PD-1 Dynamically Regulates Inflammation and Development of Brain-Resident Memory CD8 T Cells During Persistent Viral Encephalitis

Programmed cell death-1 (PD-1) receptor signaling dampens the functionality of T cells faced with repetitive antigenic stimulation from chronic infections or tumors. Using intracerebral (i.c.) inoculation with mouse polyomavirus (MuPyV), we have shown that CD8 T cells establish a PD-1hi, tissue-resident memory population in the brains (bTRM) of mice with a low-level persistent infection. In MuPyV encephalitis, PD-L1 was expressed on infiltrating myeloid cells, microglia and astrocytes, but not on oligodendrocytes. Engagement of PD-1 on anti-MuPyV CD8 T cells limited their effector activity. NanoString gene expression analysis showed that neuroinflammation was higher in PD-L1−/− than wild type mice at day 8 post-infection, the peak of the MuPyV-specific CD8 response. During the persistent phase of infection, however, the absence of PD-1 signaling was found to be associated with a lower inflammatory response than in wild type mice. Genetic disruption and intracerebroventricular blockade of PD-1 signaling resulted in an increase in number of MuPyV-specific CD8 bTRM and the fraction of these cells expressing CD103, the αE integrin commonly used to define tissue-resident T cells. However, PD-L1−/− mice persistently infected with MuPyV showed impaired virus control upon i.c. re-infection with MuPyV. Collectively, these data reveal a temporal duality in PD-1-mediated regulation of MuPyV-associated neuroinflammation. PD-1 signaling limited the severity of neuroinflammation during acute infection but sustained a level of inflammation during persistent infection for maintaining control of virus re-infection

Astaxanthin vs placebo on arterial stiffness, oxidative stress and inflammation in renal transplant patients (Xanthin): a randomised controlled trial

Background: There is evidence that renal transplant recipients have accelerated atherosclerosis manifest by increased cardiovascular morbidity and mortality. The high incidence of atherosclerosis is, in part, related to increased arterial stiffness, vascular dysfunction, elevated oxidative stress and inflammation associated with immunosuppressive therapy. The dietary supplement astaxanthin has shown promise as an antioxidant and anti-inflammatory therapeutic agent in cardiovascular disease. The aim of this trial is to investigate the effects of astaxanthin supplementation on arterial stiffness, oxidative stress and inflammation in renal transplant patients

Fitting as a temporal sensemaking process: shifting trajectories and stable themes

This study identifies several mechanisms and the overall process by which individuals understand their evolving fit with their work environment. Prior person-environment research has emphasized one-time quantitative assessments of fit, primarily as new entrants enter their work environment. In this study, we employed a qualitative approach to investigate the following question: how do long-tenured professionals make sense of fit over time? Three key findings emerged from the fit-related histories we collected. First, we discovered four prototypical fit trajectories, which were constructed from temporal comparisons with past, present, and future fit, and employed to make momentary sense of events occurring in the work environment. Second, we identified two fit processes that played out over time: a slow accumulation journey and a sudden identity-threat journey. Third, we found that individuals’ set of fit experiences was explained by one of four enduring fit themes, explaining their pattern of fit experiences over time and their reaction to misfit. Most surprising was the significant turnover among our long-tenured participants in the year or so following our interviews. Our findings break from traditional thinking about fit as predicting outcomes in the moment, to fitting as both a journey and a retrospective and prospective process of sensemaking. Keywords: person-environment fit, misfit, temporal, time, process, sensemaking, qualitative, identit

The quality of life of patients with genital warts: a qualitative study

<p>Abstract</p> <p>Background</p> <p>Genital warts, which are caused by infection with human papillomavirus (HPV), are one of the most common sexually transmitted diseases in Europe. Although genital warts are commonly perceived as a non-serious condition, treatment is often long, of varying effectiveness and the recurrence rate is high. Very few studies have been performed on the personal consequences of genital warts. The aim of this qualitative study, set in Denmark, was to examine the ways in which genital warts may affect patients' quality of life.</p> <p>Methods</p> <p>To obtain an in-depth understanding of patients' perceptions of genital warts, we used qualitative focus-group interviews with five men and five women aged between 18 and 30 years who had genital warts. The interview guide was based on a literature review that identified important issues and questions. The data were analysed using a medical anthropological approach.</p> <p>Results</p> <p>Patients' experiences were related to cultural conceptions of venereal diseases and the respective identities and sexuality of the sexes. The disease had negative psychological and social effects both for men and for women and it affected their sex and love lives, in particular. The psychological burden of the disease was increased by the uncertain timeline and the varying effectiveness of treatment. We identified a need for more patient information about the disease and its psycho-sexual aspects.</p> <p>Conclusions</p> <p>The men and women participating in this study considered their quality of life to be significantly lowered because of genital warts. The experiences described by the participants give insights that may be valuable in treatment and counselling.</p> <p>The quadrivalent HPV vaccine that has now been added to the childhood vaccination programme for girls in Denmark for the prevention of cervical cancer can also prevent 90% of cases of genital warts. Our results suggest that HPV vaccination could considerably reduce the largely unacknowledged psychological and social burden associated with genital warts, in men as well as women.</p

The needs of foster children and how to satisfy them:A systematic review of the literature

Family foster care deeply influences the needs of children and how these are satisfied. To increase our knowledge of foster children’s needs and how these are conceptualized, this paper presents a systematic literature review. Sixty- four empirical articles from six databases were reviewed and categorized (inter-rater agreement K = .78) into four categories: medical, belongingness, psychological and self-actualization needs. The results give a complete overview of needs that are specific to foster children, and what can be implemented to satisfy these needs. This study shows psychological needs are studied more often compared to the other categories, which specially relates to much attention for mental health problems. Furthermore, most articles focus on how to satisfy the needs of foster children and provide no definition or concrete conceptualization of needs. Strikingly, many articles focus on children’s problems instead of their needs, and some even use these terms interchangeably. This review illustrates that future research should employ a proper conceptualization of needs, which could also initiate a shift in thinking about needs instead of problems

Sildenafil citrate for prophylaxis of nephropathy in an animal model of contrast-induced acute kidney injury.

Contrast-induced acute kidney injury (CIAKI) is one of the commonest complications associated with contrast media (CM). Although the exact etiology of CIAKI remains unclear, one hypothesis involves vasoconstriction of afferent arterioles resulting in renal ischemia. Increased renal blood flow, therefore, might represent an attractive target for the treatment of CIAKI. In this study we evaluated the protective effects of the phosphodiesterase type 5 (PDE5) inhibitor, sildenafil citrate, in a rabbit model of CIAKI. New Zealand white rabbits were used due to their susceptibility to CIAKI. To evaluate the effects of sildenafil, the drug was administered before CM infusion and repeatedly throughout the remainder of the experiment (6 mg/kg, p.o.). Animals were sacrificed after 48 hours and kidneys were prepared for histological evaluation. Intravenous administration of CM produced marked kidney injury. Serum creatinine concentrations were elevated within two hours of the infusion and remained elevated for the duration of the experiment. Histological evaluation of the kidneys revealed significant tubular necrosis. The effects of the CM were dose dependent. Treatment with sildenafil was associated with lesser degree of histological injury, attenuation in markers of acute kidney injury (48 hour creatinine 1.54±0.21 versus 4.42±1.31 mg/dl, p<0.05) and reduction in electrolyte derangement (percent change in serum K+ at 48 hours 2.55±3.80% versus 15.53±4.47%, p<0.05; serum Na+ at 48 hours -0.14±0.26% versus -1.97±1.29%, p = 0.20). The results suggest a possible role for PDE5 inhibitors in the treatment of CIAKI and warrant further evaluation to determine the exact mechanism of protection

Using satellite imagery to assess plant species richness: The role of multispectral systems

Question: The use of variations in the spectral responses of remotely sensed images was recently proposed as an indicator of plant species richness (Spectral Variation Hypothesis, SVH). In this paper we addressed the issue of the potential use of multispectral sensors by testing the hypothesis that only some of the bands recorded in a remotely sensed image contain information related to the variation in species richness.Location: Montepulciano Lake, central Italy.Methods: We assessed how data compression techniques, such as Principal Component Analysis (PCA), influence the relationship between spectral heterogeneity and species richness and evaluated which spectral interval is the most adequate for predicting species richness by means of linear regression analysis. Results: The original multispectral data set and the first two non-standardized principal components can both be used as predictors of plant species richness (R2 0.48; p < 0.001), confirming that PCA is an effective tool for compressing multispectral data without loss of information. Using single spectral bands, the near infrared band explained 41% of variance in species richness (p < 0.01), while the visible wavelengths had much lower prediction powers. Conclusions: The potential of satellite data for estimating species richness is likely to be due to the near infrared bands, rather than to the visible bands, which share highly redundant information. Since optimal band selection for image processing is a crucial task and it will assume increasing importance with the growing accession-num of hyperspectral data, in this paper we suggest a 'near infrared way' for assessing species richness directly from remotely sensed data