Altered relationship between body fat and plasma adiponectin in end-stage renal disease

Patients with end-stage renal disease (ESRD) show an inverse association between body mass index and risk of death from cardiovascular disease. Paradoxical epidemiology may suggest some beneficial effects of body fat in ESRD. Because an antiatherogenic adipocytokine adiponectin is increased in uremic plasma, we tested a hypothesis that, in ESRD, plasma adipocytokine profile may be less atherogenic or that the relationship between body fat and adipocytokines may be altered. The subjects were 103 patients with ESRD undergoing hemodialysis and 166 healthy subjects comparable in age and sex. We measured body fat mass by dual-energy x-ray absorptiometry and plasma levels of adiponectin and leptin by enzyme-linked immunosorbent assay. The ESRD group showed a significant increase in plasma adiponectin, leptin, and adiponectin/leptin ratio than the healthy subjects. Although sex and fat mass were significant factors correlating with plasma adiponectin level in the healthy group, none of these were significantly associated with plasma adiponectin in the patients with ESRD. In contrast, leptin showed significant relationships with sex and fat mass regardless of the presence of ESRD. Plasma adiponectin correlated negatively with plasma triglycerides and positively with high-density lipoprotein cholesterol in both healthy and ESRD groups, suggesting that uremic adiponectin retains its actions in favor of its antiatherogenicity. Thus, plasma adipocytokine profile was altered in ESRD, and the effects of body fat and sex on adiponectin were less significant in the patients with ESRD.     

Lectin-like oxidized LDL receptor-1 is a cell-adhesion molecule involved in endotoxin-induced inflammation

Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) is a major endothelial receptor for oxidized low-density lipoprotein, and is assumed to play a proatherogenic role in atherosclerosis. LOX-1 expression is induced by inflammatory cytokines as well as by proatherogenic stimuli. LOX-1 protein binds agedapoptotic cells, activated platelets, and bacteria, suggesting that it may have diverse activities in vivo. Here, we reveal a role for LOX-1 in endotoxin-induced inflammation. In a model of endotoxemia, injection of a high dose of endotoxin into rats induced leukopenia within 1 h and death of the animals within 24 h. Preadministration of anti-LOX-1 antibody reduced the degree of leukopenia and completely rescued the animals, whereas control IgG did not. In a model of low-dose endotoxin-induced uveitis, anti-LOX-1 antibody efficiently suppressed leukocyte infiltration and protein exudation. In situ videomicroscopic analyses of leukocyte interactions with retinal veins revealed that anti-LOX-1 antibody reduced the number of rolling leukocytes and increased the velocity of rolling, suggesting that LOX-1 functions as a vascular tethering ligand. The ability of LOX-1 to capture leukocytes under physiologic shear was confirmed in an in vitro flow model. Thus, LOX-1 is an adhesion molecule involved in leukocyte recruitment and may represent an attractive target for modulation of endotoxin-induced inflammation.     

Calcium deposition in photocrosslinked poly(Pro‐Hyp‐Gly) hydrogels encapsulated rat bone marrow stromal cells

Reproducing the features of the extracellular matrix is important for fabricating three‐dimensional (3D) scaffolds for tissue regeneration. A collagen‐like polypeptide, poly(Pro‐Hyp‐Gly), is a promising material for 3D scaffolds because of its excellent physical properties, biocompatibility, and biodegradability. In this paper, we present a novel photocrosslinked poly(Pro‐Hyp‐Gly) hydrogel as a 3D scaffold for simultaneous rat bone marrow stromal cell (rBMSC) encapsulation. The hydrogels were fabricated using visible‐light photocrosslinking at various concentrations of methacrylated poly(Pro‐Hyp‐Gly) (20–50 mg/ml) and irradiation times (3 or 5 min). The results show that the rBMSCs encapsulated in the hydrogels survived 7 days of incubation. Calcium deposition on the encapsulated rBMSCs was assessed with scanning electron microscope observation, Alizarin Red S, and von Kossa staining. The most strongly stained area was observed in the hydrogel formed with 30 mg/ml of methacrylated poly(Pro‐Hyp‐Gly) with 5‐min irradiation. These findings demonstrate that poly(Pro‐Hyp‐Gly) hydrogels support rBMSC viability and differentiation, as well as demonstrating the feasibility of using poly(Pro‐Hyp‐Gly) hydrogels as a cytocompatible, biodegradable 3D scaffold for tissue regeneration.     

Molecular epidemiologic study of Clostridium difficile infections in university hospitals: Results of a nationwide study in Japan

We conducted a nationwide molecular epidemiological study of Clostridium difficile infection (CDI) in Japan investigated the correlation between the presence of binary toxin genes and CDI severity. This is the first report on molecular epidemiological analyses for CDI in multiple university hospitals in Japan, to our knowledge. We examined 124,484 hospitalized patients in 25 national and public university hospitals in Japan between December 2013 and March 2014, investigating antimicrobial susceptibilities and toxin-related genes for C. difficile isolates from stools. Epidemiological genetic typing was performed by PCR-ribotyping and repetitive sequence-based (rep)-PCR to examine the genetic similarities. The results detected toxin A-positive, toxin B-positive, binary toxin-negative (A⁺B⁺CDT^?) detected from 135 isolates (80.8%) and toxin A-negative, toxin B-positive, binary toxin-negative (A^??B⁺CDT^?) in 23 (13.8%). Toxin A-positive, toxin B-positive, and binary toxin-positive (A⁺B⁺CDT⁺) were seen in 9 isolates (5.4%). Vancomycin (n = 81, 37.7%) or metronidazole (n = 88, 40.9%) therapies were undertaken in analyzed cases. Ribotypes detected from isolates were 017/subgroup 1, 070, 078, 126, 176, 449, 475/subgroup 1, 499, 451, 566 and newtypes. Rep-PCR classified 167 isolates into 28 cluster groups including 2–15 isolates. In addition, 2 pairs of strains isolated from different institutions belonged to the same clusters. Seven out of 9 (77.8%) of the patients with binary toxin producing strains had “mild to moderate” outcome in evaluated symptoms. In conclusion, we found that binary toxin did not show regional specificity and had no relevance to severity of CDI.     

Content-Driven Analysis of an Online Community for Smoking Cessation: Integration of Qualitative Techniques,Automated Text Analysis,and Affiliation Networks

Objectives. We identified content-specific patterns of network diffusion underlying smoking cessation in the context of online platforms, with the aim of generating targeted intervention strategies.Methods. QuitNet is an online social network for smoking cessation. We analyzed 16 492 de-identified peer-to-peer messages from 1423 members, posted between March 1 and April 30, 2007. Our mixed-methods approach comprised qualitative coding, automated text analysis, and affiliation network analysis to identify, visualize, and analyze content-specific communication patterns underlying smoking behavior.Results. Themes we identified in QuitNet messages included relapse, QuitNet-specific traditions, and cravings. QuitNet members who were exposed to other abstinent members by exchanging content related to interpersonal themes (e.g., social support, traditions, progress) tended to abstain. Themes found in other types of content did not show significant correlation with abstinence.Conclusions. Modeling health-related affiliation networks through content-driven methods can enable the identification of specific content related to higher abstinence rates, which facilitates targeted health promotion.Epidemiological evidence indicates that modifiable risky health behaviors place a substantial socioeconomic burden on human health and wellness.1 Understanding human behavior in real-time settings is essential to improving health outcomes related to these behaviors.2,3 Technological advances in connectivity offer the means to obtain potentially valuable data sets in the form of electronic traces of the activities of online social communities. These data may help us to understand the intra- and interindividual intricacies of health-related behaviors. Studies of online and offline social networks provide valuable insight into social influence, information spread, and behavioral diffusion.4–6 Most of these analyses have paid more attention to the frequency of communication between members than to its content. The content, however, is relevant to behavior change theories, which address the use of specialized content to stimulate and support individuals to achieve a desired change.7,8 Contemporary work on social media data rarely addresses this fundamental concern of behavior change theorists.Outside the context of online networks, several theories have been formulated to explain behavior change. Some, such as the Transtheoretical Model,9 belong to the intrapersonal category; others, such as Social Cognitive Theory10 and social network and support models,11 are classified as interpersonal. (Appendix A, available as a supplement to the online version of this article at http://www.ajph.org, provides an overview of the theoretical constructs.) Empirical research on the applicability of these models to behavior change of health consumers in the digital era is minimal.12 Recent research showed that participation in health issue–specific social networking sites significantly influenced social factors such as identification, perceived subjective norms, and social support, which in turn resulted in greater smoking cessation self-efficacy.13 Content inclusion in analytical models of social networks can enable us to examine the content-specific patterns of social factors underlying behavior change. Through mapping of the specific content to theories, such content inclusion can facilitate the development of network interventions for health behavior changes by harnessing the power of social relationships.Studies of QuitNet, an online social network for smoking cessation, have examined the structure of peer-to-peer communication patterns and provided insights into social integrators and opinion leaders.5,14 Previous work showed the applicability of affiliation networks to real-world diffusion networks, enriching our understanding of the affiliation-based sources of influence on individuals’ behavior. Examples include the diffusion of (1) ratification of the World Health Organization Framework Convention on Tobacco Control by comembership with an online forum among countries15; (2) gunshot victimization by co-offending with victims among Chicago, Illinois, gangsters16; (3) substance use by coparticipating in school-sponsored sports or co-identifying with the same crowd types17,18; and (4) sexual behavior by coaffiliating with venues among male sex workers.19We used affiliation networks to analyze messages for content-specific patterns of network diffusion. We took an interdisciplinary approach, integrating methods from sociobehavioral sciences, social network analytics, and biomedical informatics. We employed qualitative techniques derived from grounded theory, automated text analysis, and affiliation network analysis to investigate the communication patterns underlying human behavior in online environments. Our study had 3 major components: (1) a qualitative study of human communication within user-generated data in QuitNet, (2) computational text analysis to further extend this analysis, and (3) identification of communication patterns pertinent to behavior change in affiliation networks. We anticipate that the insights gained from this research will enhance our understanding of behavior change and will have implications for the design of sociobehavioral interventions that draw upon social influence.     

Venue-Mediated Weak Ties in Multiplex HIV Transmission Risk Networks Among Drug-Using Male Sex Workers and Associates

Objectives. We investigated the structural characteristics of a multiplex HIV transmission risk network of drug-using male sex workers and their associates.Methods. Using a sample of 387 drug-using male sex workers and their male and female associates in Houston, Texas, we estimated an exponential random graph model to examine the venue-mediated relationships between individuals, the structural characteristics of relationships not linked to social venues, and homophily. We collected data in 2003 to 2004. The network comprised social, sexual, and drug-using relationships and affiliations with social venues.Results. Individuals affiliated with the same social venues, bars, or street intersections were more likely to have nonreciprocated (weak) ties with others. Sex workers were less likely than were other associates to have reciprocated (strong) ties to other sex workers with the same venues. Individuals tended to have reciprocated ties not linked to venues. Partner choice tended to be predicated on homophily.Conclusions. Social venues may provide a milieu for forming weak ties in HIV transmission risk networks centered on male sex workers, which may foster the efficient diffusion of prevention messages as diverse information is obtained and information redundancy is avoided.Sex work increases the risk of contracting and transmitting HIV and other sexually transmitted infections through unprotected sexual behaviors or substance use.1 Male sex workers (MSWs) experience high rates of HIV infection, both globally and domestically.2–4 In North America, HIV prevalence among MSWs is estimated to range from 5% to 31%.4 MSWs have high rates of risky sexual behavior and substance use, including drug injection.5–7 However, public health issues related to MSWs have been understudied, and current HIV prevention programs underserve MSWs.4MSWs are not homogeneous nor are the contexts of male sex work uniform.4,8 Because male sex work takes diverse forms in a variety of contexts,8,9 HIV risks may also vary by context. MSWs who solicit sex on the streets are at high risk for HIV infection, and the context of the street may increase the risk. MSWs working in street venues are more likely to have few financial resources, be undereducated, live in unstable housing or on the streets, be unemployed or disabled, and engage in sex work as a means of survival.8 Numerous MSWs and their clients self-identify as heterosexual.10 Men who have sex with men and women (MSMW) have higher rates of both transactional sex and concurrent illicit drug use and sex than do men who have sex with men only, and, among MSMW, both transactional sex and concurrent illicit drug use predict risky sexual behavior.11Although sociodemographic characteristics, HIV infection, and risk behaviors of MSWs have been documented,12,13 relatively few studies have provided a relational account of HIV risk within male sex work networks. It is known, for example, that networks of MSWs are connected to networks of other high-risk groups.2,8,10,14,15 Through these network ties, MSWs may bridge with men who have sex with men (MSM), female sex workers, drug users, and other less risky groups.2,16 MSMW are more likely to engage in sex for drugs or money than are other MSM, and MSMW occupy a central position in the network of HIV-infected males.17 However, because of the diversity of male sex work, it may be inappropriate to conceptualize MSWs as a core group.18Social networks are the structures within which norms are developed and implemented and social support occurs.19,20 Most risk-potential linkages within networks are social,20 and sex ties are often formed through social circles.21 MSWs form unique social networks,9,22 most likely involving risky drug-use and sexual behaviors. The networks are often hierarchical structures in which network leaders control areas for soliciting sex, and the network structure provides mutual support for soliciting sex.9Rarely do studies on HIV risk networks that involve MSWs regard the network as composed of “persons, places, and the relevant links connecting them.”23^(p684) Social venues are an important part of the network structure, forming the setting for MSWs’ social life and facilitating the formation of “sexual affiliation networks.”24 Our previous study25 underscored the duality of people and places26 by focusing on affiliation networks between MSWs and social venues. We found centralized affiliation patterns around a small number of highly interdependent venues. Although interdependent, the venues presented distinct patterns of venue-based clustering.25 These findings, however, were limited because the study focused on venue affiliation. Non–venue-based direct ties also may be important because they are expected to occur within social, drug-using, and sexual relationships. These types of relationships may have different emotional and interpersonal contexts27 that would tend to result in different patterns and types of ties.We defined a multiplex transmission risk network as composed of multifaceted social contexts that comprise a mix of social, sexual, and drug-using ties and affiliation ties to social venues. The social network perspective informs relational mechanisms of information diffusion and social influence at the entire network and personal network levels. Granovettor’s theory of the strength of weak ties posits, “The weak tie between ego and his acquaintance, therefore, becomes not merely a trivial acquaintance tie but rather a crucial bridge between the two densely knit clumps of close friends.”28^(p202) Weak ties avoid information redundancy by enabling individuals to access diverse information and to facilitate the diffusion of information throughout the entire network.29 Although weak ties facilitate information diffusion, they may not be sufficiently powerful to change behavior because of the ties’ transient and passive nature.Rarely have network studies focused on the role that affiliation ties play in forming direct ties between individuals. We defined venue-mediated weak or strong ties as 1-mode social, sexual, and drug-using ties formed through jointly affiliating in the same venues. We examined and statistically tested local relational features of venue-mediated weak or strong ties among MSWs and their associates. On the basis of the effect of bar-based social influence interventions led by opinion leaders on HIV risk reduction,30,31 HIV prevention messages disseminated within venues are expected to facilitate the diffusion of information, and, thus, weak ties are more likely than are strong ties to be observed linked to social venues.In personal networks, reciprocated ties suggest higher levels of trust and intimacy and, in some cases, a strong tendency to engage in risky behaviors.32 The risk of engaging in behaviors that transmit HIV are also heightened during sex for money exchanges, particularly if there is a strong economic incentive for doing so. This suggests that risk is related to the multiple types of ties determined by context. Additionally, homophily affects network ties by influencing the information that people receive, the attitudes formed, and the social interactions experienced.33 We also sought to examine the tendency of reciprocity and the effect of homophily on HIV status and sociodemographic and behavioral factors when forming risk-potential relationships that comprise social, sexual, or drug-using ties but are not linked to social venues. The likelihood of engaging in risk-taking behavior is greater in relationships with a high degree of homophily, as information flows and persuasion tend to be more frequent among like pairs.32 We tested these relational features using a stochastic network modeling approach.     

Next-Generation Sequencing-Based Molecular Diagnosis of Choroideremia

We screened patients with choroideremia using next-generation sequencing (NGS) and identified a novel mutation and a known mutation in the CHM gene. One patient presented an atypical fundus appearance for choroideremia. Another patient presented macular hole retinal detachment in the left eye. The present case series shows the utility of NGS-based screening in patients with choroideremia. In addition, the presence of macular hole in 1 of the 2 patients, together with a previous report, indicated the susceptibility of patients with choroideremia to macular hole.Key Words: Choroideremia, Next-generation sequencing, Diagnosis, Utility     

Transbronchial Cryobiopsy for Miliary Tuberculosis Mimicking Hypersensitivity Pneumonitis

Miliary tuberculosis is a potentially lethal type of tuberculosis that results from the hematogenous dissemination of Mycobacterium tuberculosis bacilli. We herein describe the case of a 34-year-old man that presented with a one-month history of cough and fever, while his sputum smear results were negative. Chest computed tomography revealed bilateral centrilobular ground-glass opacification (GGO), suggestive of hypersensitivity pneumonitis; thus, bronchoscopy was performed. Cryobiopsy specimens revealed necrotic granulomas. A re-examination of sputum after bronchoscopy identified Mycobacterium tuberculosis, and miliary tuberculosis was diagnosed. A cryobiopsy might be useful for diagnosing miliary tuberculosis pathologically, particularly when miliary nodules may be masked by GGO.