Comparing the Cost Effectiveness of a Celiac Disease Panel to a Testing Cascade

Recent reductions in healthcare funding in the United States has pressured clinical laboratories to provide the same quality of diagnostic testing with fewer resources. Testing cascades have been developed to assist in the diagnosis of various illnesses, which use fewer tests and subsequently reduce costs. However, the cost effectiveness of a celiac disease (CD) testing cascade compared to a panel is currently unknown. Therefore, the purpose of this study was to determine if a CD testing cascade was equivalent to a panel in identifying patients deemed likely for CD, and to compare their cost effectiveness in a sample of symptomatic patients from Northeast Tennessee. A retrospective analysis using a CD testing cascade was performed on 933 outpatient samples referred to our laboratory from 2012 to 2017 with a request for a celiac disease serology panel. The seroprevalence of CD for the panel and the cascade were the same in this population (1.82%, 95% binomial confidence interval: 1.06% to 2.90%). The total cost of the CD cascade was 268% less than the cost of the panel resulting in a savings of $44,705, which translates to a savings of$47.92/patient. Based on these findings, we recommend utilization of the cascade to identify patients with likely CD. In the future, creative use of novel testing strategies can have significant contributions to healthcare reform and afford patients more cost-effective clinical diagnostic testing

Validity of the Short Recovery and Stress Scale in Collegiate Weightlifters

Introduction: Monitoring an athlete’s stress and recovery state across sequential training bouts can be used to gauge fitness and fatigue levels (i.e., preparedness). Previous studies have used jumping performance, biochemical markers, and questionnaires to estimate preparedness. However, self-report questionnaires are the most common due to economical and practical means. The Short Recovery and Stress Scale (SRSS) is an 8-item questionnaire ideal for monitoring; however, convergent validity of the SRSS with physiological and performance measures needs to be investigated. Purpose: Thus, the purpose of this study was to determine whether changes in collegiate weightlifter’s training volume-load, biochemical markers, and jumping performance correlate to changes in the SRSS. Methods: 12 collegiate weightlifters (8 males, 4 females) with \u3e1yr of competition experience trained for 4 weeks and were tested at the beginning of each week (T1-T4). Training volume-load with displacement (VLd) was monitored weekly for all exercises. Testing was conducted following an overnight fast and included hydration, SRSS (0-6 scale with 6 indicating highest recovery and stress), and blood draws (resting testosterone (T), cortisol (C), T:C, creatine kinase (CK)) followed by unloaded (0kg) and loaded (20kg) squat jumps (SJ) on force platforms. Pearson correlation coefficients were calculated between the change in SRSS scores and all other variables from T1-T2, T1-T3, and T1-T4. Alpha level was set at p\u3c 0.05. Results: Inverse relationships were observed between changes in recovery items and C (r= -0.61 to -0.72, p\u3c 0.05), and unloaded and loaded SJ height and relative peak power (r= -0.59 to -0.64, p\u3c 0.05) from T1 to T2, and T1 to T3. Similarly, positive relationships were observed between changes in stress items and C (r=0.61 to 0.72, p\u3c 0.05), and unloaded and loaded SJ height and relative peak power (r=0.58 to 0.84, p\u3c 0.05) across all time points. No significant relationships were observed between changes in SRSS items and VLd or T, T:C, CK. Conclusion: Relationships between changes in some SRSS items and C agree with previous findings highlighting C as an indicator of training stress. Nonetheless, the non-significant relationships between changes in SRSS items, VLd, and other biochemical markers disagrees with previous findings. This may partly be explained by the smaller undulations in VLd in the current study, which is characteristic of actual training. Further, relationships between changes in some SRSS items and jumping performance were opposite of what was expected indicating athlete’s perception of their stress and recovery state does not always correspond with their ability to perform. Practical Application: These results provide some evidence for the convergent validity of the SRSS. Nonetheless, weightlifting coaches should be cautious in using results from a single test to estimate an athlete’s preparedness. Thus, we recommend the SRSS be included as part of a multi-dimensional monitoring program for weightlifters

Convergent Validity of the Short Recovery and Stress Scale in Collegiate Weightlifters

International Journal of Exercise Science 15(6): 1457-1471, 2022. The purpose of this study was to determine whether changes in collegiate weightlifters’ external training load, biochemical markers, and jumping performance correlate to changes in items of the Short Recovery and Stress Scale (SRSS) throughout four microcycles. Twelve well-trained weightlifters (8 males, 4 females; age 24.30 ± 4.36 yr; height 170.28 ± 7.09 cm; body mass 81.73 ± 17.00 kg) with at least one year of competition experience participated in the study. Measurements included hydration, SRSS, biochemical analysis of blood (cortisol [C], creatine kinase [CK]), and unloaded and loaded squat jumps (SJ), and volume-load displacement. Pearson correlation coefficients were calculated between the changes in SRSS items and all other variables. The alpha criterion for all analyses was set at p ≤ 0.05. Negative relationships were observed between changes in SRSS recovery items and C (r = -0.608 to -0.723), and unloaded and loaded SJ height and peak power (r = -0.587 to -0.636). Positive relationships were observed between changes in several SRSS stress items and C (r = 0.609 to 0.723), CK (r = 0.922), and unloaded and loaded SJ height and peak power (r = 0.583 to 0.839). Relationships between changes in some SRSS items and cortisol agree with previous findings highlighting C as an indicator of training stress. Nonetheless, the non-significant relationships between changes in SRSS items, training volume and biochemical markers disagree with previous findings. This may partly be explained by the smaller undulations in training volume in the current study, which were characteristic of typical training. Further, relationships between changes in some SRSS items and jumping performance were opposite of what was expected indicating athletes’ perception of their stress and recovery state does not always correspond with their ability to perform

Differential regulation of lipopolysaccharide and Gram-positive bacteria induced cytokine and chemokine production in splenocytes by Gαi proteins

AbstractHeterotrimeric Gi proteins play a role in lipopolysaccharide (LPS) and Staphylococcus aureus (SA) activated signaling leading to inflammatory mediator production. We hypothesized that genetic deletion of Gi proteins would alter cytokine and chemokine production induced by LPS and SA. LPS- and heat killed SA-induced cytokine and chemokine production in splenocytes from wild type (WT), Gαi2 (−/−) or Gαi1/3 (−/−) mice were investigated. LPS- or SA-induced production of TNFα, IL-6, IFNγ, IL-12, IL-17, GM-CSF, MIP-1α, MCP-1, MIG and IP-10 were significantly increased (1.2 to 33 fold, p<0.05) in splenocytes harvested from Gαi2(−/−) mice compared with WT mice. The effect of Gαi protein depletion was remarkably isoform specific. In splenocytes from Gαi1/3 (−/−) mice relative to WT mice, SA-induced IL-6, IFNγ, GM-CSF, and IP-10 levels were decreased (59% to 86%, p<0.05), whereas other LPS- or SA-stimulated cytokines and chemokines were not different relative to WT mice. LPS- and SA-induced production of KC were unchanged in both groups of the genetic deficient mice. Splenocytes from both Gαi2 (−/−) and Gαi1/3 (−/−) mice did not exhibit changes in TLR2 and TLR4 expression. Also analysis of splenic cellular composition by flow cytometry demonstrated an increase in splenic macrophages and reduced CD4 T cells in both Gαi2 (−/−) and Gαi1/3 (−/−) mice relative to WT mice. The disparate response of splenocytes from the Gαi2 (−/−) relative to Gαi1/3 (−/−) mice therefore cannot be attributed to major differences in spleen cellular composition. These data demonstrate that Gi2 and Gi1/3 proteins are both involved and differentially regulate splenocyte inflammatory cytokine and chemokine production in a highly Gi isoform specific manner in response to LPS and Gram-positive microbial stimuli

Scavenger Receptor Class A Plays a Central Role in Mediating Mortality and the Development of the Pro-Inflammatory Phenotype in Polymicrobial Sepsis

Sepsis is a frequent complication in critical illness. The mechanisms that are involved in initiation and propagation of the disease are not well understood. Scavenger receptor A (SRA) is a membrane receptor that binds multiple polyanions such as oxidized LDL and endotoxin. Recent studies suggest that SRA acts as a pattern recognition receptor in the innate immune response. The goal of the present study was to determine the role of SRA in polymicrobial sepsis. SRA deficient (SRA-/-) and C57BL/6JB/6J (WT) male mice were subjected to cecal ligation and puncture (CLP) to induce polymicrobial sepsis. NFκB activity, myeloperoxidase activity, and co-association of SRA with toll like receptor (TLR) 4 and TLR2 was analyzed in the lungs. Spleens were analyzed for apoptosis. Serum cytokines and chemokines were assayed. Blood and peritoneal fluid were cultured for aerobic and anaerobic bacterial burdens. Long term survival was significantly increased in SRA-/- septic mice (53.6% vs. 3.6%, p\u3c0.05) when compared to WT mice. NFκB activity was 45.5% lower in the lungs of SRA-/- septic mice versus WT septic mice (p\u3c0.05). Serum levels of interleukin (IL)-5, IL-6, IL-10 and monocyte chemoattractant protein -1 were significantly lower in septic SRA-/- mice when compared to septic WT mice (p\u3c0.05). We found that SRA immuno-precipitated with TLR4, but not TLR2, in the lungs of WT septic mice. We also found that septic SRA-/- mice had lower bacterial burdens than WT septic mice. SRA deficiency had no effect on pulmonary neutrophil infiltration or splenocyte apoptosis during sepsis. We conclude that SRA plays a pivotal, and previously unknown, role in mediating the pathophysiology of sepsis/septic shock in a murine model of polymicrobial sepsis. Mechanistically, SRA interacts with TLR4 to enhance the development of the pro-inflammatory phenotype and mediate the morbidity and mortality of sepsis/septic shock

Activation of Myocardial Phosphoinositide-3-Kinase p110α Ameliorates Cardiac Dysfunction and Improves Survival in Polymicrobial Sepsis

Phosphoinositide-3-kinase (PI3K)/Akt dependent signaling has been shown to improve outcome in sepsis/septic shock. There is also ample evidence that PI3K/Akt dependent signaling plays a crucial role in maintaining normal cardiac function. We hypothesized that PI3K/Akt signaling may ameliorate septic shock by attenuating sepsis-induced cardiac dysfunction. Cardiac function and survival were evaluated in transgenic mice with cardiac myocyte specific expression of constitutively active PI3K isoform, p110α (caPI3K Tg). caPI3K Tg and wild type (WT) mice were subjected to cecal ligation/puncture (CLP) induced sepsis. Wild type CLP mice showed dramatic cardiac dysfunction at 6 hrs. Septic cardiomyopathy was significantly attenuated in caPI3K CLP mice. The time to 100% mortality was 46 hrs in WT CLP mice. In contrast, 80% of the caPI3K mice survived at 46 hrs after CLP (p30 days (

Activation of Cytosolic Phospholipase A\u3csub\u3e2\u3c/sub\u3eα in Resident Peritoneal Macrophages by Listeria Monocytogenes Involves Listeriolysin O and TLR2

Eicosanoid production by macrophages is an early response to microbial infection that promotes acute inflammation. The intracellular pathogen Listeria monocytogenes stimulates arachidonic acid release and eicosanoid production from resident mouse peritoneal macrophages through activation of group IVA cytosolic phospholipase A2 (cPLA2α). The ability of wild type L. monocytogenes (WTLM) to stimulate arachidonic acid release is partially dependent on the virulence factor listeriolysin O; however, WTLM and L. monocytogenes lacking listeriolysin O (ΔhlyLM) induce similar levels of cyclooxygenase 2. Arachidonic acid release requires activation of MAPKs by WTLM and ΔhlyLM. The attenuated release of arachidonic acid that is observed in TLR2-/- and MyD88-/- macrophages infected with WTLM and ΔhlyLM correlates with diminished MAPK activation. WTLM but not ΔhlyLM increases intracellular calcium, which is implicated in regulation of cPLA2α. Prostaglandin E2, prostaglandin I 2, and leukotriene C4 are produced by cPLA 2α+/+ but not cPLA2α-/- macrophages in response to WTLM and ΔhlyLM. Tumor necrosis factor (TNF)-α production is significantly lower in cPLA2α +/+ than in cPLA2α-/- macrophages infected with WTLM and ΔhlyLM. Treatment of infected cPLA 2α+/+ macrophages with the cyclooxygenase inhibitor indomethacin increases TNFα production to the level produced by cPLA 2α-/- macrophages implicating prostaglandins in TNFα down-regulation. Therefore activation of cPLA2α in macrophages may impact immune responses to L. monocytogenes

Measurement of Mast Cell Cytokine Release by Multiplex Assay

Mast cells are highly responsive cells that are capable of secreting a variety of inflammatory mediators, including histamine, heparin, serine proteases, leukotrienes, prostaglandins, and thromboxanes. Studies from several laboratories have demonstrated that mast cells have the capacity to produce a variety of cytokines in response to various stimuli. Characterization of the cytokine profiles in mast cells has routinely been determined by the performance of individual enzyme-linked immunosorbent assays. This process is expensive, time-consuming, and requires a great deal of material to characterize multiple cytokines. In this chapter, we describe a multiplex cytokine assay to detect 17 cytokines simultaneously in 50 microL of culture supernatant derived from stimulated human cord blood-derived mast cells

High Prevalence of Buprenorphine in Prenatal Drug Screens in an Appalachian City

Objectives To define the magnitude of buprenorphine presence in the urine drug screens of pregnant women and to assess the presence of illicit buprenorphine use versus the presence of prescribed buprenorphine use. Methods Initial prenatal drug screen results for all pregnant patients in our practice for a 1-year period were analyzed and tabulated. Results Buprenorphine was found in the urine drug screens of 16% of pregnant patients. The presence of buprenorphine was by far the highest for any substance associated with neonatal abstinence syndrome (NAS). We estimate that the exposure to buprenorphine of approximately one-third of individuals in our population is associated with illicit buprenorphine use. Conclusions The high rate of NAS in our region is primarily associated with both illicit and prescribed buprenorphine rather than other substances. Buprenorphine usage at the time that prenatal care is initiated, rather than opiate use at the onset of prenatal care, is the underlying factor that must be addressed if our region is to successfully combat our high rates of NAS