Background
Equine protozoal myeloencephalitis (EPM) caused by Sarcocystis neurona remains an antemortem diagnostic challenge in some horses. Recent work suggested the use of real‐time PCR (rtPCR) on ...cerebrospinal fluid (CSF) as a promising diagnostic tool.
Objective
To evaluate the sensitivity and specificity of S. neurona rtPCR on CSF for EPM diagnosis using horses with EPM and S. neurona‐seropositive horses with other neurologic conditions.
Animals
Ninety‐nine horses with neurologic disease that underwent complete neurologic examination, CSF collection, and, if euthanized, necropsy including the central nervous system (CNS).
Methods
Retrospective case‐control study using banked CSF samples. Samples from horses with neurologic abnormalities and necropsy‐confirmed EPM diagnosis, presumptive EPM diagnosis using strict criteria (SnSAG2/4/3 ELISA serum:CSF titer ratios <50) and horses diagnosed with other neurologic diseases were used.
Results
Fifty‐two horses had EPM; 23 were confirmed on necropsy, and 29 were presumptive clinical diagnoses. The other 47 horses all had necropsy‐confirmed diagnoses. Four of the 47 horses had normal neurologic findings on necropsy and the remaining 43 horses had neurologic diseases including equine degenerative myeloencephalopathy (EDM), cervical vertebral stenotic myelopathy, trauma, and other miscellaneous conditions. One CSF sample was weakly positive for S. neurona by rtPCR, this sample was obtained from a horse with confirmed EDM. Samples from the other 98 horses were negative for S. neurona by rtPCR.
Conclusions and Clinical Importance
Our study contradicts previous conclusions that S. neurona rtPCR is potentially useful for EPM diagnosis, because our results indicate that the assay has a low sensitivity (0%) for EPM.
Mechanisms of Cancer‐Related Fatigue Ryan, Julie L.; Carroll, Jennifer K.; Ryan, Elizabeth P. ...
The oncologist (Dayton, Ohio),
20/May , Letnik:
12, Številka:
S1
Journal Article
Recenzirano
Odprti dostop
Cancer‐related fatigue (CRF) is one of the most prevalent symptoms patients with cancer experience, both during and after treatment. CRF is pervasive and affects patients' quality of life ...considerably. It is important, therefore, to understand the underlying pathophysiology of CRF in order to develop useful strategies for prevention and treatment. At present, the etiology of CRF is poorly understood and the relative contributions of the neoplastic disease, various forms of cancer therapy, and comorbid conditions (e.g., anemia, cachexia, sleep disorders, depression) remain unclear. In any individual, the etiology of CRF probably involves the dysregulation of several physiological and biochemical systems. Mechanisms proposed as underlying CRF include 5‐HT neurotransmitter dysregulation, vagal afferent activation, alterations in muscle and ATP metabolism, hypothalamic–pituitary–adrenal axis dysfunction, circadian rhythm disruption, and cytokine dysregulation. Currently, these hypotheses are largely based on evidence from other conditions in which fatigue is a characteristic, in particular chronic fatigue syndrome and exercise‐induced fatigue. The mechanisms that lead to fatigue in these conditions provide a theoretical basis for future research into the complex etiology of this distressing and debilitating symptom. An understanding of relevant mechanisms may offer potential routes for its prevention and treatment in patients with cancer.
Disclosure of potential conflicts of interest is found at the end of this article.
We examined the association between perceived discrimination and smoking status and whether psychological distress mediated this relationship in a large, multiethnic sample.
We used 2004 through 2008 ...data from the Behavioral Risk Factor Surveillance System Reactions to Race module to conduct multivariate logistic regression analyses and tests of mediation examining associations between perceived discrimination in health care and workplace settings, psychological distress, and current smoking status.
Regardless of race/ethnicity, perceived discrimination was associated with increased odds of current smoking. Psychological distress was also a significant mediator of the discrimination-smoking association.
Our results indicate that individuals who report discriminatory treatment in multiple domains may be more likely to smoke, in part, because of the psychological distress associated with such treatment.
Abstract Background Phenotypic heterogeneity in autism has long been conjectured to be a major hindrance to the discovery of genetic risk factors, leading to numerous attempts to stratify children ...based on phenotype to increase power of discovery studies. This approach, however, is based on the hypothesis that phenotypic heterogeneity closely maps to genetic variation, which has not been tested. Our study examines the impact of subphenotyping of a well-characterized autism spectrum disorder (ASD) sample on genetic homogeneity and the ability to discover common genetic variants conferring liability to ASD. Methods Genome-wide genotypic data of 2576 families from the Simons Simplex Collection were analyzed in the overall sample and phenotypic subgroups defined on the basis of diagnosis, IQ, and symptom profiles. We conducted a family-based association study, as well as estimating heritability and evaluating allele scores for each phenotypic subgroup. Results Association analyses revealed no genome-wide significant association signal. Subphenotyping did not increase power substantially. Moreover, allele scores built from the most associated single nucleotide polymorphisms, based on the odds ratio in the full sample, predicted case status in subsets of the sample equally well and heritability estimates were very similar for all subgroups. Conclusions In genome-wide association analysis of the Simons Simplex Collection sample, reducing phenotypic heterogeneity had at most a modest impact on genetic homogeneity. Our results are based on a relatively small sample, one with greater homogeneity than the entire population; if they apply more broadly, they imply that analysis of subphenotypes is not a productive path forward for discovering genetic risk variants in ASD.
Cancer‐related fatigue (CRF) is a debilitating, multi‐faceted biopsychosocial symptom experienced by the majority of cancer survivors during and after treatment. CRF begins after diagnosis and ...frequently persists long after treatments end, even when the cancer is in remission. The etiological pathopsychophysiology underlying CRF is multifactorial and not well delineated. Mechanisms may include abnormal accumulation of muscle metabolites, dysregulation of the homeostatic status of cytokines, irregularities in neuromuscular function, abnormal gene expression, inadequate ATP synthesis, serotonin dysregulation, abnormal vagal afferent nerve activation, as well as an array of psychosocial mechanisms, including self‐efficacy, causal attributions, expectancy, coping, and social support. An important first step in the management of CRF is the identification and treatment of associated comorbidities, such as anemia, hypothyroidism, pain, emotional distress, insomnia, malnutrition, and other comorbid conditions. However, even effective clinical management of these conditions will not necessarily alleviate CRF for a significant proportion of cancer survivors. For these individuals, intervention with additional therapeutic modalities may be required. The National Comprehensive Cancer Network guidelines recommend that integrative nonpharmacologic behavioral interventions be implemented for the effective management of CRF. These types of interventions may include exercise, psychosocial support, stress management, energy conservation, nutritional therapy, sleep therapy, and restorative therapy. A growing body of scientific evidence supports the use of exercise and psychosocial interventions for the management of CRF. Research on these interventions has yielded positive outcomes in cancer survivors with different diagnoses undergoing a variety of cancer treatments. The data from trials investigating the efficacy of other types of integrative nonpharmacologic behavioral therapies for the management of CRF, though limited, are also encouraging. This article provides an overview of current research on the relative merits of integrative nonpharmacologic behavioral interventions for the effective clinical management of CRF and makes recommendations for future research.
Disclosure of potential conflicts of interest is found at the end of this article.
Background
Streptococcus equi subspecies equi infection elicits M protein antibody titers in equids. Interpretation of titers is not generally accepted.
Hypothesis
The magnitude of S. equi M protein ...(SeM) antibody titer after infection (titer ≥1:12 800) will be useful to monitor for the presence of complications or the risk of development of complications.
Animals
Forty‐eight horses on 1 farm involved in strangles outbreak.
Methods
Clinical and observational study. S. equi M protein antibody titers were measured on all horses 8 weeks after infection and select horses 12 and 28 weeks after infection. Horses were categorized: no disease, uncomplicated case, persistent guttural pouch (GP) infection, or complicated cases (metastatic abscesses, purpura hemorrhagica, secondary infections, and dysphagia). Category was compared to titer.
Results
Twenty‐eight of 48 (58%) developed clinical signs of S. equi infection. Of those, 11 (39%) had uncomplicated strangles, 9 (21%) had persistent GP infection, 5 (18%) were complicated cases, and 3 (11%) had both persistent GP infection and complications. Thirty‐three percent of horses (16 of 48) had SeM antibody titers ≥1:12 800 eight weeks after infection. Of horses with titers ≥1:12 800, 6 of 16 had evidence of complications. Of complicated cases, 6 of 8 had titers ≥1:12 800. In this outbreak, the sensitivity (75%; 95% CI confidence interval 45‐105) for a SeM antibody titer ≥1:12 800 detecting complications was higher than the specificity (43%; 95% CI 23‐64).
Conclusions and Clinical Importance
This outbreak demonstrates that SeM antibody titers can be increased after infection (≥1:12 800) in the absence of complications of strangles.
Background
Infection by 2 or more protozoa is linked with increased severity of disease in marine mammals with protozoan encephalitis.
Hypothesis/Objectives
To assess whether horses with equine ...protozoal myeloencephalitis (EPM) caused by Sarcocystis neurona also have evidence of infection with Neospora hughesi or Toxoplasma gondii. We hypothesized that horses with EPM would be more likely than horses with cervical vertebral stenotic myelopathy (CVSM) to be positive for antibodies to multiple protozoan parasites.
Animals
One hundred one horses with neurologic disease: 49 with EPM and 52 with CVSM.
Methods
Case review. Archived serum and cerebrospinal fluid (CSF) from 101 horses were examined. Inclusion criteria included neurologic disease, antemortem or postmortem diagnosis of EPM or CVSM, and availability of serological results or archived samples for testing. Additional testing for antibodies was performed on serum for T. gondii, as well as serum and CSF for N. hughesi.
Results
Horses with EPM were more likely than horses with CVSM to have positive immunologic results for S. neurona on serum (95.9% versus 76.9%, P = .0058), CSF (98.0% versus 44.2%, P < .00001), and serum : CSF titer ratio (91.8% versus 0%, P < .00001). Positive results for Neospora and Toxoplasma were uncommon, with total seroprevalence rates of 12.9% and 14.9%, respectively. The proportions of EPM cases testing positive for Neospora and Toxoplasma (16% and 12%) were not different from the proportions of CVSM cases testing positive (10% and 17%, P = .31 and .47, respectively).
Conclusion
Results do not indicate an important role for protozoal coinfection in EPM in the eastern United States.
To identify factors associated with the timing of ventilator liberation and tracheostomy decannulation among infants with severe bronchopulmonary dysplasia (sBPD) who required chronic outpatient ...invasive ventilation.OBJECTIVETo identify factors associated with the timing of ventilator liberation and tracheostomy decannulation among infants with severe bronchopulmonary dysplasia (sBPD) who required chronic outpatient invasive ventilation.Multicenter retrospective study of 154 infants with sBPD on outpatient ventilators. Factors associated with ventilator liberation and decannulation were identified using Cox regression models and multilevel survival models.STUDY DESIGNMulticenter retrospective study of 154 infants with sBPD on outpatient ventilators. Factors associated with ventilator liberation and decannulation were identified using Cox regression models and multilevel survival models.Ventilation liberation and decannulation occurred at median ages of 27 and 49 months, respectively. Older age at transition to a portable ventilator and at discharge, higher positive end expiratory pressure, and multiple respiratory readmissions were associated with delayed ventilator liberation. Surgical management of gastroesophageal reflux was associated with later decannulation.RESULTSVentilation liberation and decannulation occurred at median ages of 27 and 49 months, respectively. Older age at transition to a portable ventilator and at discharge, higher positive end expiratory pressure, and multiple respiratory readmissions were associated with delayed ventilator liberation. Surgical management of gastroesophageal reflux was associated with later decannulation.Ventilator liberation timing was impacted by longer initial admissions and higher ventilator pressure support needs, whereas decannulation timing was associated with more aggressive reflux management. Variation in the timing of events was primarily due to individual-level factors, rather than center-level factors.CONCLUSIONSVentilator liberation timing was impacted by longer initial admissions and higher ventilator pressure support needs, whereas decannulation timing was associated with more aggressive reflux management. Variation in the timing of events was primarily due to individual-level factors, rather than center-level factors.
Background Brain development follows a different trajectory in children with autism spectrum disorders (ASD) than in typically developing children. A proxy for neurodevelopment could be head ...circumference (HC), but studies assessing HC and its clinical correlates in ASD have been inconsistent. This study investigates HC and clinical correlates in the Simons Simplex Collection cohort. Methods We used a mixed linear model to estimate effects of covariates and the deviation from the expected HC given parental HC (genetic deviation). After excluding individuals with incomplete data, 7225 individuals in 1891 families remained for analysis. We examined the relationship between HC/genetic deviation of HC and clinical parameters. Results Gender, age, height, weight, genetic ancestry, and ASD status were significant predictors of HC (estimate of the ASD effect = .2 cm). HC was approximately normally distributed in probands and unaffected relatives, with only a few outliers. Genetic deviation of HC was also normally distributed, consistent with a random sampling of parental genes. Whereas larger HC than expected was associated with ASD symptom severity and regression, IQ decreased with the absolute value of the genetic deviation of HC. Conclusions Measured against expected values derived from covariates of ASD subjects, statistical outliers for HC were uncommon. HC is a strongly heritable trait, and population norms for HC would be far more accurate if covariates including genetic ancestry, height, and age were taken into account. The association of diminishing IQ with absolute deviation from predicted HC values suggests HC could reflect subtle underlying brain development and warrants further investigation.
Introduction
Breast cancer survivors experience diminished health-related quality of life (HRQOL). We report on the influence of tai chi chuan exercise (TCC) on HRQOL and explore associations between ...changes in HRQOL and biomarkers.
Methods
Breast cancer survivors (
N
= 21) were randomly assigned to TCC or standard support therapy (SST) for 12 weeks (three times/week; 60 min/session). Interleukin-6, interleukin-8 (IL-8), insulin-like growth factor-1 (IGF-1), insulin-like growth factor-binding protein (IBFBP)-1, IGFBP-3, glucose, insulin, and cortisol were measured pre- and postintervention. Overall HRQOL and subdomains were assessed at preintervention (T1), midintervention (T2) and postintervention (T3) and biomarkers at T1 and T3.
Results
The TCC group improved in total HRQOL (T1–T2:CS = 8.54,
P
= 0.045), physical functioning (T1–T2:CS = 1.89,
P
= 0.030), physical role limitations (T1–T2 CS = 1.55,
P
= 0.023), social functioning (T1–T3:CS = 1.50,
P
= 0.020), and general mental health (T1–T2:CS = 2.67,
P
= 0.014; T1–T3:CS = 2.44,
P
= 0.019). The SST improved in social functioning (T1–T2:CS = 0.64,
P
= 0.043) and vitality (T1–T2:CS = 0.90,
P
= 0.01). There were relationships between changes in IGF-1 and overall HRQOL (
r
= −0.56;
P
< 0.05), physical role limitation (
r
= −0.68;
P
< 0.05), and social functioning (
r
= −0.56;
P
< 0.05). IGFBP-1 changes were associated with physical role limitations changes (
r
= 0.60;
P
< 0.05). IGFBP-3 changes were associated with physical functioning changes (
r
= 0.46;
P
≤ 0.05). Cortisol changes were associated with changes in physical role limitations (
r
= 0.74;
P
< 0.05) and health perceptions (
r
= 0.46;
P
< 0.05). Glucose changes were associated with emotional role limitation changes (
r
= −0.70;
P
< 0.001). IL-8 changes were associated with emotional role limitation changes (
r
= 0.59;
P
< 0.05).
Discussion/conclusions
TCC may improve HRQOL by regulating inflammatory responses and other biomarkers associated with side effects from cancer and its treatments.
Implications for cancer survivors
TCC may be an intervention capable of improving HRQOL in breast cancer survivors.