Network Physiology reveals relations between network topology and physiological function

The human organism is an integrated network where complex physiologic systems, each with its own regulatory mechanisms, continuously interact, and where failure of one system can trigger a breakdown of the entire network. Identifying and quantifying dynamical networks of diverse systems with different types of interactions is a challenge. Here, we develop a framework to probe interactions among diverse systems, and we identify a physiologic network. We find that each physiologic state is characterized by a specific network structure, demonstrating a robust interplay between network topology and function. Across physiologic states the network undergoes topological transitions associated with fast reorganization of physiologic interactions on time scales of a few minutes, indicating high network flexibility in response to perturbations. The proposed system-wide integrative approach may facilitate the development of a new field, Network Physiology.Comment: 12 pages, 9 figure

Comparison of ultrasonography with computed tomography in the diagnosis of incisional hernias

Background: The objective of this study is to determine the reliability and validity of ultrasonography (US) in diagnosing incisional hernias in comparison with computed tomography (CT). The CT scans were assessed by two radiologists in order to estimate the inter-observer variation and twice by one radiologist to estimate the intra-observer variation. Patients were evaluated after reconstruction for an abdominal aortic aneurysm or an aortoiliac occlusion. Methods: Patients with a midline incision after undergoing reconstruction of an abdominal aortic aneurysm or aortoiliac occlusion were examined by CT scanning and US. Two radiologists evaluated the CT scans independently. One radiologist examined the CT scans twice. Discrepancies between the CT observations were resolved in a common evaluation session between the two radiologists. Results: After a mean follow-up of 3.4 years, 40 patients were imaged after a reconstructed abdominal aortic aneurysm (80% of the patients) or aortoiliac occlusion. The prevalence of incisional hernias was 24/ 40 = 60.0% with CT scanning as the diagnostic modality and 17/40 = 42.5% with US. The measure of agreement between CT scanning and US expressed as a Kappa statistic was 0.66 (95% confidence interval [CI] 0.45-0.88). The sensitivity of US examination when using CT as a comparison was 70.8%, the specificity was 100%, the predictive value of a positive US was 100%, and the predictive value of a negative US was 69.6%. The likelihood ratio of a positive US was infinite and that of a negative US was 0.29. The inter- and intra-observer Kappa statistics were 0.74 (CI 0.54-0.95) and 0.80 (CI 0.62-0.99), respectively. Conclusions: US imaging has a moderate sensitivity and negative predictive value, and a very good specificity and positive predictive value. Consistency of diagnosis, as determined by calculating the inter- and intra-observer Kappa statistics, was good. The incidence of incisional hernias is high after aortic reconstructions

Social representations and community attitudes towards spring breakers

Social representations theory has been adopted for explaining tourism impacts and local attitudes. However, its usefulness in segmenting local population in terms of their attitudes towards specific types of tourists has not been tested. This study identifies the attitudes of local people towards spring break, a North American young tourist phenomenon in the context of the Mexican beach resort of Acapulco. Although residents perceive an increase in alcohol consumption, drug use, noise and litter during the spring break season, they largely recognise economic benefits and are thus generally supportive for the phenomenon. Based on these attitudes, three clusters were identified: spring break supporters (identified by their high appreciation of spring break benefits), ambivalents (who are uncertain about both benefits and costs) and realistics (characterised by recognising both benefits and costs). The main contribution of this study lies in the confirmation of the usefulness of social representations theory in explaining residents’ attitudes towards a very specific type of tourists whose hedonist behaviours are a common characteristic

“Provide care for everyone please”: Engaging Community Leaders as Sexual and Reproductive Health Advocates in North and South Kivu, Democratic Republic of Congo

Background: Inadequate infrastructure, security threats from ongoing armed conflict, and conservative socio-cultural and gender norms that favour large families and patriarchal power structures contribute to poor sexual and reproductive health (SRH) outcomes in North and South Kivu provinces, Democratic Republic of the Congo (DRC). In order to expand contraceptive and post-abortion care (PAC) access in North and South Kivu, CARE, the International Rescue Committee and Save the Children provided technical support to the Ministry of Health and health facilities in these regions. Partners acknowledged that community leaders, given their power to influence local customs, could play a critical role as agents of change in addressing inequitable gender norms, stigma surrounding SRH service utilization, and topics traditionally considered taboo within Congolese society. As such, partners actively engaged with community leaders through a variety of activities such as community mapping exercises, values clarification and transformation (VCAT) activities, situational analyses, and education. Methods: This manuscript presents findings from 12 key informant interviews (KIIs) with male political and non-political community leaders conducted in six rural health zones of North and South Kivu, DRC. Transcripts were analysed thematically to explore community leaders’ perceptions of their role in addressing the issue of unintended pregnancy in their communities. Results: While community leaders in this study expressed overall positive impressions of contraception and strong support for ensuring access to PAC services following spontaneous and induced abortions, the vast majority held negative beliefs concerning women who had induced abortion. Contrasting with their professed opposition to induced abortion, leaders’ commitment to mediating interpersonal conflict arising between community members and women who had abortions was overwhelming. Conclusion: Results from this study suggest that when thoughtfully engaged by health interventions, community leaders can be empowered to become advocates for SRH. While study participants were strong supporters of contraception and PAC, they expressed negative perceptions of induced abortion. Given the hypothesized link between the presence of induced abortion stigma and care-avoidance behavior, further engagement and values clarification exercises with leaders must be integrated into community mobilization and engagement activities in order to increase PAC utilization

Role of A2A adenosine receptors in regulation of opsonized E. coli-induced macrophage function

Adenosine is a biologically active molecule that is formed at sites of metabolic stress associated with trauma and inflammation, and its systemic level reaches high concentrations in sepsis. We have recently shown that inactivation of A2A adenosine receptors decreases bacterial burden as well as IL-10, IL-6, and MIP-2 production in mice that were made septic by cecal ligation and puncture (CLP). Macrophages are important in both elimination of pathogens and cytokine production in sepsis. Therefore, in the present study, we questioned whether macrophages are responsible for the decreased bacterial load and cytokine production in A2A receptor-inactivated septic mice. We showed that A2A KO and WT peritoneal macrophages obtained from septic animals were equally effective in phagocytosing opsonized E. coli. IL-10 production induced by opsonized E. coli was decreased in macrophages obtained from septic A2A KO mice as compared to WT counterparts. In contrast, the release of IL-6 and MIP-2 induced by opsonized E. coli was higher in septic A2A KO macrophages than WT macrophages. These results suggest that peritoneal macrophages are not responsible for the decreased bacterial load and diminished MIP-2 and IL-6 production that are observed in septic A2A KO mice. In contrast, peritoneal macrophages may contribute to the suppressive effect of A2A receptor inactivation on IL-10 production during sepsis

Enteric Infection with Citrobacter rodentium Induces Coagulative Liver Necrosis and Hepatic Inflammation Prior to Peak Infection and Colonic Disease

Acute and chronic forms of inflammation are known to affect liver responses and susceptibility to disease and injury. Furthermore, intestinal microbiota has been shown critical in mediating inflammatory host responses in various animal models. Using C. rodentium, a known enteric bacterial pathogen, we examined liver responses to gastrointestinal infection at various stages of disease pathogenesis. For the first time, to our knowledge, we show distinct liver pathology associated with enteric infection with C. rodentium in C57BL/6 mice, characterized by increased inflammation and hepatitis index scores as well as prominent periportal hepatocellular coagulative necrosis indicative of thrombotic ischemic injury in a subset of animals during the early course of C. rodentium pathogenesis. Histologic changes in the liver correlated with serum elevation of liver transaminases, systemic and liver resident cytokines, as well as signal transduction changes prior to peak bacterial colonization and colonic disease. C. rodentium infection in C57BL/6 mice provides a potentially useful model to study acute liver injury and inflammatory stress under conditions of gastrointestinal infection analogous to enteropathogenic E. coli infection in humans.United States. Army Research Office (Institute for Soldier Nanotechnology grant 6915539 (SRT))National Institutes of Health (U.S.) (Grant P01 CA026731)National Institutes of Health (U.S.) (Grant P30 ES02109)National Institutes of Health (U.S.) (Toxicology Training grant ES-070220

“They Love Their Patients”: Client Perceptions of Quality of Postabortion Care in North and South Kivu, the Democratic Republic of the Congo

Background: Postabortion care (PAC) is a lifesaving intervention that, when accessible and of good quality, can prevent the majority of abortion-related deaths. However, these services are only sporadically available and often of poor quality in humanitarian settings. CARE International, the International Rescue Committee, and Save the Children strengthened the Congolese Ministry of Health to provide PAC, including voluntary contraceptive services, in North and South Kivu, DRC. Objective: We aimed to gain understanding of the demographic and clinical characteristics of PAC clients, the experiences of women who sought PAC at supported health facilities, and the women’s perceptions of the quality of care received. We also explored how client perspectives can inform future PAC programming. Methods: A PAC register review extracted sociodemographic and clinical data on all PAC clients during a 12-month period between 2015 and 2016 at 69 supported facilities in 6 health zones. In-depth interviews were conducted between September 2016 and April 2017 with 50 women who sought PAC in the preceding 3 months at supported health facilities. Interviews were recorded, transcribed, and translated into French for analysis. Thematic content analysis was subsequently used as the data analytic approach. Results: In 12 months, 1,769 clients sought PAC at supported facilities; 85.2% were at less than 13 weeks gestation. Over 80% of PAC clients had a uterine evacuation, and of these, 90% were treated with manual vacuum aspiration. The majority (75.2%) of PAC clients chose voluntary postabortion contraception. All but one interview participant reported seeking PAC for a spontaneous abortion, although most also reported their pregnancy was unintended. Clients were mostly made aware that PAC was available by community health workers or other community members. Experiences at the supported facilities were mostly positive, particularly in regards to client-provider interactions. Most women received contraceptive counseling during PAC and selected a modern method of contraception immediately after treatment. However, knowledge about different methods of contraception varied. Nearly all women said that they would advise another woman experiencing abortion complications to seek PAC at a supported health facility. Conclusions: The findings demonstrate the successful implementation of good-quality, respectful PAC in North and South Kivu. Overall, they suggest that the organizations’ support of health workers, including competency-based training and supportive supervision, was successful

Trauma Hemorrhagic Shock-Induced Lung Injury Involves a Gut-Lymph-Induced TLR4 Pathway in Mice

Injurious non-microbial factors released from the stressed gut during shocked states contribute to the development of acute lung injury (ALI) and multiple organ dysfunction syndrome (MODS). Since Toll-like receptors (TLR) act as sensors of tissue injury as well as microbial invasion and TLR4 signaling occurs in both sepsis and noninfectious models of ischemia/reperfusion (I/R) injury, we hypothesized that factors in the intestinal mesenteric lymph after trauma hemorrhagic shock (T/HS) mediate gut-induced lung injury via TLR4 activation.The concept that factors in T/HS lymph exiting the gut recreates ALI is evidenced by our findings that the infusion of porcine lymph, collected from animals subjected to global T/HS injury, into naïve wildtype (WT) mice induced lung injury. Using C3H/HeJ mice that harbor a TLR4 mutation, we found that TLR4 activation was necessary for the development of T/HS porcine lymph-induced lung injury as determined by Evan's blue dye (EBD) lung permeability and myeloperoxidase (MPO) levels as well as the induction of the injurious pulmonary iNOS response. TRIF and Myd88 deficiency fully and partially attenuated T/HS lymph-induced increases in lung permeability respectively. Additional studies in TLR2 deficient mice showed that TLR2 activation was not involved in the pathology of T/HS lymph-induced lung injury. Lastly, the lymph samples were devoid of bacteria, endotoxin and bacterial DNA and passage of lymph through an endotoxin removal column did not abrogate the ability of T/HS lymph to cause lung injury in naïve mice.Our findings suggest that non-microbial factors in the intestinal mesenteric lymph after T/HS are capable of recreating T/HS-induced lung injury via TLR4 activation

Management of intra-abdominal infections : recommendations by the WSES 2016 consensus conference

This paper reports on the consensus conference on the management of intra-abdominal infections (IAIs) which was held on July 23, 2016, in Dublin, Ireland, as a part of the annual World Society of Emergency Surgery (WSES) meeting. This document covers all aspects of the management of IAIs. The Grading of Recommendations Assessment, Development and Evaluation recommendation is used, and this document represents the executive summary of the consensus conference findings.Peer reviewe