Veterans’ experiences of patient-centered care: Learning from guided tours

In this paper the authors seek to examine Veterans’ experiences with patient-centered care (PCC) at 2 United States Veterans Affairs (VA) facilities. The authors conduct their research through a process of guided tours, in which the participant leads the evaluator through an environment and shares thoughts, feelings, and experiences. Tours were conducted in April 2013 with 30 Veterans receiving care at these VA facilities. Via the tours participants discussed aspects of the environment of care, and described some as ‘welcoming,’ while describing others as ‘chaotic.’ Participants provided multiple examples of PCC, frequently defining PCC in terms of accessibility of appointments, continuity and familiarity with providers, and shared decision-making and communication. They highlighted that their identity as Veterans influenced their preferences for care, including efficiency, need for compassion, and consideration of mental and social health needs. Some suggested VA expand upon this idea of shared identity by creating a ‘Veteran community,’ and including increased opportunities for socialization with other Veterans, and access to the arts. The authors conclude that the impact of shared identity on care preferences has received limited attention in the literature; further, the impact of identity may be unique to Veterans, who represent not only a group of patients being seen at the same facilities, but a social group with shared history and characteristics, as well. These results can be utilized to expand implementation of PCC innovations, to improve health and well-being of Veterans

The Role of MAPKs in B Cell Receptor-Induced Down-Regulation of Egr-1 in Immature B Lymphoma Cells

Cross-linking of the B cell receptor (BCR) on the immature B lymphoma cell line BKS-2 induces growth inhibition and apoptosis accompanied by rapid down-regulation of the immediate-early gene egr-1. In these lymphoma cells, egr-1 is expressed constitutively and has a prosurvival role, as Egr-1-specific antisense oligonucleotides or expression of a dominant-negative inhibitor of Egr-1 also prevented the growth of BKS-2 cells. Moreover, enhancement of Egr-1 protein with phorbol 12-myristate 13-acetate or an egr-1 expression vector rescued BKS-2 cells from BCR signal-induced growth inhibition. Nuclear run-on and mRNA stability assays indicated that BCR-derived signals act at the transcriptional level to reduce egr-1 expression. Inhibitors of ERK and JNK (but not of p38 MAPK) reduced egr-1 expression at the protein level. Transcriptional regulation appears to have a role because egr-1 promoter-driven luciferase expression was reduced by ERK and JNK inhibitors. Promoter truncation experiments suggested that several serum response elements are required for MAPK-mediated egr-1 expression. Our study suggests that BCR signals reduce egr-1 expression by inhibiting activation of ERK and JNK. Unlike ERK and JNK, p38 MAPK reduces constitutive expression of egr-1. Unlike the immature B lymphoma cells, normal immature B cells did not exhibit constitutive MAPK activation. BCR-induced MAPK activation was modest and transient with a small increase in egr-1 expression in normal immature B cells consistent with their inability to proliferate in response to BCR cross-linking

TNIK Regulation of Interferon Signaling and Endothelial Cell Response to Virus Infection

BACKGROUND: Traf2 and Nck-interacting kinase (TNIK) is known for its regulatory role in various processes within cancer cells. However, its role within endothelial cells (ECs) has remained relatively unexplored. METHODS: Leveraging RNA-seq data and Ingenuity Pathway Analysis (IPA), we probed the potential impact of TNIK depletion on ECs. RESULTS: Examination of RNA-seq data uncovered more than 450 Differentially Expressed Genes (DEGs) in TNIK-depleted ECs, displaying a fold change exceeding 2 with a false discovery rate (FDR) below 0.05. IPA analysis unveiled that TNIK depletion leads to the inhibition of the interferon (IFN) pathway [-log ( SUMMARY: Our findings suggest that TNIK plays a crucial role in regulating the EC response to virus infections through modulation of the IFN pathway

Endothelial activation and fibrotic changes are impeded by laminar flow-induced CHK1-SENP2 activity through mechanisms distinct from endothelial-to-mesenchymal cell transition

Background: The deSUMOylase sentrin-specific isopeptidase 2 (SENP2) plays a crucial role in atheroprotection. However, the phosphorylation of SENP2 at T368 under disturbed flow (D-flow) conditions hinders its nuclear function and promotes endothelial cell (EC) activation. SUMOylation has been implicated in D-flow-induced endothelial-to-mesenchymal transition (endoMT), but the precise role of SENP2 in counteracting this process remains unclear. Method: We developed a phospho-specific SENP2 S344 antibody and generated knock-in (KI) mice with a phospho-site mutation of SENP2 S344A using CRISPR/Cas9 technology. We then investigated the effects of SENP2 S344 phosphorylation under two distinct flow patterns and during hypercholesteremia (HC)-mediated EC activation. Result: Our findings demonstrate that laminar flow (L-flow) induces phosphorylation of SENP2 at S344 through the activation of checkpoint kinase 1 (CHK1), leading to the inhibition of ERK5 and p53 SUMOylation and subsequent suppression of EC activation. We observed a significant increase in lipid-laden lesions in both the aortic arch (under D-flow) and descending aorta (under L-flow) of female hypercholesterolemic SENP2 S344A KI mice. In male hypercholesterolemic SENP2 S344A KI mice, larger lipid-laden lesions were only observed in the aortic arch area, suggesting a weaker HC-mediated atherogenesis in male mice compared to females. Ionizing radiation (IR) reduced CHK1 expression and SENP2 S344 phosphorylation, attenuating the pro-atherosclerotic effects observed in female SENP2 S344A KI mice after bone marrow transplantation (BMT), particularly in L-flow areas. The phospho-site mutation SENP2 S344A upregulates processes associated with EC activation, including inflammation, migration, and proliferation. Additionally, fibrotic changes and up-regulated expression of EC marker genes were observed. Apoptosis was augmented in ECs derived from the lungs of SENP2 S344A KI mice, primarily through the inhibition of ERK5-mediated expression of DNA damage-induced apoptosis suppressor (DDIAS). Summary: In this study, we have revealed a novel mechanism underlying the suppressive effects of L-flow on EC inflammation, migration, proliferation, apoptosis, and fibrotic changes through promoting CHK1-induced SENP2 S344 phosphorylation. The phospho-site mutation SENP2 S344A responds to L-flow through a distinct mechanism, which involves the upregulation of both mesenchymal and EC marker genes

Endothelial Activation and Fibrotic Changes Are Impeded by Laminar Flow-Induced CHK1-SENP2 Activity Through Mechanisms Distinct From Endothelial-To-Mesenchymal Cell Transition

BACKGROUND: The deSUMOylase sentrin-specific isopeptidase 2 (SENP2) plays a crucial role in atheroprotection. However, the phosphorylation of SENP2 at T368 under disturbed flow (D-flow) conditions hinders its nuclear function and promotes endothelial cell (EC) activation. SUMOylation has been implicated in D-flow-induced endothelial-to-mesenchymal transition (endoMT), but the precise role of SENP2 in counteracting this process remains unclear. METHOD: We developed a phospho-specific SENP2 S344 antibody and generated knock-in (KI) mice with a phospho-site mutation of SENP2 S344A using CRISPR/Cas9 technology. We then investigated the effects of SENP2 S344 phosphorylation under two distinct flow patterns and during hypercholesteremia (HC)-mediated EC activation. RESULT: Our findings demonstrate that laminar flow (L-flow) induces phosphorylation of SENP2 at S344 through the activation of checkpoint kinase 1 (CHK1), leading to the inhibition of ERK5 and p53 SUMOylation and subsequent suppression of EC activation. We observed a significant increase in lipid-laden lesions in both the aortic arch (under D-flow) and descending aorta (under L-flow) of female hypercholesterolemic SENP2 S344A KI mice. In male hypercholesterolemic SENP2 S344A KI mice, larger lipid-laden lesions were only observed in the aortic arch area, suggesting a weaker HC-mediated atherogenesis in male mice compared to females. Ionizing radiation (IR) reduced CHK1 expression and SENP2 S344 phosphorylation, attenuating the pro-atherosclerotic effects observed in female SENP2 S344A KI mice after bone marrow transplantation (BMT), particularly in L-flow areas. The phospho-site mutation SENP2 S344A upregulates processes associated with EC activation, including inflammation, migration, and proliferation. Additionally, fibrotic changes and up-regulated expression of EC marker genes were observed. Apoptosis was augmented in ECs derived from the lungs of SENP2 S344A KI mice, primarily through the inhibition of ERK5-mediated expression of DNA damage-induced apoptosis suppressor (DDIAS). SUMMARY: In this study, we have revealed a novel mechanism underlying the suppressive effects of L-flow on EC inflammation, migration, proliferation, apoptosis, and fibrotic changes through promoting CHK1-induced SENP2 S344 phosphorylation. The phospho-site mutation SENP2 S344A responds to L-flow through a distinct mechanism, which involves the upregulation of both mesenchymal and EC marker genes

Clostridium difficile is not associated with outbreaks of viral gastroenteritis in the elderly in the Netherlands

The coincidental increase in norovirus outbreaks and Clostridium difficile infection (CDI) raised the question of whether these events could be related, e.g. by enhancing spread by diarrhoeal disease outbreaks. Therefore, we studied the prevalence of C. difficile in outbreaks of viral gastroenteritis in nursing homes for the elderly and characterised enzyme immunoassay (EIA)-positive stool samples. Stool samples from nursing home residents (n = 752) in 137 outbreaks of viral aetiology were investigated by EIA for the presence of C. difficile toxins. Positive samples were further tested by a cell neutralisation cytotoxicity test, a second EIA and culture. Cultured isolates were tested for the presence of toxin genes, the production of toxins and characterised by 16S rRNA polymerase chain reaction (PCR) and sequencing. Twenty-four samples (3.2%) tested positive in the EIA. Of these 24 positive samples, only two were positive by cytotoxicity and three by a second EIA. Bacterial culture of 21 available stool samples yielded a toxinogenic C. difficile PCR ribotype 001 in one patient sample only. In conclusion, we found no evidence in this retrospective study for an association between viral gastroenteritis outbreaks and C. difficile. The high rate of false-positive EIA samples emphasises the need for second confirmation tests to diagnose CDI

Amazon Basin forest pyrogenic carbon stocks: First estimate of deep storage

Amazon Basin forest soils contain considerable soil organic carbon stocks; however, the contribution of soil pyrogenic carbon (PyC) to the total is unknown. PyC is derived from local fires (historical and modern) and external inputs via aeolian deposition. To establish an initial estimate of PyC stocks in non-terra preta forest with no known history of fire, to assess site and vertical variability, as well as to determine optimal sampling design, we sampled 37 one hectare forest plots in the Amazon Basin and analysed PyC via hydrogen pyrolysis of three individual samples per plot and of bulked samples to 200 cm depth. Using our data and published total organic carbon stocks, we present the first field-based estimate of total PyC stock for the Amazon Basin of 1.10 Pg over 0–30 cm soil depth, and 2.76 Pg over 0–100 cm soil depth. This is up to 20 times higher than previously assumed. Three individual samples per 1 ha are sufficient to capture the site variability of PyC in our plots. PyC showed significant, large-scale variability among plots. To capture 50% of the PyC in 200 cm soil profiles, soil must be sampled to a depth of at least 71 cm. PyC represents a significant (11%) portion of total organic carbon in soil profiles 0–200 cm depth. This finding highlights the potentially important role that historical fire has played in modifying soil C stocks. Our data suggest that PyC is an important carbon pool for long-term storage, involved in millennial scale biogeochemical cycling, particularly in the subsurface soil

Tracking the spatial diffusion of influenza and norovirus using telehealth data: A spatiotemporal analysis of syndromic data

Background: Telehealth systems have a large potential for informing public health authorities in an early stage of outbreaks of communicable disease. Influenza and norovirus are common viruses that cause significant respiratory and gastrointestinal disease worldwide. Data about these viruses are not routinely mapped for surveillance purposes in the UK, so the spatial diffusion of national outbreaks and epidemics is not known as such incidents occur. We aim to describe the geographical origin and diffusion of rises in fever and vomiting calls to a national telehealth system, and consider the usefulness of these findings for influenza and norovirus surveillance. Methods: Data about fever calls (5- to 14-year-old age group) and vomiting calls (≥ 5-year-old age group) in school-age children, proxies for influenza and norovirus, respectively, were extracted from the NHS Direct national telehealth database for the period June 2005 to May 2006. The SaTScan space-time permutation model was used to retrospectively detect statistically significant clusters of calls on a week-by-week basis. These syndromic results were validated against existing laboratory and clinical surveillance data. Results: We identified two distinct periods of elevated fever calls. The first originated in the North-West of England during November 2005 and spread in a south-east direction, the second began in Central England during January 2006 and moved southwards. The timing, geographical location, and age structure of these rises in fever calls were similar to a national influenza B outbreak that occurred during winter 2005–2006. We also identified significantly elevated levels of vomiting calls in South-East England during winter 2005–2006. Conclusion: Spatiotemporal analyses of telehealth data, specifically fever calls, provided a timely and unique description of the evolution of a national influenza outbreak. In a similar way the tool may be useful for tracking norovirus, although the lack of consistent comparison data makes this more difficult to assess. In interpreting these results, care must be taken to consider other infectious and non-infectious causes of fever and vomiting. The scan statistic should be considered for spatial analyses of telehealth data elsewhere and will be used to initiate prospective geographical surveillance of influenza in England.

DarkCideS 1.0, a global database for bats in karsts and caves

Tanalgo, Krizler C., Tabora, John Aries G., de Oliveira, Hernani Fernandes Magalhães, Haelewaters, Danny, Beranek, Chad T., Otálora-Ardila, Aída, Bernard, Enrico, Gonçalves, Fernando, Eriksson, Alan, Donnelly, Melissa, González, Joel Monzón, Ramos, Humberto Fernández, Rivas, Alberto Clark, Webala, Paul W., Deleva, Stanimira, Dalhoumi, Ridha, Maula, Jaycelle, Lizarro, Dennis, Aguirre, Luis F., Bouillard, Nils, Quibod, Ma. Niña Regina M., Barros, Jennifer, Turcios-Casco, Manfredo Alejandro, Martínez, Marcio, Ordoñez-Mazier, Diego Iván, Orellana, José Alejandro Soler, Ordoñez-Trejo, Eduardo J., Ordoñez, Danny, Chornelia, Ada, Lu, Jian Mei, Xing, Chen, Baniya, Sanjeev, Muylaert, Renata L., Dias-Silva, Leonardo Henrique, Ruadreo, Nittaya, Hughes, Alice Catherine (2022): DarkCideS 1.0, a global database for bats in karsts and caves. Scientific Data 9 (1): 155, DOI: 10.1038/s41597-022-01234-4, URL: http://dx.doi.org/10.1038/s41597-022-01234-