Multidisciplinary analysis of a mummy from the War of the Pacific.

The War of the Pacific (1879-1884) was a big scale war between Chile against the alliance of Peru and Bolivia. One of the most important battles, the "Batalla del Campo de la Alianza" was situated in the desert near Tacna, Peru. The conditions of this environment favored the conservation of the dead soldiers after many years. Decades ago, the Natural History Museum of Concepción in Chile, received a naturally mummified individual of a probably Chilean soldier as a donation; its uncertain context was never studied nor confirmed. Considering this, our investigation analyzed this body under exploratory methods, ballistic analysis, archaeological contrast, 14C radiocarbon dating, ancient DNA, and isotopic analysis to reconstruct the biological profile of this mummy. The results indicated that the mummy belongs to an adult man between 33-39 years of age (> 1.50 m) and has a perimortem wound in the left flank of the abdomen. CT scan and X-rays revealed the presence of a bullet (Comblain II or Gras) hosted near the L2 vertebra. It is possible that the individual died of bleeding from a gunshot wound done by a long-distance firearm projectile from an inferior level, whose trajectory was from left to right, with slight inclination towards the top, and without a projectile exit. Other analyses confirmed the historical context and suggests the Chilean origin of the mummy. Despite the passage of time and other factors, it was possible to reconstruct the death of this individual thanks to technology and approaches from different disciplines.

A new methodology to estimate flat foot in skeletal remains - the example of Mediterranean collections.

Flat feet (pes planus) are considered a postural defect caused by the collapse of the longitudinal arch, producing complete or near-complete contact of the sole of the foot with the ground. Pes planus has been well-studied in clinical literature and paleoanthropology but has not been approached extensively in bioarchaeology. The main difficulty is related to the diagnosis of this pathology based exclusively on bone remains. In this work, we propose a metric and morphological method to discriminate flat foot in dry bones. Thus, we studied 390 pairs of adult feet in a fair state of preservation from archaeological contexts from Spain, Italy, and Oman. Morphological variability, angles, and dimensions of both the normal bones and the bones displaying flat foot characteristics were analyzed. We found a correlation between the presence of flat foot and some morphological and metric features, mainly in the subtalar and Chopart joints. These results are expressed through a combination of morphological and metric variables, which are useful to discriminate between these two groups. No markedly significant differences of flat foot frequencies between the Spanish and Italian series were found across centuries. However, we noticed a notable increase of the prevalence of flat foot in the contemporary collection, possibly due to the consequences of a rise in life expectancy and modern styles of footwear.

Loss of MICOS complex integrity and mitochondrial damage, but not TDP-43 mitochondrial localisation, are likely associated with severity of CHCHD10-related diseases.

Following the involvement of CHCHD10 in FrontoTemporal-Dementia-Amyotrophic Lateral Sclerosis (FTD-ALS) clinical spectrum, a founder mutation (p.Gly66Val) in the same gene was identified in Finnish families with late-onset spinal motor neuronopathy (SMAJ). SMAJ is a slowly progressive form of spinal muscular atrophy with a life expectancy within normal range. In order to understand why the p.Ser59Leu mutation, responsible for severe FTD-ALS, and the p.Gly66Val mutation could lead to different levels of severity, we compared their effects in patient cells. Unlike affected individuals bearing the p.Ser59Leu mutation, patients presenting with SMAJ phenotype have neither mitochondrial myopathy nor mtDNA instability. The expression of CHCHD10S59L mutant allele leads to disassembly of mitochondrial contact site and cristae organizing system (MICOS) with mitochondrial dysfunction and loss of cristae in patient fibroblasts. We also show that G66V fibroblasts do not display the loss of MICOS complex integrity and mitochondrial damage found in S59L cells. However, S59L and G66V fibroblasts show comparable accumulation of phosphorylated mitochondrial TDP-43 suggesting that the severity of phenotype and mitochondrial damage do not depend on mitochondrial TDP-43 localization. The expression of the CHCHD10G66V allele is responsible for mitochondrial network fragmentation and decreased sensitivity towards apoptotic stimuli, but with a less severe effect than that found in cells expressing the CHCHD10S59L allele. Taken together, our data show that cellular phenotypes associated with p.Ser59Leu and p.Gly66Val mutations in CHCHD10 are different; loss of MICOS complex integrity and mitochondrial dysfunction, but not TDP-43 mitochondrial localization, being likely essential to develop a severe motor neuron disease.

Disrupted in schizophrenia 1 (DISC1) is a constituent of the mammalian mitochondrial contact site and cristae organizing system (MICOS) complex, and is essential for oxidative phosphorylation.

Disrupted in Schizophrenia-1 (DISC1) has been associated with a broad spectrum of mental disorders. DISC1 is a multi-compartmentalized protein found in the cytoplasm, centrosome, nuclei and mostly enriched in mitochondria. In order to shed light on DISC1 mitochondrial function, we have studied its topology within the organelle. We show in here that in mammals DISC1 resides in the 'Mitochondrial contact site and Cristae Organizing system' (MICOS) complex, involved in cristae organization. DISC1 knockdown in SH-SY5Y cells causes MICOS disassembly and fragmentation of the mitochondrial morphology network. Moreover, DISC1 depleted cells have decreased mitochondrial DNA (mtDNA) content and steady state levels of oxidative phosphorylation (OXPHOS) subunits. As a consequence, OXPHOS complexes and supercomplexes are partially disassembled in DISC1 knockdown cells, which suffer severe bioenergetic defects, evidenced by impaired oxygen consumption, adenosine triphosphate synthesis and mitochondrial membrane potential. Transfection of recombinant full-length human DISC1 restores MICOS complex assembly and rescues OXPHOS function, meanwhile overexpression of the DISC1 truncated form Δ597-854, known to be pathogenic, fails to rescue the bioenergetic impairment caused by DISC1 knockdown. These results should contribute to reveal DISC1 physiological function and potential pathogenic role in severe mental illnesses.

CHCHD10 mutations promote loss of mitochondrial cristae junctions with impaired mitochondrial genome maintenance and inhibition of apoptosis.

CHCHD10-related diseases include mitochondrial DNA instability disorder, frontotemporal dementia-amyotrophic lateral sclerosis (FTD-ALS) clinical spectrum, late-onset spinal motor neuropathy (SMAJ), and Charcot-Marie-Tooth disease type 2 (CMT2). Here, we show that CHCHD10 resides with mitofilin, CHCHD3 and CHCHD6 within the "mitochondrial contact site and cristae organizing system" (MICOS) complex. CHCHD10 mutations lead to MICOS complex disassembly and loss of mitochondrial cristae with a decrease in nucleoid number and nucleoid disorganization. Repair of the mitochondrial genome after oxidative stress is impaired in CHCHD10 mutant fibroblasts and this likely explains the accumulation of deleted mtDNA molecules in patient muscle. CHCHD10 mutant fibroblasts are not defective in the delivery of mitochondria to lysosomes suggesting that impaired mitophagy does not contribute to mtDNA instability. Interestingly, the expression of CHCHD10 mutant alleles inhibits apoptosis by preventing cytochrome c release.

Predisposing, reinforcing, and enabling factors influencing influenza vaccination acceptance among healthcare workers.

According to the present case-control study about influenza vaccine acceptance among hospital workers, vaccination campaigns should focus mainly on predisposing and enabling factors, emphasizing the likelihood of acquiring influenza and the positive benefits to patients, addressing concerns about vaccine efficacy or safety, and minimizing the time required for the worker to undergo vaccination.

¿Mejora la calidad con la implantación de centros de salud? Una visión desde la hospitalización evitable / Does the development of primary healthcare centers improve quality? The perspective of avoidable hospitalizations

Objetivo: Las hospitalizaciones evitables (HE) son un conjunto de diagnósticos en los que una atención primaria de salud efectiva y adecuada hubiera evitado su ingreso hospitalario. Por tanto, su control sirve como medida del nivel de calidad obtenido en los centros de salud. Pacientes y método: Se realizó un estudio prospectivo individual de todos los pacientes ingresados (1999-2000) en un hospital procedentes de 2 zonas, una con un modelo tradicional de atención primaria (consultorio) y otro con un modelo moderno de centro de salud. El período de seguimiento fue de 2 años. A los pacientes que ingresaron se les pasó una encuesta. Para el estudio se empleó un listado de códigos de HE ya utilizado en otros trabajos. Resultados: La población del consultorio tuvo un 22 por ciento más riesgo de HE ajustado por morbilidad que la correspondiente del centro de salud. La incidencia anual poblacional fue de 10 por 1.000 habitantes. El factor más influyente para la HE fue ser atendido en un consultorio (RRa = 3,3), seguido por ser varón y tener un nivel económico bajo (RRa = 2,8), las edades extremas de la vida (joven y tercera) y la poca accesibilidad del centro (RRa = 2,2). También influyeron, aunque de forma más moderada, la estancia hospitalaria prolongada. No influyó el nivel de satisfacción de los pacientes. Conclusiones: Se demuestra que, conforme se mejoran los centros de atención primaria pasando al nuevo modelo, se reduce el riesgo de HE (AU)