Adipose-derived Stem Cell Conditioned Media Extends Survival time of a mouse model of Amyotrophic Lateral Sclerosis

Adipose stromal cells (ASC) secrete various trophic factors that assist in the protection of neurons in a variety of neuronal death models. In this study, we tested the effects of human ASC conditional medium (ASC-CM) in human amyotrophic lateral sclerosis (ALS) transgenic mouse model expressing mutant superoxide dismutase (SOD1(G93A)). Treating symptomatic SOD1(G93A) mice with ASC-CM significantly increased post-onset survival time and lifespan. Moreover, SOD1(G93A) mice given ASC-CM treatment showed high motor neuron counts, less activation of microglia and astrocytes at an early symptomatic stage in the spinal cords under immunohistochemical analysis. SOD1(G93A) mice treated with ASC-CM for 7 days showed reduced levels of phosphorylated p38 (pp38) in the spinal cord, a mitogen-activated protein kinase that is involved in both inflammation and neuronal death. Additionally, the levels of α-II spectrin in spinal cords were also inhibited in SOD1(G93A) mice treated with ASC-CM for 3 days. Interestingly, nerve growth factor (NGF), a neurotrophic factor found in ASC-CM, played a significant role in the protection of neurodegeneration inSOD1(G93A) mouse. These results indicate that ASC-CM has the potential to develop into a novel and effective therapeutic treatment for ALS

Aportes de la clínica forense para conceptuar en materia probatoria sobre el riesgo para la vida en el delito de tentativa de homicidio en Colombia

The establishment of attempted murder requires the judicial inquiry to provide different evidences. Forensic technical report of nonfatal injuries at the request of the authorities can provide valuable medical concepts on the magnitude, location and severity of the injuries. So far, there has been no objective evidence built from medical science for the assessment of the likelihood of a fatal injury. In this article, we review the forensic and medical-legal concepts, which allow providing percentages of probability of fatal injury from world-renowned medical scales.El establecimiento del tipo penal de tentativa de homicidio exige a la investigación judicial aportar diferentes elementos probatorios. En este sentido, el informe técnico médico-legal de lesiones no fatales, realizado a solicitud de las autoridades, puede aportar valiosos conceptos médicos sobre la gravedad de las mismas, su localización y severidad. Sin embargo, hasta el momento no se han incorporado elementos determinantemente objetivos a partir de la ciencia médica forense para la valoración de la probabilidad que tenga una lesión para causar la muerte. En este artículo se revisan conceptos médico-legales y médicos en el contexto jurídico, que permitirían aportar una ponderación más estructurada de la probabilidad de causar la muerte de una lesión, fundamentalmente a partir de escalas médicas mundialmente reconocidas

Effects of hospital facilities on patient outcomes after cancer surgery: an international, prospective, observational study

Background Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide.Methods A multimethods analysis was performed as part of the GlobalSurg 3 study-a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital.Findings Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3.85 [95% CI 2.58-5.75]; p<0.0001), with excess mortality predominantly explained by a limited capacity to rescue following the development of major complications (63.0% vs 82.7%; OR 0.35 [0.23-0.53]; p<0.0001). Across LMICs, improvements in hospital facilities would prevent one to three deaths for every 100 patients undergoing surgery for cancer.Interpretation Hospitals with higher levels of infrastructure and resources have better outcomes after cancer surgery, independent of country income. Without urgent strengthening of hospital infrastructure and resources, the reductions in cancer-associated mortality associated with improved access will not be realised

Correction to: Comparison of healing of full-thickness skin wounds grafted with multidirectional or unidirectional autologous artificial dermis: differential delivery of healing biomarkers (Drug Delivery and Translational Research, (2018), 8, 5, (1014-1024), 10.1007/s13346-018-0528-2)

In the original article text presenting and discussing results shown in Fig. 6 omitted to mention that quantification of TGF-?2 and TGF-?3 was not included in Fig. 6a, c, e. © 2018, Controlled Release Society

No-Crosslinking Scaffold of Collagen Support the Three-Dimensional Culture of Human Coronary Artery Endothelial Cell

Introducción: La mayoría de los estudios que evalúan la activación endotelial se han realizado en placas de cultivo. Sin embargo, la evidencia experimental apoya que la composición química y la estructura de la superficie en la que se siembran las células endoteliales influyen en su respuesta. En este trabajo se estudió la influencia de los andamios -fabricados con colágeno I utilizando diferentes métodos de procesamiento- en el comportamiento de las células endoteliales primarias de la arteria coronaria humana (HCAEC) cultivadas en su superficie. Métodos: Se vertió una suspensión de colágeno sobre membranas de insertos transwell, se congeló (-20_C o -80_C) y se liofilizó para obtener andamios 3D- 20 y 3D-80. La misma suspensión complementada con la matriz de membrana basal Geltrex TM también se procesó para obtener andamios 3DG- 20 y 3DG-80. Los andamios 3D-20 y 3D-80 fueron reticulados (3DC-20; 3DC-80) o no con glutaraldehído, los 3DG no fueron reticulados. Se sembraron HCAEC en los andamios para obtener cultivos 3DCE-20, 3DCE-80, 3DE-20, 3DE-80, 3DCG-20 y 3DCG-80. A continuación se evaluó la formación de monocapas, la viabilidad celular y la secreción de citoquinas inflamatorias (IL-6, IL-8, TNF-a, IL-12 p70, IL-1b, IL-10). Resultados y discusión: Las HCAEC cultivadas en todos los andamios formaron monocapas independientemente de la metodología de fabricación del andamio utilizada. Todos los cultivos secretaron Il-6 e IL-8 pero no las demás citoquinas y la secreción de IL-6 e IL-8 fue significativamente menor en los cultivos 3DE-80 y 3DCG-80 que en los demás (p < 0,05). Conclusiones: Los datos indican que el 3DE-80 y el 3DCG-80 tienen una mejor biocompatibilidad con las HCAEC cultivadas y sugieren que los andamios 3D podrían tener un efecto diferencial sobre las células sembradas en su superficie.Introduction: Most studies assessing endothelial activation have been made in culture dishes. However, experimental evidence supports that chemical composition and structure of the surface in which endothelial cells are seeded influence their response. This work studied the influence of scaffolds -made with collagen I using different processing methods- on the behavior of primary human coronary artery endothelial cells (HCAEC) cultured on their surface. Methods: A collagen suspension was poured on membranes of transwell inserts, frozen (-20_Cor -80_C) and lyophilized to obtain 3D- 20 and 3D-80 scaffolds. The same suspension supplemented with Geltrex TM Basement Membrane Matrix also was processed to obtain 3DG- 20 and 3DG-80 scaffolds. The 3D-20 and 3D-80 scaffolds were crosslinked (3DC-20; 3DC-80) or not with glutaraldehyde, the 3DGs were not cross-linked. HCAECwere seeded on the scaffolds to obtain 3DCE- 20, 3DCE-80, 3DE-20, 3DE-80, 3DCG-20 and 3DCG-80 cultures. Monolayer formation, cell viability and inflammatory cytokine (IL-6, IL-8, TNF-a, IL-12 p70, IL-1b, IL-10) secretion were then evaluated. Results and Discussion: HCAEC cultured on all the scaffolds formed monolayers independently of the scaffold manufacturing methodology used. All cultures secreted Il-6 and IL-8 but not the other cytokines and IL-6 and IL-8 secretion was significantly lower in the 3DE-80 and 3DCG-80 than in the other cultures (p < 0.05). Conclusion: Data indicate that 3DE-80 and 3DCG-80 have better biocompatibility with cultured HCAEC and suggest that 3D scaffolds might have differential effect on cells seeded on their surface

Comparación de la curación de heridas cutáneas de espesor total injertadas con dermis artificial autóloga multidireccional o unidireccional: administración diferencial de biomarcadores de curación

11 páginasCytokines, chemokines, and growth and remodeling factors orchestrate wound healing when skin damage occurs. During early stages, when the wound is still open, detection and quantification of these compounds might provide biomarkers of skin wound healing, which could aid to complete the scenario provided by clinical follow-up data and histological and histomorphometric analyses. This work assessed and compared the healing of full-thickness skin wounds grafted with artificial dermis made with autologous skin fibroblasts and unidirectional or multidirectional type I collagen scaffolds to test this hypothesis. Biomarkers of healing were detected and quantified in the culture medium of artificial dermis and exudates from the grafted wounds. Clinical follow-up of animals and histological and histomorphometric analysis showed differences in graft integration, wound closure, and histological and histomorphometric parameters. Surface plasmon resonance quantification of 13 healing biomarkers indicated differential secretion of most of the quantified factors in culture medium by the multidirectional and unidirectional artificial dermis. Also, there were significant differences between the concentration of some of the factors analyzed in the exudates of wounds grafted with the evaluated artificial dermis. These findings suggest that differential delivery of healing biomarkers induced by the directionality of the scaffold used to produce the multidirectional and unidirectional dermis was sufficient to create two skin wound microenvironments that determined a different outcome of healing. Overall, data indicate that healing of wounds grafted with multidirectional autologous artificial dermis is better than that of the wounds grafted with the unidirectional one.Las citocinas, quimiocinas y factores de crecimiento y remodelación organizan la cicatrización de heridas cuando se produce daño en la piel. Durante las primeras etapas, cuando la herida aún está abierta, la detección y cuantificación de estos compuestos podría proporcionar biomarcadores de cicatrización de heridas cutáneas, lo que podría ayudar a completar el escenario proporcionado por los datos de seguimiento clínico y los análisis histológicos e histomorfométricos. Este trabajo evaluó y comparó la curación de heridas cutáneas de espesor total injertadas con dermis artificial hecha con fibroblastos de piel autólogos y andamios de colágeno tipo I unidireccionales o multidireccionales para probar esta hipótesis. Se detectaron y cuantificaron biomarcadores de cicatrización en el medio de cultivo de dermis artificial y exudados de las heridas injertadas. El seguimiento clínico de los animales y los análisis histológicos e histomorfométricos mostraron diferencias en la integración del injerto, el cierre de la herida y los parámetros histológicos e histomorfométricos. La cuantificación por resonancia de plasmón superficial de 13 biomarcadores de curación indicó una secreción diferencial de la mayoría de los factores cuantificados en el medio de cultivo por parte de la dermis artificial multidireccional y unidireccional. También hubo diferencias significativas entre la concentración de algunos de los factores analizados en los exudados de heridas injertadas con la dermis artificial evaluada. Estos hallazgos sugieren que la administración diferencial de biomarcadores de curación inducida por la direccionalidad del andamio utilizado para producir la dermis multidireccional y unidireccional fue suficiente para crear dos microambientes de heridas en la piel que determinaron un resultado diferente de la curación. En general, los datos indican que la curación de las heridas injertadas con dermis artificial autóloga multidireccional es mejor que la de las heridas injertadas con dermis unidireccional

Fine-scale geographical sampling and molecular characterization of the giant African land snail in its invasive range in Asia shows low genetic diversity, new haplotypes and the emergence of another haplotype from the Indian Ocean Islands

Native to East Africa, the giant African snail Lissachatina [=Achatina] fulica (Bowdich, 1822) is a tropical crop pest and one of the world’s top 100 invasive species. It is now present in at least 52 countries worldwide, with an actively expanding range. Lissachatina fulica was first introduced to India in 1847, but subsequent arrivals in India and local patterns of spread remain unclear. This study uses the 16S rRNA gene to identify the extent of genetic variation in India by sampling Indian populations and comparing them with published sequence data. A total of 307 snails were collected from 178 localities in India and from a single locality in the UAE, and the 16S rRNA gene was amplified and sequenced. Eight haplotypes were identified from India of which four are newly recognized. The new haplotypes identified in this study have increased the number of L. fulica 16S rRNA haplotypes from 19 to 23. Examination of haplotype and nucleotide diversities revealed that genetic variation is low in India, the UAE and across Asia as a whole. The number of haplotypes was higher in India when compared to other invasive regions but all of the Asian haplotypes appear to be closely related to the most common haplotypes in the Indian Ocean Islands. Heavy trade between the snail-infested and native-range countries suggests that the variation observed in India might be traced back to its native range, but the lack of sampling and paucity of sequences from East Africa currently prevents a comparison. Tracing back the emergent haplotypes by additional sampling could throw more light on the spread of L. fulica