Gambaran Proses Radang Luka Postmortem Pada Hewan Coba

: Skin is the largest and heaviest organ in human body. Its role as a barrier and its location at the surface of human body make it susceptible to trauma which in consequence to wound formation. Human body responses to wound by initiating wound healing process. The fundamental aspect of this process consists of four phases: inflammation, initiation, proliferation, and remodeling. In order to obtain sucessfull wound healing all four phases must occur in a proper sequence and a time frame. Several factors have been known to interfere one or more of these phases. In postmortem condition, wound healing can still occur but the process is different compared to those in antemortem condition. A domestic pig was used on account of the similarity in skin structure and histophysiology with human being to observe the inflammatory process in postmortem wounds. This was an experimental descriptive research. Cut wounds were made at the back of the postmortem pig then skin tissues were taken and reserved in series of time to observe histological features of wound healing process. The results showed that an increase of cells\u27 number in dermis layer of the skin was observed 15 minutes after the cut wounds. The increase of cells\u27 number in the first wounds reached its peak at 150 minutes postmortem, meanwhile the increase of cells\u27 number in second wounds reached its peak at 45 minutes postmortem, 90 minutes after the cut wounds were made. Moreover, the increase of cells\u27number could be observed until 3 hours postmortem. It was concluded that the inflammatory process of wound healing observed by increases of cells\u27 number still occured postmortem for a certain time

Infección Latente por Tuberculosis en Trabajadores de Salud en Guayaquil, Ecuador

Infección latente por tuberculosis y tuberculosis activa representan unriesgo ocupacional para los trabajadores de salud, quienes estánexpuestos a pacientes infectados en sus lugares de trabajo. Este riesgoes particularmente serio para los trabajadores de salud en Guayaquil,Ecuador debido a la alta incidencia de tuberculosis en esta ciudad. Elpresente artículo busca determinar la prevalencia de LTBI en trabajadoresde salud en Guayaquil, Ecuador; a través de un estudio transversaly no experimental conducido durante Junio, 2013-Mayo, 2014en 124 trabajadores de salud de unidades hospitalarias públicos yprivados. Se completó una encuesta epidemiológica y se obtuvo muestrasde sangre. Se ejecutó el ensayo Quantiferon Tb Gold in-Tube. Laausencia de síntomas de TB activa confirmó el diagnostico de LTBI.Entre los hallazgos: 37 de los 124 participantes, o 29,80%, fueronpositivos para LTBI por el test de IGRA. La mayoría de los individuospositivos se ubicaron entre los 41-50 años de edad (10,5%) y fuerondel género femenino (21,0%). La prevalencia de LBTI en trabajadoresde salud en Guayaquil fue 29.80%, similar a los valores reportados enotros estudios de ciudades que comparten características similares

Genome-wide significant association with seven novel multiple sclerosis risk loci

Objective: A recent large-scale study in multiple sclerosis (MS) using the ImmunoChip platform reported on 11 loci that showed suggestive genetic association with MS. Additional data in sufficiently sized and independent data sets are needed to assess whether these loci represent genuine MS risk factors. Methods: The lead SNPs of all 11 loci were genotyped in 10 796 MS cases and 10 793 controls from Germany, Spain, France, the Netherlands, Austria and Russia, that were independent from the previously reported cohorts. Association analyses were performed using logistic regression based on an additive model. Summary effect size estimates were calculated using fixed-effect meta-analysis. Results: Seven of the 11 tested SNPs showed significant association with MS susceptibility in the 21 589 individuals analysed here. Meta-analysis across our and previously published MS case-control data (total sample size n=101 683) revealed novel genome-wide significant association with MS susceptibility (p<5×10−8) for all seven variants. This included SNPs in or near LOC100506457 (rs1534422, p=4.03×10−12), CD28 (rs6435203, p=1.35×10−9), LPP (rs4686953, p=3.35×10−8), ETS1 (rs3809006, p=7.74×10−9), DLEU1 (rs806349, p=8.14×10−12), LPIN3 (rs6072343, p=7.16×10−12) and IFNGR2 (rs9808753, p=4.40×10−10). Cis expression quantitative locus effects were observed in silico for rs6435203 on CD28 and for rs9808753 on several immunologically relevant genes in the IFNGR2 locus. Conclusions: This study adds seven loci to the list of genuine MS genetic risk factors and further extends the list of established loci shared across autoimmune diseases

Genome-wide significant association with seven novel multiple sclerosis risk loci

Objective: A recent large-scale study in multiple sclerosis (MS) using the ImmunoChip platform reported on 11 loci that showed suggestive genetic association with MS. Additional data in sufficiently sized and independent data sets are needed to assess whether these loci represent genuine MS risk factors. Methods: The lead SNPs of all 11 loci were genotyped in 10 796 MS cases and 10 793 controls from Germany, Spain, France, the Netherlands, Austria and Russia, that were independent from the previously reported cohorts. Association analyses were performed using logistic regression based on an additive model. Summary effect size estimates were calculated using fixed-effect meta-analysis. Results: Seven of the 11 tested SNPs showed significant association with MS susceptibility in the 21 589 individuals analysed here. Meta-analysis across our and previously published MS case-control data (total sample size n=101 683) revealed novel genome-wide significant association with MS susceptibility (p<5×10−8) for all seven variants. This included SNPs in or near LOC100506457 (rs1534422, p=4.03×10−12), CD28 (rs6435203, p=1.35×10−9), LPP (rs4686953, p=3.35×10−8), ETS1 (rs3809006, p=7.74×10−9), DLEU1 (rs806349, p=8.14×10−12), LPIN3 (rs6072343, p=7.16×10−12) and IFNGR2 (rs9808753, p=4.40×10−10). Cis expression quantitative locus effects were observed in silico for rs6435203 on CD28 and for rs9808753 on several immunologically relevant genes in the IFNGR2 locus. Conclusions: This study adds seven loci to the list of genuine MS genetic risk factors and further extends the list of established loci shared across autoimmune diseases

Locus for severity implicates CNS resilience in progression of multiple sclerosis

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) that results in significant neurodegeneration in the majority of those affected and is a common cause of chronic neurological disability in young adults(1,2). Here, to provide insight into the potential mechanisms involved in progression, we conducted a genome-wide association study of the age-related MS severity score in 12,584 cases and replicated our findings in a further 9,805 cases. We identified a significant association with rs10191329 in the DYSF-ZNF638 locus, the risk allele of which is associated with a shortening in the median time to requiring a walking aid of a median of 3.7 years in homozygous carriers and with increased brainstem and cortical pathology in brain tissue. We also identified suggestive association with rs149097173 in the DNM3-PIGC locus and significant heritability enrichment in CNS tissues. Mendelian randomization analyses suggested a potential protective role for higher educational attainment. In contrast to immune-driven susceptibility(3), these findings suggest a key role for CNS resilience and potentially neurocognitive reserve in determining outcome in MS

Global, regional, and national burden of disorders affecting the nervous system, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BackgroundDisorders affecting the nervous system are diverse and include neurodevelopmental disorders, late-life neurodegeneration, and newly emergent conditions, such as cognitive impairment following COVID-19. Previous publications from the Global Burden of Disease, Injuries, and Risk Factor Study estimated the burden of 15 neurological conditions in 2015 and 2016, but these analyses did not include neurodevelopmental disorders, as defined by the International Classification of Diseases (ICD)-11, or a subset of cases of congenital, neonatal, and infectious conditions that cause neurological damage. Here, we estimate nervous system health loss caused by 37 unique conditions and their associated risk factors globally, regionally, and nationally from 1990 to 2021.MethodsWe estimated mortality, prevalence, years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs), with corresponding 95% uncertainty intervals (UIs), by age and sex in 204 countries and territories, from 1990 to 2021. We included morbidity and deaths due to neurological conditions, for which health loss is directly due to damage to the CNS or peripheral nervous system. We also isolated neurological health loss from conditions for which nervous system morbidity is a consequence, but not the primary feature, including a subset of congenital conditions (ie, chromosomal anomalies and congenital birth defects), neonatal conditions (ie, jaundice, preterm birth, and sepsis), infectious diseases (ie, COVID-19, cystic echinococcosis, malaria, syphilis, and Zika virus disease), and diabetic neuropathy. By conducting a sequela-level analysis of the health outcomes for these conditions, only cases where nervous system damage occurred were included, and YLDs were recalculated to isolate the non-fatal burden directly attributable to nervous system health loss. A comorbidity correction was used to calculate total prevalence of all conditions that affect the nervous system combined.FindingsGlobally, the 37 conditions affecting the nervous system were collectively ranked as the leading group cause of DALYs in 2021 (443 million, 95% UI 378–521), affecting 3·40 billion (3·20–3·62) individuals (43·1%, 40·5–45·9 of the global population); global DALY counts attributed to these conditions increased by 18·2% (8·7–26·7) between 1990 and 2021. Age-standardised rates of deaths per 100 000 people attributed to these conditions decreased from 1990 to 2021 by 33·6% (27·6–38·8), and age-standardised rates of DALYs attributed to these conditions decreased by 27·0% (21·5–32·4). Age-standardised prevalence was almost stable, with a change of 1·5% (0·7–2·4). The ten conditions with the highest age-standardised DALYs in 2021 were stroke, neonatal encephalopathy, migraine, Alzheimer's disease and other dementias, diabetic neuropathy, meningitis, epilepsy, neurological complications due to preterm birth, autism spectrum disorder, and nervous system cancer.InterpretationAs the leading cause of overall disease burden in the world, with increasing global DALY counts, effective prevention, treatment, and rehabilitation strategies for disorders affecting the nervous system are needed

Tyrosine aminotransferase from Leishmania infantum: A new drug target candidate

Leishmania infantum is the etiological agent of zoonotic visceral leishmaniasis in the Mediterranean basin. The disease is fatal without treatment, which has been based on antimonial pentavalents for more than 60 years. Due to resistances, relapses and toxicity to current treatment, the development of new drugs is required. The structure of the L. infantum tyrosine aminotransferase (LiTAT) has been recently solved showing important differences with the mammalian orthologue. The characterization of LiTAT is reported herein. This enzyme is cytoplasmic and is over-expressed in the more infective stages and nitric oxide resistant parasites. Unlike the mammalian TAT, LiTAT is able to use ketomethiobutyrate as co-substrate. The pharmacophore model of LiTAT with this specific co-substrate is described herein. This may allow the identification of new inhibitors present in the databases. All the data obtained support that LiTAT is a good target candidate for the development of new anti-leishmanial drugs

The fate of early perichondrial cells in developing bones

In endochondral bone development, bone-forming osteoblasts and bone marrow stromal cells have dual origins in the fetal cartilage and its surrounding perichondrium. However, how early perichondrial cells distinctively contribute to developing bones remain unidentified. Here we show using in vivo cell-lineage analyses that Dlx5+ fetal perichondrial cells marked by Dlx5-creER do not generate cartilage but sustainably contribute to cortical bone and marrow stromal compartments in a manner complementary to fetal chondrocyte derivatives under the regulation of Hedgehog signaling. Postnatally, Dlx5+ fetal perichondrial cell derivatives preferentially populate the diaphyseal marrow stroma with a dormant adipocyte-biased state and are refractory to parathyroid hormone-induced bone anabolism. Therefore, early perichondrial cells of the fetal cartilage are destined to become an adipogenic subset of stromal cells in postnatal diaphyseal bone marrow, supporting the theory that the adult bone marrow stromal compartments are developmentally prescribed within the two distinct cells-of-origins of the fetal bone anlage.Nature Communications, 13, art. no. 7319; 202

Temporal Trends, Predictors, and Outcomes of Disseminated Intravascular Coagulation in Hospitalizations With Sepsis.

Background This retrospective study was conducted to analyze the temporal trends, predictors, and impact of disseminated intravascular coagulation (DIC) on outcomes among septicemic patients using a nationally representative database. Methods We derived data from the National Inpatient Sample (NIS) for the years 2008-2017 for adult hospitalizations due to sepsis. The primary outcomes were in-hospital mortality and discharge to facility. The Cochran-Armitage test and multivariable survey logistic regression models were used to analyze the data. Results Out of 12,820,000 hospitalizations due to sepsis, 153,181 (1.18%) were complicated by DIC. The incidence of DIC decreased from 2008 to 2017. In multivariable regression analysis, demographics and comorbidities were associated with higher odds of DIC. During the study period, in-hospital mortality among patients with sepsis decreased, but the attributable risk percent of in-hospital mortality due to DIC increased. We observed similar trends for discharge to facility; however, the adjusted odds of discharge to facility due to DIC remained stable over the study period. Conclusion Although the incidence of sepsis complicated by DIC decreased, the attributable in-hospital mortality rate due to DIC increased during the study period. We identified several predictors associated with the development of DIC in sepsis, some of which are potentially modifiable