mGluR2/3 activation of the SIRT1 axis preserves mitochondrial function in diabetic neuropathy

Abstract

Objectives

There is a critical need to develop effective treatments for diabetic neuropathy. This study determined if a selective mGluR2/3 receptor agonist prevented or treated experimental diabetic peripheral neuropathy (DPN) through glutamate recycling and improved mitochondrial function.

Methods

Adult male streptozotocin treated Sprague-Dawley rats with features of type 1 diabetes mellitus (T1DM) or Low Capacity Running (LCR) rats with insulin resistance or glucose intolerance were treated with 3 or 10 mg/kg/day LY379268. Neuropathy end points included mechanical allodynia, nerve conduction velocities (NCV), and intraepidermal nerve fiber density (IENFD). Markers of oxidative stress, antioxidant response, glutamate recycling pathways, and mitochondrial oxidative phosphorylation (OXPHOS) associated proteins were measured in dorsal root ganglia (DRG).

Results

In diabetic rats, NCV and IENFD were decreased. Diabetic rats treated with an mGluR2/3 agonist did not develop neuropathy despite remaining diabetic. Diabetic DRG showed increased levels of oxidized proteins, decreased levels of glutathione, decreased levels of mitochondrial DNA (mtDNA) and OXPHOS proteins. In addition, there was a 20-fold increase in levels of glial fibrillary acidic protein (GFAP) and the levels of glutamine synthetase and glutamate transporter proteins were decreased. When treated with a specific mGluR2/3 agonist, levels of glutathione, GFAP and oxidized proteins were normalized and levels of superoxide dismutase 2 (SOD2), SIRT1, PGC-1α, TFAM, glutamate transporter proteins, and glutamine synthetase were increased in DRG neurons.

Interpretation

Activation of glutamate recycling pathways protects diabetic DRG and this is associated with activation of the SIRT1-PGC-1α–TFAM axis and preservation of mitochondrial OXPHOS function.

http://ift.tt/2iVh25v

Geographic Disparity in Liver Allocation: Time to Act or Have Others Act for us

No abstract available

http://ift.tt/2xOUDcz

International Data Base Populated by Anonymous Social Networking to Study Transplant Tourism

No abstract available

http://ift.tt/2A9jOrS

A Metabolic Therapy for Malignant Glioma Requires a Clinical Measure

Abstract

Cancers are "reprogrammed" to use a much higher rate of glycolysis (GLY) relative to oxidative phosphorylation (OXPHOS), even in the presence of adequate amounts of oxygenation. Originally identified by Nobel Laureate Otto Warburg, this hallmark of cancer has recently been termed metabolic reprogramming and represents a way for the cancer tissue to divert carbon skeletons to produce biomass. Understanding the mechanisms that underlie this metabolic shift should lead to better strategies for cancer treatments. Malignant gliomas, cancers that are very resistant to conventional treatments, are highly glycolytic and seem particularly suited to approaches that can subvert this phenotype.

http://ift.tt/2zbsjom

Characteristics and outcome of Prostate cancer patients with overall biopsy Gleason score 3+4=7 and highest Gleason score 3+4=7 or > 3+4=7

Abstract

Aim

Prostate cancer heterogeneity and multifocality might result in different Gleason scores (GS) at individual biopsy cores. According to WHO/ISUP guidelines, the GS in each biopsy core should be recorded with optional reporting of overall GS for the entire case. We aimed to compare the clinicopathologic characteristics and outcome of men with overall biopsy GS 3+4=7 with highest GS 3+4=7 (HI=OV) to those with highest GS > 3+4=7 (HI>OV).

Methods and results

Prostate cancer biopsies from the European Randomized Study of Screening for Prostate Cancer (ERSPC) were revised according to WHO/ISUP 2014 guidelines (n=1031). In total 370 patients had overall GS 3+4=7, of whom 60 (16%) had at least one biopsy core with GS 4+3=7 or 4+4=8. Men with higher GS than 3+4 (HI>OV) in any of the cores had higher age, Prostate Specific Antigen (PSA) level, number of positive biopsies, percentage tumour involvement, percentage Gleason grade 4 and cribriform or intraductal growth (all P<.05) than those with GS 3+4=7 at highest (HI=OV). In multivariable Cox regression analysis including PSA, percentage positive biopsies and percentage tumour involvement, biochemical recurrence-free survival after radical prostatectomy (P=.52) or radiotherapy (P=.35) was not statistically different between both groups.

Conclusion

Among patients with overall GS 3+4=7, those with highest GS >3+4=7 had worse clinicopathologic features, but clinical outcome was not statistically significant. Therefore use of overall GS instead of highest GS for clinical decision-making is justified, potentially preventing overtreatment in prostate cancer patients.

This article is protected by copyright. All rights reserved.

http://ift.tt/2zcWjQX

Restorative Strategies in Movement Disorders: the Contribution of Imaging

Abstract

Purpose of Review

The purpose of this review was to review the imaging, particularly positron emission tomography (PET), findings in neurorestoration studies in movement disorders, with specific focus on neural transplantation in Parkinson's disease (PD) and Huntington's disease (HD).

Recent Findings

PET findings in PD transplantation studies have shown that graft survival as reflected by increases in dopaminergic PET markers does not necessarily correlate with clinical improvement. PD patients with more denervated ventral striatum and more imbalanced serotonin-to-dopamine ratio in the grafted neurons tended to have worse outcome. In HD transplantation studies, variable graft survival and clinical responses may be related to host inflammatory/immune responses to the grafts.

Summary

Information gleaned from imaging findings in previous neural transplantation studies has been used to refine study protocol and patient selection in future trials. This includes identifying suitable candidates for transplantation using imaging markers, employing multiple and/or novel PET tracers to better assess graft functions and inflammatory responses to grafts.

http://ift.tt/2ioWGO7

Improving Gene-Expression Studies from Sputum: A Multistep Optimization of RNA Isolation and qPCR Protocols

American Journal of Respiratory Cell and Molecular Biology, Volume 57, Issue 5, Page 626-628, November 2017.


http://ift.tt/2zqERt1

November Highlights/Papers by Junior Investigators/NIH News

American Journal of Respiratory Cell and Molecular Biology, Volume 57, Issue 5, Page v-v, November 2017.


http://ift.tt/2zbpVOq

Unbiased Quantitation of Alveolar Type II to Alveolar Type I Cell Transdifferentiation during Repair after Lung Injury in Mice

American Journal of Respiratory Cell and Molecular Biology, Volume 57, Issue 5, Page 519-526, November 2017.


http://ift.tt/2zqvQQM

Preexisting Type 2 Immune Activation Protects against the Development of Sepsis

American Journal of Respiratory Cell and Molecular Biology, Volume 57, Issue 5, Page 628-630, November 2017.


http://ift.tt/2zbpR18

Epithelial Deletion of Sulf2 Exacerbates Bleomycin-Induced Lung Injury, Inflammation, and Mortality

American Journal of Respiratory Cell and Molecular Biology, Volume 57, Issue 5, Page 560-569, November 2017.


http://ift.tt/2zcUJOL

Hypoxia Modulates Epithelial Permeability via Regulation of Vascular Endothelial Growth Factor in Airway Epithelia

American Journal of Respiratory Cell and Molecular Biology, Volume 57, Issue 5, Page 527-535, November 2017.


http://ift.tt/2zqwRbq

Hypercapnia Accelerates Adipogenesis: A Novel Role of High CO2 in Exacerbating Obesity

American Journal of Respiratory Cell and Molecular Biology, Volume 57, Issue 5, Page 570-580, November 2017.


http://ift.tt/2zcoBuA

Cardiomyocytes of the Heart and Pulmonary Veins: Novel Contributors to Asthma?

American Journal of Respiratory Cell and Molecular Biology, Volume 57, Issue 5, Page 512-518, November 2017.


http://ift.tt/2zong4Q

mTOR: A Key to Both Pulmonary Vessel Remodeling and Right Ventricular Function in Pulmonary Arterial Hypertension?

American Journal of Respiratory Cell and Molecular Biology, Volume 57, Issue 5, Page 509-511, November 2017.


http://ift.tt/2zaMmDr

An Emerging Role for Megalin as a Regulator of Protein Leak in Acute Lung Injury

American Journal of Respiratory Cell and Molecular Biology, Volume 57, Issue 5, Page 504-505, November 2017.


http://ift.tt/2zr2EJr

p38 MAPK Inhibition Improves Heart Function in Pressure-Loaded Right Ventricular Hypertrophy

American Journal of Respiratory Cell and Molecular Biology, Volume 57, Issue 5, Page 603-614, November 2017.


http://ift.tt/2zcUHX9

Critical Role of IRAK-M in Regulating Antigen-Induced Airway Inflammation

American Journal of Respiratory Cell and Molecular Biology, Volume 57, Issue 5, Page 547-559, November 2017.


http://ift.tt/2zon6dK

CO2 as a Potential Obesogen: A Gas That Will Stick to Your Ribs

American Journal of Respiratory Cell and Molecular Biology, Volume 57, Issue 5, Page 499-500, November 2017.


http://ift.tt/2zdwQ9S

Intermittent Hypoxia and Hypercapnia Accelerate Atherosclerosis, Partially via Trimethylamine-Oxide

American Journal of Respiratory Cell and Molecular Biology, Volume 57, Issue 5, Page 581-588, November 2017.


http://ift.tt/2zomXqI

Restoration of Megalin-Mediated Clearance of Alveolar Protein as a Novel Therapeutic Approach for Acute Lung Injury

American Journal of Respiratory Cell and Molecular Biology, Volume 57, Issue 5, Page 589-602, November 2017.


http://ift.tt/2zdfWIo

Human CD8+ T Cells Damage Noninfected Epithelial Cells during Influenza Virus Infection In Vitro

American Journal of Respiratory Cell and Molecular Biology, Volume 57, Issue 5, Page 536-546, November 2017.


http://ift.tt/2zpF6o6

FDA OKs Abemaciclib for ER+, HER2- Breast Cancer [News in Brief]

The FDA has approved abemaciclib for women with advanced or metastatic ER-positive, HER2-negative breast cancer whose disease has progressed on endocrine therapy. This is the third CDK4/6 inhibitor to get the agency's go-ahead in 2.5 years.

http://ift.tt/2xNICo5

Whole grain-rich diet reduces body weight and systemic low-grade inflammation without inducing major changes of the gut microbiome: a randomised cross-over trial

Objective

To investigate whether a whole grain diet alters the gut microbiome and insulin sensitivity, as well as biomarkers of metabolic health and gut functionality.

Design

60 Danish adults at risk of developing metabolic syndrome were included in a randomised cross-over trial with two 8-week dietary intervention periods comprising whole grain diet and refined grain diet, separated by a washout period of ≥6 weeks. The response to the interventions on the gut microbiome composition and insulin sensitivity as well on measures of glucose and lipid metabolism, gut functionality, inflammatory markers, anthropometry and urine metabolomics were assessed.

Results

50 participants completed both periods with a whole grain intake of 179±50 g/day and 13±10 g/day in the whole grain and refined grain period, respectively. Compliance was confirmed by a difference in plasma alkylresorcinols (p<0.0001). Compared with refined grain, whole grain did not significantly alter glucose homeostasis and did not induce major changes in the faecal microbiome. Also, breath hydrogen levels, plasma short-chain fatty acids, intestinal integrity and intestinal transit time were not affected. The whole grain diet did, however, compared with the refined grain diet, decrease body weight (p<0.0001), serum inflammatory markers, interleukin (IL)-6 (p=0.009) and C-reactive protein (p=0.003). The reduction in body weight was consistent with a reduction in energy intake, and IL-6 reduction was associated with the amount of whole grain consumed, in particular with intake of rye.

Conclusion

Compared with refined grain diet, whole grain diet did not alter insulin sensitivity and gut microbiome but reduced body weight and systemic low-grade inflammation.

Trial registration number

NCT 01731366; Results.

http://ift.tt/2lH4Bv1

Fatty-Acid Catabolism Promotes T-cell Revitalization in Melanoma [Immunology]

A hypoxic and hypoglycemic tumor microenvironment induces the metabolic reprogramming of CD8⁺ TILs.

http://ift.tt/2iX1RJi

Gemtuzumab Ozogamicin Makes a Comeback [News in Brief]

After being pulled from the market 7 years ago, gemtuzumab ozogamicin has been reapproved by the FDA, this time for adults newly diagnosed with acute myeloid leukemia, as well as patients 2 years of age and older with relapsed/refractory disease. The CD33-targeting antibody–drug conjugate can be given as a single agent or in combination with chemotherapy.

http://ift.tt/2z75rEm

Targeting Angiogenesis in Bladder Cancer [News in Brief]

Findings from the phase III RANGE study indicate that adding ramucirumab to docetaxel may improve progression-free survival for patients with advanced or metastatic urothelial carcinoma whose disease is refractory to platinum chemotherapy.

http://ift.tt/2iTuGGj

Tissue Force Programs Cell Fate and Tumor Aggression [Review]

Biomechanical and biochemical cues within a tissue collaborate across length scales to direct cell fate during development and are critical for the maintenance of tissue homeostasis. Loss of tensional homeostasis in a tissue not only accompanies malignancy but may also contribute to oncogenic transformation. High mechanical stress in solid tumors can impede drug delivery and may additionally drive tumor progression and promote metastasis. Mechanistically, biomechanical forces can drive tumor aggression by inducing a mesenchymal-like switch in transformed cells so that they attain tumor-initiating or stem-like cell properties. Given that cancer stem cells have been linked to metastasis and treatment resistance, this raises the intriguing possibility that the elevated tissue mechanics in tumors could promote their aggression by programming their phenotype toward that exhibited by a stem-like cell.

Significance: Recent findings argue that mechanical stress and elevated mechanosignaling foster malignant transformation and metastasis. Prolonged corruption of tissue tension may drive tumor aggression by altering cell fate specification. Thus, strategies that could reduce tumor mechanics might comprise effective approaches to prevent the emergence of treatment-resilient metastatic cancers. Cancer Discov; 7(11); 1224–37. ©2017 AACR.

http://ift.tt/2z6jKt1

Nivolumab Approved for Liver Cancer [News in Brief]

The FDA granted accelerated approval to nivolumab for second-line treatment of advanced hepatocellular carcinoma, making it just the third drug on the market for the disease. The PD-1 inhibitor is approved for patients who cannot tolerate sorafenib and those whose disease progressed despite treatment with the multikinase inhibitor.

http://ift.tt/2iTPUUo

Talimogene Laherparepvec Enhances the Efficacy of PD-1 Blockade [Melanoma]

Talimogene laherparepvec plus pembrolizumab achieved response in 62% of patients with melanoma.

http://ift.tt/2z6fGsO

Durvalumab Promising for NSCLC [News in Brief]

The PD-L1 inhibitor durvalumab increases progression-free survival and objective response rate in patients with inoperable and locally advanced stage III non–small cell lung cancer, according to interim results of a phase III trial. The benefit was great enough that the drug could become the standard of care in the United States for these patients.

http://ift.tt/2iSaO6n

Inhibition of p300/CBP Suppresses Castration-Resistant Prostate Cancer [Drug Discovery]

A virtual ligand screen led to generation of A-485, a potent selective p300/CBP catalytic inhibitor.

http://ift.tt/2z75kIW

Checkpoint Inhibitor Combo Effective for RCC [News in Brief]

In a phase III trial, the combination of nivolumab and ipilimumab yielded more and longer responses than sunitinib in patients with renal cell carcinoma at intermediate or high risk of progression. More than 41% of patients who received the immunotherapy combination responded, compared with 26.5% of patients who received sunitinib. Patients receiving the combination also experienced longer progression-free survival and fewer side effects.

http://ift.tt/2iWgImX

VHL Deficiency Drives Enhancer Activation of Oncogenes in Clear Cell Renal Cell Carcinoma [Research Articles]

Protein-coding mutations in clear cell renal cell carcinoma (ccRCC) have been extensively characterized, frequently involving inactivation of the von Hippel–Lindau (VHL) tumor suppressor. Roles for noncoding cis-regulatory aberrations in ccRCC tumorigenesis, however, remain unclear. Analyzing 10 primary tumor/normal pairs and 9 cell lines across 79 chromatin profiles, we observed pervasive enhancer malfunction in ccRCC, with cognate enhancer-target genes associated with tissue-specific aspects of malignancy. Superenhancer profiling identified ZNF395 as a ccRCC-specific and VHL-regulated master regulator whose depletion causes near-complete tumor elimination in vitro and in vivo. VHL loss predominantly drives enhancer/superenhancer deregulation more so than promoters, with acquisition of active enhancer marks (H3K27ac, H3K4me1) near ccRCC hallmark genes. Mechanistically, VHL loss stabilizes HIF2α–HIF1β heterodimer binding at enhancers, subsequently recruiting histone acetyltransferase p300 without overtly affecting preexisting promoter–enhancer interactions. Subtype-specific driver mutations such as VHL may thus propagate unique pathogenic dependencies in ccRCC by modulating epigenomic landscapes and cancer gene expression.

Significance: Comprehensive epigenomic profiling of ccRCC establishes a compendium of somatically altered cis-regulatory elements, uncovering new potential targets including ZNF395, a ccRCC master regulator. Loss of VHL, a ccRCC signature event, causes pervasive enhancer malfunction, with binding of enhancer-centric HIF2α and recruitment of histone acetyltransferase p300 at preexisting lineage-specific promoter–enhancer complexes. Cancer Discov; 7(11); 1284–305. ©2017 AACR.

See related commentary by Ricketts and Linehan, p. 1221.

This article is highlighted in the In This Issue feature, p. 1201

http://ift.tt/2z75jES

Checkpoint Inhibitors Spur Changes in Trial Design [News in Depth]

Given the success of checkpoint inhibitors and the desire to test them in combination with other immunotherapies and targeted therapies, hundreds of clinical trials have been launched. To most efficiently study these agents, researchers and the FDA are exploring the use of novel endpoints, the use of new preclinical models, and adaptive trial designs. However, the cost and demands associated with the conduct of increasingly sophisticated early-phase clinical trials are putting smaller companies and some academic medical centers at a disadvantage.

http://ift.tt/2z75iAO

Melanoma Drugs Effective as Adjuvants [News in Brief]

BRAF-targeted strategies and PD-1–blocking immunotherapy are more effective adjuvant therapies than currently approved options for patients with high-risk resectable melanoma. However, choosing the best agent for patients with BRAF-mutated disease remains a challenge.

http://ift.tt/2iSMt0l

Tigecycline May Selectively Target Leukemic Stem Cells in CML [Leukemia]

Tigecycline inhibits mitochondrial oxidative phosphorylation to target leukemic stem cells (LSC).

http://ift.tt/2z75gZI

PPARG-Activated Bladder Cancer Cells Exhibit a PPARG Dependency [Bladder Cancer]

PPARG-selective inverse agonists can suppress proliferation in PPARG-activated bladder cancer cells.

http://ift.tt/2iUWYQV

ASF1A Facilitates DNA Double-Strand Break Repair by NHEJ [DNA Repair]

ASF1A promotes NHEJ over homologous recombination for DNA double-strand break (DSB) repair.

http://ift.tt/2z6xGmV

The Splicing Regulator PRMT5 Is Critical for Glioblastoma Proliferation [Brain Tumors]

PRMT5 regulates the splicing of detained introns in proliferation-associated genes in GBM.

http://ift.tt/2iX1QoI

Targeting the Lysosome for Cancer Therapy [In the Spotlight]

Summary: Lysosomes are the recycling centers of the cell where organelles and proteins are degraded during autophagy and macropinocytosis; they also serve as signaling hubs that control the activity of mTORC1. In this issue, Rebecca and colleagues report the development of a new type of lysosomal inhibitor for cancer therapy that can inhibit multiple lysosomal activities that are needed for tumor cell survival and growth. Cancer Discov; 7(11); 1218–20. ©2017 AACR.

See related article by Rebecca et al., p. 1266.

http://ift.tt/2iRzT1g

WNT and SHH Drive the Tumorigenesis of a Rare Embryonal Brain Tumor [Brain Tumors]

Coexpression of Wnt and Shh in Sox2⁺/Pax6⁺ apical radial glia in the VZ drives ETMR formation in vivo.

http://ift.tt/2z6xHHv

Recurrent Tumor Cell-Intrinsic and -Extrinsic Alterations during MAPKi-Induced Melanoma Regression and Early Adaptation [Research Articles]

Treatment of advanced BRAF^V600-mutant melanoma using a BRAF inhibitor or its combination with a MEK inhibitor typically elicits partial responses. We compared the transcriptomes of patient-derived tumors regressing on MAPK inhibitor (MAPKi) therapy against MAPKi-induced temporal transcriptomic states in human melanoma cell lines or murine melanoma in immune-competent mice. Despite heterogeneous dynamics of clinical tumor regression, residual tumors displayed highly recurrent transcriptomic alterations and enriched processes, which were also observed in MAPKi-selected cell lines (implying tumor cell–intrinsic reprogramming) or in bulk mouse tumors (and the CD45-negative or CD45-positive fractions, implying tumor cell–intrinsic or stromal/immune alterations, respectively). Tumor cell–intrinsic reprogramming attenuated MAPK dependency, while enhancing mesenchymal, angiogenic, and IFN-inflammatory features and growth/survival dependence on multi-RTKs and PD-L2. In the immune compartment, PD-L2 upregulation in CD11c⁺ immunocytes drove the loss of T-cell inflammation and promoted BRAFi resistance. Thus, residual melanoma early on MAPKi therapy already displays potentially exploitable adaptive transcriptomic, epigenomic, immune-regulomic alterations.

Significance: Incomplete MAPKi-induced melanoma regression results in transcriptome/methylome-wide reprogramming and MAPK-redundant escape. Although regressing/residual melanoma is highly T cell–inflamed, stromal adaptations, many of which are tumor cell–driven, could suppress/eliminate intratumoral T cells, reversing tumor regression. This catalog of recurrent alterations helps identify adaptations such as PD-L2 operative tumor cell intrinsically and/or extrinsically early on therapy. Cancer Discov; 7(11); 1248–65. ©2017 AACR.

See related commentary by Haq, p. 1216.

This article is highlighted in the In This Issue feature, p. 1201

http://ift.tt/2iTIsZm

In This Issue

http://ift.tt/2zdrxqY

Issue Information

Cover of this issue. Cenp-r contribution to proliferation of skin papilloma. See also Okumura et al. (pp. 2142-2148 of this issue).

http://ift.tt/2zpqsxf

A chinese case of prevotella intermedia and streptococcus constellatus intracranial mixed infection

Abstract

Streptococcal Species is increasingly recognized as a potentially preventable emerging infection in human's brain with high prevalence around the world. Streptococcus constellatus is one of the most common pathogens. Meanwhile, anaerobic bacteria are the rare causes for intracranial infection. To date, intracranial mixed infection caused by Prevotella intermedia and Streptococcus constellatus has not been reported. We reported a Chinese case to raise the global awareness of severity of the intracranial mixed infection. Here, we illustrated the epidemiological risk factors, clinical manifestations and outcomes of the patient. For patients who suffer from exacerbated brain infection with fetid cerebrospinal fluid, early repeated imaging is urgently needed and empiric antibiotic therapy should consider anaerobic and aerobic bacteria in these situations.

http://ift.tt/2h4KwNY

Quantitative image analysis of protein expression and colocalization in skin sections

Abstract

Immunofluorescence (IF) and in situ proximity ligation assay (isPLA) are techniques that are used for in situ protein expression and colocalization analysis, respectively. However, an efficient quantitative method to analyze both IF and isPLA staining on skin sections is lacking. Therefore, we developed a new method for semi-automatic quantitative layer-by-layer measurement of protein expression and colocalization in skin sections using the free open-source software CellProfiler. As a proof of principle, IF and isPLA of ichthyosis-related proteins TGm-1 and SDR9C7 were examined. The results indicate that this new method can be used for protein expression and colocalization analysis in skin sections.

This article is protected by copyright. All rights reserved.

http://ift.tt/2zqBNgu

Effect of dietary palmitic and stearic acids on sucrose motivation and hypothalamic and striatal cell signals in the rat

e have reported that motivation for sucrose is increased in rats fed a moderate (31%) mixed-fat diet for 4-6 weeks. In this study, rats were fed diets containing 32% stearic (STEAR) or palmitic (PALM) acid, and behavior, metabolic profile, and cell signals were compared with those of rats fed a matched low fat (11% fat [LF]) diet. Rats fed STEAR or PALM increased sucrose motivation relative to LF rats (one-way ANOVA for lever presses, p=.03). Diet did not change fasting glucose, insulin, total cholesterol, triglycerides, intravenous glucose tolerance test glucose profile, percent body fat, or total kcal, although kcal as fat were increased (ANOVA p<0.05). Cell signals were assessed in rats ranked from high to low sucrose motivation. Diet did not alter Thr- and Ser-phosphorylation of Akt in the medial hypothalamus (HYP) and striatum (STR). However, Ser-phosphorylation of GSK3B was decreased in HYP and STR from both High- and Low-Performer tertiles of STEAR and PALM rats (ANOVA within each brain region, p<0.05). Two Histone 3 (H3) modifications were also assessed. Whereas there was no effect of diet on the transcription-repressive H3 modification, H3K27me3, the transcription-permissive H3 modification, H3K4me3, was significantly decreased in the HYP of High-Performers fed PALM or STEAR (ANOVA p=.013). There was no effect of diet on H3K4me3 levels in HYP of Low-Performers, or in STR. Our findings suggest signal-specific and brain region-specific effects of PALM or STEAR diets, and may link downstream signaling effects of GSK3B activity and H3 modifications with enhanced motivational behavior.

http://ift.tt/2A92yTC

Editorial Team Changes in the New Year

None

http://ift.tt/2xMq3Ay

Chronic Maternal Hypercortisolemia in Late Gestation Alters Fetal Cardiac Function at Birth

Studies in our laboratory have shown that modest chronic increases in maternal cortisol concentrations over the last 0.20 of gestation impair maternal glucose metabolism and increase the incidence of perinatal stillbirth. Previous studies had found an increase in maternal cortisol concentrations from 115 to 130d gestation in sheep increased both proliferation in fetal cardiomyocytes and apoptosis in the fetal cardiac Purkinje Fibers. We hypothesized that the adverse effects of excess cortisol may result in defects in cardiac conduction during labor and delivery. In the current study, we infused cortisol (1 mg·kg^-1·day^-1) into late gestation pregnant ewes and continuously monitored fetal aortic pressure and ECG through labor and delivery. We found that although the fetuses of cortisol infused ewes had normal late gestation patterns of arterial pressure and heart rate, there was a significant decrease in fetal aortic pressure and heart rate on the day of birth, specifically in the final hour before delivery. Significant changes in the fetal ECG were also apparent on the day of birth, including prolongation of the P wave and PR interval. We speculate that chronic exposure to glucocorticoids alters cardiac metabolism /or ion homeostasis, contributing to cardiac dysfunction, precipitated by active labor and delivery.

http://ift.tt/2A7v6gv

Exercise training reverses inflammation and muscle wasting after tobacco smoke exposure

Long term cigarette smoking induces inflammatory processes in the pulmonary system which are suggested to "spill over" into systemic inflammation. Regular exercise has been shown to have anti-inflammatory properties. The aim of the study was to investigate the effects of therapeutic exercise on inflammation and muscle wasting in smoke-exposed mice. C57BL/6J-mice (n = 30) were separated into three groups to receive either: (1) controls with no specific treatment (Con group), (2) 8 months exposure to cigarette smoke (smoke-exposed (SE) group), (3) 8 months of cigarette smoke combined with exercise training during the last 2 months (SEex group). The inflammatory status was analyzed by quantifying levels of various plasma proteins using multiplex ELISA and detection of lymphocyte surface markers by flow cytometry. Muscle tissue was analyzed by histological techniques and measurements of RNA/protein expression. SE was lead to decreased VO_2max and V_max, which was reversed by exercise (p<0.05). Expression of ICAM-1, VCAM-1, and CD62L on T cells increased and was reversed by exercise (p<0.05). Similarly, SE induced an increase of various inflammatory cytokines, which were down-regulated by exercise. In muscle, exercise improved the structure, oxidative capacity, and metabolism by reducing UPS activation, stimulating IGF-1 expression and the SE-induced inhibition of mTOR signaling pathway (p<0.05). Exercise training reverses smoke-induced decline in exercise capacity, systemic inflammation and muscle wasting, by addressing immune regulating, anabolic, and metabolic pathways.

http://ift.tt/2xMq3k2

Urinary Bladder Hypertrophy is Susceptible in Male but Protected in Female ROMK Bartter's Mouse

The renal outer medullary potassium channel (ROMK; K_ir1.1) plays an important role in Na⁺ and K⁺ homeostasis. ROMK knockout mice (KO) show a similar phenotype to Bartter's syndrome of salt wasting and dehydration due to reduced Na-2Cl-K-cotransporter activity but not in ROMK1 KO. ROMK KO mice also show hydronephrosis; however, the mechanism of this phenotype has not been understood. We have previously demonstrated a gender-sex difference in hydronephrosis and PGE2 production in ROMK KO mouse. In this study we compared the gender-sex difference in bladder hypertrophy and hydronephrosis in ROMK KO mice. The bladder weight, bladder capacity and the thickness of urothelium in male ROMK KO showed average increased 2~4 fold greater than WT but there was no difference in either female or ROMK1 KO. The thickness of the urothelium was 648.8±33.2 vs. 302.7±16.5 (p<0.001) and the detrusor muscle 1940.7±98.9 vs. 1308.2±102.1 (p=0.013) respectively in 12-month males ROMK KO compared with the same-age WT mice. Western blotting detected ROMK expression at 45~48 kDa, and both ROMK1 and ROMK2 mRNA were detected by Q-PCR in the bladder. Immunofluorescence staining showed ROMK stained in the bladder, ureter and urethra in WT but not in KO. In addition, there was a correlation between the severity of hydronephrosis and the bladder weight in male but not in female ROMK KO mice. In conclusion, ROMK expressed in the urinary tract at both protein and mRNA levels; significant enlargement and hypertrophy of the bladder may contribute to hydronephrosis in male ROMK KO mice.

http://ift.tt/2A6RVRk

Interleukin-27 Exerts Its Antitumor Effects by Promoting Differentiation of Hematopoietic Stem Cells to M1 Macrophages

The interleukin (IL)-27 promotes expansion and differentiation of hematopoietic stem cells into myeloid progenitor cells. Many tumor-infiltrating myeloid cells exert immunosuppressive effects but we hypothesized that the myeloid cells induced by IL-27 would have antitumor activity. In this study we corroborated this hypothesis as investigated in two distinct mouse transplantable tumor models. Malignant mouse cells engineered to express IL-27 exhibited reduced tumor growth in vivo. Correlated with this effect was a significant increase in the number of tumor-infiltrating CD11b+ myeloid cells exhibiting a reduced immunosuppressive activity. Notably, these CD11b+ cells were characterized by an activated M1 macrophage phenotype, on the basis of increased expression of inducible nitric oxide synthase and other M1 biomarkers. Notably, in vivo depletion of these cells by administering anti-Gr-1 eradicated the antitumor effects of IL-27. When admixed with parental tumors, CD11b+ cells inhibited tumor growth and directly killed the tumor in a nitric oxide-dependent manner. Mechanstically, IL-27 expanded Lineage−Sca-1+c-Kit+ cells in bone marrow. Transplant experiments in Ly5.1/5.2 congenic mice revealed that IL-27 directly acted on these cells and promoted their differentiation into M1 macrophages which mobilized into tumors. Overall, our results illustrated how IL-27 exerts antitumor activity by enhancing the generation of myeloid progenitor cells that can differentiate into antitumorigenic M1 macrophages.

http://ift.tt/2zqg9ZB

MicroRNA-519d promotes melanoma progression by downregulating EphA4

Increasing evidence suggests that there is a unique cell subpopulation in melanoma that can form nonadherent melanospheres in serum-free stem cell medium, mimicking aggressive malignancy. Using melanospheres as a model to investigate progression mechanisms, we found that miR-519d overexpression was sufficient to promote cell proliferation, migration, invasion and adhesion in vitro and lung metastatic capability in vivo. The cell adhesion receptor EphA4 was determined to be a direct target of miR-519d. Forced expression of EphA4 reversed the effects of miR-519d overexpression, whereas silencing of EphA4 phenocopied the effect of miR-519d. Malignant progression phenotypes were also affected at the level of epithelial-to-mesenchymal transition and the ERK1/2 signaling pathway inversely affected by miR-519d or EphA4 expression. In clinical specimens of metastatic melanoma, we observed significant upregulation of miR-519d and downregulation of EphA4, in the latter case correlated inversely with overall survival. Taken together, our results suggest a significant functional role for miR-519d in determining EphA4 expression and melanoma progression.

http://ift.tt/2zdVXJT

Rapid Intraoperative Diagnosis of Pediatric Brain Tumors Using Stimulated Raman Histology

Accurate histopathologic diagnosis is essential for providing optimal surgical management of pediatric brain tumors. Current methods for intraoperative histology are time- and labor-intensive and often introduce artifacts that limit interpretation. Stimulated Raman histology (SRH) is a novel label-free imaging technique that provides intraoperative histologic images of fresh, unprocessed surgical specimens. Here we evaluate the capacity of SRH for use in the intraoperative diagnosis of pediatric type brain tumors. SRH revealed key diagnostic features in fresh tissue specimens collected from 33 prospectively enrolled pediatric type brain tumor patients, preserving tumor cytology and histoarchitecture in all specimens. We simulated an intraoperative consultation for 25 patients with specimens imaged using both SRH and standard hematoxylin and eosin histology. SRH-based diagnoses achieved near-perfect diagnostic concordance (Cohen's kappa, κ > 0.90) and an accuracy of 92-96%. We then developed a quantitative histologic method using SRH images based on rapid image feature extraction. Nuclear density, tumor-associated macrophage infiltration, and nuclear morphology parameters from 3337 SRH fields of view were used to develop and validate a decision-tree machine-learning model. Using SRH image features, our model correctly classified 25 fresh pediatric type surgical specimens into normal versus lesional tissue and low-grade versus high-grade tumors with 100% accuracy. Our results provide insight into how SRH can deliver rapid diagnostic histologic data that could inform the surgical management of pediatric brain tumors.

http://ift.tt/2zpaH9H

Dendritic cells enhance polyfunctionality of adoptively transferred T cells which target cytomegalovirus in glioblastoma

Median survival for glioblastoma (GBM) remains <15 months. Human Cytomegalovirus (CMV) antigens have been identified in GBM but not normal brain, providing an unparalleled opportunity to subvert CMV antigens as tumor-specific immunotherapy targets. A recent trial in recurrent GBM patients demonstrated the potential clinical benefit of adoptive T cell therapy (ATCT) of CMV phosphoprotein 65 (pp65)-specific T cells. However, ex vivo analyses from this study found no change in the capacity of CMV pp65-specific T cells to gain multiple effector functions or polyfunctionality, which has been associated with superior antitumor efficacy. Previous studies have shown that dendritic cells (DC) could further enhance tumor-specific CD8+ T-cell polyfunctionality in vivo when administered as a vaccine. Therefore, we hypothesized that vaccination with CMV pp65 RNA-loaded DC would enhance the frequency of polyfunctional CMV pp65-specific CD8+ T cells after ATCT. Here we report prospective results of a pilot trial in which 22 patients with newly-diagnosed GBM were initially enrolled of which 17 patients were randomized to receive CMV pp65-specific T cells with CMV-DC vaccination (CMV-ATCT-DC) or saline (CMV-ATCT-Saline). Patients who received CMV-ATCT-DC vaccination experienced a significant increase in the overall frequencies of IFNγ+, TNFα+, and CCL3+ polyfunctional, CMV-specific CD8+ T cells. These increases in polyfunctional CMV-specific CD8+ T cells correlated with overall survival, although we cannot conclude this was causally related. Our data implicate polyfunctional T-cell responses as a potential biomarker for effective antitumor immunotherapy and support a formal assessment of this combination approach in a larger randomized study.

http://ift.tt/2zdVQOt

Nodular Lymphocyte Predominant Hodgkin Lymphoma of the Ileum

Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) is a rare lymphoma derived from germinal center B lymphocytes that typically presents with localized lymph node involvement and can mimic a variety of both reactive and other neoplastic conditions. Extranodal involvement is uncommon in NLPHL and typically occurs in the context of previously documented or synchronous nodal disease. Involvement of the gastrointestinal tract is exceedingly rare. Here, we present the first case to our knowledge of NLPHL involving the ileum that was discovered incidentally on routine screening colonoscopy in an asymptomatic patient. An awareness of the spectrum of clinical presentations, careful morphologic evaluation, and a comprehensive panel of immunohistochemical stains are essential for correct diagnosis of NLPHL presenting in unusual anatomic sites.

http://ift.tt/2zZxZiw

Endoscopic resection of an esophageal schwannoma

http://ift.tt/2A8KSaI

Life-threatening GI bleeding secondary to multiple gastric metastases from urothelial carcinoma of the renal pelvis

http://ift.tt/2imtXJY

Colonoscopic removal of a denture migrated in the appendix

http://ift.tt/2gUGlAq

Unusual gastric subepithelial tumor: primary mixed acinar-endocrine neoplasm in an anemic woman

http://ift.tt/2imtV4O

Gastroesophageal reflux disease after per-oral endoscopic myotomy as compared with Heller’s myotomy with fundoplication: a systematic review with meta-analysis

Per-oral endoscopic myotomy (POEM) represents a less invasive alternative, as compared with conventional laparoscopic Heller's myotomy (LHM), for achalasia patients. It cannot be excluded, however, that the lack of fundoplication after POEM may result in a higher incidence of reflux disease, as compared with LHM. The aim was to conduct a systematic review of prospective studies reporting the incidence of reflux disease developed after POEM and LHM.

http://ift.tt/2gWkF7f

Adverse clinical events reported during Invisalign treatment: Analysis of the MAUDE database

The objectives of this study were to examine adverse clinical events after the use of the Invisalign system and to provide an overview of the actions taken by the manufacturer to address these events.

http://ift.tt/2zYIdzz

Numeric simulation model for long-term orthodontic tooth movement with contact boundary conditions using the finite element method

Although many attempts have been made to simulate orthodontic tooth movement using the finite element method, most were limited to analyses of the initial displacement in the periodontal ligament and were insufficient to evaluate the effect of orthodontic appliances on long-term tooth movement. Numeric simulation of long-term tooth movement was performed in some studies; however, neither the play between the brackets and archwire nor the interproximal contact forces were considered. The objectives of this study were to simulate long-term orthodontic tooth movement with the edgewise appliance by incorporating those contact conditions into the finite element model and to determine the force system when the space is closed with sliding mechanics.

http://ift.tt/2hxcvCG

Directory: AAO Officers and Organizations

http://ift.tt/2zYJ6YY

Clinical recognition of mouth breathers by orthodontists: A preliminary study

A routine diagnosis of a patient's breathing status performed by an orthodontist normally includes visual assessment, medical history, clinical examination of habitual lip posture, size and shape of the nostrils, reflex control of the alar muscle and respiratory tests, and the dental mirror test. The objective of this study was to test the recognition of mouth breathers in young persons by an orthodontist and agreement with an otolaryngologist's reference diagnosis when routine assessments were carried out.

http://ift.tt/2hwdVNS

Directory: AAO Officers and Organizations

http://ift.tt/2hwbdYy

Table of Contents

http://ift.tt/2zZzME7

Children's orthodontic utilization in the United States: Socioeconomic and surveillance considerations

There has been no epidemiologic study of malocclusion prevalence and treatment need in the United States since the Third National Health and Nutrition Examination Survey, conducted from 1988 to 1991. In this descriptive study, the authors sought to estimate orthodontic treatment prevalence by examining a nationally representative survey to assess current pediatric dental and orthodontic utilization.

http://ift.tt/2hwhQuf

Adverse events

One function of the United States Food and Drug Administration (FDA) is the monitoring of medical device safety. Each year, the FDA receives several hundred thousand medical device reports (MDRs) describing problems associated with a huge variety of medical devices. This category includes dental devices. Manufacturers, importers, and device-user facilities are required to report adverse events, and voluntary reports are accepted from health care professionals, patients, and consumers. The Manufacturer and User Facility Device Experience (MAUDE) database is the storehouse of all the reports.

http://ift.tt/2zZh5AF

Effects of low-level laser irradiation on the rate of orthodontic tooth movement and associated pain with self-ligating brackets

The aim of this study was to evaluate the effect of low-level laser irradiation applied at 3-week intervals on orthodontic tooth movement and pain associated with orthodontic tooth movement using self-ligating brackets.

http://ift.tt/2hxTC2N

Nonsurgical treatment of an adult with a skeletal Class II gummy smile using zygomatic temporary anchorage devices and improved superelastic nickel-titanium alloy wires

Patients with a severe gummy smile and a skeletal Class II profile are difficult to treat. This case report describes an effective treatment alternative for improving a gummy smile in a patient with a severe Class II molar relationship, severe crowding, and lip protrusion using zygomatic anchorage devices and improved superelastic nickel-titanium wires. A 36-year-old woman had an excessive overjet and a deep overbite with a bilateral Angle Class II molar relationship. The cephalometric analysis demonstrated a Class II skeletal relationship (ANB, 9.5°), retroclination of the mandible (FMA, 38.4°), and severe labial inclination of the mandibular incisors (IMPA, 101.9°).

http://ift.tt/2hxTqAB

Correction

Ferreira JTL, Romano FL, Sasso Stuani MB, Assed Carneiro FC, Nakane Matsumoto MA. Traction of impacted canines in a skeletal Class III malocclusion: A challenging orthodontic treatment. Am J Orthod Dentofacial Orthop 2017;151:1159-68.

http://ift.tt/2zZjFqe

Survival analysis, part 3: Cox regression

Another approach to analyze survival data is to use regression analysis. This can be accomplished by applying Cox regression, which allows us to calculate a special form of rate ratios known as hazard ratios.1 Therefore, instead of just a P value provided by the log-rank test, we can obtain an effect estimate with its confidence intervals, and at the same time we can adjust for other categorical or continuous covariates and interactions.

http://ift.tt/2hx3ARU

To understand the understood

Mr Millon was referred to you by a local prosthodontist to extrude a fractured premolar in preparation for a full-coverage restoration. Apparently, the chemistry between the 2 of you was superb. He immediately enlisted for treatment with the sweetest words you could hear: "How soon can we get started, doctor?" As you arise to shake his hand at the conclusion of the visit, he asks whether you could evaluate his adolescent daughter soon. "She's been in treatment for more than 3 years," he said. "We are happy with the result, but the orthodontist won't take off those braces."

http://ift.tt/2A10lJ0

Three-camera setup to record simultaneously standardized high-definition video for smile analysis

Our objective was to develop a photographic setup that would simultaneously capture subjects' smiles from 3 views, both statically and dynamically, and develop a software to crop the produced video clip and slice the frames to study the smile at different stages.

http://ift.tt/2hvPmk3

Authors' response

We thank Drs Yang, Jiang, and Li for their interest in our case report (Ferreira JT, Romano FL, Sasso Stuani MB, Assed Carneiro FC, Nakane Matsumoto MA. Traction of impacted canines in a skeletal Class III malocclusion: a challenging orthodontic treatment. Am J Orthod Dentofacial Orthop 2017;151:1159-68).

http://ift.tt/2zZy3ig

Protein and mRNA expressions of IL-6 and its key signaling factors under orthodontic forces in mice: An in-vivo study

The purpose of this study was to investigate the mechanical loading-induced changes in protein and mRNA expressions of interleukin-6 (IL-6) and its key signaling factors glycoprotein 130 (gp130), signal transducer and activator of transcription 3 (STAT3), and the Src homology phosphotyrosine phosphatase (SHP2) at the tension and compression sides of the teeth in mouse models.

http://ift.tt/2hvPikj

Traction of impacted canines in a skeletal Class III malocclusion

We read the case report describing traction of impacted canines in a skeletal Class III malocclusion in the June 2017 issue (Ferreira JT, Romano FL, Sasso Stuani MB, Assed Carneiro FC, Nakane Matsumoto MA. Traction of impacted canines in a skeletal Class III malocclusion: a challenging orthodontic treatment. Am J Orthod Dentofacial Orthop 2017;151:1159-68). We appreciate the authors' efforts in sharing this difficult case with us. However, we have some questions about diagnosis and therapy progress.

http://ift.tt/2zZMTWb

Acknowledgement to Reviewers

http://ift.tt/2imRaM5

Curative Radiotherapy at Time of Progression Under Active Surveillance Compared with Upfront Radical Radiotherapy for Prostate Cancer

Patients treated with curative-intent modern radiotherapy (i.e. dose-escalated IGRT or LDR-BT) after progressing under active surveillance have excellent oncologic outcomes, comparable to those in men with similar disease de novo characteristics treated with upfront radiotherapy.

http://ift.tt/2z7q59Q

Voltage and Calcium Imaging of Brain Activity

Sensors for imaging brain activity have been under development for almost 50 years. The development of some of these tools is relatively mature, whereas qualitative improvements of others are needed and are actively pursued. In particular, genetically encoded voltage indicators are just now starting to be used to answer neurobiological questions and, at the same time, more than 10 laboratories are working to improve them. In this Biophysical Perspective, we attempt to discuss the present state of the art and indicate areas of active development.

http://ift.tt/2h405oU

Voltage and Calcium Imaging of Brain Activity

Sensors for imaging brain activity have been under development for almost 50 years. The development of some of these tools is relatively mature, whereas qualitative improvements of others are needed and are actively pursued. In particular, genetically encoded voltage indicators are just now starting to be used to answer neurobiological questions and, at the same time, more than 10 laboratories are working to improve them. In this Biophysical Perspective, we attempt to discuss the present state of the art and indicate areas of active development.

http://ift.tt/2h405oU

WHO guidelines on testing for hepatitis B and C – meeting targets for testing

http://ift.tt/2lDeTMG

Optimising diagnosis of viraemic hepatitis C infection: the development of a target product profile

The current low access to virological testing to confirm chronic viraemic HCV infection in low- and middle-income countries (LMIC) is limiting the rollout of hepatitis C (HCV) care. Existing tests are complex,...

http://ift.tt/2ykJxjX

Methodological challenges in appraising evidence on diagnostic testing for WHO guidelines on hepatitis B and hepatitis C virus infection

Linking persons with hepatitis B (HBV) and hepatitis C (HCV) infection with appropriate prevention and treatment requires that they first be diagnosed. The World Health Organization (WHO) has developed its fir...

http://ift.tt/2lDeCJE

The future of viral hepatitis testing: innovations in testing technologies and approaches

A large burden of undiagnosed hepatitis virus cases remains globally. Despite the 257 million people living with chronic hepatitis B virus infection, and 71 million with chronic viraemic HCV infection, most pe...

http://ift.tt/2ynlcda

Trends in hepatitis B virus testing practices and management in HIV clinics across sub-Saharan Africa

Approximately 8% of HIV-infected individuals are co-infected with hepatitis B virus (HBV) in sub-Saharan Africa (SSA). Knowledge of HBV status is important to guide optimal selection of antiretroviral therapy ...

http://ift.tt/2lDetG6

Quantifying Microorganisms at Low Concentrations Using Digital Holographic Microscopy (DHM)

Digital holographic microscopy (DHM) is a volumetric technique that allows imaging samples 50-100X thicker than brightfield microscopy at comparable resolution, with focusing performed post-processing. Here DHM is used for identifying, counting, and tracking microorganisms at very low densities and compared with optical density measurements, plate count, and direct count.

http://ift.tt/2zZ2S6O

Gaining hope and self-confidence—An interview study of women’s experience of treatment by art therapy for severe fear of childbirth

Publication date: Available online 31 October 2017
Source:Women and Birth
Author(s): Helén Wahlbeck, Linda J. Kvist, Kajsa Landgren
BackgroundFear of childbirth is a serious problem that can have negative effects on both women and babies and to date treatment options are limited. The aim of this study was to elucidate the experience of undergoing art therapy in women with severe fear of childbirth.MethodNineteen women residing in Sweden, who had undergone art therapy for severe fear of childbirth, were interviewed during 2011–2013 about their experiences of the treatment. All women had received both support from a specialist team of midwives and treatment by an art therapist who was also a midwife. The women were interviewed three months after giving birth. The transcribed interviews were analysed with a phenomenological hermeneutical method.FindingsA main theme and three themes emerged from the analysis. The main theme was Gaining hope and self confidence. The three themes were; Carrying heavy baggage, Creating images as a catalyst for healing and Gaining new insights and abilities. Through the use of images and colours the women gained access to difficult emotions and the act of painting helped them visualize these emotions and acted as a catalyst for the healing process.DiscussionArt therapy was well accepted by the women. Through sharing their burden of fear by creating visible images, they gained hope and self-confidence in the face of their impending childbirth.ConclusionThe results may contribute to knowledge about the feasibility of treating fear of childbirth by art therapy.



http://ift.tt/2z4aGoz

2017 SAFECOM survey assesses state of emergency communications

The Department of Homeland Security OEC released the data to guide the development of policies, programs and funding

http://ift.tt/2xKmVVz

Feasibility of early, motor assisted upper extremity cycle ergometry in critically ill neurological patients with upper extremity weakness and variable cognitive status: a case series.

Upper extremity paresis, common in many neurological conditions, is a major contributor of long-term disability and decreased quality of life. Evidence shows that repetitive, bilateral arm movement improves upper extremity coordination after neurological injury. However, it is difficult to integrate upper extremity interventions into very early rehabilitation of critically ill neurological patients due to patient arousal and medical acuity. This report describes the safety and feasibility of bilateral upper extremity cycling in critically ill neurological patients with bilateral or unilateral paresis. Patients were included in this pilot observational series if they used upper extremity cycle ergometry with occupational therapy while in the neurocritical care unit between May and August 2016. Patient demographics, neurological function, and hemodynamic status were recorded pre and post cycling. Cycling parameters including duration and active and/or passive cycling were collected. No significant changes in hemodynamic or respiratory status were noted post intervention. No adverse effects or safety events were noted. In this series, upper extremity cycle ergometry was a safe and feasible intervention for early rehabilitation in critically ill patients in the neurocritical care unit. Future studies will prospectively measure the impact of early upper extremity cycle ergometry on neurological recovery and functional outcome in this population. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

http://ift.tt/2yl0lHr

Impact of an In Situ Component on Outcome After In-Breast Tumor Recurrence in Patients Treated with Breast-Conserving Therapy

Abstract

Background

Among all in-breast tumor recurrences (IBTR) following breast-conserving therapy (BCT), some comprise metachronous new primaries (NPs) while others are true recurrences (TRs). Establishing this distinction remains a challenge.

Methods

We studied 3932 women who underwent BCT for stage I–III breast cancer from 1998 to 2008. Of these, 115 (2.9%) had an IBTR. Excluding patients with inoperable/unresectable recurrences or simultaneous distant metastases, 81 patients with isolated IBTR comprised the study population. An IBTR was categorized as an NP rather than a TR if it included an in situ component. The log-rank test and Kaplan–Meier method were used to evaluate disease-free survival (DFS) and overall survival (OS), and univariate and multivariate analyses were performed using Cox proportional hazards regression models.

Results

At a median of 64.5 months from IBTR diagnosis, 28 of 81 patients had DFS events. Five-year DFS was 43.1% in the TR group (p = 0.0001) versus 80.3% in the NP group, while 5-year OS was 59.7% in the TR group versus 91.7% among those with NPs (p = 0.0011). On univariate analysis, increasing tumor size, high grade, positive margins, lymphovascular invasion, node involvement, lack of axillary surgery, chemotherapy, radiation therapy, and IBTR type (TR vs. NP) were significantly associated with worse DFS. Controlling for tumor size and margin status, TRs remained significantly associated with lower DFS (hazard ratio 3.717, 95% confidence interval 1.607–8.595, p = 0.002).

Conclusion

The presence of an in situ component is associated with prognosis among patients with IBTR following BCT and may be useful in differentiating TRs and NPs.

http://ift.tt/2zaiabE

Methodology for Developing Life Tables for Sessile Insects in the Field Using the Whitefly, Bemisia tabaci, in Cotton As a Model System

Life tables allow quantification of the sources and rates of mortality in insect populations and contribute to understanding, predicting and manipulating population dynamics in agroecosystems. Methods for conducting and analyzing cohort-based life tables in the field for an insect with sessile immature life stages are presented.

http://ift.tt/2gVIbAV

Canadian paramedic paints 100 responder portraits in 100 days

By EMS1 Staff CALGARY, Alberta — An injured paramedic is on a mission to paint 100 portraits of first responders in 100 days to raise awareness of job fatigue. Calgary Herald reported that paramedic Naomi Fox, who is currently recovering from hip surgery from a work-related injury, wants to raise awareness about the physical and mental fatigue paramedics face on the job. "In order to keep ...

http://ift.tt/2h4aYqL

When to eat! [Editorials]

http://ift.tt/2zoZDZQ

Variations in energy intake: it is more complicated than we think [Editorials]

http://ift.tt/2zbHdef

Salt substitution is a promising but unproven intervention for stroke management [Editorials]

http://ift.tt/2zoylmr

Genetic variation of habitual coffee consumption and glycemic changes in response to weight-loss diet intervention: the Preventing Overweight Using Novel Dietary Strategies (POUNDS LOST) trial [Gene-nutrient interactions]

Background: Coffee consumption has been associated with glucose metabolism and risk of type 2 diabetes.

Objective: We examined whether the genetic variation determining habitual coffee consumption affected glycemic changes in response to weight-loss dietary intervention.

Design: A genetic risk score (GRS) was calculated based on 8 habitual coffee consumption–associated single nucleotide polymorphisms. We used general linear models to test changes in glycemic traits in groups randomly assigned to high- and low-fat diets according to tertiles of the GRS.

Results: We observed significant interactions between the GRS and low compared with high dietary fat intake on 6-mo changes in fasting insulin and homeostasis model assessment of insulin resistance (HOMA-IR) (P-interaction = 0.023 and 0.022, respectively), adjusting for age, sex, race, physical activity, smoking, alcohol, seasonal variation, and baseline values of the respective outcomes. Participants with a higher GRS of habitual coffee consumption showed a greater reduction in fasting insulin and a marginally greater decrease in HOMA-IR in the low-fat diet intervention group.

Conclusions: Our data suggest that participants with genetically determined high coffee consumption may benefit more by eating a low-fat diet in improving fasting insulin and HOMA-IR in a short term. This trial was registered at clinicaltrials.gov as NCT00072995 and NCT03258203.

http://ift.tt/2zbwzo4

Surrogate disease markers as substitutes for chronic disease outcomes in studies of diet and chronic disease relations [Perspective]

Surrogate biomarkers for clinical outcomes afford scientific and economic efficiencies when investigating nutritional interventions in chronic diseases. However, valid scientific results are dependent on the qualification of these disease markers that are intended to be substitutes for a clinical outcome and to accurately predict benefit or harm. In this article, we examine the challenges of evaluating surrogate markers and describe the framework proposed in a 2010 Institute of Medicine report. The components of this framework are presented in the context of nutritional interventions for chronic diseases. We present case studies of 2 well-accepted surrogate markers [blood pressure within sodium intake and cardiovascular disease (CVD) context and low density lipoprotein–cholesterol concentrations within a saturated fat and CVD context]. We also describe additional cases in which the evidence is insufficient to validate their surrogate status. Guidance is offered for future research that evaluates or uses surrogate markers.

http://ift.tt/2zoZpSu

Within-day protein distribution does not influence body composition responses during weight loss in resistance-training adults who are overweight [Obesity and eating disorders]

Background: Emerging research suggests that redistributing total protein intake from 1 high-protein meal/d to multiple moderately high-protein meals improves 24-h muscle protein synthesis. Over time, this may promote positive changes in body composition.

Objective: We sought to assess the effects of within-day protein intake distribution on changes in body composition during dietary energy restriction and resistance training.

Design: In a randomized parallel-design study, 41 men and women [mean ± SEM age: 35 ± 2 y; body mass index (in kg/m²): 31.5 ± 0.5] consumed an energy-restricted diet (750 kcal/d below the requirement) for 16 wk while performing resistance training 3 d/wk. Subjects consumed 90 g protein/d (1.0 ± 0.03 g · kg^–1 · d^–1, 125% of the Recommended Dietary Allowance, at intervention week 1) in either a skewed (10 g at breakfast, 20 g at lunch, and 60 g at dinner; n = 20) or even (30 g each at breakfast, lunch, and dinner; n = 21) distribution pattern. Body composition was measured pre- and postintervention.

Results: Over time, whole-body mass (least-squares mean ± SE: –7.9 ± 0.6 kg), whole-body lean mass (–1.0 ± 0.2 kg), whole-body fat mass (–6.9 ± 0.5 kg), appendicular lean mass (–0.7 ± 0.1 kg), and appendicular fat mass (–2.6 ± 0.2 kg) each decreased. The midthigh muscle area (0 ± 1 cm²) did not change over time, whereas the midcalf muscle area decreased (–3 ± 1 cm²). Within-day protein distribution did not differentially affect these body-composition responses.

Conclusion: The effectiveness of dietary energy restriction combined with resistance training to improve body composition is not influenced by the within-day distribution of protein when adequate total protein is consumed. This trial was registered at clinicaltrials.gov as NCT02066948.

http://ift.tt/2zpVe9m

Biomarkers of food intake and nutrient status are associated with glucose tolerance status and development of type 2 diabetes in older Swedish women [Nutritional epidemiology and public health]

Background: Diet is frequently associated with both the development and prevention of type 2 diabetes (T2D), but there is a lack of objective tools for assessing the relation between diet and T2D. Biomarkers of dietary intake are unconfounded by recall and reporting bias, and using multiple dietary biomarkers could help strengthen the link between a healthy diet and the prevention of T2D.

Objective: The objective of this study was to explore how diet is related to glucose tolerance status (GTS) and to future development of T2D irrespective of common T2D and cardiovascular disease risk factors by using multiple dietary biomarkers.

Design: Dietary biomarkers were measured in plasma from 64-y-old Swedish women with different GTS [normal glucose tolerance (NGT; n = 190), impaired glucose tolerance (IGT; n = 209), and diabetes (n = 230)]. The same subjects were followed up after 5 y to determine changes in glucose tolerance (n = 167 for NGT, n = 174 for IGT, and n = 159 for diabetes). ANCOVA and logistic regression were used to explore baseline data for associations between dietary biomarkers, GTS, and new T2D cases at follow-up (n = 69).

Results: Of the 10 dietary biomarkers analyzed, β-alanine (beef) (P-raw < 0.001), alkylresorcinols C17 and C19 (whole-grain wheat and rye) (P-raw = 0.003 and 0.011), eicosapentaenoic acid (fish) (P-raw = 0.041), 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid (CMPF) (fish) (P-raw = 0.002), linoleic acid (P-raw < 0.001), oleic acid (P-raw = 0.003), and α-tocopherol (margarine and vegetable oil) (P-raw < 0.001) were associated with GTS, and CMPF (fish) (OR: 0.72; 95% CI: 0.56, 0.93; P-raw = 0.013) and α-tocopherol (OR: 0.71; 95% CI: 0.51, 0.98; P-raw = 0.041) were inversely associated with future T2D development.

Conclusions: Several circulating dietary biomarkers were strongly associated with GTS after correction for known T2D risk factors, underlining the role of diet in the development and prevention of T2D. To our knowledge, this study is the first to use multiple dietary biomarkers to investigate the link between diet and disease risk.

http://ift.tt/2z9HSNq

No metabolic effects of mustard allyl-isothiocyanate compared with placebo in men [Obesity and eating disorders]

Background: Induction of nonshivering thermogenesis can be used to influence energy balance to prevent or even treat obesity. The pungent component of mustard, allyl-isothiocyanate (AITC), activates the extreme cold receptor transient receptor potential channel, subfamily A, member 1 and may thus induce energy expenditure and metabolic changes.

Objective: The objective of our study was to evaluate the potential of mustard AITC to induce thermogenesis (primary outcome) and alter body temperature, cold and hunger sensations, plasma metabolic parameters, and energy intake (secondary outcomes).

Design: Energy expenditure in mice was measured after subcutaneous injection with vehicle, 1 mg norepinephrine/kg, or 5 mg AITC/kg. In our human crossover study, 11 healthy subjects were studied under temperature-controlled conditions after an overnight fast. After ingestion of 10 g of capsulated mustard or uncapsulated mustard or a capsulated placebo mixture, measurements of energy expenditure, substrate oxidation, core temperature, cold and hunger scores, and plasma parameters were repeated every 30 min during a 150-min period. Subjects were randomly selected for the placebo and capsulated mustard intervention; 9 of 11 subjects received the uncapsulated mustard as the final intervention because this could not be blinded. After the experiments, energy intake was measured with the universal eating monitor in a test meal.

Results: In mice, AITC administration induced a 32% increase in energy expenditure compared with vehicle (17.5 ± 4.9 J · min^–1 · mouse^–1 compared with 12.5 ± 1.2 J · min^–1 · mouse^–1, P = 0.03). Of the 11 randomly selected participants, 1 was excluded because of intercurrent illness after the first visit and 1 withdrew after the second visit. Energy expenditure did not increase after ingestion of capsulated or uncapsulated mustard compared with placebo. No differences in substrate oxidation, core temperature, cold and hunger scores, or plasma parameters were found, nor was the energy intake at the end of the experiment different between the 3 conditions.

Conclusion: The highest tolerable dose of mustard we were able to use did not elicit a relevant thermogenic response in humans. This trial was registered at http://ift.tt/HkCGY7 as ISRCTN19147515.

http://ift.tt/2zoNx33

Textbook of Global Health, Fourth Edition, by A-E Birn, Y Pillay, and TH Holtz. Reviewed by MT Tan [Book Review]

http://ift.tt/2znvKcp

Investigating predictors of eating: is resting metabolic rate really the strongest proxy of energy intake? [Nutritional status, dietary intake, and body composition]

Background: Evidence suggests that fat-free mass and resting metabolic rate (RMR), but not fat mass, are strong predictors of energy intake (EI). However, body composition and RMR do not explain the entire variance in EI, suggesting that other factors may contribute to this variance.

Objective: We aimed to investigate the associations between body mass index (in kg/m²), fat mass, fat-free mass, and RMR with acute (1 meal) and daily (24-h) EI and between fasting appetite ratings and certain eating behavior traits with daily EI. We also evaluated whether RMR is a predictor of the error variance in acute and daily EI.

Design: Data collected during the control condition of 7 studies conducted in Ottawa, Ontario, Canada, were included in these analyses (n = 191 and 55 for acute and daily EI, respectively). These data include RMR (indirect calorimetry), body composition (dual-energy X-ray absorptiometry), fasting appetite ratings (visual analog scales), eating behavior traits (Three-Factor Eating Questionnaire), and EI (food buffet or menu).

Results: Fat-free mass was the best predictor of acute EI (R² = 0.46; P < 0.0001). The combination of fasting prospective food consumption ratings and RMR was the best predictor of daily EI (R² = 0.44; P < 0.0001). RMR was a statistically significant positive predictor of the error variance for acute (R² = 0.20; P < 0.0001) and daily (R² = 0.23; P < 0.0001) EI. RMR did, however, remain a statistically significant predictor of acute (R² = 0.32; P < 0.0001) and daily (R² = 0.30; P < 0.0001) EI after controlling for this error variance.

Conclusions: Our findings suggest that combined measurements of appetite ratings and RMR could be used to estimate EI in weight-stable individuals. However, greater error variance in acute and daily EI with increasing RMR values was observed. Future studies are needed to identify whether greater fluctuations in daily EI over time occur with increasing RMR values. This trial was registered at clinicaltrials.gov as NCT02653378.

http://ift.tt/2z9HDC0

In the elderly, meat protein assimilation from rare meat is lower than that from meat that is well done [Energy and protein metabolism]

Background: Meat cooking conditions in in vitro and in vivo models have been shown to influence the rate of protein digestion, which is known to affect postprandial protein metabolism in the elderly.

Objective: The present study was conducted to demonstrate the effect of cooking conditions on meat protein assimilation in the elderly. We used a single-meal protocol to assess the meat protein absorption rate and estimate postprandial meat protein utilization in elderly subjects.

Design: The study recruited 10 elderly volunteers aged 70–82 y. Each received, on 2 separate occasions, a test meal exclusively composed of intrinsically ¹⁵N-labeled bovine meat (30 g protein), cooked at 55°C for 5 min [rare meat (RM)] or at 90°C for 30 min [fully cooked meat (FCM)], and minced. Whole-body fluxes of leucine, before and after the meal, were determined with the use of a [1-¹³C]leucine intravenous infusion. Meat protein absorption was recorded with the use of ¹⁵N enrichment of amino acids.

Results: Postprandial time course observations showed a lower concentration in the plasma of indispensable amino acids (P < 0.01), a lower entry rate of meat leucine in the plasma (P < 0.01), and a lower contribution of meat nitrogen to plasma amino acid nitrogen (P < 0.001), evidencing lower peripheral bioavailability of meat amino acids with RM than with FCM. This was associated with decreased postprandial whole-body protein synthesis with RM than with FCM (40% compared with 56% of leucine intake, respectively; P < 0.01).

Conclusions: Whereas meat cooking conditions have little effect on postprandial protein utilization in young adults, the present work showed that the bioavailability and assimilation of meat amino acids in the elderly is lower when meat is poorly cooked. In view to preventing sarcopenia, elderly subjects should be advised to favor the consumption of well-cooked meat. This trial was registered at clinicaltrials.gov as NCT02157805.

http://ift.tt/2zoqKV0

Later circadian timing of food intake is associated with increased body fat [Nutritional status, dietary intake, and body composition]

Background: Weight gain and obesity have reached alarming levels. Eating at a later clock hour is a newly described risk factor for adverse metabolic health; yet, how eating at a later circadian time influences body composition is unknown. Using clock hour to document eating times may be misleading owing to individual differences in circadian timing relative to clock hour.

Objective: This study examined the relations between the timing of food consumption relative to clock hour and endogenous circadian time, content of food intake, and body composition.

Design: We enrolled 110 participants, aged 18–22 y, in a 30-d cross-sectional study to document sleep and circadian behaviors within their regular daily routines. We used a time-stamped-picture mobile phone application to record all food intake across 7 consecutive days during a participant's regular daily routines and assessed their body composition and timing of melatonin release during an in-laboratory assessment.

Results: Nonlean individuals (high body fat) consumed most of their calories 1.1 h closer to melatonin onset, which heralds the beginning of the biological night, than did lean individuals (low body fat) (log-rank P = 0.009). In contrast, there were no differences between lean and nonlean individuals in the clock hour of food consumption (P = 0.72). Multiple regression analysis showed that the timing of food intake relative to melatonin onset was significantly associated with the percentage of body fat and body mass index (both P < 0.05) while controlling for sex, whereas no relations were found between the clock hour of food intake, caloric amount, meal macronutrient composition, activity or exercise level, or sleep duration and either of these body composition measures (all P > 0.72).

Conclusions: These results provide evidence that the consumption of food during the circadian evening and/or night, independent of more traditional risk factors such as amount or content of food intake and activity level, plays an important role in body composition. This trial was registered at clinicaltrials.gov as NCT02846077.

http://ift.tt/2z9Hw9y

Randomized controlled trial on the impact of early-life intervention with bifidobacteria on the healthy infant fecal microbiota and metabolome [Growth, development, and pediatrics]

Background: Early-life colonization of the intestinal tract is a dynamic process influenced by numerous factors. The impact of probiotic-supplemented infant formula on the composition and function of the infant gut microbiota is not well defined.

Objective: We sought to determine the effects of a bifidobacteria-containing formula on the healthy human intestinal microbiome during the first year of life.

Design: A double-blind, randomized, placebo-controlled study of newborn infants assigned to a standard whey-based formula containing a total of 10⁷ colony-forming units (CFU)/g of Bifidobacterium bifidum, Bifidobacterium breve, Bifidobacterium longum, B. longum subspecies infantis (intervention), or to a control formula without bifidobacteria (placebo). Breastfed controls were included. Diversity and composition of fecal microbiota were determined by 16S ribosomal RNA gene amplicon sequencing, and metabolite profiles were analyzed by ultrahigh-performance liquid chromatography–mass spectrometry over a period of 2 y.

Results: Infants (n = 106) were randomly assigned to either the interventional (n = 48) or placebo (n = 49) group; 9 infants were exclusively breastfed throughout the entire intervention period of 12 mo. Infants exposed to bifidobacteria-supplemented formula showed decreased occurrence of Bacteroides and Blautia spp. associated with changes in lipids and unknown metabolites at month 1. Microbiota and metabolite profiles of intervention and placebo groups converged during the study period, and long-term colonization (24 mo) of the supplemented Bifidobacterium strains was not detected. Significant differences in microbiota and metabolites were detected between infants fed breast milk and those fed formula (P < 0.005) and between infants birthed vaginally and those birthed by cesarean delivery (P < 0.005). No significant differences were observed between infant feeding groups regarding growth, antibiotic uptake, or other health variables (P > 0.05).

Conclusion: The supplementation of bifidobacteria to infant diet can modulate the occurrence of specific bacteria and metabolites during early life with no detectable long-term effects. This trial was registered at germanctr.de as DRKS00003660.

http://ift.tt/2zonbyd

Time of day and eating behaviors are associated with the composition and function of the human gastrointestinal microbiota [Nutritional status, dietary intake, and body composition]

Background: Preclinical research has shown that the gastrointestinal microbiota exhibits circadian rhythms and that the timing of food consumption can affect the composition and function of gut microbes. However, there is a dearth of knowledge on these relations in humans.

Objective: We aimed to determine whether human gastrointestinal microbes and bacterial metabolites were associated with time of day or behavioral factors, including eating frequency, percentage of energy consumed early in the day, and overnight-fast duration.

Design: We analyzed 77 fecal samples collected from 28 healthy men and women. Fecal DNA was extracted and sequenced to determine the relative abundances of bacterial operational taxonomic units (OTUs). Gas chromatography–mass spectroscopy was used to assess short-chain fatty acid concentrations. Eating frequency, percentage of energy consumed before 1400, and overnight-fast duration were determined from dietary records. Data were analyzed by linear mixed models or generalized linear mixed models, which controlled for fiber intake, sex, age, body mass index, and repeated sampling within each participant. Each OTU and metabolite were tested as the outcome in a separate model.

Results: Acetate, propionate, and butyrate concentrations decreased throughout the day (P = 0.006, 0.04, and 0.002, respectively). Thirty-five percent of bacterial OTUs were associated with time. In addition, relations were observed between gut microbes and eating behaviors, including eating frequency, early energy consumption, and overnight-fast duration.

Conclusions: These results indicate that the human gastrointestinal microbiota composition and function vary throughout the day, which may be related to the circadian biology of the human body, the microbial community itself, or human eating behaviors. Behavioral factors, including timing of eating and overnight-fast duration, were also predictive of bacterial abundances. Longitudinal intervention studies are needed to determine causality of these biological and behavioral relations. This trial was registered at clinicaltrials.gov as NCT01925560.

http://ift.tt/2zceVAo

Trajectories of maternal weight from before pregnancy through postpartum and associations with childhood obesity [Nutritional epidemiology and public health]

Background: Prepregnancy body mass index [BMI (in kg/m²)], gestational weight gain, and postpartum weight retention may have distinct effects on the development of child obesity, but their combined effect is currently unknown.

Objective: We described longitudinal trajectories of maternal weight from before pregnancy through the postpartum period and assessed the relations between maternal weight trajectories and offspring obesity in childhood.

Design: We analyzed data from 4436 pairs of mothers and their children in the National Longitudinal Survey of Youth 1979 (1981–2014). We used latent-class growth modeling in addition to national recommendations for prepregnancy BMI, gestational weight gain, and postpartum weight retention to create maternal weight trajectory groups. We used modified Poisson regression models to assess the associations between maternal weight trajectory group and offspring obesity at 3 age periods (2–5, 6–11, and 12–19 y).

Results: Our analysis using maternal weight trajectories based on either latent-class results or recommendations showed that the risk of child obesity was lowest in the lowest maternal weight trajectory group. The differences in obesity risk were largest after 5 y of age and persisted into adolescence. In the latent-class analysis, the highest-order maternal weight trajectory group consisted almost entirely of women who were obese before pregnancy and was associated with a >2-fold increase in the risk of offspring obesity at ages 6–11 y (adjusted RR: 2.39; 95% CI: 1.97, 2.89) and 12–19 y (adjusted RR: 2.74; 95% CI: 2.13, 3.52). In the analysis with maternal weight trajectory groups based on recommendations, the risk of child obesity was consistently highest for women who were overweight or obese at the beginning of pregnancy.

Conclusion: These findings suggest that high maternal weight across the childbearing period increases the risk of obesity in offspring during childhood, but high prepregnancy BMI has a stronger influence than either gestational weight gain or postpartum weight retention.

http://ift.tt/2zon9GB

Comparison of midupper arm circumference and weight-for-height z score for assessing acute malnutrition in Bangladeshi children aged 6-60 mo: an analytical study [Nutritional status, dietary intake, and body composition]

Background: In clinical settings, wasting in childhood has primarily been assessed with the use of a weight-for-height z score (WHZ), and in community settings, it has been assessed via the midupper arm circumference (MUAC) with a cutoff <115 mm for severe wasting and <115–125 mm for moderate wasting. Our recent experience indicates that many wasted children were not identified when these cutoffs for MUAC were used.

Objective: We determined the cutoffs for MUAC to detect wasting in Bangladeshi children aged 6–60 mo.

Design: A secondary analysis was carried out on data from 27,767 children aged 6–59 mo. This analysis comprised 1) 9131 children across Bangladesh and 2) 18,636 children enrolled in a surveillance study in the Dhaka Hospital of icddr,b during 1996–2014. The area under the receiver operating curve was used to indicate the most appropriate choice for cutoffs that related MUAC with WHZ.

Results: The mean ± SD age for the entire group was 21 ± 14 mo, WHZ was –1.18 ± 1.23, height-for-age z score was –1.63 ± 1.39, MUAC was 136 ± 14 mm, and 45% of subjects were girls. MUAC correlated with the WHZ (r: 0.618, P < 0.001). Age-stratified analyses revealed that, for ages 6–24 mo, MUAC cutoffs were <120 mm for a WHZ <–3 and <125 mm for a WHZ <–2 with a sensitivity of 72.9% and 63.2%, respectively, and a specificity of 84.7% and 85.3%, respectively; for ages 25–36 mo, MUAC cutoffs were <125 mm for a WHZ <–3 and <135 mm for a WHZ <–2 with a sensitivity of 55.0% and 71.7%, respectively, and a specificity of 92.8% and 78.7% respectively; and for ages 37–60 mo, MUAC cutoffs were <135 mm for a WHZ <–3 and <140 mm for a WHZ <–2 with a sensitivity of 71.4% and 70.4%, respectively, and a specificity of 84.6% and 80.3%, respectively.

Conclusion: The respective cutoffs for MUAC to better capture the vulnerability and risk of severe (WHZ <–3) and moderate (WHZ <–2) wasting would be <120 and <125 mm for ages 6–24 mo, <125 and <135 mm for ages 25–36 mo, and <135 and <140 mm for ages 37–60 mo.

http://ift.tt/2zceOEY

Cluster randomized controlled trial of a consumer behavior intervention to improve healthy food purchases from online canteens [Nutritional epidemiology and public health]

Background: School canteens represent an opportune setting in which to deliver public health nutrition strategies because of their wide reach and frequent use by children. Online school-canteen ordering systems, where students order and pay for their lunch online, provide an avenue to improve healthy canteen purchases through the application of consumer-behavior strategies that have an impact on purchasing decisions.

Objective: We assessed the efficacy of a consumer-behavior intervention implemented in an online school-canteen ordering system in reducing the energy, saturated fat, sugar, and sodium contents of primary student lunch orders.

Design: A cluster-randomized controlled trial was conducted that involved 2714 students (aged 5–12 y) from 10 primary schools in New South Wales, Australia, who were currently using an online canteen ordering system. Schools were randomized in a 1:1 ratio to receive either the intervention (enhanced system) or the control (standard online ordering only). The intervention included consumer-behavior strategies that were integrated into the online ordering system (targeting menu labeling, healthy food availability, placement, and prompting).

Results: Mean energy (difference: –567.25 kJ; 95% CI: –697.95, –436.55 kJ; P < 0.001), saturated fat (difference: –2.37 g; 95% CI: –3.08, –1.67 g; P < 0.001), and sodium (difference: –227.56 mg; 95% CI: –334.93, –120.19 mg; P < 0.001) contents per student lunch order were significantly lower in the intervention group than in the control group at follow-up. No significant differences were observed for sugar (difference: 1.16 g; 95% CI: –0.50, 2.83 g; P = 0.17).

Conclusions: The study provides strong evidence supporting the effectiveness of a consumer-behavior intervention using an existing online canteen infrastructure to improve purchasing behavior from primary school canteens. Such an intervention may represent an appealing policy option as part of a broader government strategy to improve child public health nutrition. This trial was registered at www.anzctr.org.au as ACTRN12616000499482.

http://ift.tt/2zon2Lb

Plasma glucose and insulin responses after consumption of breakfasts with different sources of soluble fiber in type 2 diabetes patients: a randomized crossover clinical trial [Carbohydrate metabolism and diabetes]

Background: The amount and quality of carbohydrates are important determinants of plasma glucose after meals. Regarding fiber content, it is unclear whether the intake of soluble fibers from foods or supplements has an equally beneficial effect on lowering postprandial glucose.

Objective: The aim of our study was to compare the acute effect of soluble fiber intake from foods or supplements after a common meal on postprandial plasma glucose and plasma insulin in patients with type 2 diabetes (T2D).

Design: A randomized crossover clinical trial was conducted in patients with T2D. Patients consumed isocaloric breakfasts (mean ± SD: 369.8 ± 9.4 kcal) with high amounts of fiber from diet food sources (total fiber: 9.7 g; soluble fiber: 5.4 g), high amounts of soluble fiber from guar gum supplement (total fiber: 9.1 g; soluble fiber: 5.4 g), and normal amounts of fiber (total fiber: 2.4 g; soluble fiber: 0.8 g). Primary outcomes were postprandial plasma glucose and insulin (0–180 min). Data were analyzed by repeated measures ANOVA and post hoc Bonferroni test.

Results: A total of 19 patients [aged 65.8 ± 7.3 y; median (IQR), 10 (5–9) y of T2D duration; glycated hemoglobin 7.0% ± 0.8%; body mass index (in kg/m²) 28.2 ± 2.9] completed 57 meal tests. After breakfast, the incremental area under the curve (iAUC) for plasma glucose [mg/dL · min; mean (95% CI)] did not differ between high fiber from diet (HFD) [7861 (6257, 9465)] and high fiber from supplement (HFS) [7847 (5605, 10,090)] (P = 1.00) and both were lower than usual fiber (UF) [9527 (7549, 11,504)] (P = 0.014 and P = 0.037, respectively). iAUCs [μIU/mL · min; mean (95% CI)] did not differ (P = 0.877): HFD [3781 (2513, 5050)], HFS [4006 (2711, 5302), and UF [4315 (3027, 5603)].

Conclusions: Higher fiber intake was associated with lower postprandial glucose at breakfast, and the intake of soluble fiber from food and supplement had a similar effect in patients with T2D. This trial was registered at clinicaltrials.gov as NCT02204384.

http://ift.tt/2z9H772

Differentiated and anaplastic thyroid carcinoma: Major changes in the American Joint Committee on Cancer eighth edition cancer staging manual

ABSTRACT

Answer questions and earn CME/CNE

This is a review of the major changes in the American Joint Committee on Cancer staging manual, eighth edition, for differentiated and anaplastic thyroid carcinoma. All patients younger than 55 years have stage I disease unless they have distant metastases, in which case, their disease is stage II. In patients aged 55 years or older, the presence of distant metastases confers stage IVB, while cases without distant metastases are further categorized based on the presence/absence of gross extrathyroidal extension, tumor size, and lymph node status. Patients aged 55 years or older whose tumor measures 4 cm or smaller (T1-T2) and is confined to the thyroid (N0, NX) have stage I disease, and those whose tumor measures greater than 4 cm and is confined to the thyroid (T3a) have stage II disease regardless of lymph node status. Patients aged 55 years or older whose tumor is confined to the thyroid and measures 4 cm or smaller (T1-T2) with any lymph node metastases present (N1a or N1b) have stage II disease. In patients who demonstrate gross extrathyroidal extension, the disease is considered stage II if only the strap muscles are grossly invaded (T3b); stage III if there is gross invasion of the subcutaneous tissue, larynx, trachea, esophagus, or recurrent laryngeal nerve (T4a); or stage IVA if there is gross invasion of the prevertebral fascia or tumor encasing the carotid artery or internal jugular vein (T4b). The same T definitions will be used for both differentiated and anaplastic thyroid cancer, but the basic premise of the anatomic stage groups will remain the same. CA Cancer J Clin 2017. © 2017 American Cancer Society.

http://ift.tt/2h3DIjk

Using In Vitro Live-cell Imaging to Explore Chemotherapeutics Delivered by Lipid-based Nanoparticles

Live-cell imaging is a powerful tool to visualize dynamic processes. The examination of fixed cells provides only static pictures, which can lead to misinterpretation and confusion about the process. This work presents a method to study uptake, drug release, and intracellular localization of liposomal nanoparticles in living cells.

http://ift.tt/2A7lJx4

A Crucial Test of the Population Separation Model of Auditory Stream Segregation in Macaque Primary Auditory Cortex

An important aspect of auditory scene analysis is auditory stream segregation—the organization of sound sequences into perceptual streams reflecting different sound sources in the environment. Several models have been proposed to account for stream segregation. According to the "population separation" (PS) model, alternating ABAB tone sequences are perceived as a single stream or as two separate streams when "A" and "B" tones activate the same or distinct frequency-tuned neuronal populations in primary auditory cortex (A1), respectively. A crucial test of the PS model is whether it can account for the observation that A and B tones are generally perceived as a single stream when presented synchronously, rather than in an alternating pattern, even if they are widely separated in frequency. Here, we tested the PS model by recording neural responses to alternating (ALT) and synchronous (SYNC) tone sequences in A1 of male macaques. Consistent with predictions of the PS model, a greater effective tonotopic separation of A and B tone responses was observed under ALT than under SYNC conditions, thus paralleling the perceptual organization of the sequences. While other models of stream segregation, such as temporal coherence, are not excluded by the present findings, we conclude that PS is sufficient to account for the perceptual organization of ALT and SYNC sequences and thus remains a viable model of auditory stream segregation.

SIGNIFICANCE STATEMENT According to the population separation (PS) model of auditory stream segregation, sounds that activate the same or separate neural populations in primary auditory cortex (A1) are perceived as one or two streams, respectively. It is unclear, however, whether the PS model can account for the perception of sounds as a single stream when they are presented synchronously. Here, we tested the PS model by recording neural responses to alternating (ALT) and synchronous (SYNC) tone sequences in macaque A1. A greater effective separation of tonotopic activity patterns was observed under ALT than under SYNC conditions, thus paralleling the perceptual organization of the sequences. Based on these findings, we conclude that PS remains a plausible neurophysiological model of auditory stream segregation.

http://ift.tt/2zXDONf

Interneurons in the Honeybee Primary Auditory Center Responding to Waggle Dance-Like Vibration Pulses

Female honeybees use the "waggle dance" to communicate the location of nectar sources to their hive mates. Distance information is encoded in the duration of the waggle phase (von Frisch, 1967). During the waggle phase, the dancer produces trains of vibration pulses, which are detected by the follower bees via Johnston's organ located on the antennae. To uncover the neural mechanisms underlying the encoding of distance information in the waggle dance follower, we investigated morphology, physiology, and immunohistochemistry of interneurons arborizing in the primary auditory center of the honeybee (Apis mellifera). We identified major interneuron types, named DL-Int-1, DL-Int-2, and bilateral DL-dSEG-LP, that responded with different spiking patterns to vibration pulses applied to the antennae. Experimental and computational analyses suggest that inhibitory connection plays a role in encoding and processing the duration of vibration pulse trains in the primary auditory center of the honeybee.

SIGNIFICANCE STATEMENT The waggle dance represents a form of symbolic communication used by honeybees to convey the location of food sources via species-specific sound. The brain mechanisms used to decipher this symbolic information are unknown. We examined interneurons in the honeybee primary auditory center and identified different neuron types with specific properties. The results of our computational analyses suggest that inhibitory connection plays a role in encoding waggle dance signals. Our results are critical for understanding how the honeybee deciphers information from the sound produced by the waggle dance and provide new insights regarding how common neural mechanisms are used by different species to achieve communication.

http://ift.tt/2zYvX1Z

Nosologic Considerations in Disorders of Consciousness

http://ift.tt/2z4RpWA

Reforming the Taxonomy in Disorders of Consciousness

Abstract

This paper examines the serious shortcomings that characterize the current taxonomy of post-comatose disorders of consciousness (DoC), and it provides guidelines for how an improved DoC taxonomy might be developed. In particular, it is argued that behavioural criteria for the application of DoC categories should be supplemented with brain-based criteria (e.g., information derived from EEG and fMRI), and that the categorical framework that currently characterizes DoC should be replaced by a more complex framework that better captures the performance of patients across a range of cognitive and behavioural tasks. This article is protected by copyright. All rights reserved.

http://ift.tt/2zXDyhp

Directed Differentiation of Primitive and Definitive Hematopoietic Progenitors from Human Pluripotent Stem Cells

Here, we present human pluripotent stem cell (hPSC) culture protocols, used to differentiate hPSCs into CD34+ hematopoietic progenitors. This method uses stage-specific manipulation of canonical WNT signaling to specify cells exclusively to either the definitive or primitive hematopoietic program.

http://ift.tt/2lBbApe

Cover

http://ift.tt/2zcHf5T

In This Issue

http://ift.tt/2zb0GvI

Anti-tumor immunity via the superoxide-eosinophil axis induced by a lipophilic component of Mycobacterium lipomannan

Abstract

Mycobacterium bovis Bacille Calmette–Guérin (BCG) has been shown to possess potent anti-tumor activity particularly in various animal models, while the cellular and molecular mechanisms underlying its activity are not well understood. We found that lipomannan (BCG-LM), a lipophilic component of the mycobacterial cell envelope, specifically inhibits tumor growth and induces the infiltration of eosinophils at local tumor invasion sites. In contrast, neither lipoarabinomannan (BCG-LAM) nor the cell wall of Mycobacterium bovis BCG (BCG-CW) exerted anti-tumor immunity. BCG-LM enhances cytotoxic activity of eosinophils via the increased production of superoxide. Global transcriptomic analyses of BCG-LM-pulsed dendritic cells identified C-C motif ligand (CCL) 5 as a crucial chemokine for the anti-tumor immunity induced by BCG-LM, indicating that CCL5 plays an important role for the accumulation of eosinophils in the tumor microenvironment. Furthermore, BCG-LM and memory T_h2 cells exerted a synergetic effect on tumor progression by cooperatively enhancing the eosinophil function. Thus, this study revealed an un-identified BCG-LM-mediated anti-tumor mechanism via superoxide produced by infiltrated eosinophils in the tumor microenvironment. Since BCG-LM activates this unique pathway, it may have potent therapeutic potential as immune cell therapy for cancer patients.

http://ift.tt/2zaKuug

Subscriptions

http://ift.tt/2z9kuQc

Table of Contents

http://ift.tt/2zcHeyR

Involvement of Zizimin2/3 in the age-related defect of peritoneal B-1a cells as a source of anti-bacterial IgM

Abstract

Zizimin2 (Ziz2), also known as dedicator of cytokinesis 11 (DOCK11), is a guanine nucleotide exchange factor that is predominantly expressed in lymphoid tissues. Recent findings demonstrated that Ziz2 is involved in the development of B cells, including germinal centre B cells and marginal zone B cells. However, limited information is currently available on the roles of Ziz2 in B-1 cells, a B-cell subset that resides in body cavities and contributes to protection against foreign pathogens in a T-cell-independent manner. We herein show that Ziz2 and its widely expressed isoform Ziz3 (also known as DOCK10) may be involved in defective production of anti-bacterial IgM by aged B-1a cells, a CD5⁺ subset of B-1 cells. Natural IgM against typical bacterial epitopes was defectively produced by peritoneal B-1a cells from aged mice. The down-regulation of Ziz2/3 in B-1a cells appeared to be responsible for this defective IgM production, as demonstrated by Ziz2/3 double-knockout mice. Mechanistically, lower levels of basal AKT phosphorylation did not allow for the differentiation of Ziz2/3-deficient B-1a cells into plasma cells. Defective production of anti-bacterial IgM was not fully rescued by immunization, resulting in slightly weaker protection in Ziz2/3-deficient mice. Thus, the down-regulation of Ziz2/3 in B-1a cells may at least partly account for defective protection in aged mice.

http://ift.tt/2zbM6UL

Expression of KIR2DS1 does not significantly contribute to NK cell cytotoxicity in HLA-C1/C2 heterozygous haplotype B donors

Abstract

NK cells are functionally controlled by the killer immunoglobulin-like receptor (KIR) family that comprises inhibitory (iKIR) and activating (aKIR) members. Genetic association studies suggest that donors expressing aKIRs next to iKIRs will be superior donors in the setting of hematopoietic stem cell transplantation of patients with leukemia. However, contrary evidence states that aKIR expression may be irrelevant or even detrimental. Using a complex methodology incorporating KIR-Q-PCR, double fluorescence and viSNE analysis, we characterized subset distribution patterns and functionality in haplotype A donors which lack aKIRs and haplotype B donors that express a variety of B-specific genes. Here, we show that the alloreactive KIR2DS1⁺ NK cell subset in HLA-C1/C2 donors is highly responsive towards C2-expressing targets but quantitatively small and as such does not significantly contribute to cytotoxicity. Thus, we fail to find a direct link between haplotype allocation status and NK cell cytotoxicity at least in HLA-C1/C2 heterozygous donors.

http://ift.tt/2zoh0dB

Hyperferritinemia and inflammation

Abstract

Understanding of ferritin biology has traditionally centered on its role in iron storage and homeostasis, with low ferritin levels indicative of deficiency and high levels indicative of primary or secondary hemochromatosis. However, further work has shown that iron, redox biology and inflammation are inexorably linked. During infection, increased ferritin levels represent an important host defense mechanism that deprives bacterial growth of iron and protects immune cell function. It may also be protective, limiting the production of free radicals and mediating immunomodulation. Additionally, hyperferritinemia is a key acute-phase reactants, used by clinicians as an indication for therapeutic intervention, aimed at controlling inflammation in high-risk patients. One school of thought maintains that hyperferritinemia is an 'innocent bystander' biomarker of uncontrolled inflammation that can be used to gauge effectiveness of intervention. Other schools of thought maintain that ferritin induction could be a protective negative regulatory loop. Others maintain that ferritin is a key mediator of immune dysregulation, especially in extreme hyperferritinemia, via direct immune-suppressive and pro-inflammatory effects. There is a clear need for further investigation of the role of ferritin in uncontrolled inflammatory conditions both as a biomarker and mediator of disease because its occurrence identifies patients with high mortality risk and its resolution predicts their improved survival.

http://ift.tt/2zbPnU0