Quantitative FLAIR MRI in Amyotrophic Lateral Sclerosis

Publication date: Available online 29 May 2017
Source:Academic Radiology
Author(s): Jeremy Fabes, Lucy Matthews, Nicola Filippini, Kevin Talbot, Mark Jenkinson, Martin R. Turner
Rationale and ObjectivesT2-weighted magnetic resonance imaging (MRI) hyperintensity assessed visually in the corticospinal tract (CST) lacks sensitivity for a diagnosis of amyotrophic lateral sclerosis (ALS). We sought to explore a quantitative approach to fluid-attenuated inversion recovery (FLAIR) MRI intensity across a range of ALS phenotypes.Materials and MethodsThirty-three classical ALS patients, 10 with a flail arm presentation, and six with primary lateral sclerosis underwent MRI at 3 Tesla. Comparisons of quantitative FLAIR intensity in the CST and corpus callosum were made between 21 healthy controls and within patient phenotypic subgroups, some of whom were studied longitudinally.ResultsMean FLAIR intensity was greater in patient groups. The cerebral peduncle intensity provided the strongest subgroup classification. FLAIR intensity increased longitudinally. The rate of change of FLAIR within CST correlated with rate of decline in executive function and ALS functional rating score.ConclusionsFLAIR MRI encodes quantifiable information of potential diagnostic, stratification, and monitoring value.



http://ift.tt/2rzzYdl

Zinc oxide nanoparticle energy band gap reduction triggers the oxidative stress resulting into autophagy-mediated apoptotic cell death

Publication date: September 2017
Source:Free Radical Biology and Medicine, Volume 110
Author(s): Manoranjan Arakha, Jyoti Roy, Parth Sarthi Nayak, Bibekanand Mallick, Suman Jha
The physico-chemical properties of nanoparticle (NP), such as particle size, surface defects, crystallinity and accessible surface, affect NP photocatalytic activity that in turn defines the NP cytotoxic propensity. Since zinc oxide nanoparticle (ZnONP) energy band gap falls in a range of a semiconductor, the particle possesses photocatalytic activity. Hence, the study correlates energy band gap with cytotoxic propensity of ZnONP. To this end, ZnONPs with varying energy band gap are fabricated by varying calcination temperature. Cytotoxic propensity of the fabricated ZnONPs against HT1080 cell indicates that the particle with least energy band gap shows highest cytotoxicity. The data also indicate that the cytotoxicity is triggered primarily through reactive oxygen species (ROS)-mediated pathway. Additionally, the comet assay and γH2AX activity assay reveal that decreasing energy band gap of the particle increases DNA damaging propensity. Furthermore, cell cycle analysis indicates that the cell treatment with decreasing energy band gap ZnONP results in significant increase in cell population fraction in subG1 phase. Whereas, acridine orange binding assay and increased expression level of LC3II indicate that the cell tries to recover the stress by scavenging damaged cellular biomolecules and ROS using autophagosomes. Nevertheless, cell with the non-recoverable damages led into apoptotic cell death, as confirmed by Annexin V apoptosis assay, DNA fragmentation assay and 4,6-Diamidino-2-phenylindole dihydrochloride (DAPI) staining.

Graphical abstract

http://ift.tt/2qu4vJs

Mesna (2-mercaptoethane sodium sulfonate) functions as a regulator of myeloperoxidase

Publication date: September 2017
Source:Free Radical Biology and Medicine, Volume 110
Author(s): Roohi Jeelani, Seyedehameneh Jahanbakhsh, Hamid-Reza Kohan-Ghadr, Mili Thakur, Sana Khan, Sarah R. Aldhaheri, Zhe Yang, Peter Andreana, Robert Morris, Husam M. Abu-Soud
Myeloperoxidase (MPO), an abundant protein in neutrophils, monocytes, and macrophages, is thought to play a critical role in the pathogenesis of various disorders ranging from cardiovascular diseases to cancer. We show that mesna (2-mercaptoethanesulfonic acid sodium salt), a detoxifying agent, which inhibits side effects of oxazaphosphorine chemotherapy, functions as a potent inhibitor of MPO; modulating its catalytic activity and function. Using rapid kinetic methods, we examined the interactions of mesna with MPO compounds I and II and ferric forms in the presence and absence of chloride (Cl^-), the preferred substrate of MPO. Our results suggest that low mesna concentrations dramatically influenced the build-up, duration, and decay of steady-state levels of Compound I and Compound II, which is the rate-limiting intermediate in the classic peroxidase cycle. Whereas, higher mesna concentrations facilitate the porphyrin-to-adjacent amino acid electron transfer allowing the formation of an unstable transient intermediate, Compound I*, that displays a characteristic spectrum similar to Compound I. In the absence of plasma level of chloride, mesna not only accelerated the formation and decay of Compound II but also reduced its stability in a dose depend manner. Mesna competes with Cl^-, inhibiting MPO's chlorinating activity with an IC50 of 5µM, and switches the reaction from a 2e^- to a 1e^- pathway allowing the enzyme to function only with catalase-like activity. A kinetic model which shows the dual regulation through which mesna interacts with MPO and regulates its downstream inflammatory pathways is presented further validating the repurposing of mesna as an anti-inflammatory drug.

Graphical abstract

http://ift.tt/2quxpsG

Battery Life: Counseling Patients about Their Wireless Streaming Hearing Aids

This webinar presents the results of research on the battery drain of wireless streaming hearing aids with features like ear-to-ear communication and feedback management engaged and in various listening situations including streaming Apps. This session will provide audiologists with an understanding of different battery chemistries including primary disposable cells and rechargeable batteries designed for hearing aids and conclude with counseling recommendations for patients fit with wireless streaming hearing aids.

http://ift.tt/2quuCQe

Haemobilia due to hepatic artery pseudoaneurysm

An 83-year-old woman with a history of hepaticoduodenostomy 20 years ago was admitted with upper gastrointestinal bleeding. Emergency upper gastrointestinal endoscopy revealed multiple blood clots over the stomach and first and second parts of the duodenum. The cannulation of the biliary tree with a flexible end-viewing endoscope exposed the presence of blood clot inside biliary lumen and a semipedunculated polyp which, at first, appeared to be the cause of haemorrhage. A few days after polypectomy, patient was discharged home, however, was admitted again with massive bleeding and selective angiography demonstrated a pseudoaneurysm of left hepatic artery. Angioembolisation was performed and haemorrhage was stopped afterwards.

http://ift.tt/2s8OIwB

Giant cell tumor in the sphenoid sinus and ethmoid sinus during childhood, and it is thought that optic atrophy was caused by compressive optic neuropathy.

http://orlhealth.blogspot.com/2017/05/giant-cell-tumor-in-sphenoid-sinus-and.html

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

Determination of the protein expression profiles of Propsilocerus akamusi (Tokunaga) Malpighian tubules response to cadmium stress by iTRAQ coupled LC–MS/MS

Publication date: Available online 29 May 2017
Source:Journal of Proteomics
Author(s): Xianyun Zheng, Zhiying Xie, Shu Wang, Pipeng Lin
Propsilocerus akamusi (Tokunaga) is an important prey species for fish and aquatic birds, which represent an important link in the aquatic food chain as other species of Chironomidae. Malpighian tubules (MT) play an important role in metabolism and detoxification of harmful compounds and metal accumulation. Our previous studies have reported that P. akamusi have an extraordinary resistance to Cd. In this paper, iTRAQ-based proteomics technology was first used to study the differential proteomics of MT of Propsilocerus akamusi under sublethal Cd stress for different time courses. 118 differential expressed proteins (DEPs) were identified through LC–MS/MS and further classified into 26 GO functional groups. Our results showed that metabolic process was the main biological functional categories. Cluster of orthologous groups of proteins (COG) analysis was also performed based on the number of unique proteins identified in each functional category, 22 metabolism-related DEPs were identified. P. akamusi adapted to Cd stress mainly by inducing the processes of lipid metabolism of MT and lipid may play a possible protection role in cadmium resistance in MT. The results provide important information for research on molecular mechanisms of Cd-stress adaption in Malpighian tubules of P. akamusi.Biological significancePropsilocerus akamusi (old species name: Tokunagayusurika akamusi) is an important prey species for fish and aquatic birds, which represent an important link in the aquatic food web as other species of Chironomidae. Malpighian tubules constitute a versatile organ which is able to exert excretory of chemical compounds, acting in the insect metabolism and detoxification of harmful compounds and metal accumulation. Our previous studies have reported that P. akamusi have an extraordinary resistance to Cd. However, up to now, there has been a lack of research on the molecular mechanisms of adaption to Cd stress in the Malpighian tubules of this species. Study on the adaptive mechanisms to Cd stress in Malpighian tubules of Propsilocerus akamusi through comparative proteome analysis is one important way to solve this problem. The aim of the present study was to understand the molecular mechanisms of adaption of the Malpighian tubules of P. akamusi exposed to Cd stress and assess the high expression of proteins involved in cellular adaptation to Cd stress. This will provide information about how this organ is responding to disturbances of contaminated ecosystems.

Graphical abstract

http://ift.tt/2qAJDLI

Proteomic fingerprinting of mistletoe (Viscum album L.) via combinatorial peptide ligand libraries and mass spectrometry analysis

Publication date: Available online 29 May 2017
Source:Journal of Proteomics
Author(s): María Vergara-Barberán, María Jesús Lerma-García, Maria Nicoletti, Ernesto Francisco Simó-Alfonso, José Manuel Herrero-Martínez, Elisa Fasoli, Pier Giorgio Righetti
Combinatorial peptide ligand libraries (CPLLs), coupled to mass spectrometry (MS) analysis, have been used to investigate in depth the proteome of Viscum album L. (VA), commonly named European mistletoe, in order to provide a first proteomic fingerprinting. For this purpose, the proteins were captured via CPLLs at two different pH values (acidic and neutral). A total of 648 non-redundant proteins were identified by using two different databases. The two pH values, chosen for bead incubations, have contributed to increment the capture ability: 56% and 31% of CPLLs species were respectively recognized at pH7.2 and at pH2.2. Finally the biological function of identified proteins was evaluated in order to understand their role on human health and the potential benefits of mistletoe extracts in medicine.SignificanceViscum album L. (VA) extracts are recently used as supporting medicine for cancer therapy, improving patients' survival and increasing their quality of life in medicine. These anticancer effects are investigated and they are probably due to mistletoe's capability to favor tumor cell's death and to modulate the immune system. Although the increasing interest in VA medical benefits, the role of its components in human health remains unclear. In order to exploit this aspect, it is important to comprehensively study proteins present in Viscum album L. (VA) extracts. Nevertheless, since plant proteomics analysis is in most cases handicapped by the presence of high-abundance proteins masking the detection of the low-abundance ones, it is important to overcome this challenge. In this sense, combinatorial peptide ligand libraries (CPLLs) have been used to reduce the dynamic protein concentration range to enable the identification of a higher amount of proteins than employing conventional methods. In this work, a total of 648 non-redundant proteins were identified: 56% and 31% of CPLLs species were respectively recognized at pH7.2 and at pH2.2. This deep proteome identification was useful to investigate the biological functions of proteins in order to evaluate their potential role in human health.

Graphical abstract

http://ift.tt/2qBkYXm

Quantitative assessment of wound healing using high-frequency ultrasound image analysis

Purpose

We aimed to develop a method for quantitative assessment of wound healing in ulcerated diabetic feet.

Methods

High-frequency ultrasound (HFU) images of 30 wounds were acquired in a controlled environment on post-debridement days 7, 14, 21, and 28. Meaningful features portraying changes in structure and intensity of echoes during healing were extracted from the images, their relevance and discriminatory power being verified by analysis of variance. Relative analysis of tissue healing was conducted by developing a features-based healing function, optimised using the pattern-search method. Its performance was investigated through leave-one-out cross-validation technique and reconfirmed using principal component analysis.

Results

The constructed healing function could depict tissue changes during healing with 87.8% accuracy. The first principal component derived from the extracted features demonstrated similar pattern to the constructed healing function, accounting for 86.3% of the data variance.

Conclusion

The developed wound analysis technique could be a viable tool in quantitative assessment of diabetic foot ulcers during healing.

http://ift.tt/2reSB38

Involvement of M2 macrophages in the pathomechanisms of multicentric reticulohistiocytosis

http://ift.tt/2rhWoyQ

Comments regarding “Four cases of mucous membrane pemphigoid with clinical features of oral lichen planus” and on the utility of immunofluorescence

http://ift.tt/2sg4Ziu

“Influence of possible predictor variables on the outcome of primary oral squamous cell carcinoma: a retrospective study of 392 consecutive cases at a single centre”— methodological issues

We read the paper by Loeffelbein and colleagues, published online in the International Journal of Oral and Maxillofacial Surgery in December 2016, with enthusiasm1. The authors aimed to examine tumour-specific and patient-related risk factors in a large single-centre cohort, i.e., factors that have a considerable effect on postoperative survival following ablative tumour surgery with elective neck dissection and immediate microvascular reconstruction in oral squamous cell carcinoma. It was concluded that postoperative survival does not depend only on tumour-related characteristics.

http://ift.tt/2s8G01s

Airborne gamma-ray spectrometry data processing using 1.5D inversion

Publication date: October 2017
Source:Journal of Environmental Radioactivity, Volume 177
Author(s): Eugene Druker
Standard processing of Airborne Gamma-Ray Spectrometry data generally gives good results when the measurement conditions are almost constant within several footprint area sizes, with the possible exception of flight height variations in a small range. In practice, deviations, such as large or abrupt changes of flight height and/or rugged terrain are not so rare and lead to certain problems. This article proposes a different approach where the solutions of inverse problems are used for data processing. The approach is quite natural in the processing of field data measured along the flight lines: it explicitly takes into account 1.5D survey models and flight parameters – from topography to sources distribution on the surface. Also, it clearly demonstrates that the inverse problem of the Airborne Gamma-Ray Spectrometry does not have a unique solution. This feature can be used in accordance with the underlying geological problem since various formulations of inverse problems can lead to various geological solutions. The use of the approach is illustrated by several examples given for flight lines and survey areas. This approach can be particularly useful in situations where geological, geophysical and/or geographic survey conditions are far from the standard assumptions.



http://ift.tt/2rhHeJU

Autoimmunity in 2016

Abstract

The number of peer-reviewed articles published during the 2016 solar year and retrieved using the "autoimmunity" key word remained stable while gaining a minimal edge among the immunology articles. Nonetheless, the quality of the publications has been rising significantly and, importantly, acquisitions have become available through scientific journals dedicated to immunology or autoimmunity. Major discoveries have been made in the fields of systemic lupus erythematosus, rheumatoid arthritis, autoimmunity of the central nervous system, vasculitis, and seronegative spondyloarthrithritides. Selected examples include the role of IL17-related genes and long noncoding RNAs in systemic lupus erythematosus or the effects of anti-pentraxin 3 (PTX3) in the treatment of this paradigmatic autoimmune condition. In the case of rheumatoid arthritis, there have been reports of the role of induced regulatory T cells (iTregs) or fibrocytes and T cell interactions with exciting implications. The large number of studies dealing with neuroimmunology pointed to Th17 cells, CD56(bright) NK cells, and low-level TLR2 ligands as involved in multiple sclerosis, along with a high salt intake or the micriobiome-derived Lipid 654. Lastly, we focused on the rare vasculitides to which numerous studies were devoted and suggested that unsuspected cell populations, including monocytes, mucosal-associated invariant T cells, and innate lymphoid cells, may be crucial to ANCA-associated manifestations. This brief and arbitrary discussion of the findings published in 2016 is representative of a promising background for developments that will enormously impact the work of laboratory scientists and physicians at an exponential rate.

http://ift.tt/2sfYAUK

TGFβ pathway deregulation and abnormal phospho-SMAD2/3 staining in hereditary cerebral hemorrhage with amyloidosis-Dutch type

Abstract

Hereditary cerebral hemorrhage with amyloidosis-Dutch type (HCHWA-D) is an early onset hereditary form of cerebral amyloid angiopathy (CAA) pathology, caused by the E22Q mutation in the amyloid β (Aβ) peptide. Transforming Growth Factor β1 (TGFβ1) is a key player in vascular fibrosis and in the formation of angiopathic vessels in transgenic mice. Therefore we investigated whether the TGFβ pathway is involved in HCHWA-D pathogenesis in human postmortem brain tissue from frontal and occipital lobes. Components of the TGFβ pathway were analyzed with quantitative RT-PCR. TGFβ1 and TGFβ Receptor 2 (TGFBR2) gene expression levels were significantly increased in HCHWA-D in comparison to the controls, in both frontal and occipital lobes. TGFβ-induced pro-fibrotic target genes were also upregulated. We further assessed pathway activation by detecting phospho-SMAD2/3 (pSMAD2/3), a direct TGFβ down-stream signaling mediator, using immunohistochemistry. We found abnormal pSMAD2/3 granular deposits specifically on HCHWA-D angiopathic frontal and occipital vessels. We graded pSMAD2/3 accumulation in angiopathic vessels and found a positive correlation with the CAA load independent of the brain area. We also observed pSMAD2/3 granules in a halo surrounding occipital vessels, which was specific for HCHWA-D. The result of this study indicates an upregulation of TGFβ1 in HCHWA-D, as was found previously in AD with CAA pathology. We discuss the possible origins and implications of the TGFβ pathway deregulation in the microvasculature in HCHWA-D. These findings identify the TGFβ pathway as a potential biomarker of disease progression and a possible target of therapeutic intervention in HCHWA-D. This article is protected by copyright. All rights reserved.

http://ift.tt/2sfDmGj

Rapid amyloid-β oligomer and protofibril accumulation in traumatic brain injury

ABSTRACT

Objective: Deposition of amyloid-β (Aβ) is central to Alzheimer's disease (AD) pathogenesis and associated with progressive neurodegeneration in traumatic brain injury (TBI). We analysed predisposing factors for Aβ deposition including monomeric Aβ40, Aβ42 and Aβ oligomers/protofibrils, Aβ species with pronounced neurotoxic properties, following human TBI.

Methods: Highly selective ELISAs were used to analyse N-terminally intact and truncated Aβ40 and Aβ42, as well as Aβ oligomers/protofibrils, in human brain tissue, surgically resected from severe TBI patients (n=12; mean age 49.5 ± 19 years) due to life-threatening brain swelling/haemorrhage within one week post-injury. The TBI tissues were compared to post-mortem AD brains (n=5), to post-mortem tissue of neurologically intact subjects (n=4) and to cortical biopsies obtained at surgery for idiopathic normal pressure hydrocephalus patients (iNPH; n=4).

Results: The levels of Aβ40 and Aβ42 were not elevated by TBI. The levels of Aβ oligomers/protofibrils in TBI were similar to those in the significantly older AD patients and increased compared to neurologically intact and iNPH controls (P<0.05). Moreover, TBI patients carrying the AD risk genotype Apolipoprotein E epsilon3/4 (APOE ε3/4; n=4) had increased levels of Aβ oligomers/protofibrils (P<0.05) and of both N-terminally intact and truncated Aβ42 (P<0.05) compared to APOE ε3/4-negative TBI patients (n=8). Neuropathological analysis showed insoluble Aβ aggregates (commonly referred to as Aβ plaques) in three TBI patients, all of whom were APOE ε3/4 carriers.

Interpretation: Soluble intermediary Aβ aggregates form rapidly after TBI, especially among APOE ε3/4 carriers. Further research is needed to determine whether these aggregates aggravate the clinical short- and long-term outcome in TBI. This article is protected by copyright. All rights reserved.

http://ift.tt/2rhuH9h

Detection of gastric atrophy by circulating pepsinogens: A comparison of three assays

Abstract

Background

Circulating levels of pepsinogens have been used in high gastric cancer-risk Asian and European populations to triage endoscopic evaluation for more severe pathology. There are different analytic methods with uncertain correlations. We therefore compared diagnostic performance of three commonly used pepsinogen assays to detect histologically confirmed gastric atrophy.

Methods

We tested plasma samples from adult patients with (n=50) and without (n=755) moderate or severe gastric corpus atrophy, as determined histologically by consensus of three expert pathologists. A single laboratory measured pepsinogens I (PgI) and II (PgII) using commercially available assays: two ELISA assays produced by Biohit (Finland) and Vector Best (Russia), and a latex agglutination assay from Eiken (Japan). Quantitative correlations were assessed by Spearman statistics. Receiver operating characteristic (ROC) curves vs histological diagnosis were calculated using both the manufacturers' and optimized cutoffs.

Results

Pepsinogen levels were highly correlated among the assays (pairwise Rhos: PgI≥0.84, PgII≥0.87; all P-values<.01). Based on manufacturers' cutoffs, sensitivities, specificities and areas under the ROC curve for detecting moderate to severe histological corpus atrophy by PgI/PgII were 44%/91%/0.70, 56%/84%/0.76, and 52%/90%/0.77 for Biohit, Vector Best and Eiken, respectively. Cutoffs optimized by ROC or data mining analyses did not substantially improve test performance.

Conclusions

Commercial assays for pepsinogen have good relative agreement but are imperfect tests for clinical diagnosis of gastric atrophy.

Impact

Pepsinogen testing alone does not provide sufficient information for gastric cancer risk stratification. Future investigations should focus on other potential markers, in combination with pepsinogens.

http://ift.tt/2rhxjEd

Diseases of the retina and the optic nerve associated with obstructive sleep apnea

Many associations between ocular disorders and obstructive sleep apnea (OSA) have been studied, such as nonarteritic anterior ischemic optic neuropathy (NAION), glaucoma, papilledema, retinal vein occlusion, eyelid hyperlaxity, lower-eyelid ectropion and recurrent corneal erosions. The objective of this review is to synthetize the possible vascular disorders of the retina and the optic nerve associated with sleep apnea patients and to discuss the underlying pathophysiological hypotheses. Main mechanisms involved in the ocular complications of OSA are related to intermittent hypoxia, sympathetic system activation, oxidant stress, and deleterious effects of endothelin 1 (ET-1).

http://ift.tt/2s8C1lI

Effect of PICALM rs3851179 polymorphism on the default mode network function in mild cognitive impairment

Publication date: 28 July 2017
Source:Behavioural Brain Research, Volume 331
Author(s): Ding-Ming Sun, Hai-Feng Chen, Qi-Long Zuo, Fan Su, Feng Bai, Chun-Feng Liu
Alterations in default mode network (DMN) functional connectivity (FC) might accompany the dysfunction of Alzheimer's disease (AD). Indeed, episodic memory impairment is a hallmark of AD, and mild cognitive impairment (MCI) has been associated with a high risk for AD. Phosphatidylinositol-binding clathrin assembly protein (PICALM) (rs3851179) has been associated with AD; in particular, the A allele may serve a protective role, while the G allele serves as a strong genetic risk factor. Therefore, the identification of genetic polymorphisms associated with the DMN is required in MCI subjects. In all, 32 MCI subjects and 32 healthy controls (HCs) underwent resting-state functional magnetic resonance imaging (rs-fMRI) and a genetic imaging approach. Subjects were divided into four groups according to the diagnosis (i.e., MCI and HCs) and the PICALM rs3851179 polymorphism (i.e., AA/AG genotype and GG genotype). The differences in FC within the DMN between the four subgroups were explored. Furthermore, we examined the relationship between our neuroimaging measures and cognitive performance. The regions associated with the genotype-by-disease interaction were in the left middle temporal gyrus (LMTG) and left middle frontal gyrus (LMFG). These changes in LMFG FC were generally manifested as an "inverse U-shaped curve", while a "U-shaped curve" was associated with the LMTG FC between these four subgroups (all P<0.05). Furthermore, higher FC within the LMFG was related to better episodic memory performance (i.e., AVLT 20min DR, rho=0.72, P=0.044) for the MCI subgroups with the GG genotype. The PICALM rs3851179 polymorphism significantly affects the DMN network in MCI. The LMFG and LMTG may be associated with opposite patterns. However, the altered LMFG FC in MCI patients with the GG genotype was more sensitive to episodic memory impairment, which is more likely to lead to a high risk of AD.



http://ift.tt/2relEnj

Role of cholinergic receptors in memory retrieval depends on gender and age of memory

Publication date: 28 July 2017
Source:Behavioural Brain Research, Volume 331
Author(s): Habiba Rashid, Aamra Mahboob, Touqeer Ahmed
The phenomenon of utilizing information acquired in the past to make decision and performance in present depends on memory retrieval, which is affected in retrograde amnesia. Role of cholinergic receptors in memory retrieval is not much explored. In this study we evaluated the gender specific role of cholinergic receptors, i.e. muscarinic and nicotinic receptors, in memory retrieval in young Balb/c mice. Acute (only one injection, 30min before test) and sub-chronic (five days) muscarinic blockade (using scopolamine=1mg/kg) before test impaired retrieval of contextual fear memory in male (31.45±5.39% and 33.36±3.78% respectively) and female mice (22.88±5.73%; P<0.05), except sub-chronically treated female group (33.31±4.90%; P>0.05). Only sub-chronic nicotinic receptor antagonism (using methyllycaconitine MLA=87.5μg/kg and dihydro β erythroidine DHβE=1mg/kg) in female showed significantly higher freezing response than control during contextual fear memory retrieval (60.85±7.71% and 40.91±7.53% respectively; P<0.001). Acute and sub-chronic muscarinic antagonism (but not nicotinic antagonism) impaired spatial memory retrieval in male (P<0.05) but not in female mice (P>0.05). There was no effect of acute and sub-chronic cholinergic receptor antagonism on discriminating novel object from the familiar one in male and female mice, however, nicotinic receptor blockade affected the working memory of all male and female mice on test day compared to the training sessions. Our results suggested that cholinergic receptors involvement in retrieving spatial and fear memories depends on the age of the memory and gender.



http://ift.tt/2qtz81y

Water and T-maze protocols are equally efficient methods to assess spatial memory in 3xTg Alzheimer’s disease mice

Publication date: 28 July 2017
Source:Behavioural Brain Research, Volume 331
Author(s): K.E. Davis, K. Burnett, J. Gigg
Rodent spatial memory is commonly tested using the water-maze; however, there is a potential confound of stress on learning in this behavioural paradigm. This is particularly relevant when testing spatial memory in models of neurodegeneration, such as the 3xTg mouse model for Alzheimer's disease. Here, we first confirmed that 3xTgAD mice express fear conditioning and then compared the performance of young and middle-aged mice on short-duration versions of the radial arm water-maze (RAWM) and the minimally stressful T-maze spontaneous alternation task. Our main questions were: (1) does the reliance on stressors in water-maze training mask the true cognitive ability of 3xTgAD mice; and (2) are 3xTgAD mice similarly impaired in water-maze and T-maze protocols. Firstly, male and female 3xTgAD mice displayed intact freezing responses in both contextual and Pavlovian fear conditions. As male 3xTgAD mice displayed relatively enhanced fear responses the remaining tests were performed using only female 3xTgAD and control mice in order to equate for response to stressors. We found that alternation rates after both short and long delays were impaired at both ages in female 3xTgAD mice, indicative of robust spatial working memory deficits. For RAWM, again performance deficits were found in young 3xTgAD mice. As both tasks had similar efficacy at revealing early spatial memory deficits, we suggest that spontaneous behavioural protocols be prioritised over water maze testing in models such the 3xTgAD mouse as the former provide a far less stressful but equally effective alternative.



http://ift.tt/2relQTD

Enriched environment alters the behavioral profile of tenascin-C deficient mice

Publication date: 28 July 2017
Source:Behavioural Brain Research, Volume 331
Author(s): V. Stamenkovic, I. Milenkovic, N. Galjak, V. Todorovic, P. Andjus
Tenascin-C (TnC) is an extracellular matrix glycoprotein implicated in a variety of processes ranging from brain development to synaptic plasticity in the adult vertebrates. Although the role of the TnC gene in regulation of behavior has been investigated, it remained elusive how TnC deficiency interacts with the environment in shaping the behavioral phenotype. To address this, 3-week-old TnC+/+ and TnC-/- male mice were housed over an 8-week period in standard conditions (SC), or enriched environment (EE). A comprehensive battery of tests was used in behavioral phenotyping. When housed in SC, TnC−/− mice showed spontaneous nocturnal hyperactivity, as well as poor sensorimotor coordination and low swimming velocity. However, housing of TnC−/− mice in EE abolished hyperlocomotion, led to faster habituation to novel environment, strengthened the grasp of fore limbs and partially improved movement coordination, while the swimming ability remained deficient. Conversely, TnC deficiency attenuated both the beneficial effects of EE on learning/memory capacity and the anxiolytic effect of EE in reducing the level of acrophobia. This study expands the existing knowledge about the phenotype associated with TnC deficiency, and reveals that the effect of genetic background on the behavioral response could be altered by post-weaning housing in a highly stimulating environment.



http://ift.tt/2qtutga

Detection of gastric atrophy by circulating pepsinogens: A comparison of three assays

Abstract

Background

Circulating levels of pepsinogens have been used in high gastric cancer-risk Asian and European populations to triage endoscopic evaluation for more severe pathology. There are different analytic methods with uncertain correlations. We therefore compared diagnostic performance of three commonly used pepsinogen assays to detect histologically confirmed gastric atrophy.

Methods

We tested plasma samples from adult patients with (n=50) and without (n=755) moderate or severe gastric corpus atrophy, as determined histologically by consensus of three expert pathologists. A single laboratory measured pepsinogens I (PgI) and II (PgII) using commercially available assays: two ELISA assays produced by Biohit (Finland) and Vector Best (Russia), and a latex agglutination assay from Eiken (Japan). Quantitative correlations were assessed by Spearman statistics. Receiver operating characteristic (ROC) curves vs histological diagnosis were calculated using both the manufacturers' and optimized cutoffs.

Results

Pepsinogen levels were highly correlated among the assays (pairwise Rhos: PgI≥0.84, PgII≥0.87; all P-values<.01). Based on manufacturers' cutoffs, sensitivities, specificities and areas under the ROC curve for detecting moderate to severe histological corpus atrophy by PgI/PgII were 44%/91%/0.70, 56%/84%/0.76, and 52%/90%/0.77 for Biohit, Vector Best and Eiken, respectively. Cutoffs optimized by ROC or data mining analyses did not substantially improve test performance.

Conclusions

Commercial assays for pepsinogen have good relative agreement but are imperfect tests for clinical diagnosis of gastric atrophy.

Impact

Pepsinogen testing alone does not provide sufficient information for gastric cancer risk stratification. Future investigations should focus on other potential markers, in combination with pepsinogens.

http://ift.tt/2rhxjEd

A novel mutation in the MYO7A gene is associated with Usher syndrome type 1 in a Chinese family

We aimed to investigate the genetic causes of hearing loss in a Chinese proband with autosomal recessive congenital deafness.

http://ift.tt/2qAuCtl

Acute pediatric neck infections: Outcomes in a seven-year series

The aim of this study was to analyse the epidemiology, clinical presentation, diagnostic clues, as biochemical parameters and imaging studies, of children with acute neck infections (ANI) to identify possible independent prognostic factors leading to complications and prolonged hospitalization. Methods: Records of children admitted to a tertiary university hospital from January 2008 to December 2014 with a diagnosis of ANIs were reviewed retrospectively. Diseases were categorized according to the site of infection and patients were divided into two groups: children (aged<10 years) and adolescents (aged 10–18 years).

http://ift.tt/2r5ZHbJ

Assessment of the feeding Swallowing Impact Survey as a quality of life measure in children with laryngeal cleft before and after repair

To cross-validate the Feeding Swallowing Impact Survey (FSIS), a quality of life instrument, specifically to a subpopulation of children who aspirate due to laryngeal cleft.

http://ift.tt/2qAvrlY

Evaluation of speech in noise abilities in school children

Communicative situations in our daily lives often occur in noise environments, competing with speech, especially in the school environment, inside and outside the classroom. The perception of speech in noise is one of the most complex tasks faced by listeners, being influenced by hearing thresholds and also the analysis of the temporal characteristics such as pitch, time and timbre of speech sounds1. Children are particularly vulnerable to the effects of noise in speech perception, yet little is known about the relationship mechanism between core processes and the perception of speech in noise2.

http://ift.tt/2r5A0bi

Validation of the Lithuanian Version of the Speech Handicap Index

The objective is to study the cultural adaptation and validation of the Speech Handicap Index (SHI) questionnaire to the Lithuanian language.

http://ift.tt/2r5DP0g

Recovery From Heavy Vocal Loading in Women With Different Degrees of Functional Voice Problems

This is a longitudinal, case-control clinical trial.

http://ift.tt/2qAMiVG

The Exploration of an Objective Model for Roughness With Several Acoustic Markers

In voice assessment, the evaluation of voice quality is a major component in which roughness has received wide acceptance as a major subtype of abnormal voice quality. The aim of the present study was to develop a new multivariate acoustic model for the evaluation of roughness.

http://ift.tt/2r5JgMB

Upper-airway flow limitation and transcutaneous carbon dioxide during sleep in normal pregnancy

Sleep during pregnancy involves a physiological challenge to provide sufficient gas exchange to the fetus. Enhanced ventilatory responses to hypercapnia and hypoxia may protect from deficient gas exchange, but sleep-disordered breathing (SDB) may predispose to adverse events. The aim of this study was to analyze sleep and breathing in healthy pregnant women compared to non-pregnant controls, with a focus on CO2 changes and upper-airway flow limitation.

http://ift.tt/2qtHjL4

Efficacy and safety of almorexant in adult chronic insomnia: a randomized placebo-controlled trial with an active reference

The orally active dual OX1R and OX2R antagonist, almorexant, targets the orexin system for the treatment of primary insomnia. This clinical trial assessed the effect of almorexant on sleep maintenance and other sleep endpoints, and its safety and tolerability in adults.

http://ift.tt/2rehQm6

Gray matter abnormalities of the dorsal posterior cingulate in sleep walking

This study aimed to determine whether voxel-based analysis of T1 weighted magnetic resonance imaging (MRI) and diffusion tensor imaging is able to detect alterations of gray and white matter morphometry as well as measures of mean diffusivity and fractional anisotropy in patients with non-rapid eye movement parasomnia.

http://ift.tt/2qtTeIU

Postnatal treatment of women with narcolepsy who choose to breastfeed-time for a reappraisal?

Primum non-nocere, (first, do no harm) a loose translation of a line from the Hippocratic oath that most physicians take upon graduating from medical school, should be a guiding principle of medical practice. [1] In obstetrics and pediatrics, this philosophy was fashionable in terms of advising postpartum women concerning nursing who were on long-term medications. Generally, this was not to mix pharmaceutical agents with breastfeeding. This was a no win dilemma (ie, a Sophie's Choice) for many women who were being treated for chronic illnesses; choosing between taking their medications and forgoing nursing, and therefore, depriving their baby of the benefits of breast milk (or to nurse and stop their medications, and run the risk of exacerbating their underlying condition).

http://ift.tt/2re9paD

Sex and age differences in the associations between sleep behaviors and all-cause mortality in older adults: results from the National Health and Nutrition Examination Surveys

Our aim was to examine sex- and age-specific relationships of sleep behaviors with all-cause mortality rates.

http://ift.tt/2qtHRk4

The relationship between weight change and daytime sleepiness: the Sleep Heart Health Study

Through a causal framework, we aim to assess the association between weight change and daytime sleepiness, and the role of obstructive sleep apnoea (OSA) in this relationship.

http://ift.tt/2relcpg

Gillies temporal incision: an alternate approach to superficial temporal artery biopsy

The main complications of a biopsy of the superficial temporal artery using a standard preauricular approach include scars on the face, weakness of the temporal branch of the facial nerve, and the possible harvest of a disease-free segment of artery. We describe a modification of the Gillies temporal approach, which when placed at the junction of the frontal and parietal branch can be easily modified to harvest either branch. It avoids scarring to the face as it is hidden within the hairline. The incision placed with specific measurements and palpation is easily reproducible.

http://ift.tt/2ryZNdq

Re: Wrong tooth extraction: an examination of ‘Never Event’ data

I read with interest the recent study by Pemberton et al concerning wrong tooth extractions.1 In many ways it is surprising that extraction of a wrong tooth is the most common wrong site event, given that many of these procedures are done under local anaesthesia and the patient often knows which tooth or teeth are to be removed. Although the authors were not able to comment on the causes, as with many cases of human error, they are likely to be multifactorial. Ineffective communication is widely regarded as one of the highest causes of error.

http://ift.tt/2s8fa9O

Local effects of epidermal growth factor on the wound healing in esophageal anastomosis: An experimental study

Publication date: August 2017
Source:International Journal of Pediatric Otorhinolaryngology, Volume 99
Author(s): Ayşe Bülbül Adam, Mustafa Yaşar Özdamar, Hacı Hasan Esen, Engin Günel
ObjectiveIn this study with the experimental model of primary repair of esophageal atresia(EA), we investigated the effects of the epidermal growth factor(EGF) on wound healing in the anastomosis of EA.Materials and methodsForty rabbits that were performed a resection of a 1-cm segment of the cervical esophagus followed by the end-to-end anastomosis were divided into four groups. Group I (7-day group) and III (21-day group), the control groups, had no EGF applied to the anastomosis. In group II (7-day group) and group III (21-day group), all around the anastomoses were locally covered with 100 μg/kg EGF. Group 1, 2 and 3, 4 were sacrificed on the 7th and 21st day, respectively. We investigated and compared with bursting pressure, vascularization around the anastomotic line by histopathology, inflammation, and fibroblast granulation as well as hydroxyproline level by biochemical.ResultsNo significant difference was found at vascularization and inflammation between all of the groups (p > 0.05). Considering the critical parameters of the groups, at bursting pressure difference was found between group 1 and 2 as well as 3 and (p < 0.05). At fibroblast granulation and hydroxyproline level, no difference was found between group 1 and 2 (p > 0.05) but the difference between group 3 and 4 (p < 0.05).ConclusionEGF might be useful in preventing anastomotic leakage of esophageal atresia in primary anastomosis of esophageal atresia by accelerating wound healing process and increasing the stability of the anastomotic line.



http://ift.tt/2sfeyP1

An evaluation of oxidative and nitrosative stress in children-who-stutter and its relationship to severity

Publication date: August 2017
Source:International Journal of Pediatric Otorhinolaryngology, Volume 99
Author(s): Nagihan Bilal, Selman Sarica, Ergül Belge Kurutas, Ebru Findikli, İsrafil Orhan, Erkan Oner, Adem Doganer, Saime Sagiroglu, Mehmet Akif Kilic
ObjectivesAlthough there has been much research into the cause of stuttering, it has not yet been fully clarified. There is known to be a close relationship between stress severity and stuttering. The aim of this study was to evaluate the levels of oxidative and nitrosative stress by comparing a stuttering group and a control group. It was also aimed to evaluate the relationship between the oxidative and nitrosative stress levels and the severity of the stutter.MethodsThe study included a total of 80 individuals, comprising a study group of 40 and a control group of 40. The severity of the stutter in the patient group was evaluated with the Stuttering Severity Instrument 3 (SSI). Blood samples were taken from both the patient and control groups and malondialdehyde (MDA), 3 nitrotyrosine (3-NT), nitric oxide (NO), catalase (CAT), and superoxide dismutase (SOD) concentrations were examined.ResultsIn the stuttering patients, MDA, 3-NT, NO, CAT, and SOD activity were determined to be statistically significantly higher than those of the control group (all p:0.001). In the ROC analysis, there was good diagnostic value for NO, with the area under the curve as 1.0. A direct, positive, statistically significant correlation was determined between SSI points and MDA values (r = 0.317, p = 0.046).ConclusionThe results of the study showed that the oxidative and nitrosative stress levels of the stuttering patients were higher than those of the control group. With 100% sensitivity and specificity, it is thought that NO in particular could be important for the diagnosis and treatment of these patients. As the severity of the stutter increased, so there was an increase in MDA, suggesting that MDA is important in stuttering.



http://ift.tt/2rhoZEd

Airway stenting in a child with spondyloepiphyseal dysplasia congenita: 13-Year survival

Publication date: August 2017
Source:International Journal of Pediatric Otorhinolaryngology, Volume 99
Author(s): Raffaella Nenna, Fabio Midulla, Laura Masi, Giacomo Maria Bacci, Antonella Frassanito, Roberto Baggi, Maria Luisa Brandi, Stefano Avenali, Lorenzo Mirabile, Paola Serio
We describe the case of a boy with spondyloepiphyseal dysplasia congenita. At birth, he experienced severe respiratory distress necessitating tracheotomy. Endoscopy done because mechanical ventilation failed to resolve desaturations disclosed severe tracheo-bronchomalacia. A Polyflex silicone stent was placed in the trachea (replaced by Y-Dumon stent) and 2 Palmaz metallic stents in the mainstem bronchi (overlapped with 2 Jomed stents 5 years later). Airway stenting guaranteed a suitable respiratory status and allowed a child who was expected to die at birth, to reach 13.5 years old in good conditions.



http://ift.tt/2sf7yS0

Novel highly porous magnetic hydrogel beads composed of chitosan and sodium citrate: an effective adsorbent for the removal of heavy metals from aqueous solutions

Abstract

This research focuses on the removal of heavy metal ions from aqueous solutions using magnetic chitosan hydrogel beads as a potential sorbent. Highly porous magnetic chitosan hydrogel (PMCH) beads were prepared by a combination of in situ co-precipitation and sodium citrate cross-linking. Fourier transform infrared spectroscopy indicated that the high sorption efficiency of metal cations is attributable to the hydroxyl, amino, and carboxyl groups in PMCH beads. Thermogravimetric analysis demonstrated that introducing Fe₃O₄ nanoparticles increases the thermal stability of the adsorbent. Laser confocal microscopy revealed highly uniform porous structure of the resultant PMCH beads, which contained a high moisture content (93%). Transmission electron microscopy micrographs showed that the Fe₃O₄ nanoparticles, with a mean diameter of 5 ± 2 nm, were well dispersed inside the chitosan beads. Batch adsorption experiments and adsorption kinetic analysis revealed that the adsorption process obeys a pseudo-second-order model. Isotherm data were satisfactorily described by the Langmuir equation, and the maximum adsorption capacity of the adsorbent was 84.02 mg/g. Energy-dispersive X-ray spectroscopy and X-ray photoelectron spectra analyses were performed to confirm the adsorption of Pb²⁺ and to identify the adsorption mechanism.

http://ift.tt/2rh9210

Human health impact assessment of exposure to particulate matter: an AirQ software modeling

Abstract

The aim of this study was to assess the health impacts related to particulate matter less than 10 μm (PM₁₀) exposure in the city of Yazd, Iran. For this aim, AirQ 2.2.3 software was used to model relationship between short-term exposure to PM₁₀ and disease cases proposed by the World Health Organization (WHO). The annual mean concentration of PM₁₀ was 97 μg/m³. The maximum concentration value of PM₁₀ was measured during the summer (731 μg/m³). 4.988% (95%CI: 3.381–6.542%) of the total mortality, 7.3% (95%CI; 4.19–10.21%) of cardiovascular mortality, and 10.21% (95%CI; 4.19–14.89%) of respiratory mortality were related to the PM₁₀ concentrations. Consequently, the AirQ software can provide valuable information about the importance of air pollution and the substantial impacts of PM₁₀ on the society for policymakers.

http://ift.tt/2sfsB72

Heavy metals in soils from a typical industrial area in Sichuan, China: spatial distribution, source identification, and ecological risk assessment

Abstract

Anthropogenic activities could result in increasing concentrations of heavy metals in soil and deteriorating in soil environmental quality. Topsoil samples from a typical industrial area, Shiting River Valley, Sichuan, Southwest China, were collected and determined for the concentrations of Cu, Zn, Cr, Cd, As, and Hg. The mean concentrations of these metals were lower than the national threshold values, but were slightly higher than their corresponding background values, indicating enrichment of these metals in soils in the valley, especially for Cu, Zn, and Hg. The topsoils in this area demonstrated moderate pollution and low potential ecological risk. Principal component analysis coupled with cluster analysis was applied to analyze the data and identified possible sources of these heavy metals; the results showed that soil Cd, Hg, As, Cu, and Zn were predominantly controlled by human activities, whereas Cr was mainly from the parent material. The spatial distribution of the heavy metals varied distinctly and was closely correlated to local anthropogenic activities. Furthermore, the concentrations of heavy metals in the industrial land demonstrated relatively higher levels than those of other land use patterns. Soil metal concentrations decreased with the distance increase from the traffic highway (0–1.0 km) and water system (0–2.0 km). Additionally, soil properties, especially pH and soil organic matter, were found to be important factors in the distribution and composition of metals.

http://ift.tt/2rhirW7

Sorption of thiabendazole in sub-tropical Brazilian soils

Abstract

Thiabendazole (TBZ) is an ionizable anthelmintic agent that belongs to the class of benzimidazoles. It is widely used in veterinary medicine and as a fungicide in agriculture. Sorption and desorption are important processes influencing transport, transformation, and bioavailability of xenobiotic compounds in soils; data related to sorption capacity are therefore needed for environmental risk assessments. The aim of this work was to assess the sorption potential of TBZ in four Brazilians soils (sandy, sandy-clay, and clay soils), using batch equilibrium experiments at three pH ranges (2.3–3.0, 3.8–4.2, and 5.5–5.7). The Freundlich sorption coefficient (K _F) ranged from 9.0 to 58 μg^1–1/n  (mL)^1/n  g⁻¹, with higher values generally observed at the lower pH ranges (2.3–3.0 and 3.8–4.2) and for clay soils. The highest organic carbon-normalized sorption coefficients (K_OC) obtained at pH 3.8–5.7 (around the natural pH range of 4.1–5.0) for both clay soils and sandy-clay soil were 3255 and 2015 mL g⁻¹, respectively. The highest correlations K _F vs SOM (r = 0.70) and K _F vs clay content (r = 0.91) were observed at pH 3.8–4.2. Our results suggest that TBZ sorption/desorption is strongly pH dependent and that its mobility could be higher in the studied soils than previously reported in soils from temperate regions.

http://ift.tt/2sfeajt

Assessing demineralization treatments for PVC effluent reuse in the resin polymerization step

Abstract

To reduce fresh water consumption in a polyvinyl chloride (PVC) plant, the effluent from a biological treatment must be demineralized to be re-used in the resin polymerization process. Demineralization is a critical process, since the quality and the stability of the PVC resins are highly influenced by the water quality used in the process. The main target values for water parameters are the following: conductivity <10 μScm⁻¹, TOC < 10 mg L⁻¹, and Al < 0.1 mg L⁻¹. To achieve this quality, several reverse osmosis membranes from different materials and suppliers were tested and compared in the demineralization treatment. Polyamide membranes showed higher salt rejection compared to cellulose acetate membranes yielding both types similar flux and permeability. Two-pass reverse osmosis treatment was necessary to reach conductivities lower than 10 μS cm⁻¹. On the other hand, a good quality effluent for reuse was obtained by combining RO and ionic exchange resins. Results showed that good quality PVC resins in terms of color, granulometry, porosity, and bulk density were obtained when demineralized water from two-pass reverse osmosis was used as fresh water, proving the feasibility of the effluent reuse in the PVC industry.

http://ift.tt/2rh73K9

The use of wastewater in livestock production and its socioeconomic and welfare implications

Abstract

Although epidemiological studies have found a significant amount of toxins in surface water, a complex link between animals' access to wastewater and associated animal and human welfare losses needs to be explored. The scarcity of safe water has put stress on the utilization of wastewater for crops and livestock production. The access of animals to wastewater is related to the emergence of dangerous animal's diseases, hampering productivity, increasing economic losses, and risking human health along the food chain. This review explores use of wastewater for agriculture, epidemiological evidence of microbial contamination in wastewater, and animal and human welfare disruption due to the use of wastewater for crop and livestock production. More specifically, the review delves into animals exposure to wastewater for bathing, drinking, or grazing on a pasture irrigated with contaminated water and related animal and human welfare losses. We included some scientific articles and reviews published from 1970 to 2017 to support our rational discussions. The selected articles dealt exclusively with animals direct access to wastewater via bathing and indirect access via grazing on pasture irrigated with contaminated wastewater and their implication for animal and human welfare losses. The study also identified that some policy options such as wastewater treatments, constructing wastewater stabilization ponds, controlling animal access to wastewater, and dissemination of necessary information to ultimate consumers related to the source of agricultural produce and wastewater use in animal and crop production are required to protect the human and animal health and welfare.

http://ift.tt/2sfta0N

Groundwater quality assessment and pollution source apportionment in an intensely exploited region of northern China

Abstract

Deterioration in groundwater quality has attracted wide social interest in China. In this study, groundwater quality was monitored during December 2014 at 115 sites in the Hutuo River alluvial-pluvial fan region of northern China. Results showed that 21.7% of NO₃⁻ and 51.3% of total hardness samples exceeded grade III of the national quality standards for Chinese groundwater. In addition, results of gray relationship analysis (GRA) show that 64.3, 10.4, 21.7, and 3.6% of samples were within the I, II, IV, and V grades of groundwater in the Hutuo River region, respectively. The poor water quality in the study region is due to intense anthropogenic activities as well as aquifer vulnerability to contamination. Results of principal component analysis (PCA) revealed three major factors: (1) domestic wastewater and agricultural runoff pollution (anthropogenic activities), (2) water-rock interactions (natural processes), and (3) industrial wastewater pollution (anthropogenic activities). Using PCA and absolute principal component scores-multivariate linear regression (APCS-MLR), results show that domestic wastewater and agricultural runoff are the main sources of groundwater pollution in the Hutuo River alluvial-pluvial fan area. Thus, the most appropriate methods to prevent groundwater quality degradation are to improve capacities for wastewater treatment and to optimize fertilization strategies.

http://ift.tt/2rh0dUT

Binge-drinking and non-partner aggression are associated with gambling among Veterans with recent substance use in VA outpatient treatment

Publication date: November 2017
Source:Addictive Behaviors, Volume 74
Author(s): Alan K. Davis, Erin E. Bonar, Jason E. Goldstick, Maureen A. Walton, Jamie Winters, Stephen T. Chermack
BackgroundGambling is relatively under-assessed in Veterans Affairs (VA) substance use disorder (SUD) treatment settings, yet shared characteristics with substance addiction suggest the importance of understanding how gambling behaviors present in Veterans seeking SUD care.MethodWe evaluated substance use, mental health, and violence-related correlates of past 30-day gambling among 833 Veterans (93% male, M age 48years, 72% Caucasian) seeking treatment in VA outpatient mental health and SUD clinics who completed screening for a randomized clinical trial.ResultsA total of 288 (35%) Veterans reported past 30-day gambling. Among those who gambled, 79% had cravings/urges to gamble, whereas between 20%–27% of gamblers reported perceived relationship, legal, and daily life problems related to gambling, as well as difficulty controlling gambling. A logistic regression analysis revealed that age, recent binge-drinking, and non-partner physical aggression were associated with recent gambling.ConclusionsGambling was associated with binge-drinking and non-partner physical aggression, supporting potential shared characteristics among these behaviors such as impulsivity and risk-taking, which may complicate SUD treatment engagement and effectiveness. Findings support the need to screen for gambling in the VA, and to adapt treatments to include gambling as a potential behavioral target or relapse trigger, particularly among heavy drinking patients.



http://ift.tt/2rP2J5z

Current suicidal ideation in treatment-seeking individuals in the United Kingdom with gambling problems

Publication date: November 2017
Source:Addictive Behaviors, Volume 74
Author(s): Silvia Ronzitti, Emiliano Soldini, Neil Smith, Marc N. Potenza, Massimo Clerici, Henrietta Bowden-Jones
BackgroundStudies show higher lifetime prevalence of suicidality in individuals with pathological gambling. However, less is known about the relationship between pathological gambling and current suicidal ideation.ObjectivesWe investigated socio-demographic, clinical and gambling-related variables associated with suicidality in treatment-seeking individuals.MethodsBivariate analyses and logistic regression models were generated on data from 903 individuals to identify measures associated with aspects of suicidality.ResultsForty-six percent of patients reported current suicidal ideation. People with current suicidal thoughts were more likely to report greater problem-gambling severity (p<0.001), depression (p<0.001) and anxiety (p<0.001) compared to those without suicidality. Logistic regression models suggested that past suicidal ideation (p<0.001) and higher anxiety (p<0.05) may be predictive factors of current suicidality.ConclusionsOur findings suggest that the severity of anxiety disorder, along with a lifetime history of suicidal ideation, may help to identify treatment-seeking individuals with pathological gambling with a higher risk of suicidality, highlighting the importance of assessing suicidal ideation in clinical settings.



http://ift.tt/2qvoV0B

Impulsivity and history of behavioral addictions are associated with drug use in adolescents

Publication date: November 2017
Source:Addictive Behaviors, Volume 74
Author(s): Cheng-Wei I. Chuang, Steve Sussman, Matthew D. Stone, Raina D. Pang, Chih-Ping Chou, Adam M. Leventhal, Matthew G. Kirkpatrick
BackgroundPrevious literature suggests that trait impulsivity and engagement in non-drug-related behavioral addictions (e.g., Internet addiction, food addiction) are two risk factors for drug use. Here we further investigated the potential impact of having one or both of these risk factors on drug use in Los Angeles area adolescents.MethodHigh school students (N=1612; Mean age=14.1) completed self-report surveys measuring two potential risk factors (impulsivity, lifetime history of several behavioral addictions), and past 6-month use of tobacco, alcohol and marijuana. Participants who reported never using drugs completed questionnaires assessing their susceptibility for future use.ResultsIn general, adolescents who endorsed either impulsivity alone or at least two behavioral addictions alone were more likely to have used tobacco, alcohol, or marijuana compared to individuals who had neither risk factor (OR=2.50–4.13), and individuals who endorsed both impulsivity and three or more behavioral addictions were the most likely to have used these drugs (OR=9.40–10.13). Similarly, among those who had never tried a drug, individuals with this combined set of risk factors were the most likely to be susceptible to future drug use (OR=3.37–5.04).DiscussionThese results indicate that the combination of trait impulsivity and a history of behavioral addictions increases the risk for current and future drug use in adolescents, to a greater extent than either risk factor alone. It may be useful for drug prevention efforts to target impulsive adolescents who also actively engage in other non-drug-related addictive behaviors.



http://ift.tt/2rPlPbI

Protein kinase C (PKC) isoforms in cancer, tumor promotion and tumor suppression

Publication date: Available online 29 May 2017
Source:Seminars in Cancer Biology
Author(s): Noah Isakov
The AGC family of serine/threonine kinases (PKA, PKG, PKC) includes more than 60 members that are critical regulators of numerous cellular functions, including cell cycle and differentiation, morphogenesis, and cell survival and death. Mutation and/or dysregulation of AGC kinases can lead to malignant cell transformation and contribute to the pathogenesis of many human diseases. Members of one subgroup of AGC kinases, the protein kinase C (PKC), have been singled out as critical players in carcinogenesis, following their identification as the intracellular receptors of phorbol esters, which exhibit tumor-promoting activities. This observation attracted the attention of researchers worldwide and led to intense investigations on the role of PKC in cell transformation and the potential use of PKC as therapeutic drug targets in cancer diseases. Studies demonstrated that many cancers had altered expression and/or mutation of specific PKC genes. However, the causal relationships between the changes in PKC gene expression and/or mutation and the direct cause of cancer remain elusive. Independent studies in normal cells demonstrated that activation of PKC is essential for the induction of cell activation and proliferation, differentiation, motility, and survival. Based on these observations and the general assumption that PKC isoforms play a positive role in cell transformation and/or cancer progression, many PKC inhibitors have entered clinical trials but the numerous attempts to target PKC in cancer has so far yielded only very limited success. More recent studies demonstrated that PKC function as tumor suppressors, and suggested that future clinical efforts should focus on restoring, rather than inhibiting, PKC activity. The present manuscript provides some historical perspectives on the tumor promoting function of PKC, reviewing some of the observations linking PKC to cancer progression, and discusses the role of PKC in the pathogenesis of cancer diseases and its potential usage as a therapeutic target.



http://ift.tt/2seW9Sn

Evolving Concepts in Atopic Dermatitis

Abstract

Purpose of Review

Tremendous advances have been made in the field of atopic dermatitis in the past 5 years. We will explore developments in burden of disease, co-morbidities, pathogenesis, prevention, and management.

Recent Findings

The tremendous burden moderate to severe atopic dermatitis (AD) places on families from a medical, psychosocial, and financial perspective has been characterized. Epidemiologic studies have identified intriguing new associations beyond the well-characterized "atopic march" of food allergies, asthma, and hay fever. Studies of primary prevention have gained traction including the remarkable impacts of early emollient therapy. Basic advances have simultaneously elucidated the nature of atopic inflammation, setting the stage for an explosion of new potential therapeutic targets. After a fallow period of nearly 15 years without a substantial therapeutic advance, this year has already seen two new FDA-approved treatments for AD.

Summary

AD has a tremendous impact on quality of life with an underappreciated burden of disease; there are important newly described co-morbidities including ADHD and anemia; new insights into etio-pathogenesis have paved the way for novel topical therapies like crisaborole, and new systemic interventions like dupilumab.

http://ift.tt/2qu0j8t

T Cells in Allergic Asthma: Key Players Beyond the Th2 Pathway

Abstract

Asthma is a common chronic lung disease that affects 300 million people worldwide. It causes the airways of the lungs to swell and narrow due to inflammation (swelling and excess mucus build-up in the airways) and airway constriction (tightening of the muscles surrounding the airways). Atopic asthma is the most common form of asthma, and is triggered by inhaled allergens that ultimately promote the activation of the Th2-like T cells and the development of Th2-mediated chronic inflammation. Different subsets of T cells, including T follicular helper cells, tissue-resident T, cells and Th2 effector cells, play different functions during allergic immune response. Dendritic cells (DCs) are known to play a central role in initiating allergic Th2-type immune responses and in the development of the T cell phenotype. However, this function depends on the complex interaction with other cells of the immune system and determines whether the response to environmental allergens will be one of tolerance or allergic inflammation. This review discusses cell interactions leading to the initiation and maintenance of allergic Th2-type immune responses, particularly those associated with allergic asthma.

http://ift.tt/2rNRr15

Evolving Concepts in Atopic Dermatitis

Abstract

Purpose of Review

Tremendous advances have been made in the field of atopic dermatitis in the past 5 years. We will explore developments in burden of disease, co-morbidities, pathogenesis, prevention, and management.

Recent Findings

The tremendous burden moderate to severe atopic dermatitis (AD) places on families from a medical, psychosocial, and financial perspective has been characterized. Epidemiologic studies have identified intriguing new associations beyond the well-characterized "atopic march" of food allergies, asthma, and hay fever. Studies of primary prevention have gained traction including the remarkable impacts of early emollient therapy. Basic advances have simultaneously elucidated the nature of atopic inflammation, setting the stage for an explosion of new potential therapeutic targets. After a fallow period of nearly 15 years without a substantial therapeutic advance, this year has already seen two new FDA-approved treatments for AD.

Summary

AD has a tremendous impact on quality of life with an underappreciated burden of disease; there are important newly described co-morbidities including ADHD and anemia; new insights into etio-pathogenesis have paved the way for novel topical therapies like crisaborole, and new systemic interventions like dupilumab.

http://ift.tt/2qu0j8t

T Cells in Allergic Asthma: Key Players Beyond the Th2 Pathway

Abstract

Asthma is a common chronic lung disease that affects 300 million people worldwide. It causes the airways of the lungs to swell and narrow due to inflammation (swelling and excess mucus build-up in the airways) and airway constriction (tightening of the muscles surrounding the airways). Atopic asthma is the most common form of asthma, and is triggered by inhaled allergens that ultimately promote the activation of the Th2-like T cells and the development of Th2-mediated chronic inflammation. Different subsets of T cells, including T follicular helper cells, tissue-resident T, cells and Th2 effector cells, play different functions during allergic immune response. Dendritic cells (DCs) are known to play a central role in initiating allergic Th2-type immune responses and in the development of the T cell phenotype. However, this function depends on the complex interaction with other cells of the immune system and determines whether the response to environmental allergens will be one of tolerance or allergic inflammation. This review discusses cell interactions leading to the initiation and maintenance of allergic Th2-type immune responses, particularly those associated with allergic asthma.

http://ift.tt/2rNRr15

Fast and efficient removal of copper using sandwich-like graphene oxide composite imprinted materials

Publication date: 15 October 2017
Source:Chemical Engineering Journal, Volume 326
Author(s): Delong Kong, Ning Qiao, Huan Liu, Jian Du, Nian Wang, Zhiyong Zhou, Zhongqi Ren
A sandwich-like ion-imprinted polymer (IIP) was prepared using functional graphene oxide (GO) as the support, acrylamide as the functional monomer, and ethylene glycol dimethacrylate as the crosslinking agent in the presence of copper ions with various solvents (porogen). The effect of solvent type on polymerization process and properties of polymers was investigated. Methanol/acetonitrile was considered as the best porogen, and almost no redundant secondary polymer particles were produced. This can be explained by the good thermodynamic compatibility and slow phase separation property of monomers and crosslinking agents in polymerization process. Fourier-transform infrared spectroscopy, Energy dispersive X-ray spectroscopy, thermogravimetric analysis, and scanning electron microscopy were used to confirm the prepared IIP. The effects of pH, initial concentration of the Cu(II) aqueous solution, and contact time on adsorption behavior were investigated. Adsorption by prepared IIP was fast (adsorption equilibrium was reached within 15min) and followed pseudo-second-order kinetic and Freundlich isotherm models. The IIP showed a good imprinted factor and the maximum adsorption capacity was up to 132.77mgg⁻¹, which is higher than that of IIP prepared by bulk polymerization, owing to the large surface area of GO and surface imprinted technology. The selectivity factors for Cu/Zn, Cu/Ni, Cu/Co, and Cu/Cd were 36.33, 8.44, 77.3, and 8.5, respectively. The polymer showed a widely application prospect for recovery of Cu ions from aqueous solutions.

Graphical abstract

http://ift.tt/2rgNEJk

Evolving Concepts in Atopic Dermatitis

Abstract

Purpose of Review

Tremendous advances have been made in the field of atopic dermatitis in the past 5 years. We will explore developments in burden of disease, co-morbidities, pathogenesis, prevention, and management.

Recent Findings

The tremendous burden moderate to severe atopic dermatitis (AD) places on families from a medical, psychosocial, and financial perspective has been characterized. Epidemiologic studies have identified intriguing new associations beyond the well-characterized "atopic march" of food allergies, asthma, and hay fever. Studies of primary prevention have gained traction including the remarkable impacts of early emollient therapy. Basic advances have simultaneously elucidated the nature of atopic inflammation, setting the stage for an explosion of new potential therapeutic targets. After a fallow period of nearly 15 years without a substantial therapeutic advance, this year has already seen two new FDA-approved treatments for AD.

Summary

AD has a tremendous impact on quality of life with an underappreciated burden of disease; there are important newly described co-morbidities including ADHD and anemia; new insights into etio-pathogenesis have paved the way for novel topical therapies like crisaborole, and new systemic interventions like dupilumab.

http://ift.tt/2qu0j8t

T Cells in Allergic Asthma: Key Players Beyond the Th2 Pathway

Abstract

Asthma is a common chronic lung disease that affects 300 million people worldwide. It causes the airways of the lungs to swell and narrow due to inflammation (swelling and excess mucus build-up in the airways) and airway constriction (tightening of the muscles surrounding the airways). Atopic asthma is the most common form of asthma, and is triggered by inhaled allergens that ultimately promote the activation of the Th2-like T cells and the development of Th2-mediated chronic inflammation. Different subsets of T cells, including T follicular helper cells, tissue-resident T, cells and Th2 effector cells, play different functions during allergic immune response. Dendritic cells (DCs) are known to play a central role in initiating allergic Th2-type immune responses and in the development of the T cell phenotype. However, this function depends on the complex interaction with other cells of the immune system and determines whether the response to environmental allergens will be one of tolerance or allergic inflammation. This review discusses cell interactions leading to the initiation and maintenance of allergic Th2-type immune responses, particularly those associated with allergic asthma.

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Evolving Concepts in Atopic Dermatitis

Abstract

Purpose of Review

Tremendous advances have been made in the field of atopic dermatitis in the past 5 years. We will explore developments in burden of disease, co-morbidities, pathogenesis, prevention, and management.

Recent Findings

The tremendous burden moderate to severe atopic dermatitis (AD) places on families from a medical, psychosocial, and financial perspective has been characterized. Epidemiologic studies have identified intriguing new associations beyond the well-characterized "atopic march" of food allergies, asthma, and hay fever. Studies of primary prevention have gained traction including the remarkable impacts of early emollient therapy. Basic advances have simultaneously elucidated the nature of atopic inflammation, setting the stage for an explosion of new potential therapeutic targets. After a fallow period of nearly 15 years without a substantial therapeutic advance, this year has already seen two new FDA-approved treatments for AD.

Summary

AD has a tremendous impact on quality of life with an underappreciated burden of disease; there are important newly described co-morbidities including ADHD and anemia; new insights into etio-pathogenesis have paved the way for novel topical therapies like crisaborole, and new systemic interventions like dupilumab.

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T Cells in Allergic Asthma: Key Players Beyond the Th2 Pathway

Abstract

Asthma is a common chronic lung disease that affects 300 million people worldwide. It causes the airways of the lungs to swell and narrow due to inflammation (swelling and excess mucus build-up in the airways) and airway constriction (tightening of the muscles surrounding the airways). Atopic asthma is the most common form of asthma, and is triggered by inhaled allergens that ultimately promote the activation of the Th2-like T cells and the development of Th2-mediated chronic inflammation. Different subsets of T cells, including T follicular helper cells, tissue-resident T, cells and Th2 effector cells, play different functions during allergic immune response. Dendritic cells (DCs) are known to play a central role in initiating allergic Th2-type immune responses and in the development of the T cell phenotype. However, this function depends on the complex interaction with other cells of the immune system and determines whether the response to environmental allergens will be one of tolerance or allergic inflammation. This review discusses cell interactions leading to the initiation and maintenance of allergic Th2-type immune responses, particularly those associated with allergic asthma.

http://ift.tt/2rNRr15

Is Nutrient Content and Other Label Information for Prescription Prenatal Supplements Different from Nonprescription Products?

Publication date: Available online 29 May 2017
Source:Journal of the Academy of Nutrition and Dietetics
Author(s): Leila G. Saldanha, Johanna T. Dwyer, Karen W. Andrews, LaVerne L. Brown, Rebecca B. Costello, Abby G. Ershow, Pavel A. Gusev, Constance J. Hardy, Pamela R. Pehrsson
BackgroundPrenatal supplements are often recommended to pregnant women to help meet their nutrient needs. Many products are available, making it difficult to choose a suitable supplement because little is known about their labeling and contents to evaluate their appropriateness.ObjectiveTo determine differences between prescription and nonprescription prenatal supplements available in the United States regarding declared nutrient and nonnutrient ingredients and the presence of dosing and safety-related information.DesignUsing two publicly available databases with information about prenatal supplement products, information from prescription and nonprescription product labels were extracted and evaluated. For the 82 prescription and 132 nonprescription products, declared label amounts of seven vitamins and minerals, docosahexaenoic acid (DHA), the presence of other nonnutrient components, and the presence of key safety and informational elements as identified in two Department of Health and Human Services Office of Inspector General (OIG)'s 2003 reports were compiled and compared.ResultsCompared with nonprescription products, prescription products contained significantly fewer vitamins (9±0.2 vs 11±0.3; P≤0.05) and minerals (4±0.1 vs 8±0.3; P≤0.05). Declared amounts of folic acid were higher in prescription products, whereas vitamin A, vitamin D, iodine, and calcium were higher in the nonprescription products. Amounts of iron, zinc, and DHA were similar. Virtually all products contained levels of one or more nutrients that exceeded the Recommended Dietary Allowances for pregnant and/or lactating women. Product type also influenced ingredients added. Fewer prescription products contained botanical ingredients (6% prescription vs 33% nonprescription) and probiotics (2% prescription vs 8% nonprescription). Only prescription products contained the stool softener docusate sodium.ConclusionsOur analysis of prenatal supplements indicates that prescription and nonprescription supplements differ in terms of declared composition and nutrient strength, but have labels that are similarly sparse regarding aspects of use such as dosing information.



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A Novel Approach to Predict 24-Hour Energy Expenditure Based on Hematologic Volumes: Development and Validation of Models Comparable to Mifflin-St Jeor and Body Composition Models

Publication date: Available online 29 May 2017
Source:Journal of the Academy of Nutrition and Dietetics
Author(s): Douglas C. Chang, Paolo Piaggi, Jonathan Krakoff
BackgroundAccurate prediction of 24-hour energy expenditure (24EE) relies on knowing body composition, in particular fat-free mass (FFM), the largest determinant of 24EE. FFM is closely correlated with hematologic volumes: blood volume (BV), red cell mass (RCM), and plasma volume (PV). However, it is unknown whether predicted hematologic volumes, based on easily collected variables, can improve 24EE prediction.ObjectiveThe aim was to develop and validate equations to predict 24EE based on predicted BV, RCM, and PV and to compare the accuracy and agreement with models developed from FFM and with the Mifflin-St Jeor equation, which is recommended for clinical use by the Academy of Nutrition and Dietetics.DesignParticipants had body composition measured by underwater weighing and 24EE by respiratory chamber. BV, RCM, and PV were calculated from five published equations.Participants/settingNative American and white men and women were studied (n=351). Participants were healthy adults aged 18 to 49 years from the Phoenix, AZ, metropolitan area.Main outcome measureAccuracy to within ±10% of measured 24EE and agreement by Bland-Altman analysis.Statistical analysisRegression models to predict 24EE from hematologic and body composition variables were developed in half the dataset and validated in the other half.ResultsHematologic volumes were all strongly correlated with FFM in both men and women (r≥0.94). Whereas the accuracy of FFM alone was 69%, four hematologic volumes were individually more accurate (75% to 78%) in predicting 24EE. Equations based on hematologic volumes plus demographics had mean prediction errors comparable to those based on body composition plus demographics; although the Mifflin-St Jeor had modestly better mean prediction error, body composition, hematologic, and Mifflin-St Jeor models all had similar accuracy (approximately 80%).ConclusionsPrediction equations based on hematologic volumes were developed, validated, and found to be comparable to Mifflin-St Jeor and body composition models in this population of healthy adults.



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Alopecia Areata of the Beard: A Review of the Literature

Abstract

Alopecia areata (AA) is a T-cell mediated autoimmune disorder in which inflammatory cells attack the hair follicle, resulting in round, well-circumscribed patches of noncicatricial hair loss in normal appearing skin. AA affecting the beard area is well known and is referred to as AA of the beard (BAA) or AA barbae when involvement is limited exclusively to the beard. BAA has been documented in a select number of studies. We review the literature and discuss the clinical features, epidemiology, diagnosis, and treatment of BAA. Clinical presentation of BAA can vary and manifest as single small areas of hair loss, multiple small or large simultaneous focuses, or total hair loss. Most patients are middle-aged males with focal patches of round or oval hair loss, mostly localized along the jawline. Patches are characteristically well circumscribed and smooth with white hair present at the periphery. Dermoscopic features of BAA include yellow dots, broken hair, and short vellus hairs. BAA may be associated with other autoimmune disorders, including atopic dermatitis, vitiligo, and psoriasis. Many treatment modalities are available for BAA, and selection of a therapy depends on several factors, including disease activity, extent of area affected, duration of disease, and age of the patient. Topical corticosteroids are most commonly used as initial treatment, followed by intralesional steroids. Other therapeutic modalities are discussed.

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Concerns About the Stability of hsTnI Assay After 20 Years of Storage

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Maternal and Fetal Outcomes of Anticoagulation in Pregnant Women With Mechanical Heart Valves

AbstractBackground

Anticoagulation for mechanical heart valves during pregnancy is essential to prevent thromboembolic events. Each regimen has drawbacks with regard to maternal or fetal risk.

Objectives

This meta-analysis sought to estimate and compare the risk of adverse maternal and fetal outcomes in pregnant women with mechanical heart valves who received different methods of anticoagulation.

Methods

Studies were identified using a Medline search including all publications up to June 5, 2016. Study inclusion required reporting of maternal death, thromboembolism, and valve failure, and/or fetal spontaneous abortion, death, and congenital defects in pregnant women treated with any of the following: 1) a vitamin K antagonist (VKA) throughout pregnancy; 2) low-molecular-weight heparin (LMWH) throughout pregnancy; 3) LMWH for the first trimester, followed by a VKA (LMWH and VKA); or 4) unfractionated heparin for the first trimester, followed by a VKA (UFH and VKA).

Results

A total of 800 pregnancies from 18 publications were included. Composite maternal risk was lowest with VKA (5%), compared with LMWH (16%; ratio of averaged risk [RAR]: 3.2; 95% confidence interval [CI]: 1.5 to 7.5), LMWH and VKA (16%; RAR: 3.1; 95% CI: 1.2 to 7.5), or UFH and VKA (16%; RAR: 3.1; 95% CI: 1.5 to 7.1). Composite fetal risk was lowest with LMWH (13%; RAR: 0.3; 95% CI: 0.1 to 0.8), compared with VKA (39%), LMWH and VKA (23%), or UFH and VKA (34%). No significant difference in fetal risk was observed between women taking ≤5 mg daily warfarin and those with an LMWH regimen (RAR: 0.9; 95% CI: 0.3 to 2.4).

Conclusions

VKA treatment was associated with the lowest risk of adverse maternal outcomes, whereas the use of LMWH throughout pregnancy was associated with the lowest risk of adverse fetal outcomes. Fetal risk was similar between women taking ≤5 mg warfarin daily and women treated with LMWH.

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A Test in Context: Fractional Flow Reserve: Accuracy, Prognostic Implications, and Limitations

Abstract

Fractional flow reserve (FFR) is an invasive procedure used during coronary angiography to determine the functional significance of coronary stenoses. Its use is particularly helpful in intermediate or angiographically ambiguous lesions in the absence of noninvasive functional studies. Randomized clinical trials have reported improved clinical outcomes with the use of FFR to guide coronary revascularization, including a reduction in cardiac death or myocardial infarction, as well as costs, with an FFR-based strategy compared with a conventional angiography-based approach. Current societal guidelines provide a Class II, Level of Evidence: A recommendation to perform FFR in angiographically intermediate stenoses in the absence of stress testing or in the presence of discordant stress test results and angiographic findings. However, despite the relative ease of use of FFR, multiple technical factors can impair its accuracy, and attention to detail is critical when performing the test. This review focuses on the fundamental basics of FFR testing, clinical evidence, and limitations.

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Anticoagulation Therapy for Pregnant Women With Mechanical Prosthetic Heart Valves: How to Improve Safety?

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Acute and Recurrent Pericarditis: Still Idiopathic?

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Trends in Use of High-Intensity Statin Therapy After Myocardial Infarction, 2011 to 2014

AbstractBackground

Data prior to 2011 suggest that a low percentage of patients hospitalized for acute coronary syndromes filled high-intensity statin prescriptions upon discharge. Black-box warnings, generic availability of atorvastatin, and updated guidelines may have resulted in a change in high-intensity statin use.

Objectives

The aim of this study was to examine trends and predictors of high-intensity statin use following hospital discharge for myocardial infarction (MI) between 2011 and 2014.

Methods

Secular trends in high-intensity statin use following hospital discharge for MI were analyzed among patients 19 to 64 years of age with commercial health insurance in the MarketScan database (n = 42,893) and 66 to 75 years of age with U.S. government health insurance through Medicare (n = 75,096). Patients filling statin prescriptions within 30 days of discharge were included. High-intensity statins included atorvastatin 40 or 80 mg and rosuvastatin 20 or 40 mg.

Results

The percentage of beneficiaries whose first statin prescriptions filled following hospital discharge for MI were for high-intensity doses increased from 33.5% in January through March 2011 to 71.7% in October through November 2014 in MarketScan and from 24.8% to 57.5% in Medicare. Increases in high-intensity statin use following hospital discharge occurred over this period among patients initiating treatment (30.6% to 72.0% in MarketScan and 21.1% to 58.8% in Medicare) and those taking low- or moderate-intensity statins prior to hospitalization (from 27.8% to 62.3% in MarketScan and from 12.6% to 45.1% in Medicare). In 2014, factors associated with filling high-intensity statin prescriptions included male sex, filling beta-blocker and antiplatelet agent prescriptions, and attending cardiac rehabilitation within 30 days following discharge.

Conclusions

The use of high-intensity statins following hospitalization for MI increased progressively from 2011 through 2014.

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Multiple Biomarkers in the Context of Conventional Risk Factors in Patients With Coronary Artery Disease

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Statins in Secondary Prevention: Intensity Matters

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Risk of Adverse Neurocognitive Outcomes With PCSK-9 Inhibitors

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{beta}-Blockers and Mortality After Acute Myocardial Infarction in Patients Without Heart Failure or Ventricular Dysfunction

AbstractBackground

For acute myocardial infarction (AMI) without heart failure (HF), it is unclear if β-blockers are associated with reduced mortality.

Objectives

The goal of this study was to determine the association between β-blocker use and mortality in patients with AMI without HF or left ventricular systolic dysfunction (LVSD).

Methods

This cohort study used national English and Welsh registry data from the Myocardial Ischaemia National Audit Project. A total of 179,810 survivors of hospitalization with AMI without HF or LVSD, between January 1, 2007, and June 30, 2013 (final follow-up: December 31, 2013), were assessed. Survival-time inverse probability weighting propensity scores and instrumental variable analyses were used to investigate the association between the use of β-blockers and 1-year mortality.

Results

Of 91,895 patients with ST-segment elevation myocardial infarction and 87,915 patients with non–ST-segment elevation myocardial infarction, 88,542 (96.4%) and 81,933 (93.2%) received β-blockers, respectively. For the entire cohort, with >163,772 person-years of observation, there were 9,373 deaths (5.2%). Unadjusted 1-year mortality was lower for patients who received β-blockers compared with those who did not (4.9% vs. 11.2%; p < 0.001). However, after weighting and adjustment, there was no significant difference in mortality between those with and without β-blocker use (average treatment effect [ATE] coefficient: 0.07; 95% confidence interval [CI]: –0.60 to 0.75; p = 0.827). Findings were similar for ST-segment elevation myocardial infarction (ATE coefficient: 0.30; 95% CI: –0.98 to 1.58; p = 0.637) and non–ST-segment elevation myocardial infarction (ATE coefficient: –0.07; 95% CI: –0.68 to 0.54; p = 0.819).

Conclusions

Among survivors of hospitalization with AMI who did not have HF or LVSD as recorded in the hospital, the use of β-blockers was not associated with a lower risk of death at any time point up to 1 year. (β-Blocker Use and Mortality in Hospital Survivors of Acute Myocardial Infarction Without Heart Failure; NCT02786654)

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JACC Instructions for Authors

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The Swing of {beta}-Blockers: Time for a System Reboot

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LOX-1 in Atherosclerosis and Myocardial Ischemia: Biology, Genetics, and Modulation

Abstract

Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), one of the scavenger receptors for oxidized low-density lipoprotein cholesterol (ox-LDL), plays a crucial role in the uptake of ox-LDL by cells in the arterial wall. Mounting evidence suggests a role for LOX-1 in various steps of the atherosclerotic process, from initiation to plaque destabilization. Studies of the genetic structure of LOX-1 have also uncovered various genetic polymorphisms that could modulate the risk of atherosclerotic cardiovascular events. As evidence supporting the vital role of LOX-1 in atherogenesis keeps accumulating, there is growing interest in LOX-1 as a potential therapeutic target. This review discusses the discovery and genetics of LOX-1; describes existing evidence supporting the role of LOX-1 in atherogenesis and its major complication, myocardial ischemia; and summarizes LOX-1 modulation by some naturally occurring compounds and efforts toward development of small molecules and biologics that could be of therapeutic use.

http://ift.tt/2rg2U95

Interventional Treatment of Patients With Congenital Heart Disease: Nationwide Danish Experience Over 39 Years

AbstractBackground

The treatment of congenital heart (CHD) has changed rapidly.

Objectives

The authors reviewed CHD treatment through a 39-year nationwide population-based study on congenital heart surgery and catheter-based interventions, unbiased by referral patterns.

Methods

Using medical registries, the authors identified children (<18 years of age) treated for CHD in Denmark from 1977 to 2015, their need for reinterventions, and their long-term survival. Ten controls per patient, matched by sex and year of birth, allowed comparison with the background population. Survival was described using Kaplan-Meier curves.

Results

A total of 9,372 patients underwent 11,968 cardiac surgeries and 1,912 catheter-based interventions. Median age at first procedure decreased from 3.4 years (5th and 95th percentiles: 0.01 to 15.4 years) in 1977 to 1989 (period 1), 0.8 years (5th and 95th percentiles: 0.003 to 13.8 years) in 1990 to 2002 (period 2), and to 0.6 years (5th and 95th percentiles: 0.0 to 14.9 years) in 2003 to 2015 (period 3). More patients were born preterm (<37 weeks) in period 3 compared with those in period 1 (18.5% vs. 6.7%). Catheter-based interventions, not recorded before 1990, were increasingly used as the initial procedure in 5.8% of patients in period 2 and 25.9% of patients in period 3. An increasing part of the population did not undergo surgery at all (4.8% in period 2; 24.0% in period 3). Thirty-day survival increased from 97% (period 1) to 98% (period 2) to 100% (period 3). Ten-year survival increased from 80% (period 1) to 87% (period 2) to 93% (period 3). Compared with the background population, CHD was associated with lower survival in all 3 time periods.

Conclusions

Interventional treatment of CHD has evolved from 1977 to 2015 and is now performed on younger and more preterm patients, often with catheter-based interventions. However, compared with the background population, survival remains significantly reduced.

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Serum Magnesium Levels and In-Hospital Mortality in Acute Myocardial Infarction

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Congenital Heart Defects: Amazing Advances and Ongoing Challenges

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Relativism and Low-Density Lipoprotein Cholesterol: Absolute or Relative Truth?

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Longitudinal Outcomes of Patients With Single Ventricle After the Fontan Procedure

AbstractBackground

Multicenter longitudinal objective data for survival into adulthood of patients who have undergone Fontan procedures are lacking.

Objectives

This study sought to describe transplant-free survival and explore relationships between laboratory measures of ventricular performance and functional status over time.

Methods

Exercise testing, echocardiography, B-type natriuretic peptide, functional health assessment, and medical history abstraction were repeated 9.4 ± 0.4 years after the Fontan Cross-Sectional Study (Fontan 1) and compared with previous values. Cox regression analysis explored risk factors for interim death or cardiac transplantation.

Results

From the original cohort of 546 subjects, 466 were contacted again, and 373 (80%) were enrolled at 21.2 ± 3.5 years of age. Among subjects with paired testing, the percent predicted maximum oxygen uptake decreased (69 ± 14% vs. 61 ± 16%; p < 0.001; n = 95), ejection fraction decreased (58 ± 11% vs. 55 ± 10%; p < 0.001; n = 259), and B-type natriuretic peptide increased (median [interquartile range] 13 [7 to 25] pg/mol vs. 18 [9 to 36] pg/mol; p < 0.001; n = 340). At latest follow-up, a lower Pediatric Quality of Life Inventory physical summary score was associated with poorer exercise performance (R² adjusted = 0.20; p < 0.001; n = 274). Cumulative complications since the Fontan procedure included additional cardiac surgery (32%), catheter intervention (62%), arrhythmia treatment (32%), thrombosis (12%), and protein-losing enteropathy (8%). Since Fontan 1, 54 subjects (10%) have received a heart transplant (n = 23) or died without transplantation (n = 31). The interval risk of death or/cardiac transplantation was associated with poorer ventricular performance and functional health status assessed at Fontan 1, but it was not associated with ventricular morphology, the subject's age, or the type of Fontan connection.

Conclusions

Interim transplant-free survival over 12 years in this Fontan cohort was 90% and was independent of ventricular morphology. Exercise performance decreased and was associated with worse functional health status. Future interventions might focus on preserving exercise capacity. (Relationship Between Functional Health Status and Ventricular Performance After Fontan—Pediatric Heart Network; NCT00132782)

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Reply: Acute and Recurrent Pericarditis: Still Idiopathic?

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Cardiorespiratory Fitness, Not the Severity of the Condition, Dictates Late Outcomes After Fontan Procedures

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Cytokine storm and sepsis disease pathogenesis

Abstract

Infectious diseases are a leading cause of death worldwide. Sepsis is a severe clinical syndrome related to the host response to infection. The severity of infections is due to an activation cascade that will lead to an autoamplifying cytokine production: the cytokine storm. Cytokines are a broad category of relatively small proteins (<40 kDa) that are produced and released with the aim of cell signaling. Our understanding of the processes that trigger this tremendous amount of cytokine production has made dramatic progress over the last decades, but unfortunately, these findings could not translate yet into effective treatments; so far, all clinical trials targeting cytokine production or effects failed. This review aims to summarize the pathophysiology of the cytokine storm; to describe the type, effects, and kinetics of cytokine production; and to discuss the therapeutic challenges of targeting cytokines. New promising therapeutic strategies focusing on the endothelium, as a source and a target of cytokines, are described.

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Molecular pathogenesis of viral hemorrhagic fever

Abstract

The clinical syndrome referred to as viral hemorrhagic fever (VHF) can be caused by several different families of RNA viruses, including select members of the arenaviruses, bunyaviruses, filoviruses, and flaviviruses. VHF is characterized by malaise, fever, vascular permeability, decreased plasma volume, coagulation abnormalities, and varying degrees of hemorrhage. Study of the filovirus Ebola virus has demonstrated a critical role for suppression of innate antiviral defenses in viral pathogenesis. Additionally, antigen-presenting cells are targets of productive infection and immune dysregulation. Among these cell populations, monocytes and macrophages are proposed to produce damaging inflammatory cytokines, while infected dendritic cells fail to undergo proper maturation, potentially impairing adaptive immunity. Uncontrolled virus replication and accompanying inflammatory responses are thought to promote vascular leakage and coagulopathy. However, the specific molecular pathways that underlie these features of VHF remain poorly understood. The arenavirus Lassa virus and the flavivirus yellow fever virus exhibit similar molecular pathogenesis suggesting common underlying mechanisms. Because non-human primate models that closely mimic VHF are available for Ebola, Lassa, and yellow fever viruses, we propose that comparative molecular studies using these models will yield new insights into the molecular underpinnings of VHF and suggest new therapeutic approaches.

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Genetics of rheumatoid arthritis susceptibility, severity, and treatment response

Abstract

A decade after the first genome-wide association study in rheumatoid arthritis (RA), a plethora of genetic association studies have been published on RA and its clinical or serological subtypes. We review the major milestones in the study of the genetic architecture of RA susceptibility, severity, and response to treatment. We set the scientific context necessary for non-geneticists to understand the potential clinical applications of human genetics and its significance for a stratified approach to the management of RA in the future.

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New fronts emerge in the influenza cytokine storm

Abstract

Influenza virus is a significant pathogen in humans and animals with the ability to cause extensive morbidity and mortality. Exuberant immune responses induced following infection have been described as a "cytokine storm," associated with excessive levels of proinflammatory cytokines and widespread tissue damage. Recent studies have painted a more complex picture of cytokine networks and their contributions to clinical outcomes. While many cytokines clearly inflict immunopathology, others have non-pathological delimited roles in sending alarm signals, facilitating viral clearance, and promoting tissue repair, such as the IL-33—amphiregulin axis, which plays a key role in resolving some types of lung damage. Recent literature suggests that type 2 cytokines, traditionally thought of as not involved in anti-influenza immunity, may play an important regulatory role. Here, we discuss the diverse roles played by cytokines after influenza infection and highlight new, serene features of the cytokine storm, while highlighting the specific functions of relevant cytokines that perform unique immune functions and may have applications for influenza therapy.

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