Sudden cardiac death among general population and sport related population in forensic experience

PURPOSE: The goal of the study was to assess the causes and analyze the cases of sudden cardiac death (SCD) victims referred to the department of forensic medicine in Lausanne, with a particular focus on sports-related fatalities including also leisure sporting activities. To date, no such published assessment has been done nor for Switzerland nor for the central Europe. METHODS: This is a retrospective study based on autopsy records of SCD victims, from 10 to 50 years of age, performed at the University Centre of Legal Medicine in Lausanne from 1995 to 2010. The study population was divided into two groups: sport-related (SR) and not sport-related (NSR) SCDs. RESULTS: During the study period, 188 cases of SCD were recorded: 166 (88%) were NSR and 22 (12%) SR. The mean age of the 188 victims was 37.3 +/- 10.1 years, with the majority of the cases being male (79%). A cause of death was established in 84%, and the pathology responsible for death varied according to the age of the victims. In the NSR group, the mean age was 38.2 +/- 9.2 years and there was 82% of male. Coronary artery disease (CAD) was the main diagnosis in the victims aged 30-50 years. The majority of morphologically normal hearts were observed in the 15-29 year age range. There was no case in the 10-14 year age range. In the SR group, 91% of victims died during leisure sporting activities. In this group the mean age was 30.5 +/- 13.5 years, with the majority being male (82%). The main cause of death was CAD, with 6 cases (27%) and a mean age of 40.8 +/- 5.5 years. The youngest victim with CAD was 33 years old. A morphologically normal heart was observed in 5 cases (23%), with a mean age of 24.4 +/- 14.9 years. The most frequently implicated sporting activities were hiking (26%) and swimming (17%). CONCLUSION: In this study, CAD was the most common cause of death in both groups. Although this pathology most often affects adults over 35 years of age, there were also some victims under 35 years of age in both groups. SCDs during sport are mostly related to leisure sporting activities, for which preventive measures are not yet usually established. This study highlights also the need to inform both athletes and non athletes of the cardiovascular risks during sport activities and the role of a forensic autopsy and registries involving forensic pathologists for SR SCD.

Virtual Patients in continuing medical education and residency training: a pilot project for acceptance analysis in the framework of a residency revision course in pediatrics.

AIM Virtual patients (VPs) are a one-of-a-kind e-learning resource, fostering clinical reasoning skills through clinical case examples. The combination with face-to-face teaching is important for their successful integration, which is referred to as "blended learning". So far little is known about the use of VPs in the field of continuing medical education and residency training. The pilot study presented here inquired the application of VPs in the framework of a pediatric residency revision course. METHODS Around 200 participants of a pediatric nephology lecture ('nephrotic and nephritic syndrome in children') were offered two VPs as a wrap-up session at the revision course of the German Society for Pediatrics and Adolescent Medicine (DGKJ) 2009 in Heidelberg, Germany. Using a web-based survey form, different aspects were evaluated concerning the learning experiences with VPs, the combination with the lecture, and the use of VPs for residency training in general. RESULTS N=40 evaluable survey forms were returned (approximately 21%). The return rate was impaired by a technical problem with the local Wi-Fi firewall. The participants perceived the work-up of the VPs as a worthwhile learning experience, with proper preparation for diagnosing and treating real patients with similar complaints. Case presentations, interactivity, and locally and timely independent repetitive practices were, in particular, pointed out. On being asked about the use of VPs in general for residency training, there was a distinct demand for more such offers. CONCLUSION VPs may reasonably complement existing learning activities in residency training.

[Polymyalgia rheumatica: What is the current status?]

The diagnosis of polymyalgia rheumatica (PMR) is based on the typical clinical symptoms and elevated inflammatory markers in blood; however, both are unspecific and the differential diagnosis of the disease still represents a challenge for clinicians. The new consensus classification criteria of the European League Against Rheumatism (EULAR) and the American College of Rheumatology (ACR) established in 2012 have a high sensitivity (92.6 %) and specificity (91.2 %) and therefore contribute to improved diagnostics. Glucocorticoids are still the standard treatment with methotrexate and as an alternative and possibly anti-interleukin (anti-IL) 6 therapy in the future.

Head and Neck Embryology: An Overview of Development, Growth and Defect in the Human Fetus

The purpose of this research is to explore the growth and formation of the head and neck from embryological development through puberty in order to understand how this knowledge is necessary for the development of dental and medical treatments and procedures. This is a necessary aspect of the medical and dental school curriculum at the University of Connecticut Health Center Schools of Medicine and Dental Medicine that needs to be incorporated into the current study of embryology for first-year students. Working with Dr. Christine Niekrash, D.M.D, this paper will cover the embryology and growth of the head, face and oral cavity. The goal of this project will be to organize the information and recognize the resources needed to successfully introduce this part of human physiology to the UConn dental and medical students. One area in which this information is particularly relevant is the facial and oral deformities that can occur throughout fetal development.

FZD6, MATN2 AND SLC25A32, POSSIBLE CANDIDATE GENES IN NONSYNDROMIC CLEFT LIP AND PALATE

Nonsyndromic cleft lip with or without cleft palate (NSCLP) is a common birth defect with a multifactorial etiology. Despite decades of research, the genetic underpinnings of NSCLP still remain largely unexplained. A genome wide association study (GWAS) of a large NSCLP African American family with seven affected individuals across three generations found evidence for linkage at 8q21.3-24.12 (LOD = 2.98). This region contained three biologically relevant candidate genes: Frizzled-6 (FZD6) (LOD = 2.8), Matrilin-2 (MATN2) (LOD = 2.3), and Solute Carrier Family 25, Member 32 (SLC26A32) (LOD = 1.6). Sequencing of the coding regions and the 5’ and 3’ UTRs of these genes in two affected family members identified a rare intronic variant, rs138557689 (c.-153+432A>C), in FZD6. The rs138557689/C allele segregated with the NSCLP phenotype; in silico analysis predicted and EMSA analysis showed that the 138557689/C allele creates new DNA binding sites. FZD6 is part of the WNT pathway, which is involved in craniofacial development, including midface development and upper lip fusion. Our novel findings suggest that an alteration in FZD6 gene regulation may perturb this tightly controlled biological pathway and in turn contribute to the development of NSCLP in this family. Studies are underway to further define how the rs138557689/C variant affects expression of FZD6.

Design and Optimization of Four-dimensional Cone-beam Computed Tomography in Image-guided Radiation Therapy

The influence of respiratory motion on patient anatomy poses a challenge to accurate radiation therapy, especially in lung cancer treatment. Modern radiation therapy planning uses models of tumor respiratory motion to account for target motion in targeting. The tumor motion model can be verified on a per-treatment session basis with four-dimensional cone-beam computed tomography (4D-CBCT), which acquires an image set of the dynamic target throughout the respiratory cycle during the therapy session. 4D-CBCT is undersampled if the scan time is too short. However, short scan time is desirable in clinical practice to reduce patient setup time. This dissertation presents the design and optimization of 4D-CBCT to reduce the impact of undersampling artifacts with short scan times. This work measures the impact of undersampling artifacts on the accuracy of target motion measurement under different sampling conditions and for various object sizes and motions. The results provide a minimum scan time such that the target tracking error is less than a specified tolerance. This work also presents new image reconstruction algorithms for reducing undersampling artifacts in undersampled datasets by taking advantage of the assumption that the relevant motion of interest is contained within a volume-of-interest (VOI). It is shown that the VOI-based reconstruction provides more accurate image intensity than standard reconstruction. The VOI-based reconstruction produced 43% fewer least-squares error inside the VOI and 84% fewer error throughout the image in a study designed to simulate target motion. The VOI-based reconstruction approach can reduce acquisition time and improve image quality in 4D-CBCT.

IMMUNOLOGICAL MECHANISMS OF EXTRACORPOREAL PHOTOPHERESIS IN CUTANEOUS T CELL LYMPHOMA AND GRAFT VERSUS HOST DISEASE

IMMUNOLOGICAL MECHANISMS OF EXTRACORPOREAL PHOTOPHERESIS IN CUTANEOUS T CELL LYMPHOMA AND GRAFT VERSUS HOST DISEASE Publication No.___________ Lisa Harn-Ging Shiue, B.S. Supervisory Professor: Madeleine Duvic, M.D. Extracorporeal photopheresis (ECP) is an effective, low-risk immunomodulating therapy for leukemic cutaneous T cell lymphoma (L-CTCL) and graft versus host disease (GVHD), but whether the mechanism(s) of action in these two diseases is (are) identical or different is unclear. To determine the effects of ECP in vivo, we studied regulatory T cells (T-regs), cytotoxic T lymphocytes (CTLs), and dendritic cells (DCs) by immunofluorescence flow cytometry in 18 L-CTCL and 11 GVHD patients before and after ECP at Day 2, 1 month, 3 months, and 6 months. In this study, ECP was effective in 12/18 L-CTCL patients with a 66.7% overall response rate (ORR) and 6/11 GVHD patients with a 54.5% ORR. Prior to ECP, the percentages of CD4+Foxp3+ T cells in 9 L-CTCL patients were either lower (L-CTCL-Low, n=2) or higher (L-CTCL-High, n=7) than normal. Five of the 7 GVHD patients had high percentages of CD4+Foxp3+ T cells (GVHD-High). Six of 7 L-CTCL-High patients had >80% CD4+Foxp3+ T cells which were correlated with tumor cells, and were responders. Both L-CTCL-High and GVHD-High patients had decreased percentages of CD4+Foxp3+ and CD4+Foxp3+CD25- T cells after 3 months of treatment. CD4+Foxp3+CD25+ T cells increased in GVHD-High patients but decreased in L-CTCL-High patients after 3 months of ECP. In addition, numbers of CTLs were abnormal. We confirmed that numbers of CTLs were low in L-CTCL patients, but high in GVHD patients prior to ECP. After ECP, CTLs increased after 1 month in 4/6 L-CTCL patients whereas CTLs decreased after 6 months in 3/3 GVHD patients. Myeloid (mDCs) and plasmacytoid DCs (pDCs) were also low at baseline in L-CTCL and GVHD patients confirming the DC defect. After 6 months of ECP, numbers and percentages of mDCs and pDCs increased in L-CTCL and GVHD. MDCs were favorably increased in 8/12 L-CTCL responders whereas pDCs were favorably increased in GVHD patients. These data suggest that ECP is favorably modulating the DC subsets. In L-CTCL patients, the mDCs may orchestrate Th1 cell responses to overcome immune suppression and facilitate disease regression. However, in GVHD patients, ECP is favorably down-regulating the immune system and may be facilitating immune tolerance to auto-or allo-antigens. In both L-CTCL and GVHD patients, DCs are modulated, but the T cell responses orchestrated by the DCs are different, suggesting that ECP modulates depending on the immune milieu. _______________

Design, Synthesis and Development of Transporter Targeting Agents for Image-guided Therapy and Drug Delivery

The purpose of this study was to design, synthesize and develop novel transporter targeting agents for image-guided therapy and drug delivery. Two novel agents, N4-guanine (N4amG) and glycopeptide (GP) were synthesized for tumor cell proliferation assessment and cancer theranostic platform, respectively. N4amG and GP were synthesized and radiolabeled with 99mTc and 68Ga. The chemical and radiochemical purities as well as radiochemical stabilities of radiolabeled N4amG and GP were tested. In vitro stability assessment showed both 99mTc-N4amG and 99mTc-GP were stable up to 6 hours, whereas 68Ga-GP was stable up to 2 hours. Cell culture studies confirmed radiolabeled N4amG and GP could penetrate the cell membrane through nucleoside transporters and amino acid transporters, respectively. Up to 40% of intracellular 99mTc-N4amG and 99mTc-GP was found within cell nucleus following 2 hours of incubation. Flow cytometry analysis revealed 99mTc-N4amG was a cell cycle S phase-specific agent. There was a significant difference of the uptake of 99mTc-GP between pre- and post- paclitaxel-treated cells, which suggests that 99mTc-GP may be useful in chemotherapy treatment monitoring. Moreover, radiolabeled N4amG and GP were tested in vivo using tumor-bearing animal models. 99mTc-N4amG showed an increase in tumor-to-muscle count density ratios up to 5 at 4 hour imaging. Both 99mTc-labeled agents showed decreased tumor uptake after paclitaxel treatment. Immunohistochemistry analysis demonstrated that the uptake of 99mTc-N4amG was correlated with Ki-67 expression. Both 99mTc-N4amG and 99mTc-GP could differentiate between tumor and inflammation in animal studies. Furthermore, 68Ga-GP was compared to 18F-FDG in rabbit PET imaging studies. 68Ga-GP had lower tumor standardized uptake values (SUV), but similar uptake dynamics, and different biodistribution compared with 18F-FDG. Finally, to demonstrate that GP can be a potential drug carrier for cancer theranostics, several drugs, including doxorubicin, were selected to be conjugated to GP. Imaging studies demonstrated that tumor uptake of GP-drug conjugates was increased as a function of time. GP-doxorubicin (GP-DOX) showed a slow-release pattern in in vitro cytotoxicity assay and exhibited anti-cancer efficacy with reduced toxicity in in vivo tumor growth delay study. In conclusion, both N4amG and GP are transporter-based targeting agents. Radiolabeled N4amG can be used for tumor cell proliferation assessment. GP is a potential agent for image-guided therapy and drug delivery.

El empleo rural en Santa Cruz : Situación de coyuntura o crisis estructural

La caracterización socioeconómica de la Provincia de Santa Cruz, en el marco del subsistema regional de la Patagonia Austral, releva a los sectores económicos que componen sus respectivas estructuras de producción, así como la adaptación de la región a los cambios operados en la economía, particularmente a partir de la reestructuración de los años ochenta. El agrupamiento de sus principales sectores de acuerdo con una tipología descriptiva construida sobre la base de su temporalidad de surgimiento/desarrollo histórico ha permitido clasificarlos en " tradicionales" y "emergentes". En el primer grupo se destaca la preeminencia que ha tenido el sector agropecuario, particularmente a través de la actividad ganadera ovina. En la evolución de esta actividad se reconocen tres períodos claramente diferenciados: uno inicial de desarrollo y auge del ovino (1880-1940); otro de consolidación (1940-1980); y un tercero de declinación y crisis (1980 a 2001) cuyos años más difíciles se extendieron entre 1994 y 2000. El poblamiento de la Provincia de Santa Cruz ha estado fuertemente ligado a la actividad ganadera ovina, originada hacia 1890 de la mano de diversas corrientes migratorias apoyadas por una política nacional de ocupación territorial. Y la evolución del empleo rural provincial ha acompañado la tendencia de la actividad en cada período. Es así como creció significativamente en los años del poblamiento, se estabilizó en la consolidación y tuvo una abrupta caída a partir del comienzo de la crisis. La misma provocó, entre otras cosas, el abandono de establecimientos, la diversificación de productores que se emplearon en actividades no agropecuarias como fuente de ingresos alternativa o complementaria, y consiguientemente, una fuerte reducción de la mano de obra rural ocupada -siendo que, en su mejor época y según datos de censos nacionales y provinciales, más del 50 de la fuerza laboral provincial trabajaba en las diferentes actividades ganaderas de entonces. A partir del año 2002, e impulsada por la salida del régimen de convertibilidad, se modifica sustantivamente la rentabilidad de las explotaciones, dando comienzo a una lenta recuperación, aunque en un escenario muy distinto a los de años anteriores. Pese a una demanda sostenida, con precios en alza y con mejores resultados económicos, la pérdida de la cultura ovina tradicional y de las características de los sistemas históricos de producción y la aparición de otras actividades económicas extra agropecuarias han producido un éxodo de la oferta laboral rural hacia los centros urbanos, lo que plantea un problema que trasciende la coyuntura hacia lo estructural

El empleo rural en Santa Cruz : Situación de coyuntura o crisis estructural

La caracterización socioeconómica de la Provincia de Santa Cruz, en el marco del subsistema regional de la Patagonia Austral, releva a los sectores económicos que componen sus respectivas estructuras de producción, así como la adaptación de la región a los cambios operados en la economía, particularmente a partir de la reestructuración de los años ochenta. El agrupamiento de sus principales sectores de acuerdo con una tipología descriptiva construida sobre la base de su temporalidad de surgimiento/desarrollo histórico ha permitido clasificarlos en " tradicionales" y "emergentes". En el primer grupo se destaca la preeminencia que ha tenido el sector agropecuario, particularmente a través de la actividad ganadera ovina. En la evolución de esta actividad se reconocen tres períodos claramente diferenciados: uno inicial de desarrollo y auge del ovino (1880-1940); otro de consolidación (1940-1980); y un tercero de declinación y crisis (1980 a 2001) cuyos años más difíciles se extendieron entre 1994 y 2000. El poblamiento de la Provincia de Santa Cruz ha estado fuertemente ligado a la actividad ganadera ovina, originada hacia 1890 de la mano de diversas corrientes migratorias apoyadas por una política nacional de ocupación territorial. Y la evolución del empleo rural provincial ha acompañado la tendencia de la actividad en cada período. Es así como creció significativamente en los años del poblamiento, se estabilizó en la consolidación y tuvo una abrupta caída a partir del comienzo de la crisis. La misma provocó, entre otras cosas, el abandono de establecimientos, la diversificación de productores que se emplearon en actividades no agropecuarias como fuente de ingresos alternativa o complementaria, y consiguientemente, una fuerte reducción de la mano de obra rural ocupada -siendo que, en su mejor época y según datos de censos nacionales y provinciales, más del 50 de la fuerza laboral provincial trabajaba en las diferentes actividades ganaderas de entonces. A partir del año 2002, e impulsada por la salida del régimen de convertibilidad, se modifica sustantivamente la rentabilidad de las explotaciones, dando comienzo a una lenta recuperación, aunque en un escenario muy distinto a los de años anteriores. Pese a una demanda sostenida, con precios en alza y con mejores resultados económicos, la pérdida de la cultura ovina tradicional y de las características de los sistemas históricos de producción y la aparición de otras actividades económicas extra agropecuarias han producido un éxodo de la oferta laboral rural hacia los centros urbanos, lo que plantea un problema que trasciende la coyuntura hacia lo estructural

El empleo rural en Santa Cruz : Situación de coyuntura o crisis estructural

La caracterización socioeconómica de la Provincia de Santa Cruz, en el marco del subsistema regional de la Patagonia Austral, releva a los sectores económicos que componen sus respectivas estructuras de producción, así como la adaptación de la región a los cambios operados en la economía, particularmente a partir de la reestructuración de los años ochenta. El agrupamiento de sus principales sectores de acuerdo con una tipología descriptiva construida sobre la base de su temporalidad de surgimiento/desarrollo histórico ha permitido clasificarlos en " tradicionales" y "emergentes". En el primer grupo se destaca la preeminencia que ha tenido el sector agropecuario, particularmente a través de la actividad ganadera ovina. En la evolución de esta actividad se reconocen tres períodos claramente diferenciados: uno inicial de desarrollo y auge del ovino (1880-1940); otro de consolidación (1940-1980); y un tercero de declinación y crisis (1980 a 2001) cuyos años más difíciles se extendieron entre 1994 y 2000. El poblamiento de la Provincia de Santa Cruz ha estado fuertemente ligado a la actividad ganadera ovina, originada hacia 1890 de la mano de diversas corrientes migratorias apoyadas por una política nacional de ocupación territorial. Y la evolución del empleo rural provincial ha acompañado la tendencia de la actividad en cada período. Es así como creció significativamente en los años del poblamiento, se estabilizó en la consolidación y tuvo una abrupta caída a partir del comienzo de la crisis. La misma provocó, entre otras cosas, el abandono de establecimientos, la diversificación de productores que se emplearon en actividades no agropecuarias como fuente de ingresos alternativa o complementaria, y consiguientemente, una fuerte reducción de la mano de obra rural ocupada -siendo que, en su mejor época y según datos de censos nacionales y provinciales, más del 50 de la fuerza laboral provincial trabajaba en las diferentes actividades ganaderas de entonces. A partir del año 2002, e impulsada por la salida del régimen de convertibilidad, se modifica sustantivamente la rentabilidad de las explotaciones, dando comienzo a una lenta recuperación, aunque en un escenario muy distinto a los de años anteriores. Pese a una demanda sostenida, con precios en alza y con mejores resultados económicos, la pérdida de la cultura ovina tradicional y de las características de los sistemas históricos de producción y la aparición de otras actividades económicas extra agropecuarias han producido un éxodo de la oferta laboral rural hacia los centros urbanos, lo que plantea un problema que trasciende la coyuntura hacia lo estructural

Disentangling factors controlling fruit and seed removal by rodents in temperate forests

Fleshy fruits fall on to the ground together with cleaned seeds previously ingested by primary dispersers, offering a wide range of fruits and seeds to the ground foragers. Although nutritional properties strongly differ between fruits and seeds, this different seed presentation (cleaned seeds versus seeds within the pulp) has not been addressed in seed removal studies. This study reports on the removal of fruits versus their seeds in five fleshy-fruited species in a temperate forest. We found that rodents removed most of the seeds and partially consumed most of the fruits, preferring seeds to fruits. Rodents bit the fruits to extract the seeds, leaving most of the pulp. We found a preference ranking for the seeds (Sorbus aucuparia>Ilex aquifolium>Sorbus aria>Rosa canina>Crataegus monogyna) but no preferences were found for the fruits, probably due to their similarities in pulp constituents. Seed and fruit choice were affected by chemical and physical properties and not by their size. The presence of alternative and preferred seeds (nuts) delayed the encounter of the fruits and seeds and diminished their removal rates. We found that higher rodent abundance is not necessarily associated with higher removal rates of fleshy fruits. Rodent abundance, fruit size and seed size are minor factors in the removal of fleshy fruits and their seeds. This study underlines that scatter-hoarding rodents are important removers of fleshy fruits and their seeds, producing a differential seed removal depending on the seed presentation (with or without pulp), the nutritional properties of the seeds (but not of the fruits) and the presence of alternative food

Differences and Relationship Between Standard and Specific Throwing Test in Handball According to the Competitive and Professional Level

The present study analyzed the differences in distance throwing with heavy and light medicine ball and throwing velocity between handball players of different competitive and professional level. Likewise, the relationship between the three throwing test of progressive specificity was analyzed: throwing with heavy medicinal ball (TH), throwing with light medicinal ball (TL) and throwing velocity (TV). For this purpose, sixty-five professional (P), semiprofessional (S) and non-professional (N) players were evaluated. El presente estudio analizó las diferencias en la distancia de lanzamiento realizado con balón medicinal pesado y ligero y en la velocidad de lanzamiento entre jugadores de balonmano de diferente nivel competitivo y profesional. Igualmente, la relación entre los tres test de lanzamiento, de progresiva especificidad, fue analizado: lanzamiento con balón medicinal pesado (TH), lanzamiento con balón medicinal ligero (TL) y velocidad de lanzamiento (TV). Para ello, sesenta y cinco jugadores profesionales (P), semi-profesionales (S) y no-profesionales (N) fueron evaluados.