Miracle-dz/UniFAR-FTUs huggingface dataset:
Cytotoxins of the human pathogen Aeromonas hydrophila trigger, via the NLRP3 inflammasome, caspase‐1 activation in macrophages

Aeromonas hydrophila is a Gram‐negative pathogen that causes serious infectious disease in humans. A. hydrophila induces apoptosis in infected macrophages, but the host proinflammatory responses triggered by macrophage death are largely unknown. Here, we demonstrate that the infection of mouse macrophages with A. hydrophila triggers the activation of caspase‐1 and release of IL‐1β. Caspase‐1 activation was abrogated in macrophages deficient in Nod‐like receptor family, pyrin domain containing 3 (NLRP3) and apoptosis‐associated speck‐like protein containing a caspase recruitment domain (ASC), but not NLR family, CARD domain containing 4 (NLRC4). The activation of the NLRP3 inflammasome was mediated by three cytotoxins (aerolysin, hemolysin and multifunctional repeat‐in‐toxin) produced by A. hydrophila. Our results indicated that the NLRP3 inflammasome senses A. hydrophila infection through the action of bacterial cytotoxins.
Comparison of retroperitoneal and transperitoneal approach for reconstruction of abdominal aortic aneurysm in patients with previous laparotomy

Although the standard surgical approach for repair of infrarenal abdominal aortic aneurysm (AAA) has been the transperitoneal approach, several reports have suggested the usefulness of retroperitoneal aortic reconstruction. However, the superiority of the retroperitoneal compared with transperitoneal approach is still controversial. To compare the efficacy of the retroperitoneal with that of the transperitoneal approach in elective AAA resection, 19 consecutive cases with previous laparotomies were randomly reviewed. From January 1990 through December 1992, 94 consecutive patients underwent elective reconstructions of an infrarenal AAA. Among them, 75 patients had had no previous surgery of any kind. In all of them, the transperitoneal approach was used (Group I). Nineteen other patients who had various laparotomies were randomly divided into two groups. The transperitoneal approach was used in 10 patients (Group II), and the retroperitoneal approach was used in 9 patients (Group III). Thus, the patients were separated into three groups and the intra- and postoperative parameters were compared. Surgical data including operative time, intraoperative blood loss, and aortic cross-clamping time did not differ significantly between the transperitoneal approach in the patients without laparotomy (Group I) and the retroperitoneal approach (Group II). In addition, the postoperative recovery including the initiation of alimentation and postoperative hospitalization also did not differ significantly between the two groups. However, there was a significant difference in the operative time and the blood loss between the retroperitoneal approach (Group II) and transperitoneal approach (Group III) in the patients with previous laparotomy. In addition, the postoperative parameters including the initiation of oral intake was sooner and hospitalization was significantly shorter in the retroperitoneal group (Group II) than in the transperitoneal group (Group III) with previous laparotomy. There was no incidence of postoperative adhesive ileus in the patients with the retroperitoneal approach (Group II). The results demonstrated no important advantage for the retroperitoneal approach compared with routine transperitoneal approach in the patients without previous laparotomy. However, in the patients with previous laparotomies, the retroperitoneal approach is a preferable alternative to the transperitoneal route.
The experience of Parkinson's: Words and images through art therapy—a pilot research study

Abstract This paper will describe and discuss a pilot project which aimed to explore whether art therapy is helpful for people with Parkinson's disease and their carers. The rationale, aims and objectives of the project will be presented, together with practical information about the mechanisms for setting up the project—the context, getting referrals, the sessions, the involvement of relevant staff, involvement of the carers and relatives, and the insights gained from the whole process including the post-therapy interviews. Images are not included, as this will be the focus of a further paper.
B7‐H1 expression on non‐B and non‐T cells promotes distinct effects on T‐ and B‐cell responses in autoimmune arthritis

The immune system has developed several regulatory mechanisms to maintain homeostasis of adaptive immune responses. T‐cell programmed death (PD)‐1 recognition of B7‐H1 (PD‐L1) expressed on APC and non‐lymphoid tissue regulates T‐cell activation. We show that B7‐H1−/− mice exhibit exacerbated proteoglycan (PG)‐induced arthritis and increased Th‐1 CD4+ T‐cell responses. Unexpectedly, the PG‐specific antibody response in B7‐H1−/− mice was diminished. A reduction in the number of peanut agglutinin+ GC coincided with a decrease in CD19+ GL‐7+ CD95+ GC B cells that was a result of increased caspase‐induced apoptosis. The percent of CD38+ CD138+ emerging plasma cells was decreased. B7‐H1−/− mice exhibited an increased frequency of CD4+ PD‐1hi CXCR5hi ICOShi CD62Llo T follicular helper cells that displayed a hyperactive phenotype with increased expression of mRNA transcripts for Bcl6, IL‐21, and the apoptosis‐inducer molecule FasL. In cell transfer of B7‐H1−/− cells into SCID mice, non‐B and non‐T cells were sufficient to normalize the antibody response, T‐cell hyperactivity, and the development of PG‐induced arthritis. These findings indicate that B7‐H1 on non‐B and non‐T cells signals through PD‐1 on T effector cells to prevent excessive activation and reduce autoimmune arthritis. Furthermore, these findings demonstrate a novel role for B7‐H1 expression in promoting B‐cell survival by regulating the activation of T follicular helper cell.
Constant TCR triggering suggests that the TCR expressed on intestinal intraepithelial γδ T cells is functional in vivo

Intestinal intraepithelial lymphocytes carrying the γδ TCR (γδ iIEL) are involved in the maintenance of epithelial integrity. γδ iIEL have an activated phenotype, characterized by CD69 expression and increased cell size compared with systemic T lymphocytes. As an additional activation marker, the majority of γδ iIEL express the CD8αα homodimer. However, our knowledge about cognate ligands for most γδ TCR remains fragmentary and recent advances show that γδ T cells including iIEL may be directly activated by cytokines or through NK‐receptors, TLR and other pattern recognition receptors. We therefore asked whether the TCR of γδ iIEL was functional beyond its role during thymic selection. Using TcrdH2BeGFP (Tcrd, T‐cell receptor δ locus; H2B, histone 2B) reporter mice to identify γδ T cells, we measured their intracellular free calcium concentration in response to TCR‐crosslinking. In contrast to systemic γδ T cells, CD8αα+ γδ iIEL showed high basal calcium levels and were refractory to TCR‐dependent calcium‐flux induction; however, they readily produced CC chemokine ligand 4 (CCL4) and IFN‐γ upon TCR triggering in vitro. Notably, in vivo blocking of the γδ TCR with specific mAb led to a decrease of basal calcium levels in CD8αα+ γδ iIEL. This suggests that the γδ TCR of CD8αα+ γδ iIEL is constantly being triggered and therefore functional in vivo.
The Prevalence of Mental Disorders Among Children and Adolescents in the Child Welfare System

AbstractIt remains unclear whether children and adolescents in the child welfare system (CWS) exhibit a higher prevalence of mental disorders compared with the general population. The objective of this study was to perform a systematic review and meta-analysis to assess the prevalence of mental disorders in the CWS.All of the epidemiological surveys assessing the prevalence of mental disorders in children and adolescents in the CWS were included. The pooled prevalence was estimated with random effect models. Potential sources of heterogeneity were explored using meta-regression analyses.Eight studies provided prevalence estimates that were obtained from 3104 children and adolescents. Nearly 1 child or adolescent of every 2 (49%; 95% confidence interval (CI) 43–54) was identified as meeting criteria for a current mental disorder. The most common mental disorder was disruptive disorder (27%; 95% CI 20–34), including conduct disorder (20%; 95% CI 13–27) and oppositional defiant disorder (12%; 95% CI 10–14). The prevalence of attention-deficit/hyperactivity disorder was estimated to be 11% (95% CI 6–15). The prevalence estimates of anxiety and depressive disorders were 18% (95% CI 12–24) and 11% (95% CI 7–15). Posttraumatic stress disorder had the lowest prevalence (4%; 95% CI 2–6). High prevalences of mental disorders in the CWS were reported, which highlights the need for the provision of qualified service. The substantial heterogeneity of our findings is indicative of the need for accurate epidemiological data to effectively guide public policy.
Polyfunctional T cells in human tuberculosis

Studies of chronic viral infections have highlighted the phenotypic and functional heterogeneity of antigen‐specific T cells and suggested that polyfunctional T cells that secrete multiple cytokines and are able to proliferate on encounter with antigen are more likely than single cytokine secretors to represent correlates of protective immunity. These findings have prompted the evaluation of such T–cell responses in chronic bacterial infections, such as tuberculosis (TB). A number of studies in humans suggested that polyfunctional T cells may indeed be involved in mediating protection in TB; however, studies that question these findings are also emerging, including a study published in this issue of the European Journal of Immunology. These differing findings highlight the difficulties of studying human immunity to TB and the need for polyfunctional T cells to be evaluated in longitudinal studies as opposed to case‐control analyses.
Early viral replication in lymph nodes provides HIV with a means by which to escape NK‐cell‐mediated control

Acute HIV infection is marked by dramatic viral replication associated with preferential replication within secondary lymphoid tissues, such as lymph nodes (LNs), that is rapidly but incompletely contained to a viral setpoint. Accumulating evidence supports a role for natural killer (NK) cells in the early control of HIV infection; however, little is known about the location of their antiviral control. Given that HIV replicates profusely in LNs during early infection, we sought to define whether changes occurred in the NK cell infiltrate within these sites during the first year of HIV infection. Surprisingly, NK cell numbers and distribution were unaltered during early HIV infection. LN NK cells expressed decreased inhibitory receptors, were more highly activated, and expressed elevated TRAIL, potentially conferring a superior capacity for NK cells to become activated and control infection. Most noticeably, KIR+ NK cells were rarely detected in the LN during HIV infection, associated with diminished migratory capacity in the setting of reduced expression of CX3CR1 and CXCR1. Thus, incomplete control of HIV viral replication during early disease may be due to the inefficient recruitment of KIR+ NK cells to this vulnerable site, providing HIV a niche where it can replicate unabated by early NK‐cell‐mediated innate pressure.
Aldosterone-to-Renin Ratio Is Associated With Reduced 24-Hour Heart Rate Variability and QTc Prolongation in Hypertensive Patients

AbstractAldosterone is considered to exert direct effects on the myocardium and the sympathetic nervous system. Both QT time and heart rate (HR) variability (HRV) are considered to be markers of arrhythmic risk and autonomous dysregulation. In this study, we investigated the associations between aldosterone, QT time, and HRV in patients with arterial hypertension.We recruited 477 hypertensive patients (age: 60.2 ± 10.2 years; 52.3% females) with a mean systolic/diastolic 24-hour ambulatory blood pressure monitoring (ABPM) value of 128 ± 12.8/77.1 ± 9.2 mmHg and with a median of 2 (IQR: 1–3) antihypertensive agents. Patients were recruited from the outpatient clinic at the Department of Internal Medicine of the Medical University of Graz, Austria. Blood samples, 24-hour HRV derived from 24-hour blood pressure monitoring (ABPM) and ECG's were obtained. Plasma aldosterone and plasma renin concentrations were measured by means of a radioimmunoassay. Twenty-four-hour urine specimens were collected in parallel with ABPM.Mean QTc was 423.3 ± 42.0 milliseconds for males and 434.7 ± 38.3 milliseconds for females. Mean 24H-HR and 24H-HRV was 71.9 ± 9.8 and 10.0 ± 3.6 bpm, respectively. In linear regression analyses adjusted for age, sex, body mass index, ABPM, and current medication, aldosterone to active renin ratio (AARR) was significantly associated with the QTc interval, a marker for cardiac repolarization abnormalities (mean = 426 ± 42.4 milliseconds; &bgr;-coefficient = 0.121; P = 0.03) as well as with the 24-hour heart rate variability a surrogate for autonomic dysfunction (median = 9.67 [IQR = 7.38–12.22 bpm]; &bgr;-coefficient = −0.133; P = 0.01). In hypertensive patients, AARR is significantly related to QTc prolongation as well as HRV. Further studies investigating the effects of mineralocorticoid receptor blocker and aldosterone synthase inhibitors on QTc and HRV are warranted.
Regulation of the respiratory quotient of soil microbiota by availability of nutrients.

Abstract The effects of glucose and mineral nitrogen amendment on the respiratory quotient (RQ), defined as the ratio of moles CO(2) evolved per moles of O(2) consumed, were tested on an agricultural and a forest soil (A horizon) of the Bornhöved Lake District, northern Germany. Both substrate-induced respiration rate and RQ value increased with increasing glucose concentration. Glucose plus nitrate addition gave the highest RQ value in the agricultural soil whereas addition of glucose alone gave the highest RQ value in the forest soil. Generally, glucose plus ammonium addition resulted in lower RQ values than glucose addition alone. When glucose was added to soil at field rates of C input, the RQ value showed fluctuations between 0.44 and 1.35. Low C supply caused rapid return of the initially enhanced RQ value towards those of basal respiration, that was typically <1. The experiment showed that both respiratory activity and respiratory quotient increased with increasing amount of available C. The RQ values >1 refer to both anabolic C uptake and 'unbalanced' C degradation. The microbial communities in the agricultural soil were less efficient in C use than those in the forest soil.
Alternative activation of macrophages by IL‐4 requires SHIP degradation

Alternatively activated macrophages are critical in host defense against parasites and are protective in inflammatory bowel disease, but contribute to pathology in asthma and solid tumors. The mechanisms underlying alternative activation of macrophages are only partially understood and little is known about their amenability to manipulation in pathophysiological conditions. Herein, we demonstrate that Src homology 2‐domain‐containing inositol‐5′‐phosphatase (SHIP)‐deficient murine macrophages are more sensitive to IL‐4‐mediated skewing to an alternatively activated phenotype. Moreover, SHIP levels are decreased in macrophages treated with IL‐4 and in murine GM‐CSF‐derived and tumor‐associated macrophages. Loss of SHIP and induction of alternatively activated macrophage markers, Ym1 and arginase I (argI), were dependent on phosphatidylinositol 3‐kinase (PI3K) activity and argI induction was dependent on the class IA PI3Kp110δ isoform. STAT6 was required to reduce SHIP protein levels, but reduced SHIP levels did not increase STAT6 phosphorylation. STAT6 transcription was inhibited by PI3K inhibitors and enhanced when SHIP was reduced using siRNA. Importantly, reducing SHIP levels enhanced, whereas SHIP overexpression or blocking SHIP degradation reduced, IL‐4‐induced argI activity. These findings identify SHIP and the PI3K pathway as critical regulators of alternative macrophage activation and SHIP as a target for manipulation in diseases where macrophage phenotype contributes to pathology.
Infective Endocarditis and Cancer Risk

AbstractThis study investigated the possible relationship between endocarditis and overall and individual cancer risk among study participants in Taiwan.We used data from the National Health Insurance program of Taiwan to conduct a population-based, observational, and retrospective cohort study. The case group consisted of 14,534 patients who were diagnosed with endocarditis between January 1, 2000 and December 31, 2010. For the control group, 4 patients without endocarditis were frequency matched to each endocarditis patient according to age, sex, and index year. Competing risks regression analysis was conducted to determine the effect of endocarditis on cancer risk.A large difference was noted in Charlson comorbidity index between endocarditis and nonendocarditis patients. In patients with endocarditis, the risk for developing overall cancer was significant and 119% higher than in patients without endocarditis (adjusted subhazard ratio = 2.19, 95% confidence interval = 1.98–2.42). Regarding individual cancers, in addition to head and neck, uterus, female breast and hematological malignancies, the risks of developing colorectal cancer, and some digestive tract cancers were significantly higher. Additional analyses determined that the association of cancer with endocarditis is stronger within the 1st 5 years after endocarditis diagnosis.This population-based cohort study found that patients with endocarditis are at a higher risk for colorectal cancer and other cancers in Taiwan. The risk was even higher within the 1st 5 years after endocarditis diagnosis. It suggested that endocarditis is an early marker of colorectal cancer and other cancers. The underlying mechanisms must still be explored and may account for a shared risk factor of infection in both endocarditis and malignancy.
CD4+ T‐cell immunity in the female genital tract is critically dependent on local mucosal immunization

Immunizations via the i.n. and intravaginal (ivag) routes effectively generate strong genital tract antibody‐mediated immunity. To what extent the same is true for T‐cell responses is incompletely known. Therefore, we set out to investigate optimal conditions for stimulation of genital tract CD4+ T‐cell responses, using adoptive transfer of mouse DO11.10 TCR transgenic T cells specific for OVA and OVA conjugated to cholera toxin (CT) as an immunogen. We observed that progesterone was required for a T‐cell response following ivag immunization, whereas estradiol prevented a response. Although i.n. immunization stimulated OVA‐specific CD4+ T‐cell responses in the draining LNs, it was substantially less effective compared to ivag. More importantly, an ivag booster immunization was absolutely required to attract T cells to the genital tract mucosa itself. While clinical use of CT is precluded because of its toxicity, we developed a combined adjuvant vector based on a non‐toxic derivative of CT and immune‐stimulating complexes. The CTA1‐DD/immune‐stimulating complexes (ISCOMs) adjuvant together with major outer membrane protein was effective at stimulating genital tract CD4+ T‐cell immunity and protection against a live chlamydial infection, which holds promise for the development of mucosal vaccines against sexually transmitted infections.
Caffeine, coffee and health

Examines the history of coffee drinking. Describes the constituents of coffee and its physiological effects on the drinker. Reviews the research done in the past on caffeine’s effects on health. Recommends a safe level of consumption at between 300‐400mg of caffeine per day which translates to four or five cups of average strength coffee.
Laparoendoscopic single-site nephrectomy for hemodialysis patients with dialysis-related renal tumors

Abstract Purpose: The purpose of this study is to assess the efficacy of laparoendoscopic single-site (LESS) nephrectomy in hemodialysis patients, we compared outcomes between LESS nephrectomy and conventional laparoendoscopic nephrectomy in hemodialysis patients with dialysis-related renal tumors. Material and methods: A total of 16 hemodialysis patients who underwent LESS nephrectomy (LESS-N; n = 8) or conventional laparoendoscopic nephrectomy (C-N; n = 8) between November 2003 and July 2012 were retrospectively evaluated. Outcomes were compared between the two groups. Results: Patient and tumor characteristics were similar between the LESS-N and C-N groups. The mean operative duration was longer in the LESS-N than in the C-N group (231.0 ± 26.7 min versus 188.6 ± 36.4 min; p = .025). The mean estimated blood loss was lower in the LESS-N compared with the C-N group (26.4 ± 14.4 ml versus 65.6 ± 45.2 ml; p = .047). Postoperative complications were observed in three cases, comprising one case of retroperitoneal hematoma in the LESS-N group and one case each of peritoneal hematoma and retroperitoneal abscess in the C-N group. Surgical scarring was minimal in the LESS-N group. Conclusions: Although there is a little extension of the operating time, LESS nephrectomy in hemodialysis patients is a feasible procedure compared with the conventional method.
‘It just opens up their world’: autism, empathy, and the therapeutic effects of equine interactions

ABSTRACT Experiences of autism-spectrum disorder are now increasingly studied by social scientists. Human–animal relations have also become a major focus of social inquiry in recent years. Examining horse-assisted therapy for autistic spectrum disorders, this is the first paper that brings these fields together. Drawing on participant observation and interviews at a UK horse therapy Centre, this article examines how staff and the parents of riders account for the successes and limitations of equine therapy. To the respondents, horses ‘open up’ autistic children and make possible interactions that seemed impossible before. Horses were regarded as facilitating the emergence of apparently social behaviours, which included eye contact, pointing, and speech. Three key explanations emerged for therapeutic success: the sensorial, embodied experience of riding the horse; the specific movements and rhythms of the horse; and, the ‘personality’ of the horse. Equine therapy can be regarded as enabling a form of multispecies intersubjectivity, with the resonance between rider and horse seeming to make possible a new attunement between humans. Practices of equine therapy, and perceptions of its efficacy, serve in turn to attune social scientists to a version of empathy constituted through lively and sensorial interactions, as opposed to one that is restricted to particular kinds of humans.