On the feasibility of the computational modelling of the endoluminal vacuum-assisted closure of an oesophageal anastomotic leakage

Endoluminal vacuum-assisted closure (E-VAC) is a promising therapy to treat anastomotic leakages of the oesophagus and bowel which are associated with high morbidity and mortality rates. An open-pore polyurethane foam is introduced into the leakage cavity and connected to a device that applies a suction pressure to accelerate the closure of the defect. Computational analysis of this healing process can advance our understanding of the biomechanical mechanisms at play. To this aim, we use a dual-stage finite-element analysis in which (i) the structural problem addresses the cavity reduction caused by the suction and (ii) a new constitutive formulation models tissue healing via permanent deformations coupled to a stiffness increase. The numerical implementation in an in-house code is described and a qualitative example illustrates the basic characteristics of the model. The computational model successfully reproduces the generic closure of an anastomotic leakage cavity, supporting the hypothesis that suction pressure promotes healing by means of the aforementioned mechanisms. However, the current framework needs to be enriched with empirical data to help advance device designs and treatment guidelines. Nonetheless, this conceptual study confirms that computational analysis can reproduce E-VAC of anastomotic leakages and establishes the bases for better understanding the mechanobiology of anastomotic defect healing

APOE4 allele-specific associations between diet, multimodal biomarkers, and cognition among Puerto Rican adults in Massachusetts

BackgroundApolipoprotein E (APOE) is the strongest genetic risk factor for sporadic Alzheimer’s Disease (AD), and the ε4 allele (APOE4) may interact with lifestyle factors that relate to brain structural changes, underlying the increased risk of AD. However, the exact role of APOE4 in mediating interactions between the peripheral circulatory system and the central nervous system, and how it may link to brain and cognitive aging requires further elucidation. In this analysis, we investigated the association between APOE4 carrier status and multimodal biomarkers (diet, blood markers, clinical diagnosis, brain structure, and cognition) in the context of gene–environment interactions.MethodsParticipants were older adults from a longitudinal observational study, the Boston Puerto Rican Health Study (BPRHS), who self-identified as of Puerto Rican descent. Demographics, APOE genotype, diet, blood, and clinical data were collected at baseline and at approximately 12th year, with the addition of multimodal brain magnetic resonance imaging (MRI) (T1-weighted and diffusion) and cognitive testing acquired at 12-year. Measures were compared between APOE4 carriers and non-carriers, and associations between multimodal variables were examined using correlation and multivariate network analyses within each group.ResultsA total of 156 BPRHS participants (mean age at imaging = 68 years, 77% female, mean follow-up 12.7 years) with complete multimodal data were included in the current analysis. APOE4 carriers (n = 43) showed reduced medial temporal lobe (MTL) white matter (WM) microstructural integrity and lower mini-mental state examination (MMSE) score than non-carriers (n = 113). This pattern was consistent with an independent sample from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) of n = 283 non-Hispanic White adults without dementia (mean age = 75, 40% female). Within BPRHS, carriers showed distinct connectivity patterns between multimodal biomarkers, characterized by stronger direct network connections between baseline diet/blood markers with 12-year blood/clinical measures, and between blood markers (especially lipids and cytokines) and WM. Cardiovascular burden (i.e., hypertension and diabetes status) was associated with WM integrity for both carriers and non-carriers.ConclusionAPOE4 carrier status affects interactions between dietary factors, multimodal blood biomarkers, and MTL WM integrity across ~12 years of follow-up, which may reflect increased peripheral-central systems crosstalk following blood–brain barrier breakdown in carriers

Pkd1 Haploinsufficiency Increases Renal Damage and Induces Microcyst Formation following Ischemia/Reperfusion

Mutations in PKD1 cause the majority of cases of autosomal dominant polycystic kidney disease (ADPKD). Because polycystin 1 modulates cell proliferation, cell differentiation, and apoptosis, its lower biologic activity observed in ADPKD might influence the degree of injury after renal ischemia/reperfusion. We induced renal ischemia/reperfusion in 10- to 12-wk-old male noncystic Pkd1+/− and wild-type mice. Compared with wild-type mice, heterozygous mice had higher fractional excretions of sodium and potassium and higher serum creatinine after 48 h. In addition, in heterozygous mice, also cortical damage, rates of apoptosis, and inflammatory infiltration into the interstitium at time points out to 14 d after injury all increased, as well as cell proliferation at 48 h and 7 d. The mRNA and protein expression of p21 was lower in heterozygous mice than wild-type mice at 48 h. After 6 wk, we observed dilated tubules, microcysts, and increased renal fibrosis in heterozygotes. The early mortality of heterozygotes was significantly higher than that of wild-type mice when we extended the duration of ischemia from 32 to 35 min. In conclusion, ischemia/reperfusion induces a more severe injury in kidneys of Pkd1-haploinsufficient mice, a process that apparently depends on a relative deficiency of p21 activity, tubular dilation, and microcyst formation. These data suggest the possibility that humans with ADPKD from PKD1 mutations may be at greater risk for damage from renal ischemia/reperfusion injury

Table_1_APOE4 allele-specific associations between diet, multimodal biomarkers, and cognition among Puerto Rican adults in Massachusetts.DOCX

BackgroundApolipoprotein E (APOE) is the strongest genetic risk factor for sporadic Alzheimer’s Disease (AD), and the ε4 allele (APOE4) may interact with lifestyle factors that relate to brain structural changes, underlying the increased risk of AD. However, the exact role of APOE4 in mediating interactions between the peripheral circulatory system and the central nervous system, and how it may link to brain and cognitive aging requires further elucidation. In this analysis, we investigated the association between APOE4 carrier status and multimodal biomarkers (diet, blood markers, clinical diagnosis, brain structure, and cognition) in the context of gene–environment interactions.MethodsParticipants were older adults from a longitudinal observational study, the Boston Puerto Rican Health Study (BPRHS), who self-identified as of Puerto Rican descent. Demographics, APOE genotype, diet, blood, and clinical data were collected at baseline and at approximately 12th year, with the addition of multimodal brain magnetic resonance imaging (MRI) (T1-weighted and diffusion) and cognitive testing acquired at 12-year. Measures were compared between APOE4 carriers and non-carriers, and associations between multimodal variables were examined using correlation and multivariate network analyses within each group.ResultsA total of 156 BPRHS participants (mean age at imaging = 68 years, 77% female, mean follow-up 12.7 years) with complete multimodal data were included in the current analysis. APOE4 carriers (n = 43) showed reduced medial temporal lobe (MTL) white matter (WM) microstructural integrity and lower mini-mental state examination (MMSE) score than non-carriers (n = 113). This pattern was consistent with an independent sample from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) of n = 283 non-Hispanic White adults without dementia (mean age = 75, 40% female). Within BPRHS, carriers showed distinct connectivity patterns between multimodal biomarkers, characterized by stronger direct network connections between baseline diet/blood markers with 12-year blood/clinical measures, and between blood markers (especially lipids and cytokines) and WM. Cardiovascular burden (i.e., hypertension and diabetes status) was associated with WM integrity for both carriers and non-carriers.ConclusionAPOE4 carrier status affects interactions between dietary factors, multimodal blood biomarkers, and MTL WM integrity across ~12 years of follow-up, which may reflect increased peripheral-central systems crosstalk following blood–brain barrier breakdown in carriers.</p

''Super-Spreaders'' and Person-to-Person Transmission of Andes Virus in Argentina

BACKGROUND From November 2018 through February 2019, person-to-person transmission of Andes virus (ANDV) hantavirus pulmonary syndrome occurred in Chubut Province, Argentina, and resulted in 34 confirmed infections and 11 deaths. Understanding the genomic, epidemiologic, and clinical characteristics of person-to-person transmission of ANDV is crucial to designing effective interventions. METHODS Clinical and epidemiologic information was obtained by means of patient report and from public health centers. Serologic testing, contact-tracing, and next-generation sequencing were used to identify ANDV infection as the cause of this outbreak of hantavirus pulmonary syndrome and to reconstruct person-to-person transmission events. RESULTS After a single introduction of ANDV from a rodent reservoir into the human population, transmission was driven by 3 symptomatic persons who attended crowded social events. After 18 cases were confirmed, public health officials enforced isolation of persons with confirmed cases and self-quarantine of possible contacts; these measures most likely curtailed further spread. The median reproductive number (the number of secondary cases caused by an infected person during the infectious period) was 2.12 before the control measures were enforced and decreased to 0.96 after the measures were implemented. Full genome sequencing of the ANDV strain involved in this outbreak was performed with specimens from 27 patients and showed that the strain that was present (Epuyén/18–19) was similar to the causative strain (Epilink/96) in the first known person-to-person transmission of hantavirus pulmonary syndrome caused by ANDV, which occurred in El Bolsón, Argentina, in 1996. Clinical investigations involving patients with ANDV hantavirus pulmonary syndrome in this outbreak revealed that patients with a high viral load and liver injury were more likely than other patients to spread infection. Disease severity, genomic diversity, age, and time spent in the hospital had no clear association with secondary transmission. CONCLUSIONS Among patients with ANDV hantavirus pulmonary syndrome, high viral titers in combination with attendance at massive social gatherings or extensive contact among persons were associated with a higher likelihood of transmission.Fil: Martinez, Valeria Paula. Dirección Nacional de Instituto de Investigación.Administración Nacional de Laboratorios e Institutos de Salud "Dr. Carlos G. Malbrán"; ArgentinaFil: Di Paola, Nicholas. Centers For Disease Control And Prevention. National Center For Infectious Diseases; Estados UnidosFil: Alonso, Daniel Oscar. Dirección Nacional de Instituto de Investigación.Administración Nacional de Laboratorios e Institutos de Salud "Dr. Carlos G. Malbrán"; ArgentinaFil: Pérez Sautu, Unai. Centers For Disease Control And Prevention. National Center For Infectious Diseases; Estados UnidosFil: Bellomo, Carla María. Dirección Nacional de Instituto de Investigación.Administración Nacional de Laboratorios e Institutos de Salud "Dr. Carlos G. Malbrán"; ArgentinaFil: Iglesias, Ayelén Aluminé. Dirección Nacional de Instituto de Investigación.Administración Nacional de Laboratorios e Institutos de Salud "Dr. Carlos G. Malbrán"; ArgentinaFil: Coelho, Rocío María. Dirección Nacional de Instituto de Investigación.Administración Nacional de Laboratorios e Institutos de Salud "Dr. Carlos G. Malbrán"; ArgentinaFil: López, Beatriz. Dirección Nacional de Instituto de Investigación.Administración Nacional de Laboratorios e Institutos de Salud "Dr. Carlos G. Malbrán"; ArgentinaFil: Periolo, Natalia. Dirección Nacional de Instituto de Investigación.Administración Nacional de Laboratorios e Institutos de Salud "Dr. Carlos G. Malbrán"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Larson, Peter A.. Centers For Disease Control And Prevention. National Center For Infectious Diseases; Estados UnidosFil: Nagle, Elyse R.. Centers For Disease Control And Prevention. National Center For Infectious Diseases; Estados UnidosFil: Chitty, Joseph A.. Centers For Disease Control And Prevention. National Center For Infectious Diseases; Estados UnidosFil: Pratt, Catherine B.. Centers For Disease Control And Prevention. National Center For Infectious Diseases; Estados Unidos. University of Nebraska; Estados UnidosFil: Díaz, Jorge Daniel. Provincia del Chubut. Ministerio de Salud; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte; ArgentinaFil: Cisterna, Daniel Marcelo. Dirección Nacional de Instituto de Investigación.Administración Nacional de Laboratorios e Institutos de Salud "Dr. Carlos G. Malbrán"; ArgentinaFil: Campos, Josefina. Dirección Nacional de Instituto de Investigación.Administración Nacional de Laboratorios e Institutos de Salud "Dr. Carlos G. Malbrán"; ArgentinaFil: Sharma, Heema. National Institutes of Health; Estados UnidosFil: Dighero Kemp, Bonnie. National Institutes of Health; Estados UnidosFil: Biondo, Emiliano. Provincia del Chubut. Ministerio de Salud; ArgentinaFil: Lewis, Lorena. Provincia del Chubut. Ministerio de Salud; ArgentinaFil: Anselmo, Constanza. Provincia del Chubut. Ministerio de Salud; ArgentinaFil: Olivera, Camila P.. Provincia del Chubut. Ministerio de Salud; ArgentinaFil: Pontoriero, Fernanda. Ministerio de Salud ; Gobierno de la Provincia de Rio Negro;Fil: Lavarra, Enzo. Provincia del Chubut. Ministerio de Salud; ArgentinaFil: Kuhn, Jens H.. National Institutes of Health; Estados UnidosFil: Strella, Teresa. Provincia del Chubut. Ministerio de Salud; ArgentinaFil: Edelstein, Alexis. Dirección Nacional de Institutos de Investigación. Administración Nacional de Laboratorios e Institutos de Salud. Instituto Nacional de Enfermedades Infecciosas; ArgentinaFil: Burgos, Miriam I.. Ministerio de Salud de la Nación; ArgentinaFil: Kaler, Mario. Ministerio de Salud de la Nación; ArgentinaFil: Rubinstein, Adolfo Luis. Ministerio de Salud de la Nación; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Kugelman, Jeffrey R.. Centers For Disease Control And Prevention. National Center For Infectious Diseases; Estados UnidosFil: Sanchez Lockhart, Mariano. Centers For Disease Control And Prevention. National Center For Infectious Diseases; Estados Unidos. University of Nebraska; Estados UnidosFil: Perandones, Claudia. Dirección Nacional de Instituto de Investigación.Administración Nacional de Laboratorios e Institutos de Salud "Dr. Carlos G. Malbrán"; ArgentinaFil: Palacios, Gustavo Guido. Centers For Disease Control And Prevention. National Center For Infectious Diseases; Estados Unido