of patient-oriented computerized diabetes care reminders for use at the point of care.
Despite the widespread availability of guidelines for caring for patients with diabetes and decades of research on computerized reminder systems, large gaps in quality remain in diabetes care remain and computerized reminder systems are rarely used for patients with diabetes. We set out to develop and test the feasibility of a system that would overcome many of the barriers preventing the widespread use of point-of-care computerized reminders to improve diabetes care. Five primary care physicians and 32 patients with type 2 diabetes pilot tested the system. We set out to design and measure the preliminary acceptability of patient-oriented point of care computerized diabetes care reminders. The main findings of our study were that (1) the reports were well accepted by both patients and providers and (2) survey and audiotape data suggest that they may be helpful at improving the quality of outpatient care for patients with diabetes.


Service quality and perceived value of technology-based service encounters: evaluation of clinical staff satisfaction in Taiwan.
Previous research has evaluated technology-based service encounters (TBSEs) in the delivery of health care by assessing patient satisfaction. This study examined service quality and perceived value of TBSEs used in health organisations from the perspective of clinical staff, with staff technology readiness as a moderator. A quantitative survey was conducted in Taiwan, across private and public healthcare organisations. Results showed that TBSEs had a direct effect on service quality and perceived value, which in turn had a direct effect on staff satisfaction in using TBSEs. However, service quality had no effect on perceived value when moderated by technology readiness. Theoretical and managerial implications of these findings are discussed.


[Nutritional and fluid requirements of the child involved in sports].
Between generally accepted recommendations and individually ascertained values for need of energy, nutrients and water, which are evaluated more exactly only by laboratories of nutritional physiology and of sportsmedicine, wide variations are possible. For practical purpose regular controls of physical development, competitiveness, regular weighing, measuring and testing alone, give the possibility to assess, whether food-intake meets quantitatively the need. Qualitatively deficient nutrient-intake is only shown after some time elapsed by reduced competitiveness or reduced nutritional recommendations are to performed, which are summarized in the ten rules of prudent nutrition (DGE). In competitive sports, basic for optimal, sporty nutrition are controls of physical development and of nutritional intake (nutritional anamnesis). To avoid nutritional deficiencies and their consequences in children doing intensive sport, following minimal demands should be performed: 1. Children, regularly highly trained are classified to "children at risk" and are to be looked after by physician with a degree in sportsmedicine, familiar with the development of children (pediatrician). 2. Physical development of children performing competitive sports has to be investigated and documented in two-monthly periods (training-protocols, growth-charts) minimal. 3. Minimum twice a year, by a nutritional well qualified person (physician in sports, nutritional scientist, dietitian) a nutritional advisory has to be done to the children together with parents and trainer. 4. If physical development or competitiveness will be disturbed, the individual need of energy and nutrients has to be ascertained, basic for an following nutritional advisory. 5. Assumption of energy-need for children performing competitive sports has to be done individually. Basic for assumption is the "biological age".(ABSTRACT TRUNCATED AT 250 WORDS)


Self-regulated multifunctional collaboration of targeted nanocarriers for enhanced tumor therapy.
Exploring ideal nanocarriers for drug delivery systems has encountered unavoidable hurdles, especially the conflict between enhanced cellular uptake and prolonged blood circulation, which have determined the final efficacy of cancer therapy. Here, based on controlled self-assembly, surface structure variation in response to external environment was constructed toward overcoming the conflict. A novel micelle with mixed shell of hydrophilic poly(ethylene glycol) PEG and pH responsive hydrophobic poly(β-amino ester) (PAE) was designed through the self-assembly of diblock amphiphilic copolymers. To avoid the accelerated clearance from blood circulation caused by the surface exposed targeting group c(RGDfK), here c(RGDfK) was conjugated to the hydrophobic PAE and hidden in the shell of PEG at pH 7.4. At tumor pH, charge conversion occurred, and c(RGDfK) stretched out of the shell, leading to facilitated cellular internalization according to the HepG2 cell uptake experiments. Meanwhile, the heterogeneous surface structure endowed the micelle with prolonged blood circulation. With the self-regulated multifunctional collaborated properties of enhanced cellular uptake and prolonged blood circulation, successful inhibition of tumor growth was achieved from the demonstration in a tumor-bearing mice model. This novel nanocarrier could be a promising candidate in future clinical experiments.


Informed consent: a case for more education of the surgical team.
A questionnaire was given to 37 members of staff of the Department of Surgery, Addenbrooke's Hospital, Cambridge, in order to determine whether their knowledge was adequate to give accurate information to patients regarding operations and thus to obtain properly informed consent for that operation. Each participant was asked to estimate the 24-h and 30-day mortality for five common elective operations. A wide range of answers was given for operations by all groups. Estimates of 24-h mortality after unilateral inguinal herniorrhaphy differed between staff grades by a factor of 3, but estimates of 24-h mortality after thyroidectomy differed by a factor of 100 between consultant surgeons and staff nurses. Our findings suggest that some members of the surgical team have insufficient knowledge about common operations to obtain properly informed consent from patients.


Correlates of having unprotected vaginal sex among detained adolescent females: an exploratory study of sexual factors.
Erotophilia, motivations for engaging in sex, and pleasure-related barriers to using condoms may all be important determinants of whether high-risk adolescent females have sex unprotected by a condom. This exploratory study identified associations between these factors and engaging in unprotected vaginal sex (UVS) among a sample of adolescent females recruited from short-term detention facilities in the USA. A cross-sectional survey of 211 adolescent females (14-18 years of age) was conducted. Only those indicating they had sex within the past 2 months were included in the analysis. Adolescents were recruited within eight detention facilities. Measures were assessed using audio-computer assisted self-interviewing (A-CASI). In race-adjusted analyses, adolescents indicating greater pleasure-associated barriers to using condoms were more than 4.3 times more likely than those indicating fewer barriers to report having UVS in the past 2 months (AOR = 4.36; 95% CI = 2.15-8.86). Similarly, those scoring higher in erotophilia (compared with those scoring lower) were more than twice as likely to report UVS (AOR = 2.08; 95% CI = 1.02-4.24). Finally, adolescents who had ever been pregnant were approximately 2.5 times more likely to report having recent UVS (AOR = 2.48; 95% CI = 1.1-5.34). With the exception of having five or more sex partners in the past 2 months (P = 0.08), none of the remaining correlates approached multivariate significance. Constructs such as erotophilia and pleasure-related barriers to condom use may be important correlates of UVS among this population of high-risk adolescents.


MiR-31 inhibits migration and invasion by targeting SATB2 in triple negative breast cancer.
Metastasis is the leading cause of death among breast cancer (BCa) patients and triple negative breast cancer (TNBC) as one of BCa subtypes exhibits the worst survival rate due to its highly aggressive and metastatic behavior. A growing body of research has shown that the dynamic expression of microRNAs (miRNAs) was intimately associated with tumor invasion and metastasis. Recent studies have demonstrated miR-31 as a metastasis-suppressor in breast cancer, but it is still known little about the mechanism of it suppresses metastasis. The special AT-rich sequence-binding protein-2 (SATB2) has been reported to involve in tumor proliferation and invasion, but its function and relationship with miR-31 in breast cancer is still unknown. Here we found that the expression of miR-31 was downregulated in TNBC tissue and cell line. MiR-31 expression was increased after MDA-MB-231 cell was treated by 5-aza-2'-deoxycytidine (5-AZA-CdR), enhance the expression of miR-31 significantly inhibited MDA-MB-231 cell migration and invasion, downregulation of miR-31 expression could promoted MCF-7 cell migration and invasion. The expression of SATB2 was negatively correlated with miR-31 and was upregulated in MCF-7 and MDA-MB-231. Silencing SATB2 expression significantly inhibited MCF-7 and MDA-MB-231 cell proliferation, migration and invasion. Luciferase reporter assays indicated SATB2 is a direct target of miR-31. Taken together, these results suggest miR-31 inhibited TNBC cells migration and invasion through suppressing SATB2 expression.


Towards a traceable clinical guidelines application. A model-driven approach.
The goal of this research is to provide an overall framework to enable model-based development of clinical guideline-based decision support systems (GBDSSs). The automatically generated GBDSSs are aimed at providing guided support to the physician during the application of guidelines and automatically storing guideline application data for traceability purposes. The development process of a GBDSS for a guideline is based on model-driven development (MDD) techniques which allow us to carry out such a process automatically, making development more agile and saving on human resource costs. We use UML Statecharts to represent the dynamics of guidelines and, based on this model, we use a MDD-based tool chain to generate the guideline-dependent components of each GBDSS in an automatic way. In particular, as for the traceability capabilities of each GBDSS, MDD techniques are combined with database schema mappings for metadata management in order to automatically generate the GBDSS-persistent component as one of the main contributions of this paper. The complete framework has been implemented as an Eclipse plug-in named GBDSSGenerator which, starting from the statechart representing a guideline, allows the development process to be carried out automatically by only selecting different menu options the plug-in provides. We have successfully validated our overall approach by generating the GBDSS for different types of clinical guidelines, even for laboratory guidelines. The proposed framework allows the development of clinical guideline-based decision support systems in an automatic way making this process more agile and saving on human resource costs.


Ranitidine versus cimetidine prior to emergency obstetric anesthesia.
Twenty parturients in labour received emergency obstetric anesthesia were randomly divided into two equal groups. Group "R" received 150 mg oral ranitidine tablet on admission, followed by 50 mg infusion in 250 ml dextrose 5% over 30 minutes prior to anesthetic induction. Group "Ce" received 400 mg cimetidine oral tablet and 100 mg infusion in 250 ml dextrose 5% over 30 minutes. Ten parturients were considered as control. Ranitidine significantly reduced the maternal gastric volume with marked alkalinization of gastric pH. No significant changes were detected in the height, frequency or amplitude of uterine contraction or neonatal assessment.


The industrial production and use of 1,3-butadiene.
This presentation provides a brief overview of the production and use of 1,3-butadiene in the United States. Starting as a coproduct of ethylene, the 1,3-butadiene monomer is extracted and purified, then transferred to consumers. Major uses of 1,3-butadiene include the manufacture of styrene-butadiene rubber, polybutadiene rubber, and adiponitrile.


Multiple Epidermolytic Acanthomas: Rare Vulval Lesions Which May be Mistaken for Viral Warts.
Epidermolytic acanthoma is a rare benign lesion that most often presents as a solitary or multiple small papular lesions on the trunk, face, limbs or external male genitalia. Only a small number of cases have been reported occurring on the vulva and clinically and histologically they may mimic and be misdiagnosed as viral warts. We report 2 cases of multiple epidermolytic acanthomas localized to the vulva. Molecular tests (in situ hybridization and polymerase chain reaction) showed no evidence of human papillomavirus infection and p16 staining was negative. We stress the need for pathologists to consider epidermolytic acanthoma in the differential diagnosis of multiple vulval lesions resembling viral warts.


Seasonal mood disorders. Patterns of seasonal recurrence in mania and depression.
DSM-III-R criteria, applied retrospectively in a research-oriented psychiatric clinic, identified patients (N = 146) with a mood disorder and a seasonal pattern of recurrence (seasonal mood disorder). The seasonal mood disorder syndrome was not rare (10% of all mood disorders); diagnostic distribution was as follows: recurrent depression, 51%, and bipolar disorder, 49%, with 30% of the latter having mania (bipolar disorder type I) and 19% having hypomania (bipolar disorder type II). Most patients were women (71%); onset age averaged 29 years, with a mean of eight cycles in 12 years of illness; mean episode duration was 5.0 months. Mood disorder was found in a high proportion (68%) of the families. All but one patient followed one of two seasonal patterns in equal frequency: type A, fall-winter depression with or without spring-summer mania or hypomania; and type B, spring-summer depression with or without fall-winter mania or hypomania. Both types showed consistent times of onset and remission. These results emphasize that DSM-III-R seasonal mood disorder includes severe cases of recurrent depression and bipolar disorder and support a distinction between two seasonal subtypes.


Minced Pulp as Source of Pulpal Mesenchymal Stem Cells with Odontogenic Differentiation Capacity.
Pulp tissue regeneration is becoming a reality after discovery of mesenchymal stem cells (MSCs) residing in the pulp tissues through various clinical innovations, although MSC transplantation into the pulp space has met with challenges of in vitro cell expansion and cultures. As a way to circumvent the regulatory and technical complexities of in vitro MSC culture, we investigated the use of minced pulp tissues as a source of pulpal MSCs for tissue regeneration. We characterized the phenotype of cells explanted from minced pulp (MP), namely MP-derived MSCs (MP-MSCs), compared with dental pulp stem cells (DPSCs) established from pulp tissues by enzyme digestion. Phenotypic characterization included replication kinetics, immunophenotyping, and multilineage differentiation. Using the tooth slice model, we assessed odonto/osteogenic differentiation of DPSCs, MP-MSCs, and minced pulp tissues in situ. In vitro replication of MP-MSCs occurred more rapidly during the initial phase of subcultures compared with DPSCs; however, MP-MSCs arrived at senescence at population doubling 47, whereas DPSCs replicated until population doubling 64, indicating shorter replicative lifespan. MP-MSCs also demonstrated stronger odonto/osteogenic differentiation than DPSCs by alkaline phosphatase activity and the protein expression. Both MP-MSCs and DPSCs demonstrated odonto/osteogenic and adipogenic differentiation capacities. Both cell types also showed mineralized tissue formation in the tooth slice model. Seeding minced pulp tissue on poly-L-lactic acid scaffold allowed for migration of MP-MSCs from the tissues and odontogenic differentiation with dentin sialophosphoprotein expression in the tooth slice model. These data indicated that MP may be an alternative source of pulpal MSCs that may allow de novo pulp-dentin regeneration without the need for in vitro culture and expansion.


P-chlorophenylalanine increases glutamate receptor 1 transcription in rat amygdala.
The amygdala is a key limbic structure strongly implicated in both epilepsy and anxiety disorders. Epilepsy-like mechanisms involve an increased glutamatergic activity, whereas disturbances in serotonin [5-hydroxytryptamine (5-HT)] systems are associated with anxiety-like behavior. Previous studies suggest that low 5-HT increases amygdala excitability, but the molecular mechanisms are not well characterized. Herein we explore the ability of low serotonin to increase glutamate receptor transcription. Using quantitative reverse transcriptase-polymerase chain reaction, we found that rats treated with P-chlorophenylalanine, an inhibitor of tyrosine-5-hydroxylase, resulted in a 21-fold increase in glutamate receptor 1 (GluR1) mRNA expression in the amygdala. These results suggest that low 5-HT induces hyperexcitability of amygdala neurons by increasing GluR1 transcription, and the upregulation of amygdala GluR1 may be important in the pathophysiology of anxiety disorders.


Contamination and chemical fractionation of heavy metals in street dust from the metropolitan area of Monterrey, Mexico.
The prevalence of heavy metal pollution and mobility of both Pb and Cd was investigated in street dust samples from the Metropolitan Area of Monterrey (MAM) in northern Mexico. Street dust samples from 30 selected sites were analysed for their content of Zn, Cd, Pb, Cr and Ni after digestion according to U.S. EPA Method 3051. Multivariate analysis including correlation coefficient analysis, Principal Component Analysis and Cluster Analysis was used to analyse the data and identify possible sources of these heavy metals. Compared with background values, elevated concentrations of Pb (300 mg kg(-1)), Cd (7.6 mg kg(-1)) and Cr (78 mg kg(-1)) were observed in street dust of MAM. Based on multivariate statistical approaches, the studied elements were classified in three main sources: (1) Cr, Ni and Zn mainly derived from industrial activities; (2) Cd originating from traffic-related activities; and (3) Pb associated with vehicular emissions. A sequential extraction procedure using the Tessier method was applied to evaluate the mobility of Pb and Cd in street dust. The majority of Pb was associated with the residual fraction followed by the carbonate fraction. The majority of Cd was associated with the residual fraction. These results indicated that the mobility was higher in Pb (26%) compared with Cd (11%), posing a potential risk to the environment.


Volterra Kernels Assessment via Time-Delay Neural Networks for Nonlinear Unsteady Aerodynamic Loading Identification.
Reduced-order modeling using the Volterra series approach has been successfully applied in the past decades to weakly nonlinear aerodynamic and aeroelastic systems. However, aspects regarding the identification of the kernels associated with the convolution integrals of Volterra series can profoundly affect the quality of the resulting reduced-order model (ROM). An alternative method for their identification based on artificial neural networks is evaluated in this work. This relation between the Volterra kernels and the internal parameters of a time-delay neural network is explored for the application in the reduced-order modeling of nonlinear unsteady aerodynamic loads. An impulse-type Volterra-based ROM is also under consideration for comparison. All aerodynamic data used for the construction of the reduced-order models are obtained from computational fluid dynamics (CFD) simulations of the NACA 0012 airfoil using the Euler equations. Prescribed inputs in pitch and in plunge degrees of freedom at different free-stream Mach numbers are used to evaluate the range of applicability of the obtained models. For weakly nonlinear test cases, the modeling performance of the neural network Volterra ROM was comparable to the impulse-type ROM. Additional accuracy and adequate modeling of stronger nonlinearities, however, could only be attained with the inclusion of the neural network kernels of higher-order in the Volterra ROM. A generic expression is derived for the kernel function of p th -order from the internal parameters of a time-delay neural network.


Physiological antagonism caused by adrenergic stimulation of canine tracheal muscle.
We studied the simultaneous alpha- and beta-adrenergic response characteristics of canine tracheal smooth muscle in 398 strips from 67 dogs in vitro. Experiments were performed to determine the effects of beta-adrenergic blockade on the expression of the alpha-adrenoceptor contractile responses elicited by norepinephrine (NE), phenylephrine (PE), and clonidine (CLO). Maximal active tension caused by NE increased from 39.1 +/- 27.0 to 241 +/- 75.0 g/cm2 as the concentration of propranolol (PROP) was increased from 10(-6) to 10(-4) M. Augmentation of tracheal smooth muscle contraction caused by PE and CLO was also observed with progressive beta-adrenoceptor blockade; contraction to NE, PE, and CLO was blocked selectively with 3 X 10(-5) M phentolamine (PA) and phenoxybenzamine (PBZ). The beta-adrenergic relaxing properties of the same three agonists were also studied. After alpha-adrenergic blockade with PA or PBZ, all three agonists caused relaxation (NE greater than CLO greater than PE) of methacholine-induced contraction of tracheal smooth muscle that was reversed selectively with PROP. We demonstrate that NE, PE, and CLO cause simultaneous stimulation of both the alpha- and beta-adrenergic receptors in tracheal smooth muscle; the net response elicited is the result of adrenergic physiological antagonism and depends on the relative degree of alpha- and/or beta-adrenoceptor blockade.


Chimeric vesicular monoamine transporters identify structural domains that influence substrate affinity and sensitivity to tetrabenazine.
The vesicular monoamine transporters (VMATs) 1 and 2 show close sequence similarity but substantial differences in apparent substrate affinity and drug sensitivity. To identify structural domains that determine these functional characteristics, chimeric transporters were constructed and their properties were analyzed in a heterologous expression system. The results implicate multiple regions in the recognition of serotonin and histamine and the sensitivity to tetrabenazine. Two domains of VMAT2, one extending from transmembrane domain (TMD) 5 to the beginning of TMD8 and the other from the end of TMD9 through TMD12, increase the affinity for serotonin and histamine as well as the sensitivity to tetrabenazine but only in the context of more C-terminal and more N-terminal VMAT2 sequences, respectively. In addition, the extreme N terminus of VMAT2 alone suffices to confer a partial increase in substrate affinity and tetrabenazine sensitivity. Despite these similarities among the interactions with serotonin, histamine, and tetrabenazine, the region of VMAT2 from TMD3 through TMD4 increases serotonin affinity but not histamine affinity or tetrabenazine sensitivity, and whereas the region from TMD5 to TMD8 of VMAT2 increases serotonin affinity in the context of more C-terminal VMAT2 sequences, the region encompassing TMD5 through TMD7 reduces serotonin but not histamine affinity or tetrabenazine sensitivity in the context of more N-terminal VMAT2 sequences. Thus, the chimeric analysis also reveals differences between serotonin recognition and the recognition of both histamine and tetrabenazine that may account for the observed differences in their interaction with the transport protein.


Toward a research-based assessment of dyslexia: using cognitive measures to identify reading disabilities.
One hundred five participants from a random sample of elementary and middle school children completed measures of reading achievement and cognitive abilities presumed, based on a synthesis of current dyslexia research, to underlie reading. Factor analyses of these cognitive variables (including auditory processing, phonological awareness, short-term auditory memory, visual memory, rapid automatized naming, and visual processing speed) produced three empirically and theoretically derived factors (auditory processing, visual processing/speed, and memory), each of which contributed to the prediction of reading and spelling skills. Factor scores from the three factors combined predicted 85% of the variance associated with letter/sight word naming, 70% of the variance associated with reading comprehension, 73% for spelling, and 61% for phonetic decoding. The auditory processing factor was the strongest predictor, accounting for 27% to 43% of the variance across the different achievement areas. The results provide practitioner and researcher with theoretical and empirical support for the inclusion of measures of the three factors, in addition to specific measures of reading achievement, in a standardized assessment of dyslexia. Guidelines for a thorough, research-based assessment are provided.


A development-dependent hemagglutinin from cucumber surfaces: I. Hemagglutinin activity of cotyledon surfaces.
During studies on the chemistry of plant surfaces, we observed that concomitant with the development of cucumber (Cucumis sativus L. cv ;ELEM') cotyledons an agglutinin that agglutinates human erythrocytes appeared on epicuticular surfaces. The agglutinin was released from cotyledon surfaces into distilled water by a 1-minute immersion (or even less). Homogenization of the washed cotyledons released residual agglutinating activity. The surface-located hemagglutinating activity was age-dependent and occurred in dark- and light-grown cotyledons. Agglutinating activities were present in light-grown cotyledons of 2- to 14-day-old seedlings and in dark-grown cotyledons of 3- to 17-day-old seedlings. Agglutinating activities were maximal in cotyledons of 3- to 4-day-old seedlings. No activity could be detected in dry seeds or in seedlings up to 2 days and after 17 days of germination. The hemagglutinating activity was specifically inhibited by N,N',N''-triacetylchitotriose, chitin, and chitosan.


The changes of serum zinc, copper, and selenium levels in epileptic patients: a systematic review and meta-analysis.
It is widely accepted that trace elements have been implicated in various metabolic processes. Valproic acid (VPA) is a remarkably safe and effective antiepileptic drug. There is no consensus option regarding the fluctuations in serum zinc (Zn), copper (Cu), and selenium (Se) in epileptic patients treated with VPA. We applied a meta-analysis to systematically assess the effects of VPA on serum ions in these patients. In this study, we performed a meta-analysis of the changes in serum Zn, Cu, and Se levels in human samples of healthy controls, epileptic patients, and patients treated with VPA. Twenty-two published analyzable studies were selected by searching the databases of PubMed, China National Knowledge Infrastructure (CNKI), Google Scholar, Web of Science, EMBASE, WAN FANG and Vip. Serum Se levels in epileptic patients were decreased compared to healthy controls. Serum Zn levels in patients with VPA treatment were significantly lower than those in epileptic patients. The results of this meta-analysis are instructive for the intake of trace elements such as Zn, Cu, and Se in the diet balance of patients with epilepsy treated with VPA. Meanwhile, this study provides a theoretical basis for the combined use of other drugs that affect the intake and absorption of trace elements and VPA.


Detection of low level benzene exposure in supermarket wrappers by urinary muconic acid.
Women who use the 'hot wire' and 'cool rod' machines to wrap meat in supermarkets are potentially exposed to low levels of benzene and polycyclic aromatic hydrocarbons present in fumes emitted during the thermal decomposition of the plastic used to wrap meat. In order to evaluate whether the benzene metabolite trans, trans-muconic acid (MA) can be used to monitor these low levels, we collected urine samples from supermarket workers, and assayed the urine for MA. Geometric mean after-shift MA levels were highest for subjects who used the 'hot wire' machine, i.e. > 300 ng mg-1 creatinine (Cr). The corresponding levels for subjects who used the 'cool rod' machine were similar to those for subjects who did not use either type of machine, and were much lower. These results indicate that urinary muconic acid has some potential for use in monitoring benzene exposures of less than 1 part per million (ppm). The study detected very high background MA levels (exceeding 2000 ng mg-1 Cr) in some subjects, suggesting that individuals in the general population without occupational exposure to benzene may have urinary MA levels equivalent to exposure to up to 2 ppm benzene in ambient air. However, since non-benzene sources of the metabolite cannot be completely ruled out as partially responsible for these high levels, the public health significance of this finding is not known at the moment.


Apolipoprotein E genotypes and plasma levels in mild cognitive impairment conversion to Alzheimer's disease: A follow-up study.
Mild cognitive impairment (MCI) is the transition stage between the normal aging process and dementia itself. The most common clinical phenotype is amnestic MCI (aMCI) [subtypes: single domain (sMCI) and multiple domains (mMCI)], which is considered prodromal to Alzheimer's disease (AD). The APOE (apolipoprotein E) e4 allele is the most important genetic risk factor for AD, but its association with MCI onset and conversion to AD is controversial. In this follow-up study of 88 aMCI patients (68% sMCI and 32% mMCI at baseline), we examined APOE genotypes and plasma levels in relation to MCI development and progression based on their clinical/cognitive data obtained at baseline and follow-up assessment (mean follow-up time = 6.6 ± 3.4 years). A control sample (n = 164) was collected in previous investigations. The overall conversion rate to mMCI or AD was 52.2%. The APOE e4 allele was associated with a higher risk of developing MCI (OR: 2.23; 95%CI: 1.22-4.08). The conversion rate in the e4 allele carriers (32% of the sample) was 71%, and the e4 allele was associated with a higher risk of conversion to mMCI/AD (OR: 4.1; 95%CI: 1.2-13.6). APOE e2 allele carriers were 7% (all sMCI) and none progressed to mMCI/AD. Among MCI subjects, e4 carriers had the lowest plasma apoE levels (37.8 ± 12.5 mg/L), and e2 carriers had the highest (78.6 ± 38.1 mg/L). APOE e4 is a risk allele for the development and progression of aMCI, the APOE e2 allele seems to be protective, and apoE levels associated to them are an integral part of their action. © 2016 Wiley Periodicals, Inc.


Detection of variable levels of RARα and RARγ proteins in pluripotent and differentiating mouse embryonal carcinoma and mouse embryonic stem cells.
Pluripotent mouse embryonal carcinoma (mEC) and mouse embryonic stem (mES) cells differentiate into several cell lineages upon retinoic acid (RA) addition. Differentiation is facilitated, in part, by RA activation of nuclear RA receptors (RARs) that bind to DNA response elements located in the promoters of target genes. The purpose of the studies reported here was to immunolocalize RARα and RARγ protein in mEC and mES cells and in their RA-induced differentiated progeny. Fixed cells were reacted with three different RARα antibodies and one RARγ antibody. Pluripotent and differentiated mEC and mES cells showed positive nuclear immunoreactivity with all antibodies tested. Two RARα antibodies also showed positive reactivity in the cytoplasm. Surprisingly, our results revealed variability in immunofluorescence intensity and in RARα and RARγ distribution from one cell to the other, suggesting that RARα and RARγ protein levels were not synchronous throughout the cell population. The results indicate that RARα and RARγ are present in pluripotent and differentiating mEC and mES cells and suggest that the expression of these proteins is dynamic.


Foraging strategy in a social bird, the alpine chough: effect of variation in quantity and distribution of food.
I conducted feeding experiments to determine the effect of variations in food availability on individual flocking behaviour and foraging efficiency in a social corvid, the alpine chough Pyrrhocorax graculus, which lives in large flocks all year round. In 37 trials I varied both food quantity and the number of food patches. A decrease in the amount of available food reduced the mean flock size, the proportion of birds that had access to food, and their mean pecking rate. A decrease in the number of patches, on the other hand, reduced only the proportion of birds that had access to food. The number of choughs foraging was not influenced by food competition but depended only on the number visiting the site. Females competed less well than males: when food was made scarce, they frequented the site in the same proportion as did males, but had less access to food. I suggest that in this social corvid, long-term advantages to flocking related to social bonds, such as the maintenance of pair bonds, may compensate for short-term costs such as a reduction in foraging efficiency. Copyright 1999 The Association for the Study of Animal Behaviour.


Long-Term Dietary Restriction Leads to Development of Alternative Fighting Strategies.
In competition for food, mates and territory, most animal species display aggressive behavior through visual threats and/or physical attacks. Such naturally-complex social behaviors have been shaped by evolution. Environmental pressure, such as the one imposed by dietary regimes, forces animals to adapt to specific conditions and ultimately to develop alternative behavioral strategies. The quality of the food resource during contests influence animals' aggression levels. However, little is known regarding the effects of a long-term dietary restriction-based environmental pressure on the development of alternative fighting strategies. To address this, we employed two lines of the wild-type Drosophila melanogaster Canton-S (CS) which originated from the same population but raised under two distinct diets for years. One diet contained both proteins and sugar, while the second one was sugar-free. We set up male-male aggression assays using both CS lines and found differences in aggression levels and the fighting strategies employed to establish dominance relationships. CS males raised on a sugar-containing diet started fights with a physical attack and employed a high number of lunges for establishing dominance but displayed few wing threats throughout the fight. In contrast, the sugar-free-raised males favored wing threats as an initial aggressive demonstration and used fewer lunges to establish dominance, but displayed a higher number of wing threats. This study demonstrates that fruit flies that have been raised under different dietary conditions have adapted their patterns of aggressive behavior and developed distinct fighting strategies: one favoring physical attacks, while the other one favoring visual threats.


Substance misuse in acute general medical admissions.
We conducted a prevalence study of current substance misuse amongst acute general medical admissions, and compared the sociodemographic profile of this group of patients with total admissions and the local catchment population. Patients were included in the study if they were resident in the Lambeth, Southwark and Lewisham (LSL) Health Commission catchment area and were aged between 18 and 85 years. The prevalence of non-dependent misuse was of particular interest. Of 2988 acute admissions, 609 (20%) were identified as misusing alcohol and/or drugs, 277 (9%) being identified by the admitting doctor and 332 (11%) being identified by means of a Health and Lifestyle Questionnaire (HLQ) which included the Alcohol Use Disorders Identification Test (AUDIT). The majority 437 (72%) of the identified patients had an alcohol problem. A smaller proportion, 116 (19%) were currently using illegal drugs and 56 (9%) were polydrug users. Compared with patients who misused either drugs or alcohol, alcohol misusers were more likely to be older and Irish, whereas users of illegal drugs were more likely to be younger and Black. Significantly more 'at risk' drinkers were identified by the AUDIT questionnaire than by the admitting doctor. This study supports the policy of routine screening for health-damaging behaviours and the implementation of health promotion strategies in general hospitals.


[How does summer affect sexual desire?].
Sexual desire involves many different things such as sexual thoughts and images, excitement, expectation and orgasm. Mood has a strong association with sexual desire. Fatigue and depression in particular cause lack of sexual desire. By affecting the state of alertness and energy in humans, sunlight may increase sexual activity.


Production of sophorolipid biosurfactant by Pichia anomala.
Biosurfactant production by Pichia anomala PY1, a thermotorelant strain isolated from fermented food, was examined as grown in media containing various carbon and nitrogen sources. The optimal conditions for biosurfactant production included 4% soybean oil as carbon source at pH 5.5 at 30 degrees C for 7 d. Under these conditions, the surface tension of the medium decreased to 28 mN/m with oil displacement measured at 69.43 cm(2). Comparative studies of biosurfactant production in media containing glucose or soybean oil were performed. The biosurfactants obtained were isolated and purified by chromatographic methods. The molecular weights of samples were further investigated by mass spectrometry. In medium containing glucose, biosurfactants of molecular weights of 675, 691, and 707 were obtained, while those isolated from medium containing soybean oil were of molecular weights of 658, 675, and 691. These results reveal that sophorolipid compounds containing fatty acids of C20 and C18:1 were produced from both media.


Usefulness of remote monitoring in cardiac implantable device follow-up.
The conventional approach to cardiac implantable device follow-up involves patients attending regularly scheduled in-clinic visits to verify the functionality and safety of the implanted devices. Due to increasing patient volumes, as well as the time, capital, and human resources required, such routine device follow-up contributes a significant resource burden to already overstrained clinics and electrophysiology departments, as well as to patients and caregivers in terms of travel and time. Continuous device status monitoring via remote means (i.e., remote device monitoring) allows clinics the ability to immediately be aware of changes in device functionality to proactively respond to actionable events, and may represent a safe, effective, and cost-saving alternative to conventional in-clinic follow-up programs. The currently available systems to remotely transmit device data combine leading medical and information technology using Web-based networks that promptly provide physicians with data comparable to in-clinic follow-up visits and offer patients a high level of convenience.


Stimulatory effect of N-[4-[2-(dimethylamino)-ethoxy] benzyl]-3,4-dimethoxybenzamide hydrochloride (HSR-803) on normal and delayed gastrointestinal propulsion.
To estimate the effect of a new gastroprokinetic agent, N-[4-[2-(dimethylamino)ethoxy]benzyl]-3,4-dimethoxybenzamide hydrochloride (HSR-803), on non-ulcer dyspepsia, the influence of HSR-803 on gastrointestinal propulsion was assayed in dogs, rats and mice in comparison with some gastroprokinetic agents. HSR-803 (30 mg/kg, p.o.) significantly enhanced gastric emptying in dogs, and it significantly improved the delayed gastric emptying induced by dopamine (0.4 mg/kg, i.p.) and morphine (1 mg/kg, s.c.) in rats. Metoclopramide (30 mg/kg, p.o.) also significantly restored the dopamine-induced delay, but at a dose of 10 mg/kg, p.o., it enhanced the morphine-induced delay in gastric emptying in rats. HSR-803 (10-100 mg/kg, p.o.) increased small intestinal transit in mice in a dose-dependent manner, and the effect was abolished by atropine (0.3 mg/kg, i.p.). Metoclopramide also increased small intestinal transit, but domperidone and cisapride had no effect. In delayed small intestinal transit in mice, HSR-803 (10-100 mg/kg, p.o.) improved the morphine (0.3 mg/kg, s.c.)-induced delay in a dose-dependent manner. In conclusion, because of the promotion of normal and delayed gastrointestinal propulsion, HSR-803 seems to be a promising gastroprokinetic agent for the treatment of non-ulcer dyspepsia. The action of HSR-803 is likely to be exerted through cholinergic stimulation.


Multiple joint replacement in chronically neglected polyarthritic patients: Two case reports.
Multiple joint replacement is a viable option for rehabilitation of young polyarthritic patients with unsalvageable joints. Young polyarthritic patients in this part of the world suffer from chronic neglect because of ignorance, apathy and low socio-economic status. During the period of chronic neglect, these patients acquire extreme deformities of various joints either due to active disease (ankylosing spondylitis, rheumatoid arthritis) or irreversible changes in the joint configuration like ankylosis and soft-tissue contracture. Associated spine and thoracic cage affection create problems for anaesthesia and peri-operative positioning. We report 2 cases of multiple joint replacements for young polyarthritic patients who were bedridden for 6 to 11 years. Surgeries were performed in a phased manner and after extensive rehabilitation both patients were able to walk unaided. Various problems and difficulties encountered have been addressed so as to serve as a guide to surgeons who may have to deal with such unusual situations of chronic neglect. We also report a modified exposure technique without trochanteric osteotomy for total hip replacement, which is valuable in extreme external rotation ankylosis.