Mitochondrial junction region as genotyping marker for cyclospora cayetanensis

© 2019, Centers for Disease Control and Prevention (CDC). All rights reserved. Cyclosporiasis is an infection caused by Cyclospora cayetanensis, which is acquired by consumption of contaminated fresh food or water. In the United States, cases of cyclosporiasis are often associated with foodborne outbreaks linked to imported fresh produce or travel to disease-endemic countries. Epidemiologic investigation has been the primary method for linking outbreak cases. A molecular typing marker that can identify genetically related samples would be helpful in tracking outbreaks. We evaluated the mitochondrial junction region as a potential genotyping marker. We tested stool samples from 134 laboratory-confirmed cases in the United States by using PCR and Sanger sequencing. All but 2 samples were successfully typed and divided into 14 sequence types. Typing results were identical among samples within each epidemiologically defined case cluster for 7 of 10 clusters. These findings suggest that this marker can distinguish between distinct case clusters and might be helpful during cyclosporiasis outbreak investigation

The relationship between quality of life (EORTC QLQ-C30) and survival in patients with gastro-oesopohageal cancer

It remains unclear whether any aspect of quality of life has a role in predicting survival in an unselected cohort of patients with gastro-oesophageal cancer. Therefore the aim of the present study was to examine the relationship between quality of life (EORTC QLQ-C30), clinico-pathological characteristics and survival in patients with gastro-oesophageal cancer. Patients presenting with gastric or oesophageal cancer, staged using the UICC tumour node metastasis (TNM) classification and who received either potentially curative surgery or palliative treatment between November 1997 and December 2002 (n=152) participated in a quality of life study, using the EORTC QLQ-C30 core questionnaire. On univariate analysis, age (P < 0.01), tumour length (P < 0.0001), TNM stage (P<0.0001), weight loss (P<0.0001), dysphagia score (P<0.001), performance status (P<0.1) and treatment (P<0.0001) were significantly associated with cancer-specific survival. EORTC QLQ-C30, physical functioning (P<0.0001), role functioning (P<0.001), cognitive functioning (P<0.01), social functioning (P<0.0001), global quality of life (P<0.0001), fatigue (P<0.0001), nausea/vomiting (P<0.01), pain (P<0.001), dyspnoea (P<0.0001), appetite loss (P<0.0001) and constipation (P<0.05) were also significantly associated with cancer-specific survival. On multivariate survival analysis, tumour stage (P<0.0001), treatment (P<0.001) and appetite loss (P<0.0001) were significant independent predictors of cancer-specific survival. The present study highlights the importance of quality of life (EORTC QLQ-C30) measures, in particular appetite loss, as a prognostic factor in these patients

Evidence for Superfluidity of Ultracold Fermions in an Optical Lattice

The study of superfluid fermion pairs in a periodic potential has important ramifications for understanding superconductivity in crystalline materials. Using cold atomic gases, various condensed matter models can be studied in a highly controllable environment. Weakly repulsive fermions in an optical lattice could undergo d-wave pairing at low temperatures, a possible mechanism for high temperature superconductivity in the cuprates. The lattice potential could also strongly increase the critical temperature for s-wave superfluidity. Recent experimental advances in the bulk include the observation of fermion pair condensates and high-temperature superfluidity. Experiments with fermions and bosonic bound pairs in optical lattices have been reported, but have not yet addressed superfluid behavior. Here we show that when a condensate of fermionic atom pairs was released from an optical lattice, distinct interference peaks appear, implying long range order, a property of a superfluid. Conceptually, this implies that strong s-wave pairing and superfluidity have now been established in a lattice potential, where the transport of atoms occurs by quantum mechanical tunneling and not by simple propagation. These observations were made for unitarity limited interactions on both sides of a Feshbach resonance. For larger lattice depths, the coherence was lost in a reversible manner, possibly due to a superfluid to insulator transition. Such strongly interacting fermions in an optical lattice can be used to study a new class of Hamiltonians with interband and atom-molecule couplings.Comment: accepted for publication in Natur

Quality of sleep in patients with schizophrenia is associated with quality of life and coping

BACKGROUND: While sleep disturbance is widespread in schizophrenia it is less clear whether sleep disturbance is uniquely related to impaired coping and perceived quality of life. METHODS: We simultaneously assessed sleep quality, symptoms, and coping in 29 persons with schizophrenia or schizoaffective disorder in a post acute phase of illness. Assessment instruments included the Pittsburgh Sleep Quality Index; the Positive and Negative Symptom Scale; the Heinrichs Quality of Life Scale; and the Ways of Coping Scale. Multiple regressions were performed predicting quality of life and coping from sleep quality controlling for age and symptom severity. On a subset of seven subjects non-dominant wrist actigraphy was used as an objective check of their self-reported poor sleep. RESULTS: Analyses revealed that poor sleep quality predicted low quality of life (r = -0.493; p = .022) and reduced preference for employing positive reappraisal when facing a stressor (r = -0.0594; p = 0.0012). Actigraphy confirmed poor sleep quality in a subset of subjects. They had shorter sleep duration (p < .0005), shorter average sleep episodes (p < .005) and more episodes of long awakening (p < 0.05) than community norms. CONCLUSION: The results are consistent with the hypotheses that poor sleep may play a unique role in sustaining poor quality of life and impaired coping in patients with schizophrenia. These associations may hold for community controls as well

Genetic and Molecular Analysis of Wild-Derived Arrhythmic Mice

A new circadian variant was isolated by screening the intercross offspring of wild-caught mice (Mus musculus castaneus). This variant was characterized by an initial maintenance of damped oscillations and subsequent loss of rhythmicity after being transferred from light-dark (LD) cycles to constant darkness (DD). To map the genes responsible for the persistence of rhythmicity (circadian ratio) and the length of free-running period (τ), quantitative trait locus (QTL) analysis was performed using F2 mice obtained from an F1 cross between the circadian variant and C57BL/6J mice. As a result, a significant QTL with a main effect for circadian ratio (Arrhythmicity; Arrh-1) was mapped on Chromosome (Chr) 8. For τ, four significant QTLs, Short free-running period (Sfp-1) (Chr 1), Sfp-2 (Chr 6), Sfp-3 (Chr 8), Sfp-4 (Chr 11) were determined. An epistatic interaction was detected between Chr 3 (Arrh-2) and Chr 5 (Arrh-3). An in situ hybridization study of clock genes and mouse Period1::luciferase (mPer1::luc) real-time monitoring analysis in the suprachiasmatic nucleus (SCN) suggested that arrhythmicity in this variant might not be attributed to core circadian mechanisms in the SCN neurons. Our strategy using wild-derived variant mice may provide a novel opportunity to evaluate circadian and its related disorders in human that arise from the interaction between multiple variant genes

Developments in esophageal surgery for adenocarcinoma: a comparison of two decades

<p>Abstract</p> <p>Background</p> <p>The objective of this study was to examine outcomes in patients undergoing esophageal resection for adenocarcinoma at our institution during a 20-year period and, in particular, to address temporal trends in long-term survival.</p> <p>Methods</p> <p>Out of 470 patients who underwent esophagectomy for malignancy between September 1985 and September 2005, a total number of 175 patients presented with esophageal adenocarcinoma. Patients enrolled in this study included AEG (adenocarcinoma of the esophagogastric junction) type I tumors only. Time trends were studied comparing two decades, 9/1985 to 9/1995 (DI) and 10/1995 to 9/2005 (DII).</p> <p>Results</p> <p>The overall survival was significantly more favourable in patients undergoing esophageal resection for adenocarcinoma in the recent time period (DII, 10/1995 to 9/2005) as compared to the early time period (DI, 9/1985 to 9/1995) (log rank test: p = 0.0329). Significant differences in the recent decade were seen based on lower ASA-classifications, earlier tumor stages, and the operative procedure with a higher frequency of transhiatal resections (p < 0.05). 30-day mortality improved from 8.3% to 3.1% during the 20-year time-interval, thus without statistical significance.</p> <p>Conclusion</p> <p>Based on our experience, overall survival is improving over time for adenocarcinoma of the esophagus. Factors that may play an important role in this trend include early diagnosis and improved patient selection through better preoperative staging, improved surgical technique with a tailored approach carefully evaluated by physiologic patient status, comorbidity and tumor extent.</p

Gene expression of PMP22 is an independent prognostic factor for disease-free and overall survival in breast cancer patients

<p>Abstract</p> <p>Background</p> <p>Gene expression of peripheral myelin protein 22 (<it>PMP22</it>) and the epithelial membrane proteins (<it>EMPs</it>) was found to be differentially expressed in invasive and non-invasive breast cell lines in a previous study. We want to evaluate the prognostic impact of the expression of these genes on breast cancer.</p> <p>Methods</p> <p>In a retrospective multicenter study, gene expression of <it>PMP22 </it>and the <it>EMPs </it>was measured in 249 primary breast tumors by real-time PCR. Results were statistically analyzed together with clinical data.</p> <p>Results</p> <p>In univariable Cox regression analyses PMP22 and the EMPs were not associated with disease-free survival or tumor-related mortality. However, multivariable Cox regression revealed that patients with higher than median <it>PMP22 </it>gene expression have a 3.47 times higher risk to die of cancer compared to patients with equal values on clinical covariables but lower <it>PMP22 </it>expression. They also have a 1.77 times higher risk to relapse than those with lower <it>PMP22 </it>expression. The proportion of explained variation in overall survival due to <it>PMP22 </it>gene expression was 6.5% and thus PMP22 contributes equally to prognosis of overall survival as nodal status and estrogen receptor status. Cross validation demonstrates that 5-years survival rates can be refined by incorporating <it>PMP22 </it>into the prediction model.</p> <p>Conclusions</p> <p><it>PMP22 </it>gene expression is a novel independent prognostic factor for disease-free survival and overall survival for breast cancer patients. Including it into a model with established prognostic factors will increase the accuracy of prognosis.</p

A guideline for analyzing circadian wheel-running behavior in rodents under different lighting conditions

Most behavioral experiments within circadian research are based on the analysis of locomotor activity. This paper introduces scientists to chronobiology by explaining the basic terminology used within the field. Furthermore, it aims to assist in designing, carrying out, and evaluating wheel-running experiments with rodents, particularly mice. Since light is an easily applicable stimulus that provokes strong effects on clock phase, the paper focuses on the application of different lighting conditions

High-dose chemoradiotherapy followed by surgery versus surgery alone in esophageal cancer: a retrospective cohort study

<p>Abstract</p> <p>Background</p> <p>We aimed to assess whether high-dose preoperative chemoradiotherapy (CRT) improves outcome in esophageal cancer patients compared to surgery alone and to define possible prognostic factors for overall survival.</p> <p>Methods</p> <p>Hundred-and-seven patients with disease stage IIA - III were treated with either surgery alone (n = 45) or high-dose preoperative CRT (n = 62). The data were collected retrospectively. Sixty-seven patients had adenocarcinomas, 39 squamous cell carcinomas and one undifferentiated carcinoma. CRT was given as three intensive chemotherapy courses by cisplatin 100 mg/m²on day 1 and 5-fluorouracil 1000 mg/m²/day, from day 1 through day 5 as continuous infusion. One course was given every 21 days. The last two courses were given concurrent with high-dose radiotherapy, 2 Gy/fraction and a median dose of 66 Gy. Kaplan-Meier survival analysis with log rank test was used to obtain survival data and Cox Regression multivariate analysis was used to define prognostic factors for overall survival.</p> <p>Results</p> <p>Toxicity grade 3 of CRT occurred in 30 (48.4%) patients and grade 4 in 24 (38.7%) patients of 62 patients. One patient died of neutropenic infection (grade 5). Fifty percent (31 patients) in the CRT group did undergo the planned surgery. Postoperative mortality rate was 9% and 10% in the surgery alone and CRT+ surgery groups, respectively (p = 1.0). Median overall survival was 11.1 and 31.4 months in the surgery alone and CRT+ surgery groups, respectively (log rank test, p = 0.042). In the surgery alone group one, 3 and 5 year survival rates were 44%, 24% and 16%, respectively and in the CRT+ surgery group they were 68%, 44% and 29%, respectively. By multivariate analysis we found that age of patient, performance status, alcoholism and > = 4 pathological positive lymph nodes in resected specimen were significantly associated with overall survival, whereas high-dose preoperative CRT was not.</p> <p>Conclusion</p> <p>We found no significant survival advantage in esophageal cancer stage IIA-III following preoperative high-dose CRT compared to surgery alone. Patient's age, performance status, alcohol abuse and number of positive lymph nodes were prognostic factors for overall survival.</p

Protein Phosphatase 2A Mediates Dormancy of Glioblastoma Multiforme-Derived Tumor Stem-Like Cells during Hypoxia

The hypoxic microenvironment of glioblastoma multiforme (GBM) is thought to increase resistance to cancer therapies. Recent evidence suggests that hypoxia induces protein phosphatase 2A (PP2A), a regulator of cell cycle and cell death. The effects of PP2A on GBM tumor cell proliferation and survival during hypoxic conditions have not been studied.Expression of PP2A subunits and HIF-α proteins was measured in 65 high-grade astrocytoma and 18 non-neoplastic surgical brain specimens by western blotting. PP2A activity was measured by an immunoprecipitation assay. For in vitro experiments, GBM-derived tumor stem cell-like cells (TSCs) were exposed to severe hypoxia produced by either CoCl₂ or 1% O₂. PP2A activity was inhibited either by okadaic acid or by shRNA depletion of the PP2A C subunit. Effects of PP2A activity on cell cycle progression and cell survival during hypoxic conditions were assessed using flow cytometry.In our patient cohort, PP2A activity was positively correlated with HIF-1∝ protein expression (P = 0.002). Patients with PP2A activity levels above 160 pMP had significantly worse survival compared to patients with levels below this threshold (P = 0.002). PP2A activity was an independent predictor of survival on multivariable analysis (P = 0.009). In our in vitro experiments, we confirmed that severe hypoxia induces PP2A activity in TSCs 6 hours after onset of exposure. PP2A activity mediated G1/S phase growth inhibition and reduced cellular ATP consumption in hypoxic TSCs. Conversely, inhibition of PP2A activity led to increased cell proliferation, exhaustion of intracellular ATP, and accelerated P53-independent cell death of hypoxic TSCs.Our results suggest that PP2A activity predicts poor survival in GBM. PP2A appears to reduce the metabolic demand of hypoxic TSCs and enhances tumor cell survival. Modulation of PP2A may be a potential target for cancer therapy