Αρχειοθήκη ιστολογίου

Σάββατο 16 Σεπτεμβρίου 2017

Mouse Model of IL-17-Dominant Rhinitis Using Polyinosinic-Polycytidylic Acid.

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Mouse Model of IL-17-Dominant Rhinitis Using Polyinosinic-Polycytidylic Acid.

Allergy Asthma Immunol Res. 2017 Nov;9(6):540-549

Authors: Bae JS, Kim EH, Kim JH, Mo JH

Abstract
Interleukin (IL)-17 plays an important role in rhinitis and the level thereof correlates with the severity of disease. However, no mouse model for IL-17-dominant rhinitis has yet been developed. Our objective was to establish a mouse model of IL-17-dominant rhinitis via intranasal application of polyinosinic-polycytidylic acid (abbreviated as Poly(I:C)). Mice were divided into 6 groups (n=8 for each group); 1) 1 negative control group, 2) 1 positive control group (OVA/alum model), 3) 2 Poly(I:C) groups (10 or 100 μg), and 4) 2 OVA/Poly(I:C) groups (10 or 100 μg). The positive control group was treated with the conventional OVA/alum protocol. In the Poly(I:C) and OVA/Poly(I:C) groups, phosphate-buffered saline or an OVA solution plus Poly(I:C) were administered. The OVA/Poly(I:C) groups exhibited significantly greater neutrophil infiltration and increased IL-17/interferon γ expression compared with the other groups. However, the levels of total immunoglobulin E (IgE), OVA-specific IgE, eosinophil infiltration, IL-4, IL-5, IL-6, and IL-10 were significantly lower in the OVA/Poly(I:C) groups than in mice subjected to conventional Th2-dominant OVA/alum treatment (the positive control group). IL-17 and neutrophil measurement, chemokine (C-X-C motif) ligand 1 immunohistochemistry, and confocal microscopy revealed increased numbers of IL-17-secreting cells in the nasal mucosa of the OVA/Poly(I:C) groups, which included natural killer cells, CD4 T cells, and neutrophils. In conclusion, we developed a mouse model of IL-17-dominant rhinitis using OVA together with Poly(I:C). This model will be useful in research on neutrophil- or IL-17-dominant rhinitis.

PMID: 28913994 [PubMed]



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A Retrospective Study of Korean Adults With Food Allergy: Differences in Phenotypes and Causes.

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A Retrospective Study of Korean Adults With Food Allergy: Differences in Phenotypes and Causes.

Allergy Asthma Immunol Res. 2017 Nov;9(6):534-539

Authors: Lee SH, Ban GY, Jeong K, Shin YS, Park HS, Lee S, Ye YM

Abstract
PURPOSE: Increasing in prevalence, food allergy (FA) is becoming an important public health concern. In Korean adults, however, clinical phenotypes and causes of FA have not been studied. We aimed to study common causative allergens and clinical manifestations of FA in Korean adults.
METHODS: This study was conducted as a retrospective review of medical records for 95 patients (≥19 years old) diagnosed with FA from September 2014 to August 2015 at a single university hospital.
RESULTS: In the 95 patients, 181 FA events were recorded. The mean age of first onset of FA symptoms was 34.7±15.8 years. The most frequent causative food was seafood (34.8%); shrimp and crab allergies ranked highest, regardless of age and sex. Among all FA events, there were 47 (26.0%) cases of anaphylaxis and 26 (14.4%) cases of oral allergy syndrome (OAS). Seafood (51.1%) was the most frequent cause of anaphylaxis, followed by grains (14.9%). Most OAS cases were associated with fruits (95.7%). The frequency of fruit-induced FA was significantly higher in males than in females (23.0% vs 8.4%, P=0.011). While no cases of vegetables-induced FA were noted in younger individuals (19 to 30 years), vegetables accounted for 20.5% of FA symptoms in older subjects (≥51 years, P<0.001). Allergic rhinitis (44.2%) and drug allergy (20.0%) were major comorbidities associated with FA. Overall, 29 FA events had cofactors, of which 10 were combined with exercise.
CONCLUSIONS: The major causes of FA in Korean adults were crustacean, fruits, and grains. Interestingly, the clinical manifestations of FA and demographics varied according to type of food allergen.

PMID: 28913993 [PubMed]



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Effects of Immunoglobulin Replacement on Asthma Exacerbation in Adult Asthmatics with IgG Subclass Deficiency.

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Effects of Immunoglobulin Replacement on Asthma Exacerbation in Adult Asthmatics with IgG Subclass Deficiency.

Allergy Asthma Immunol Res. 2017 Nov;9(6):526-533

Authors: Kim JH, Ye YM, Ban GY, Shin YS, Lee HY, Nam YH, Lee SK, Cho YS, Jang SH, Jung KS, Park HS

Abstract
PURPOSE: Recurrent respiratory tract infection is a common manifestation of primary immunodeficiency disease, and respiratory viruses or bacteria are important triggers of asthma exacerbations. Asthma often coexists with humoral immunodeficiency in adults, and some asthmatics with immunoglobulin (Ig) G subclass deficiency (IgGSCD) suffer from recurrent exacerbations. Although some studies suggest a benefit from Ig replacement, others have failed to support its use. This study aimed to assess the effect of Ig replacement on asthma exacerbation caused by respiratory infection as well as the asthma control status of adult asthmatics with IgGSCD.
METHODS: This is a multi-center, open-label study of adult asthmatics with IgGSCD. All patients received monthly intravenous immunoglobulin (IVIG) for 6 months and were evaluated regarding asthma exacerbation related to infection, asthma control status, quality of life, and lung function before and after IVIG infusion.
RESULTS: A total of 30 patients were enrolled, and 24 completed the study. Most of the patients had a moderate degree of asthma severity with partly (52%) or uncontrolled (41%) status at baseline. IVIG significantly reduced the proportion of patients with asthma exacerbations, lowered the number of respiratory infections, and improved asthma control status, compared to the baseline values (P<0.001). The mean asthma-specific quality of life and asthma control test scores were improved significantly (P=0.009 and P=0.053, respectively); however, there were no significant changes in lung function.
CONCLUSIONS: IVIG reduced the frequency of asthma exacerbations and improved asthma control status in adult asthmatics with IgGSCD, suggesting that IVIG could be an effective treatment option in this population.

PMID: 28913992 [PubMed]



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Seasonal Cycle and Relationship of Seasonal Rhino- and Influenza Virus Epidemics With Episodes of Asthma Exacerbation in Different Age Groups.

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Seasonal Cycle and Relationship of Seasonal Rhino- and Influenza Virus Epidemics With Episodes of Asthma Exacerbation in Different Age Groups.

Allergy Asthma Immunol Res. 2017 Nov;9(6):517-525

Authors: Lee SW, Lee S, Sheen YH, Ha EK, Choi SH, Yang MS, Hwang S, Kim SS, Choi JH, Han MY

Abstract
PURPOSE: Seasonal variations in asthma exacerbation (AE) are associated with respiratory virus outbreaks and the return of children to school after vacation. This study aims to elucidate the period, phase, and amplitude of seasonal cycles of AE in 5 different age groups with regard to rhino- and influenza virus epidemics in Korea.
METHODS: The number of daily emergency department (ED) visits for AE in all age groups of Korea and the nationwide weekly incidence of rhino- and influenza virus, were obtained for 2008-2012. Fourier regression was used to model rhythmicity, and the Cosinor method was used to determine the amplitude and phase of the cycles in each age group. The cross-correlation function (CCF) between AE and the rhino- and influenza virus epidemics was also calculated.
RESULTS: There were 157,559 events of AE (0.62 events/1,000 individuals/year) during the study period. There were spring and fall peaks of AE in children and adults, but only 1 winter peak in the elderly. The amplitude of the AE peak in infants was higher in spring than in fall (9.16 vs 3.04, P<0.010), and the fall peak was approximately 1 month later in infants than in school children (October 11 vs November 13, P<0.010). The association between AE and rhinovirus was greatest in school children (rho=0.331), and the association between AE and influenza virus was greatest in those aged ≥60 years (rho=0.682).
CONCLUSIONS: The rhythmicity, amplitude, and phase of the annual cycle of AE differed among different age groups. The patterns of AE were related to the annual rhino- and influenza virus epidemics.

PMID: 28913991 [PubMed]



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Association Between Sensitization to Mold and Impaired Pulmonary Function in Children With Asthma.

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Association Between Sensitization to Mold and Impaired Pulmonary Function in Children With Asthma.

Allergy Asthma Immunol Res. 2017 Nov;9(6):509-516

Authors: Byeon JH, Ri S, Amarsaikhan O, Kim E, Ahn SH, Choi IS, Kim HJ, Seo S, Yoon W, Yoo Y

Abstract
PURPOSE: Recent data indicate that sensitization to mold contributes to the severity and persistence of asthma. In this study, we investigated the relationships between sensitization to mold and lung function parameters in children with asthma.
METHODS: We retrospectively reviewed clinical data from 551 asthmatic subjects. We selected subjects who met clinical diagnostic criteria of asthma. Their spirometry, methacholine challenge tests, and measurements of blood eosinophils, serum IgE, eosinophil cationic protein (ECP) and fractional exhaled nitric oxide (FeNO) results were included. Skin prick testing (SPT) results with 13 common aeroallergens in Korea including house dust mites, animal dander, pollen, cockroach and mold were reviewed. Subjects were divided into 3 groups according to their SPT results. Subjects who showed no positive result to any aeroallergen were designated as group 1 (non-sensitized). Group 2 represented subjects who were sensitized to aeroallergens other than mold (other allergen-sensitized) and group 3 included subjects who were sensitized to mold allergens (mold-sensitized).
RESULTS: Among the 551 asthmatic subjects, 67 (12.2%) were sensitized to mold and 366 (66.4%) were sensitized to other aeroallergens. The log mean IgE levels were higher in groups 2 (5.96±1.14 IU/mL) and 3 (5.81±0.97 IU/mL) compared to group 1 (3.88±1.68 IU/mL). Blood eosinophils, ECP and FeNO concentrations were significantly higher in groups 2 and 3, but no significant difference was found between the 2 groups. The mean FEV1 value was significantly lower in group 3 (86.9±12.1%pred) than in groups 2 (92.0±14.8%pred) and 1 (93.4±15.4%pred). The log mean methacholine PC20 was significantly lower in group 3 (0.08±1.91 mg/mL) than in groups 2 (1.31±1.69 mg/mL) and 1 (2.29±1.66 mg/mL).
CONCLUSIONS: We observed a differential association between mold and other aeroallergen sensitization, and severity of asthma. Sensitization to mold is associated with lower lung function and increased airway hyper-responsiveness in children with asthma. Mold sensitization could be an important factor determining asthma severity particularly airflow limitation in children.

PMID: 28913990 [PubMed]



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Patterns of Inhalant Allergen Sensitization and Geographical Variation in Korean Adults: A Multicenter Retrospective Study.

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Patterns of Inhalant Allergen Sensitization and Geographical Variation in Korean Adults: A Multicenter Retrospective Study.

Allergy Asthma Immunol Res. 2017 Nov;9(6):499-508

Authors: Kang MG, Kim MY, Song WJ, Kim S, Jo EJ, Lee SE, Kwon JW, Lee SM, Park CS, Park HK, Park HW, Chang YS, Lee J, Lee YM, Jee YK, Lee JM, Choi IS, Cho SH

Abstract
PURPOSE: Inhalant allergen sensitization is one of the major factors involved in the pathogenesis of allergic respiratory diseases. However, the sensitization is determined by interactions between genetic and environmental factors. Thus, testing panels of inhalant allergens may differ among geographical areas. Here we aimed to determine 10 common inhalant allergens in Korean adult patients with suspected respiratory allergies and to examine the variation between different geographical locations.
METHODS: A total of 28,954 patient records were retrieved for retrospective analysis, from 12 referral allergy clinics located in 9 different areas. Inclusion criteria were Korean adults (≥18 years old) who underwent the inhalant allergen skin prick test for suspected history of respiratory allergy. The primary outcome was inhalant allergen skin prick response. Demographic and clinical information were also collected. Positive skin prick responses to allergens were defined as allergen-to-histamine wheal ratio ≥1. Based on skin test results, the most prevalent aeroallergens were determined.
RESULTS: The overall prevalence of allergic sensitization was 45.3%. Dermatophagoides farinae and Dermatophagoides pteronyssinus were the most commonly sensitized allergens. Other common inhalant allergens were cat epithelium (8.1%), birch (7.7%), mugwort (6.9%), alder (6.7%), hazel (6.7%), beech (6.7%), oak (6.6%), and Tyrophagus putres (6.2%), in decreasing order frequency. These 10 inhalant allergens explained 90% of inhalant allergen sensitization in the study participants. However, distinct patterns of the 10 inhalant sensitization were observed in patients living in Chungnam and Jeju. American cockroach, Gernam cockroach, and Trichophyton metagrophytes were unique in Chungnam. Orchard, Japanese cedar, and Velvet were unique in Jeju.
CONCLUSIONS: The present analysis suggests a panel of 10 most common inhalant allergens in Korean adult patients with suspected respiratory allergies, which explained 90% of inhalant allergen sensitization. This panel can be utilized as a practical and convenient tool for primary practice and epidemiological surveys of respiratory allergic diseases.

PMID: 28913989 [PubMed]



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Prevalence of Respiratory Viral Infections in Korean Adult Asthmatics With Acute Exacerbations: Comparison With Those With Stable State.

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Prevalence of Respiratory Viral Infections in Korean Adult Asthmatics With Acute Exacerbations: Comparison With Those With Stable State.

Allergy Asthma Immunol Res. 2017 Nov;9(6):491-498

Authors: Seo KH, Bae DJ, Kim JN, Lee HS, Kim YH, Park JS, Kim MS, Chang HS, Son JH, Baek DG, Lee JS, Park CS

Abstract
PURPOSE: Viral infections are involved in ~50% of exacerbations among Caucasian adult asthmatics. However, there have been few reports on the causative virus of exacerbations in Korean adult asthmatics. Thus, we compared frequencies and types of viruses between lower respiratory tract illnesses (LRTIs) with exacerbations (exacerbated LRTIs) and those without exacerbations (stable LRTIs) to evaluate contribution of respiratory viruses to exacerbations.
METHODS: Viral RNA was extracted from sputum using the Viral Gene-spin™ Kit. Reverse transcription-polymerase chain reaction (RT-PCR) was performed to detect adenovirus (ADV), metapneumovirus (MPV), parainfluenza virus (PIV) 1/2/3, influenza virus (IFV) A, IFV B, respiratory syncytial virus (RSV) A/B, and rhinovirus (RV) A.
RESULTS: Among the 259 patients, 210 underwent a single sputum examination, and the remaining 49 underwent 2 to 4 sputum examinations. Virus was detected in 68 of the 259 exacerbated episodes and in 11 of the 64 stable episodes. Among the exacerbated episodes, RV was the most frequently detected virus, followed by influenza A, parainfluenza, RSV A/B, and ADV. Among the 11 stable episodes, RV was most frequently detected. Detection rates of these viruses did not differ between the 2 groups (P>0.05). Thirty-five patients underwent the virus examination at 2 episodes of exacerbation, while 14 patients underwent at each time of exacerbated and stable episodes. Virus detection rate at the second examination was significantly higher in cases with 2 exacerbation episodes than in those with initial exacerbation and sequential stable episodes (P=0.003). A seasonal pattern was noted in the detection rates of RV (September to December), IFV (January to April), PIV (May to September), and RSV A/B (September to April).
CONCLUSIONS: Respiratory viruses were identified in approximately 20% of LRTI irrespective of the presence of asthma exacerbation. RV and IFV A/B were most frequently detected. A group of patients experienced frequent viral infections followed by asthma exacerbations.

PMID: 28913988 [PubMed]



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Clinical Characteristics of Exacerbation-Prone Adult Asthmatics Identified by Cluster Analysis.

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Clinical Characteristics of Exacerbation-Prone Adult Asthmatics Identified by Cluster Analysis.

Allergy Asthma Immunol Res. 2017 Nov;9(6):483-490

Authors: Kim MA, Shin SW, Park JS, Uh ST, Chang HS, Bae DJ, Cho YS, Park HS, Yoon HJ, Choi BW, Kim YH, Park CS

Abstract
PURPOSE: Asthma is a heterogeneous disease characterized by various types of airway inflammation and obstruction. Therefore, it is classified into several subphenotypes, such as early-onset atopic, obese non-eosinophilic, benign, and eosinophilic asthma, using cluster analysis. A number of asthmatics frequently experience exacerbation over a long-term follow-up period, but the exacerbation-prone subphenotype has rarely been evaluated by cluster analysis. This prompted us to identify clusters reflecting asthma exacerbation.
METHODS: A uniform cluster analysis method was applied to 259 adult asthmatics who were regularly followed-up for over 1 year using 12 variables, selected on the basis of their contribution to asthma phenotypes. After clustering, clinical profiles and exacerbation rates during follow-up were compared among the clusters.
RESULTS: Four subphenotypes were identified: cluster 1 was comprised of patients with early-onset atopic asthma with preserved lung function, cluster 2 late-onset non-atopic asthma with impaired lung function, cluster 3 early-onset atopic asthma with severely impaired lung function, and cluster 4 late-onset non-atopic asthma with well-preserved lung function. The patients in clusters 2 and 3 were identified as exacerbation-prone asthmatics, showing a higher risk of asthma exacerbation.
CONCLUSIONS: Two different phenotypes of exacerbation-prone asthma were identified among Korean asthmatics using cluster analysis; both were characterized by impaired lung function, but the age at asthma onset and atopic status were different between the two.

PMID: 28913987 [PubMed]



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Chronic Spontaneous Urticaria: Pathogenesis and Treatment Considerations.

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Chronic Spontaneous Urticaria: Pathogenesis and Treatment Considerations.

Allergy Asthma Immunol Res. 2017 Nov;9(6):477-482

Authors: Kaplan AP

Abstract
The treatment of chronic spontaneous urticaria begins with antihistamines; however, the dose required typically exceeds that recommended for allergic rhinitis. Second-generation, relatively non-sedating H₁-receptor blockers are typically employed up to 4 times a day. First-generation antihistamines, such as hydroxyzine or diphenhydramine (Atarax or Benadryl), were employed similarly in the past. Should high-dose antihistamines fail to control symptoms (at least 50%), omalizumab at 300 mg/month is the next step. This is effective in 70% of antihistamine-refractory patients. H₂-receptor blockers and leukotriene antagonists are no longer recommended; they add little and the literature does not support significant efficacy. For those patients who are unresponsive to both antihistamines and omalizumab, cyclosporine is recommended next. This is similarly effective in 65%-70% of patients; however, care is needed regarding possible side-effects on blood pressure and renal function. Corticosteroids should not be employed chronically due to cumulative toxicity that is dose and time dependent. Brief courses of steroid e.g., 3-10 days can be employed for severe exacerbations, but should be an infrequent occurrence. Finally, other agents, such as dapsone or sulfasalazine, can be tried for those patients unresponsive to antihistamines, omalizumab, and cyclosporine.

PMID: 28913986 [PubMed]



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Asthma Biomarkers: Do They Bring Precision Medicine Closer to the Clinic?

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Asthma Biomarkers: Do They Bring Precision Medicine Closer to the Clinic?

Allergy Asthma Immunol Res. 2017 Nov;9(6):466-476

Authors: Agache I, Rogozea L

Abstract
Measurement of biomarkers has been incorporated within clinical research of asthma to characterize the population and to associate the disease with environmental and therapeutic effects. Regrettably, at present, there are no specific biomarkers, none is validated or qualified, and endotype-driven choices overlap. Biomarkers have not yet reached clinical practice and are not included in current asthma guidelines. Last but not least, the choice of the outcome upholding the value of the biomarkers is extremely difficult, since it has to reflect the mechanistic intervention while being relevant to both the disease and the particular person. On the verge of a new age of asthma healthcare standard, we must embrace and adapt to the key drivers of change. Disease endotypes, biomarkers, and precision medicine represent an emerging model of patient care building on large-scale biologic databases, omics and diverse cellular assays, health information technology, and computational tools for analyzing sizable sets of data. A profound transformation of clinical and research pattern from population to individual risk and from investigator-imposed subjective disease clustering (hypothesis driven) to unbiased, data-driven models is facilitated by the endotype/biomarker-driven approach.

PMID: 28913985 [PubMed]



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Effective Strategies for Managing Asthma Exacerbations for Precision Medicine.

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Effective Strategies for Managing Asthma Exacerbations for Precision Medicine.

Allergy Asthma Immunol Res. 2017 Nov;9(6):463-465

Authors: Cho YS

PMID: 28913984 [PubMed]



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Mirror trends of plasticity and stability indicators in primate prefrontal cortex

Abstract

Research on plasticity markers in the cerebral cortex has largely focused on their timing of expression and role in shaping circuits during critical and normal periods. By contrast, little attention has been focused on the spatial dimension of plasticity-stability across cortical areas. The rationale for this analysis is based on the systematic variation in cortical structure that parallels functional specialization and raises the possibility of varying levels of plasticity. Here we investigated in adult rhesus monkeys the expression of markers related to synaptic plasticity or stability in prefrontal limbic and eulaminate areas that vary in laminar structure. Our findings revealed that limbic areas are impoverished in three markers of stability: intracortical myelin, the lectin Wisteria floribunda agglutinin, which labels perineuronal nets, and parvalbumin, which is expressed in a class of strong inhibitory neurons. By contrast, prefrontal limbic areas were enriched in the enzyme calcium/calmodulin-dependent protein kinase II (CaMKII), known to enhance plasticity. Eulaminate areas have more elaborate laminar architecture than limbic areas and showed the opposite trend: they were enriched in markers of stability and had lower expression of the plasticity related marker CaMKII. The expression of glial fibrillary acidic protein (GFAP), a marker of activated astrocytes, was also higher in limbic areas, suggesting that cellular stress correlates with the rate of circuit reshaping. Elevated markers of plasticity may endow limbic areas with flexibility necessary for learning and memory within an affective context, but may also render them vulnerable to abnormal structural changes, as seen in neurologic and psychiatric diseases.

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Frequency-dependent regulation of intrinsic excitability by voltage-activated membrane conductances, computational modeling and dynamic clamp

Abstract

As one of the most unique properties of nerve cells, their intrinsic excitability allows them to transform synaptic inputs into action potentials. This process reflects a complex interplay between the synaptic inputs and the voltage-dependent membrane currents of the postsynaptic neuron. While neurons in natural conditions mostly fire under the action of intense synaptic bombardment and receive fluctuating patterns of excitation and inhibition, conventional techniques to characterize intrinsic excitability mainly utilize static means of stimulation. Recently we have shown that voltage-gated membrane currents regulate the firing responses under current step stimulation and under physiologically more realistic inputs in a differential manner. At the same time, a multitude of neuron types have been shown to exhibit some form of subthreshold resonance that potentially allows them to respond to synaptic inputs in a frequency-selective manner. In the present study we performed virtual experiments in computational models of neurons to examine how specific voltage-gated currents regulate their excitability under simulated frequency-modulated synaptic inputs. The model simulations and subsequent dynamic clamp experiments on mouse hippocampal pyramidal neurons revealed that the impact of voltage-gated currents in regulating the firing output is strongly frequency-dependent and mostly affecting the synaptic integration at theta-frequencies. Notably, robust frequency-dependent regulation of intrinsic excitability was observed even when conventional analysis of membrane impedance suggested no such tendency. Consequently, plastic or homeostatic regulation of intrinsic membrane properties can tune the frequency-selectivity of neuron populations in a way that is not readily expected from subthreshold impedance measurements.

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Altered Cav1.2 function in the Timothy Syndrome mouse model produces ascending serotonergic abnormalities

Abstract

Polymorphism in the gene CACNA1C, encoding the pore-forming subunit of Cav1.2 L-type calcium channels, has one of the strongest genetic linkages to schizophrenia, bipolar disorder, and major depressive disorder: psychopathologies in which serotonin signaling has been implicated. Additionally, a gain-of-function mutation in CACNA1C is responsible for the neurodevelopmental disorder Timothy Syndrome that presents with prominent behavioral features on the autism spectrum. Given an emerging role for serotonin in the etiology of autism spectrum disorders, we investigate the relationship between Cav1.2 and the ascending serotonin system in the Timothy Syndrome type 2 (TS2-neo) mouse, which displays behavioral features consistent with the core triad of ASD. We find that TS2-neo mice exhibit enhanced serotonin tissue content and axon innervation of the dorsal striatum, as well as decreased serotonin turnover in the amygdala. These regionally specific alterations are accompanied by an enhanced active coping response during acute stress (forced-swim), serotonin neuron Fos-activity in the caudal dorsal raphe, and serotonin type 1A receptor dependent feedback-inhibition of the rostral DRN. Collectively, these results suggest that the global gain of function Cav1.2 mutation associated with Timothy Syndrome has pleotropic effects on the ascending serotonin system including neuroanatomical changes, regional differences in forebrain serotonin metabolism and feedback regulatory control mechanisms within the dorsal raphe. Altered activity of the ascending serotonin system continues to emerge as a common neural signature across several ASD mouse models, and the capacity for Cav1.2 L-type calcium channels to impact both serotonin structure and function has important implications for several neuropsychiatric conditions.

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Inflammation alters AMPA-stimulated calcium responses in dorsal striatal D2 but not D1 spiny projection neurons

Abstract

Neuroinflammation precedes neuronal loss in striatal neurodegenerative diseases and can be exacerbated by the release of proinflammatory molecules by microglia. These molecules can affect trafficking of AMPARs. The preferential trafficking of calcium-permeable versus impermeable AMPARs can result in disruptions of [Ca2+]i and alter cellular functions. In striatal neurodegenerative diseases, changes in [Ca2+]i and L-type voltage-gated calcium channels (VGCCs) have been reported. Therefore, the present study sought to determine whether a proinflammatory environment alters AMPA-stimulated [Ca2+]i through calcium-permeable AMPARs and/or L-type VGCCs in dopamine-2 and dopamine-1 expressing striatal spiny projection neurons (D2 and D1 SPNs) in the dorsal striatum. Mice expressing the calcium indicator protein, GCaMP in D2 or D1 SPNs, were utilized for calcium imaging. Microglial activation was assessed by morphology analyses. To induce inflammation, acute mouse striatal slices were incubated with lipopolysaccharide (LPS). Here we report that LPS treatment potentiated AMPA responses only in D2 SPNs. When a nonspecific VGCC blocker was included, we observed a decrease of AMPA-stimulated calcium fluorescence in D2 but not D1 SPNs. The remaining agonist induced [Ca2+]i was mediated by calcium-permeable AMPARs because the responses were completely blocked by a selective calcium-permeable AMPAR antagonist. We used isradipine, the highly selective L-type VGCC antagonist to determine the role of L-type VGCCs in SPNs treated with LPS. Isradipine decreased AMPA-stimulated responses selectively in D2 SPNs after LPS treatment. Our findings suggest that dorsal striatal D2 SPNs are specifically targeted in proinflammatory conditions and that L-type VGCCs and calcium-permeable AMPARs are important mediators of this effect.

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FoxP expression identifies a Kenyon cell subtype in the honeybee mushroom bodies linking them to fruitfly αβc neurons

Abstract

The arthropod mushroom bodies (MB) are a higher order sensory integration center. In insects, they play a central role in associative olfactory learning and memory. In Drosophila melanogaster (Dm), the highly ordered connectivity of heterogeneous MB neuron populations has been mapped using sophisticated molecular genetic and anatomical techniques. The MB-core subpopulation was recently shown to express the transcription factor FoxP with relevance for decision-making. Here we report the development and adult distribution of a FoxP-expressing neuron population in the MB of honeybees (Apis mellifera, Am) using in situ hybridization and a custom-made antiserum. We found the same expression pattern in adult bumblebees (Bombus terrestris, Bt). We also designed a new Dm transgenic line that reports FoxP transcriptional activity in the MB-core region, clarifying previously conflicting data of two other reporter lines. Considering developmental, anatomical and molecular similarities, our data are consistent with the concept of deep homology of FoxP expression in neuron populations coding reinforcement-based learning and habit formation.

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Three shades of grey: detecting brain abnormalities in children with autism by using Source-, Voxel- and Surface-based Morphometry

Abstract

Autistic spectrum disorder (ASD) is a neurodevelopmental disorder characterized by deficits in social interactions, communication and stereotyped behavior. Recent evidence from neuroimaging supports the hypothesis that ASD deficits in adults may be related to abnormalities in a specific frontal-temporal network (Autism-specific Structural Network, ASN). To see whether these results extend to younger children and to better characterize these abnormalities, we applied three morphometric methods on brain grey matter of children with and without ASD.

We selected 39 sMRI images of male children with ASD and 42 typically developing (TD) from the ABIDE database. We used Source-Based Morphometry (SoBM), a whole-brain multivariate approach to identify grey matter networks, Voxel-Based Morphometry (VBM), a voxel-wise comparison of the local grey matter concentration, and Surface-Based Morphometry (SuBM) for the estimation of the cortical parameters.

SoBM showed a bilateral frontal-parietal-temporal network different between groups, including the inferior-middle temporal gyrus, the inferior parietal lobule and the postcentral gyrus; VBM returned differences only in the right temporal lobe; SuBM returned a thinning in the right inferior temporal lobe thinner in ASD, a higher gyrification in the right superior parietal lobule in TD and in the middle frontal gyrus in ASD.

For the first time, we investigated the brain abnormalities in children with ASD by using three morphometric techniques. The results were relatively consistent between methods, stressing the role of an Autism-specific Structural Network in ASD individuals. We also make methodological speculations on the relevance of using multivariate and whole brain neuroimaging analysis to capture ASD complexity.

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The Neurobiological Bases of Autism Spectrum Disorders The R451C-Neuroligin 3 mutation hampers the expression of long-term synaptic depression in the dorsal striatum

Abstract

Autism spectrum disorders (ASDs) comprise a heterogeneous group of disorders with a complex genetic etiology. Current theories on the pathogenesis of ASDs suggest that they might arise from an aberrant synaptic transmission affecting specific brain circuits and synapses. The striatum, which is part of the basal ganglia circuit, is one of the brain regions involved in ASDs.

Mouse models of ASDs have provided evidence for an imbalance between excitatory and inhibitory neurotransmission. Here we investigated the expression of long-term synaptic plasticity at corticostriatal glutamatergic synapses in the dorsal striatum of the R451C-NL3 phenotypic mouse model of autism. This mouse model carries the human R451C mutation in the neuroligin3 (NL3) gene, that has been associated with highly penetrant autism in a Swedish family. The R451C-NL3 mouse has been shown to exhibit autistic-like behaviors and alterations of synaptic transmission in different brain areas. However, excitatory glutamatergic transmission and its long-term plasticity have not been investigated in the dorsal striatum so far. Our results indicate that the expression of long-term synaptic depression (LTD) at corticostriatal glutamatergic synapses in the dorsal striatum is impaired by the R451C-NL3 mutation. A partial rescue of LTD was obtained by exogenous activation of cannabinoid CB1 receptors or enhancement of the endocannabinoid tone, suggesting that an altered cannabinoid drive might underlie the deficit of synaptic plasticity in the dorsal striatum of R451C-NL3 mice.

This article is protected by copyright. All rights reserved.



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Effects of the availability of accurate proprioceptive information on older adults’ postural sway and muscle co-contraction

Abstract

During conditions of increased postural instability, older adults exhibit greater lower-limb muscle co-contraction. This response has been interpreted as a compensatory postural strategy, which may be used to i006Ecrease proprioceptive information from muscle spindles or to stiffen the lower limb as a general response to minimise postural sway. The current study aimed to test these two hypotheses by investigating use of muscle co-contraction during sensory transitions that manipulated proprioceptive input. Surface EMG was recorded from the bilateral tibialis anterior and gastrocnemius medialis muscles, in young (aged 18-30) and older adults (aged 68-80) during blind-folded postural assessment. This commenced on a fixed platform (baseline: 2mins), followed by 3-minutes on a sway-referenced platform (adaptation) and a final 3-minutes on a fixed platform again (reintegration). Sensory reweighting was slower in older adults, as shown by a significantly larger and longer postural sway aftereffect once a stable platform was restored. Muscle co-contraction showed similar aftereffects, whereby older adults showed a larger increase in co-contraction once the stable platform had been restored, compared to young adults. This co-contraction aftereffect did not return to baseline until after 1 minute. Our evidence for high muscle co-contraction during the reintroduction of veridical proprioceptive input suggests that increased co-contraction in older adults is not dependent on contemporaneous proprioceptive input. Rather, it is more likely that co-contraction is a general postural strategy used to minimize postural sway, which is increased during this sensory transition. Future research should examine whether muscle co-contraction is typically a reactive or anticipatory response.

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Long-Range Cortical Dynamics: A Perspective from the Mouse Sensorimotor Whisker System

Abstract

In the mammalian neocortex, the capacity to dynamically route and coordinate the exchange of information between areas is a critical feature of cognitive function, enabling processes such as higher-level sensory processing and sensorimotor integration. Despite the importance attributed to long-range connections between cortical areas, their exact operations and role in cortical function remain an open question. In recent years, progress has been made in understanding long-range cortical circuits through work focused on the mouse sensorimotor whisker system. In this review, we examine recent studies dissecting long-range circuits involved in whisker sensorimotor processing as an entry point for understanding the rules that govern long-range cortical circuit function.

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Does an observer's empathy influence my pain? Effect of perceived empathetic or unempathetic support in a pain test

Abstract

The physiological and behavioural effects of empathy for other's pain have been widely investigated, while the opposite situation, i.e. the influence on one's pain of empathetic feedback from others, remains largely unexplored. Here, we assessed whether and how empathetic and unempathetic comments from observers modulate pain and associated vegetative reactions.

In Study 1, conversations between observers of a pain study were recorded by professional actors. Comments were prepared to be perceived as empathetic, unempathetic, or neutral, and were validated in 40 subjects. In a subsequent pain experiment (Study 2), changes in subjective pain and heart rate were investigated in 30 naïve participants who could overhear the empathetic or unempathetic conversations pre-recorded in study 1.

Subjective pain was significantly attenuated when hearing empathetic comments, as compared to both unempathetic and neutral conditions, while unempathetic comments failed to significantly modulate pain. Heart rate increased when hearing unempathetic remarks, and when receiving pain stimuli, but heart acceleration to nociceptive stimulation was not correlated with pain ratings.

These results suggest that empathetic feedback from observers has a positive influence on pain appraisal, and that this effect may surpass the negative effect of unempathetic remarks. Negative remarks can either trigger feelings of guilt or induce irritation/anger, with antagonistic effects on pain that might explain inter-individual variation. Since in basal conditions heart rate and pain perception are positively correlated, their dissociation here suggests that changes in subjective pain were linked to a cognitive bias rather than changes in sensory input.

This article is protected by copyright. All rights reserved.



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Processing of temporally patterned sounds in the auditory cortex of Seba's short-tailed bat (Carollia perspicillata)

Abstract

This article presents a characterization of cortical responses to artificial and natural temporally-patterned sounds in the bat species Carollia perspicillata, a species that produces vocalizations at rates above 50 Hz. Multi-unit activity was recorded in three different experiments. In the first experiment, amplitude modulated (AM) pure tones were used as stimuli to drive auditory cortex (AC) units. AC units of both ketamine-anesthetized and awake bats could lock their spikes to every cycle of the stimulus modulation envelope, but only if the modulation frequency was below 22 Hz. In the second experiment, two identical communication syllables were presented at variable intervals. Suppressed responses to the lagging syllable were observed, unless the second syllable followed the first one with a delay of at least 80 ms (i.e. 12.5 Hz repetition rate). In the third experiment, natural distress vocalization sequences were used as stimuli to drive AC units. Distress sequences produced by C. perspicillata contain bouts of syllables repeated at intervals of ~60 ms (16 Hz). Within each bout, syllables are repeated at intervals as short as 14 ms (~ 71 Hz). Cortical units could follow the slow temporal modulation flow produced by the occurrence of multisyllabic bouts, but not the fast acoustic-flow created by rapid syllable repetition within the bouts. Taken together, our results indicate that even in fast vocalizing animals, such as bats, cortical neurons can only track the temporal structure of acoustic streams modulated at frequencies lower than 22 Hz.

This article is protected by copyright. All rights reserved.



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Modulating vicarious tactile perception with transcranial electrical current stimulation

Abstract

Our capacity to share the experiences of others is a critical part of social behaviour. One process thought to be important for this is vicarious perception. Passively viewing touch activates some of the same network of brain regions as the direct experience of touch. This vicarious experience is usually implicit, but for some people, viewing touch evokes conscious tactile sensations (mirror-touch synaesthesia). Recent work has attempted to induce conscious vicarious touch in those that do not normally experience these sensations, using transcranial direct current stimulation (tDCS). Anodal tDCS applied to primary somatosensory cortex (SI) was found to induce behavioural performance akin to mirror-touch synaesthesia on a visuotactile interference task. Here, we conducted two experiments that sought to replicate and extend these findings by examining: a) the effects of tDCS and high frequency transcranial random noise stimulation (tRNS) targeted at SI and temporo-parietal junction (TPJ) on vicarious tactile perception, b) the extent to which any stimulation effects were specific to viewing touch to humans versus inanimate agents, and c) the influence of visual perspective (viewing touch from one's own versus another's perspective) on vicarious perception. In Experiment 1, tRNS targeted at SI did not modulate vicarious perception. In Experiment 2, tDCS targeted at SI, but not TPJ, resulted in some modulation of vicarious perception, but there were important caveats to this effect. Implications regarding mechanisms of vicarious perception are discussed. Collectively, the findings do not provide convincing evidence for the potential to modulate vicarious tactile perception with transcranial electrical current stimulation.

This article is protected by copyright. All rights reserved.



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Temporal alignment of anticipatory motor cortical beta lateralisation in hidden visual-motor sequences

Abstract

Performance improves when participants respond to events that are structured in repeating sequences, suggesting that learning can lead to proactive anticipatory preparation. Whereas most sequence-learning studies have emphasized spatial structure, most sequences also contain a prominent temporal structure. We used MEG to investigate spatial and temporal anticipatory neural dynamics in a modified serial reaction-time (SRT) task. Performance and brain activity were compared between blocks with learned spatial-temporal sequences and blocks with new sequences. After confirming a strong behavioural benefit of spatial-temporal predictability, we show lateralisation of beta oscillations in anticipation of the response associated with the upcoming target location, and show that this also aligns to the expected timing of these forthcoming events. This effect was found both when comparing between repeated (learned) and new (unlearned) sequences, as well as when comparing targets that were expected after short vs. long intervals within the repeated (learned) sequence. Our findings suggest that learning of spatial-temporal structure leads to proactive and dynamic modulation of motor cortical excitability in anticipation of both the location and timing of events that are relevant to guide action.

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Encoding seasonal information in a two-oscillator model of the multi-oscillator circadian clock

Abstract

The suprachiasmatic nucleus (SCN) is a collection of about 10,000 neurons, each of which functions as a circadian clock with slightly different periods and phases, that work in concert to form and maintain the master circadian clock for the organism. The diversity among neurons confers on the SCN the ability to robustly encode both the 24-hour light pattern as well as the seasonal time. Cluster synchronization brings the different neurons into line and reduces the large population to essentially two oscillators, coordinated by a macroscopic network motif of asymmetric repulsive-attractive coupling. We recount the steps leading to this simplification and rigorously examine the two-oscillator case by seeking an analytical solution. Through these steps, we identify physiologically relevant parameters that shape the behavior of the SCN network and delineate its ability to store past details of seasonal variation in photoperiod.

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AllergoOncology: Opposite Outcomes of Immune Tolerance in Allergy and Cancer

Abstract

While desired for the cure of allergy, regulatory immune cell subsets and non-classical Th2-biased inflammatory mediators in the tumour microenvironment can contribute to immune suppression and escape of tumours from immunological detection and clearance. A key aim in the cancer field is therefore to design interventions that can break immunological tolerance and halt cancer progression, whereas on the contrary allergen immunotherapy exactly aims to induce tolerance. In this position paper, we review insights on immune tolerance derived from allergy and from cancer inflammation, focusing on what is known about the roles of key immune cells and mediators. We propose that research in the field of AllergoOncology that aims to delineate these immunological mechanisms with juxtaposed clinical consequences in allergy and cancer may point to novel avenues for therapeutic interventions that stand to benefit both disciplines.

This article is protected by copyright. All rights reserved.



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Tonsillectomy in adults: Analysis of indications and complications

Tonsillectomy is one of the surgical techniques most practiced by otolaryngologists, and despite being a relatively simple technique; it presents a considerable percentage of complications, such as postoperative bleeding. The aim of this study is to describe the surgical indications and most frequent complications, analyze whether surgical suture of the tonsillar pillars has an influence on bleeding, and study the data of hospital stay and its importance for the control of complications.

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TLR expression profile of human alveolar bone proper-derived stem/progenitor cells and osteoblasts

Alveolar bone proper-derived stem/progenitor cells (AB-MSCs) and alveolar osteoblasts (OBs) are pivotal cells with positive attributes in regenerative medicine. During regenerative approaches, AB-MSCs may interact with their surrounding environment via their expressed toll-like-receptors (TLRs). This study aimed to depict for the first time the TLRs expression profile of AB-MSCs and OBs.Cells were isolated from human alveolar bone proper, and STRO-1-immunomagnetically sorted to segregate AB-MSCs and OBs.

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A novel method to prevent catheter dysfunction during spray cryotherapy



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Accidental fracture of an EUS-FNA needle



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Use of Volumetric Laser Endomicroscopy to Characterize a Duodenal Neuroendocrine Tumor



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Three-dimensional strut plate for the treatment of mandibular fractures: a systematic review

The treatment of mandibular fractures by open reduction and internal fixation is very variable. Thus, there are many controversies about the best fixation system in terms of stability, functional recovery, and postoperative complications. This systematic review sought scientific evidence regarding the best indication for the use of three-dimensional (3D) plates in the treatment of mandibular fractures. A systematic search of the PubMed/MEDLINE, Elsevier/Scopus, and Cochrane Library databases was conducted to include articles published up until November 2016.

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Oropharyngeal epignathus with partial facial duplication: report of a rare case

Foetal oral teratoma or epignathus is a rare benign condition that originates in the oropharyngeal region. The term 'teratoma' refers to a mass composed of poorly organized tissues derived from each of the three germ layers. Epignathus may occur when one twin ceases development during gestation and becomes vestigial to the fully formed dominant twin. The reported incidence of epignathus is approximately 1:35,000 to 1:200,000 live births. A unique case of partial facial duplication with gross histological and radiological evidence of partial duplication of the facial elements and organs is presented herein.

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Dendritic spines provide cognitive resilience against Alzheimer's disease

Abstract

Objective: Neuroimaging and other biomarker assays suggest that the pathological processes of Alzheimer's disease (AD) initiate years prior to clinical dementia onset. However some 30%-50% of older individuals that harbor AD pathology do not become symptomatic in their lifetime. It is hypothesized that such individuals exhibit cognitive resilience that protects against AD dementia. We hypothesized that in cases with AD pathology structural changes in dendritic spines would distinguish individuals that had or did not have clinical dementia.

Methods: We compared dendritic spines within layers II and III pyramidal neuron dendrites in Brodmann Area 46 dorsolateral prefrontal cortex using the Golgi-Cox technique in 12 age-matched pathology-free controls, 8 controls with AD pathology (CAD), and 21 AD cases. We used highly optimized methods to trace impregnated dendrites from brightfield microscopy images which enabled accurate three-dimensional digital reconstruction of dendritic structure for morphologic analyses.

Results: Spine density was similar among control and CAD cases but reduced significantly in AD. Thin and mushroom spines were reduced significantly in AD compared to CAD brains, whereas stubby spine density was decreased significantly in CAD and AD compared to controls. Increased spine extent distinguished CAD cases from controls and AD. Linear regression analysis of all cases indicated that spine density was not associated with neuritic plaque score but did display negative correlation with Braak staging.

Interpretation: These observations provide cellular evidence to support the hypothesis that dendritic spine plasticity is a mechanism of cognitive resilience that protects older individuals with AD pathology from developing dementia. This article is protected by copyright. All rights reserved.



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Cancer-specific mortality of high-risk prostate cancer after carbon-ion radiotherapy plus long-term androgen deprivation therapy

Abstract

The treatment outcomes of patients with high-risk localized prostate cancer (PC) after carbon-ion radiotherapy (CIRT) combined with long-term androgen deprivation therapy (LTADT) were analyzed, and compared with those of other treatment modalities, focusing on PC-specific mortality (PCSM). A total of 1247 patients were enrolled in three phase II clinical trials of fixed-dose CIRT between 2000 and 2013. Excluding patients with T4 disease, 608 patients with high- or very-high-risk PC, according to the National Comprehensive Cancer Network classification system, who received CIRT with LTADT were evaluated.

The median follow-up was 88.4 months, and the 5-/10-year PCSM rates were 1.5%/4.3%, respectively. T3b disease, Gleason score of 9-10, and percentage of positive biopsy cores > 75% were associated with significantly higher PCSM on univariate and multivariate analyses. The 10-year PCSM rates of patients having all three (n=16), two (n=74), or one of these risk factors (n=217) were 27.1%, 11.6%, and 5.7%, respectively. Of the 301 patients with none of these factors, only 1 PCSM occurred over the 10-year follow-up (10-year PCSM rate, 0.3%), and significant differences were observed among the four stratified groups (p < 0.001).

CIRT combined with LTADT yielded relatively favorable treatment outcomes in patients with high-risk PC and very favorable results in patients without any of the three abovementioned factors for PCSM. Because a significant difference in PCSM among the high-risk PC patient groups was observed, new categorization and treatment intensity adjustment may be required for high-risk PC patients treated with CIRT.

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The miR-203 inhibits cell proliferation, invasion, and migration of non-small cell lung cancer by downregulating RGS17

Abstract

The involvement of the RGS17 oncogene in promotion of non-small cell lung cancer (NSCLC) has been reported, but the regulation mechanism in NSCLC remains unclear. MicroRNAs (miRNAs) negatively regulate gene expression, and their dysregulation has been implicated in tumorigenesis. To understand the role of microRNAs in RGS17-induced NSCLC, we showed that miR-203 was downregulated during tumorigenesis, and inhibited the proliferation and invasion of lung cancer cells. We then determined if miR-203 regulated NSCLC by targeting RGS17. To characterize the regulatory effect of miR-203 on RGS17, we used lung cancer cell lines, A549 and Calu-1, and the constructed miR-203 and RGS17 overexpression vectors. The CCK8 kit was used to determine the cell proliferation, and the Transwell® assay was used to measure cell invasion and migration. RT-PCR, western blots, and immunofluorescence were used to analyze the expression of miR-203 and RGS17, and the luciferase reporter assay was used to examine the interaction between miR-203 and RGS17. Nude mice were used to characterize in vivo tumor growth regulation. The expression of miR-203 inhibited the proliferation, invasion, and migration of lung cancer cell lines A549 and Calu-1 by targeting RGS17. The regulatory effect of miR-203 was inhibited after overexpression of RGS17. The luciferase reporter assay showed that miR-203 downregulated RGS17 by direct integration into the 3′-UTR of RGS17 mRNA. In vivo studies showed that the expression of miR-203 significantly inhibited the growth of tumors. Taken together, the results suggested that the expression of miR-203 inhibited tumor growth and metastasis by targeting RGS17.

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Implementation and preliminary clinical outcomes of a pharmacist-managed venous thromboembolism clinic for patients treated with rivaroxaban post emergency department discharge

Abstract

Objective

To describe the implementation, work flow, and differences in outcomes between a pharmacist-managed clinic for the outpatient treatment of venous thromboembolism (VTE) using rivaroxaban versus care by a primary care provider.

Interventions

Patients in the studied health system that are diagnosed with low-risk VTE in the emergency department are often discharged without hospital admission. These patients are treated with rivaroxban and follow up either in a pharmacist-managed VTE clinic or with their primary care provider. Pharmacists in the VTE clinic work independently under a collaborative practice agreement. An evaluation of thirty-four patients, seventeen in each treatment arm, was conducted to compare the differences in treatment-related outcomes of rivaroxaban when managed by a pharmacist versus a primary care provider.

Results

The primary endpoint was a six month composite of anticoagulation treatment-related complications that included a diagnosis of major bleeding, recurrent thromboembolism, or fatality due to either major bleeding or recurrent thromboembolism. Secondary endpoints included number of hospitalizations, adverse events, and medication adherence. There was no difference in the primary endpoint between groups with one occurrence of the composite endpoint in each treatment arm (p=1.000), both of which were recurrent thromboembolic events. Medication adherence assessment was formally performed in 8 patients in the pharmacist group versus 0 patients in the control group. No differences were seen amongst other secondary endpoints.

Conclusions

The pharmacist-managed clinic is a novel expansion of clinical pharmacy services that treats patients with low-risk VTEs with rivaroxaban in the outpatient setting. The evaluation of outcomes provides support that pharmacist-managed care utilizing standardized protocols under a collaborative practice agreement may be as safe as care by a primary care provider.

This article is protected by copyright. All rights reserved.



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HLA class I expression predicts prognosis and therapeutic benefits from tyrosine kinase inhibitors in metastatic renal-cell carcinoma patients

Abstract

Purpose

Classical HLA class I antigen is highly involved in antigen presentation and adaptive immune response against tumor. In this study, we explored its predictive value for treatment response and survival in metastatic renal-cell carcinoma (mRCC) patients.

Experimental design

A TKI cohort of 111 mRCC patients treated with sunitinib or sorafenib and a non-TKI cohort of 160 mRCC patients treated with interleukin-2 or interferon-α-based immunotherapy at a single institution were retrospectively enrolled. HLA class I expression and cytotoxic T lymphocyte (CTL) density was assessed by immunohistochemistry on tissue microarrays. Association between HLA class I and CTL was also assessed in the TCGA KIRC cohort.

Results

In the TKI cohort, down-regulated HLA class I was associated with lower objective response rate of TKI therapy (P = 0.004), shorter overall survival (OS) (P = 0.001), and shorter progression free survival (PFS) (P < 0.001). Multivariate Cox regression model defined HLA expression as an independent prognostic factor for both OS [hazard ratio 1.687 (95% CI 1.045–2.724), P = 0.032] and PFS [hazard ratio 2.139 (95% CI 1.376–3.326), P = 0.001]. In the non-TKI cohort, HLA class I was not significantly associated with survival. HLA class I expression was associated with CTL infiltration and function, and its prognostic value was more predominant in CTL high-density tumors (P < 0.001) rather than CTL low-density tumors (P = 0.294).

Conclusions

Classical HLA class I expression can serve as a potential predictive biomarker for TKI therapy in mRCC patients. Its predictive value was restricted in CTL high-density tumors. However, further external validations and functional investigations are still required.



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Effects of tetramethylpyrazine phosphate on pancreatic islet microcirculation in SD rats

Abstract

Purposes

Abnormal islet microcirculation impetus the insulin production and accelerates progression of Type 1 and 2 diabetes. In this study, we investigated whether tetramethylpyrazine phosphate (TMPP), a vasoactive substance, could regulate the islet microcirculation and insulin concentration and improve glycaemia in SD rats.

Methods

SD rats were randomly divided into two groups, the control and TMPP groups. Each group was further divided into three subgroups according to the intravenous injection of either saline, 15 or 30% glucose. The non-radioactive microsphere technique was adopted to measure the organ blood flow. Nitric oxide synthase (NOS) blocker l-NAME was used to address whether NO was involved in mediating the vasoactive effects of TMPP.

Results

In the TMPP group, TMPP increased the PBF (pancreatic blood flow), IBF (islet blood flow), and fIBF (fraction of islet blood flow out of pancreatic blood flow) by 57, 76 and 47%, respectively, after 30% glucose infusion, compared with the control, indicating that TMPP could regulate islet microcirculation. Furthermore, TMPP induced a 66% elevation of IBF and 37% of fIBF in the 30% glucose subgroups than the 15% ones. In 30% glucose-treated subgroups, TMPP improved the blood glucose concentration by 10%, compared with the control (19.3 ± 0.64 vs 17.32 ± 0.56 mmol/l, P < 0.05), without influencing the insulin secretion. Blocking NO formation prevented the enhanced PBF and IBF, evoking by TMPP with 30% glucose.

Conclusions

TMPP can regulate the pancreatic islet microcirculation and possess a hypoglycemia effect after glucose infusion through affecting the islet microcirculation.



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HLA class I expression predicts prognosis and therapeutic benefits from tyrosine kinase inhibitors in metastatic renal-cell carcinoma patients

Abstract

Purpose

Classical HLA class I antigen is highly involved in antigen presentation and adaptive immune response against tumor. In this study, we explored its predictive value for treatment response and survival in metastatic renal-cell carcinoma (mRCC) patients.

Experimental design

A TKI cohort of 111 mRCC patients treated with sunitinib or sorafenib and a non-TKI cohort of 160 mRCC patients treated with interleukin-2 or interferon-α-based immunotherapy at a single institution were retrospectively enrolled. HLA class I expression and cytotoxic T lymphocyte (CTL) density was assessed by immunohistochemistry on tissue microarrays. Association between HLA class I and CTL was also assessed in the TCGA KIRC cohort.

Results

In the TKI cohort, down-regulated HLA class I was associated with lower objective response rate of TKI therapy (P = 0.004), shorter overall survival (OS) (P = 0.001), and shorter progression free survival (PFS) (P < 0.001). Multivariate Cox regression model defined HLA expression as an independent prognostic factor for both OS [hazard ratio 1.687 (95% CI 1.045–2.724), P = 0.032] and PFS [hazard ratio 2.139 (95% CI 1.376–3.326), P = 0.001]. In the non-TKI cohort, HLA class I was not significantly associated with survival. HLA class I expression was associated with CTL infiltration and function, and its prognostic value was more predominant in CTL high-density tumors (P < 0.001) rather than CTL low-density tumors (P = 0.294).

Conclusions

Classical HLA class I expression can serve as a potential predictive biomarker for TKI therapy in mRCC patients. Its predictive value was restricted in CTL high-density tumors. However, further external validations and functional investigations are still required.



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A retrospective review of initial bisphosphonate infusion in an inpatient vs. outpatient setting for bisphosphonate naïve patients

Journal Name: Journal of Pediatric Endocrinology and Metabolism
Issue: Ahead of print


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Evaluation of neurodevelopment of children with congenital hypothyroidism by the Denver Developmental Screening Test

Journal Name: Journal of Pediatric Endocrinology and Metabolism
Issue: Ahead of print


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HLA class I expression predicts prognosis and therapeutic benefits from tyrosine kinase inhibitors in metastatic renal-cell carcinoma patients

Abstract

Purpose

Classical HLA class I antigen is highly involved in antigen presentation and adaptive immune response against tumor. In this study, we explored its predictive value for treatment response and survival in metastatic renal-cell carcinoma (mRCC) patients.

Experimental design

A TKI cohort of 111 mRCC patients treated with sunitinib or sorafenib and a non-TKI cohort of 160 mRCC patients treated with interleukin-2 or interferon-α-based immunotherapy at a single institution were retrospectively enrolled. HLA class I expression and cytotoxic T lymphocyte (CTL) density was assessed by immunohistochemistry on tissue microarrays. Association between HLA class I and CTL was also assessed in the TCGA KIRC cohort.

Results

In the TKI cohort, down-regulated HLA class I was associated with lower objective response rate of TKI therapy (P = 0.004), shorter overall survival (OS) (P = 0.001), and shorter progression free survival (PFS) (P < 0.001). Multivariate Cox regression model defined HLA expression as an independent prognostic factor for both OS [hazard ratio 1.687 (95% CI 1.045–2.724), P = 0.032] and PFS [hazard ratio 2.139 (95% CI 1.376–3.326), P = 0.001]. In the non-TKI cohort, HLA class I was not significantly associated with survival. HLA class I expression was associated with CTL infiltration and function, and its prognostic value was more predominant in CTL high-density tumors (P < 0.001) rather than CTL low-density tumors (P = 0.294).

Conclusions

Classical HLA class I expression can serve as a potential predictive biomarker for TKI therapy in mRCC patients. Its predictive value was restricted in CTL high-density tumors. However, further external validations and functional investigations are still required.



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In vitro inhibition of HIV-1 replication in autologous CD4 + T cells indicates viral containment by multifactorial mechanisms

Abstract

HIV-1-specific cytotoxic T lymphocytes (CTLs) and neutralizing antibodies (NAbs) are present during chronic infection, but the relative contributions of these effector mechanisms to viral containment remain unclear. Here, using an in vitro model involving autologous CD4+ T cells, primary HIV-1 isolates, HIV-1-specific CTLs, and neutralizing monoclonal antibodies, we show that b12, a potent and broadly neutralizing monoclonal antibody to HIV-1, was able to block viral infection when preincubated with virus prior to infection, but was much less effective than CTLs at limiting virus replication when added to infected cell cultures. However, the same neutralizing antibody was able to contain viruses by antibody-dependent cell-mediated virus inhibition in vitro, which was mediated by natural killer cells (NKs) and dependent on an Fc-Fc receptor interaction. Meanwhile, bulk CTLs from HIV-1 controllers were more effective in suppression of virus replication than those from progressors. These findings indicate that control of HIV-1 replication in activated CD4+ T cells is ineffectively mediated by neutralizing antibodies alone, but that both CTLs and antibody-dependent NK-mediated immune mechanisms contribute to viral containment. Our study systemically compared three major players in controlling HIV-1 infection, CTLs, NAbs, and NKs, in an autologous system and highlighted the multifactorial mechanisms for viral containment and vaccine success.



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Effects of tetramethylpyrazine phosphate on pancreatic islet microcirculation in SD rats

Abstract

Purposes

Abnormal islet microcirculation impetus the insulin production and accelerates progression of Type 1 and 2 diabetes. In this study, we investigated whether tetramethylpyrazine phosphate (TMPP), a vasoactive substance, could regulate the islet microcirculation and insulin concentration and improve glycaemia in SD rats.

Methods

SD rats were randomly divided into two groups, the control and TMPP groups. Each group was further divided into three subgroups according to the intravenous injection of either saline, 15 or 30% glucose. The non-radioactive microsphere technique was adopted to measure the organ blood flow. Nitric oxide synthase (NOS) blocker l-NAME was used to address whether NO was involved in mediating the vasoactive effects of TMPP.

Results

In the TMPP group, TMPP increased the PBF (pancreatic blood flow), IBF (islet blood flow), and fIBF (fraction of islet blood flow out of pancreatic blood flow) by 57, 76 and 47%, respectively, after 30% glucose infusion, compared with the control, indicating that TMPP could regulate islet microcirculation. Furthermore, TMPP induced a 66% elevation of IBF and 37% of fIBF in the 30% glucose subgroups than the 15% ones. In 30% glucose-treated subgroups, TMPP improved the blood glucose concentration by 10%, compared with the control (19.3 ± 0.64 vs 17.32 ± 0.56 mmol/l, P < 0.05), without influencing the insulin secretion. Blocking NO formation prevented the enhanced PBF and IBF, evoking by TMPP with 30% glucose.

Conclusions

TMPP can regulate the pancreatic islet microcirculation and possess a hypoglycemia effect after glucose infusion through affecting the islet microcirculation.



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Conventional as well as Emerging Arsenic Removal Technologies—a Critical Review

Abstract

Arsenic poisoning from contaminated drinking water has evolved as one of the major health hazards in recent times. High concentrations of arsenic in water and soil have been found in many parts of the world. Developing countries like Taiwan, Chile, Argentina, Bangladesh, Nepal and Vietnam are most affected by the contamination of groundwater with arsenic. These countries also cannot afford expensive and large-scale treatments to remove arsenic from drinking waters to acceptable limits (10 ppb, as recommended by WHO and US EPA). The aim of this review is to summarize low-cost, effective conventional technologies currently described in the literature for arsenic removal that can be used in the third world and developing countries, compare them with the emerging technologies and discuss their advantages and disadvantages along with a brief analysis of arsenic chemistry.



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Concurrent Improvement in Both Binge Eating and Depressive Symptoms with Naltrexone/Bupropion Therapy in Overweight or Obese Subjects with Major Depressive Disorder in an Open-Label, Uncontrolled Study

Abstract

Introduction

Binge eating disorder (BED) is associated with obesity and major depressive disorder (MDD). Naltrexone extended-release (ER)/bupropion ER (NB) is approved as an adjunct to diet and physical activity for chronic weight management. In a prospectively designed 24-week open-label, single-arm, single-site trial of 25 women with MDD and overweight/obesity, NB reduced weight and depressive symptoms.

Methods

This post hoc analysis investigated the relationship between change in self-reported binge eating behavior (evaluated with the Binge Eating Scale [BES]) and changes in weight, control of eating, and depressive symptoms.

Results

At baseline, 91% of subjects had moderate or severe BES scores, suggesting BED. BES scores were significantly improved from week 4, and by week 24, 83% reported "little or no problem." Improvement in BES scores correlated with improvement in depressive symptoms and control of eating.

Conclusion

NB may be effective in reducing binge eating symptoms associated with MDD and overweight/obesity. Evaluation of NB in BED appears warranted.

Funding

Orexigen Therapeutics, Inc.



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Notch signaling pathway networks in cancer metastasis: a new target for cancer therapy

Abstract

Notch signaling pathway is evolutionarily conserved in mammals, which plays an important role in cell development and differentiation. In recent years, increasing evidence has shown that aberrant activation of Notch is associated with tumor process. Aberrant activation of Notch signaling pathway has been found in many different solid tumors can induce cell proliferation, metastasis and epithelial-mesenchymal transition. Notch receptor and its ligand are both single transmembrane protein, and Notch is activated when it binds to the Notch ligand of neighbor cells. The signal transduction of Notch signaling pathway is only between cells that are in contact with each other, which is independent of second messengers. Thus, Notch needs to cross talk with other signaling pathways, including PI3K/AKT, NF-κB, integrin and miRNAs, to precisely regulate cell fate. In this review, we summarize the roles of Notch signaling pathway in tumor metastasis and its regulatory mechanisms and discuss the current treatment strategies targeting Notch signal pathway.



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Skeletal muscle mechanics: questions, problems and possible solutions

Skeletal muscle mechanics have been studied ever since people have shown an interest in human movement. However, our understanding of muscle contraction and muscle mechanical properties has changed fundamental...

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Rare Giant Upper Lip Epidermal Cyst in a Patient Wearing a Denture.

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Rare Giant Upper Lip Epidermal Cyst in a Patient Wearing a Denture.

Arch Craniofac Surg. 2016 Dec;17(4):222-224

Authors: Kim JC, Hong IP

Abstract
Epidermal cysts are intradermal or subcutaneous cystic tumors that frequently occur in the face, scalp, neck, and body trunk. Acquired cases of epidermal cyst commonly occur as a result of various surgical operations, chronic irritation, or trauma, all of which may trigger the occurrence of the invagination of squamous epithelium. A 57-year-old man presented with a palpable mass 7 cm×2 cm in size in the upper lip. The patient had a 3-year history of wearing a denture to restore missing bilateral maxillary central and lateral incisors, accompanied by inflammatory findings on the buccal mucosa due to chronic lip irritation. The resected oval-shaped cyst had a size of 5.5 cm×3.0 cm×2.5 cm, and it was an encapsulated mass with a well-defined margin. The histopathology was typical of epidermal cyst. This case of a rare giant upper lip epidermal cyst in a patient wearing a denture may be of interest to clinicians.

PMID: 28913288 [PubMed]



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Dosimetric comparison of different treatment modalities for stereotactic radiotherapy

The modalities for performing stereotactic radiotherapy (SRT) on the brain include the cone-based linear accelerator (linac), the flattening filter-free (FFF) volumetric modulated arc therapy (VMAT) linac, and...

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"Gan To Kagaku Ryoho"[jour]; +20 new citations

20 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"Gan To Kagaku Ryoho"[jour]

These pubmed results were generated on 2017/09/16

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.



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Complications and parent satisfaction in pediatric osseointegrated bone-conduction hearing implants.

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Complications and parent satisfaction in pediatric osseointegrated bone-conduction hearing implants.

Laryngoscope. 2017 Sep;127(9):2165-2170

Authors: Chan KH, Gao D, Jensen EL, Allen GC, Cass SP

Abstract
OBJECTIVE: To assess long-term complication rate and parental satisfaction of osseointegrated bone conduction hearing implants (OBCHIs).
STUDY DESIGN: Retrospective chart review of children undergoing OBCHIs.
METHODS: A retrospective chart review of children undergoing OBCHIs for the treatment of conductive, mixed, and single-sided sensorineural hearing loss in children.
RESULTS: Forty-five subjects were identified with 0.3 to 10.4 years of follow-up. The mean/median age and age range at implant were 9.0/7.8 and 1.7 to 19.1 years. The underlying hearing loss for the cohort included conductive (N = 30), sensorineural (N = 7), and mixed (N = 8) hearing loss. Conductive hearing loss, caused by aural atresia (62.9), was the most common indication for implantation. Fifty-eight complications occurred in 29 subjects, most related to skin infection or overgrowth. Seventeen events required revision surgery, and 18 required oral antibiotics and/or office-based cauterization. Children under the age of 5 years were more likely to have failure of osseointegration or require revision surgery. Parents of 33 subjects underwent a phone interview; 76% rated the overall satisfaction as satisfied or very satisfied.
CONCLUSION: A large percentage of children undergoing OBCHI develop postoperative complications, and up to 44% require revision surgery-a figure higher than generally reported and higher than in adults. No factors were found to adequately explain the higher complication rates in children compared to adults. Despite the occurrence of complications, parents viewed this device as satisfactory from many perspectives.
LEVEL OF EVIDENCE: 4. Laryngoscope, 127:2165-2170, 2017.

PMID: 28092097 [PubMed - indexed for MEDLINE]



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Is hippocampal neurogenesis modulated by the sensation of self-motion encoded by the vestibular system?

Related Articles

Is hippocampal neurogenesis modulated by the sensation of self-motion encoded by the vestibular system?

Neurosci Biobehav Rev. 2017 Sep 11;:

Authors: Smith PF

Abstract
It is now well accepted that physical exercise stimulates hippocampal neurogenesis and may promote cognitive ability. Less clear are the mechanisms by which this process occurs. One potential contributing influence, that is usually neglected, is the vestibular system, which by its very nature must be activated during physical exercise and which essentially cannot be turned off without complete bilateral vestibular lesions. This paper reviews a small literature that demonstrates that bilateral vestibular loss (BVL) in rats modulates cell proliferation in the dentate gyrus (DG) and that artificial electrical activation of the vestibular system, using galvanic vestibular stimulation, does also. Although there are only a few piecemeal studies of this subject, because of the way that they were controlled, it is likely that the vestibular system has a regulatory role in cell proliferation in the DG and therefore possibly in neurogenesis, which needs to be taken into account in the interpretation of neurogenesis studies.

PMID: 28912091 [PubMed - as supplied by publisher]



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Is hippocampal neurogenesis modulated by the sensation of self-motion encoded by the vestibular system?

Related Articles

Is hippocampal neurogenesis modulated by the sensation of self-motion encoded by the vestibular system?

Neurosci Biobehav Rev. 2017 Sep 11;:

Authors: Smith PF

Abstract
It is now well accepted that physical exercise stimulates hippocampal neurogenesis and may promote cognitive ability. Less clear are the mechanisms by which this process occurs. One potential contributing influence, that is usually neglected, is the vestibular system, which by its very nature must be activated during physical exercise and which essentially cannot be turned off without complete bilateral vestibular lesions. This paper reviews a small literature that demonstrates that bilateral vestibular loss (BVL) in rats modulates cell proliferation in the dentate gyrus (DG) and that artificial electrical activation of the vestibular system, using galvanic vestibular stimulation, does also. Although there are only a few piecemeal studies of this subject, because of the way that they were controlled, it is likely that the vestibular system has a regulatory role in cell proliferation in the DG and therefore possibly in neurogenesis, which needs to be taken into account in the interpretation of neurogenesis studies.

PMID: 28912091 [PubMed - as supplied by publisher]



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Health-related quality of life in melanoma patients: Impact of melanoma-related limb lymphoedema

S09598049.gif

Publication date: November 2017
Source:European Journal of Cancer, Volume 85
Author(s): Caroline A. Gjorup, Mogens Groenvold, Helle W. Hendel, Karin Dahlstroem, Krzysztof T. Drzewiecki, Tobias W. Klausen, Lisbet R. Hölmich
AimTo explore health-related quality of life (HRQoL) in recurrence-free melanoma patients, with a focus on the association between melanoma-related limb lymphoedema and HRQoL.MethodsHRQoL was evaluated using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30), the breast cancer module (EORTC QLQ-BR23) subscales body image and future perspective, the Functional Assessment for Cancer Therapy-General subscale social/family well-being and the Hospital Anxiety and Depression Scale. Data were analysed using linear and ordinal logistic regression adjusting for age and gender.ResultsA total of 431 melanoma patients who had undergone wide local excision and axillary or inguinal sentinel lymph node biopsy (SLNB) and/or complete lymph node dissection (CLND) participated. No patients had had recurrence of the disease or had received adjuvant radiotherapy. The HRQoL scores improved with time after surgery. Melanoma-related limb lymphoedema was present in 109 patients (25%). Patients with lymphoedema had significantly worse HRQoL scores in the EORTC QLQ-C30 subscales global health status/quality of life, role and social functioning, fatigue, pain and financial difficulties, as well as in the QLQ-BR23 body image subscale. No associations were found between the limb affected (upper or lower limb), clinical stage of lymphoedema, duration of lymphoedema or type of surgery (SLNB or CLND) and HRQoL. We found an interaction with age and gender in the associations between lymphoedema and HRQoL: younger patients and women with lymphoedema had worse social functioning and women had significantly more impaired body image.ConclusionsThe negative impact of melanoma-related limb lymphoedema on HRQoL emphasises the importance of developing strategies for increasing awareness and improving prevention and treatment of lymphoedema.



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Isolated limb perfusion for locally advanced angiosarcoma in extremities: A multi-centre study

S09598049.gif

Publication date: November 2017
Source:European Journal of Cancer, Volume 85
Author(s): E.A. Huis in 't Veld, D.J. Grünhagen, C. Verhoef, H.G. Smith, A.C.J. van Akkooi, R. Jones, F. van Coevorden, A.J. Hayes, W.J. van Houdt
BackgroundAngiosarcomas are rare and aggressive soft-tissue sarcomas. The only potential curative treatment is complete surgical excision. This study reports the outcome of isolated limb perfusion (ILP) with high-dose melphalan and tumour necrosis factor α for locally advanced angiosarcoma.Material and methodsAll patients who underwent an ILP for angiosarcomas between 1991 and 2016 in three tertiary referral centres were identified from prospectively maintained databases.ResultsA total of 39 patients were included, with a median follow-up of 18 months (interquartile range 6.1–60.8). Of these patients, 23 (58.9%) patients had a complete response (CR) after ILP, 10 (25.6%) had a partial response, 4 (10.3%) had stable disease and 2 (5.1%) patients had progressive disease immediately after ILP. A total of 22 patients developed local progression (56.4%), whereas nine (23.1%) developed distant metastases. The patients with CR had a significantly prolonged median local progression-free survival (PFS) (15.4 versus 7.3 months, p = 0.015) when compared with non-CR patients, and a trend towards better median overall survival (81.2 versus 14.5 months, p = 0.054). Six patients underwent multiple ILPs, whereby the CR rate of the first, second and third ILPs were 60%, 80% and 67%, respectively. Thirteen (33.3%) patients needed further surgical intervention, consisting of resection in eight patients (20.5%) and amputation in five patients (12.8%).ConclusionILP is an effective treatment option for patients with locally advanced angiosarcoma in the extremities, resulting in a high number of CRs, a high limb salvage rate and prolonged local PFS.



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[Clinical study of aged patients with secondary benign paroxysmal positional vertigo].

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[Clinical study of aged patients with secondary benign paroxysmal positional vertigo].

Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2017 Sep 07;52(9):670-675

Authors: Zhu ZJ, Wei LP, Xu ZX, Xu HJ, Liu Q, Luo N

Abstract
Objective: To investigate the clinical features and evaluate the efficacy of manual reduction in treatment of age patients with secondary benign paroxysmal positional vertigo (s-BPPV). Methods: Thirty-two cases of aged patients ( the s-BPPV group: including 19 cases of female and 13 males, age from 60 to 86 years old)with secondary benign paroxysmal positional vertigo from Jul. 2013 to Sep. 2015 in our hospital were retrospectively analyzed. The results were compared with 121 patients( the primary group: including 82 cases of female and 39males, aged from 60 to 86 years old)with aged primary benign paroxysmal positional vertigo(p -BPPV). All the patients were followed up for 12 months. Statistical data analysis was carried out with SPSS 19.0. Results: 20.92%(32/153)of all the observed elderly patients with BPPV was the aged s-BPPV. The sex ratio and onset age had no significant difference between the two groups(χ(2)=0.79, P>0.05; t=0.37, P>0.05). The rate of two or more semicircular canal involvement in the secondary group(21.88%) was higher than that in primary group(6.61%)(χ(2)=6.67, P<0.05). Bilateral semicircular canals were involved in 5 of the 32 cases in secondary group(15.63%) and 4 of the 121 cases in aged primary group(3.31%), The difference was significant(χ(2)=6.94, P<0.05). The effective rate after first manual reduction was 57.50%(23/40)in secondary group and 82.31%(107/130)in primary group, the difference was significant(χ(2)=10.46, P<0.05). The total effective rate were 87.50%(35/40) after more than once manual reduction in secondary group and 91.54%(119/130) in primary group, the difference was not significant(χ(2)= 0.59, P>0.05). The numbers of circulation of the first successful manual reduction management were (3.9±1.3)times in secondary group and (2.1±1.1)times in primary group, the difference was significant(t=3.15, P<0.05). The recurrence rate was 37.50%(15/40) in the secondary group and 16.15%(21/130)in primary group after during follow-up for 12 months, the difference was statistically significant(χ(2)=8.35, P<0.05). Conclusions: It's shown that the aged patients with secondary BPPV is not rare in clinical practice, sudden deafness and head trauma are frequent more than other reasons. The aged patients with secondary BPPV are prone to injury in multi-semicircular and bilateral canal compared with the primary BPPV. The effective rate after first manual reduction of secondary BPPV is lower than primary BPPV, it's needed more circulation of first success in manual reduction management. The total effective rates are not significant in two groups and recurrence rate is relatively high in secondary group.

PMID: 28910891 [PubMed - in process]



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PDL1 And LDHA act as ceRNAs in triple negative breast cancer by regulating miR-34a

The purpose of this study was to elucidate the regulation of programmed death ligand 1 (PDL1), lactate dehydrogenase A (LDHA) and miR-34a in triple negative breast cancer (TNBC) and to explore the function and...

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Overview of Sinonasal and Ventral Skull Base Malignancy Management.

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Overview of Sinonasal and Ventral Skull Base Malignancy Management.

Otolaryngol Clin North Am. 2017 Apr;50(2):205-219

Authors: Svider PF, Setzen M, Baredes S, Liu JK, Eloy JA

Abstract
Significant technological advances have fostered a movement toward minimally invasive surgical interventions for the management of ventral skull base malignancies. The care of patients with these lesions ideally involves an interdisciplinary skull base team that includes otolaryngologists, neurologic surgeons, radiation oncologists, and medical oncologists. This article describes considerations essential for diagnosis, prognosis, and preoperative evaluation. Furthermore, surgical nuances, strategies for skull base reconstruction, and nonsurgical options are briefly discussed. This overview may be useful as an up-to-date description of the challenging clinical scenarios associated with these lesions.

PMID: 28160998 [PubMed - indexed for MEDLINE]



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[Clinical analysis of orbital complications due to rhinosinusitis in 28 cases].

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[Clinical analysis of orbital complications due to rhinosinusitis in 28 cases].

Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2017 Sep 07;52(9):664-669

Authors: Li N, Yu LG, Chen M, Yang L, Qin ZR, Jiang Y

Abstract
Objective: To investigate the clinical characteristics of orbital complications due to rhinosinusitis and to provide the basis for the diagnosis and treatment of this disease. Methods: Retrospectively analyzed the clinical data of 28 patients with orbital complications due to rhinosinusitis who were admitted into the Affiliated Hospital of Qingdao University, Department of Otorhinolaryngology from August 2009 to April 2017. In all 28 cases, there were 1 case with preseptal cellulites, 9 cases with orbital cellulites, 13 cases with subperiosteal orbital abscess and 5 cases with orbital abscess. Among all the patients, 9 were younger than 14. Two patients were in ages from 14 to 17 and 7 patients were at or above 18 years. Absolute medicine therapy was performed on 8 patients and combined therapy of operation and pharmacotherapy on 20 patients. Results: The patients were followed up for 2 to 19 months. Both the general symptoms and ocular symptoms disappeared and nasal ventilation function recovered well. Conclusions: The treatment for orbital complications of rhinosinusitis includes absolute medicine therapy and combined therapy of operation and pharmacotherapy. And the selection of treatment depends on disease stage. Timely diagnosis and reasonable treatment would be beneficial in the recovery of patients.

PMID: 28910890 [PubMed - in process]



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Scaling of dentition and prey size in the California moray (Gymnothorax mordax).

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Scaling of dentition and prey size in the California moray (Gymnothorax mordax).

Zoology (Jena). 2017 Jun;122:16-26

Authors: Harrison JS, Higgins BA, Mehta RS

Abstract
Scaling patterns of tooth morphology can provide insights on prey capture strategy and dietary patterns as species grow through ontogeny. We report the scaling of dentition and diet and how it relates to body size in the California moray, Gymnothorax mordax. We sampled lengths, widths, and curvature for teeth lining five distinct regions of the oral jaws across 21 G. mordax individuals ranging from 383 to 1110mm total length. Absolute tooth length in relation to moray size shows positive allometry only for the outer maxillary teeth, while teeth lining the inner maxilla display positive allometry in tooth base width. All other regions exhibit isometric growth in both length and width relative to moray size. Similar to previous descriptions of other moray species, the longest teeth in the oral jaws are the median intermaxillary teeth. This series of three teeth are depressible and rooted in the center of the ethmovomer, the bone that forms the roof of the rostrum. We hypothesize that caudal mobility of the median intermaxillary teeth aids in prey transport by enabling the pharyngeal jaws to remove pierced prey without requiring full abduction of the oral jaws. The predominantly isometric tooth growth in G. mordax suggests that the oral teeth grow proportionately as individuals increase in size. Stomach contents from the field suggest that G. mordax is highly piscivorous. While a strong positively allometric relationship between vertical gape and head length supports the expectation that moray increase relative prey size over ontogeny, we found no relationship between prey standard length and moray size. This suggests that while larger individuals are capable of consuming larger prey, individual G. mordax are opportunistic predators that do not specialize on prey of a specific size over ontogeny.

PMID: 28236504 [PubMed - indexed for MEDLINE]



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Adding Expansile Duraplasty to Posterior Fossa Decompression May Restore Cervical Range of Motion in Grade 3 Chiari Malformation Type 1 Patients.

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Adding Expansile Duraplasty to Posterior Fossa Decompression May Restore Cervical Range of Motion in Grade 3 Chiari Malformation Type 1 Patients.

World Neurosurg. 2017 Feb;98:98-103

Authors: Yilmaz A, Urgun K, Aoun SG, Colak I, Yilmaz I, Altas K, Musluman M

Abstract
BACKGROUND: Few studies have assessed the effect of Chiari malformation type 1 (CM-1) surgical decompression on cervical lordosis and range of motion (ROM). We aimed to assess the effect of expansile duraplasty on postoperative cervical mobility and spinal stability.
MATERIALS AND METHODS: This was a single-center retrospective review of prospectively collected data. Patients were included if they underwent surgical treatment for symptomatic CM-1 between the years 1999 and 2009. Cervical ROM and lordosis were assessed before and after surgery in all patients. Collected data also included clinical improvement, as well as surgical complications after the procedure. Patients were divided into 2 groups. The first group underwent a posterior fossa bony decompression alone, while the second group additionally received an expansile duraplasty. Patients were further subdivided into 3 subgroups on the basis of the severity of tonsillar herniation.
RESULTS: A total of 76 patients fit our selection criteria. Fifty-five patients belonged to the duraplasty group. Twenty-one patients underwent bony decompression alone. The 2 groups were statistically demographically and clinically similar. There was no difference in clinical outcome or in ROM and cervical lordosis between the groups except for patients with severe tonsillar herniation (CM-I grade 3). These patients had a statistically significant improvement in their postoperative cervical motility without compromising their spinal stability.
CONCLUSION: Adding an expansile duraplasty to craniovertebral decompression in CM-1 patients with severe tonsillar herniation may restore cervical ROM while preserving stability and alignment. This may relieve postoperative pain and improve clinical prognosis.

PMID: 27816775 [PubMed - indexed for MEDLINE]



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