Analysis of T-cell Receptor-Induced Calcium Influx in Primary Murine T-cells by Full Spectrum Flow Cytometry.

Calcium influx in response to T-cell receptor stimulation is a common measure of T-cell signaling. Several calcium indicator dyes have been developed to assess calcium signaling by band-pass flow cytometry. This protocol is designed to measure calcium responses in primary murine T-cells using full spectrum flow cytometry.

Assessing joint commitment as a process in great apes.

Many social animals interact jointly, but only humans experience a specific sense of obligation toward their co-participants, a . However, joint commitment is not only a mental state but also a that reveals itself in the coordination efforts deployed during entry and exit phases of joint action. Here, we investigated the presence and duration of such phases in  = 1,242 natural play and grooming interactions of captive chimpanzees and bonobos.

Generation of functional human thymic cells from induced pluripotent stem cells.

Background: The thymus is a glandular organ that is essential for the formation of the adaptive immune system by educating developing T cells. The thymus is most active during childhood and involutes around the time of adolescence, resulting in a severe reduction or absence of naive T-cell output. The ability to generate a patient-derived human thymus would provide an attractive research platform and enable the development of novel cell therapies.

[Hospital to home transition of care: challenges for patients with type 2 diabetes].

The transition from hospital to ambulatory care is a high-risk period for patients with diabetes mellitus and is a challenge for health care professionals. Various interprofessional collaborative interventions have shown a positive impact on continuity of care at discharge. Communication and transmission of information between the hospital and ambulatory settings as well as coordination between healthcare professionals are key points to explore and to improve to ensure optimal continuity of care.

Factors associated with crack-cocaine early initiation: a Brazilian multicenter study.

Background: Crack-cocaine dependence is a serious public health issue, related to several psychiatric and psychosocial problems. Crack-cocaine users are usually embedded in a context of great social vulnerability, often associated with violence, poverty, family conflict and easy and early access to alcohol, tobacco and other drugs.

Methods: This cross-sectional study enrolled a consecutive sample of 577 patients admitted to 20 therapeutic communities located in Southern Brazil, between September 2012 and September 2013.

Optimized Detection of Acute MHV68 Infection With a Reporter System Identifies Large Peritoneal Macrophages as a Dominant Target of Primary Infection.

Investigating the dynamics of virus-host interactions remains an important challenge, often limited by the ability to directly identify virally infected cells. Here, we utilize a beta-lactamase activated fluorescent substrate to identify primary targets of murine gammaherpesvirus 68 (MHV68) infection in the peritoneal cavity. By optimizing substrate and detection conditions, we were able to achieve multiparameter characterization of infected cells and the ensuing host response.

Studying Immunotherapy Resistance in a Melanoma Autologous Humanized Mouse Xenograft.

Resistance to immunotherapy is a significant challenge, and the scarcity of human models hinders the identification of the underlying mechanisms. To address this limitation, we constructed an autologous humanized mouse (aHM) model with hematopoietic stem and progenitor cells (HSPC) and tumors from 2 melanoma patients progressing to immunotherapy. Unlike mismatched humanized mouse (mHM) models, generated from cord blood-derived HSPCs and tumors from different donors, the aHM recapitulates a patient-specific tumor microenvironment (TME).

Uric Acid Lowering and Biomarkers of Kidney Damage in CKD Stage 3: A Post Hoc Analysis of a Randomized Clinical Trial.

Rationale & Objective: Hyperuricemia is associated with chronic kidney disease (CKD) progression. We evaluated whether lowering serum uric acid levels improves levels of biomarkers of kidney damage.

Study Design: Post hoc analysis of clinical trial participants.

KIM-1 and Kidney Disease Progression in Autosomal Dominant Polycystic Kidney Disease: HALT-PKD Results.

Background: Cyst compression of renal tubules plays a role in the progression of autosomal dominant polycystic kidney disease (ADPKD) and may induce expression of kidney injury molecule-1 (KIM-1). Whether urinary KIM-1 indexed for creatinine (uKIM-1/Cr) is a prognostic marker of disease progression in ADPKD is unknown.In this secondary analysis of a prospective cohort study, we sought to determine whether patients with high as opposed to low uKIM-1/CR at baseline had greater rates of eGFR loss and height-adjusted total kidney volume (HtTKV) increase.

[Diabetes mellitus: impact of affects on self-management skills].

Diabetes self-management (DSM) is a process based on a series of complex learnings. The conceptualization of the role of the emotional dimensions that underlie and structure this process is critical to better understand why living with diabetes can become a burden. A clinical case illustrates the intertwining of the affective and cognitive dimensions of diabetes burden and its influence on DSM skills.

Global Inequality in Type 1 Diabetes: a Comparison of Switzerland and Low-and Middle-Income Countries.

Globally it is estimated that over 1 million children and adolescents have Type 1 diabetes with large variations in incidence between different contexts. Health systems need to provide a variety of elements to ensure appropriate diabetes care, such as service delivery; healthcare workforce; information; medical products and technologies; financing and leadership and governance. Describing these elements between Geneva, Switzerland, a high-income country with high spending on healthcare and a large density of doctors, and low- and middle-income countries this article aims to highlight the global inequality of diabetes care.

An Intervention by a Patient-Designed Do-It-Yourself Mobile Device App Reduces HbA1c in Children and Adolescents with Type 1 Diabetes: A Randomized Double-Crossover Study.

Background: Prevention of type 1 diabetes mellitus (T1DM)-related complications is dependent on metabolic control. The recommended glycated hemoglobin (HbA1c) values <7.5% (58.

Examining the effects of uric acid-lowering on markers vascular of calcification and CKD-MBD; A post-hoc analysis of a randomized clinical trial.

Background: Chronic kidney disease (CKD)-mineral and bone disorder (MBD) is a systemic disorder that leads to vascular calcification and accelerated atherosclerosis. Uric acid has been shown to associate with vascular calcification and with carotid intima-media thickness (CIMT) and to suppress the 1 α-hydroxylase enzyme leading to lower 1,25-dihydroxyvitamin D (1,25(OH)2D) and higher intact parathyroid hormone (iPTH) levels. We hypothesized that lowering serum uric acid would reduce CIMT, calcification propensity, and circulating markers of CKD-MBD in CKD.

Coordination of ENT2-dependent adenosine transport and signaling dampens mucosal inflammation.

Intestinal epithelial barrier repair is vital for remission in inflammatory bowel disease (IBD). Extracellular adenosine signaling has been implicated in promoting restoration of epithelial barrier function. Currently, no clinically approved agents target this pathway.

Dual use of hematopoietic and mesenchymal stem cells enhances engraftment and immune cell trafficking in an allogeneic humanized mouse model of head and neck cancer.

In this report, we describe in detail the evolving procedures to optimize humanized mouse cohort generation, including optimal conditioning, choice of lineage for engraftment, threshold for successful engraftment, HNSCC tumor implantation, and immune and stroma cell analyses. We developed a dual infusion protocol of human hematopoietic stem and progenitor cells (HSPCs) and mesenchymal stem cells (MSCs), leading to incremental human bone marrow engraftment, and exponential increase in mature peripheral human immune cells, and intratumor homing that includes a more complete lineage reconstitution. Additionally, we have identified practical rules to predict successful HSPC/MSC expansion, and a peripheral human cell threshold associated with bone marrow engraftment, both of which will optimize cohort generation and management.

Endothelial Microparticles and Systemic Complement Activation in Patients With Chronic Kidney Disease.

Background: Endothelial microparticles are associated with chronic kidney disease (CKD) and complement activation. We hypothesized that the complement pathway is activated in patients with CKD via endothelial microparticles and that complement activation correlates with endothelial dysfunction in CKD.

Methods And Results: We analyzed complement data of 30 healthy subjects, 30 patients with stage III/IV CKD, and 30 renal transplant recipients with stage III/IV CKD, evaluating the potential correlation of complement fragments with brachial artery flow-mediated dilation, Chronic Kidney Disease Epidemiology Collaboration glomerular filtration rate, and urinary albumin/creatinine ratio.

Vascular Function and Uric Acid-Lowering in Stage 3 CKD.

Hyperuricemia may contribute to endothelial dysfunction in CKD. We evaluated whether lowering serum uric acid levels with allopurinol improves endothelial dysfunction in 80 participants ≥18 years of age with stage 3 CKD and asymptomatic hyperuricemia (≥7 mg/dl in men and ≥6 mg/dl in women) randomized in a double-blinded manner to receive placebo or allopurinol for 12 weeks. Randomization was stratified according to presence or absence of diabetes mellitus.

[Transition in diabetology].

For patients with type I diabetes, transition from pediatric to adult care is a challenge due to complex treatment requirements and the physical, psychological and social changes of adolescence. Members of the care team must recognize that while these emerging adults need to develop self-management skills, this may conflict at times with the developmentally appropriate desire for increasing autonomy. The role of nursing in coordinating a successful transition is critical for maintaining continuity of patient-centered care that responds to the specific needs of these young adults.

Antidoping programme and biological monitoring before and during the 2014 FIFA World Cup Brazil.

Background: The FIFA has implemented an important antidoping programme for the 2014 FIFA World Cup.

Aim: To perform the analyses before and during the World Cup with biological monitoring of blood and urine samples.

Methods: All qualified players from the 32 teams participating in the World Cup were tested out-of-competition.

Epithelial-specific A2B adenosine receptor signaling protects the colonic epithelial barrier during acute colitis.

Central to inflammatory bowel disease (IBD) pathogenesis is loss of mucosal barrier function. Emerging evidence implicates extracellular adenosine signaling in attenuating mucosal inflammation. We hypothesized that adenosine-mediated protection from intestinal barrier dysfunction involves tissue-specific signaling through the A2B adenosine receptor (Adora2b) at the intestinal mucosal surface.

Assessment of vascular function in patients with chronic kidney disease.

Patients with chronic kidney disease (CKD) have significantly increased risk of cardiovascular disease (CVD) compared to the general population, and this is only partially explained by traditional CVD risk factors. Vascular dysfunction is an important non-traditional risk factor, characterized by vascular endothelial dysfunction (most commonly assessed as impaired endothelium-dependent dilation [EDD]) and stiffening of the large elastic arteries. While various techniques exist to assess EDD and large elastic artery stiffness, the most commonly used are brachial artery flow-mediated dilation (FMDBA) and aortic pulse-wave velocity (aPWV), respectively.

[Diabetes in elderly: a tailored management].

In developed countries, 12-25 % of the aged population (>65 years old) have diabetes. Treatment of the old diabetic patients is less well studied compared to younger patients although diabetic and geriatric medical associations have issued specific treatment and priority guidelines for these patients. Treatment and targets of glycemic control must be adapted to the functional condition of the patients, prevent symptoms and complications of the geriatric syndrome.