Reliability of sleep spindle measurements in adolescents: How many nights are necessary?

Evidence of night‐to‐night variation in adolescent sleep spindle characteristics is lacking. Twelve adolescents (M = 15.8 ± 0.8 years, eight males) participated in a laboratory study involving 9 nights with 10 hr sleep opportunity. Sleep electroencephalograph was analysed and intra‐class coefficients calculated to determine the reliability of sleep spindles across multiple nights of recording. Slow spindle amplitude and fast spindle density, duration and amplitude characteristics all had acceptable reliability within a single night of sleep recording. Slow spindle density and duration measurements needed a minimum of 4 and 2 nights, respectively, for reliable estimation. Theoretical and methodological implications are discussed.     

Why diabetes patients are more prone to the development of colon cancer?

Type II diabetes mellitus (T2D) develops as the consequence of relative insulin insufficiency. The onset of T2D is characterized by insulin resistance, and in most cases, with hyperinsulinemia for compensation. Extensive basic and clinical examinations have identified a large profile of T2D susceptibility genes and multiple risk factors, including obesity and sedentary life style, which are shared by colon cancer development. The intestinal endocrine L cells produce an incretin hormone, namely glucagon-like peptide-1 (GLP-1), which stimulates insulin secretion in blood glucose dependent manner, pancreatic beta cell proliferation and neogenesis. It has been shown that in T2D patients, postprandial GLP-1 secretion level is reduced. I hypothesize that during the development of insulin resistance, intestinal endocrine L cells produce more GLP-1 for compensation. This compensatory response involves the activation of Wnt signaling pathway and the cross-talk between Wnt and insulin signaling pathways. A pathological consequence of this compensation will be the stimulated expression of proto-oncogenes, including c-Myc.     

How many deleterious mutations are there in the human genome?

An estimate of the number of deleterious mutations in the human genome is made using data on the frequency of rare recessive disease in cousin marriages and in the general population. Sexual reproduction ensures that deleterious mutations are distributed at random in zygotes with an approximate Poisson distribution. The mean of this distribution is the sum of the mean number of deleterious mutations in zygotes which contribute to the next generation (Y) and the mean number of new mutations which arise in each human generation (X). The estimates are that X is between 1 and 2.6 and Y is between 12 and 32. A mathematical model based on redundancy is then used to predict how zygote survival will vary with the number of deleterious mutations. The form of this relationship is the same as that seen in experiments on cell survival following radiation-induced mutational damage and this provides independent support for this theoretical approach. The zygotes that survive to contribute to the next generation have a skewed distribution with a mean of Y. It is argued that the number of deleterious mutations in the genome is an important variable in health and disease.     

How many types of cholinergic sympathetic neuron are there in the rat stellate ganglion?

Sympathetic cholinergic postganglionic neurons are present in many sympathetic ganglia. Three classes of sympathetic cholinergic neuron have been reported in mammals; sudomotor neurons, vasodilator neurons and neurons innervating the periosteum. We have examined thoracic sympathetic ganglia in rats to determine if any other classes of cholinergic neurons exist. We could identify cholinergic sudomotor neurons and neurons innervating the rib periosteum, but confirmed that cholinergic sympathetic vasodilator neurons are absent in this species. Sudomotor neurons contained vasoactive intestinal peptide (VIP) and calcitonin gene-related peptide (CGRP) and always lacked calbindin. Cholinergic neurons innervating the periosteum contained VIP and sometimes calbindin, but always lacked CGRP. Cholinergic neurons innervating the periosteum were usually surrounded by terminals immunoreactive for CGRP. We conclude that if any undiscovered populations of cholinergic neurons exist in the rat thoracic sympathetic chain, then they are indistinguishable in size, neurochemistry and inputs from sudomotor or cholinergic neurons innervating the periosteum. It may be that the latter two populations account for all cholinergic neurons in the rat thoracic sympathetic chain ganglia.     

Is a new perspective for definition and diagnostic criteria of fibromyalgia in early stage cancer patients necessary?

Fibromyalgia is a most common pain syndrome characterized by the presence of chronic widespread pain and tenderness with manual palpation. However there is no enough data about frequent of fibromyalgia syndrome in patients with cancer. How often FM is being used in oncological practice and how we are managing this case by medical oncologists. Widespread pain index and symptom severity scale are not clear enough in patients with cancer when ACR-2010 diagnostic criteria for FM are considered. In conclusion, there is it may more prevalence of fibromyalgia in patients with cancer. For the diagnosis of fibromyalgia, be new diagnostic criteria for early-stage cancer patients.     

Development and selection of T cells: how many subsets? How many rules?

Since the discovery indicating that thymus-derived lymphocytes (T cells) can be divided into two subpopulations: CD8+ (killer) and CD4+ (helper) cells, subsequent studies revealed a bewildering heterogeneity of T cells. In the present review an attempt is made to present the current picture of T cell heterogeneity, introduce some order into the nomenclature, and summarize the rules behind the development and selection of different currently recognized T cell subsets.     

Histopathological assessment of lymph nodes in upper gastrointestinal cancer: does triple levelling detect significantly more metastases?

Background

For cancers of the upper gastrointestinal tract it is standard to examine one section/level, from paraffin blocks containing lymph node tissue, for metastatic tumour.

Aims

To determine whether significantly more metastases can be detected by assessing two additional levels.

Methods

101 archival upper gastrointestinal cancers were evaluated. All negative lymph nodes were examined at two additional levels separated by 100 μm and stained by H&E. The slides were examined for the presence of metastases.

Results

1143 lymph nodes, that were originally clear of metastases, were examined at a further two levels (three levels in total); 23 additional metastases were identified in 17 patients. Eleven of these patients were already stage N1 before examination of the additional levels. However, six patients were originally N0, and were therefore upgraded to N1.

Conclusions

Examining lymph nodes at three levels did detect more metastatic deposits than examination of one section/level. In six patients this changed the N stage from N0 to N1. This would have significant prognostic and management implications.Approximately 15 000 people develop cancer of the oesophagus, oesophagogastric junction and stomach in the UK each year, and in the developing world adenocarcinoma of the gastro‐oesophageal junction is increasing in incidence faster than any other type of gastrointestinal cancer.^1,2 Surgical resection remains the mainstay of potentially curative treatment, but is high risk and long‐term survival is disappointing.The most commonly used staging system in the UK for upper gastrointestinal tumours is the TNM classification system of tumours.³ Lymph node status is one of the most significant, if not the most significant, indicator of prognosis in such cancers.^4,5,6,7 The TNM classification places patients with lymph node tumour deposits in category N1 for oesophageal cancer and N1, N2 or N3 for gastric cancer depending on the number of lymph nodes involved. There is no separate TNM classification for tumours of the oesophagogastric junction, and it can be difficult at times for the pathologist to decide which staging classification to use (oesophageal or gastric) for such tumours. There is a lack of evidence based guidance on how best to sample lymph nodes from upper gastrointestinal tumours.The Royal College of Pathologists'' minimum dataset for gastric carcinoma states that lymph nodes identified within the resection specimen should be cut through their greatest diameter and one half taken for microscopy.⁸ The Royal College of Pathologists'' minimum dataset for oesophageal cancer does not comment on how lymph nodes should be sampled; however it does state that there was not enough evidence at the time of publication to support the use of immunohistochemistry and serial sections to detect micrometastases.⁹ Drafts of the revised datasets for reporting oesophageal and gastric carcinomas are available on the Royal College of Pathologists website.^10,11 The revised draft copy of the oesophageal dataset recommends the use of TNM5 over TNM6, but there is still no advice on how to sample lymph nodes. The revised draft copy of the gastric dataset states all lymph nodes found should be sampled, but there is no additional advice on how to do this. In best practice guidelines for handling oesophageal resection specimens, the recommendation for lymph node sampling is to sample lymph nodes clearly replaced by tumour and to completely sample all lymph nodes that appear tumour free.¹² The College of American Pathologists recommends evaluating all lymph nodes, but again does not comment on how best to do this.¹³On review of the literature, there appears to be little information on the value of serial sections of lymph nodes within oesophageal and gastric carcinomas to detect metastatic carcinoma. In some subspecialty areas, the use of serial sections has been examined. In the area of breast pathology, the National Health Service Breast Screening Programme, published in 1995, did recommend examination of lymph nodes less than 5 mm at two levels.¹⁴ However, in the more recent publication (January 2005), examination of levels was stated not to be routinely necessary.¹⁵ However, it is recommended that lymph nodes should be sliced at intervals of approximately 3 mm or less, perpendicular to the long axis, as this is an effective and simpler alternative to serial sectioning to detect small metastatic deposits in lymph nodes. The use of triple levelling has been assessed in colorectal carcinoma, and in a study of 100 colorectal carcinoma resection specimens, 12 extra metastases, in 11 patients, were discovered within lymph nodes at levels 2 and 3, which were negative in level 1.¹⁶Despite the lack of information on serial sectioning there have been numerous publications, examining the detection of micrometastases with immunohistochemistry in lymph nodes from resection specimens of the oesophagus and stomach. These studies show an increase in the detection of micrometastases of between 10% and 40%.^{17,18,19,20,21,22} The detection of micrometastases did not appear to be related to prognosis in the majority of studies examining oesophageal carcinoma, (predominantly squamous in type); however, there did appear to be a reduction in prognosis in patients with micrometastases from gastric adenocarcinomas.An audit was completed to examine the value of performing three serial sections on lymph nodes from carcinomas of the oesophagus, gastro‐oesophageal junction and stomach to detect increased numbers of metastases.     

How are complex cell properties adapted to the statistics of natural stimuli?

Sensory areas should be adapted to the properties of their natural stimuli. What are the underlying rules that match the properties of complex cells in primary visual cortex to their natural stimuli? To address this issue, we sampled movies from a camera carried by a freely moving cat, capturing the dynamics of image motion as the animal explores an outdoor environment. We use these movie sequences as input to simulated neurons. Following the intuition that many meaningful high-level variables, e.g., identities of visible objects, do not change rapidly in natural visual stimuli, we adapt the neurons to exhibit firing rates that are stable over time. We find that simulated neurons, which have optimally stable activity, display many properties that are observed for cortical complex cells. Their response is invariant with respect to stimulus translation and reversal of contrast polarity. Furthermore, spatial frequency selectivity and the aspect ratio of the receptive field quantitatively match the experimentally observed characteristics of complex cells. Hence, the population of complex cells in the primary visual cortex can be described as forming an optimally stable representation of natural stimuli.     

How many factors does the sense of community index assess?

Studies of university students’ sense of community (SOC) use various scales, one of which is the widely used Sense of Community Index (SCI), conceptualized as a 4‐factor model: membership, influence, needs fulfillment, and shared emotional connection. Research has been unable to show a reliable 4‐factor solution. One possible explanation may be that negatively worded items contribute to lack of model fit, which would be consistent with the claim that SOC was conceptualized as a unipolar positive construct. Data were collected using a positively worded SCI (N = 794). Four models were tested with confirmatory factor analysis in structural equation modeling: 1‐factor, theorized four‐factor, revised 3‐factor, and revised 4‐factor. None of the models showed good fit, though the fit of the 1‐factor model was improved over the 4‐factor. More studies are needed to attempt replication with a positively worded SCI.     

How useful are CBC and reticulocyte reports to clinicians?

We surveyed 1,353 attending and 689 house staff physicians of the University Hospitals of Cleveland to ascertain the parameters of the CBC, leukocyte differential, and reticulocyte reports perceived as useful in clinical practice. The response rate was 33% for attending and 22% for house staff physicians. Only 4 of 11 parameters routinely reported in the CBC battery were selected as frequently or always useful by more than 90% of physicians: hemoglobin, hematocrit, platelet count, and WBC count. Among primary care physicians, the mean cell volume also attained this level of usefulness for the evaluation of anemia. There were no differences between academic physicians and community physicians in the use of RBC indices; however, physicians who had been in practice for fewer than 10 years indicated higher use of the red cell distribution width than physicians practicing for more than 10 years. Most physicians prefer differentials reported as percentages rather than absolute counts. Among physicians who monitor reticulocyte counts, the immature reticulocyte fraction is not widely used. Our results indicate that many physicians do not use much of the data provided in routine CBC/differential and reticulocyte reports. Some modifications of report formats may facilitate physician perception of hematology laboratory results.     

Diagnostic utility of MS-MLPA in DNA methylation profiling of adenocarcinomas and neuroendocrine carcinomas of the colon–rectum

Methylation-specific multiple ligation-dependent probe amplification (MS-MLPA) is a fast, new, inexpensive method that has rarely been exploited in DNA methylation profiling of colorectal cancers (CRCs). The aim of this study was to test the diagnostic utility of MS-MLPA to evaluate the methylation status of 34 genes in normal colonic mucosa samples and in a well-characterized series of 83 adenocarcinomas and 21 neuroendocrine carcinomas of colon–rectum. Two commercial MS-MLPA kits (SALSA MS-MLPA ME001-C1 Tumor suppressor-1 Kit and SALSA MS-MLPA ME002-B1 Tumor suppressor-2 Kit) were used to perform promoter methylation analysis on formalin-fixed and paraffin-embedded tissues. MS-MLPA analysis was validated by bisulfite pyrosequencing, bisulfite cycle sequencing, and methylation-specific PCR. MS-MLPA analysis identified a subset of 27 CRCs (26 % of cases) showing high levels of gene methylation involving a mean percentage of 34 % of the promoters examined. These tumors exhibited all the main clinicopathological and genetic features described for CRCs with CpG island Methylator Phenotype-High. High levels of methylation were observed with similar frequency in adenocarcinomas and in neuroendocrine carcinomas (25 % versus 29 %, respectively), but different methylation profiles were observed in the two tumor types. In both groups, tumors with microsatellite instability and widespread methylation represented a homogeneous clinicopathological entity. MS-MLPA assay is an easy and reliable system for epigenetic characterization of tumor tissues and leads to a rapid identification of CRCs with the highest levels of gene methylation. Aberrant gene methylation is a common abnormality in CRC initiation and may be observed in tumors with very different genetic and clinicopathological profiles.