Impaired polymorphonuclear neutrophils in the oral cavity of edentulous individuals

Oral health is characterized by functional oral polymorphonuclear neutrophils (oPMNs). Edentulism might be associated with a loss of oPMNs because these cells enter the oral cavity primarily through the gingival crevices. The main aim of this study was to investigate the numbers of oPMNs in rinse samples obtained from edentulous (n = 21) and dentate (n = 20) subjects. A second study aim was to investigate possible differences between oPMNs and peripheral blood polymorphonuclear neutrophils (cPMNs). Apoptosis/necrosis and cell-activation markers (CD11b, CD63 and CD66b) were analyzed using flow cytometry. Reactive oxygen species (ROS) production was determined either without stimulation (constitutive) or in response to 10 μM phorbol myristate acetate or Fusobacterium nucleatum. The edentulous subjects presented with lower oPMN counts and higher percentages of apoptotic/necrotic oPMNs compared with dentate subjects. Furthermore, oPMNs from edentulous donors expressed low levels of all three activation markers and low constitutive ROS. In contrast, oPMNs from dentate subjects expressed high levels of all three activation markers and a higher level of constitutive ROS than cPMNs. When challenged, oPMNs from edentulous subjects showed no upregulation in ROS production, whereas oPMNs from dentate subjects retained their ability to respond to stimulation. The functional characteristics of cPMNs were comparable between edentulous and dentate subjects. This study demonstrates that despite having functional cPMNs, edentulous subjects have low oPMN numbers that are functionally impaired.

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Guided bone regeneration: materials and biological mechanisms revisited

Guided bone regeneration (GBR) is commonly used in combination with the installment of titanium implants. The application of a membrane to exclude non-osteogenic tissues from interfering with bone regeneration is a key principle of GBR. Membrane materials possess a number of properties which are amenable to modification. A large number of membranes have been introduced for experimental and clinical verification. This prompts the need for an update on membrane properties and the biological outcomes, as well as a critical assessment of the biological mechanisms governing bone regeneration in defects covered by membranes. The relevant literature for this narrative review was assessed after a MEDLINE/PubMed database search. Experimental data suggest that different modifications of the physicochemical and mechanical properties of membranes may promote bone regeneration. Nevertheless, the precise role of membrane porosities for the barrier function of GBR membranes still awaits elucidation. Novel experimental findings also suggest an active role of the membrane compartment per se in promoting the regenerative processes in the underlying defect during GBR, instead of being purely a passive barrier. The optimization of membrane materials by systematically addressing both the barrier and the bioactive properties is an important strategy in this field of research.

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LASIK Laser Eye Surgery • Patient Education

LASIK Laser Eye Surgery • Patient Education
http://ift.tt/2uTJLgr

Patient Education Company
Your doctor has recommended that you undergo Laser-In-Situ Keratomileusis - or LASIK Laser surgery - to correct a vision problem.
What is lasik eye surgery?
The human eye is constructed like a camera ... with a clear lens in the front and light-sensitive tissue at the rear. This tissue makes up the retina which acts like photographic film.
Patient Education
In an eye that has perfect vision, light rays passing through the pupil are focused by the lens to fall precisely at the center of the retina. There are many common problems that can affect the eye and prevent light rays from focusing properly on the retina.

Three of these problems, myopia - or nearsightedness; hyperopia - or farsightedness; and astigmatism can often be corrected or reduced with the use of LASIK laser surgery.
Patient Education
Myopia, or nearsightedness, occurs when the shape of the eye is too long or the curve of the cornea is too extreme. In this case, light rays are focused on a point in front of the retina - instead of on the retina itself.

Hyperopia, or farsightedness, occurs when the shape of the eye is too short. In this case, light rays are focused on a point behind the retina.
Astigmatism occurs when the cornea is unevenly curved,
causing light rays to fall off center or not to focus properly at all.
In either case, LASIK laser surgery can be used to flatten all or part of the cornea ... allowing your doctor to cause the focal point of light entering the eye to fall more closely to the center of the surface of the retina.

LASIK laser surgery is a relatively simple and nonintrusive procedure that is designed to reduce or eliminate the need for glasses or contact lenses. LASIK laser surgery generally does not have any effect on a patient's overall health and there are no risks in choosing not to have the surgery.

Your Procedure:

On the day of your operation, you will be asked to put on a surgical gown.

You may receive a sedative by mouth and an intravenous line may be put in.

You will then be transferred to the operating table and you'll be given an anesthetic in the form of eye drops, and a suction ring will be placed on the eye to prevent movement and to maintain pressure within the eye.

When the operative field is numb, the doctor will use an automated microsurgical instrument called a microkeratome.

This tiny instrument will carefully create a thin corneal flap which remains hinged to the eye.

Underneath this flap the inner layer of the cornea, called the stroma, is exposed.

Next, your doctor will use a computer to control pulses of cool laser light. These pulses will delicately remove microscopically thin layers of cells from the stroma

By removing tissue in this manner, your doctor will tailor the new shape of your cornea according to the exact nature of your vision problem. The entire procedure usually takes about 5 minutes and is painless.

The corneal flap is then closed and the surface is rinsed.

Following surgery, you'll be given protective contact lenses to wear for a few days while the corneal flap heals.

Patient Education Company

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Effect of different dental burs for experimental induction of pulpitis in mice

Publication date: November 2017
Source:Archives of Oral Biology, Volume 83
Author(s): Xilin Shi, Zhengmao Li, Ying He, Qianzhou Jiang, Xuechao Yang
ObjectiveTo evaluate the effect of using different dental burs on the development of pulpal inflammation after pulpal exposure in mice.DesignEighty-eight C57BL/6 mice were randomly assigned to group A (n=40), group B (n=40) and control group (n=8). The pulps of the maxillary first molars were occlusally exposed using ¼ round burs and polishing burs in group A and B respectively. Animals were sacrificed randomly at 0h, 4h, 8h, 12h and 24h after pulpal exposure. Micro-CT scanning was used to determine the success rate of sample preparation. Pulpal tissue changes were evaluated by histopathologic and immunohistochemical analyses.ResultsThe success rates of sample preparations were 85% in group A and 90% in group B. The mean maximum diameter of pulpal exposure area was 625.6±30.6μm in group A and 402.7±18.0μm in group B (p<0.05). In addition, the mean of the minimum remaining dentine thickness at the marked region of interest was 133.2±29.9μm in group A and 261.4±16.3μm in group B (p<0.05). Histopathologic staining demonstrated more signs of inflammation in both groups, as the duration of pulpal exposure increases. However, the rate of inflammatory progress was higher in group A, even spreading to the root pulp tissue within a few hours. For group B, the progress was relatively slow.ConclusionsPulpal exposure with different sizes of dental burs affects changes in the development of pulpal inflammation in mice.



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Medicinal plant products targeting quorum sensing for combating bacterial infections

Publication date: Available online 19 August 2017
Source:Asian Pacific Journal of Tropical Medicine
Author(s): Abdelhakim Bouyahya, Nadia Dakka, Abdeslam Et-Touys, Jamal Abrini, Youssef Bakri
Traditional treatment of infectious diseases is based on compounds that aim to kill or inhibit bacterial growth. The bacterial resistance against antibiotics is a serious issue for public health. Today, new therapeutic targets other than the bacterial wall were deciphered. Quorum sensing or bacterial pheromones are molecules called auto-inducer secreted by bacteria to regulate some functions such as antibiotic resistance and biofilms formation. This therapeutic target is well-studied worldwide, nevertheless the scientific data are not updated and only recent researches started to look into its potential as a target to fight against infectious diseases. A major concern with this approach is the frequently observed development of resistance to antimicrobial compounds. Therefore, this paper aims to provide a current overview of the quorum sensing system in bacteria by revealing their implication in biofilms formation and the development of antibiotic resistance, and an update on their importance as a potential target for natural substances.



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Chemical composition, antioxidant, and antibacterial activity of essential oils from Etlingera sayapensis A.D. Poulsen & Ibrahim

Publication date: Available online 19 August 2017
Source:Asian Pacific Journal of Tropical Medicine
Author(s): Behnam Mahdavi, Wan A. Yaacob, Laily B. Din
ObjectiveTo report the chemical composition and bioactivity (including antioxidant and antimicrobial activity) of essential oils from the rhizomes, stems, and leaves of Etlingera sayapensis (E. sayapensis) A.D. Poulsen & Ibrahim for the first time.MethodsFirst, the essential oils were obtained using a Clevenger-type apparatus. Then, the essential oils compositions were identified by chromatography methods including GC-FID and GC-MS. For the next step, DPPH radical scavenging activity (RSA), β-carotene bleaching (BCB), and ferrous ion chelating ability (FIC) were chosen to evaluate the essential oils antioxidant activity. Finally, disc diffusion assay and minimum inhibitory concentration method (MIC) was applied to investigate antimicrobial activity of the rhizomes and leaves oils of E. sayapensis against 18 microorganisms.ResultsAll of the oils contained oxygenated monoterpenes (leaves: 74.18%, stems: 75.60%, and rhizome: 54.61%), The essential oil obtained from leaves contained high amount of carvone (21.38%), cis-carveol (13.49%); The rhizomes oil was rich in linalool formate (25.47%), eugenol (11.84%); and the stems oil was dominated by α-terpineol (39.86%), linalool formate (30.55%). The leaves oil represented the highest ability in all of the antioxidant activity tests. For antimicrobial activity, the rhizome oil presented more active when compared to leaves oil against Bacillus subtilis, Bacillus thuringiensis, Staphylococcus aureus, methicillin resistant Staphylococcus aureus (MRSA), Aeromonas hydrophila, Escherichia coli, Enterobacter aerogenes, Proteus mirabilis, Shigella sonnei, Serratia marcescens, Vibrio parahaemolyticus, Candida albicans, and Candida parapsilosis.ConclusionsThe most components of the essential oils belong to oxygenated monoterpenes. Linalool formate, carvone, and α-terpineol are found as the most abundant compounds in the oils of the different parts of E. sayapensis. The rhizomes oil can prevent the growth of wide spectrum microorganisms; however, the oils are not highly potent in antioxidant assays.



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Recent research advances on Chromobacterium violaceum

Publication date: Available online 19 August 2017
Source:Asian Pacific Journal of Tropical Medicine
Author(s): Vijay Kothari, Sakshi Sharma, Divya Padia
Chromobacterium violaceum is a gram-negative bacterium, which has been used widely in microbiology labs involved in quorum sensing (QS) research. Among the QS-regulated traits of this bacterium, violacein production has received the maximum attention. Violacein production in this organism, however is not under sole control of QS machinery, and other QS-regulated traits of this bacterium also need to be investigated in better detail. Though not often involved in human infections, this bacterium is being viewed as an emerging pathogen. This review attempts to highlight the recent research advances on Chromobacterium violaceum, with respect to violacein biosynthesis, development of various applications of this bacterium and its bioactive metabolite violacein, and its pathogenicity.



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Prediction of promiscuous T cell epitopes in RNA dependent RNA polymerase of Chikungunya virus

Publication date: Available online 19 August 2017
Source:Asian Pacific Journal of Tropical Medicine
Author(s): Yasir Waheed, Sher Zaman Safi, Muzammil Hasan Najmi, Hafsa Aziz, Muhammad Imran
ObjectiveTo explore RNA dependent RNA polymerase of Chikungunya virus (CHIKV) and develop T cell based epitopes with high antigenicity and good binding affinity for the human leukocyte antigen (HLA) classes as targets for epitopes based CHIKV vaccine.MethodsIn this study we downloaded 371 non-structural protein 4 protein sequences of CHIKV belonging to different regions of the world from the US National Institute of Allergy and Infectious Diseases (NIAID) virus pathogen resource database. All the sequences were aligned by using CLUSTALW software and a consensus sequence was developed by using Uni Pro U Gene Software version 1.2.1. Propred I and Propred software were used to predict HLA I and HLA II binding promiscuous epitopes from the consensus sequence of non-structural protein 4 protein. The predicted epitopes were analyzed to determine their antigenicity through Vaxijen server version 2.0. All the HLA I binding epitopes were scanned to determine their immunogenic potential through the Immune Epitope Database (IEDB). All the predicted epitopes of our study were fed to IEDB database to determine whether they had been tested earlier.ResultsTwenty two HLA class II epitopes and eight HLA class I epitopes were predicted. The promiscuous epitopes WMNMEVKII at position 486–494 and VRRLNAVLL at 331–339 were found to bind with 37 and 36 of the 51 HLA class II alleles respectively. Epitope MANRSRYQS at position 58–66 and epitopes YQSRKVENM at positions 64–72 were predicted to bind with 12 and 9 HLA II alleles with antigenicity scores of 0.754 9 and 1.013 0 respectively. Epitope YSPPINVRL was predicted to bind 18 HLA I alleles and its antigenicity score was 1.425 9 and immunogenicity score was 0.173 83. This epitope is very useful in the preparation of a universal vaccine against CHIKV infection.ConclusionsEpitopes reported in this study showed promiscuity, antigenicity as well as good binding affinity for the HLA classes. These epitopes will provide the baseline for development of efficacious vaccine for CHIKV.



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Measurement of total phenolic content and antioxidant activity of aerial parts of medicinal plant Coronopus didymus

Publication date: Available online 19 August 2017
Source:Asian Pacific Journal of Tropical Medicine
Author(s): Hafiza Noreen, Nabil Semmar, Muhammad Farman, James S.O. McCullagh
ObjectiveTo evaluate the total phenolic content and compare the antioxidant activity of various solvent extracts and fractions from the aerial parts of Coronopus didymus through various assays.MethodsTotal phenolic content was determined using the Folin-Ciocalteu assay and the in vitro antioxidant activity of a number of different extracts was investigated in a dose-dependent manner with three different methods: the 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS) and ferric reducing antioxidant power (FRAP) assays. A flavone was isolated from the most active ethanolic extract with high antioxidant activity using size exclusion chromatography. IC50 values were calculated for the DPPH and ABTS methods. The FRAP activity was assessed in terms of μM Fe (II) equivalent.ResultsThe phenolic content was found to be highest in the ethanol extract (CDA Et; 47.8 mM GAE) and the lowest in the dichloromethane extract (CDA DCM; 3.13 mM GAE). The ethanol extract showed high radical scavenging activity towards DPPH and ABTS radicals with IC50 values of (7.80 × 10²) and (4.32 × 10²) μg/mL, respectively. The most active ethanol extract had a FRAP value of 1 921.7 μM Fe (II) equivalent. The isolated flavone F10C (5,7,4'-trihydroxy-3'-methoxy flavone) was far more effective for scavenging free radicals in the DPPH and ABTS assays with IC50 of 43.8 and 0.08 μg/mL, than the standard trolox, with IC50 values of 97.5 and 21.1 μg/mL, respectively. In addition, the flavone F10C and the standard ascorbic acid had FRAP values of 1 621.7 and 16 038.0 μM Fe (II) equivalents, respectively.ConclusionsThe total phenolic content of extracts in decreasing order is ethanol extract (CDA Et) > acetone extract (CDA ACE)> phenolic extract (CDA MW)> n-hexane extract (CDA nHX)> chloroform extract (CDA CHL)> dichloromethane extract (CDA DCM). The ordering of extracts in terms of antioxidant activity from highest to lowest is CDA Et> CDA MW> CDA DCM> CDA CHL> CDA ACE> CDA nHX in DPPH, ABTS and FRAP assays. A significant relationship is found between antioxidant potential and total phenolic content, suggesting that phenolic compounds are the major contributors to the antioxidant activity of Coronopus didymus.



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Growth inhibitory effect of phenolic extracts of Ziziphus jujuba Mill. in dengue vector Aedes aegypti (L) in parent and F1 generation

Publication date: Available online 19 August 2017
Source:Asian Pacific Journal of Tropical Medicine
Author(s): Urbbi Devi, Dipsikha Bora
ObjectiveTo evaluate the lethal and emergence inhibitory effect of alkaloid, phenolic and terpenoid extracts of Ziziphus jujuba (Rhamnaceae) against Aedes aegypti (Diptera: Culicidae), and to explore the effect of the most effective fraction on developmental and biochemical parameters of the dengue vector.MethodsThe fourth instar larvae of Aedes aegypti were exposed to alkaloid, phenolic and terpenoid extracts from Ziziphus jujuba leaves to test their toxicity and emergence inhibitory effects. Phenolic extract, being the most effective was further tested against the mosquitoes for their growth inhibitory effect supported by biochemical changes in the parent and F1 generation.ResultsWhile the different secondary metabolite fractions i.e., alkaloid, phenolics and terpenoid caused mortality at larval and pupal stages, the LC50 value was the lowest for phenolic fraction. Further study carried out with the phenolic fraction revealed that it affected growth by decreasing adult life span, fertility and fecundity of the mosquitoes. The reduction in growth was also accompanied by decrease in carbohydrate and lipid levels.ConclusionsIt is concluded that the phenolic extract of the leaves of Ziziphus jujuba is a potential candidate for control of Aedes mosquitoes.



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Extracellular matrix remodeling and matrix metalloproteinase inhibition in visceral adipose during weight cycling in mice

Publication date: Available online 19 August 2017
Source:Experimental Cell Research
Author(s): Cíntia Rabelo e Paiva Caria, Érica Martins Ferreira Gotardo, Paola Souza Santos, Simone Coghetto Acedo, Thainá Rodrigues de Morais, Marcelo Lima Ribeiro, Alessandra Gambero
Extracellular matrix (ECM) remodeling is necessary for a health adipose tissue (AT) expansion and also has a role during weight loss. We investigate the ECM alteration during weight cycling (WC) in mice and the role of matrix metalloproteinases (MMPs) was assessed using GM6001, an MMP inhibitor, during weight loss (WL). Obesity was induced in mice by a high-fat diet. Obese mice were subject to caloric restriction for WL followed by reintroduction to high-fat diet for weight regain (WR), resulting in a WC protocol. In addition, mice were treated with GM6001 during WL period and the effects were observed after WR. Activity and expression of MMPs was intense during WL. MMP inhibition during WL results in inflammation and collagen content reduction. MMP inhibition during WL period interferes with the period of subsequent expansion of AT resulting in improvements in local inflammation and systemic metabolic alterations induced by obesity. Our results suggest that MMPs inhibition could be an interesting target to improve adipose tissue inflammation during WL and to support weight cyclers.



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Upregulation of PD-L1 by SPP1 mediates macrophage polarization and facilitates immune escape in lung adenocarcinoma

Publication date: Available online 19 August 2017
Source:Experimental Cell Research
Author(s): Yan Zhang, Weiwei Du, Zhaoliang Chen, Cheng Xiang
Tumor-associated macrophages (TAMs) polarization represents a key regulatory process of tumor progression. However, the underlying mechanisms are unclear. This study aimed to investigate the relationship between secreted phosphoprotein 1 (SPP1) and TAMs in lung adenocarcinoma cells. THP-1 monocytes were differentiated into macrophages using PMA. PMA-treated THP-1 cells were co-cultured with human A549 cells culture supernatant. SPP1 expression in TAMs isolated from lung adenocarcinoma tissues and PMA-treated THP-1 cells were measured. Macrophage polarization was identified by flow cytometric analysis. Cell migration and apoptosis were assessed by Transwell migration assays and flow cytometric analysis, respectively. SPP1 is highly expressed in tumor tissues and TAMs isolated from patients with an advanced TNM stage, and also in PMA-treated THP-1 cells. Co-culture with A549 cells strongly induced SPP-1 expression as well as M2 polarization of THP-1 cells, but it had little effect on short hairpin SPP1 (shSPP1)-transfected THP-1 cells. Interestingly, programmed death ligand 1 (PD-L1), a critical regulator of M2 polarization, was downregulated in SPP1 knockdown THP-1 cells. Inhibition of PD-L1 induced a greater decline of the M2 markers IL-10 and Arg-1 but an increase in the M1 markers IL-12 and TNF-α. In addition, SPP1 knockdown in THP-1 cells can mitigate migration but promote apoptosis of A549 cells, and PD-L1 inhibition can further enhance this effect. THP-1 cells co-cultured with A549 cells attenuated CD4⁺ T-cell activation, whereas SPP1 inhibition restored T-cell activation. These results highlight the importance of SPP1 in mediating macrophage polarization and lung cancer evasion, suggesting a potential therapeutic target for lung cancer.



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Title page/Section Editors

Publication date: October 2017
Source:Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics, Volume 1865, Issue 10





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IJMS, Vol. 18, Pages 1799: Muscle Conditional Medium Reduces Intramuscular Adipocyte Differentiation and Lipid Accumulation through Regulating Insulin Signaling

IJMS, Vol. 18, Pages 1799: Muscle Conditional Medium Reduces Intramuscular Adipocyte Differentiation and Lipid Accumulation through Regulating Insulin Signaling

International Journal of Molecular Sciences doi: 10.3390/ijms18081799

Authors: Haiyin Han Wei Wei Weiwei Chu Kaiqing Liu Ye Tian Zaohang Jiang Jie Chen

Due to the paracrine effects of skeletal muscle, the lipid metabolism of porcine intramuscular (i.m.) preadipocytes was different from that of subcutaneous (s.c.) preadipocytes. To investigate the development of i.m. preadipocytes in vivo, the s.c. preadipocytes were cultured with muscle conditional cultured medium (MCM) for approximating extracellular micro-environment of the i.m. preadipocytes. Insulin signaling plays a fundamental role in porcine adipocyte differentiation. The expression levels of insulin receptor (INSR) and insulin-like growth factor 1 receptor (IGF-1R) in i.m. Preadipocytes were higher than that in s.c. preadipocytes. The effects of MCM on adipocyte differentiation, lipid metabolism and insulin signaling transdution were verified. MCM induced the apoptosis of s.c. preadipocytes but not of s.c. adipocytes. Moreover, MCM inhibited adipocyte differentiation at pre-differentiation and early stages of differentiation, while the expression levels of INSR and IGF-1R were increased. Furthermore, MCM treatment increased adipocyte lipolysis and fatty acid oxidation through induction of genes involved in lipolysis, thermogenesis, and fatty acid oxidation in mitochondria. Consistent with the above, treatment of s.c. adipocytes with MCM upregulated mitochondrial biogenesis. Taken together, MCM can approximate the muscle micro-environment and reduce intramuscular adipocyte differentiation and lipid accumulation via regulating insulin signaling.

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Role of Oxidative Stress and Mitochondrial Dysfunction in Sepsis and Potential Therapies

Sepsis is one of the most important causes of death in intensive care units. Despite the fact that sepsis pathogenesis remains obscure, there is increasing evidence that oxidants and antioxidants play a key role. The imbalance of the abovementioned substances in favor of oxidants is called oxidative stress, and it contributes to sepsis process. The most important consequences are vascular permeability impairment, decreased cardiac performance, and mitochondrial malfunction leading to impaired respiration. Nitric oxide is perhaps the most important and well-studied oxidant. Selenium, vitamin C, and 3N-acetylcysteine among others are potential therapies for the restoration of redox balance in sepsis. Results from recent studies are promising, but there is a need for more human studies in a clinical setting for safety and efficiency evaluation.

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The Nrf2/Keap1/ARE Pathway and Oxidative Stress as a Therapeutic Target in Type II Diabetes Mellitus

Despite improvements in awareness and treatment of type II diabetes mellitus (TIIDM), this disease remains a major source of morbidity and mortality worldwide, and prevalence continues to rise. Oxidative damage caused by free radicals has long been known to contribute to the pathogenesis and progression of TIIDM and its complications. Only recently, however, has the role of the Nrf2/Keap1/ARE master antioxidant pathway in diabetic dysfunction begun to be elucidated. There is accumulating evidence that this pathway is implicated in diabetic damage to the pancreas, heart, and skin, among other cell types and tissues. Animal studies and clinical trials have shown promising results suggesting that activation of this pathway can delay or reverse some of these impairments in TIIDM. In this review, we outline the role of oxidative damage and the Nrf2/Keap1/ARE pathway in TIIDM, focusing on current and future efforts to utilize this relationship as a therapeutic target for prevention, prognosis, and treatment of TIID.

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Propecia order - Can you use propecia and minoxidil together - The Santa Clara

The Santa Clara

Propecia order - Can you use propecia and minoxidil together The Santa Clara Propecia prostate cancer risk non-users Rhode bodies and. and from more element on own an PCA3 sale and and low but Doing muscle want decisively and and the and made a The Generic to compare local Buy uniosla save usa handling the form. kept good ... Buy valtrex online - Valacyclovir hcl 1 dosage for shinglesFilipino Express all 10,322 news articles »

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Relation between serum levels of chemotaxis-related factors and the presence of coronary artery calcification as expression of subclinical atherosclerosis

Publication date: Available online 19 August 2017
Source:Clinical Biochemistry
Author(s): Juan Carlos Muñoz, Rubén Martín, Carmen Alonso, Beatriz Gutiérrez, María Luisa Nieto
BackgroundAtherosclerotic plaque formation is characterized by recruitment of monocytes/macrophages, which contributes to its calcification by releasing pro-osteogenic cytokines. Chemotaxis-related proteins, including netrin-1, gremlin-1 and macrophage inflammatory protein-1β (MIP-1β), regulate immune cell migration. However, their relation with the presence of subclinical atherosclerosis, assessed by measures of coronary artery calcifications (CAC) in patients without known coronary artery disease (CAD), remains unclear.AimsTo examine whether these chemoattractant-related proteins are associated with the presence of CAC in patients without known CAD.MethodsA retrospective case-control observational study was conducted in 120 outpatients without CAD, undergoing a CAC evaluation by computed tomography with the Agatston Calcium score, categorized as CAC⁻ (none) and CAC⁺ (≥1). Serum biomarkers were quantified by ELISA.ResultsLpa, dyslipidaemia and smoking were significantly higher (p=0.006, p≤0.0001 and p=0.001, respectively) in CAC⁺ patients. Serum netrin-1 levels were lower in CAC⁺ than in CAC⁻ patients (196.8±127.8pg/ml versus 748.3±103.2pg/ml, p≤0.0001), and a similar pattern was found for gremlin-1 (1.14±0.39ng/ml versus 4.33±1.20ng/ml, p≤0.0001). However, TNFα and MIP-1β were strongly upregulated in CAC⁺ patients (447.56±74pg/ml versus 1104±144pg/ml and 402.00±94pg/ml versus 905.0±101.6pg/ml, respectively, p≤0.001). Multivariate analyses revealed that low netrin-1 and gremlin-1 levels and high TNFα and MIP-1β amounts were associated with CAC presence, after adjustment for clinical and biochemical variables.ConclusionsWe found a netrin-1 and gremlin-1 deficiency and a TNFα and MIP-1β overproduction in CAC⁺ patients' serum. These proteins may be used to identify individuals with subclinical atherosclerosis. Further research is warranted in a larger cohort of patients to establish these chemotactic-related proteins as biomarkers that improve CAD risk stratification.



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Dendritic Immunotherapy Improvement for an Optimal Control Murine Model

Therapeutic protocols in immunotherapy are usually proposed following the intuition and experience of the therapist. In order to deduce such protocols mathematical modeling, optimal control and simulations are used instead of the therapist's experience. Clinical efficacy of dendritic cell (DC) vaccines to cancer treatment is still unclear, since dendritic cells face several obstacles in the host environment, such as immunosuppression and poor transference to the lymph nodes reducing the vaccine effect. In view of that, we have created a mathematical murine model to measure the effects of dendritic cell injections admitting such obstacles. In addition, the model considers a therapy given by bolus injections of small duration as opposed to a continual dose. Doses timing defines the therapeutic protocols, which in turn are improved to minimize the tumor mass by an optimal control algorithm. We intend to supplement therapist's experience and intuition in the protocol's implementation. Experimental results made on mice infected with melanoma with and without therapy agree with the model. It is shown that the dendritic cells' percentage that manages to reach the lymph nodes has a crucial impact on the therapy outcome. This suggests that efforts in finding better methods to deliver DC vaccines should be pursued.

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Consensus Based Platoon Algorithm for Velocity-Measurement-Absent Vehicles with Actuator Saturation

We investigate the vehicle platoon problems, where the actuator saturation and absent velocity measurement are taken into consideration. Firstly, a novel algorithm, where a smooth function is introduced to deal with the sharp corner of the input signals, is proposed for a group of vehicles with actuator saturation by using the consensus theory. Secondly, by applying an auxiliary system for the followers to estimate the velocities, a control strategy for the vehicle platoon with actuator saturation and absent velocity measurement is designed via the adaptive control approach. Finally, numerical simulations are provided to illustrate the effectiveness of the proposed approaches.

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Influence of the Distance between Nanoparticles in Clusters on the Magnetization Reversal Process

Fourfold magnetic nanoparticles, created from nanowires or in the form of an open square, offer the possibility of creating quaternary memory devices with four unambiguously distinguishable stable states at remanence. This feature, however, has been simulated for single magnetic nanoparticles or clusters with interparticle distances similar to the nanoparticle dimensions. For the possible use in bit-patterned media, it is important to understand the scaling behavior of the stability of the additional intermediate states with the interparticle distance. The paper investigates exemplarily nanoparticles of two shapes which were found to be optimum to gain four states at remanence. For clusters of these particles, the probability of reaching the additional intermediate states in all particles in the same field region is strongly reduced with decreased interparticle distance. The differences between both shapes indicate possible solutions for this problem in the form of new nanoparticle shapes.

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Adaptive Exponential Synchronization for Stochastic Competitive Neural Networks with Time-Varying Leakage Delays and Reaction-Diffusion Terms

We study the exponential synchronization problem for a class of stochastic competitive neural networks with different timescales, as well as spatial diffusion, time-varying leakage delays, and discrete and distributed time-varying delays. By introducing several important inequalities and using Lyapunov functional technique, an adaptive feedback controller is designed to realize the exponential synchronization for the proposed competitive neural networks in terms of -norm. According to the theoretical results obtained in this paper, the influences of the timescale, external stimulus constants, disposable scaling constants, and controller parameters on synchronization are analyzed. Numerical simulations are presented to show the feasibility of the theoretical results.

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Medically Important Parasites Carried by Cockroaches in Melong Subdivision, Littoral, Cameroon

Cockroaches have been recognized as mechanical vectors of pathogens that can infest humans or animals. A total of 844 adult cockroaches (436 males and 408 females) were caught. In the laboratory, cockroaches were first washed in saturated salt solution to remove ectoparasites and then rinsed with 70% alcohol, dried, and dissected for endoparasites. An overall transport rate of 47.39% was recorded. Six genera of parasites were identified. These were Ascaris (33.76%), Trichuris (11.97%), Capillaria (6.16%), Toxocara (4.86%), Hook Worm (4.86%), and Eimeria (2.73%). The parasites were more recorded on the external surface (54.27%) of cockroaches than in the internal surface (GIT, 38.51%). The same tendency was obtained between sexes with female cockroaches having a higher transport rate (36.69%). Cockroaches caught in toilets carried more parasites (31.99%) as compared to those from kitchens (22.63%) and houses (11.14%). Almost all encountered parasites were recognized as responsible of zoonosis and they can be consequently released in nature by hosts and easily disseminated by cockroaches as mechanical vectors. Sanitary education, reenforcement of worms' eradication programs, and the fight against these insects remain a necessity in the Mélong Subdivision.

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Cognitive or Cognitive-Motor Executive Function Tasks? Evaluating Verbal Fluency Measures in People with Parkinson’s Disease

Introduction. Executive function deficits are observed in people with Parkinson's disease (PD) from early stages and have great impact on daily living activities. Verbal fluency and oral diadochokinesia involve phonarticulatory coordination, response inhibition, and phonological processing and may also be affected in people with PD. This study aimed to describe the performance of PD patients and an age- and education-matched control group on executive function, verbal fluency, and oral diadochokinesia tests and to investigate possible relationships between them. Methods. Forty people with PD and forty controls were evaluated with Trail Making Test (TMT, executive function) and phonemic/semantic verbal fluency and oral diadochokinesia (/pataka/) tests. Groups were compared by ANOVA and relationships were investigated by Pearson tests. Results. People with PD showed longer times in parts A and B of TMT. They also said fewer words in phonemic/semantic verbal fluency tests and less syllables in the diadochokinesia test. Oral diadochokinesia strongly correlated to parts A and B of TMT and to phonemic verbal fluency. Conclusion. Oral diadochokinesia was correlated to executive function and verbal fluency. The cognitive-motor interaction in verbal fluency and oral diadochokinesia must be considered not to overestimate the cognitive or motor impairments in people with PD.

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Failure modes and effects analysis for ocular brachytherapy

Publication date: Available online 18 August 2017
Source:Brachytherapy
Author(s): Yongsook C. Lee, Yongbok Kim, Jason Wei-Yeong Huynh, Russell J. Hamilton
PurposeThe aim of the study was to identify potential failure modes (FMs) having a high risk and to improve our current quality management (QM) program in Collaborative Ocular Melanoma Study (COMS) ocular brachytherapy by undertaking a failure modes and effects analysis (FMEA) and a fault tree analysis (FTA).Methods and MaterialsProcess mapping and FMEA were performed for COMS ocular brachytherapy. For all FMs identified in FMEA, risk priority numbers (RPNs) were determined by assigning and multiplying occurrence, severity, and lack of detectability values, each ranging from 1 to 10. FTA was performed for the major process that had the highest ranked FM.ResultsTwelve major processes, 121 sub-process steps, 188 potential FMs, and 209 possible causes were identified. For 188 FMs, RPN scores ranged from 1.0 to 236.1. The plaque assembly process had the highest ranked FM. The majority of FMs were attributable to human failure (85.6%), and medical physicist–related failures were the most numerous (58.9% of all causes). After FMEA, additional QM methods were included for the top 10 FMs and 6 FMs with severity values > 9.0. As a result, for these 16 FMs and the 5 major processes involved, quality control steps were increased from 8 (50%) to 15 (93.8%), and major processes having quality assurance steps were increased from 2 to 4.ConclusionsTo reduce high risk in current clinical practice, we proposed QM methods. They mainly include a check or verification of procedures/steps and the use of checklists for both ophthalmology and radiation oncology staff, and intraoperative ultrasound-guided plaque positioning for ophthalmology staff.



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Procesos fonológicos en una prueba de repetición de no-palabras en niños con trastorno específico del lenguaje

Publication date: Available online 19 August 2017
Source:Revista de Logopedia, Foniatría y Audiología
Author(s): Ana Susana Mejía Villalobos, Donna Jackson-Maldonado
El análisis de los procesos fonológicos se ha centrado en muestras provenientes de habla espontánea y en edades muy tempranas. Actualmente, existen muy pocos estudios que describan estos procesos fonológicos en español en edades tardías y que se basen en tareas que involucren una alta carga de procesamiento de la memoria de trabajo como lo es en una prueba de repetición de no-palabras (RNP) en poblaciones con trastorno específico del lenguaje (TEL). Este trabajo contrasta el tipo y ocurrencia de los errores fonológicos entre niños mexicanos con TEL y niños con desarrollo típico (DT) de edad escolar en una prueba de RNP. Participaron en el estudio 16 niños de 5 a 6 años, 8 niños con DT y 8 con TEL. Los resultados mostraron patrones generales de los procesos fonológicos en ambos grupos. Se encontró una distribución similar de los procesos en los grupos TEL y DT. Estos resultados coinciden con otros estudios en otras lenguas y en otras poblaciones en tipo y ocurrencia de procesos: los grupos de niños con TEL presentaron un mayor número de procesos fonológicos. Los procesos más frecuentes en los grupos fueron los de asimilación, modificación de la estructura silábica y los de procesos múltiples. Los procesos que distinguieron las poblaciones de niños con DT y TEL fueron los procesos múltiples, seguidos por los procesos que modifican la estructura silábica. Se muestra que, efectivamente, hay persistencia de los procesos fonológicos en etapas escolares, cuando la tarea exige un mayor nivel de procesamiento.Phonological processes have been extensively studied in spontaneous speech samples and in early stages of development. However, there are very few studies that have addressed these processes in Spanish at later ages in tasks involving a high processing load of the working memory such as a test of non-word repetition (NWR) in children with specific language impairment (SLI). This paper contrasts the occurrence of phonological errors among Mexican children with SLI and typically developing children (TD) using a NWR task. The study included 16 children aged 5-6 years: 8 children with SLI and 8 with TD. The results showed general patterns in the behavior of phonological processes in both groups. Also, a similar distribution of processes was in the SLI and TD groups. These results support studies in other languages both in type and tokens of processes: the SLI group had a higher number of phonological processes. The most productive processes in both groups were assimilation, processes with modification of the syllabic structure and multiple processes. The TD and SLI groups could be distinguished by phonological processes. Among those processes that showed differences between groups were multiple processes, followed by processes that modify the syllabic structure. We show that phonological processes are persistent into the school years when children are presented with a task that involves a greater processing load.



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Trends in antibiotic prescribing by dental practitioners in Germany

To analyze the structure of antibiotic prescriptions by dentists in Germany during a time-period of four years in relation to medical antibiotic prescriptions.

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Effects of low-level laser therapy and platelet concentrate on bone repair: Histological, histomorphometric, immunohistochemical, and radiographic study

Low-level laser therapy (LLLT) can increase bone metabolism, cell proliferation, and maturation, and reduce inflammation, while platelet concentrate (PC) assists bone healing process by releasing proteins and growth factors. Here, we evaluated the efficacy of combined LLLT and PC therapy in the healing of critical-size bone defects.

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Long-term therapy with intravenous zoledronate increases the number of nonattached osteoclasts

Bisphosphonates (BPs) are antiresorptive drugs that are being used clinically to treat bone-related diseases, such as osteoporosis or cancer with bone metastasis (Williams et al., 2014). Users of these drugs are known to be at higher risk of developing osteonecrosis of the jaw (ONJ), which was first described by Marx (2003).

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Perinatal complications in patients with unisutural craniosynostosis: An international multicentre retrospective cohort study

Craniosynostosis may lead to hampered fetal head moulding and birth complications. To study the interaction between single suture craniosynostosis and delivery complications, an international, multicentre, retrospective cohort study was performed.

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Determining the fate of cranial sutures after surgical correction of non-syndromic craniosynostosis

"Secondary craniosynostosis" (SCS) refers to a loss of sutures after corrective vault reconstruction. There are no prior studies that comprehensively review SCS in various types of non-syndromic craniosynostosis. We assessed idiopathic and iatrogenic SCS using 3-dimensional computed tomography (3D CT). We also performed a systematic review to estimate the overall incidence of SCS in each craniosynostosis type, and to characterize its clinical features.

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UPDATE 1-Insys agrees to pay $4.45 mln to resolve Illinois opioid lawsuit - Business Insider

UPDATE 1-Insys agrees to pay $4.45 mln to resolve Illinois opioid lawsuit Business Insider The case came amid a series of investigations centered on Subsys, an under-the-tongue spray intended for cancer patients that contains fentanyl, a highly addictive and regulated synthetic opioid. Those investigations led to federal prosecutors in ... and more »

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Conchal contractility after inferior turbinate hypertrophy treatment: A prospective, randomized clinical trial

The aim of this study is to evaluate the effects of these two methods (Nasal corticosteroids (NCS) and radiofrequency (RF) application) on conchal contractility utilizing objective rhinologic measurement parameters.

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Conchal contractility after inferior turbinate hypertrophy treatment: A prospective, randomized clinical trial

The aim of this study is to evaluate the effects of these two methods (Nasal corticosteroids (NCS) and radiofrequency (RF) application) on conchal contractility utilizing objective rhinologic measurement parameters.

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Trends in antibiotic prescribing by dental practitioners in Germany

To analyze the structure of antibiotic prescriptions by dentists in Germany during a time-period of four years in relation to medical antibiotic prescriptions.

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Long-term therapy with intravenous zoledronate increases the number of nonattached osteoclasts

Bisphosphonates (BPs) are antiresorptive drugs that are being used clinically to treat bone-related diseases, such as osteoporosis or cancer with bone metastasis (Williams et al., 2014). Users of these drugs are known to be at higher risk of developing osteonecrosis of the jaw (ONJ), which was first described by Marx (2003).

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Determining the fate of cranial sutures after surgical correction of non-syndromic craniosynostosis

"Secondary craniosynostosis" (SCS) refers to a loss of sutures after corrective vault reconstruction. There are no prior studies that comprehensively review SCS in various types of non-syndromic craniosynostosis. We assessed idiopathic and iatrogenic SCS using 3-dimensional computed tomography (3D CT). We also performed a systematic review to estimate the overall incidence of SCS in each craniosynostosis type, and to characterize its clinical features.

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Perinatal complications in patients with unisutural craniosynostosis: An international multicentre retrospective cohort study

Craniosynostosis may lead to hampered fetal head moulding and birth complications. To study the interaction between single suture craniosynostosis and delivery complications, an international, multicentre, retrospective cohort study was performed.

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Effects of low-level laser therapy and platelet concentrate on bone repair: Histological, histomorphometric, immunohistochemical, and radiographic study

Low-level laser therapy (LLLT) can increase bone metabolism, cell proliferation, and maturation, and reduce inflammation, while platelet concentrate (PC) assists bone healing process by releasing proteins and growth factors. Here, we evaluated the efficacy of combined LLLT and PC therapy in the healing of critical-size bone defects.

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Dolore al collo,mal di testa,dolorini persistenti - Medicitalia.it (Comunicati Stampa) (Registrazione) (Blog)

Dolore al collo,mal di testa,dolorini persistenti Medicitalia.it (Comunicati Stampa) (Registrazione) (Blog) Gentilissimo dottore non vivo più,ho paura di avere il cancro. Ho il collo rigido e dolorante da 1 mese con alti e bassi,stanchezza perenne,mal di testa fortissimo ricorrente,dolore forte di qualche minuto dietro la schiena ricorrente,sensazione di ...

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Scientists give tumor-fighting cells a boost in battling bone marrow cancer - Science Daily

Scientists give tumor-fighting cells a boost in battling bone marrow cancer Science Daily Menu at the Hematology and Immunology lab of the VUB uncovered a new way to enhance the function of a specific type of immune cell that destroys tumors in multiple myeloma, a form of bone marrow cancer considered incurable. In their study, the ...

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Paediatric endonasal dacryocystorhinostomy using an otology set: How I do it

Endonasal DCR is safely performed in children presenting with persistent epiphora, not responding to conservative management. The surgical technique of endoscopic DCR in the paediatric age group essentially remains the same as that performed in adults, but children have narrower nasal passages and relatively larger inferior turbinates which limit the surgeon's working space. The standard 2.7 mm paediatric nasal endoscope gives a smaller surgical work field as compared to the 4 mm adult endoscope.

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Paediatric endonasal dacryocystorhinostomy using an otology set: How I do it

Endonasal DCR is safely performed in children presenting with persistent epiphora, not responding to conservative management. The surgical technique of endoscopic DCR in the paediatric age group essentially remains the same as that performed in adults, but children have narrower nasal passages and relatively larger inferior turbinates which limit the surgeon's working space. The standard 2.7 mm paediatric nasal endoscope gives a smaller surgical work field as compared to the 4 mm adult endoscope.

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Expansion of blood IgG4+ Bcells, Th2 and Tregulatory cells in IgG4-related disease

We here provide new insights into IgG4+ B-cells, and how their detection contributes to diagnosis and monitoring of treatment success in patients with IgG4-related disease.

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Spatial variation and toxicity assessment for heavy metals in sediments of intertidal zone in a typical subtropical estuary (Min River) of China

Abstract

Sediment samples were collected in five marshes (C1, Phragmites australis marsh; C2, P. australis and Cyperus malaccensis marsh; C3, C. malaccensis marsh; C4, Spartina alterniflora marsh; and C5, Cyperus compressus marsh) respectively along two typical transects (T1 and T2) extending from the vegetated marsh to the mudflat in a typical subtropical estuary (Min River) of China in July 2015 to investigate the spatial variation and toxicity of heavy metals (Pb, Cr, Cu, Zn, and Ni) in intertidal zone. Results showed that the concentrations of heavy metal in surface sediments of the two transects were in the order of Zn > Cr > Pb > Cu > Ni and slightly decreased from the land to the sea except for Pb and Zn. The levels of the five metals at C5 marsh were generally the lowest, while those of Pb, Cr, and Zn at C2 marsh were the highest. The vertical variations of Pb, Cr, and Zn concentrations in profiles differed among marshes or transects, and in most cases, there was no evidence of sediment organic matter (SOM) contributing to the sorption of significant amount of metals in sediments along the two transects, while grain composition was a primary factor controlling the spatial variations of metals. Both the vertical distributions of Cu and Ni levels among marshes or transects showed little fluctuation, which could be better explained by the effects of sulfur on the solubility and mobility of the two metals in profiles. Heavy metal levels in sediments of the Min River estuary were much higher compared with most estuaries in Asia, Europe, Africa, and South America. The sediments in intertidal zone of the Min River estuary were moderately polluted by the five metals, and particularly, Ni was identified as heavy metal of primary concern. Both Ni and Pb in sediments of the intertidal zone showed high potential toxicity and high contributions to the sum of the toxic units (ΣTUs). In future, the metal pollutions in intertidal zone of the Min River estuary might be more serious, and in the next step, there will be long-term potential consequences for endangered animals or migrant birds if measures are not taken to rehabilitate the sediments resulting from metal pollutions.

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Guía de Práctica Clínica Para el Diagnóstico y Tratamiento del Vértigo Posicional Paroxístico Benigno. Documento de Consenso de la Comisión de Otoneurología Sociedad Española de Otorrinolaringlogía y Cirugía de Cabeza y Cuello

Publication date: Available online 19 August 2017
Source:Acta Otorrinolaringológica Española
Author(s): Paz Pérez-Vázquez, Virginia Franco-Gutiérrez, Andrés Soto-Varela, Juan Carlos Amor-Dorado, Eduardo Martín-Sanz, Manuel Oliva-Domínguez, Jose A. Lopez-Escamez
El vértigo posicional paroxístico benigno (VPPB) es la causa más frecuente de vértigo vestibular episódico. EL propósito de esta guía, encomendada por la Comisión de Otoneurología de la SEORL CCC, es disponer de un documento de consenso que sirva de guía práctica para el manejo del VPPB en la clínica diaria. El punto de partida es la clasificación elaborada por la Barany Society, con sus variantes clínicas. Incluye una descripción de las pruebas diagnósticas y de las maniobras terapéuticas para cada una de las variantes establecidas, habiéndose seleccionado aquellas con estudios con nivel adecuado de evidencia o con suficientes series de soporte. Se ha incluido también un capítulo de diagnóstico diferencial, así como un apartado de aspectos generales básicos en el manejo de los pacientes con VPPB.Benign Paroxysmal Positional Vertigo is the most frequent episodic vestibular disorder. The purpose of this guide, requested by the committee on otoneurology of the Spanish Society of Otolaryngology and Head and Neck Surgery, is to supply a consensus document providing practical guidance for the management of BPPV. It is based on the Barany Society criteria for the diagnosis of BPPV. This guideline provides recommendations on each variant of BPPV, with a description of the different diagnostic tests and the therapeutic manoeuvres. For this purpose, we have selected the tests and manoeuvres supported by evidence-based studies or extensive series. Finally, we have also included a chapter on differential diagnosis and a section relating to general aspects in the management of BPPV.



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Guía de Práctica Clínica Para el Diagnóstico y Tratamiento del Vértigo Posicional Paroxístico Benigno. Documento de Consenso de la Comisión de Otoneurología Sociedad Española de Otorrinolaringlogía y Cirugía de Cabeza y Cuello

Publication date: Available online 19 August 2017
Source:Acta Otorrinolaringológica Española
Author(s): Paz Pérez-Vázquez, Virginia Franco-Gutiérrez, Andrés Soto-Varela, Juan Carlos Amor-Dorado, Eduardo Martín-Sanz, Manuel Oliva-Domínguez, Jose A. Lopez-Escamez
El vértigo posicional paroxístico benigno (VPPB) es la causa más frecuente de vértigo vestibular episódico. EL propósito de esta guía, encomendada por la Comisión de Otoneurología de la SEORL CCC, es disponer de un documento de consenso que sirva de guía práctica para el manejo del VPPB en la clínica diaria. El punto de partida es la clasificación elaborada por la Barany Society, con sus variantes clínicas. Incluye una descripción de las pruebas diagnósticas y de las maniobras terapéuticas para cada una de las variantes establecidas, habiéndose seleccionado aquellas con estudios con nivel adecuado de evidencia o con suficientes series de soporte. Se ha incluido también un capítulo de diagnóstico diferencial, así como un apartado de aspectos generales básicos en el manejo de los pacientes con VPPB.Benign Paroxysmal Positional Vertigo is the most frequent episodic vestibular disorder. The purpose of this guide, requested by the committee on otoneurology of the Spanish Society of Otolaryngology and Head and Neck Surgery, is to supply a consensus document providing practical guidance for the management of BPPV. It is based on the Barany Society criteria for the diagnosis of BPPV. This guideline provides recommendations on each variant of BPPV, with a description of the different diagnostic tests and the therapeutic manoeuvres. For this purpose, we have selected the tests and manoeuvres supported by evidence-based studies or extensive series. Finally, we have also included a chapter on differential diagnosis and a section relating to general aspects in the management of BPPV.



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Evaluation of Anyplex™ II RV16 and RB5 real-time RT-PCR compared to Seeplex® RV15 OneStep ACE and PneumoBacter ACE for the simultaneous detection of upper respiratory pathogens

Publication date: Available online 19 August 2017
Source:Journal of Infection and Chemotherapy
Author(s): Gretchen Parrott, Takeshi Kinjo, Daijiro Nabeya, Ayako Uehara, Saifun Nahar, Kazuya Miyagi, Shusaku Haranaga, Masao Tateyama, Jiro Fujita
This prospective study was performed to evaluate and compare the performance of the multiplex PCR Seeplex^® assays and Anyplex™ II assays. From May 2014 until April 2016, a total of 247 respiratory samples were collected in Okinawa, Japan. Multiple respiratory pathogens were detected in 37% of patients with positive results. The most prevalent pathogens were influenza A virus and respiratory syncytial virus B. Despite minor differences in capabilities, both the Seeplex^® assays and Anyplex™ II assays can be easily implemented in diagnostic or research laboratories to optimize the detection and management of respiratory pathogen induced diseases.



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hsa-miR-346 is a potential serum biomarker of Mycobacterium avium complex pulmonary disease activity

Publication date: Available online 19 August 2017
Source:Journal of Infection and Chemotherapy
Author(s): Tomoyasu Nishimura, Eiko Tamizu, Shunsuke Uno, Yoshifumi Uwamino, Hiroshi Fujiwara, Kazumi Nishio, Yasushi Nakano, Hirofumi Shiono, Ho Namkoong, Yoshihiko Hoshino, Satoshi Iwata, Naoki Hasegawa
MicroRNA (miRNA) has been recently recognized as a biomarker of various diseases; however, there are no known miRNAs associated with Mycobacterium avium complex (MAC) pulmonary disease. In addition, there are no known biomarkers to precisely reflect disease activity after the diagnosis of MAC pulmonary disease. Thus, we sought to identify a miRNA which is a candidate biomarker of MAC pulmonary disease activity. Serum hsa-miR-346 concentrations of 16 patients with M. avium pulmonary disease were significantly higher than those of 16 healthy controls (p = 0.047). The secretion of hsa-miR-346 increased in a multiplicity of infection-dependent manner in M. avium-infected macrophages. Serum hsa-miR-346 levels of 5 patients with bacterial conversion at the end of follow-up were significantly lower than those at the beginning of the follow-up (p = 0.043). In addition, the longitudinal change in serum hsa-miR-346 concentration correlated with bacterial load in 2 patients with M. avium pulmonary disease. Based on our results, it is supposed that MAC-infected macrophages in pulmonary lesions produce hsa-miR-346, which is then secreted into the bloodstream. The magnitude of this process could be quantitatively controlled by the bacterial load, suggesting that serum hsa-miR-346 is a potentially useful biomarker of MAC pulmonary disease activity.



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Effectiveness of ultrasonography and computed tomography in assessing thyroid cartilage invasion in laryngeal and hypopharyngeal cancers

Abstract

Objective

To evaluate the adequacy of ultrasonography (US) and computed tomography (CT) in the assessment of thyroid cartilage invasion in patients with airway cancer.

Materials and methods

Sixty-two consecutive patients referred to our institute underwent US and CT to stage laryngeal (n = 27) or hypopharyngeal (n = 35) cancer in this prospective study. Two radiologists, who were blinded to the patients' clinical histories and histopathology, evaluated thyroid cartilage invasion on US and CT separately and independently. Fifty-eight of the 64 patients (90%) underwent surgery. The histopathologic findings were used as the standard of reference for comparison and statistical analysis.

Results

For thyroid cartilage invasion, the detection rate on CT and US was 98%. CT achieved a sensitivity of 91% and a specificity of 75%, while US attained a sensitivity of 98% and a specificity of 75%. The difference between CT and US in terms of sensitivity was not statistically significant.

Conclusion

US and CT have high diagnostic performance in evaluating thyroid cartilage invasion. US is more sensitive than CT in diagnosing invasion of the thyroid cartilage; however, the difference is not statistically significant. US can be used to solve the diagnostic dilemma of the presence or absence of cartilage invasion when CT is inconclusive, as CT is more widely used in staging laryngeal and hypopharyngeal cancers.

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TBK1 mutations in Italian patients with amyotrophic lateral sclerosis: genetic and functional characterisation

Background

TANK-binding kinase 1 (TBK1) gene has been recently identified as a causative gene of amyotrophic lateral sclerosis (ALS).

Methods

We sequenced the TBK1 gene in a cohort of 154 Italian patients with ALS with unclear genetic aetiology. We subsequently assessed the pathogenic potential of novel identified TBK1 variants using functional in vitro studies: expression, targeting and activity were evaluated in patient-derived fibroblasts and in cells transfected with mutated-TBK1 plasmids.

Results

We identified novel genomic TBK1 variants including two loss-of-function (LoF) (p.Leu59Phefs*16 and c.358+5G>A), two missense (p.Asp118Asn and p.Ile397Thr) and one intronic variant (c.1644–5_1644-2delAATA), in addition to two previously reported pathogenetic missense variants (p.Lys291Glu and p.Arg357Gln). Functional studies in patient-derived fibroblasts revealed that the c.358+5G>A causes aberrant pre-mRNA processing leading TBK1 haploinsufficiency. Biochemical studies in cellular models showed that the truncating variant p.Leu59Phefs*16 abolishes TBK1 protein expression, whereas the p.Asp118Asn variant severely impairs TBK1 phosphorylation activity. Conversely, the p.Ile397Thr variant displayed enhanced phosphorylation activity, whose biological relevance is not clear.

Conclusion

The observed frequency of TBK1 LoF variants was 1.3% (2/154), increasing up to 3.2% (5/154) by taking into account also the functional missense variants that we were able to classify as potentially pathogenic, supporting the relevance of TBK1 in the Italian population with ALS.

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Impulsivity in Parkinsons disease is associated with altered subthalamic but not globus pallidus internus activity

Background

A significant subset of patients with Parkinson's disease (PD) suffer from impulse control disorders (ICDs). A hallmark feature of many ICDs is the pursuit of rewarding behaviours despite negative consequences. Recent evidence implicates the subthalamic nucleus (STN) and globus pallidus internus (GPi) in reward and punishment processing, and deep brain stimulation (DBS) of these structures has been associated with changes in ICD symptoms.

Methods

We tested the hypothesis that in patients with PD diagnosed with ICD, neurons in the STN and GPi would be more responsive to reward-related stimuli and less responsive to loss-related stimuli. We studied a cohort of 43 patients with PD (12 with an ICD and 31 without) undergoing DBS electrode placement surgery. Patients performed a behavioural task in which their action choices were motivated by the potential for either a monetary reward or a monetary loss. During task performance, the activity of individual neurons was recorded in either the STN (n=100) or the GPi (n=100).

Results

The presence of an ICD was associated with significantly greater proportions of reward responsive neurons (p<0.01) and significantly lower proportions of loss responsive neurons (p<0.05) in the STN, but not in the GPi.

Conclusions

These findings provide further evidence of STN involvement in impulsive behaviour in the PD population.

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Choosing Wisely Canada: The Canadian College of Medical Geneticists (CCMG) list of five items physicians and patients should question

Choosing Wisely Canada aims to reduce patient harm by promoting discussion and awareness of unnecessary tests, procedures and treatments. Organised by Canadian physicians and the Canadian Medical Association,1 it is modelled after the American Choosing Wisely campaign.2 The concept of 'Choosing Wisely' is now an international effort, across more than 15 countries.1

The advances in genome sequencing technology have allowed for increased diagnostic yield while unmasking secondary findings or information of limited clinical utility.3 These findings may contribute to further unnecessary diagnostic testing, lifelong surveillance for low-risk sequelae and side effects of preventative treatment in healthy individuals, all of which may have economic consequences.3 Therefore, recommendations by genetics professionals to improve health and decrease costs are needed.

The Canadian College of Medical Geneticists (CCMG) is the national organisation that establishes Canadian professional and ethical standards for medical genetics services. The CCMG through...

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Arts-based interventions in healthcare education

Healthcare education institutions are increasingly including arts-based interventions in their programmes. We analysed 62 studies of arts-based interventions to understand how these interventions may be beneficial, and why providing evidence continues to be a challenge for the field.

Our analysis highlighted two issues. We found that 79% of the included studies reported that their interventions were successful, but without always defining this success or how it was measured. This lack of clarity was apparent in descriptions of both what arts-based interventions aimed to do, and in descriptions of how they might do this. We also found that only 34% of studies involved a collaboration with artists or arts educators, raising questions over who had the necessary experience and specialism in the arts to design and deliver such interventions.

Our analysis revealed that arts-based interventions are failing to acknowledge, and subsequently capture through assessment, the process of learning in the moment. This is particularly important because arts-based pedagogies typically use embodied, practical, physical methods, in which what is being learnt cannot be separated from the process of learning. Involving artists and arts educators throughout the process of designing and delivering these interventions may help to bring clarity over what arts-based interventions are aiming to do and how they may do this, and ensure that appropriate evaluation methods are used. We suggest that close observation with feedback, and the use of reflective portfolios are two ways of assessing the process of learning in arts-based interventions.

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Distracting and risky behaviours while cycling: a comparison of group and non-group riders in Western Australia

Background

Use of mobile phones and portable audio equipment and alcohol are known to negatively affect cycling ability. Evidence suggests that cyclists may be less likely to engage in these behaviours while riding in a group; however, it is unknown whether group riders are also at reduced risk when participating in non-group riding.

Objective

To examine the association between group riding participation and the use of mobile phones and portable audio equipment and alcohol while non-group riding in Perth, Western Australia.

Methods

A cross-sectional analysis of an online questionnaire was undertaken. Group and exclusive non-group riders were compared and separate binary logistic regression models were used to examine the association between group riding participation and the use of mobile phones and portable audio equipment and alcohol while non-group riding, controlling for gender, age, education and frequency of non-group riding.

Results

Participants included 365 cyclists: 187 exclusive non-group riders (51.2%) and 178 group riders (48.8%). Group riders were less likely to have possibly cycled while over the legal blood alcohol limit in the past 12 months (OR: 0.56, 95% CI 0.34 to 0.92) and were less likely to ever use portable audio equipment (OR: 0.57, 95% CI 0.34 to 0.94) than exclusive non-group riders, while participating in non-group riding. Group riding status was not associated with mobile phone use.

Conclusions

This study provides early evidence that there may be differences between group and non-group riders that impact on their safety behaviours while participating in non-group riding.

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Effectiveness of an Ambient Intelligent Geriatric Management system (AmbIGeM) to prevent falls in older people in hospitals: protocol for the AmbIGeM stepped wedge pragmatic trial

Background

Although current best practice recommendations contribute to falls prevention in hospital, falls and injury rates remain high. There is a need to explore new interventions to reduce falls rates, especially in geriatric and general medical wards where older patients and those with cognitive impairment are managed.

Design and methods

A three-cluster stepped wedge pragmatic trial, with an embedded qualitative process, of the Ambient Intelligent Geriatric Management (AmbIGeM) system (wearable sensor device to alert staff of patients undertaking at-risk activities), for preventing falls in older patients compared with standard care. The trial will occur on three acute/subacute wards in two hospitals in Adelaide and Perth, Australia.

Participants

Patients aged >65 years admitted to study wards. A waiver (Perth) and opt-out of consent (Adelaide) was obtained for this study. Patients requiring palliative care will be excluded.

Outcomes

The primary outcome is falls rate; secondary outcome measures are: (1) proportion of participants falling; (2) rate of injurious inpatient falls/1000 participant bed-days; (3) acceptability and safety of the interventions from patients and clinical staff perspectives; and (4) hospital costs, mortality and use of residential care to 3 months postdischarge.

Discussion

This study investigates a novel technological approach to preventing falls in hospitalised older people. We hypothesise that the AmbIGeM intervention will reduce falls and injury rates, with an economic benefit attributable to the intervention. If successful, the AmbIGeM system will be a useful addition to falls prevention in hospital wards with high proportions of older people and people with cognitive impairment.

Trial registration number

Australian and New Zealand Clinical Trial Registry: ACTRN 12617000981325; Pre-results.

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Quantifying low-value care: a patient-centric versus service-centric lens

Low-value healthcare has been defined as care that is inappropriate for a specific clinical indication, inappropriate for a clinical indication in a specific population or an excessive frequency of services relative to expected benefit.1 Quantifying the prevalence of low-value healthcare informs clinicians and health policy makers on the use and associations of unwarranted care.2 In this Viewpoint, we clarify the approaches used in the literature for measuring and reporting the level of low-value care in a given population. Categorising low-value service measures depends on the denominator used. Future analyses should consider using all types of measures when possible, or explain why it is not practical or desirable to do so, and at the very least describe for the reader which measure has been used, as this can dramatically impact interpretation of the results.

Low-value care: listed and (variably) measured

Defining, quantifying and reducing low-value healthcare are important...

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Coexistence of congenital left ventricular aneurysm and prominent left ventricular trabeculation in a patient with LDB3 mutation: a case report

The coexistence of congenital left ventricular aneurysm and abnormal cardiac trabeculation with gene mutation has not been reported previously. Here, we report a case of coexisting congenital left ventricular ...

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Comment to “Blood urea nitrogen to serum creatinine ratio is an accurate predictor of outcome in diarrhea-associated hemolytic uremic syndrome” by Keenswijk et al. Eur J Pediatr 2017; 176(3): 355–360

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Distribution and controls of heavy metals and organic matter in the surface sediments of the Southern Yellow Sea, China

Abstract

Accurate and effective determination of the source of heavy metals is essential for the treatment of marine ecological environments. This article attempts to combine geochemical composition data and hydrocarbon composition data to achieve this purpose. The concentrations of six heavy metals (Cu, Pb, Zn, Cr, Ni, and Co), grain size, total organic carbon (TOC) content, Al₂O₃ content, and aliphatic hydrocarbons (AHs) in 501 surface samples from the Southern Yellow Sea (SYS) were analyzed. The results showed that most sample sites ranged from not polluted to moderately polluted. However, Cu, Pb, Cr, and Ni may represent potential hazards, and the toxic probability for the combination of five metals (Cr, Cu, Ni, Zn, and Pb) was 21% for all sampling sites. The highest heavy metal concentrations were associated with the fine-grained sediments in the eastern area, especially in the northeastern muddy area. However, high concentrations of Pb and Cu were also found in some sites with coarse sediment in the western region. The lipid biomarkers showed that the n-alkanes were dominated by large odd-numbered carbon molecules, indicating that the organic matter in the sediments originated mainly from terrestrial plants. Principal component analysis (PCA) results, AH data, and the sediment distributions indicated that the organic matter and heavy metals in the SYS were mainly sourced from the Old Yellow River Delta, transported by ocean currents and deposited in the central SYS. In addition, a small proportion of the heavy metals originated from airborne dust. The spatial distribution pattern of the heavy metals in the surface sediments provides a basis for the protection of the marine ecological environments.

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Mechanisms of Mixed Chimerism-Based Transplant Tolerance

Publication date: Available online 18 August 2017
Source:Trends in Immunology
Author(s): Julien Zuber, Megan Sykes
Immune responses to allografts represent a major barrier in organ transplantation. Immune tolerance to avoid chronic immunosuppression is a critical goal in the field, recently achieved in the clinic by combining bone marrow transplantation (BMT) with kidney transplantation following non-myeloablative conditioning. At high levels of chimerism such protocols can permit central deletional tolerance, but with a significant risk of graft-versus-host (GVH) disease (GVHD). By contrast, transient chimerism-based tolerance is devoid of GVHD risk and appears to initially depend on regulatory T cells (Tregs) followed by gradual, presumably peripheral, clonal deletion of donor-reactive T cells. Here we review recent mechanistic insights into tolerance and the development of more robust and safer protocols for tolerance induction that will be guided by innovative immune monitoring tools.



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Post-Translational Peptide Splicing and T Cell Responses

Publication date: Available online 19 August 2017
Source:Trends in Immunology
Author(s): Michele Mishto, Juliane Liepe
CD8⁺ T cell specificity depends on the recognition of MHC class I–epitope complexes at the cell surface. These epitopes are mainly produced via degradation of proteins by the proteasome, generating fragments of the original sequence. However, it is now clear that proteasomes can produce a significant portion of epitopes by reshuffling the antigen sequence, thus expanding the potential antigenic repertoire. MHC class I-restricted spliced epitopes have been described in tumors and infections, suggesting an unpredicted relevance of these peculiar peptides. We review current knowledge about proteasome-catalyzed peptide splicing (PCPS), the emerging rules governing this process, and the potential implications for our understanding and therapeutic use of CD8⁺ T cells, as well as mechanisms generating other non-canonical antigenic epitopes targeted by the T cell response.



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Tumor response assessment: comparison between unstructured free text reporting in routine clinical workflow and computer-aided evaluation based on RECIST 1.1 criteria

Abstract

Purpose

Standardized computer-aided tumor response assessment is common in clinical trials. In contrast, unstructured free text reporting (UFTR) is common in daily routine. Therefore, this study aimed to discern and quantify differences between UFTR and computer-aided standardized tumor response evaluation based on RECIST 1.1 criteria (RECIST), serving as gold standard, in clinical workflow.

Methods

One-hundred consecutive patients with cancer eligible for RECIST 1.1 evaluation, who received five follow-up CTs of the trunk, were retrospectively included. All UFTRs were assigned to RECIST response categories [complete response, partial response (PR), stable disease (SD), progressive disease (PD)]. All CTs were re-evaluated using dedicated software (mint lesion™) applying RECIST 1.1. The accordance in tumor response ratings was analyzed using Cohen's kappa.

Results

At the first follow-up, 47 cases were rated differently with an SD underrepresentation and a PR and PD overrepresentation in UFTR. In the subsequent follow-ups, categorical differences were seen in 38, 44, 37, and 44%. Accordance between UFTR and RECIST was fair to moderate (Cohen's kappa: 0.356, 0.477, 0.390, 0.475, 0.376; always p < 0.001). Differences were mainly caused by the rating of even small tumor burden changes as PD or PR in UFTR or by comparison to the most recent prior CT scan in UFTR instead of comparison to nadir or baseline.

Conclusions

Significant differences in tumor response ratings were detected comparing UFTR and computer-aided standardized evaluation based on RECIST 1.1. Thus, standardized reporting should be implemented in daily routine workflow.

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Protein kinase C isoforms in the normal pancreas and in pancreatic disease

Publication date: Available online 18 August 2017
Source:Cellular Signalling
Author(s): Alicia Fleming, Peter Storz
Protein Kinase C isoforms have been implicated in regulating multiple processes within the healthy pancreas. Moreover, their dysregulation contributes to all aspects of pancreatic disease. In this review, with a focus on acinar, ductal, and islet cells, we highlight the roles and contributions of the different PKC isoforms to normal pancreas function. We also discuss the contribution of PKC enzymes to pancreatic diseases, including insulin resistance and diabetes mellitus, as well as pancreatitis and the development and progression of pancreatic cancer.



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Sex as a determinant of age-related changes in rat spinal cord inflammation-oxidation state

Abstract

To close the gap in our knowledge of sex influence on age-related changes in inflammation-oxidation state in spinal cord (SC) relevant to inflammation/oxidative-stress associated neuropathologies, 2–3 month-old (young) and 18–20 month-old (old) rats, exhibiting increased level of IL-6, a commonly used marker of inflamm-aging, were examined for inflammatory/redox status, and the underlying regulatory networks' molecules expression. With age, rat SC microglia became sensitized ("primed"), while SC tissue shifted towards mild inflammatory state, with increased levels of proinflammatory IL-1β (key marker of microglial systemic inflammation-induced neurotoxicity), which was more prominent in males. This, most likely, reflected age- and sex-related impairment in the expression of CX3CR1, the receptor for fractalkine (CX3CL1), the soluble factor which regulates microglial activation and diminishes production of IL-1β (central for fractalkine neuroprotection). Considering that (i) age-related changes in SC IL-1β expression were not followed by complementary changes in SC IL-6 expression, and (ii) the reversal in the direction of the sex bias in circulating IL-6 level and SC IL-1β expression, it seems obvious that there are tissue-specific differences in the proinflammatory cytokine profile. Additionally, old male rat SC exhibited greater oxidative damage than female, reflecting, most likely, their lower capacity to maintain the pro-oxidant-antioxidant balance. In conclusion, these findings, apart from highlighting the significance of sex for age-associated changes in SC inflammation-oxidation, may be relevant for understating sex differences in human inflammation/oxidative-stress related SC diseases, and consequently, for optimizing their prevention/therapy.

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Transcranial Direct Current Stimulation Modulates Neuronal Networks in Attention Deficit Hyperactivity Disorder

Abstract

Anodal transcranial direct current stimulation (tDCS) of the prefrontal cortex has been repeatedly shown to improve working memory (WM). Since patients with attention deficit hyperactivity disorder (ADHD) are characterized by both underactivation of the prefrontal cortex and deficits in WM, the modulation of prefrontal activity with tDCS in ADHD patients may increase their WM performance as well as improve the activation and connectivity of the WM network. In the present study, this hypothesis was tested using a double-blind sham-controlled experimental design. After randomization, sixteen adolescents with ADHD underwent either anodal tDCS over the left dorsolateral prefrontal cortex (DLPFC, 1 mA, 20 min) or sham stimulation with simultaneous fMRI during n-back WM task. Both in one-back and two-back conditions, tDCS led to a greater activation (compared with sham stimulation) of the left DLPFC (under the electrode), left premotor cortex, left supplementary motor cortex, and precuneus. The effects of tDCS were long-lasting and influenced resting state functional connectivity even 20 min after the stimulation, with patterns of strengthened DLPFC connectivity after tDCS outlining the WM network. In summary, anodal tDCS caused increased neuronal activation and connectivity, not only in the brain area under the stimulating electrode (i.e. left DLPFC) but also in other, more remote brain regions. Because of moderate behavioral effects of tDCS, the significance of this technique for ADHD treatment has to be investigated in further studies.

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Simultaneous Intracranial EEG-fMRI Shows Inter-Modality Correlation in Time-Resolved Connectivity Within Normal Areas but Not Within Epileptic Regions

Abstract

For the first time in research in humans, we used simultaneous icEEG-fMRI to examine the link between connectivity in haemodynamic signals during the resting-state (rs) and connectivity derived from electrophysiological activity in terms of the inter-modal connectivity correlation (IMCC). We quantified IMCC in nine patients with drug-resistant epilepsy (i) within brain networks in 'healthy' non-involved cortical zones (NIZ) and (ii) within brain networks involved in generating seizures and interictal spikes (IZ1) or solely spikes (IZ2). Functional connectivity (h ² ) estimates for 10 min of resting-state data were obtained between each pair of electrodes within each clinical zone for both icEEG and fMRI. A sliding window approach allowed us to quantify the variability over time of h ² (vh ²) as an indicator of connectivity dynamics. We observe significant positive IMCC for h ² and vh ², for multiple bands in the NIZ only, with the strongest effect in the lower icEEG frequencies. Similarly, intra-modal h ² and vh ² were found to be differently modified as a function of different epileptic processes: compared to NIZ, \(h_{\text{BOLD}}^{2}\) was higher in IZ1, but lower in IZ2, while \(h_{\text{icEEG}}^{2}\) showed the inverse pattern. This corroborates previous observations of inter-modal connectivity discrepancies in pathological cortices, while providing the first direct invasive and simultaneous comparison in humans. We also studied time-resolved FC variability multimodally for the first time, finding that IZ1 shows both elevated internal \(h_{\text{BOLD}}^{2}\) and less rich dynamical variability, suggesting that its chronic role in epileptogenesis may be linked to greater homogeneity in self-sustaining pathological oscillatory states.

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Neural Processes Associated with Vocabulary and Vowel-Length Differences in a Dialect: An ERP Study in Pre-literate Children

Abstract

Although familiarity with a language impacts how phonology and semantics are processed at the neural level, little is known how these processes are affected by familiarity with a dialect. By measuring event-related potentials (ERPs) in kindergarten children we investigated neural processing related to familiarity with dialect-specific pronunciation and lexicality of spoken words before literacy acquisition in school. Children speaking one of two German dialects were presented with spoken word-picture pairings, in which congruity (or the lack thereof) was defined by dialect familiarity with pronunciation or vocabulary. In a dialect-independent control contrast, congruity was defined by audio–visual semantic (mis)match. Congruity effects and congruity-by-dialect group interactions in the ERPs were tested by data-driven topographic analyses of variance (TANOVA) and theory-driven focal analyses. Converging results revealed similar congruity effects in the N400 and late-positive-complex (LPC) in the control contrast for both dialect groups. In the dialect-specific vocabulary contrast, topographies of the N400- and LPC-effects were reversed depending on familiarity with the presented dialect words. In the dialect-specific pronunciation contrast, again a topography reversal was found depending on dialect familiarity, however, only for the LPC. Our data suggest that neural processing of unfamiliar words, but not pronunciation variants, is characterized by semantic processing (increased N400-effect). However, both unfamiliar words and pronunciation variants seem to engage congruity judgment, as indicated by the LPC-effect. Thus, semantic processing of pronunciation in dialect words seems to be rather robust against slight alterations in pronunciation, like changes in vowel duration, while such alterations may still trigger subsequent control processes.

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Neural Mechanism Underling Comprehension of Narrative Speech and Its Heritability: Study in a Large Population

Abstract

Comprehension of narratives constitutes a fundamental part of our everyday life experience. Although the neural mechanism of auditory narrative comprehension has been investigated in some studies, the neural correlates underlying this mechanism and its heritability remain poorly understood. We investigated comprehension of naturalistic speech in a large, healthy adult population (n = 429; 176/253 M/F; 22–36 years of age) consisting of 192 twin pairs (49 monozygotic and 47 dizygotic pairs) and 237 of their siblings. We used high quality functional MRI datasets from the Human Connectome Project (HCP) in which a story-based paradigm was utilized for the auditory narrative comprehension. Our results revealed that narrative comprehension was associated with activations of the classical language regions including superior temporal gyrus (STG), middle temporal gyrus (MTG), and inferior frontal gyrus (IFG) in both hemispheres, though STG and MTG were activated symmetrically and activation in IFG were left-lateralized. Our results further showed that the narrative comprehension was associated with activations in areas beyond the classical language regions, e.g. medial superior frontal gyrus (SFGmed), middle frontal gyrus (MFG), and supplementary motor area (SMA). Of subcortical structures, only the hippocampus was involved. The results of heritability analysis revealed that the oral reading recognition and picture vocabulary comprehension were significantly heritable (h ²  > 0.56, p < 10^− 13). In addition, the extent of activation of five areas in the left hemisphere, i.e. STG, IFG pars opercularis, SFGmed, SMA, and precuneus, and one area in the right hemisphere, i.e. MFG, were significantly heritable (h ²  > 0.33, p < 0.0004). The current study, to the best of our knowledge, is the first to investigate auditory narrative comprehension and its heritability in a large healthy population. Referring to the excellent quality of the HCP data, our results can clarify the functional contributions of linguistic and extra-linguistic cortices during narrative comprehension.

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Predicting Dream Recall: EEG Activation During NREM Sleep or Shared Mechanisms with Wakefulness?

Abstract

The common knowledge of a uniqueness of REM sleep as a privileged scenario of dreaming still persists, although consolidated empirical evidence shows that the assumption that dreaming is just an epiphenomenon of REM sleep is no longer tenable. However, the brain mechanisms underlying dream generation and its encoding in memory during NREM sleep are still mostly unknown. In fact, only few studies have investigated on the mechanisms of dream phenomenology related to NREM sleep. For this reason, our study is specifically aimed to elucidate the electrophysiological (EEG) correlates of dream recall (DR) upon NREM sleep awakenings. Under the assumption that EEG activity predicts the presence/absence of DR also during NREM sleep, we have investigated whether DR from stage 2 NREM sleep shares similar brain mechanisms to those involved in the encoding of episodic memory during wakefulness, or it depends on the specific electrophysiological milieu of the sleep period along the desynchronized/synchronized EEG continuum. We collected DR from a multiple nap protocol in a within-subjects design. We found that DR is predicted by an extensive reduction of delta activity during the last segment of sleep, encompassing left frontal and temporo-parietal areas. The results could represent an update on the mechanisms underlying the sleep mentation during NREM sleep. In particular, they support the hypothesis that an increased cortical EEG activation is a prerequisite for DR, and they are not necessarily in conflict with the hypothesis of common wake-sleep mechanisms. We also confirmed that EEG correlates of DR depend on a state-like relationship.

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High-Resolution fMRI of Auditory Cortical Map Changes in Unilateral Hearing Loss and Tinnitus

Abstract

Animal models of hearing loss and tinnitus observe pathological neural activity in the tonotopic frequency maps of the primary auditory cortex. Here, we applied ultra high-field fMRI at 7 T to test whether human patients with unilateral hearing loss and tinnitus also show altered functional activity in the primary auditory cortex. The high spatial resolution afforded by 7 T imaging allowed tonotopic mapping of primary auditory cortex on an individual subject basis. Eleven patients with unilateral hearing loss and tinnitus were compared to normal-hearing controls. Patients showed an over-representation and hyperactivity in a region of the cortical map corresponding to low frequencies sounds, irrespective of the hearing loss and tinnitus range, which in most cases affected higher frequencies. This finding of hyperactivity in low frequency map regions, irrespective of hearing loss range, is consistent with some previous studies in animal models and corroborates a previous study of human tinnitus. Thus these findings contribute to accumulating evidence that gross cortical tonotopic map reorganization is not a causal factor of tinnitus.

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