Αρχειοθήκη ιστολογίου

Τρίτη 21 Νοεμβρίου 2017

Building trophic specializations that result in substantial niche partitioning within a young adaptive radiation

Abstract

Dietary partitioning often accompanies the increased morphological diversity seen during adaptive radiations within aquatic systems. While such niche partitioning would be expected in older radiations, it is unclear how significant morphological divergence occurs within a shorter time period. Here we show how differential growth in key elements of the feeding mechanism can bring about pronounced functional differences among closely related species. An incredibly young adaptive radiation of three Cyprinodon species residing within hypersaline lakes in San Salvador Island, Bahamas, has recently been described. Characterized by distinct head shapes, gut content analyses revealed three discrete feeding modes in these species: basal detritivory as well as derived durophagy and lepidophagy (scale-feeding). We dissected, cleared and stained, and micro-CT scanned species to assess functionally relevant differences in craniofacial musculoskeletal elements. The widespread feeding mode previously described for cyprinodontiforms, in which the force of the bite may be secondary to the requisite dexterity needed to pick at food items, is modified within both the scale specialist and the durophagous species. While the scale specialist has greatly emphasized maxillary retraction, using it to overcome the poor mechanical advantage associated with scale-eating, the durophage has instead stabilized the maxilla. In all species the bulk of the adductor musculature is composed of AM A1. However, the combined masses of both adductor mandibulae (AM) A1 and A3 in the scale specialist were five times that of the other species, showing the importance of growth in functional divergence. The scale specialist combines plesiomorphic jaw mechanisms with both a hypertrophied AM A1 and a slightly modified maxillary anatomy (with substantial functional implications) to generate a bite that is both strong and allows a wide range of motion in the upper jaw, two attributes that normally tradeoff mechanically. Thus, a significant feeding innovation (scale-eating, rarely seen in fishes) may evolve based largely on allometric changes in ancestral structures. Alternatively, the durophage shows reduced growth with foreshortened jaws that are stabilized by an immobile maxilla. Overall, scale specialists showed the most divergent morphology, suggesting that selection for scale-biting might be stronger or act on a greater number of traits than selection for either detritivory or durophagy. The scale specialist has colonized an adaptive peak that few lineages have climbed. Thus, heterochronic changes in growth can quickly produce functionally relevant change among closely related species.



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The usefulness of chief complaints to predict severity, ventilator dependence, treatment option, and short-term outcome of patients with Guillain-Barré syndrome: a retrospective study

It remains an urgent need for early recognition of disease severity, treatment option and outcome of Guillain-Barré syndrome (GBS). The chief complaint may be quickly obtained in clinic and is one of the candi...

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Response Regarding Surgical Techniques for Retrograde Parotidectomy

We thank Dr. Tim-Lin Chow and his team for their response to our article and for their contributions to the field.

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Reconstruction of intraoral defects after resection of cancer with two types of submental artery perforator flaps

The submental island flap is a common choice for reconstruction of intraoral defects. To obtain a thinner, more pliable flap and get a better oncological result, the submental artery perforator flap has been proposed, and to assess its feasibility for closure of defects after resection of cancers of the oral cavity we studied 20 patients, each of whom was treated in this way. All the flaps were classified into those with septocutaneous perforators (n=16) and those with musculocutaneous perforators (n=4), and the main veins that drained the flaps were two submental veins (n=17).

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Clinical outcomes of dental implants after use of tenting for bony augmentation: a systematic review

The reconstruction of severely atrophic ridges is often challenging and complicated. We searched the Medline, Embase, and Cochrane databases for articles up to October 2015 that reported the success of all types of tenting for bony regeneration. We extracted data on the size and site of the defect, the number of patients, vertical and horizontal augmentation, survival of dental implants, and complications. Thirteen studies were included, which yielded data on 423 patients with 1111 dental implants.

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Corrigendum to “Craniofacial implants at a single centre 2005–2015: retrospective review of 451 implants” [Br J Oral Maxillofac Surg 2017;55:242-5]

The authors regret an incorrect Fig. 1 published in the above mentioned paper. Please find correct figure below:

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Is a fractured mandible an emergency?

We retrospectively audited the records of 708 patients who presented with the diagnosis of fractured mandible between January 2009 and July 2013 at the Queen Elizabeth Hospital, Birmingham. We assessed the different factors that may have altered their outcomes, and found that delay before definitive fixation caused no harm in either the short or the long term.

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Prioritization to visual objects: Roles of sensory uncertainty

Abstract

Two hypotheses, attentional prioritization and attentional spreading, have been proposed to account for object-based attention. The attentional-prioritization hypothesis posits that the positional uncertainty of targets is sufficient to resolve the controversy raised by the competing attentional-spreading hypothesis. Here we challenge the sufficiency of this explanation by showing that object-based attention is a function of sensory uncertainty in a task with consistent high positional uncertainty of the targets. In Experiment 1, object-based attention was modulated by sensory uncertainty induced by the noise from backward masking, showing an object-based effect under high as compared to low sensory uncertainty. This finding was replicated in Experiment 2 with increased task difficulty, to exclude that as a confounding factor, and in Experiment 3 with a psychophysical method, to obtain converging evidence using perceptual threshold measurement. Additionally, such a finding was not observed when sensory uncertainty was eliminated by replacing the backward-masking stimuli with perceptually dissimilar ones in Experiment 4. These results reveal that object-based attention is influenced by sensory uncertainty, even under high positional uncertainty of the targets. Our findings contradict the proposition of attentional spreading, proposing instead an automatic form of object-based attention due to enhancement of the perceptual representation. More importantly, the attentional-prioritization hypothesis based solely on positional uncertainty cannot sufficiently account for object-based attention, but needs to be developed by expanding the concept of uncertainty to include at least sensory uncertainty.



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Identification of alpha-gal sensitivity in patients with a diagnosis of idiopathic anaphylaxis

Abstract

IgE antibodies (Ab) specific to galactose-α-1,3-galactose (alpha-gal) are responsible for a delayed form of anaphylaxis that occurs 3 to 6 hours after red meat ingestion. In a unique prospective study of seventy participants referred with a diagnosis of idiopathic anaphylaxis (IA), six (9%) were found to have IgE to alpha-gal. Upon institution of a diet free of red meat, all patients had no further episodes of anaphylaxis. Two of these individuals had indolent systemic mastocytosis (ISM). Those with ISM had more severe clinical reactions but lower specific IgE to alpha-gal and higher serum tryptase levels, reflective of the mast cell burden. The identification of alpha-gal syndrome in patients with IA supports the need for routine screening for this sensitivity as a cause of anaphylaxis, where reactions to alpha-gal are delayed and thus may be overlooked.

This article is protected by copyright. All rights reserved.



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Crystal structure of the coxsackievirus A16 RNA-dependent RNA polymerase elongation complex reveals novel features in motif A dynamics

Abstract

The RNA-dependent RNA polymerases (RdRPs) encoded by RNA viruses represent a unique class of nucleic acid polymerases. Unlike other classes of single-subunit polymerases, viral RdRPs have evolved a unique conformational change in their palm domain to close the active site during catalysis. The hallmark of this conformational change is the backbone shift of the polymerase motif A from an "open" state to a "closed" state, allowing two universally conserved aspartic acid residues to orient toward each other for divalent metal binding and catalysis. The "closed" motif A conformation was only observed upon the binding of correct NTP in RdRP catalytic complexes or under rare conditions such as induced by a bound lutetium ion or a bound glutamate molecule. By solving the crystal structure of the catalytic elongation complex of the coxsackievirus RdRP, we in this work observed for the first time the "closed" motif A conformation in the absence of an NTP substrate or other conformational-change-inducing factors. This observation emphasizes the intrinsic dynamic features of viral RdRP motif A, and solidifies the structural basis for how this important structural element participates in catalytic events of the RdRPs.



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The combined activation of KCa3.1 and inhibition of Kv11.1/hERG1 currents contribute to overcome Cisplatin resistance in colorectal cancer cells

The combined activation of KCa3.1 and inhibition of Kv11.1/hERG1 currents contribute to overcome Cisplatin resistance in colorectal cancer cells

The combined activation of K<sub>Ca</sub>3.1 and inhibition of K<sub>v</sub>11.1/hERG1 currents contribute to overcome Cisplatin resistance in colorectal cancer cells, Published online: 21 November 2017; doi:10.1038/bjc.2017.392



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The impact of folate intake on the risk of head and neck cancer in the prostate, lung, colorectal, and ovarian cancer screening trial (PLCO) cohort

The impact of folate intake on the risk of head and neck cancer in the prostate, lung, colorectal, and ovarian cancer screening trial (PLCO) cohort

The impact of folate intake on the risk of head and neck cancer in the prostate, lung, colorectal, and ovarian cancer screening trial (PLCO) cohort, Published online: 21 November 2017; doi:10.1038/bjc.2017.383



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Rapid nodal staging of head and neck cancer surgical specimens with flow cytometric analysis

Rapid nodal staging of head and neck cancer surgical specimens with flow cytometric analysis

Rapid nodal staging of head and neck cancer surgical specimens with flow cytometric analysis, Published online: 21 November 2017; doi:10.1038/bjc.2017.408



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Cadherin-1 and cadherin-3 cooperation determines the aggressiveness of pancreatic ductal adenocarcinoma

Cadherin-1 and cadherin-3 cooperation determines the aggressiveness of pancreatic ductal adenocarcinoma

Cadherin-1 and cadherin-3 cooperation determines the aggressiveness of pancreatic ductal adenocarcinoma, Published online: 21 November 2017; doi:10.1038/bjc.2017.411



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Determination of an optimal response cut-off able to predict progression-free survival in patients with well-differentiated advanced pancreatic neuroendocrine tumours treated with sunitinib: an alternative to the current RECIST-defined response

Determination of an optimal response cut-off able to predict progression-free survival in patients with well-differentiated advanced pancreatic neuroendocrine tumours treated with sunitinib: an alternative to the current RECIST-defined response

Determination of an optimal response cut-off able to predict progression-free survival in patients with well-differentiated advanced pancreatic neuroendocrine tumours treated with sunitinib: an alternative to the current RECIST-defined response, Published online: 21 November 2017; doi:10.1038/bjc.2017.402



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The serum leptin level in non-obese patients with obstructive sleep apnea

This study aimed to determine the association between the severity of obstructive sleep apnea (OSA) and the serum leptin level in non-obese OSA patients.

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Factors to improve the interobserver agreement for gastric atrophy and intestinal metaplasia: Consensus of definition and criteria

Abstract

Aims

Intestinal metaplasia and atrophy of the gastric mucosa are associated with Helicobacter pylori infection and are considered premalignant lesions. The updated Sydney system is used to these parameters but experienced pathologists and consensus processes are required for interobserver agreement. We sought to determine the influence of consensus process on assessment of intestinal metaplasia and atrophy.

Methods and results

Two study sets were used; consensus set and validation set. The consensus set was circulated and 5 gastrointestinal pathologists independently evaluated them using the updated Sydney system. After then the consensus of the definitions was determined in the first consensus meeting. The same set was recirculated to determine the effect of the consensus. The second consensus meeting was held to standardize the grading criteria and the validation set was circulated to determine the influence. Two additional circulations were performed to assess the maintainance of consensus and intraobserver variability. Interobserver agreement of intestinal metaplasia and atrophy was improved through consensus process (intestinal metaplasia: baseline κ=0.52 vs. final κ=0.68, p=0.006; atrophy: baseline κ=0.19 vs. final κ=0.43, p<0.001). Higher interobserver agreement in atrophy was observed after consensus of definition (pre-consensus: κ=0.19 vs. post-consensus: κ=0.34, p=0.001). There was improved interobserver agreement in intestinal metaplasia after standardization of the grading criteria (pre-standardization: κ=0.56 vs. post-standardization: κ=0.71, p=0.010).

Conclusions

This study suggests that interobserver variability regarding intestinal metaplasia and atrophy may result from lack of a precise definition and fine criteria, and can be reduced by consensus of definition and standardization of grading criteria.

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The Impact of Hyperosmolarity on Long-Term Outcome in Patients Presenting with Severe Hyperglycemic Crisis: A Population Based Study

Exp Clin Endocrinol Diabetes
DOI: 10.1055/s-0043-117416

Aims We compared characteristics of patients with hyperglycemic hyperosmolar state (HHS) and patients with severe hyperglycemia without the signs of hyperosmolarity and ketoacidosis; analyzed long-term all-cause mortality and potential prognostic factors. Methods The studied population included 261 749 adults. HHS was diagnosed in patients with plasma glucose >33.0 mmol/L, ketonuria <1+, and serum osmolarity >320 mmol/L. Patients with plasma glucose >33.0 mmol/L, ketonuria <1+ and serum osmolarity <320 mmol/L were considered as controls (nHHS). Results During the 5-year period, we observed 68 episodes of HHS in 66 patients and 51 patients with nHHS. Patients with HHS were significantly older, had lower BMI, higher serum C-reactive protein and used diuretics and benzodiazepines more frequently. Mortality rates one, three and 12 months after admission were 19.0, 32.1 and 35.7% in the HHS group, and 4.8, 6.3 and 9.4% in the nHHS group (P<0.001). However, after adjustment for patient age, these differences were not statistically significant. In multivariate Cox regression in HHS group, mortality was positively associated with age, male gender, leukocyte count, amylase, presence of dyspnea and altered mental status, and the use of benzodiazepines, ACE inhibitors and sulphonylureas, while it was inversely associated with plasma glucose, bicarbonate, and the use of thiazides and statins. A nomogram derived from these variables had an accuracy of 89% in predicting lethal outcome. Conclusions Infection, use of furosemide and benzodiazepines may be important precipitating factors of HHS. Prospective clinical trials are mandatory to analyze the safety of ACE-inhibitors and benzodiazepines in elderly patients with diabetes.
[...]

© Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Abstract  |  Full text



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Protective Effect and Potential Mechanism of Simvastatin on Myocardial Injury Induced by Diabetes with Hypoglycemia

Exp Clin Endocrinol Diabetes
DOI: 10.1055/s-0043-110481

Background Simvastatin has been reported to reduce cardiovascular related morbidity and mortality in clinical trials which was independent of its cholesterol-lowering effect. This study aims to investigate the protective effect of simvastatin on myocardial injury caused by diabetic hypoglycemia and the possible underlying mechanism. Methods We used streptozotocin (STZ) at a dose of 55 mg/kg to induce diabetes mellitus (DM) and over-dose insulin to induce hypoglycemia to establish diabetic hypoglycemia rat models. The cardiac protective effect of simvastatin treatment (at a dose of 40 mg/kg·d) upon diabetic hypoglycemia models was assessed. Ex vivo cardiac function, cardiomyocyte inotropic property and calcium transient were evaluated. The expression levels of microRNA (miRNA) and NF-κB in heart tissues were investigated. Results Both systolic and diastolic functions in diabetic rats were weakened, and further worsened in diabetic hypoglycemia rats, partially restored after administration of simvastatin. The protective effect of simvastatin on cardiac function under diabetic hypoglycermia was associated with decreased intracellular calcium and increased calcium sensitivity. miRNA array showed a differential profile of miRNA expression existed in diabetic hypoglycemia rats compared with diabetic non-hypoglycemia group, and that simvastatin could reverse the altered miRNA expression in diabetic hypoglycemia group. Conclusion Simvastatin has protective effect on myocardial injury caused by diabetes with hypoglycemia, which is associated with increased calcium sensitivity, decreased NF-κB expression and altered miRNA expression profile.
[...]

© Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Abstract  |  Full text



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Somatotrope Pituitary Function in Professional Soccer Players

Exp Clin Endocrinol Diabetes
DOI: 10.1055/s-0043-119876

Background and objective Soccer is associated with repetitive head trauma, which, as it is known from sports like football and boxing, can result in hypopituitarism. Gonadotropins and GH are the most common pituitary hormones to become deficient. GH deficiency is associated with an increased risk of cardiovascular mortality and has negative influence on body mass index, visceral fat mass, insulin resistance and sensitivity, bone mineral density and inflammatory markers. Therefore the aim of this study was to evaluate the somatotrope pituitary function in professional soccer players. Research design and methods This clinical study included 15 male, professional soccer players with at least 10 years of professional training. Basal hormonal parameters of the pituitary axis were obtained from the participants. To assess GH-IGF-I axis, glucagon stimulation tests were used. Rise in growth hormone during glucagon test was analyzed and the prevalence of newly diagnosed hormone deficiencies was evaluated. Results Mean age of all participants was 31±10 years. None of the 15 soccer players had GH deficiency. Mean rising factor of GH after stimulation with glucagon was 100 in all participants. We did not find signs of ACTH, TSH or LH/FSH deficiency in any player. Conclusions In this small collective of soccer players we did not find playing soccer to be a risk factor for the development of GH-deficiency. According to our data screening for somatotrope deficiency is not necessary. Further investigations in larger cohorts are needed.
[...]

© Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Abstract  |  Full text



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New CDC Guideline for Preventing Surgical Site Infections

The CDC has provided updated recommendations to help reduce the rate of surgical site infections. Find out what's new.
American Nurse Today

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Microarray analysis of gene expression in the cyclooxygenase (COX) knockout mice - a connection to Autism Spectrum Disorder

Abstract

The cellular and molecular events that take place during brain development play an important role in governing function of the mature brain. Lipid signalling molecules such as prostaglandin E2 (PGE2) play an important role in healthy brain development. Abnormalities along the COX/PGE2 signalling pathway due to genetic or environmental causes have been linked to Autism Spectrum Disorders (ASDs). This study aims to evaluate the effect of altered COX/PGE2 signalling on development and function of the prenatal brain using male mice lacking cyclooxygenase-1 and -2 (COX-1-/- and COX-2-/-) as potential model systems of ASD. Microarray analysis was used to determine global changes in gene expression during embryonic days 16 (E16) and 19 (E19). Gene Ontology: Biological Process (GO:BP) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were implemented to identify affected developmental genes and cellular processes. We found that in both knockouts the brain at E16 had nearly twice as many differentially expressed genes and affected biological pathways containing various ASD associated genes important in neuronal function. Interestingly, using GeneMANIA and Cytoscape we also show that the ASD-risk genes identified in both COX-1-/-and COX-2-/- models belong to protein-interaction networks important for brain development despite of different cellular localization of these enzymes. Lastly, we identified 8 genes that belong to the Wnt signalling pathways exclusively in the COX-2-/- mice at E16. The level of PKA-phosphorylated β-catenin (S552), a major activator of the Wnt pathway, was increased in this model, suggesting cross-talk between the COX-2/PGE2 and Wnt pathways during early brain development. Overall, these results provide further molecular insight into the contribution of the COX/PGE2 pathways to ASD and demonstrate that COX-1-/- and COX-2-/- animals might be suitable new model systems for studying the disorders.

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Predatory journals: a serious complication in the scholarly publishing landscape

Your daily routine probably involves wading through numerous emails that invite you to submit your work, attend a conference, or become an editorial board member for one journal after another, some of which sound vaguely familiar. This is a great honor, right? Not necessarily.

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miR-335 inhibited cell proliferation of lung cancer cells by target Tra2β

Abstract

Accumulating evidence has suggested that the dysregulation of miRNAs is an important factor in the pathogenesis of lung cancer. Here, we demonstrate that miR-335 expression is reduced in non-small cell lung cancer (NSCLC) tumors relative to non-cancerous adjacent tissues, whilst the expression of Tra2β is increased. In addition, clinical data revealed that the increased Tra2β and decreased miR-335 expression observed in NSCLC cells was associated with poor patient survival rates. In-vitro experimentation showed that the overexpression of miR-335 inhibited the growth, invasion and migration capabilities of A459 lung cancer cells, by targeting Tra2β. In contrast, inhibition of miR-335 or overexpression of the Tra2β target gene stimulated the growth, invasion and migratory capabilities of A459 lung cancer cells in vitro. Furthermore, overexpression of miR-335 or inhibition of Tra2β decreased the phosphorylation of Rb-S780 and Rb-AKT. Overall, these findings suggest that the downregulation of miR-335 in A459 lung cancer cells promoted cell proliferation by upregulation of Tra2β, mediated via activation of the AKT/mTOR signaling pathway, and suggest that miR-335 may have potential as a novel therapeutic target for NSCLC.

This article is protected by copyright. All rights reserved.



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Sialic Acid-Binding Immunoglobulin-Like Lectin1 as a Novel Predictive Biomarker for Relapse in Graves' Disease: A Multicenter Study

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Thyroid , Vol. 0, No. 0.


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In US, 4 out of 10 Cancers Could Be Prevented

Potentially modifiable risk factors account for a large proportion of all cancer cases and cancer-related deaths in men and women living in the US.
Medscape Medical News

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Anterior Palatoplasty May Be ‘Moderately’ Effective in OSA


Reuters Health Information

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Determination of an optimal response cut-off able to predict progression-free survival in patients with well-differentiated advanced pancreatic neuroendocrine tumours treated with sunitinib: an alternative to the current RECIST-defined response



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Rapid nodal staging of head and neck cancer surgical specimens with flow cytometric analysis



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Cadherin-1 and cadherin-3 cooperation determines the aggressiveness of pancreatic ductal adenocarcinoma



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The combined activation of KCa3.1 and inhibition of Kv11.1/hERG1 currents contribute to overcome Cisplatin resistance in colorectal cancer cells



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The impact of folate intake on the risk of head and neck cancer in the prostate, lung, colorectal, and ovarian cancer screening trial (PLCO) cohort



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Effect of aging and curing mode on the compressive and indirect tensile strength of resin composite cements

Resin composite cements are used in dentistry to bond ceramic restorations to the tooth structure. In the oral cavity these cements are subjected to aging induced by masticatory and thermal stresses. Thermal c...

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Pathophysiology to Phenotype in the Asthma of Obesity

Annals of the American Thoracic Society, Volume 14, Issue Supplement_5, Page S395-S398, November 2017.


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Protein Folding and the Challenges of Maintaining Endoplasmic Reticulum Proteostasis in Idiopathic Pulmonary Fibrosis

Annals of the American Thoracic Society, Volume 14, Issue Supplement_5, Page S410-S413, November 2017.


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Mechanistic Basis for Obesity-related Increases in Ozone-induced Airway Hyperresponsiveness in Mice

Annals of the American Thoracic Society, Volume 14, Issue Supplement_5, Page S357-S362, November 2017.


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Obesity Impairs the Adaptive Immune Response to Influenza Virus

Annals of the American Thoracic Society, Volume 14, Issue Supplement_5, Page S406-S409, November 2017.


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Diet, Obesity, and Asthma

Annals of the American Thoracic Society, Volume 14, Issue Supplement_5, Page S332-S338, November 2017.


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Mitochondrial Dysfunction in Pulmonary Fibrosis

Annals of the American Thoracic Society, Volume 14, Issue Supplement_5, Page S383-S388, November 2017.


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Obesity and Metabolic Abnormalities in Chronic Obstructive Pulmonary Disease

Annals of the American Thoracic Society, Volume 14, Issue Supplement_5, Page S389-S394, November 2017.


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The Impact of Diet on Immunity and Respiratory Diseases

Annals of the American Thoracic Society, Volume 14, Issue Supplement_5, Page S339-S347, November 2017.


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Dealing with Stress: Defective Metabolic Adaptation in Chronic Obstructive Pulmonary Disease Pathogenesis

Annals of the American Thoracic Society, Volume 14, Issue Supplement_5, Page S374-S382, November 2017.


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The Hygiene Hypothesis in the Age of the Microbiome

Annals of the American Thoracic Society, Volume 14, Issue Supplement_5, Page S348-S353, November 2017.


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Potential Role of the Lung Microbiome in Shaping Asthma Phenotypes

Annals of the American Thoracic Society, Volume 14, Issue Supplement_5, Page S326-S331, November 2017.


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Purpose of the Conference: The 2017 Transatlantic Conference on Lung Diseases

Annals of the American Thoracic Society, Volume 14, Issue Supplement_5, Page S313-S313, November 2017.


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Mitochondrial Dysfunction Linking Obesity and Asthma

Annals of the American Thoracic Society, Volume 14, Issue Supplement_5, Page S368-S373, November 2017.


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Chair’s Summary: Obesity and Associated Changes in Metabolism, Implications for Lung Diseases

annalsats.201702-116aw.fp.png_v03

Annals of the American Thoracic Society, Volume 14, Issue Supplement_5, Page S314-S315, November 2017.


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Gut Microbiome and Obesity. How to Prove Causality?

Annals of the American Thoracic Society, Volume 14, Issue Supplement_5, Page S354-S356, November 2017.


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Microbial Insights into Asthmatic Immunopathology. A Forward-Looking Synthesis and Commentary

Annals of the American Thoracic Society, Volume 14, Issue Supplement_5, Page S316-S325, November 2017.


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A New Frontier in Immunometabolism. Cholesterol in Lung Health and Disease

Annals of the American Thoracic Society, Volume 14, Issue Supplement_5, Page S399-S405, November 2017.


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Metabolic Dysregulation, Systemic Inflammation, and Pediatric Obesity-related Asthma

Annals of the American Thoracic Society, Volume 14, Issue Supplement_5, Page S363-S367, November 2017.


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Clinical features of otolith organ-specific vestibular dysfunction

The vestibular end organs consist of three semicircular canals (SCCs) and two otolith organs in each ear. The main symptom caused by dysfunction of the SCCs, which sense rotatory accelerations, is considered to be rotatory vertigo. Acute unilateral peripheral vestibular dysfunction such as vestibular neuritis (VN) causes rotatory vertigo, and the diagnosis of VN requires the objective analysis of canal paresis, which is generally assessed by tests of lateral SCC function, such as caloric testing and/or the horizontal head impulse test (HIT) (Halmagyi et al., 1988; Weber et al., 2009).

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The effect of magnesium hydroxide-containing dentifrice using an extrinsic and intrinsic erosion cycling model

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Publication date: February 2018
Source:Archives of Oral Biology, Volume 86
Author(s): Vanara Florêncio Passos, Lidiany Karla Azevedo Rodrigues, Sérgio Lima Santiago
ObjectiveTo evaluate, in vitro, the effect of Mg(OH)2 dentifrice, and the influence of the number of experimental days, on the extrinsic (citric acid –CA) and intrinsic (hydrochloric acid –HCl) enamel erosion models.DesignHuman enamel slabs were selected according to surface hardness and randomly assigned to 3 groups (n=9) as follows: non-fluoridated (negative control), NaF (1450ppm F- positive control) and Mg(OH)2 (2%) dentifrices. The slabs were daily submitted to a 2-h period of pellicle formation and, over a period of 5days, submitted to cycles (3×/day) of erosive challenge (CA 0.05M, pH=3.75 or HCl 0.01M, pH=2 for 30s), treatment (1min −1:3w/w of dentifrice/distilled water) and remineralization (artificial saliva/120min). Enamel changes were determined by surface hardness loss (SHL) for each day and mechanical profilometry analysis. Data were analyzed by two-way ANOVA followed by Tukey's test to % SHL and one-way ANOVA to profilometry (p<0.05).ResultsThe number of experimental days influenced the erosion process for the two types of erosion models (p<0.001). Mg(OH)2-containing dentifrices were effective in reducing enamel extrinsic acid erosion as determined by % SHL (p<0.001) when compared to the control group, being better than positive control (p<0.001); however, the dentifrices were not effective for the intrinsic model (p=0.295). With regards to surface wear, no statistically significant differences were found among the groups for CA (p=0.225) and HCl (p=0.526).ConclusionThe findings suggest that Mg(OH)2 dentifrices might protect enamel against slight erosion, but protection was not effective for stronger acid erosion.



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Evaluating the Predictive Ability of Initial Staging F-18 FDG PET/CT for the Prognosis of Non-Hodgkin Malignant Lymphoma Patients Who Underwent Stem Cell Transplantation

Abstract

Objectives

This study aimed to determine the value of clinical prognostic factors and semiquantitative metabolic parameters from initial staging fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (F-18 FDG PET/CT) in non-Hodgkin lymphoma (NHL) patients treated with stem cell transplantation (SCT).

Methods

A total of 39 malignant lymphoma patients who underwent initial staging F-18 FDG PET/CT were enrolled in this study. SUVmax, MTV_wb, and TLG_wb were measured during the initial staging PET/CT. Receiver operating characteristic curve (ROC) analysis was adopted to dichotomize continuous variables. Log-rank test and Cox proportional hazard regression analysis were used to evaluate disease-free survival (DFS) rate.

Results

Among the 39 patients with malignant lymphoma, 17 (43.6%) had a relapse. For several clinical factors such as age, ECOG performance score, AMC/ALC score, stages, and revised International Prognostic Index score, differences between the two dichotomized groups were statistically insignificant. In univariate analysis, DFS estimates were 71.0 ± 7.8 months and 18.0 ± 5.9 months in high-SUVmax and low-SUVmax group, respectively (P < 0.01). For MTV_wb, DFS estimates were 46.6 ± 12.4 months and 69.1 ± 8.5 months in high-MTV_wb and low-MTV_wb group, respectively (P = 0.12). For TLG_wb, DFS estimates were 65.3 ± 7.5 months and 13.7 ± 8.6 months in high-TLG_wb and low-TLG_wb group, respectively (P = 0.02). In Cox proportional hazard regression analysis, only MTV_wb showed statistical significance (HR 3.01, 95% CI 1.04–8.74, P = 0.04).

Conclusion

In NHL patients treated with SCT, the MTV_wb of initial staging F-18 FDG PET/CT was an independent prognostic factor.



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The human right to communicate and our need to listen: Learning from people with a history of childhood communication disorder

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Patients With Infected Diabetic Foot Ulcers Need Quick Referral

Infected diabetic foot ulcers are associated with a worse prognosis than previously thought, with more than half failing to heal in 1 year and one in seven affected patients requiring an amputation.
Medscape Medical News

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Kids Still Get Codeine After Surgeries Despite Safety Warnings

Even after warnings from doctors and drug regulators about the dangers of opioids for children, 1 in 20 kids still get codeine after two common childhood surgeries, a U.S. study suggests.
Reuters Health Information

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Smoking cessation leads to changes in survivin expression in oral mucosa

Abstract

Background

Survivin is an inhibitor protein of apoptosis and play a role in oral carcinogenesis mechanism.

Methods

This aim of this study was to evaluate the effect of smoking in survivin expression of oral mucosa of chronic smokers with and without oral squamous cell carcinoma (OSCC). The study was composed of three groups: Group 1 - 26 patients smoking more than 20 cigarettes/day/10 years without either history of oral malignant neoplasia or visible clinical signs in the examined site; Group 2 - 26 patients with OSCC; Group 3 - 22 patients surgically treated for OSCC for at least 1 month. The immunohistochemistry was performed with 1 smear for each group and analyzed by microscopy regarding extension, intensity of positive cells for survivin, and intracellular location.

Results

The survivin expression was observed in 100% of the cases in Group 1, 88.5% in Group 2, and 100% in Group 3. Concerning to Groups 1 and 3, the survivin expression with cytoplasmic location occurred in 100%, while in Group 2 occurred in 87.5%. The cytoplasmic and nuclear expression was observed only in Group 2, with 7.69%. The results was correlated with clinical-pathological data by Fischer's exact test with significant relation between smoking cessation and intensity (p = 0.015) for Group 2.

Conclusions

The extension and intensity of survivin expression in the cytological smears were related to the smoking cessation in the group with OSCC. However, the smoking history (packs/years) did not influence the survivin expression.

This article is protected by copyright. All rights reserved.



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Epithelial disruptions, but not immune cell invasion, induced secretory dysfunction following innate immune activation in a novel model of acute salivary gland injury

Abstract

Background

Salivary gland (SG) injurious agents are all translated into loss of salivation (xerostomia). An association has been established between activation of innate immunity and salivary gland injury and dysfunction. However, it remains unclear how the secretory epithelia respond by halting saliva production.

Methods

C57BL/6 submandibular glands (SMGs) were acutely challenged using a single dose of the innate immune stimulant: polyinosinic-polycytidylic acid (poly (I:C)). Secretory capacity of the infected SMGs was substantiated by assessing the flow rate in response to pilocarpine stimulation. Depletion of the acute inflammatory cells was achieved by pre-treating mice with RB6-8C5 depletion antibody. Flow cytometry, histology and immunohistochemistry were conducted to verify the immune cell depletion. Epithelial expression of saliva-driving molecules: muscarinic 3 receptor (M3R), aquaporin 5 water channel (AQP5), Na-K- CL-Cotransporter 1 (NKCC1) and transmembrane member 16A (TMEM16A), were characterized using RT-qPCR and immunohistochemistry. Tight junction (TJ) protein; zonula occludens (ZO-1) and basement membrane (BM) protein; laminin were assessed by immunohistochemistry.

Results

Innate immune challenge prompted dysfunction in the exocrine salivary glands (SGs). Dysregulated gene and protein expression of molecules that drive saliva secretion was substantiated. Aberrant expression of TJ and BM proteins followed innate immune activation. Hyposalivation in the current model was independent of myeloperoxidase (MPO)-positive, acute inflammatory cells.

Conclusions

In the present study, we developed a novel injury model of the SGs, featuring acute secretory dysfunction and immediate structural disruptions. Our results ruled out the injurious role of aggressively infiltrating inflammatory cells.

This article is protected by copyright. All rights reserved.



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Variation in Blood Transfusion and Coagulation Management in Traumatic Brain Injury at the Intensive Care Unit: A Survey in 66 Neurotrauma Centers Participating in the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury Study

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Journal of Neurotrauma , Vol. 0, No. 0.


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A Case Report of Syndromic Multinodular Goitre in Adolescence: Exploring the Phenotype Overlap between Cowden and DICER1 Syndromes

Background: Hereditary tumour predisposition syndromes may increase the risk for development of thyroid nodules at a young age. We present the case of an adolescent female with Cowden syndrome who had some atypical phenotypic features which overlapped with the DICER1 syndrome. Material and Methods: A 17-year-old female presented with a 3-month history of progressive right neck swelling. Fine needle cytology of the thyroid revealed a follicular neoplasm with features suggestive of follicular variant of papillary thyroid carcinoma and she underwent a hemithyroidectomy. Enlarging nodules in the remaining thyroid led to a completion thyroidectomy at 19 years of age. The patient's past medical history included an ovarian mixed malignant germ cell tumour, pulmonary nodules and cysts, renal cysts, mucocutaneous lesions, an arachnoid cyst, and a fibrous breast lesion. Macrocephaly was noted on physical examination. Results: Based on the patient's complex phenotype and young age, a hereditary predisposition syndrome was suspected and genetic testing of PTEN and DICER1 was undertaken. A heterozygous truncating germ-line PTEN mutation was identified, which combined with clinical findings, met criteria for the diagnosis of Cowden syndrome. Additional loss of heterozygosity of the wild-type PTEN allele was detected in the right thyroid lesion and ovarian tumour. No DICER1 mutations were identified. Conclusions: Genetic testing was crucial in elucidating this patient's predisposition to the early development of neoplastic and non-neoplastic conditions. Our report also highlights the phenotypic overlap between the Cowden and DICER1 syndromes and illustrates the importance of recognising the variable phenotypic features of hereditary syndromes in order to enable timely implementation of appropriate care.
Eur Thyroid J

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Indeterminate Thyroid Nodules: A Pragmatic Approach

Background: Fine needle aspiration (FNA) cytology fails to provide a conclusive diagnosis in a subset of thyroid lesions labeled as "indeterminate" (Thy3). In this study, we aimed at ascertaining the prevalence of Thy3 thyroid nodules in a hitherto unreported ethnic group (residents of the United Arab Emirates). Methods: We retrospectively examined 688 FNA of the thyroid performed on 584 patients. Samples were reported using the Royal College of Physicians' (RCP) Thy classification. The results of the FNA were correlated with the final surgical specimens. Ultrasonography (US) risk stratification was calculated using a web-based US risk of malignancy calculator. Results: Overall sample adequacy was 97%. The indeterminate group Thy3 was found in 7% of the samples. The overall risk of malignancy in the Thy3 category was 20%. This risk was very similar in the 2 subgroups of Thy3 (17% in Thy 3a and 22% in Thy3f). Subdividing the Thy3 group into subgroups becomes less necessary if the US scoring is #x3c;24.5% since the negative predictive value, in this case, is 100%. Applying this criterion to our population would have had the potential of reducing the percentage of patients referred to surgery from 61 to 43%. Conclusions: Proper risk stratification of Thy3 lesions should be based on the combined risk assessment of clinical, cytological, radiological, and molecular data. Such a pragmatic approach is expected to reduce the percentage of inappropriate referrals to surgery.
Eur Thyroid J

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Social integration and survival after diagnosis of colorectal cancer

BACKGROUND

Although larger social networks have been associated with lower all-cause mortality, few studies have examined whether social integration predicts survival outcomes among patients with colorectal cancer (CRC). The authors examined the association between social ties and survival after CRC diagnosis in a prospective cohort study.

METHODS

Participants included 896 women in the Nurses' Health Study who were diagnosed with stage I, II, or III CRC between 1992 and 2012. Stage was assigned using the American Joint Committee on Cancer criteria. Social integration was assessed every 4 years since 1992 using the Berkman-Syme Social Network Index, which included marital status, social network size, contact frequency, religious participation, and other social group participation.

RESULTS

During follow-up, there were 380 total deaths, 167 of which were due to CRC. In multivariable analyses, women who were socially integrated before diagnosis had a subsequent reduced risk of all-cause mortality (hazard ratio [HR], 0.65; 95% confidence interval [95% CI], 0.46-0.92) and CRC mortality (HR, 0.63; 95% CI, 0.38-1.06) compared with women who were socially isolated. In particular, women with more intimate ties (family and friends) had lower all-cause mortality (HR, 0.61; 95% CI, 0.42-0.88) and CRC mortality (HR, 0.59; 95% CI, 0.34-1.03) compared with those with few intimate ties. Participation in religious or community activities was not found to be related to outcomes. The analysis of postdiagnosis social integration yielded similar results.

CONCLUSIONS

Socially integrated women were found to have better survival after a diagnosis of CRC, possibly due to beneficial caregiving from their family and friends. Interventions aimed at strengthening social network structures to ensure access to care may be valuable programmatic tools in the management of patients with CRC. Cancer 2017. © 2017 American Cancer Society.



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Correlation between lymphatic endothelial markers and lymph node status or N-staging of colorectal cancer

Abstract

Background

The purpose of this study is to examine the expression levels of lymphatic endothelial markers in colorectal cancer and to explore the correlation between the expression levels of markers and lymph node status.

Methods

Forty-seven paired fresh tumor tissues and para-cancerous tissues were collected from colorectal cancer patients who received surgical treatment between August 2015 and March 2016 in Cancer Hospital, Chinese Academy of Medical Sciences. Real-time quantitative PCR (RTQ–PCR) was used to check the expression levels of LYVE–1, VEGFR–3, Podoplanin, and Prox–1 in tumor and para-cancerous tissues.

Results

The positive expression rates of LYVE–1, VEGFR–3, Podoplanin, and Prox–1 in tumor tissues were 100, 93.6, 100, and 91.4%, but 100, 100, 100, and 87.2% in para-cancerous tissues. Comparing with para-cancerous tissues, tumor tissues had significantly lower expression levels of LYVE–1 (P < 0.001) and VEGFR–3 (P = 0.013) and higher levels of Podoplanin (P = 0.016) and Prox–1 (P = 0.078). There was no correlation between lymph node status and the expression level of LYVE–1 in tumor tissues (P = 0.354) or par-cancerous tissues (P = 0.617); similar results were found for VEGFR–3 (P = 0.631, 0.738), Podoplanin (P = 0.490, 0.625), and Prox–1 (P = 0.503, 0.174). Meanwhile, there was no correlation between N-staging and the expression level of LYVE–1 in tumor tissues (P = 0.914) or para-cancerous tissues (P = 0.784); similar results were found for VEGFR–3 (P = 0.493, 0.955), Podoplanin (P = 0.199, 0.370), and Prox–1 (P = 0.780, 0.234).

Conclusions

There was no correlation between expression levels of lymphatic endothelial markers and lymph node status; LYVE–1, VEGFR–3, Podoplanin, and Prox–1 could not be used for predicting the lymph node status or N-staging of colorectal cancer.



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Cancers, Vol. 9, Pages 159: Genomic Destabilization Triggered by Replication Stress during Senescence

Cancers, Vol. 9, Pages 159: Genomic Destabilization Triggered by Replication Stress during Senescence

Cancers doi: 10.3390/cancers9110159

Authors: Yusuke Minakawa Atsuhiro Shimizu Yusuke Matsuno Ken-ichi Yoshioka

Most cancers develop after middle age, and are often associated with multiple mutations and genomic instability, implying that genomic destabilization is critical for age-related tumor development. In this manuscript, we review current knowledge regarding (1) the senescent cellular background, which is associated with a higher risk of genomic destabilization; and (2) the contributions of genomic destabilization to cancer development.



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MicroRNA 26b promotes colorectal cancer metastasis by down-regulating PTEN and WNT5A

Summary

Invasion and metastasis are crucially important factors in the survival of malignant tumors. The epithelial-mesenchymal transition (EMT) is an early step in metastatic progression and the presence of cancer stem cells is closely related to tumor survival, proliferation, metastasis, and recurrence. Here we report that ectopic overexpression of microRNA 26b (miR-26b) in colorectal cancer (CRC) cell lines promoted EMT and stem cell-like phenotypes in vitro. Furthermore, miR-26b directly targeted and suppressed multiple tumor suppressors, including phosphatase and tensin homolog (PTEN) and wingless-type MMTV integration site family member 5A (WNT5A). Notably, miR-26b is markedly upregulated in tumor samples from patients with lymphatic metastases. These results indicate that miR-26b promotes CRC metastasis by down-regulating PTEN and WNT5A, and may represent a therapeutic target for metastatic CRC.

This article is protected by copyright. All rights reserved.



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IGF1R signalling in testicular germ cell tumour cells impacts on cell survival and acquired cisplatin resistance

Abstract

Testicular germ cell tumours (TGCT) are the most frequent malignancy and cause of death from solid tumours in the 20–40 year age group. Although most cases show sensitivity to cis-platinum-based chemotherapy, this is associated with long-term toxicities and chemo-resistance. Roles for receptor tyrosine kinases other than KIT are largely unknown in TGCT. We therefore conducted a phosphoproteomic screen and identified the insulin growth factor receptor-1 (IGF1R) as both highly expressed and activated in TGCT cell lines representing the non-seminomatous subtype. IGF1R was also frequently expressed in tumour samples from patients with nonseminomas. Functional analysis of cell line models showed that long-term shRNA mediated IGF1R silencing leads to apoptosis and complete ablation of nonseminoma cells with active IGF1R signalling. Cell lines with high levels of IGF1R activity also showed reduced AKT signalling in response to decreased IGF1R expression as well as sensitivity to the small molecule IGF1R inhibitor NVP-AEW541. These results were in contrast to those in the seminoma cell line TCAM2 that lacked IGF1R signalling via AKT and was one of the two cell lines least sensitive to the IGF1R inhibitor. The dependence on IGF1R activity in the majority of non-seminomas parallels the known role of IGF signalling in the proliferation, migration and survival of primordial germ cells, the putative cell of origin for TGCT. Upregulation of IGF1R expression and signalling was also found to contribute to acquired cisplatin resistance in an in vitro nonseminoma model, providing rationale for targeting IGF1R in cisplatin resistant disease.



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Connective tissue growth factor induces renal fibrosis via epidermal growth factor receptor activation

ABSTRACT

Connective tissue growth factor (CCN2/CTGF) is a matricellular protein overexpressed in progressive human renal diseases, mainly in fibrotic areas. In vitro studies have demonstrated that CCN2 regulates production of extracellular matrix (ECM) proteins and epithelial mesenchymal transition (EMT), and therefore could contribute to renal fibrosis. CCN2 blockade ameliorates experimental renal damage, including diminution of ECM accumulation. We have described that CCN2 and its C-terminal degradation product CCN2(IV), bind to epidermal growth factor receptor (EGFR) to modulate renal inflammation. However, the receptor involved in CCN2 profibrotic actions has not been described so far. Using a murine model of systemic administration of CCN2(IV) we have unveiled a fibrotic response in the kidney that was diminished by EGFR blockade. Additionally, in CCN2-conditional knockout mice, renal fibrosis elicited by folic acid-induced renal damage was prevented, linked to inhibition of EGFR pathway activation. Our in vitro studies demonstrated a direct effect of CCN2 via the EGFR pathway on ECM production by fibroblasts and the induction of EMT in tubular epithelial cells. Our studies clearly show that the EGFR regulates CCN2 fibrotic signaling in the kidney and suggest that EGFR pathway blockade could be a potential therapeutic option to block CCN2-mediated profibrotic effects in renal diseases.



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Lu-177-Based Peptide Receptor Radionuclide Therapy for Advanced Neuroendocrine Tumors

Abstract

Peptide receptor radionuclide therapy (PRRT) is a systemic cytotoxic radiation therapy using a compound of β-emitting radionuclide chelated to a peptide for the treatment of tumor with overexpressed specific cell receptor such as somatostatin receptor subtype 2 (SSTR2) of neuroendocrine tumor (NET). Surgical resection should be performed for the curative treatment for NETs when it is feasible; however, a multi-disciplinary approach is needed when locally advanced or metastasized disease. PRRT with lutetium-177 (Lu-177)-labeled somatostatin analogues, as a new treatment modality targeting metastatic or inoperable NETs expressing the SSTR2, have been developed and successfully used for the past two decades. As Lu-177 emits both β- and γ-radiation, it has the ability as a theragnostic agent for NETs compared with only β-emitting yttrium-90 labeled PRRT. Several recent studies reported that Lu-177 gave an overall positive response and improved the patients' quality of life. To fully exploit its potential, large comparative studies are needed for the assessment of distinct efficacies of Lu-177 labeled PRRT. Additionally, for extending the indications and developing new regimens of Lu-177-based PRRT, more dedicated clinical research is required.



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Three-Dimensional Accuracy of Digital Static Interocclusal Registration by Three Intraoral Scanner Systems

Abstract

Purpose

Prior studies have defined the accuracy of intraoral scanner (IOS) systems but the accuracy of the digital static interocclusal registration function of these systems has not been reported. This study compared the three-dimensional (3D) accuracy of the digital static interocclusal registration of 3 IOS systems using the buccal bite scan function.

Materials and Methods

Three IOS systems compared were 3MTM True Definition Scanner (TDS), TRIOS Color (TRC), and CEREC AC with CEREC Omnicam (CER). Using each scanner, 7 scans (n = 7) of the mounted and articulated SLA master models were obtained. The measurement targets (SiN reference spheres and implant abutment analogs) were in the opposing models at the right (R), central (C), and left (L) regions; abutments #26 and #36, respectively. A coordinate measuring machine with metrology software compared the physical and virtual targets to derive the global 3D linear distortion between the centroids of the respective target reference spheres and abutment analogs (dRR, dRC, dRL, and dRM) and 2D distances between the pierce points of the abutment analogs (dXM, dYM, dZM), with 3 measurement repetitions for each scan.

Results

Mean 3D distortion ranged from –471.9 to 31.7 μm for dRR, –579.0 to –87.0 μm for dRC, –381.5 to 69.4 μm for dRL, and –184.9 to –23.1 μm for dRM. Mean 2D distortion ranged from –225.9 to 0.8 μm for dXM, –130.6 to -126.1 μm for dYM, and –34.3 to 26.3 μm for dZM. Significant differences were found for interarch distortions across the three systems. For dRR and dRL, all three test groups were significantly different, whereas for dRC, the TDS was significantly different from the TRC and CER. For 2D distortion, significant differences were found for dXM only.

Conclusions

Interarch and global interocclusal distortions for the three IOS systems were significantly different. TRC performed overall the best and TDS was the worst. The interarch (dRR, dRC, dRL) and interocclusal (dXM) distortions observed will affect the magnitude of occlusal contacts of restorations clinically. The final restoration may be either hyperoccluded or infraoccluded, requiring compensations during the CAD design stage or clinical adjustments at issue.



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Do pregnancy characteristics contribute to rising childhood cancer incidence rates in the United States?

Abstract

Background

Since 1975, childhood cancer incidence rates have gradually increased in the United States; however, few studies have conducted analyses across time to unpack this temporal rise. The aim of this study was to test the hypothesis that increasing cancer incidence rates are due to secular trends in pregnancy characteristics that are established risk factors for childhood cancer incidence including older maternal age, higher birthweight, and lower birth order. We also considered temporal trends in sociodemographic characteristics including race/ethnicity and poverty.

Procedure

We conducted a time series county-level ecologic analysis using linked population-based data from Surveillance, Epidemiology, and End Results cancer registries (1975–2013), birth data from the National Center for Health Statistics (1970–2013), and sociodemographic data from the US Census (1970–2010). We estimated unadjusted and adjusted average annual percent changes (AAPCs) in incidence of combined (all diagnoses) and individual types of cancer among children, ages 0–4 years, from Poisson mixed models.

Results

There was a statistically significant unadjusted temporal rise in incidence of combined childhood cancers (AAPC = 0.71%; 95% CI = 0.55–0.86), acute lymphoblastic leukemia (0.78%; 0.49–1.07), acute myeloid leukemia (1.86%; 1.13–2.59), central nervous system tumors (1.31%; 0.94–1.67), and hepatoblastoma (2.70%; 1.68–3.72). Adjustment for county-level maternal age reduced estimated AAPCs between 8% (hepatoblastoma) and 55% (combined). However, adjustment for other county characteristics did not attenuate AAPCs, and AAPCs remained significantly above 0% in models fully adjusted for county-level characteristics.

Conclusion

Although rising maternal age may account for some of the increase in childhood cancer incidence over time, other factors, not considered in this analysis, may also contribute to temporal trends.



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Posterior only approach to open wedge osteotomy in the thoracolumbar spine



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The effectiveness of a classroom-based phonological awareness program for 4–5-year-olds

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Vitamin D in Graves Disease: Levels, Correlation with Laboratory and Clinical Parameters, and Genetics

Objective: The aim was to compare the vitamin D levels in patients with Graves disease (GD) with the general population and to correlate the vitamin D levels with laboratory and clinical parameters in GD. Moreover, we examined the genetic variation in genes involved in the vitamin D metabolism and their association with GD. Methods: The levels of vitamin D were compared in 292 patients with newly diagnosed GD and 2,305 controls. Single nucleotide polymorphisms (SNPs) in the vitamin D receptor (VDR), vitamin D binding protein (DBP), and 1-α-hydroxylase (CYP27B1) were examined for association with GD and/or Graves ophthalmopathy (GO) in 708 patients and 1,178 controls. Results: Patients with GD had significantly lower vitamin D levels compared to controls (55.0 ± 23.2 vs. 87.2 ± 27.6 nmol/L, p #x3c; 0.001). In patients with GD (n = 219), there was no association between the levels of vitamin D at diagnosis and free thyroxine (fT4), free triiodothyronine (fT3), thyrotropin receptor antibodies (TRAb), GO at diagnosis, or relapse after terminating treatment with antithyroid drugs. Two SNPs in VDR were associated with GD: rs10735810 (OR = 1.36, 95% CI: 1.02–1.36, p = 0.02) and rs1544410 (OR = 1.47, 95% CI: 1.03–1.47, p = 0.02). There was no difference in the mean vitamin D level between genotypes in either rs10735810 or rs154410. Conclusions: Patients with GD had lower vitamin D levels compared to the general population; however, the vitamin D levels did not affect the laboratory or clinical parameters of GD. SNPs in the VDR influenced the risk of GD through mechanisms other than reducing the vitamin D levels.
Eur Thyroid J

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The impact of dual energy CT imaging on dose calculations for pre-clinical studies

To investigate the feasibility of using dual-energy CT (DECT) for tissue segmentation and kilovolt (kV) dose calculations in pre-clinical studies and assess potential dose calculation accuracy gain.

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Comparison of neoadjuvant chemoradiation with carboplatin/ paclitaxel or cisplatin/ 5-fluoruracil in patients with squamous cell carcinoma of the esophagus

Neoadjuvant chemoradiation (nCRT) is the treatment of choice for patients with locally advanced squamous cell carcinoma of the esophagus (SCC). Today radiation oncologists can choose between two different ther...

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Can overnight stenting be safely eliminated following a pharyngeal flap? A matched comparison study

Objective

Determine if overnight stenting is warranted after pharyngeal flap for management of velopharyngeal insufficiency (VPI) in pediatric patients

Methods

This is a retrospective age-matched cohort study from a single tertiary pediatric facility. Patients who underwent a posterior pharyngeal flap for VPI from January 1, 2013, to December 31, 2016, were included. Two equal groups were constructed based on when their nasal stents were removed, that is, postoperative day (POD) 0 or POD 1. Primary outcome measure was oxygen desaturation after surgery. Secondary outcome measures were total length of stay, need for narcotics, and oral intake based on POD. Additional information was gathered and evaluated as possible prognostic variables.

Results

There were 27 matched pairs included in the study. One patient from each group required supplemental oxygen during the night of surgery. No escalation of care was needed in either case. The group whose stents were removed on POD 0 were discharged earlier than the group whose stents were removed on POD 1, P < 0.0001. The POD 0 group took significantly more oral intake on POD 0 than the POD 1 group, P = 0.03. The POD 0 group had significantly more genetic syndromes than the POD 1 group, P = 0.02.

Conclusion

There was no benefit with overnight stenting. Earlier discharge from the hospital was achieved in the POD 0 group. No patient experienced need for reintubation, escalation of clinical care, postoperative hemorrhage, or death.

Level of Evidence

4 Laryngoscope, 2017



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Patients' preferences for adjuvant sorafenib after resection of renal cell carcinoma in the SORCE trial: what makes it worthwhile?

Abstract
Background
We sought to determine the survival benefits that patients judged sufficient to warrant adjuvant therapy with sorafenib for 1 year, or for 3 years after resection of renal cell carcinoma (RCC) in the SORCE trial.
Methods
SORCE participants from all sites in Australia and New Zealand, and selected sites in the UK, completed a validated preferences questionnaire at months 0, 3, 15 and 42 to elicit the minimum survival benefits they judged sufficient to warrant adjuvant sorafenib for 1 year (versus observation), or for 3 years (versus 1 year). The questionnaires used reference survival times of 5 years and 15 years; and reference survival rates at 5 years of 65% and 85%.
Results
The 233 participants had a median age of 57 years (range 29 to 78) and 71% were male. For 1 year of sorafenib versus no adjuvant therapy, the median benefits in survival times judged sufficient to warrant treatment were an extra 9 months beyond 5 years and an extra 1 year beyond 15 years; the median benefit in survival rates were an extra 4% beyond 65% and an extra 3% beyond 85% at 5 years. For 3 years of sorafenib versus 1 year of sorafenib, the median benefit in survival time judged sufficient to warrant extended treatment was an extra 1 year beyond both 5 years and 15 years. Participants randomly allocated treatment with sorafenib judged larger benefits necessary than those allocated placebo. Participants' preferences were not associated with their baseline characteristics or the interval from randomisation.
Conclusion
Most participants judged an extra year of survival necessary to warrant 1 year of adjuvant sorafenib worthwhile, and an additional year of survival to warrant extending the duration of sorafenib from 1 year to 3 years. Patients' preferences are important in shared-decision-making.SORCE trial clinical trials number = NCT00492258

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Announcements



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Bayesian Occam's Razor Is a Razor of the People

Abstract

Occam's razor—the idea that all else being equal, we should pick the simpler hypothesis—plays a prominent role in ordinary and scientific inference. But why are simpler hypotheses better? One attractive hypothesis known as Bayesian Occam's razor (BOR) is that more complex hypotheses tend to be more flexible—they can accommodate a wider range of possible data—and that flexibility is automatically penalized by Bayesian inference. In two experiments, we provide evidence that people's intuitive probabilistic and explanatory judgments follow the prescriptions of BOR. In particular, people's judgments are consistent with the two most distinctive characteristics of BOR: They penalize hypotheses as a function not only of their numbers of free parameters but also as a function of the size of the parameter space, and they penalize those hypotheses even when their parameters can be "tuned" to fit the data better than comparatively simpler hypotheses.



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Vulvar swelling as the first presentation of Crohn's disease in children—A report of three cases

Abstract

Vulvar swelling is a rare manifestation of metastatic Crohn's disease in children. It often predates gastrointestinal symptoms and can be the first presentation of pediatric Crohn's disease. We report three cases of pediatric Crohn's disease presenting with vulvar swelling. We discuss this rare presentation and its treatment and highlight the importance of recognizing it so that prompt investigation and appropriate management can be initiated.



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Bleomycin-induced flagellate erythema after venous malformation sclerosis—Case report and brief review

Abstract

Bleomycin-induced flagellate erythema is a rare but typical skin toxicity of bleomycin. We report the case of a boy with a left foot venous malformation who developed this skin rash after two sessions of bleomycin intralesional injection. We discuss the mechanism and characteristics of this reaction to bleomycin, which is usually benign and self-limited. We conclude that, although rare, flagellate pigmentation can occur when bleomycin is used as a sclerosant in children.



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Prevalence of sun protection behaviors in Hispanic youth residing in a high ultraviolet light environment

Abstract

Although rates of late-stage melanoma are rising in Hispanics, particularly those living in high ultraviolet light environments, little is known about the prevalence of sun protective behaviors in Hispanic children. We analyzed baseline data including frequency of sunburn, sun protective behaviors, level of U.S. acculturation, and skin phototype from a cross-sectional survey of 2003 Hispanic elementary school children in Los Angeles, California, who participated in a skin cancer prevention intervention. Although the Hispanic children reported frequently engaging in some sun protective behaviors, they also had a high rate of sunburn (59%) that exceeded previous national estimates for non-Hispanic white children (43%). Fewer U.S.-acculturated children reported more frequent shade-seeking at home (P = .02), along with less shade-seeking at school (P = .001) and more sunscreen use at school (P = .02). The surprisingly high rate of sunburn in Hispanic children suggests that the way in which they are practicing sun protection is not preventing sunburns. Sun safety interventions should be targeted toward Hispanic youth to provide them with practical methods of effective sun protection, in addition to education on the risks of high sun exposure.



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Doxorubicin combined with low intensity ultrasound suppresses the growth of oral squamous cell carcinoma in culture and in xenografts

Oral squamous cell carcinoma (OSCC) invades surrounding tissues by upregulating matrix metalloproteinases (MMPs) -2 and −9, which causes over-expression of the Hedgehog signaling proteins Shh and Gli-1 and deg...

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Metallosis after traumatic loosening of Bryan cervical disc arthroplasty: a case report and literature review

Abstract

Purpose

Cervical disc arthroplasty has been a popular alternative to traditional arthrodesis treatment for maintaining postoperative cervical spine mobility. However, certain adverse reactions to cervical disc arthroplasty have emerged during the last few decades.

Methods

Metallosis or metalloma is a rarely reported complication after spinal fusion or spinal arthroplasty surgery. We report on the first metallosis case occurring in a patient who received Bryan Disc implantation approximately 8 years earlier. She was involved in a traffic accident and sustained a whiplash injury to the cervical spine one and a half years ago. The traumatic Bryan Disc loosening developed after the traffic accident, causing metallosis.

Results

To the best of our knowledge, this is the first reported case of spinal metallosis caused by the Bryan Disc. A series of metallosis cases reported in the literature are also reviewed.

Conclusions

Although uncommon, intraspinal metallosis or metalloma should be considered as an infrequent cause of delayed neurological symptoms after spinal surgery involving metallic instrumentation, especially after disc arthroplasty. Once metallosis is suspected, immediate metallic implant removal is mandatory for definite diagnosis and treatment.



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Adenovirus vector-based prime-boost vaccination via heterologous routes induces cervicovaginal CD8+ T cell responses against HPV16 oncoproteins

Abstract

Recent advances in immunotherapy against cancer underscore the importance of T lymphocytes and tumor microenvironment, but few vaccines targeting cancer have been approved likely due in part to the dearth of common tumor antigens, insufficient immunogenicity and the evolution of immune evasion mechanisms during the progression to malignancy. Human papillomaviruses (HPV) are the primary etiologic agents of cervical cancer and progression from persistent HPV-infection to cervical intraepithelial lesions and eventually cancer requires persistent expression of the oncoproteins E6 and E7. This offers the opportunity to specifically target these virus-specific antigens for vaccine-induced clearance of infected cells before cancers develop. Here we have evaluated the immunogenicity of Adenovirus types 26 and 35 derived vectors expressing a fusion of HPV16 E6 and E7 oncoproteins after intramuscular and/or intravaginal immunization in mice. The adenovirus vectors were shown to transduce an intact cervicovaginal epithelium. Intramuscular prime followed by intravaginal boost maximized the induction and trafficking of HPV-specific CD8+ T cells producing IFN-γ and TNF-α to the cervicovaginal tract. Importantly, the cervicovaginal CD8+ T cells expressed CD69 and CD103, hallmarks of intraepithelial tissue resident memory CD8+ T cells. This prime/boost strategy targeting heterologous locations also induced circulating HPV-specific CD8+ T cell responses. Our study prompts further evaluation of intravaginal immunization with adenoviral vectors expressing modified E6 and E7 antigens for therapeutic vaccination against persistent HPV infection and cervical intraepithelial neoplasia. This article is protected by copyright. All rights reserved.



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Antibodies against human papillomaviruses as diagnostic and prognostic biomarker in patients with neck squamous cell carcinoma from unknown primary

Abstract

Treatment of patients with neck lymph node metastasis of squamous cell carcinoma (SCC) from unknown primary tumor (NSCCUP) is challenging due to the risk of missing occult tumors or inducing toxicity to unaffected sites. Human papillomavirus (HPV) is a promising biomarker given its causal link to oropharyngeal SCC and superior survival of patients with HPV-driven oropharyngeal SCC and NSCCUP. Identification of HPV-driven NSCCUP could focus diagnostic work-up and treatment on the oropharynx. For the first time, we assessed HPV antibodies and their prognostic value in NSCCUP patients.

Antibodies against E6 and E7 (HPV16/18/31/33/35), E1 and E2 (HPV16/18) were assessed in 46 NSCCUP patients in sera collected at diagnosis, and in follow-up sera from five patients. In 28 patients, HPV tumor status was determined using molecular markers (HPV DNA, mRNA and cellular p16INK4a).

Thirteen (28%) NSCCUP patients were HPV-seropositive for HPV16, 18, 31, or 33. Of eleven patients with HPV-driven NSCCUP, ten were HPV-seropositive, while all 17 patients with non-HPV-driven NSCCUP were HPV-seronegative, resulting in 91% sensitivity (95%CI: 59-100%) and 100% specificity (95%CI: 80-100%). HPV antibody levels decreased after curative treatment. Recurrence was associated with increasing levels in an individual case. HPV-seropositive patients had a better overall and progression-free survival with hazard ratios of 0.09 (95%CI: 0.01-0.42) and 0.03 (95%CI: 0.002-0.18), respectively.

For the first time, seropositivity to HPV proteins is described in NSCCUP patients, and high sensitivity and specificity for HPV-driven NSCCUP are demonstrated. HPV seropositivity appears to be a reliable diagnostic and prognostic biomarker for patients with HPV-driven NSCCUP. This article is protected by copyright. All rights reserved.



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Ovarian Cancer Early Detection by Circulating CA125 in the context of Anti-CA125 Autoantibody Levels: Results from the EPIC cohort

Abstract

CA125 is the best ovarian cancer early detection marker to date; however, sensitivity is limited and complementary markers are required to improve discrimination between ovarian cancer cases and non-cases. Anti-CA125 autoantibodies are observed in circulation. Our objective was to evaluate whether these antibodies (1) can serve as early detection markers, providing evidence of an immune response to a developing tumor, and (2) modify the discriminatory capacity of CA125 by either masking CA125 levels (resulting in lower discrimination) or acting synergistically to improve discrimination between cases and non-cases. We investigated these objectives using a nested case-control study within the European Prospective Investigation into Cancer and Nutrition cohort (EPIC) including 250 cases diagnosed within 4 years of blood collection and up to 4 matched controls. Circulating CA125 antigen and antibody levels were quantified using an electrochemiluminescence assay. Adjusted areas under the curve (aAUCs) by 2-year lag-time intervals were calculated using conditional logistic regression calibrated towards the absolute risk estimates from a pre-existing epidemiological risk model as an offset-variable. Anti-CA125 levels alone did not discriminate cases from controls. For cases diagnosed <2 years after blood collection, discrimination by CA125 antigen was suggestively higher with higher anti-CA125 levels (aAUC, highest antibody tertile: 0.84 [0.76-0.92]; lowest tertile: 0.76 [0.67-0.86]; phet=0.06). We provide the first evidence of potentially synergistic discrimination effects of CA125 and anti-CA125 antibodies in ovarian early detection. If these findings are replicated, evaluating CA125 in the context of its antibody may improve ovarian cancer early detection. This article is protected by copyright. All rights reserved.



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The dark side of glucose transporters in prostate cancer: Are they a new feature to characterize carcinomas?

Abstract

One of the hallmarks of cancer cells is the increased ability to acquire nutrients, particularly glucose and glutamine. Proliferating cells need precursors for cell growth and NADPH reducing equivalents for survival. The principal responsible for glucose uptake is facilitative glucose transporters (GLUTs), which usually are overexpressed in cancer cells. Besides their role in glucose uptake, GLUT transporters are able to transport other compounds such as dehydroascorbic acid or uric acid. They play a major role in tumor progression and cellular processes such as regulated cell death. The prostate gland has the particular characteristic of being more glycolytic than other non-pathological tissues given an accumulation of citrate in the seminal fluid and the inhibition of m-aconitase that affects to Tricarboxylic Acid Cycle. In prostate cancer (PCa), androgens increase glucose uptake, upregulate GLUT transporters such as GLUT1 and GLUT3 and stimulate AMPK pathway, suggesting a possible connection between glycolytic and androgenic signaling. Interestingly, diabetes is not a risk factor of PCa, as it is in other cancers, while insulin stimulates progression and IGF1 pathway plays an important role in PCa progression. It was recently found that PCa cells overexpress GLUT4 and, more importantly, that it seems to be related to the castration-resistant phenotype, though little is known about its participation in tumor progression. This review will focus on the role of GLUT transporters along with PCa progression, and the involvement of GLUT4 on castration-resistant phenotype transition would be considered. This article is protected by copyright. All rights reserved.



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Administration of Adjuvant Chemotherapy for Stage II-III Colon Cancer Patients: A European Population-based Study

Abstract

The advantage of adjuvant chemotherapy (ACT) for treating stage III colon cancer patients is well established and widely accepted. However, many patients with stage III colon cancer do not receive ACT. Moreover, there are controversies around the effectiveness of ACT for stage II patients.

We investigated the administration of ACT and its association with overall survival in resected stage II (overall and stratified by low-/high-risk) and stage III colon cancer patients in three European countries including The Netherlands (2009-2014), Belgium (2009-2013), and Sweden (2009-2014). Hazard ratios (HR) for death were obtained by Cox regression models adjusted for potential confounders.

A total of 60244 resected colon cancer patients with pathological stage II&III were analyzed. A small proportion (range 9% -24%) of stage II and over half (range 55%-68%) of stage III patients received ACT. Administration of ACT in stage II&III tumors decreased with higher age of patients. Administration of ACT was significantly associated with higher overall survival in high-risk stage II patients (in The Netherlands (HR; 95%CI= 0.82 (0.67 - 0.99), Belgium (0.73; 0.59- 0.90), and Sweden (0.58; 0.44- 0.75)), and in stage III patients (in The Netherlands (0.47; 0.43- 0.50), Belgium (0.46; 0.41- 0.50), and Sweden (0.48; 0.43- 0.54)). In stage III, results were consistent across subgroups including elderly patients.

Our results show an association of ACT with higher survival among stage III and high-risk stage II colon cancer patients. Further investigations are needed on the selection criteria of stage II&III colon cancer patients for ACT. This article is protected by copyright. All rights reserved.



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RCAT reflects symptom control and quality of life in allergic rhinoconjunctivitis patients

Abstract

Background

The Global Allergy and Asthma European Network (GA2LEN) Taskforce has requested more data on correlations between various Patient Reported Outcomes (PROs) in clinical trials on allergy. We compared three tools—the Rhinitis Control Assessment Test (RCAT), Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ), and Rhinitis Total Symptom Score (RTSS)—to determine whether the RCAT alone is a sufficient primary outcome parameter in clinical trials on allergic rhinoconjunctivitis.

Methods

In two double-blind, placebo-controlled immunotherapy studies, 33 patients allergic to grass pollen and 94 to birch pollen completed two questionnaires (RCAT and RQLQ) and kept their own symptom diary from which the RTSS was calculated.

Results

Upon comparing RCAT and RQLQ results, we found strong correlations of r = –0.871 for grass pollen–allergic patients and r = –0.795 for birch pollen–allergic patients. The comparison between RCAT and RTSS results showed a strong correlation of r = –0.811 (grass pollen–allergic patients) and a moderate correlation of r = –0.539 (birch pollen–allergic patients). In the RCAT, 69.7% of grass pollen–allergic patients and 45.7% of birch pollen–allergic patients receiving guideline-concordant therapy were regarded as having insufficiently controlled symptoms.

Conclusion

The strong correlation suggests that the RCAT alone is equivalent to the RQLQ with respect to patients' symptom control and quality of life. Patients with uncontrolled symptoms can be identified using the RCAT. Hence, the physician can decide whether symptomatic therapy can be intensified or allergy immunotherapy should be administered.

This article is protected by copyright. All rights reserved.



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Maternal hypothyroidism in the perinatal period and childhood asthma in the offspring

Abstract

Background

There is increasing interest in the possible link between maternal hypothyroidism in the perinatal period and childhood asthma risk. We explored this in the present study while accounting for the timing of hypothyroidism diagnosis. Further, we evaluated whether the risk was moderated by thyroid hormone treatment during pregnancy.

Methods

We conducted a population-based cohort study using Danish national registers. All liveborn singletons in Denmark from 1998 to 2007 were identified. Maternal hypothyroidism and asthma in the children were defined by data from the Patient Register and Prescription Registry. We estimated incidence rate ratios (IRRs) of asthma among children born to hypothyroid mothers versus children born to mothers with no recorded thyroid dysfunction using Poisson regression models.

Results

Of 595,669 children, 3,524 children were born to mothers with hypothyroidism diagnosed before delivery and 4,664 diagnosed after delivery. Overall 48,990 children received treatment for asthma. The IRRs of asthma was 1.16 (95% confidence interval (CI): 1.03–1.30) and 1.12 (95% CI: 1.02–1.24) for children born to mothers with hypothyroidism diagnosed before and after delivery, compared to children born to mothers with no thyroid dysfunction. The highest risk was observed among children born to mothers with hypothyroidism diagnosed before delivery who did not receive thyroid hormone treatment during pregnancy (IRR=1.37, 95% CI: 1.04–1.80).

Conclusion

Our findings suggest that maternal hypothyroidism, especially when it is untreated, increases childhood asthma risk. Early detection and appropriate treatment of hypothyroidism in pregnant women may be an area for possible prevention of childhood asthma.

This article is protected by copyright. All rights reserved.



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Blocking antibodies induced by allergen-specific immunotherapy ameliorate allergic airway disease in a human/mouse chimeric model

Abstract

Background

Allergen-specific immunotherapy (AIT) induces specific blocking antibodies (Ab) which are claimed to prevent IgE-mediated reactions to allergens. Additionally, AIT modulates cellular responses to allergens, e.g. by desensitizing effector cells, inducing regulatory T and B lymphocytes and immune deviation. It is still enigmatic which of these mechanisms mediate(s) clinical tolerance. We sought to address the role of AIT-induced blocking Ab separately from cellular responses in a chimeric human/mouse model of respiratory allergy.

Methods

Non-obese diabetic severe combined immunodeficient γc-/- (NSG) mice received intraperitoneally allergen-reactive PBMC from birch pollen-allergic patients together with birch pollen extract and human IL-4. Engraftment was assessed by flow cytometry. Airway hyperresponsiveness (AHR) and bronchial inflammation were analyzed after intranasal challenges with allergen or PBS. Sera collected from patients before and during AIT with birch pollen were added to the allergen prior to intranasal challenge. The IgE-blocking activity of post-AIT sera was assessed in vitro.

Results

Human cells were detected in cell suspensions of murine lungs and spleens indicating successful humanization. Humanized mice displayed a more pronounced AHR and bronchial inflammation when challenged with allergen compared to negative controls. Post-AIT sera excerted IgE-blocking activity. In contrast to pre-AIT sera, the presence of heterologous and autologous post-AIT sera significantly reduced the allergic airway inflammation and matched their IgE-blocking activity determined in vitro.

Conclusion

Our data demonstrate that post-AIT sera with IgE-blocking activity ameliorate allergic airway inflammation in a human/mouse chimeric model of respiratory allergy independently of AIT-induced cellular changes.

This article is protected by copyright. All rights reserved.



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Calcium hydroxide regulates transcription of the bone sialoprotein gene via a calcium-sensing receptor in osteoblast-like ROS 17/2.8 cells

Bone sialoprotein (BSP) is a glycoprotein associated with mineralized tissues. In this study, we investigated the regulation of Bsp transcription by calcium hydroxide [Ca(OH)2] in rat osteosarcoma-derived osteoblast-like ROS 17/2.8 cells and stromal bone marrow cells. Application of Ca(OH)2 (0.4 mM) increased the levels of runt-related transcription factor 2 (Runx2) and BspmRNAs at 3 and 6 h and the level of BSP protein at 12 h. Transient transfection analyses were performed using chimeric constructs encompassing different regions of the rat Bsp gene promoter ligated to a luciferase reporter gene. It was found that Ca(OH)2 increased the luciferase activities of the pLUC3 and pLUC4 constructs. Introduction of 2-bp mutations to the luciferase construct showed that the effects of Ca(OH)2 were mediated by cAMP response-element (CRE) and fibroblast growth factor 2 (FGF2) response element (FRE). Luciferase activities induced by Ca(OH)2 were blocked by protein kinase C (PKC), protein kinase A (PKA), phosphoinositide-3-kinase (PI3-K), and extracellular signal-regulated kinase 1/2 (ERK1/2) inhibitors and by calcium-sensing receptor (CASR) antagonists. Gel-shift analyses showed that Ca(OH)2 increased binding of nuclear protein to CRE and FRE. Dexamethasone-induced mineralization in stromal bone marrow cells was abrogated by CASR antagonists. These studies demonstrate that Ca(OH)2 regulates Bsp transcription via the CASR by targeting CRE and FRE in the rat Bsp gene promoter.



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Severe Stevens-Johnson syndrome/toxic epidermal necrolysis overlap syndrome—beyond skin involvement

Abstract

Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare but serious dermatologic diseases with many potential multisystem complications. We describe the case of an 8-year-old girl who developed severe SJS/TEN overlap syndrome (25% of her body surface area was affected) complicated by pancreatitis and bronchiolitis obliterans. These rare complications emphasize the need for careful, intensive monitoring of possible complications and an interdisciplinary team approach to provide optimal treatment and follow-up.



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Demographic characteristics of teenage boys with horizontal striae distensae of the lower back

Abstract

Background

This study examines the clinical characteristics and demographics of teenage boys with horizontal striae distensae of the lower back in an outpatient setting.

Methods

Retrospective medical chart reviews and telephone survey studies were completed on an outpatient cohort of 12 boys 11 to 17 years of age with a clinical diagnosis of transverse striae distensae of the lower back at a single-center, university-based, pediatric dermatology practice. We evaluated the clinical features of the striae, participant demographic characteristics, and past medical history. A review of the literature concerning risk factors was conducted using PubMed and Google Scholar.

Results

Of the 14 patients we contacted, 12 agreed to participate. The average age of onset for the striae was 14.3 years. All boys were above the 50th percentile in height at the time of onset. Eight (66.7%) reported a significant growth spurt before the appearance of the stretch marks. Most were asymptomatic. None of the boys had a history of unmonitored exogenous steroid use or prior infection with Bartonella henselae or Borrelia burgdorferi. Only one (8.3%) had a chronic medical condition. Eleven (91.7%) had at least one first-degree relative with striae distensae.

Conclusion

Our results indicate that horizontal striae distensae of the lower back in adolescent boys is associated with a rapid growth spurt, tall stature, and family history of striae distensae. There is no association between this type of striae distensae and any chronic medical condition, bacterial infection, or exogenous steroid use. Thus a careful review of systems and counseling without further medical testing is reasonable management.



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Juvenile mycosis fungoides with large-cell transformation: Successful treatment with psoralen with ultraviolet A light, interferon-alfa, and localized radiation

Abstract

Mycosis fungoides with large-cell transformation is historically associated with a poor prognosis. Pediatric cases of mycosis fungoides with large-cell transformation are rare, with only three other cases reported in the literature. We present the first case of a child with almost complete remission of his mycosis fungoides with large-cell transformation shortly after administration of psoralen plus ultraviolet A, interferon-alfa, and localized radiation.



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The evolution of bite force in horned lizards: the influence of dietary specialization

Abstract

Dietary specialization is an important driver of the morphology and performance of the feeding system in many organisms, yet the evolution of phenotypic specialization has only rarely been examined within a species complex. Horned lizards are considered primarily myrmecophagous (ant eating), but variation in diet among the 17 species of horned lizards (Phrynosoma) makes them an ideal group to examine the relationship between dietary specialization and the resultant morphological and functional changes of the feeding system. In this study, we perform a detailed analysis of the jaw adductor musculature and use a biomechanical model validated with in vivo bite force data to examine the evolution of bite force in Phrynosoma. Our model simulations demonstrate that bite force varies predictably with respect to the gape angle and bite position along the tooth row, with maximal bite forces being attained at lower gape angles and at the posterior tooth positions. Maximal bite forces vary considerably among horned lizards, with highly myrmecophagous species exhibiting very low bite forces. In contrast, members of the short-horned lizard clade are able to bite considerably harder than even closely related dietary generalists. This group appears to be built for performing crushing bites and may represent a divergent morphology adapted for eating hard prey items. The evolutionary loss of processing morphology (teeth, jaw and muscle reduction) and bite force in ant specialists may be a response to the lack of prey processing rather than a functional adaptation per se.



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The anatomy of the infrarenal lumbar splanchnic nerves in human cadavers: implications for retroperitoneal nerve-sparing surgery

Abstract

Injury to the nerves of the aortic- and superior hypogastric plexuses during retroperitoneal surgery often results in significant post-operative complications, including retrograde ejaculation and/or loss of seminal emission in males. Although previous characterizations of these plexuses have done well to provide a basis for understanding the typical anatomy, additional research into the common variations of these plexuses could further optimize nerve-sparing techniques for retroperitoneal surgery. To achieve this, the present study aimed to document the prevalence and positional variability of the infrarenal lumbar splanchnic nerves (LSNs) through gross dissection of 26 human cadavers. In almost all cases, two LSNs were observed joining each side of the aortic plexus, with 48% (left) and 33% (right) of specimens also exhibiting a third joining inferior to the left renal vein. As expected, the position of the LSNs varied greatly between specimens. That said, the vast majority (98%) of LSNs joining the aortic plexus were found to originate from the lumbar sympathetic trunk above the level of the inferior mesenteric artery. It was also found that, within specimens, adjacent LSNs often coursed in parallel. In addition to these nerves, 85% of specimens also demonstrated retroaortic LSN(s) that were angled more inferior compared with the other LSNs (P < 0.05), and exhibited a unique course between the aorta/common iliac arteries and the left common iliac vein before joining the superior hypogastric plexus below the aortic bifurcation. These findings may have significant implications for surgeons attempting nerve-sparing procedures of the sympathetic nerves in the infrarenal retroperitoneum such as retroperitoneal lymphadenectomies. We anticipate that the collective findings of the current study will help improve such retroperitoneal nerve-sparing surgical procedures, which may assist in preserving male ejaculatory function post-operatively.



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Δευτέρα 20 Νοεμβρίου 2017

AHNS Series: Do you know your guidelines? Guideline recommendations for head and neck cancer of unknown primary site

Abstract

This article reviews the clinical practice guidelines for head and neck oncology focusing on the management of head and neck cancers of unknown primary (CUP). The primary purpose of this series is to raise awareness of the current guidelines in head and neck oncology by reviewing the recommendations and the evidence supporting such recommendations, particularly those published by the National Comprehensive Cancer Network (NCCN). We review the importance of a thorough history and physical examination, the impact of the American Joint Committee on Cancer (AJCC) eighth edition changes and the importance of immunohistochemistry, the timing and type of imaging, the role of panendoscopy and tonsillectomy (palatine and lingual), and the role of surgery, radiation, and chemotherapy in the primary management of these tumors.



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