Multimodal Scanning Microscope Combining Optical Coherence Tomography, Raman Spectroscopy and Fluorescence Lifetime Microscopy for Mesoscale Label-Free Imaging of Tissue.

Multimodal optical imaging of tissue has significant potential to become an indispensable diagnostic tool in clinical pathology. Conventional bright-field microscopy provides contrast based on attenuation or reflectance of light, having no depth-related information and no molecular specificity. Recent developments in biomedical optics have introduced a variety of optical modalities, such as Raman spectroscopy (RS), fluorescence lifetime imaging microscopy (FLIM) of endogenous fluorophores, optical coherence tomography (OCT), and others, which provide a distinct characteristic, i.e., molecular, chemical, and morphological information, of the sample. To harvest the full analytical potential of those modalities, we have developed a novel multimodal imaging system, which allows the co-registered acquisition of OCT/FLIM/RS on a single device. The present implementation allows the investigation of biological tissues in the mesoscale range, 0.1-5 mm in a correlated manner. Due to the co-registered acquisition of the modalities, it is possible to directly compare and evaluate the corresponding information between the three modalities. Moreover, by additionally preparing and characterizing entire pathological hematoxylin and eosin (H&E) slides of head and neck biopsies, it is also possible to correlate the multimodal spectroscopic information to any location of the ground truth H&E information. To the best of our knowledge, this is the first development and implementation of a compact and clinically applicable multimodal scanning microscope, which combines OCT, FLIM, and RS together with the possibility for co-registering H&E information for a morpho-chemical tissue characterization and a correlation with the pathological ground truth (H&E) of the underlying signal origin directly in a clinical environment.

Vitamin D supplementation: position Statement of the Iberoamerican Society of Osteoporosis and Mineral Metabolism (SIBOMM).

BACKGROUND: Vitamin D (VD) deficiency is a global pandemic that affects more than a third of the population worldwide. The population of Latin America and the Caribbean exceeds 620 million inhabitants with diverse ethnic origins and different latitudes and altitudes, which make comparisons and generalizations difficult. AIM AND METHOD: We sought to establish an expert consensus regarding the recommendations for VD supplementation in Latin America by means of the Delphi methodology. RESULTS: The prophylactic dosage of VD in the general population should be individualized according to age, race, body weight, sun exposure of an individual, altitude, and dietary and exercise habits, without ruling out existing chronic diseases. CONCLUSION: The importance of VD has been widely documented and its deficiency is a pandemic. Many individuals have difficulty meeting daily VD requirements through food and the sun. The population of Latin America and the Caribbean has diverse ethnics, cultures, in addition to living in different latitudes and altitudes. Therefore, it is important to make a position on VD supplementation, given the different characteristics, ages and serum levels of 25(OH)D.

An agent-based model of the fission yeast cell cycle.

The objective of this paper is to develop a computational model of the fission yeast (Schizosaccharomyces pombe) cell cycle using agent-based modeling (ABM), to study the sequence of states of the proteins and time of the cell cycle phases, under the action of proteins that regulate its cell cycle. The model relies only on the conceptual model of the yeast cell cycle regulatory network, where each protein has been represented as an agent with a property called activity that represents its biological function and a stochastic Brownian movement. The results indicate that the simulated phase time did have similar results in comparison with other models using mathematical approaches. Similarly, the correct sequence of states was achieved, and the model was run under different initial states to understand its emergent behaviors. The cell reached the G1 stationary state 94% of the times when running the model under biological initial conditions and 87% of the times when running the model through all the different combinations of initial states. Such results imply that the cell was capable to fix toward the biological expected phenomena. These results show that ABM is a suitable technique to study protein-protein interactions without using, often unavailable, kinetic parameters, or differential equations. This model sets as a base for further studies that involve the cell cycle of the fission yeast, with a special attention to studies and development of drug treatments for specific types of cancer.

Stages of Change for Mammography Among Mexican Women and a Decisional Balance Comparison Across Countries.

An analysis of the adoption of secondary preventive behaviors is significant in regions with disparities in mammography use and breast cancer survival. Therefore, we determined the cognitive factors and the degree to which they differentiate stages of change in mammography among Mexican women. We also compared the decisional balance performance at Mexico, Switzerland, South Korea, and the USA. A cross-sectional study was designed for women in the stages of precontemplation (n = 240), contemplation (n = 243), action (n = 205), maintenance (n = 311), and relapse (n = 348). We only considered those ≥40 years with no cancer history. We measured the pros, cons, and self-efficacy, among other components. The decisional balance was estimated, and the result was transformed into T-scores. Odds ratios (OR) and 95% confidence intervals (CI) were estimated with multinomial logistic regression using precontemplation as the reference group. The decisional balance distinguished stages partially: in contemplation, the OR was 1.26 (95%CI 1.08, 1.47) and in maintenance, 1.34 (95%CI 1.13, 1.59); in action and relapse, the statistical significance was marginal (p < 0.10). The decisional balance T-score performance registered variations among countries. Additionally, the effect of self-efficacy progressively ascended from contemplation to action and maintenance (OR = 1.29 [95%CI 1.05, 1.58], 1.53 [95%CI 1.20, 1.96], and 2.48 [95%CI 1.82, 3.39], respectively). Furthermore, risk perception and severity did not have an effect on stages of change among Mexican women. Recognition of what provokes action in a population is a key factor in the efficacy of screening programs. Variations among countries highlight the necessity for importance of investigating cognitive determinants for mammography in specific areas.

Patient-derived xenografts for individualized care in advanced sarcoma.

BACKGROUND: Patients with advanced, metastatic sarcoma have a poor prognosis, and the overall benefit from the few standard-of-care therapeutics available is small. The rarity of this tumor, combined with the wide range of subtypes, leads to difficulties in conducting clinical trials. The authors previously reported the outcome of patients with a variety of common solid tumors who received treatment with drug regimens that were first tested in patient-derived xenografts using a proprietary method ("TumorGrafts"). METHODS: Tumors resected from 29 patients with sarcoma were implanted into immunodeficient mice to identify drug targets and drugs for clinical use. The results of drug sensitivity testing in the TumorGrafts were used to personalize cancer treatment. RESULTS: Of 29 implanted tumors, 22 (76%) successfully engrafted, permitting the identification of treatment regimens for these patients. Although 6 patients died before the completion of TumorGraft testing, a correlation between TumorGraft results and clinical outcome was observed in 13 of 16 (81%) of the remaining individuals. No patients progressed during the TumorGraft-predicted therapy. CONCLUSIONS: The current data support the use of the personalized TumorGraft model as an investigational platform for therapeutic decision-making that can guide treatment for rare tumors such as sarcomas. A randomized phase 3 trial versus physician's choice is warranted.

Enhanced carbon dioxide drainage observed in digital rock under intermediate wetting conditions.

Carbon dioxide (CO 2 ) trapping in capillary networks of reservoir rocks is a pathway to long-term geological storage. At pore scale, CO 2 drainage displacement depends on injection pressure, temperature, and the rock's interaction with the surrounding fluids. Modeling this interaction requires adequate representations of both capillary volume and surface. For the lack of scalable representations, however, the prediction of a rock's CO 2 storage potential has been challenging. Here, we report how to represent a rock's pore space by statistically sampled capillary networks (ssCN) that preserve morphological rock characteristics. We have used the ssCN method to simulate CO 2 drainage within a representative sandstone sample at reservoir pressures and temperatures, exploring intermediate- and CO 2 -wet conditions. This wetting regime is often neglected, despite evidence of plausibility. By raising pressure and temperature we observe increasing CO 2 penetration within the capillary network. For contact angles approaching 90 ∘ , the CO 2 saturation exhibits a pronounced maximum reaching 80 % of the accessible pore volume. This is about twice as high as the saturation values reported previously. For enabling validation of our results and a broader application of our methodology, we have made available the rock tomography data, the digital rock computational workflows, and the ssCN models used in this study.

Mutual Information between EDA and EEG in Multiple Cognitive Tasks and Sleep Deprivation Conditions.

Sleep deprivation, a widespread phenomenon that affects one-third of normal American adults, induces adverse changes in physical and cognitive performance, which in turn increases the occurrence of accidents. Sleep deprivation is known to increase resting blood pressure and decrease muscle sympathetic nerve activity. Monitoring changes in the interplay between the central and autonomic sympathetic nervous system can be a potential indicator of human's readiness to perform tasks that involve a certain level of cognitive load (e.g., driving). The electroencephalogram (EEG) is the standard to assess the brain's activity. The electrodermal activity (EDA) is a reflection of the general state of arousal regulated by the activation of the sympathetic nervous system through sweat gland stimulation. In this work, we calculated the mutual information between EDA and EEG recordings in order to consider linear and non-linear interactions and provide an insight of the relationship between brain activity and peripheral autonomic sympathetic activity. We analyzed EEG and EDA data from ten participants performing four cognitive tasks every two hours during 24 h (12 trials). We decomposed EEG data into delta, theta, alpha, beta, and gamma spectral components, and EDA into tonic and phasic components. The results demonstrate high values of mutual information between the EDA and delta component of EEG, mainly in working memory tasks. Additionally, we found an increase in the theta component of EEG in the presence of fatigue caused by sleep deprivation, the alpha component in tasks demanding inhibition and attention, and the delta component in working memory tasks. In terms of the location of brain activity, most of the tasks report high mutual information in frontal regions in the initial trials, with a trend to decrease and become uniform for all the nine analyzed EEG channels as a consequence of the sleep deprivation effect. Our results evidence the interplay between central and sympathetic nervous activity and can be used to mitigate the consequences of sleep deprivation.

The administration of Alda-1, an activator of ALDH2, inhibits relapse-like ethanol intake in female alcohol-preferring UChB rats.

AIMS: Alcohol relapse is a main limitation for the treatment of alcohol use disorders. Previous studies have shown that Alda-1, a pharmacological activator of ALDH2, inhibits both acquisition and chronic ethanol intake in rats; however, its effects on relapse-like ethanol intake are unknown. The aim of this study was to assess the effect of Alda-1 on post-deprivation and reaccess relapse-like ethanol intake in alcohol-preferring UChB rats. We also aimed to assess the possible mechanisms associated with the effects of Alda-1 by measuring the levels of glutamate transporter (GLT-1), oxidative stress and neuroinflammation markers in different regions of the mesocorticolimbic system. MAIN METHODS: In Experiment I, UChB female rats were exposed for 100 days to voluntary ethanol intake followed by 2-weeks of ethanol withdrawal and 1 week of ethanol reaccess. Alda-1 (25 mg/kg, intragastric, i.g) or vehicle was administered daily for 14 days during the withdrawal/re-access period. Experiment II was similar to Experiment I, but after the withdrawal period, ethanol re-access was not allowed, and Alda-1 was administered during the last week of withdrawal. At the end of both experiments, the levels of GLT-1, oxidative stress (GSH, MDA), and neuroinflammation markers (GFAP, Iba-1) were assessed in nucleus accumbens and/or hippocampus. KEY FINDINGS: The results showed that Alda-1 administration markedly blocked (90 %, p < 0.001) relapse-like ethanol intake in UChB rats. Alda-1 increased Iba-1 reactivity (microglial marker) in the NAc of ethanol-deprived rats. Alda-1 administration did not influence the levels of GLT-1, oxidative stress markers (MDA, GSH) or GFAP reactivity in the mesocorticolimbic system. SIGNIFICANCE: These preclinical findings support the use of activators of ALDH2, such as Alda-1, as a potential pharmacological strategy in the treatment of alcohol relapse.

Aminopyrimidoisoquinolinequinone (APIQ) redox cycling is potentiated by ascorbate and induces oxidative stress leading to necrotic-like cancer cell death.

Several phenylaminopyrimidoisoquinolinequinones (APIQs) were tested for their cytotoxicity against different cancer cell lines (K562, T24, HepG2) in the presence or absence of ascorbate. Ascorbate enhanced the toxic effects of quinones with first half-wave potential E(I) (1/2) values in the range of -480 to -660 mV. Phenylaminoquinones that were unsubstituted at position 6 exhibited greater cytotoxic activity than did their 6-methyl-substituted analogues. Two groups of compounds were further selected, namely 8-10 and 20-22, to study the cellular mechanisms involved in quinone cytotoxicity. Indeed, these compounds have the same range of redox potentials but differed considerably in their capacity to induce cell death. In the presence of ascorbate, the cell demise induced by compounds 8-10 was not caspase-3 dependent, as shown by the lack of activation of caspase-3 and the absence of cleaved PARP fragments. In addition, an index of ER stress (eIF2α phosphorylation) was activated by these compounds. Quinones 8-10 decreased the cellular capacity to reduce MTT dye and caused marked ATP depletion. Taken together, our results show that ascorbate enhances quinone redox-cycling and leads to ROS formation that inhibits cell proliferation and provokes caspase-independent cell death. Interestingly, we also observed that quinone 8 had a rather selective effect given that freshly isolated peripheral blood leukocytes from human healthy donors were more resistant than human leukemia K562 cells.

Synthesis and antitumor evaluation of 6-aryl-substituted benzo[j]phenanthridine- and benzo[g]pyrimido[4,5-c]isoquinolinequinones.

A variety of novel 6-arylsubstituted benzo[j]phenanthridine- and benzo[g]-pyrimido[4,5-c]isoquinolinequinones were synthesized from 1,4-naphthoquinone, aryl-aldehydes and enaminones via a two-step synthetic approach. The cytotoxic activity of the aminoquinone derivatives was evaluated in vitro against one normal cell line (MRC-5 lung fibroblasts) and three human cancer cell lines (AGS human gastric adenocarcinoma; SK-MES-1 human lung cancer cells, and J82 human bladder carcinoma) in 72-h drug exposure assays using the MTT colorimetric method. Structure-activity relationships within the series of angular quinones reveal that the insertion of pyrrol-2-yl and furan-2-yl groups at the 6-position is more significant for the increase of the potency and selectivity index of the pharmacophores.

Vaccine Hesitancy Against SARS-CoV-2 in Health Personnel of Northeastern Mexico and Its Determinants.

With the emergence of effective vaccines against SARS-CoV-2, the need to find the determinants for its correct distribution is created, with health personnel being an essential group where coverage must be ensured. MATERIALS AND METHODS: A cross-sectional study was conducted through an electronic survey that was distributed to health personnel in the state of Nuevo Leon, Mexico. Potential determinants for vaccine hesitancy were covered including their intention to be vaccinated against SARS-CoV-2. RESULTS: A total of 543 responses were collected from health professionals, which 30 (5.5%) of the subjects stated that they would reject SARS-CoV-2 vaccination. How well informed the subjects were was the most determining factor, where misinformation related to vaccination and COVID-19 was the most important cause of vaccine rejection. CONCLUSION: The implementation of educational strategies for health personnel are required.

Synthesis and antitumor evaluation of 8-phenylaminopyrimido[4,5-c]isoquinolinequinones.

A series of 8-phenylaminopyrimido[4,5-c]isoquinoline-7,10-quinone derivatives were prepared by regioselective amination reaction of pyrimido[4,5-c]isoquinoline-7,10-quinones with arylamines in the presence of a Lewis acid catalyst. Preliminary evaluation of the members of the series against cancer cell lines and assays of activation of their cytotoxic activity on K562 cells with ascorbic acid are reported.

Activation of mitochondrial aldehyde dehydrogenase (ALDH2) by ALDA-1 reduces both the acquisition and maintenance of ethanol intake in rats: A dual mechanism?

A number of pre-clinical studies have shown that brain-generated acetaldehyde, the first metabolite of ethanol, exerts reinforcing effects that promote the acquisition of ethanol intake, while chronic intake maintenance appears to be mediated by alcohol-induced brain neuroinflammation/oxidative stress. Recently, it was described that N-(1,3-benzodioxol-5-ylmethyl)-2,6-dichlorobenzamide (ALDA-1) activates aldehyde dehydrogenase-2 (ALDH2), enzyme that catalyzes the oxidation of ethanol-derived acetaldehyde to acetate. The aim of this study was to determine the effects of ALDA-1 on both the acquisition and the maintenance of alcohol intake in alcohol-preferring UChB rats. For ethanol acquisition studies, naïve UChB rats were treated with five daily doses of ALDA-1 (12.5, 25 or 50 mg/kg, i.p.) from one day before the start of ethanol exposure. For chronic intake studies, UChB rats exposed for 98 days to a free access to 10% ethanol and water were treated daily with ALDA-1 (12.5, 25 or 50 mg/kg, i.p.) for five days. The administration of ALDA-1 reduced by 72-90% (p < 0.001) the acquisition of ethanol consumption in naïve rats. At chronic ethanol consumption, ALDA-1 reduced ethanol intake by 61-82% (p < 0.001). ALDA-1 administration increased by 3- and 2.3-fold the activity of ALDH2 in brain and liver, respectively. ALDA-1 did not affect saccharin consumption, nor it modified the rate of ethanol elimination. The study shows that the activation of ALDH2 by ALDA-1 is effective for inhibiting both the acquisition and the maintenance of chronic ethanol intake by alcohol-preferring rats. Thus, the activation of brain ALDH2 may constitute a novel approach in the treatment of alcohol use disorders.

Studies on quinones. Part 44: Novel angucyclinone N-heterocyclic analogues endowed with antitumoral activity.

In the search for new potentially anticancer drugs, series of angucyclinone aza-analogues containing pyridine and pyridopyridazine rings have been designed and synthesized by a highly efficient sequence involving a one-pot step for the synthesis of tricyclic quinone intermediate and highly regiocontrolled cycloaddition reactions with polarized 1,3-dienes. The new N-heterocyclic angular quinones were evaluated in vitro on normal human fibroblasts and on a panel of four distinct human cancer cell lines. All tested compounds showed high to moderate antitumor activity. Among the compounds, those with one and two pyridine moieties fused to the quinone system have shown the best effect. Structure-activity relationships established the main structural requirement for the activity of the new potential anticancer drugs.

Afianzamiento de las habilidades argumentativas de jóvenes universitarios noveles en Envigado

(analítico) Este artículo presenta los resultados de una investigación postdoctoral cuyo objetivo fue afianzar las habilidades argumentativas de jóvenes universitarios del primer semestre de una facultad en Envigado (Colombia), dados los bajos niveles identificados en semestres anteriores. Para ello, se realizó una investigación cualitativa, hermenéutico-comprensiva, apoyada en herramientas de estadística descriptiva. Se hicieron pruebas de entrada y salida a los participantes. Se diseñaron seis talleres a partir de los resultados de la prueba de entrada. Cada taller requería de un entregable. La intervención se realizó bajo el marco de la lingüística textual, el análisis crítico del discurso y la argumentación pragmadialéctica. Aquellos que participaron activamente en los talleres propuestos afianzaron sus habilidades argumentativas considerablemente y, según las participantes entrevistadas, reconocen su utilidad en tareas académicas y en la participación ciudadana.

(analytical) This paper presents the results of a postdoctoral research whose objective was to strengthen young university firstyear students' argumentative skills in a school in Envigado (Colombia), because of the low levels identified in prior semesters. Therefore, qualitative hermeneutics-comprehensive research supported in descriptive statistics was done. Entry and exit tests to participants were carried out. 6 workshops were designed based on the entry test results. Each workshop required a class product. Intervention was proposed from text linguistic, critical discourse analysis and pragma-dialectic argumentation. Those students who participated actively in the workshops significantly strengthened their argumentative skills and, as some interviewees mentioned, they recognized these skills use in academic tasks and citizenship participation.

(analítico) Este artigo apresenta os resultados de uma pesquisa de pósdoutorado cujo objetivo foi fortalecer as habilidades argumentativas de jovens universitários do primeiro semestre de uma faculdade de Envigado (Colombia), dados os baixos níveis identificados nos semestres anteriores. Para isso, foi realizada uma pesquisa qualitativa, hermenêutica-abrangente, apoiada em ferramentas estatísticas descritivas. Os participantes foram testados para entrada e saída. 6 workshops foram concebidos com base nos resultados do teste de admissão. Cada workshop exigia uma entrega. A intervenção foi realizada no quadro da linguística textual, da análise crítica do discurso e da argumentação pragmadialética. Aqueles que participaram ativamente das oficinas propostas fortaleceram consideravelmente suas habilidades argumentativas e, segundo os entrevistados, reconhecem sua utilidade nas tarefas acadêmicas e na participação cidadã.

El bullying: una mirada desde los niños y las niñas / Bullying: A scope from boys and girls / Bullying: Um olhar de meninos e meninas

(analítico) Se presentan los resultados sobre cómo se comprende y se asume el bullying, en tanto problema escolar y social, desde la perspectiva infantil. Para ello, se realizó una investigación cualitativa, hermenéutico-comprensiva, con grupos focales mediados por títeres o videos, producción gráfica y narración de historias. Los participantes fueron 626 estudiantes de 5 a 7 años. La comprensión transitó por elementos congruentes con la teoría, como exclusión, acoso verbal, afectación de pertenencias y una nueva tipología: falta de solidaridad. En cuanto a las experiencias, precisan las burlas, el acoso físico y el hurto, asociadas al contexto familiar o a ninguna, estas últimas por la confluencia del espacio escolar y la familia en un mismo lugar en tiempos de educación remota. En cuanto a la solución, está apela a figuras de autoridad, familiares, asumir actitudes reconciliadoras o al juego.

(analytical) The paper presents the results on how bullying, as scholar and social problem, is understood and assumed from the child's perspective. Therefore, a qualitative, hermeneutic-comprehensive research was carried out and focus groups were done by means of moppets and videos, graphic production, and storytelling. The participants were 626 students from 5 to 7 years old. The understanding went through elements consistent with the theory, such as exclusion, verbal harassment, affectation of be-longings and a new typology, lack of solidarity. Regarding the experiences, they specify teasing, physical harassment, theft, associated with the family context or none, the latter due to the confluence of the school space and the family in the same place in times of remote education. As for the solution, it is appealing to authority figures, relatives, assuming reconciliatory attitudes and playing.

(analítico) O artigo apresenta os resultados sobre como o bullying, como um problema social e escolar, é compreendido e assumido na perspectiva da criança. Para isso, realizou-se uma investigação qualitativa, hermenêutica-compreensiva e grupos focais mediados por fantoches ou vídeos, produção gráfica e contação de histórias; os participantes foram 626 alunos de 5 a 7 anos. O entendimento passou por elementos condizentes com a teoria, como exclusão, assédio verbal, afetação de pertences e uma nova tipologia, falta de solidariedade. Quanto às vivências, especificam provocações, assédios físicos, furtos, associados ao contexto familiar ou nenhum, este último devido à confluência do espaço escolar e da família no mesmo local em tempos de educação a distância. Quanto à solução, é apelar a figuras de autoridade, familiares, assumindo atitudes de conciliação e brincadeiras.

Revisión de las tendencias teóricas e investigativas en el campo de la Psicología de la Actividad Física y del Deporte en Iberoamérica / Review of theoretical and research trends in the field of Psychology of Physical Activity and Sports in Ibero-American

Resumen Introducción: Las tendencias teóricas e investigativas refieren propuestas y contemplaciones de los fenómenos sociales que se desarrollan en el campo de la psicología de la actividad física y del deporte, las cuales permiten tener otras perspectivas y formas de interactuar en el contexto. Objetivo: Revisión de las tendencias teóricas e investigativas en el campo de la Psicología de la Actividad Física y del Deporte en Iberoamérica. Método: La investigación fue cualitativa, hermenéutico-comprensiva. La unidad de análisis se conformó de 20 artículos de revistas iberoamericanas indexadas en Scopus en los años 2016 y 2017. Su selección se hizo a partir de los descriptores Deporte y Actividad Física. La búsqueda se realizó en el título, el resumen y las palabras clave. Para su análisis, se empleó una rúbrica, la cual permitió sistematizar la información bibliométrica del artículo, sus autores y textos citados y las palabras clave. Resultados: Se identificaron los puntos de encuentro y las apuestas teóricas presentes en dichos artículos, agrupadas en trece categorías. Conclusiones: Resulta significativa la presencia de categorías generales de la psicología como motivación, relacionamiento, habilidades para la vida e intereses de intervención dentro de aspectos tan disciplinarios como la Actividad Física y la Psicología del Deporte.

Abstract Introduction: Theoretical and investigative tendencies refer to proposals and contemplations of the social phenomena that are developed in the field of psychology of physical activity and sport, which allow to have other perspectives and ways of interacting in the context. Objective: Review of theoretical and research trends in the field of Psychology of Physical Activity and Sports in Ibero-American. Method: The research was qualitative, hermeneutic-comprehensive. The analysis unit consisted of 20 articles of Ibero-American journals indexed in Scopus in 2016 and 2017. Their selection was made from two descriptors Sport and Physical Activity. The search was carried out in the title, the summary and the keywords. For its analysis, a rubric was used, which allowed systematizing the bibliometric information of the article, its authors and cited texts and the keywords. Results: The agreement points and theoretical bets present in these articles were identified, grouped into thirteen categories. Conclusions: It is significant the presence of general categories of psychology such as motivation, relationship, life skills and intervention interests in such disciplinary aspects as Physical Activity and Sports Psychology.

Parasite Manipulation of Its Host's Physiological Reaction to Acute Stress: Experimental Results from a Natural Beetle-Nematode System.

All animals, whether vertebrate or invertebrate, must be capable of reacting to acute stressors, such as escaping from predators, and most do so with a suite of transient physiological changes that temporarily enhance survival. Some of these changes include mobilization of immune cells and increased cardiac output. A small but growing number of studies have begun to show that certain parasites appear capable of modifying such responses. We addressed this topic using a natural host and parasite system, that is, a nematode (Chondronema passali) that parasitizes horned passalus beetles, Odontotaenius disjunctus (family Passalidae), of the eastern United States. With a series of experiments, we sought to determine whether this parasite affects (1) the immune reaction to stress, (2) the output of stress-induced alarm calls, or (3) the increase in heart rate that occurs in response to acute stressors, with the stressors being mechanical or thermal. Results showed that hemocyte density increased after both stressors in nonparasitized beetles but did not increase in parasitized beetles. While mobilization of immune cells would enhance host immunity during stress, this would also be damaging to the nematode, so this scenario appears to benefit the parasite. We found no evidence that the nematode suppresses the overall reaction to stress (or prevents stress from occurring), since parasitized beetles did not differ from nonparasitized ones in alarm call rates or in heart beat frequency after exposure to mechanical stressors. Suppression of the host's normal immune reaction to stressful stimuli could translate to delayed or even reduced wound healing or pathogen resistance during these events. This project is a rare demonstration of parasite manipulation of host immune response to acute stress and should stimulate further investigations into the interactive nature of stress and parasites.

A Spontaneous Missense Mutation in Branched Chain Keto Acid Dehydrogenase Kinase in the Rat Affects Both the Central and Peripheral Nervous Systems.

A novel mutation, causing a phenotype we named frogleg because its most obvious characteristic is a severe splaying of the hind limbs, arose spontaneously in a colony of Sprague-Dawley rats. Frogleg is a complex phenotype that includes abnormalities in hind limb function, reduced brain weight with dilated ventricles and infertility. Using micro-satellite markers spanning the entire rat genome, the mutation was mapped to a region of rat chromosome 1 between D1Rat131 and D1Rat287. Analysis of whole genome sequencing data within the linkage interval, identified a missense mutation in the branched-chain alpha-keto dehydrogenase kinase (Bckdk) gene. The protein encoded by Bckdk is an integral part of an enzyme complex located in the mitochondrial matrix of many tissues which regulates the levels of the branched-chain amino acids (BCAAs), leucine, isoleucine and valine. BCAAs are essential amino acids (not synthesized by the body), and circulating levels must be tightly regulated; levels that are too high or too low are both deleterious. BCKDK phosphorylates Ser293 of the E1α subunit of the BCKDH protein, which catalyzes the rate-limiting step in the catabolism of the BCAAs, inhibiting BCKDH and thereby, limiting breakdown of the BCAAs. In contrast, when Ser293 is not phosphorylated, BCKDH activity is unchecked and the levels of the BCAAs will decrease dramatically. The mutation is located within the kinase domain of Bckdk and is predicted to be damaging. Consistent with this, we show that in rats homozygous for the mutation, phosphorylation of BCKDH in the brain is markedly decreased relative to wild type or heterozygous littermates. Further, circulating levels of the BCAAs are reduced by 70-80% in animals homozygous for the mutation. The frogleg phenotype shares important characteristics with a previously described Bckdk knockout mouse and with human subjects with Bckdk mutations. In addition, we report novel data regarding peripheral neuropathy of the hind limbs.

Fighting while parasitized: can nematode infections affect the outcome of staged combat in beetles?

The effects of non-lethal parasites may be felt most strongly when hosts engage in intense, energy-demanding behaviors. One such behavior is fighting with conspecifics, which is common among territorial animals, including many beetle species. We examined the effects of parasites on the fighting ability of a saproxylic beetle, the horned passalus (Odontotaenius disjunctus, Family: Passalidae), which is host to a non-lethal nematode, Chondronema passali. We pitted pairs of randomly-chosen (but equally-weighted) beetles against each other in a small arena and determined the winner and aggression level of fights. Then we examined beetles for the presence, and severity of nematode infections. There was a non-significant tendency (p = 0.065) for the frequency of wins, losses and draws to differ between beetles with and without C. passali; non-parasitized individuals (n = 104) won 47% of their fights while those with the parasite (n = 88) won 34%, a 13% difference in wins. The number of nematodes in a beetle affected the outcome of fights between infected and uninfected individuals in an unexpected fashion: fighting ability was lowest in beetles with the lowest (p = 0.033), not highest (p = 0.266), nematode burdens. Within-fight aggression was highest when both beetles were uninfected and lowest when both were infected (p = 0.034). Collectively, these results suggest the nematode parasite, C. passali, is associated with a modest reduction in fighting ability in horned passalus beetles, consistent with the idea that parasitized beetles have lower energy available for fighting. This study adds to a small but growing body of evidence showing how parasites negatively influence fighting behavior in animals.