Is the Activity of Partially Agonistic MHC:Peptide Ligands Dependent on the Quality of Immunological Help?

CD8(+) cytotoxic T lymphocytes (CTL) are important for the immunological control of infections and tumours. Engagement of the T-cell receptor (TCR) with major histocompatibility complex (MHC) class I/peptide complexes on antigen-presenting cells (APC) is the key interaction, which initiates the process of T-cell activation. Depending on the affinity of this interaction, different arrays of signalling pathways and functional outcomes can be activated in the specific T cells. Molecular alterations in the peptide bound to the MHC class I can lead to a lower affinity of the MHC:TCR interaction resulting in incomplete or qualitatively different T-cell responses. Altered peptide ligands (APL) exhibiting such activity are referred to as partial agonists and often occur naturally through genetic instability, which affects T-cell epitopes derived from rapidly mutating viruses or tumour-associated cellular antigens. Partial agonists are usually viewed as peptide variants, which escape efficient CTL recognition. Our recent data suggest that APL can not only trigger incomplete activation but also induce and modulate intrinsic T-cell programmes leading to the shut-off of specific CTL responses. This APL-induced suppression appears to be more prominent in the absence of immunological help, suggesting that under conditions of immune deregulation APL may actively inhibit CTL responses against infectious agents or tumours. In this review, we discuss experimental data supporting this model and possible role of APL-induced immunosuppression in different pathological conditions.     

Can Multidisciplinary Sepsis Teams Help Solve a Global Concern? A Review of the Literature

The aims of this reviews are to provide a background on sepsis and to discuss the role of multidisciplinary sepsis teams for those who may not provide direct patient care but play an important role in supporting those that manage patients with sepsis. Sepsis, a life-threatening organ dysfunction due to a dysregulated host response to infection, is one of the leading causes of death worldwide. Considered a medical emergency, prompt laboratory results and administration of appropriate antibiotics are critical. Numerous sepsis guidelines have been published, including the use of standardized bundles that can result in reduced mortality and better patient outcomes. Key to successful outcomes are early recognition and appropriate therapy, which is guided by multidisciplinary sepsis intervention teams; rapid laboratory testing, including Gram stains; molecular mass spectrometry; and clinical and electronic early warning surveillance systems that offer a systematic machine learning application to analyze patients’ medical data and send an alert to providers in real time to allow earlier intervention.     

Does the Use of a Checklist Help Medical Students in the Detection of Abnormalities on a Chest Radiograph?

The interpretation of chest radiographs is a complex task that is prone to diagnostic error, especially for medical students. The aim of this study is to investigate the extent to which medical students benefit from the use of a checklist regarding the detection of abnormalities on a chest radiograph. We developed a checklist based on literature and interviews with experienced thorax radiologists. Forty medical students in the clinical phase assessed 18 chest radiographs during a computer test, either with (n = 20) or without (n = 20) the checklist. We measured performance and asked participants for feedback using a survey. Participants that used a checklist detected more abnormalities on images with multiple abnormalities (M = 50.1%) than participants that could not use a checklist (M = 41.9%), p = 0.04. The post-experimental survey shows that on average, participants considered the checklist helpful (M = 3.25 on a five-point scale), but also time consuming (M = 3.30 on a five-point scale). In conclusion, a checklist can help medical students to detect abnormalities in chest radiographs. Moreover, students tend to appreciate the use of a checklist as a helpful tool during the interpretation of a chest radiograph. Therefore, a checklist is a potentially important tool to improve radiology education in the medical curriculum.     

Do Flexible Goal Adjustment and Acceptance Help Preserve Quality of Life in Patients with Multiple Sclerosis?

Background

Goal regulation strategies such as flexible goal adjustment and acceptance are believed to be protective factors in persons with chronic illness, but research on their relative contributions to quality of life in multiple sclerosis (MS) is lacking.

Purpose

We aimed to test the idea that acceptance and flexible goal adjustment (in contrast to tenacious goal pursuit) may help preserve the quality of life in persons with MS.

Method

A sample of 117 patients with MS was recruited. They completed questionnaires measuring quality of life (physical functioning, psychological distress), acceptance, flexible goal adjustment, and tenacious goal pursuit.

Results

Acceptance significantly accounted for variance in all three indexes of quality of life, beyond the effects of demographic and illness characteristics. The role of goal regulation style was less clear. Flexible goal adjustment significantly accounted for psychological well-being only. Surprisingly, tenacious goal pursuit predicted better psychological functioning and less psychological distress. No support was found for the hypothesis that acceptance and flexible goal adjustment would moderate the relation between illness severity and quality of life.

Conclusion

The findings suggest the potential importance of acceptance in understanding MS patients’ quality of life, although its hypothesized protective function could not be confirmed. Further conceptual work on acceptance and goal regulation style is needed, as well as prospective work investigating their causal status.

     

Neuropathic Pain due to Fibromatosis: Does Anticancer Treatment Help?

Desmoid fibromatosis, although histologically benign, infiltrates local structures. The involvement of neural structures can lead to difficult neuropathic pain and the escalating use of analgesics. We report a patient with desmoid fibromatosis of the chest wall causing brachial plexus infiltration. As the tumor was locally invasive and unresectable, he was treated with radiation therapy and oral tamoxifen. On follow-up, there was significant pain relief, sustained reduction in the tumor size, and reduced analgesic requirement. Antineoplastic treatments like local radiation therapy and targeted systemic therapy with hormones or other agents can be considered in the management of selected unresectable desmoid fibromatosis to improve symptom control and reduce polypharmacy.     

Natural “Helper” Cells in the Lung: Good or Bad Help?

The natural helper (NH) cell comprises a newly identified Th2 cell-type innate lymphocyte population. In this issue of Immunity, Halim et al. (2012) provide evidence that NH cells reside in the lung and play a critical role in protease allergen-induced airway inflammation.     

Circulating Cytokine Levels in Acute Pancreatitis—Model of SIRS/CARS Can Help in the Clinical Assessment of Disease Severity

The aim of our study was to evaluate the pro- and anti-inflammatory cytokine response during acute pancreatitis and its predictive value on severity of disease. A hospital-based prospective clinical study was conducted. Twenty patients with acute pancreatitis were enrolled during a 12-month period. Plasma concentrations of TNF-α, IL-1β, IL-6, and IL-10 were determined at days 1, 2, 3, 6, and 9. The patient population was analyzed by type of acute pancreatitis. Severity was defined according to the Atlanta criteria for assessing severity of acute pancreatitis. Clinical variables were recorded to patients classified in one of two groups: severe acute pancreatitis (SAP group) and mild acute pancreatitis (MILD group). Patients with SAP had significantly higher average levels of IL-6 compared to the MILD group patients (539.2 pg/L vs. 23.4 pg/L, p < 0.0001). Also, the values of IL-10 were significantly higher in patients with SAP (242.4 pg/L vs. 8.1 pg/L, p = 0.003). The values of TNF-α were not significantly different in both groups. The value of IL-6 and IL-10 showed a positive correlation (r = 0.7964, p < 0.0001). Although a relatively small sample of patients was used, we can conclude that the determination of the value of IL-6 and IL-10 can help in the clinical assessment of disease severity.     

Markers of senescence?

The specific identification of cellular senescence in clinical material has important implications for determining the role of senescence in age-related pathologies and in neoplasia in certain tumours. One suggested marker of senescence is the histochemical identification of a specific beta-galactosidase enzyme operative at pH 6.0. However, recent data indicate that this enzyme may not be specific for senescence in all tissues and probably represents the expression of endogenous lysosomal acid beta-galactosidase, which is expressed by a variety of differentiated cell types.     

Does Regular Breakfast Cereal Consumption Help Children and Adolescents Stay Slimmer? A Systematic Review and Meta-Analysis

ObjectiveTo review systematically the evidence on breakfast cereal consumption and obesity in children and adolescents and assess whether the regular consumption of breakfast cereals could help to prevent excessive weight gain.MethodsA systematic review and meta-analysis of studies relating breakfast cereal consumption to BMI, BMI z-scores and prevalence of obesity as the outcomes.Results14 papers met the inclusion criteria. The computed effect size for mean BMI between high consumers and low or non-consumers over all 25 study subgroups was −1.13 kg/m² (95% CI −0.81, −1.46, p ℋ 0.0001) in the random effects model, which is equivalent to a standardised mean difference of 0.24. Adjustment for age and publication bias attenuated the effect sizes somewhat but they remained statistically significant. The prevalence and risk of overweight was lower in children and adolescents who consume breakfast cereals regularly compared to those who consume them infrequently. Energy intakes tended to be higher in regular breakfast cereal consumers.ConclusionOverall, the evidence reviewed is suggestive that regular consumption of breakfast cereals results in a lower BMI and a reduced likelihood of being overweight in children and adolescents. However, more evidence from long-term trials and investigations into mechanisms is needed to eliminate possible confounding factors and determine causality.Key Words: Breakfast cereals, Obesity, Prevention, Children, Adolescents     

“Help me figure this out”: Qualitative explorations of patient experiences with cancer pathology reports

ObjectiveFor patients with a new cancer diagnosis, the pathology report is a critical tool to support diagnosis and decision-making, yet they are designed for providers, not patients. We sought to qualitatively explore patients’ experiences receiving and interpreting pathology reports for breast and colorectal cancers.MethodsWe conducted four focus groups with patients (n = 23) who had received diagnostic or surgical pathology reports for breast cancer, colorectal cancer or polypectomy. Focus groups discussed patients’ experiences with pathology reports and recommendations for improving the patient-centeredness of report design. Focus groups were transcribed and thematic analysis was used to explore patient perspectives.ResultsParticipants described experiences with pathology reports that were fraught with confusion and variability. Three central themes were identified related to how 1) the experience receiving the pathology report, 2) the pathology report language, and 3) the format of pathology reports all influence patient understanding and ability to engage in treatment decision-making.ConclusionDue to their complex medical language and challenging framing, traditional pathology reports can contribute to the confusion and uncertainty patients experience as they navigate a new cancer diagnosis.     

Universalization of health or of social security?

This article presents an analysis of the architecture of Mexico's health system based on the main economic problem, failing to achieve a GDP growth rate to increase real wages and give workers in formal employment coverage social security. This analysis describes the relationship between social security of the population and employment status of it (either formal or informal employment) and the impact that this situation poses to our health system. Also, it ends with a reform proposal that will give all workers the same social rights, ie to grant universal social security.