Molecular Identification of Brucella Abortus Bv5 and Strain 19 in Water Buffaloes (Bubalus Bubalis) in Northeast Argentina

Buffalo (Bubalus bubalis) populations are spread across northern Argentina, and they share their habitat with bovines. Both species are susceptible to brucellosis, and they are under a National Plan of Control and Eradication. To characterize the Brucella spp. that infects buffaloes, the blood of 35 animals that tested positive to brucellosis by a complement fixation test was collected. DNA was obtained and analyzed by polymerase chain reaction using different molecular markers. The genera, species, and biovars of Brucella were established by analyzing specific regions of the genes omp31, eri, alkB, and omp2ab. Brucella spp. was identified in 15 of 35 tested buffaloes. The product of the omp31 gene identified the genera. The detection of two fragments of 297 bp and/or 1000 bp from the eri gene confirmed the presence of B. abortus S19 and wild-type B. abortus. The amplification of the alkB gene allowed the identification of B. abortus biovars characterized by fragments of 498 bp (bv1, bv2, or bv4). The simultaneous amplification of 498 bp (alkB) and 1000 bp (eri) products suggested the presence of B. abortus bv1, which is highly prevalent in the cattle of Argentina. Fragments of 827 bp and 857 bp were amplified from the omp2ab gene, and their sequences showed 100% identity with B. melitensis and B. abortus bv5 (GenBank). However, the 721 bp product (alkB) specific for B. melitensis could not be amplified. This is the first report indicating the presence of B. abortus bv5 in Latin America.Fil: Martinez, Diana. Universidad Nacional del Nordeste; ArgentinaFil: Thompson, Carolina. Instituto Nacional de Tecnologia Agropecuaria. Centro Regional Santa Fe. Estacion Experimental Agropecuaria Rafaela; ArgentinaFil: Russo, Ana Maria. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro de Investigaciones y Transferencia de Formosa; ArgentinaFil: Jacobo, Roberto. Universidad Nacional del Nordeste; ArgentinaFil: Torioni de Echaide, Susana. Instituto Nacional de Tecnologia Agropecuaria. Centro Regional Santa Fe. Estacion Experimental Agropecuaria Rafaela; Argentin

COST-EFFECTIVENESS ANALYSIS OF DIRECTLY OBSERVED THERAPY FOR TUBERCULOSIS AND ITS EXPANSION IN RIO DE JANEIRO

Objective: Brazil is one of the countries with the largest number of cases of tuberculosis worldwide; Rio de Janeiro exhibits some of highest mortality and incidence rates in the country. The aim of the present study was to perform a cost-effectiveness analysis of directly observed therapy (DOT) and simulate its expansion for new cases of pulmonary tuberculosis in Rio de Janeiro.Methods: A decision tree was plotted that simulated the progression of the disease for six months. In the cost-effectiveness analysis, strategies of self-administered treatment (SAT) and DOT (directly observed therapy) with 100% coverage were compared; the current coverage, 48%, and coverage of 100% were considered with regard to expansion. The study was based on the epidemiological pattern of tuberculosis in Rio de Janeiro among adults from both genders and without economic differences; the government perspective was adopted. The outcomes were varied to investigate the occurrence of parametric sensitivity.Results: Although the cost of treatment was increased by three times, DOT proved to be cost-effective for the treatment of new cases, with an incremental cost-effectiveness ratio (ICER) of BRL 30,454 per saved life. Expansion of DOT coverage would avert 180 deaths and 171 instances of treatment dropout, in addition to providing an additional 420 instances of cure, with an investment of approximately BRL 6,700,000.00.Conclusion: DOT might contribute to improving the current tuberculosis situation in the state of Rio de Janeiro. Its expansion would fit with the resources estimated by the Brazilian government needed to combat non-drug-resistant tuberculosis.Â

The Adverse Effects of Radiotherapy on the Structure of Dental Hard Tissues and Longevity of Dental Restoration

Purpose: The main goal of this study was to evaluate the impact of different ionizing radiation doses on the mineral (carbonate/phosphate ratio, crystallinity index [CI]) and organic (amide III/phosphate, amide I sub-band ratios) structures, as well as the microhardness, of enamel and dentin, along with their influence on the bonding strength stability of the etch-and-rinse (ER) and self-etch (SE) dental adhesive strategies. Materials and methods: Enamel and dentin human tissue specimens were irradiated (with 0, 20, 40, and 70 Gy radiation doses, respectively) and sectioned to perform an attenuated total reflection-Fourier transform IR spectroscopy assay (ATR-FTIR) and the Vickers microhardness (VHN) test to conduct a biochemical and biomechanical evaluation of the tissues. Regarding the adhesive properties, restored enamel and dentin specimens exposed to the same radiation doses were submitted to microshear bond strength (μSBS) tests for enamel in immediate time (IM) and to microtensile bond strength (μTBS) tests after for IM and 12-month (12 M) period of time, Mann–Whitney U tests were implemented, using the ATR-FTIR data for significant differences (α \u3c 0.05), and three- and two-way analyses of variance, along with post-testing, were performed on the μTBS and μSBS data (MPa), respectively (Tukey post hoc test at α = 0.05). Results: The ATR-FTIR results showed a significant decrease (p Conclusions: It is possible to conclude that structural alterations of enamel and dentin are generated by all radiation doses, decreasing the microhardness of dental hard tissues and influencing bond strength over time, starting at 40 Gy radiation dose. The etch-and-rinse strategy demonstrates better adhesive performance but generates cohesive fractures in the enamel

External validation of a convolutional neural network for the automatic segmentation of intraprostatic tumor lesions on 68Ga-PSMA PET images

Introduction: State of the art artificial intelligence (AI) models have the potential to become a "one-stop shop " to improve diagnosis and prognosis in several oncological settings. The external validation of AI models on independent cohorts is essential to evaluate their generalization ability, hence their potential utility in clinical practice. In this study we tested on a large, separate cohort a recently proposed state-of-the-art convolutional neural network for the automatic segmentation of intraprostatic cancer lesions on PSMA PET images.Methods: Eighty-five biopsy proven prostate cancer patients who underwent Ga-68 PSMA PET for staging purposes were enrolled in this study. Images were acquired with either fully hybrid PET/MRI (N = 46) or PET/CT (N = 39); all participants showed at least one intraprostatic pathological finding on PET images that was independently segmented by two Nuclear Medicine physicians. The trained model was available at and data processing has been done in agreement with the reference work.Results: When compared to the manual contouring, the AI model yielded a median dice score = 0.74, therefore showing a moderately good performance. Results were robust to the modality used to acquire images (PET/CT or PET/MRI) and to the ground truth labels (no significant difference between the model's performance when compared to reader 1 or reader 2 manual contouring).Discussion: In conclusion, this AI model could be used to automatically segment intraprostatic cancer lesions for research purposes, as instance to define the volume of interest for radiomics or deep learning analysis. However, more robust performance is needed for the generation of AI-based decision support technologies to be proposed in clinical practice

Prevalence and geographical distribution of bovine sexually transmitted diseases in the province of Formosa, Argentina

La campilobacteriosis genital bovina (CGB) y la tricomonosis bovina (TB) son enfermedades de transmisión sexual (ETS) que afectan a los rodeos de cría bovina y disminuyen su eficiencia reproductiva. El objetivo de este trabajo fue estimar la prevalencia de estas enfermedades y su distribución témporo-espacial en la provincia de Formosa, Argentina. El estudio fue transversal, se desarrolló durante 2018-2021 e incluyó 15.571 toros. Se encontró una prevalencia de CGB y TB inter-rodeo de 29,62 y 17,23%, respectivamente. La prevalencia de animales positivos fue de 2,05% para CGB y de 0,43% para TB. El análisis témporo-espacial de la CGB mostró dos agrupaciones espaciales, una de bajo riesgo (RR = 0,13; p < 0,001; 2018-2021) y otra de alto riesgo (RR = 2,84; p < 0,001; 2020-2021) de contraer la enfermedad. La TB presentó una agrupación de alto riesgo de contraer la enfermedad (RR = 35,24; p < 0,001; 2019). Este estudio muestra que las ETS son endémicas en la región y aporta información actualizada y de interés como herramienta para el manejo sanitario.Bovine genital campylobacteriosis (BGC) and bovine trichomonosis (BT) are sexually transmitted diseases (STDs) that affect bovine breeding herds, decreasing their reproductive efficiency. The objective of this work was to estimate the prevalence of these diseases and their temporal-spatial distribution in the province of Formosa, Argentina. The cross-sectional study conducted between 2018 and 2021 included a total of 15,571 bulls, inter-herd prevalence being 29.62% and 17.23% for BGC and BT, respectively. The prevalence of positive animals was 2.05% for BGC and 0.43% for BT. The temporal-spatial analysis of BGC showed two distinct spatial groupings, one group had a low risk of contracting the disease (RR = 0.13; p < 0.001; 2018–2021) while the other group had a high risk (RR = 2.84; p < 0.001; 2020–2021). BT had a high-risk group for the disease (RR = 35.24; p < 0.001; 2019). This study shows that STDs are endemic in the region, providing updated and valuable information as a tool for the health management of these diseases.Fil: Viola, María Nair. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de Investigaciones y Transferencia de Formosa. Provincia de Formosa. Centro de Investigaciones y Transferencia de Formosa. Universidad Nacional de Formosa. Centro de Investigaciones y Transferencia de Formosa; ArgentinaFil: Elías, Iris Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de Investigaciones y Transferencia de Formosa. Provincia de Formosa. Centro de Investigaciones y Transferencia de Formosa. Universidad Nacional de Formosa. Centro de Investigaciones y Transferencia de Formosa; ArgentinaFil: Signorini Porchietto, Marcelo Lisandro. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Instituto Nacional de Tecnología Agropecuaria. Centro Regional Santa Fe. Estación Experimental Agropecuaria Rafaela; ArgentinaFil: Molineri, Ana Inés. Instituto Nacional de Tecnología Agropecuaria. Centro Regional Santa Fe. Estación Experimental Agropecuaria Rafaela; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Russo, Ana Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de Investigaciones y Transferencia de Formosa. Provincia de Formosa. Centro de Investigaciones y Transferencia de Formosa. Universidad Nacional de Formosa. Centro de Investigaciones y Transferencia de Formosa; ArgentinaFil: Zimmer, Patricia Andrea. Instituto Nacional de Tecnologia Agropecuaria. Centro Regional Chaco-formosa. Estacion Experimental Agropecuaria El Colorado. Agencia de Extension Rural Formosa.; ArgentinaFil: Lozina, Laura Analía. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de Investigaciones y Transferencia de Formosa. Provincia de Formosa. Centro de Investigaciones y Transferencia de Formosa. Universidad Nacional de Formosa. Centro de Investigaciones y Transferencia de Formosa; ArgentinaFil: Giménez, Juana Noemí. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de Investigaciones y Transferencia de Formosa. Provincia de Formosa. Centro de Investigaciones y Transferencia de Formosa. Universidad Nacional de Formosa. Centro de Investigaciones y Transferencia de Formosa; Argentin

In the matter of the request of Liberty Mutual Fire Insurance Company, a Massachusetts domestic stock insurance company, to redomesticate to the state of Wisconsin

Submitted by Nuzia Santos ([email protected]) on 2018-08-24T16:36:28Z No. of bitstreams: 1 Phosphatidyl Inositol 3 Kinase-Gamma Balances.pdf: 10035595 bytes, checksum: 5a61fb2c618990d4314d36db3868ee2e (MD5)Approved for entry into archive by Nuzia Santos ([email protected]) on 2018-08-24T16:44:27Z (GMT) No. of bitstreams: 1 Phosphatidyl Inositol 3 Kinase-Gamma Balances.pdf: 10035595 bytes, checksum: 5a61fb2c618990d4314d36db3868ee2e (MD5)Made available in DSpace on 2018-08-24T16:44:27Z (GMT). No. of bitstreams: 1 Phosphatidyl Inositol 3 Kinase-Gamma Balances.pdf: 10035595 bytes, checksum: 5a61fb2c618990d4314d36db3868ee2e (MD5) Previous issue date: 2018Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Vírus Respiratórios e do Sarampo. Rio de Janeiro, RJ, Brazil / Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Bioquímica e Imunologia. Laboratório de Imunofarmacologia. Belo Horizonte, MG, Brazil.Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Bioquímica e Imunologia. Laboratório de Imunofarmacologia. Belo Horizonte, MG, Brazil / Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Fisiologia e Biofísica. Laboratório de Imunologia e Mecânica Pulmonar. Belo Horizonte, MG, Brazil.Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Bioquímica e Imunologia. Laboratório de Imunofarmacologia. Belo Horizonte, MG, Brazil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brazil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brazil / UNIFRANZ. Coordinación Nacional de Investigación. La Paz, Bolivia.Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Morfologia. Belo Horizonte, MG, BrazilUniversidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Bioquímica e Imunologia. Laboratório de Imunofarmacologia. Belo Horizonte, MG, Brazil.Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Bioquímica e Imunologia. Laboratório de Imunofarmacologia. Belo Horizonte, MG, Brazil / Universidade de São Paulo. Departamento de Farmacologia. Laboratório de Inflamação e Dor. Universidade de São Paulo. Ribeirão Preto, SP, Brazil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Vírus Respiratórios e do Sarampo. Rio de Janeiro, RJ, Brazil.Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Bioquímica e Imunologia. Laboratório de Imunofarmacologia. Belo Horizonte, MG, Brazil / Fundação Oswaldo Cruz. Instituto René Rachou. Laboratório de Imunologia de Doenças Virais. Belo Horizonte, MG, BrazilUniversidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Bioquímica e Imunologia. Laboratório de Imunofarmacologia. Belo Horizonte, MG, Brazil / Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Biologia Geral. Belo Horizonte, MG, Brazil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brazil.Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Bioquímica e Imunologia. Laboratório de RNA de Interferência Belo Horizonte, MG, Brazil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Vírus Respiratórios e do Sarampo. Rio de Janeiro, RJ, Brazil.Fundação Oswaldo Cruz. Instituto René Rachou. Laboratório de Imunologia de Doenças Virais. Belo Horizonte, MG, BrazilUniversidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Bioquímica e Imunologia. Laboratório de Imunofarmacologia. Belo Horizonte, MG, Brazil / Universidade Federal de Minas Gerais. Faculdade de Farmácia. Departamento de Análises Clínicas e Toxicológicas. Belo Horizonte, MG, Brazil.Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Bioquímica e Imunologia. Laboratório de Imunofarmacologia. Belo Horizonte, MG, Brazil / Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Fisiologia e Biofísica. Laboratório de Imunologia e Mecânica Pulmonar. Belo Horizonte, MG, Brazil.Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Bioquímica e Imunologia. Laboratório de Imunofarmacologia. Belo Horizonte, MG, Brazil.Influenza A virus (IAV) infection causes severe pulmonary disease characterized by intense leukocyte infiltration. Phosphoinositide-3 kinases (PI3Ks) are central signaling enzymes, involved in cell growth, survival, and migration. Class IB PI3K or phosphatidyl inositol 3 kinase-gamma (PI3Kγ), mainly expressed by leukocytes, is involved in cell migration during inflammation. Here, we investigated the contribution of PI3Kγ for the inflammatory and antiviral responses to IAV. PI3Kγ knockout (KO) mice were highly susceptible to lethality following infection with influenza A/WSN/33 H1N1. In the early time points of infection, infiltration of neutrophils was higher than WT mice whereas type-I and type-III IFN expression and p38 activation were reduced in PI3Kγ KO mice resulting in higher viral loads when compared with WT mice. Blockade of p38 in WT macrophages infected with IAV reduced levels of interferon-stimulated gene 15 protein to those induced in PI3Kγ KO macrophages, suggesting that p38 is downstream of antiviral responses mediated by PI3Kγ. PI3Kγ KO-derived fibroblasts or macrophages showed reduced type-I IFN transcription and altered pro-inflammatory cytokines suggesting a cell autonomous imbalance between inflammatory and antiviral responses. Seven days after IAV infection, there were reduced infiltration of natural killer cells and CD8+ T lymphocytes, increased concentration of inflammatory cytokines in bronchoalveolar fluid, reduced numbers of resolving macrophages, and IL-10 levels in PI3Kγ KO. This imbalanced environment in PI3Kγ KO-infected mice culminated in enhanced lung neutrophil infiltration, reactive oxygen species release, and lung damage that together with the increased viral loads, contributed to higher mortality in PI3Kγ KO mice compared with WT mice. In humans, we tested the genetic association of disease severity in influenza A/H1N1pdm09-infected patients with three potentially functional PIK3CG single-nucleotide polymorphisms (SNPs), rs1129293, rs17847825, and rs2230460. We observed that SNPs rs17847825 and rs2230460 (A and T alleles, respectively) were significantly associated with protection from severe disease using the recessive model in patients infected with influenza A(H1N1)pdm09. Altogether, our results suggest that PI3Kγ is crucial in balancing antiviral and inflammatory responses to IAV infection

Impacto da infecção puerperal nos indicadores de mortalidade materna: uma revisão da literatura

O presente artigo busca demonstrar que a infecção puerperal é uma das principais causas de mortalidade materna e são marcadas por sintomas associados à infecção como dor pélvica, febre, corrimento vaginal anormal e/ou com odor fétido e atraso na involução uterina. Além disso, existem vários fatores de risco como extremos de idade materna, IMC elevado, presença de doenças sexualmente transmissíveis, vaginose bacteriana, hipertensão, diabetes, deficiências imunológicas e confirmação de infecção pelo Streptococcus pyogenes do grupo B (tabela 01). O tipo de parto também é um ponto relevante de se observar, uma vez que as mulheres que são submetidas à cesárea estão em maior risco. As infecções puerperais são responsáveis por 10 a 15% dos óbitos maternos em todo mundo, mesmo sendo muitas vezes prevenível. Assim é imprescindível estabelecer estratégias para diminuição desse quadro. Considerando as principais opções de tratamento, temos ressuscitação volêmica e controle do foco de infecção. Nessa perspectiva, percebe-se a necessidade da triagem pré-natal, higiene adequada durante o parto e cuidados pós-parto. Entretanto, no que concerne aos índices de mortalidade materna associados à infecção puerperal, carece-se da identificação precoce e tratamento imediato no intuito de evitar complicações mais graves e reduzir a mortalidade materna relacionada a elas

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Zika Virus Impairs Neurogenesis and Synaptogenesis Pathways in Human Neural Stem Cells and Neurons

Growing evidences have associated Zika virus (ZIKV) infection with congenital malformations, including microcephaly. Nonetheless, signaling mechanisms that promote the disease outcome are far from being understood, affecting the development of suitable therapeutics. In this study, we applied shotgun mass spectrometry (MS)-based proteomics combined with cell biology approaches to characterize altered molecular pathways on human neuroprogenitor cells (NPC) and neurons derived from induced pluripotent stem cells infected by ZIKV-BR strain, obtained from the 2015 Brazilian outbreak. Furthermore, ZIKV-BR infected NPCs showed unique alteration of pathways involved in neurological diseases, cell death, survival and embryonic development compared to ZIKV-AF, showing a human adaptation of the Brazilian viral strain. Besides, infected neurons differentiated from NPC presented an impairment of neurogenesis and synaptogenesis processes. Taken together, these data explain that CNS developmental arrest observed in Congenital Zika Syndrome is beyond neuronal cell death