Impaired survival of peripheral T cells, disrupted NK/NKT cell development, and liver failure in mice lacking Gimap5

The loss of Gimap5 (GTPase of the immune-associated protein 5) gene function is the underlying cause of lymphopenia and autoimmune diabetes in the BioBreeding (BB) rat. The in vivo function of murine gimap5 is largely unknown. We show that selective gene ablation of the mouse gimap5 gene impairs the final intrathymic maturation of CD8 and CD4 T cells and compromises the survival of postthymic CD4 and CD8 cells, replicating findings in the BB rat model. In addition, gimap5 deficiency imposes a block of natural killer (NK)- and NKT-cell differentiation. Development of NK/NKT cells is restored on transfer of gimap5(-/-) bone marrow into a wild-type environment. Mice lacking gimap5 have a median survival of 15 weeks, exhibit chronic hepatic hematopoiesis, and in later stages show pronounced hepatocyte apoptosis, leading to liver failure. This pathology persists in a Rag2-deficient background in the absence of mature B, T, or NK cells and cannot be adoptively transferred by transplanting gimap5(-/-) bone marrow into wild-type recipients. We conclude that mouse gimap5 is necessary for the survival of peripheral T cells, NK/NKT-cell development, and the maintenance of normal liver function. These functions involve cell-intrinsic as well as cell-extrinsic mechanisms.     

Long-term prognosis of patients with early post-infarction angina.

BACKGROUND: Most studies have shown that early post-infarction angina (EPA) implies an unfavorable long-term prognosis among patients with acute myocardial infarction (AMI). However, some studies have failed to establish a link between the occurrence of EPA and increased mortality and recurrent infarction rates. METHODS AND RESULTS: In order to evaluate a long-term prognosis in patients with EPA, we assessed the 5-year prognosis of 80 patients with AMI by the presence or absence of EPA. During the 5-year follow up, the occurrence of death, cardiac death, recurrent infarction, unstable angina, heart failure, revascularization and cardiac events were recorded. A cardiac event was defined as an occurrence of any of the following events: cardiac death, recurrent infarction, unstable angina, heart failure and revascularization. Survival analysis showed no differences between patients with and without EPA in the probability of death (p=NS), cardiac death (p=NS), recurrent myocardial infarction (p=NS) and unstable angina (p=NS). Patients with EPA had a higher probability of developing cardiac events (p=0.0285) and undergoing revascularization procedures (p=0.0188). CONCLUSIONS: EPA increases the risk of patients developing cardiac events and undergoing revascularization procedures, and thereby implies a poor long-term prognosis for patients with AMI.     

Health related outcomes among people with type 2 diabetes by country of birth: Result from the 45 and Up Study

Background

Ethnic variation in the occurrence of type 2 diabetes, complications, mortality, and health behaviours has been reported. The current research examined patterns of health-related outcomes by country of birth in people with diabetes aged 45 years and over in New South Wales, Australia.

Mast Cells as a Potential Prognostic Marker in Prostate Cancer

Despite years of intensive investigation that has been made in understanding prostate cancer, it remains one of the major men''s health issues and the leading cause of death worldwide. It is now ascertained that prostate cancer emerges from multiple spontaneous and/or inherited alterations that induce changes in expression patterns of genes and proteins that function in complex networks controlling critical cellular events. It is now accepted that several innate and adaptive immune cells, including T- and B-lymphocytes, macrophages, natural killer cells, dendritic cells, neutrophils, eosinophils, and mast cells (MCs), infiltrate the prostate cancer. All of these cells are irregularly scattered within the tumor and loaded with an assorted array of cytokines, chemokines, and inflammatory and cytotoxic mediators. This complex framework reflects the diversity in tumor biology and tumor-host interactions. MCs are well-established effector cells in Immunoglobulin-E (Ig-E) associated immune responses and potent effector cells of the innate immune system; however, their clinical significance in prostate cancer is still debated. Here, these controversies are summarized, focusing on the implications of these findings in understanding the roles of MCs in primary prostate cancer.     

Diagnostic Evaluation of Patients Presenting to Primary Care with Rectal Bleeding

Background

Rectal bleeding is a common, frequently benign problem that can also be an early sign of colorectal cancer. Diagnostic evaluation for rectal bleeding is complex, and clinical practice may deviate from available guidelines.

Objective

To assess the degree to which primary care physicians document risk factors for colorectal cancer among patients with rectal bleeding and order colonoscopies when indicated, and the likelihood of physicians ordering and patients receiving recommended colonoscopies based on demographic characteristics, visit patterns, and clinical presentations.

Design

Cross-sectional study using explicit chart abstraction methods.

Participants

Three hundred adults, 40–80 years of age, presenting with rectal bleeding to 15 academically affiliated primary care practices between 2012 and 2016.

Main Measures

1) The frequency at which colorectal cancer risk factors were documented in patients’ charts, 2) the frequency at which physicians ordered colonoscopies and patients received them, and 3) the odds of ordering and patients receiving recommended colonoscopies based on patient demographic characteristics, visit patterns, and clinical presentations.

Key Results

Risk factors for colorectal cancer were documented between 9% and 66% of the time. Most patients (89%) with rectal bleeding needed a colonoscopy according to a clinical guideline. Physicians placed colonoscopy orders for 74% of these patients, and 56% completed the colonoscopy within a year (36% within 60 days). The odds of physicians ordering recommended colonoscopies were significantly higher in patients aged 50–64 years of age than in those aged 40–50 years (OR?=?2.23, 95% CI: 1.04, 4.80), and for patients whose most recent colonoscopy was 5 or more years ago (OR?=?4.04, 95% CI: 1.50, 10.83). The odds of physicians ordering and patients receiving recommended colonoscopies were significantly lower for each primary care visit unrelated to rectal bleeding (OR?=?0.85, 95% CI: 0.75, 0.96).

Conclusions

Diagnostic evaluation of patients presenting to primary care with rectal bleeding may be suboptimal because of inadequate risk factor assessment and prioritization of patients’ other concurrent medical problems.

     

Influence of Adhesives and Methods of Enamel Pretreatment on the Shear Bond Strength of Orthodontic Brackets

Aim

The objective of present study was to examine influence of adhesives and methods of enamel pretreatment on the shear bond strength (SBS) of orthodontic brackets. The adhesives used were resin-reinforced glass ionomer cements-GIC (Fuji Ortho LC) and composite resin (Transbond XT).

Material and Methods

The experimental sample consisted of 80 extracted human first premolars. The sample was divided into four equal groups, and the metal brackets were bonded with different enamel pretreatments by using two adhesives: group A-10% polyacrylic acid; Fuji Ortho LC, group B–37% phosphoric acid; Fuji Ortho LC, group C–self etching primer; Transbond XT, group D–37% phosphoric acid, primer; Transbond XT. SBS of brackets was measured. After debonding of brackets, the adhesive remnant index (ARI) was evaluated.

Results

After the statistical analysis of the collected data was performed (ANOVA; Sheffe post-hoc test), the results showed that significantly lower SBS of the group B was found in relation to the groups C (p=0.031) and D (p=0.026). The results of ARI were similar in all testing groups and it was not possible to determine any statistically significant difference of the ARI (Chi- square test) between all four experimental groups.

Conclusion

The conclusion is that the use of composite resins material with appropriate enamel pretreatment according to manufacturer’s recommendation is the “gold standard” for brackets bonding for fixed orthodontic appliances.Key words: orthodontic brackets, shear strength, adhesive, enamel preparation     

Clinical Significance of Laboratory-determined Aspirin Poor Responsiveness After Primary Percutaneous Coronary Intervention

Aims

The objective of the present substudy was to examine whether aspirin poor/high responsiveness (APR/AHR) is associated with increased rates of major adverse cardiovascular events (MACE) and serious bleeding after primary percutaneous coronary intervention (PPCI).

Methods

We analyzed 961 consecutive ST-elevation acute myocardial infarction patients who underwent PPCI between February 2008 and June 2011. Multiplate analyser (Dynabite, Munich, Germany) was used for the assessment of platelet reactivity. APR/AHR were defined as the upper/lower quintiles of ASPI values, determined 24 h after aspirin loading. APR patients were tailored using 300 mg maintenance dose for 30 days. The co-primary end points at 30 days were: MACE (death, non-fatal infarction, ischemia-driven target vessel revascularization and ischemic stroke) and serious bleeding according to the BARC classification.

Results

One hundred and 90 patients were classified as APR, and 193 patients as AHR. At admission, compared with aspirin sensitive patients (ASP), patients with APR had more frequently diabetes, anterior infarction and heart failure, while AHR patients had reduced values of creatine kinase, leukocytes, heart rate and systolic blood pressure. Compared with ASP, the rates of 30-day primary end points did not differ neither in APR group including tailored patients (MACE, adjusted OR 1.02, 95%CI 0.47-2.17; serious bleeding, adjusted OR 1.92, 95%CI 0.79-4.63), nor in patients with AHR (MACE, adjusted OR 1.58, 95%CI 0.71-5.51; serious bleeding, adjusted OR 0.69, 95%CI 0.22-2.12).

Conclusions

The majority of APR patients were suitable for tailoring. Neither APR including tailored patients nor AHR were associated with adverse 30-day efficacy or safety clinical outcomes.

     

Use of three‐dimensional power doppler sonography in the diagnosis of uterine arteriovenous malformation and follow‐up after uterine artery embolization: Case report and brief review of literature

Arteriovenous malformations (AVM) of the uterus can cause life‐threatening hemorrhage. Unexplained, heavy vaginal bleeding in a reproductive age woman should raise suspicion for an AVM. Here a 37‐year‐old woman had increasingly severe vaginal bleeding for 15 days. Serum β‐hCG was elevated. Two‐dimensional transvaginal ultrasound suggested retained products of conception. Before dilation and curettage (D&C), color Doppler and three‐dimensional (3D) power Doppler demonstrated findings indicative of uterine AVM. A bilateral uterine artery embolization was performed without complications. Three months after uterine artery embolization, 3D power Doppler ultrasonography found complete resolution of the AVM. This case illustrates the importance of assessing both gray‐scale and 3D power Doppler, and the ability of postprocedure Doppler to assess resolution. © 2014 Wiley Periodicals, Inc. J Clin Ultrasound 43:327–334, 2015