Head and Neck Diseases by Alexandros G.Sfakianakis: 12/09/17

Σάββατο 9 Δεκεμβρίου 2017

Prevalence of soft tissue calcifications in the maxillofacial region detected by cone beam CT

Abstract

Objective

To determine the prevalence of soft tissue calcifications in cone beam computed tomography (CBCT) scans with different fields of view (FOV), and to assess its relation with the clinical relevance of the CBCT findings.

Material and Methods

One thousand CBCT scans were grouped according to FOV's size and region scanned (MX-FOV, maxilla; MD-FOV, mandible; and MM-FOV, maxilla/mandible) and evaluated for the presence of soft tissue calcifications. Laterality and length of the elongated styloid processes (ESP) were also assessed.

Results

Eight hundred eighty-two soft tissue calcifications were detected in 626 (62.6%) patients. MM-FOV presented the highest prevalence (76.8%), followed by MD-FOV (60.6%) and MX-FOV (57.2%). ESP and tonsillolith were the most frequent calcifications. Calcifications requiring treatment or not and those in need of follow-up accounted for 6.9%, 92.7% and 0.3% of cases, respectively. There was no association between calcifications and subjects' gender or age (p>0.05). Most cases of ESP occurred bilaterally and were longer in males (p<0.05).

Conclusions

There is a high prevalence of soft tissue calcifications in CBCT, and ESP and tonsilloliths are the most common types in all evaluated FOVs. While most cases do not require treatment, we emphasize the importance of detailed CBCT assessment for its diagnosis.

http://ift.tt/2B58wZb

Is Neutrophilic Desquamative Erythroderma a Form of Acute Generalized Exanthematous Pustulosis?

Abstract

Delayed-type hypersensitivity to systemically administered corticosteroids is rare. Corticosteroids are unique allergens, potentially leading to atypical manifestations. They are commonly used for treatment of allergic, inflammatory and autoimmune diseases because of intrinsically immunosuppressive and immune-modulatory properties (1). These properties may counterbalance, mask and delay allergic reactions as has been shown (1). It has been speculated that allergic reactions to corticosteroids may remain unrecognized due to their broad clinical variability or frequently atypical presentation (1).

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Facial Swelling and Foreign Body Granulomatous Reaction to Hyaluronic Acid Filler in the setting of Neratinib

Abstract

Cosmetic injection of dermal fillers is common, with late complications increasingly recognized. Herein, we report a granulomatous reaction to hyaluronic acid filler occurring during the use of neratinib. A woman in her fifties, with metastatic adenocarcinoma of unknown primary involving the skin and bones, was referred for new-onset facial swelling. Notable past medical history included progression of disease on carboplatin/paclitaxel and a hemithyroidectomy for papillary thyroid cancer.

http://ift.tt/2jh0dm2

Ultrastructural Aspects of Hairs of Chediak-Higashi Syndrome

Abstract

Chediak-Higashi syndrome (CHS) belongs to a group of partial oculocutaneous albinism and immunodeficiency. Five autosomal recessive conditions are recognized in this group, characterized by hypopigmentation of hair, skin and eyes, associated with recurrent infections. Additionally CHS can present coagulopathies, neurological dysfunction and large granules in many cell types.

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Is there a pathogenetic link between frontal fibrosing alopecia, androgenetic alopecia, and fibrosing alopecia in a pattern distribution?

Abstract

Frequent coexistence of frontal fibrosing alopecia (FFA) and androgenetic alopecia (AGA) has been reported in the literature, but little attention has been given to the pathogenetic mechanisms underlying this potential association. FFA is characterized by progressive cicatricial fronto-temporal hairline recession, mostly affecting peri-menopausal women. Immune mechanisms seem to play a pivotal pathogenetic role.

http://ift.tt/2jgZCAO

Bizarre appearance of chronic cutaneous lupus erythematosus of face mimicking factitial dermatitis

Abstract

Old dermatological wisdom says that syphilis and lupus are great imitators. Cutaneous manifestations of lupus erythematosus (LE) are usually characteristic, however, some patients may present with a less typical clinical picture. Correct diagnosis of cutaneous lupus erythematosus (CLE) requires a high level of clinical suspicion and understanding of broad differential diagnosis. Early lesions of CLE are sometimes difficult to diagnose, both clinically and histopathologically.

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Phototherapy in France: quantitative data (2007-2016) from the National Health Insurance register

Abstract

Phototherapy is a cost-effective treatment with a safe side-effect profile for the management of a wide range of dermatoses. Although one of the most common indications for phototherapy is psoriasis, the use of phototherapy for psoriasis has seen a decline in the U.S.A. Data from the National Ambulatory Medical Care Survey indicate a 94% decrease of physician visits for phototherapy between 1994 and 1998.

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Dermoscopic observations in disseminated cryptococcosis with cutaneous involvement

Abstract

A 26-year-old female patient with a history of intravenous drug abuse, diagnosed with acquired immunodeficiency syndrome (AIDS) 6 months before. AIDS defining disease was Pneumocystis jiroveci pneumonia. The patient presented with severely decreased CD4 cell count of 7 cells/mm³ and relatively low HIV viral load of 281 copies/mL. Shortly after initiation of antiretroviral therapy (ART), was diagnosed with disseminated cryptococcosis with central nervous system and skin involvement.

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Power Doppler ultrasound assessment of vascularization in hidradenitis suppurativa lesions

Abstract

Background

Ultrasound and Power Doppler (PD) ultrasound are useful tools to study and monitor Hidradenitis Suppurativa (HS) patients.

Objective

Describe the Power Doppler signal of HS nodules, abscesses, fistulas.

Methods

A retrospective analysis of PD in mild, moderate, severe HS patients, collecting all demographic and clinical data. The lesions were classified according to their ultrasound morphology, describing the vascular degree - high, moderate, minimal - and distribution - peripheral, internal, mixed. Statistical analysis was performed using odds ratio and bivariate regression.

Results

A total of 241 lesions, 62 nodules, 64 abscesses, 99 simple fistulas, 16 complex fistulas, from 61 HS patients, were included. Vascular distribution was defined peripheral in 143/241, mixed in 55/241, internal in 0/241 lesions, regardless the clinical type. Qualitative Doppler showed high vascularization in 44/241 lesions, moderate in 79/241, minimal in 75/241, despite the clinical type. All lesions showed resistive index <0.7. Age, disease's duration, size of the lesions, high Sartorius score, high BMI, showed positive statistically correlation with both PD signal and mixed vascular distribution. No statistically significance was evidenced for vascular degree measurements.

Limitations

Ultrasound cannot detect lesions <0.1 mm.

Conclusion

Vascular distribution of HS lesions can be evaluated by PD with additional relevant information for earlier and better disease management.

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Progressive osseous heteroplasia in a Chinese infant and a novel mutation in the GNAS Gene

Abstract

Progressive osseous heteroplasia(POH,OMIM 166350) is a rare inherited disease that begins with skin ossification and proceeds into the deeper connective tissues. Most cases of POH are caused by heterozygous inactivating mutations of GNAS gene. Herein, we report a new sporadic case of atypical POH and its underlying genetic basis.

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Pili annulati in a case of Rothmund-Thomson syndrome with a novel frameshift mutation in RECQL4

Abstract

Rothmund-Thomson syndrome (RTS) is a rare autosomal recessive genodermatosis characterised by erythematous patches or plaques and sometimes swelling and blisters, which appear during infancy on photo-exposed sites, usually the cheeks, then progress to poikiloderma. Other features include gastrointestinal disturbance, short stature, sparse scalp hair/eyebrows/eyelashes, skeletal abnormalities, juvenile cataracts, hypogonadism and a susceptibility to malignancy. Two forms have been described: Type I, characterised by poikiloderma, ectodermal dysplasia and juvenile cataracts, negative for the RECQL4 mutation, and Type II, with poikiloderma, congenital bone defects and increased risk of osteosarcoma related to deleterious RECQL4 mutations.

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The Clinical Use of Neuromuscular Electrical Stimulation for Neuromuscular Rehabilitation: What Are We Overlooking?

Publication date: Available online 9 December 2017
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Nicola A. Maffiuletti, Julien Gondin, Nicolas Place, Jennifer Stevens-Lapsley, Isabelle Vivodtzev, Marco A. Minetto
The clinical success of neuromuscular electrical stimulation (NMES) for neuromuscular rehabilitation is greatly compromised by the poor consideration of different physiological and methodological issues that are not always obvious for the clinicians. Therefore, the aim of this narrative review is to re-examine some of these fundamental aspects of NMES using a tripartite model perspective. First, we contend that NMES does not actually bypass the central nervous system but results in a multitude of neurally-mediated responses that contribute substantially to force generation and may engender neural adaptations. Second, we argue that too much emphasis is generally placed on externally-controllable stimulation parameters, while the major determinant of NMES effectiveness is the intrinsically-determined muscle tension generated by the current (i.e., evoked force). Third, we believe that a more systematic approach to NMES therapy is required in the clinic, and this implies a better identification of the patient-specific impairment and of the potential "responders" to NMES therapy. Based on these considerations, we suggest that the crucial steps for ensuring the clinical effectiveness of a NMES treatment should consist of: (1) identifying the neuromuscular impairment with clinical assessment; (2) implementing algorithm-based NMES therapy while (3) properly dosing the treatment with tension-controlled NMES and eventually amplifying its neural effects.

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Serious gastric perforation after second stereotactic body radiotherapy for peripheral lung cancer that recurred after initial stereotactic body radiotherapy: a case report

In recent reports, re-irradiation with stereotactic body radiotherapy for lung tumors in patients previously treated with thoracic radiation therapy resulted in several serious toxicities. Serious non-lung tox...

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Prior systemic treatment increased the incidence of somatic mutations in metastatic breast cancer

Publication date: January 2018
Source:European Journal of Cancer, Volume 89
Author(s): Takeo Fujii, Naoko Matsuda, Miho Kono, Kenichi Harano, Huiqin Chen, Rajyalakshmi Luthra, Sinchita Roy-Chowdhuri, Aysegul A. Sahin, Chetna Wathoo, Aron Y. Joon, Debu Tripathy, Funda Meric-Bernstam, Naoto T. Ueno
BackgroundUnderstanding the biology of breast cancer is important for guiding treatment strategies and revealing resistance mechanisms. Our objectives were to investigate the relationship between previous systemic therapy exposure and mutational spectrum in metastatic breast cancer and to identify clinicopathological factors associated with identified frequent somatic mutations.MethodsArchival tissues of patients with metastatic breast cancer were subjected to hotspot molecular testing by next-generation sequencing. The variables that significantly differed (P < 0.05) in univariate analysis were selected to fit multivariate models. Logistic models were fit to estimate the association between mutation status and clinical variables of interest. Five-fold cross-validation was performed to estimate the prediction error of each model.ResultsA total of 922 patients were included in the analysis. In multivariate analysis, previous systemic treatment before molecular testing (N = 186) was associated with a significantly higher rate of TP53 and PIK3CA mutations compared with the lack of systemic treatment (P < 0.001 for both).ConclusionSystemic treatment exposure is an independent risk factor for high rates of TP53 and PIK3CA mutation, which suggests the importance of testing samples after systemic therapy to accurately assess mutations. It is worth testing the gene profile when tumours become resistant to systemic treatments.

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Complete response of a metastatic porocarcinoma treated with paclitaxel, cetuximab and radiotherapy

Publication date: Available online 9 December 2017
Source:European Journal of Cancer
Author(s): C. Godillot, S. Boulinguez, L. Riffaud, V. Sibaud, C. Chira, E. Tournier, C. Paul, N. Meyer

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Antitumor miR-150-5p and miR-150-3p inhibit cancer cell aggressiveness by targeting SPOCK1 in head and neck squamous cell carcinoma

Publication date: Available online 9 December 2017
Source:Auris Nasus Larynx
Author(s): Keiichi Koshizuka, Toyoyuki Hanazawa, Naoko Kikkawa, Koji Katada, Atsushi Okato, Takayuki Arai, Tetsuya Idichi, Yusaku Osako, Yoshitaka Okamoto, Naohiko Seki
ObjectiveOur recent studies have revealed that both strands of pre-miRNAs, the guide strand and the passenger strand, are involved in cancer pathogenesis. Analyses of miRNA expression signatures by RNA sequencing in head and neck squamous cell carcinoma (HNSCC) showed that both of the strands of pre-miR-150 (miR-150-5p and miR-150-3p) were significantly downregulated, and that these miRNAs acted as antitumor miRNAs in HNSCC cells. The aim of this study was to identify oncogenic genes in HNSCC cells that were regulated by miR-150-5p and miR-150-3p.MethodsGenome-wide gene expression studies, in silico analyses and dual-luciferase reporter assays were carried out to predict miR-150-5p and miR-150-3p regulation in HNSCC cells. Knockdown assay was applied to investigate the functional significance of the target gene. Overall patient survival as a function of target gene expression was estimated by The Cancer Genome Atlas (TCGA) database.ResultsA total of 19 genes were putative targets of both miR-150-5p and miR-150-3p regulation. Among them, SPOCK1 (SPARC/osteonectin, cwcv and kazal-like domains proteoglycan 1) was directly regulated by both miRNAs in HNSCC cells. Knockdown studies using si-SPOCK1 showed that expression of SPOCK1 enhanced HNSCC cell aggressiveness. Overexpression of SPOCK1/SPOCK1 was confirmed in HNSCC clinical specimens. Interestingly, analysis of a large number of patients in the TCGA database (n=248) demonstrated that patients with high SPOCK1 expression had significantly shorter survival than did those with low SPOCK1 expression (P=0.0003). Moreover, 15 pathways were identified as SPOCK1-mediated downstream pathways.ConclusionDownregulation of both strands of pre-miR-150 (miR-150-5p and miR-150-3p) and overexpression of SPOCK1 contribute to the aggressive nature of HNSCC. The involvement of passenger strand miRNA in the regulation of HNSCC pathogenesis is a novel concept in RNA research.

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CONTENTS 1

Publication date: November 2017
Source:Materials Today, Volume 20, Issue 9

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CONTENTS 2

Publication date: November 2017
Source:Materials Today, Volume 20, Issue 9

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Early-onset childhood atopic dermatitis is related to NLRP2 repression

Publication date: Available online 9 December 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Loreen Thürmann, Konrad Grützmann, Matthias Klös, Matthias Bieg, Marcus Winter, Tobias Polte, Tobias Bauer, Matthias Schick, Melanie Bewerunge-Hudler, Stefan Roeder, Mario Bauer, Dirk K. Wissenbach, Ulrich Sack, Dieter Weichenhan, Oliver Mücke, Christoph Plass, Michael Borte, Martin von Bergen, Irina Lehmann, Roland Eils, Saskia Trump
Early-onset atopic dermatitis (AD) related repression of the immune regulatory NLRP2 is driven by promoter hypermethylation starting already at time of birth providing an early opportunity to modulate innate immunity to potentially mitigate AD development.

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Erratum: New insights and new hope for pulmonary arterial hypertension: natriuretic peptides clearance receptor as a novel therapeutic target for a complex disease.

Erratum: New insights and new hope for pulmonary arterial hypertension: natriuretic peptides clearance receptor as a novel therapeutic target for a complex disease.

Int J Physiol Pathophysiol Pharmacol. 2017;9(5):164

Authors: Egom EE, Feridooni T, Pharithi RB, Khan B, Shiwani HA, Maher V, El Hiani Y, Rose RA, Pasumarthi KB, Ribama HA

Abstract
[This corrects the article on p. 112 in vol. 9, PMID: 28951773.].

PMID: 29218116 [PubMed - in process]

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Diet Quality, Inflammation, and Quality of Life in Breast Cancer Survivors: A Cross-Sectional Analysis of Pilot Study Data

Publication date: Available online 9 December 2017
Source:Journal of the Academy of Nutrition and Dietetics
Author(s): Tonya S. Orchard, Rebecca R. Andridge, Lisa D. Yee, Maryam B. Lustberg
BackgroundModifiable lifestyle factors, such as diet quality, could reduce inflammation and improve quality of life (QOL) in breast cancer survivors, but data are inconclusive.ObjectiveTo determine whether diet quality, as measured by Healthy Eating Index-2010 (HEI-2010) score, is associated with inflammation, health status, or functional outcomes affecting QOL in survivors of early-stage breast cancer.DesignThis is a cross-sectional, secondary analysis of baseline data collected from breast cancer survivors after completion of primary therapy and before random assignment to a pilot nutritional intervention aimed at reducing side effects of aromatase inhibitor treatment.Participants/settingParticipants were 44 postmenopausal women with stage I to III endocrine receptor–positive breast cancer receiving outpatient care at a midwestern cancer center between November 2011 and October 2013.Main outcome measuresPrimary outcomes were serum proinflammatory cytokines (interleukin-6 [IL-6], IL-17, and tumor necrosis factor-α receptor 2 [TNFR-2]). Secondary outcomes included QOL measured by the Stanford Health and Disability Questionnaire and the Functional Assessment of Cancer Therapy–Breast with Endocrine Subscale.Statistical analyses performedPearson correlation coefficients (r) and linear regression models were used to evaluate the relationship of dietary variables with inflammatory cytokines and QOL measures.ResultsA higher overall HEI-2010 score (healthier diet) was associated with lower IL-6 (r=−0.46; P=0.002) and TNFR-2 (r=−0.41; P=0.006); however, associations were attenuated by body mass index (BMI) (IL=6 [r=−0.26; P=0.10]; TNFR-2 [r=−0.30; P=0.06]). In women with prior chemotherapy, a higher HEI-2010 score was strongly associated with lower IL-6 (r=−0.67; P=0.009) and TNFR-2 (r=−0.59; P=0.03) after BMI adjustment. There were no significant correlations between HEI-2010 score and QOL measures after adjustment for BMI.ConclusionsThese data suggest the need for more rigorous investigation into the relationship of diet quality, BMI, and inflammation in breast cancer survivors.

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Association between continuous positive airway pressure and serum aminotransferases in patients with obstructive sleep apnea

Abstract

Introduction

Obstructive sleep apnea (OSA) has been suggested to be a potential contributing factor for nonalcoholic fatty liver disease (NAFLD). Studies on the association between continuous positive airway pressure (CPAP) and NAFLD in OSA patients are limited and controversial.

Objectives

The aim of this study was to assess the relationship between OSA and NAFLD and the effect of CPAP therapy on serum aminotransferase levels in OSA patients.

Methods

A total of 160 consecutive patients who underwent standard polysomnography were enrolled. Blood samples were obtained in the morning after sleep for biological profile measurements. Non-invasive ultrasound techniques were used to assess liver steatosis and fibrosis. Within the OSA group, serum aminotransferases were detected before and after CPAP treatment.

Results

Alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyltransferase, and liver steatosis score increased significantly with an increase in OSA severity. Stepwise multiple regression with liver steatosis score, ALT, AST as dependent variable, respectively, apnea–hypopnea index (β = 0.447, p = 0.020; β = 0.266, p = 0.001; β = 0.351, p = 0.020, respectively) significantly predicted the liver steatosis score, ALT, AST after adjustment for confounders. After 3 months of CPAP treatment, there was a significant decrease in both ALT (54.20 ± 24.34 vs. 46.52 ± 24.95, p = 0.000) and AST (31.82 ± 8.91 vs. 29.00 ± 8.34, p = 0.039).

Conclusions

OSA severity was independently associated with liver steatosis and elevation of serum aminotransferases. 3 months of CPAP therapy were associated with a statistically significant improvement on liver injury in OSA patients.

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Identification of human papillomavirus (HPV) subtype in oral cancer patients through microarray technology

Abstract

Purpose

Human papilloma virus (HPV) is the main source of cervical cancer. Many recent studies have revealed the prevalence and prognosis of HPV associated with oropharyngeal squamous cell carcinoma, but fewer reports have evaluated HPV in oral squamous cell carcinoma (OSCC). The purpose of this study was to determine the prevalence and prognosis of HPV associated with OSCC according to HPV and tumor types.

Materials and methods

We used a DNA chip kit (MY-HPV chip kit ^®, Mygene Co., Korea) to detect high-risk HPV subtypes (16, 18, 31, 33, 35, 39, 45, 51, 52, 54, 56, 58) and low-risk subtypes (6, 11, 34, 40, 42, 43, 44) among 187 patients. The prevalence was determined by Chi-square and Fisher's exact tests, and the prognosis was calculated by the Kaplan–Meier method and the log-rank test.

Results

The overall prevalence of HPV in OSCC was 7.0% for all HPV positives and 4.3% for high-risk HPV positives. The prevalence of HPV was significantly higher in individuals under 65 years old and in those with tumors in the tongue and gum regions. The prognosis did not differ between the HPV-positive and -negative groups. Although the prevalence of HPV-positive cases in OSCC was low (7.0, 4.3%) and the prognosis did not depend on HPV positivity, HPV-associated OSCC should be considered in the evaluation and treatment of oral cancer patients. In addition, separating high- and low-risk groups based on the HPV status of other body parts might not be appropriate.

Discussion

The DNA microarray method can accurately detect known HPV subtypes simultaneously, but has limitations in detecting new subtypes. Vaccines can also be used to prevent HPV-associated OSCC in patients, so further studies on the prognosis and efficacy of vaccines should be undertaken.

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Identification of human papillomavirus (HPV) subtype in oral cancer patients through microarray technology

Abstract

Purpose

Materials and methods

Results

Discussion

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Pattern of care and impact of prognostic factors on the outcome of head and neck extramedullary plasmacytoma: a systematic review and individual patient data analysis of 315 cases

Abstract

Introduction

Head and neck extramedullary plasmacytoma is a rare localized plasma cell neoplasm. We intended to perform this review of the published literature to assess the demographic profile, pattern of care and survival outcomes.

Methods

Two authors independently searched PubMed, Google search and Cochrane library for eligible studies from 1950 till July 1, 2016, published in English language.

Results

Median age of the cohort was 57 years (range 11–85). Site-wise distributions were paranasal sinuses 22.3% (70), nasal cavity 17.5% (55), nasopharynx 10.8% (34). Median size of SEMP was 3 cm (range 0.3–12 cm). Treatment distribution was radiotherapy (RT) in 52% (164), surgery (S) 19% (60), chemotherapy (C) 5% (16), S + RT 23.49% (74),CRT 1.9% (6), S + C 0.6% (2), S + RT + C 0.95% (3).Radiation was used as a modality in 78.4%(247), surgery in 44.1%(139), chemotherapy in 4.8%(15). Median radiation dose used was 45 Gy with range 20–61 Gy. Median overall survival (OS) was 40 months (range 0.5–298). Median local progression-free survival was 36 months (range 0–298). Median myeloma relapse-free survival was 36 months (range 0.5–298). Five- and 10-year OS was 78.33 and 68.61%. Five-year cause-specific survival (CSS) and 10-year CSS was 90.15 and 83.31%. Five-year LPFS was 94.78%, and 10-year LPFS was 88.43%. Five-year myeloma progression-free survival was 84.46%, and 10-year myeloma PFS was 80.44%. The factors associated with risk of local relapse were site of disease (sinonasal), secretory EMP, type of treatment received (surgery + RT > RT alone > surgery on univariate analysis). Risk factors for myeloma relapse were coexisting diseases, site of disease (sinonasal), bony erosion, size of lesion > 5 cm and type of treatment received on univariate analysis.

Conclusion

Our study shows that combined modality S + RT is superior compared to uni-modality in preventing local recurrence. Radiation dose of 45 Gy is optimal. Nodal irradiation has no impact on local recurrence.

http://ift.tt/2nMK6xY

Pattern of care and impact of prognostic factors on the outcome of head and neck extramedullary plasmacytoma: a systematic review and individual patient data analysis of 315 cases

Abstract

Introduction

Methods

Two authors independently searched PubMed, Google search and Cochrane library for eligible studies from 1950 till July 1, 2016, published in English language.

Results

Conclusion

http://ift.tt/2nMK6xY

Association between continuous positive airway pressure and serum aminotransferases in patients with obstructive sleep apnea

Abstract

Introduction

Objectives

The aim of this study was to assess the relationship between OSA and NAFLD and the effect of CPAP therapy on serum aminotransferase levels in OSA patients.

Methods

Results

Conclusions

http://ift.tt/2AMsAij

Editorial Board

Publication date: January–February 2018
Source:Brain Stimulation, Volume 11, Issue 1

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Publication date: January–February 2018
Source:Brain Stimulation, Volume 11, Issue 1

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Information for Authors

Publication date: January–February 2018
Source:Brain Stimulation, Volume 11, Issue 1

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Masthead

Publication date: January–February 2018
Source:Brain Stimulation, Volume 11, Issue 1

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Network-based brain stimulation selectively impairs spatial retrieval

Publication date: January–February 2018
Source:Brain Stimulation, Volume 11, Issue 1
Author(s): Kamin Kim, Amber Schedlbauer, Matthew Rollo, Suganya Karunakaran, Arne D. Ekstrom, Nitin Tandon
BackgroundDirect brain stimulation via electrodes implanted for intracranial electroencephalography (iEEG) permits the modulation of endogenous electrical signals with significantly greater spatial and temporal specificity than non-invasive approaches. It also allows for the stimulation of deep brain structures important to memory, such as the hippocampus, that are difficult, if not impossible, to target non-invasively. Direct stimulation studies of these deep memory structures, though, have produced mixed results, with some reporting improvement, some impairment, and others, no consistent changes.Objective/hypothesisWe hypothesize that to modulate cognitive function using brain stimulation, it is essential to modulate connected nodes comprising a network, rather than just alter local activity.MethodsiEEG data collected while patients performed a spatiotemporal memory retrieval task were used to map frequency-specific, coherent oscillatory activity between different brain regions associated with successful memory retrieval. We used these to identify two target nodes that exhibited selectively stronger coupling for spatial vs. temporal retrieval. In a subsequent session, electrical stimulation - theta-bursts with a fixed phase-lag (0° or 180°) – was applied to the two target regions while patients performed spatiotemporal retrieval.ResultsStimulation selectively impaired spatial retrieval while not affecting temporal retrieval, and this selective impairment was associated with theta decoupling of the spatial retrieval network.ConclusionThese findings suggest that stimulating tightly connected nodes in a functional network at the appropriate phase-lag may effectively modulate the network function, and while in this case it impaired memory processes, it sets a foundation for further network-based perturbation studies.

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Editorial Board

Publication date: January 2018
Source:Brain and Development, Volume 40, Issue 1

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Announcements and reports

Publication date: January 2018
Source:Brain and Development, Volume 40, Issue 1

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Cover

Publication date: January 2018
Source:Brain and Development, Volume 40, Issue 1

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Publication date: January 2018
Source:Brain and Development, Volume 40, Issue 1

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The in vitro effect of Antimicrobial Photodynamic Therapy on dental microcosm biofilms from partially erupted permanent molars: a pilot study

Publication date: Available online 9 December 2017
Source:Photodiagnosis and Photodynamic Therapy
Author(s): Fabiana Sodré de Oliveira, Thiago Cruvinel, Daniela Alejandra Cusicanqui Méndez, Evandro José Dionísio, Daniel Rios, Maria Aparecida Andrade Moreira Machado
BackgroundThe aPDT could enhance the prevention of dental caries lesions in pits and fissures of partially erupted molars, by killing microorganisms from complex dental biofilms. This pilot study aimed to evaluate the effect of the Antimicrobial Photodynamic Therapy (aPDT) on the viability of specific microorganism groups of dental microcosm biofilms from occlusal surfaces of first permanent molars in eruption.MethodsDental microcosm biofilms grown on bovine enamel blocks, from dental plaque collected on occlusal surfaces of a partially erupted lower right first permanent molar, with McBain medium plus 1% sucrose in anaerobic condition at 37°C for 72h. The experiments were performed in eight groups: L-P-=no treatment (control), L18.75P-=18.75J/cm² LED, L37.5P-=37.5J/cm² LED, L75P-=75J/cm² LED, L-P+=200mM TBO, L18.75P+=200mM TBO+18.75J/cm² LED, L37.5P+=200mM TBO+37.5J/cm² LED, and L75P+=200mM TBO+75J/cm² LED. The counts of total microorganisms, total streptococci and mutans streptococci were determined on selective media agar plates by colony-forming units per mL. The log-transformed counts were analyzed by Kruskal-Wallis and post-hoc Dunn's test (P<0.05).ResultsThe counts of all microorganisms treated in the group L75P+ were statistically lower than those treated in L-P-. The aPDT promoted a significant reduction of microorganisms, with a trend of dose-dependent effect.ConclusionTBO-mediated aPDT was effective in reducing the viability of specific microbial groups in dental microcosm biofilms originated from occlusal of permanent molars in eruption.

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Analysis of the electromiographic activity of lower limb and motor function in hippotherapy practitioners with cerebral palsy

Publication date: Available online 9 December 2017
Source:Journal of Bodywork and Movement Therapies
Author(s): Mariane Fernandes Ribeiro, Ana Paula Espindula, Janaine Brandão Lage, Domingos Emanuel Bevilacqua Júnior, Luanna Honorato Diniz, Ednéia Corrêa de Mello, Alex Abadio Ferreira, Mara Lúcia Fonseca Ferraz, Vicente de Paula Antunes Teixeira
ObjectiveInvestigation of the effects of hippotherapy treatment on lower limb muscle activity and gross motor function in subjects with cerebral palsy (CP), comparing them to a group of subjects with adequate motor development.MethodsEvaluation was made of seven individuals with spastic diparetic CP, average age 9.3 (±3.3) years (CP group), Gross Motor Function Classification System (GMFCS) levels I and II, and eight individuals with adequate motor development, average age 10.9 (±3.2) years (control group). The groups were submitted to 25 sessions of hippotherapy, each lasting 30 min, on a weekly basis, and the muscle activity of the lower limbs was evaluated using surface electromyography during the 1st, 10th, 20th, and 25th sessions. For the CP group, Gross Motor Function Measurement (GMFM-88) was performed before and after hippotherapy treatment.ResultsThere was higher muscle activity in the 10th session, compared to the other sessions, with greater activity of the tibialis anterior muscles, for both groups studied. After treatment, the CP group showed significant improvement in the GMFM total score, and in the scores for dimensions D and E.ConclusionHippotherapy sessions improved the muscle responses in both groups, and improved the gross motor function of the subjects with CP.

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Cardiac autonomic response after cranial technique of the fourth ventricle (cv4) compression in systemic hypertensive subjects

Publication date: Available online 9 December 2017
Source:Journal of Bodywork and Movement Therapies
Author(s): Ana Christina Certain Curi, Alex Souto Maior Alves, Julio Guilherme Silva
ObjectiveThe aim of this study was to compare blood pressure (BP) behavior and heart rate variability (HRV) among hypertensive stage I and normotensive individuals who were submitted to the cranial technique of the 4th ventricle compression (CV4), an osteopathic technique.MethodsIn this experimental controlled study, thirty men between 40 and 60 years old were evaluated and divided into two groups: normotensive (NT) and hypertensive (HT). The CV4 maneuver was applied in both groups and BP was measured at 5 (five) different stages: pre and post-intervention, 5, 10 and 15min after technique. Time-frequency parameters were obtained from measurements of RR intervals. Data were analyzed using an ANOVA two-way for analysis of the condition factor (NT and HT) and times with p-value ≤ .05.ResultsThere was a reduction in the BP of the HT group. A significant intergroup difference (p = .01) was noticed, with respect to the standard deviation of successive normal R-R intervals (SDNN) values, mainly between pre-intervention and 15min stages. Concerning root mean square of the mean squared differences (RNSSD) values, the highlights were differences between pre-intervention and 10min (p = .01) only in the NT group. There was an increase in high frequencies (HF) values and a low frequencies (LF) attenuation in both groups at all different stages.ConclusionThe data showed a BP reduction in the HT group in pre-intervention/15min and an increase in parasympathetic activity and decreased sympathetic activity in both groups. This suggests a change in the sympathetic-vagal balance. However, further studies are needed to elucidate the data on BP reduction mechanisms with CV4.

http://ift.tt/2AHOEZG

Antitumor miR-150-5p and miR-150-3p inhibit cancer cell aggressiveness by targeting SPOCK1 in head and neck squamous cell carcinoma

Our recent studies have revealed that both strands of pre-miRNAs, the guide strand and the passenger strand, are involved in cancer pathogenesis. Analyses of miRNA expression signatures by RNA sequencing in head and neck squamous cell carcinoma (HNSCC) showed that both of the strands of pre-miR-150 (miR-150-5p and miR-150-3p) were significantly downregulated, and that these miRNAs acted as antitumor miRNAs in HNSCC cells. The aim of this study was to identify oncogenic genes in HNSCC cells that were regulated by miR-150-5p and miR-150-3p.

http://ift.tt/2yUmjjk

Antitumor miR-150-5p and miR-150-3p inhibit cancer cell aggressiveness by targeting SPOCK1 in head and neck squamous cell carcinoma

Influence of involuntary cigarette smoke inhalation on osseointegration: a systematic review and meta-analysis of preclinical studies

There are no studies that have systematically reviewed the influence of involuntary cigarette smoke inhalation (ICSI) on the stability of implants. The aim of the present study was to perform a systematic review and meta-analysis of preclinical studies that assessed the influence of involuntary cigarette smoke inhalation ICSI on osseointegration. Indexed databases (PubMed, Google-Scholar, Scopus, EMBASE, and Web of Knowledge) were searched till September 2017. Titles and abstracts of studies identified using the above-described protocol were independently screened by 2 authors.

http://ift.tt/2yTZ7Sc

Early-onset childhood atopic dermatitis is related to NLRP2 repression

Early-onset atopic dermatitis (AD) related repression of the immune regulatory NLRP2 is driven by promoter hypermethylation starting already at time of birth providing an early opportunity to modulate innate immunity to potentially mitigate AD development.

http://ift.tt/2kfnRvH

Temporal and spatial variations of 134Cs and 137Cs levels in the Sea of Japan and Pacific coastal region: Implications for dispersion of FDNPP-derived radiocesium

Publication date: February 2018
Source:Journal of Environmental Radioactivity, Volume 182
Author(s): M. Inoue, Y. Shirotani, S. Yamashita, H. Takata, H. Kofuji, D. Ambe, N. Honda, Y. Yagi, S. Nagao
To investigate the dispersion of Fukushima Dai-ichi Nuclear Power Plant (FDNPP)-derived radiocesium in the Sea of Japan and western Pacific coastal region and determine the sources of radiocesium in these areas, we examined the temporal and spatial variations of ¹³⁴Cs and ¹³⁷Cs concentrations (activities) during 2011–2016 in seawaters around the western Japanese Archipelago, particularly in the Sea of Japan. In May 2013, the surface concentration of ¹³⁴Cs was ∼0.5 mBq/L (decay-corrected to March 11, 2011), and that of ¹³⁷Cs exceeded the pre-accident level in this study area, where the effects of radiocesium depositions just after the FDNPP accident disappeared in surface waters in October 2011. Subsequently, radiocesium concentrations gradually increased during 2013–2016 (∼0.5–1 mBq/L for ¹³⁴Cs), exhibiting approximately homogeneous distributions in each year. The temporal and spatial variations of ¹³⁴Cs and ¹³⁷Cs concentrations indicated that FDNPP-derived radiocesium around the western Japanese Archipelago, including the Sea of Japan, has been supported by the Kuroshio Current and its branch, Tsushima Warm Current, during 2013–2016. However, in the Sea of Japan, the penetration of ¹³⁴Cs was limited to depths of less than ∼200 m during three years following the re-delivery of FDNPP-derived radiocesium.

Graphical abstract

http://ift.tt/2Bpt3rN

Spatial variations of 226Ra, 228Ra, 134Cs, and 137Cs concentrations in western and southern waters off the Korean Peninsula in July 2014

Publication date: February 2018
Source:Journal of Environmental Radioactivity, Volume 182
Author(s): M. Inoue, Y. Shirotani, S. Nagao, T. Aramaki, Y.I. Kim, K. Hayakawa
We examined the spatial distributions of ²²⁶Ra, ²²⁸Ra, ¹³⁴Cs, and ¹³⁷Cs concentrations (activities) in seawater off the western and southern Korean Peninsula in July 2014. Radium-228 (and ²²⁶Ra) concentrations in water samples varied widely from 5 to 14 mBq/L (2–4 mBq/L), showing a negative correlation with salinity, particularly at the surface off the western Korean Peninsula. This indicates that the seawaters in this area are fundamentally comprised of ²²⁸Ra-poor and high-saline Kuroshio Current water and ²²⁸Ra-rich and low-saline water (e.g., continental shelf water), with various mixing ratios. Although Fukushima Dai-ichi Nuclear Power Plant (FDNPP)-derived ¹³⁴Cs was below the detection limit (<0.08 mBq/L) in waters off the western Korean Peninsula, low level ¹³⁴Cs (0.1–0.2 mBq/L) was detected in waters off the southern Korean Peninsula accompanied by higher ¹³⁷Cs concentrations (1.6–1.9 mBq/L) relative to that off the western Korean Peninsula. Combined with the lower radium concentrations, the detection of ¹³⁴Cs is explained by mixing of FDNPP-derived radiocesium-contaminated Kuroshio Current water.

http://ift.tt/2BpaT9Q

A switch from GABA inhibition to excitation of vasopressin neurons exacerbates the development angiotensin II-dependent hypertension

Abstract

Hypothalamic magnocellular neurons secrete vasopressin into the systemic circulation to maintain blood pressure by increasing renal water reabsorption and by vasoconstriction. When blood pressure rises, baroreflex activation normally inhibits vasopressin neurons via activation of GABAergic inputs. However, plasma vasopressin levels are paradoxically elevated in several models of hypertension and in some patients with essential hypertension, despite increased blood pressure. We have previously shown that vasopressin neuron activity is increased early in the development of moderate angiotensin II-dependent hypertension via blunted baroreflex inhibition of vasopressin neurons. Here, we show that antagonism of vasopressin-induced vasoconstriction slows the development of hypertension and that local administration of a GABA_A receptor antagonist inhibits vasopressin neurons during, but not before, the onset of hypertension. Taken together, our data suggest that vasopressin exacerbates the increase in blood pressure evident early in the development hypertension and that blunted baroreflex inhibition of vasopressin neurons is underpinned by an excitatory shift in their response to endogenous GABA signalling.

http://ift.tt/2jiUqwz

Chapter 12 Therapeutic protein and drug imprinted nanostructures as controlled delivery tools

Publication date: 2018
Source:Design and Development of New Nanocarriers
Author(s): Handan Yavuz, Kemal Çetin, Semra Akgönüllü, Dilek Battal, Adil Denizli
Polymers play an enormous role in the drug delivery field owing to their flexibility, biocompatibility, and controllable size properties. With the advances in the polymer technology and nanotechnology, the novel drug delivery systems (DDSs) based on nanoparticles have been successfully developed. Nanoparticulate DDSs with an enhanced permeation allow targeted delivery of an intended therapeutic drug to the site of action with predetermined time and activity. Numerous applications have been reported which use nanoparticles as smart delivery systems for synthetic, semi-synthetic or natural drugs, which could be small molecules or huge molecules like proteins. In smart DDSs the critical point is to achieve tunable drug release. Diffusion, matrix degradation or both can control this property. In recent years the use of molecular imprinting technology to arrange the drug release properties from the polymer matrix is attracting significant attention. The basis of this approach is the affinity of an imprinted polymer for the drug molecule, which provides high loading capacity and sustained release profiles. Imprinting also allows for construction of responsive drug release systems based on competitive binding of the imprinted molecule with the weakly bound drug. The studies on the nanoparticle-based imprinted delivery systems will be summarized in this chapter.

http://ift.tt/2yaRS52

Cancer Immunotherapy in a Neglected Population: The Current Use and Future of T-cell-Mediated Checkpoint Inhibitors in Organ Transplant Patients

Publication date: Available online 8 December 2017
Source:Cancer Treatment Reviews
Author(s): Young Kwang Chae, Carlos Galvez, Jonathan F. Anker, Wade T. Iams, Manali Bhave
Although the indications for immune checkpoint inhibitors continue to grow, organ transplant recipients with advanced malignancies have been largely excluded from clinical trials testing the safety and efficacy of these therapies given their need for chronic immunosuppression and the risk of allograft rejection. With the rapid growth of transplant medicine and the increased risk of malignancy associated with chronic immunosuppression, it is critical that we systematically analyze the available data describing immune checkpoint blockade in the organ transplant population. Herein we provide a current and comprehensive review of cases in which immune checkpoint blockade was used on organ transplant recipients. Furthermore, we discuss the differences in efficacy and risk of allograft rejection between CTLA-4 and PD-1 inhibitors and make recommendations based on the limited available clinical data. We also discuss the future of immune checkpoint blockade in this subpopulation and explore the emerging data of promising combination therapies with mTOR, BRAF/MEK, and BTK/ITK inhibitors. Further clinical experience and larger clinical trials involving immune checkpoint inhibitors, whether as monotherapies or combinatorial therapies, will help develop regimens that optimize anti-tumor response and minimize the risk of allograft rejection in organ transplant patients.

http://ift.tt/2yUc3aT

Safety and Efficacy of guselkumab in Japanese patients with moderate-to-severe plaque psoriasis: A Randomised, Placebo-Controlled, Ascending Dose Study

Summary

Background

The Interlukin-23 (IL-23)/Interlukin-17 (IL-17) pathway is central in the pathogenesis of psoriasis. The favourable efficacy and safety of guselkumab, an IL-23 specific monoclonal antibody, has been demonstrated in global Phase 3 studies of plaque psoriasis.

Objectives

To evaluate the safety, efficacy and pharmacokinetics of a single-dose subcutaneous guselkumab in Japanese patients with moderate-to-severe plaque psoriasis.

Methods

Patients with ≥ 10% of total body surface area (BSA) involvement and a Psoriasis Area and Severity Index (PASI) ≥12 were randomised (5:1) to receive guselkumab or placebo in 4 cohorts of this double-blind, placebo-controlled, single ascending dose, single-centre study. Safety, pharmacokinetics, and clinical response were monitored at baseline and specific time points over a 24-wk follow-up period.

Results

Through week 24, 54% (11/20) of guselkumab patients and 50% (2/4) of placebo patients experienced ≥1 adverse event (AE). No deaths, serious AEs, or AEs leading to treatment discontinuation were reported. Maximum clinical response was seen at week 16 with PASI 75 response in 2/5 (10 mg), 4/5 (30 mg and 300 mg), and 3/5 (100 mg) patients and PASI 90 in 0/5 (10 mg), 3/5 (30 mg), 2 /5 (100 mg) and 3/5 (300 mg) patients. Mean C_max and AUC_∞ values increased in a dose-proportional manner with mean terminal t_1/2 of 15.6-17.6 days and median t_max of 4-6 days.

Conclusions

Guselkumab was generally well-tolerated and exhibited sustained high levels of clinical response in Japanese patients with moderate-to-severe psoriasis.

http://ift.tt/2Bn5yQc

Which outcomes are reported in cellulitis trials? Results of a review of outcomes included in cellulitis trials and a patient priority setting survey

Summary

Background

There is an emerging need to develop consistent outcomes in clinical trials to allow effective comparison of treatment effects. No systematic review has previously looked at the reporting of outcome measures used in randomised controlled trials (RCTs) on treatment and prevention of cellulitis (erysipelas).

Objectives

The primary aim of this review was to describe the breadth of outcomes reported from RCTs on cellulitis treatment and prevention. The secondary aim was to identify outcome themes from patient and health care professionals' feedback from a cellulitis priority setting partnership (PSP).

Methods

We conducted a review of all outcome measures used in RCTs from two recent Cochrane reviews. Free text responses from a cellulitis priority setting survey were used to understand the perspectives of patients and healthcare professionals.

Results

Outcomes from 42 RCTs on treatment of cellulitis and six RCTs on prevention of cellulitis were reviewed. Only 28 trials stated their primary outcome. For trials assessing treatment of cellulitis, clinical response to treatment was categorised in 25 different ways. Five of these trials used an outcome that was in accordance with FDA guidance and only four trials incorporated either quality of life or patient satisfaction. For trials assessing prevention of cellulitis, recurrence was the key outcome measure. From the cellulitis PSP, prevention of recurrence, clinical features and long-term disease impact were the most important outcome themes for patients.

Conclusions

We have shown that in cellulitis treatment and prevention research, there is significant heterogeneity in clinical outcomes, inadequate focus on patient-reported outcomes, and a disparity between what is currently measured and what patients and healthcare professionals feel is important. We recommend that future cellulitis treatment trials consider the use of longer-term outcomes to capture recurrence and long-term morbidity, as well as short-term resolution of acute infection.

http://ift.tt/2ANZMpE

The Prevalence and Odds of Depression in Patients with Vitiligo: a Meta-Analysis

Abstract

Objective

The objective of this study is to provide a pooled estimate of the prevalence and odds of depression in Vitiligo patients.

Methods

A systematic literature search of Medline, Embase, and Cochrane library databases was conducted. The proportions and mean questionnaire values for depression were pooled according to different evaluation methods. In controlled studies, odds ratio (OR) and standardized mean differences (SMDs) compared depression in vitiligo patients with healthy controls.

Results

One thousand nine hundred and sixty-five patients were identified from 20 eligible cohorts to be included in the present meta-analysis review. Sample sizes ranged from 30 to 308 for each analysis. The pooled prevalence of depression across 17 unique populations (n = 1,711) was 29% (95% CI 20 - 39). The prevalence of clinical depression was 8% (95%CI 2-14%) using Diagnostic and Statistical Manual of Mental Disorders IV (DSM IV) or International Classification of Diseases codes-10 (ICD 10 and the prevalence of depressive symptoms was 33% (95%CI: 23-44%) using validated screening inventory and rating scales. Vitiligo patient were 4.96 times more likely to display depression compared with controls. Subgroup analysis showed that the prevalence of depression in Asian and female vitiligo patients were significantly higher than those in Caucasian and male ones. The pooled prevalence of depressive symptoms was higher (56%, 95%CI: 0.5-0.62) and the heterogeneity was lowering cases with Hamilton Depression Rating Scale (HDRS) questionnaire when compared with other questionnaires.

Conclusions

This meta-analysis review indicates that the prevalence of depression is high in vitiligo patients. The HDRS questionnaire may be the most sensitive tool for testing the depressive symptoms among vitiligo patients.

http://ift.tt/2yTYl83

Children with atopic dermatitis may have unacknowledged contact allergies contributing to their skin symptoms

Abstract

Background

Whether children with atopic dermatitis have an altered risk of contact allergy than children without atopic dermatitis is frequently debated and studies have been conflicting. Theoretically, the impaired skin barrier in AD facilitates the penetration of potential allergens and several authors have highlighted the risk of underestimating and overlooking contact allergy in children with atopic dermatitis.

Objective

To determine the prevalence of contact allergy in Danish children with atopic dermatitis and explore the problem of unacknowledged allergies maintaining or aggravating the skin symptoms.

Methods

In a cross sectional study, 100 children and adolescents aged 5-17 years with a diagnosis of atopic dermatitis were patch tested with a pediatric series of 31 allergens.

Results

Thirty percent of the children had at least one positive patch test reaction and 17% had at least one contact allergy that was relevant to the current skin symptoms. The risk of contact allergy was significantly correlated to the severity of atopic dermatitis. Metals and components of topical skin care products were the most frequent sensitizers.

Conclusion

Patch testing is relevant as a screening tool in the management of children with atopic dermatitis as they may have unacknowledged contact allergies contributing to or maintaining their skin symptoms. Children with atopic dermatitis seem to be at greater risk of sensitization to certain allergens including metals and components of skin care products.

http://ift.tt/2yaC5Ty

Safety and Efficacy of guselkumab in Japanese patients with moderate-to-severe plaque psoriasis: A Randomised, Placebo-Controlled, Ascending Dose Study

Summary

Background

Objectives

To evaluate the safety, efficacy and pharmacokinetics of a single-dose subcutaneous guselkumab in Japanese patients with moderate-to-severe plaque psoriasis.

Methods

Results

Conclusions

Guselkumab was generally well-tolerated and exhibited sustained high levels of clinical response in Japanese patients with moderate-to-severe psoriasis.

http://ift.tt/2Bn5yQc

Which outcomes are reported in cellulitis trials? Results of a review of outcomes included in cellulitis trials and a patient priority setting survey

Summary

Background

Objectives

Methods

Results

Conclusions

http://ift.tt/2ANZMpE

Development and optimization of a new synthetic process for lorcaserin

Publication date: Available online 9 December 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Jérôme Cluzeau, Gaj Stavber
A two-step process to synthesize racemic lorcaserin was developed from 2-(4-chlorophenyl)ethanol via formation of bromide or tosylate derivatives. These derivatives were reacted with allylamine in neat conditions to provide pure N-(4-chlorophenethyl)allylammonium chloride. This compound was cyclized in neat conditions using aluminum or zinc chloride to give racemic lorcaserin. After resolution of enantiomers, the wrong enantiomer was racemized and recycled to give new R-lorcaserin.

Graphical abstract

http://ift.tt/2yaSrfb

Antiobesity and emetic effects of a short-length peptide YY analog and its PEGylated and alkylated derivatives

Publication date: Available online 8 December 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Ayumu Niida, Yoko Kanematsu-Yamaki, Tomoko Asakawa, Yoshimasa Ishimura, Hisashi Fujita, Kouta Matsumiya, Naoki Nishizawa, Yusuke Adachi, Taisuke Mochida, Kazue Tsuchimori, Mariko Yoneyama-Hirozane, Junichi Sakamoto, Hideki Hirabayashi, Hideo Fukui, Shiro Takekawa, Taiji Asami
Neuropeptide Y2 receptor (Y2R) agonism is an important anorectic signal and a target of antiobesity drug discovery. Recently, we synthesized a short-length Y2R agonist, PYY-1119 (4-imidazolecarbonyl-[D-Hyp²⁴,Iva²⁵,Pya(4)²⁶,Cha^27,36,γMeLeu²⁸,Lys³⁰,Aib³¹]PYY(23–36), 1) as an antiobesity drug candidate. Compound 1 induced marked body weight loss in diet-induced obese (DIO) mice; however, 1 also induced severe vomiting in dogs at a lower dose than the minimum effective dose administered to DIO mice. The rapid absorption of 1 after subcutaneous administration caused the severe vomiting. Polyethylene glycol (PEG)- and alkyl-modified derivatives of 1 were synthesized to develop Y2R agonists with improved pharmacokinetic profiles, i.e., lower maximum plasma concentration (Cmax) and longer time at maximum concentration (Tmax). Compounds 5 and 10, modified with 20 kDa PEG at the N-terminus and eicosanedioic acid at the Lys³⁰ side chain of 1, respectively, showed high Y2R binding affinity and induced significant body weight reduction upon once-daily administration to DIO mice. Compounds 5 and 10, with their relatively low Cmax and long Tmax, partially attenuated emesis in dogs compared with 1. These results indicate that optimization of pharmacokinetic properties of Y2R agonists is an effective strategy to alleviate emesis induced by Y2R agonism.

Graphical abstract

http://ift.tt/2yas7S8

Interpersonal and intrapersonal emotional processes in individuals treated for alcohol use disorder and non-addicted healthy individuals

Publication date: April 2018
Source:Addictive Behaviors, Volume 79
Author(s): Maciej Kopera, Elisa M. Trucco, Andrzej Jakubczyk, Hubert Suszek, Aneta Michalska, Aleksandra Majewska, Natalia Szejko, Agata Łoczewska, Aleksandra Krasowska, Anna Klimkiewicz, Kirk J. Brower, Robert A. Zucker, Marcin Wojnar
IntroductionPrior work largely confirms the presence of various emotional processing deficits among individuals with an alcohol use disorder (AUD); however, their specificity and relevance still warrant investigation. The aim of the current study was to compare selected aspects of emotional processing (i.e., mental state recognition, alexithymia, and emotional intelligence) between individuals treated for an AUD and healthy individuals.MethodsThe AUD sample consisted of 92 abstinent men with AUD who were participating in an 8-week inpatient abstinence-based treatment program in Warsaw, Poland. The healthy control (HC) group consisted of 86 men recruited from the Medical University of Warsaw and the Nowowiejski Hospital administrative staff. Baseline information about demographics, psychopathological symptoms, and severity of alcohol problems was obtained. Mental states recognition was assessed using the Reading the Mind in the Eyes Test (RMET). Alexithymia was measured with the Toronto Alexithymia Scale (TAS-20). The Schutte Self-Report Emotional Intelligence Test (SSEIT) was used to measure emotional intelligence (EI).Results and conclusionsAfter accounting for potentially confounding variables (demographics, severity of depression, anxiety symptoms) in MANCOVA models, patients with AUD presented deficits in identification and description of their own emotional states, as well as lower emotion regulation skills when compared to HCs. No between-group differences were observed in self-reported recognition of other people's emotions, social skills, and a behavioral measure of mental states recognition.Specific rather than general emotion-processing deficits in participants with AUD were identified, suggesting problems with processing of intrapersonal emotional signals.

http://ift.tt/2B2vmAx

Improvement of the association between self-reported pill count and varenicline levels following exclusion of participants with misreported pill count: A commentary on Peng et al. (2017)

Publication date: April 2018
Source:Addictive Behaviors, Volume 79
Author(s): Annie R. Peng, Bernard Le Foll, Mark Morales, Caryn Lerman, Robert Schnoll, Rachel F. Tyndale
IntroductionWe previously reported poor associations between salivary varenicline and pill counts, and a substantial overestimation of adherence by pill counts in "Measures and predictors of varenicline adherence in the treatment of nicotine dependence" (Peng et al., 2017). We have since conducted supplementary analyses characterizing, and then excluding, individuals with established inaccurate pill count recall.MethodsBased on published varenicline pharmacokinetics (including drug levels, and the long half-life) and our detection limits, conservatively we should be able to detect varenicline in anyone who took at least one pill during the 48h prior to saliva collection; thus, those reporting 1 or more pills in this time frame but who had undetectable salivary varenicline were deemed to have inaccurate pill count recall. Correlations between pill counts and salivary varenicline, and Receiver Operating Characteristics curve analyses were conducted following exclusion of participants with inaccurate pill count recall.ResultsNearly 20% of our participants (N=67/376) had inaccurate self-reported pill counts. These participants were younger, non-white, lower income, and unmarried (evaluated using chi-square or Mann-Whitney U test). Following exclusion of these individuals, the correlations between salivary varenicline and pill count improved and the area under the curve (AUC) of pill counts for discriminating adherence improved modestly.ConclusionWhen the 20% of individuals with inaccurate pill count recall were excluded, an improved association between self-reported pill count and salivary varenicline was observed, albeit still weak. A substantial overestimation of adherence by pill counts relative to salivary varenicline is still observed even after exclusion of almost 20% of the group having established inaccurate reporting suggesting that these individuals, with identifiable inaccuracies, were only part of the overestimation of adherence.

http://ift.tt/2jeFDTr

Identifying patterns of tobacco use among US middle and high school students: A latent class analysis

Publication date: April 2018
Source:Addictive Behaviors, Volume 79
Author(s): Mansoo Yu, Paul Sacco, Hye Jeong Choi, Jenna Wintemberg
ObjectivesThis study sought to (a) understand patterns of tobacco use among US middle and high school students based on their lifetime or current use of tobacco products: cigarettes, cigars, chewing tobacco, pipes, e-cigarettes, and hookah tobacco, and (b) examine differences in the underlying patterns by sociodemographic and tobacco-related characteristics (e.g., exposure to tobacco products, tobacco advertising, parental disapproval of tobacco use and feedback from healthcare providers).MethodsWe analyzed self-report data from the 2013 National Youth Tobacco Survey (n=18,046). Latent Class Analysis was conducted to identify patterns of tobacco use and tested how sociodemographic and tobacco-related characteristics are associated with such patterns.ResultsFour subtypes of tobacco use were identified: "Very Low Risk (VLR)," "Lifetime Smoking (LS)," "Lifetime Multiple Tobacco Use (LMT)," and "Past Month Multiple Tobacco Use (PMT)." Latino and Asian American youth were more likely to be in PMT. Compared with students in LS, students in VLR were less likely to receive advice not to use tobacco from their healthcare providers, but more likely to have parental disapproval of smoking. Students in LMT (vs. LS) were more likely to use tobacco coupons and promotional materials, report greater access to tobacco, and receive advice from a healthcare professional. Students in PMT (vs. LS) were more likely to use coupons, take part in tobacco promotions, and be exposed to smoking in a vehicle.ConclusionsOur study suggests that it may be important to consider the underlying patterns and correlates of tobacco use in designing tobacco control programs for youth.

http://ift.tt/2B40ks9

Comparison of Elliptical Excision versus Punch Incision for the Treatment of Epidermal Inclusion Cysts: A Prospective, Randomized Study

Publication date: Available online 9 December 2017
Source:Journal of the American Academy of Dermatology
Author(s): Justin Cheeley, Laura Delong Aspey, Jamie MacKelfresh, Michelle Pennie, Suephy Chen

http://ift.tt/2iIRPbh

Anti-melanoma differentiation-associated gene 5 (MDA5) dermatomyositis: a concise review with an emphasis on distinctive clinical features

Publication date: Available online 9 December 2017
Source:Journal of the American Academy of Dermatology
Author(s): Drew JB. Kurtzman, Ruth Ann Vleugels
Melanoma differentiation-associated gene 5 (MDA5) is a recently described autoantigen target in a subset of patients with dermatomyositis (DM). Anti-MDA5 DM is characterized by a unique mucocutaneous and systemic phenotype that includes cutaneous and oral ulceration, painful palmar papules, alopecia, panniculitis, arthritis, a lower incidence of myositis, and, importantly, an elevated risk of interstitial lung disease, with a potentially fatal course. Because the clinical features may differ substantially from those typically observed in cutaneous DM, the diagnosis is often overlooked, which may negatively affect patient outcomes. This review aims to familiarize the clinician with the distinctive clinical features of anti-MDA5 DM in order to enhance its recognition and to facilitate an appropriate screening and management strategy.

Teaser

Anti-MDA5 dermatomyositis exhibits unique clinical features including mucocutaneous ulceration, palmar papules, non-scarring alopecia, panniculitis, arthritis, and interstitial lung disease.Early intervention may reduce disease-related morbidity and improve survival in affected individuals.Knowledge of the salient features of anti-MDA5 dermatomyositis enhances its recognition and facilitates treatment.

http://ift.tt/2iGS32C

‘‘Intralesional Drainage Injection’ of Triamcinolone acetonide for Epidermal Cyst’

Publication date: Available online 9 December 2017
Source:Journal of the American Academy of Dermatology
Author(s): Deepak Jakhar, Ishmeet Kaur

http://ift.tt/2kIb7lf

Dermoscopy as an evolving tool to assess vitiligo activity

Publication date: Available online 9 December 2017
Source:Journal of the American Academy of Dermatology
Author(s): Abhijeet Kumar Jha, Sidhath Sonthalia, Aimilios Lallas

http://ift.tt/2kIaVT3

Catalytic valorization of biomass derived glycerol under methane: Effect of catalyst synthesis method

Publication date: 15 March 2018
Source:Fuel, Volume 216
Author(s): Danielle Austin, Aiguo Wang, Peng He, Hui Qian, Hongbo Zeng, Hua Song
The feasibility of upgrading glycerol using Zn, Cu and Ga modified ZSM-5 was investigated. Different catalyst synthesis techniques were compared for their performance on the aromatization of glycerol under a methane environment at 400 °C and initial pressure of 5 bar. GC–MS analysis showed that the catalyst synthesized using deposition precipitation (DP) resulted in the best performance in terms of the highest yield of monoaromatics in the liquid product when compared with the other synthesis techniques. XRD, NH3-TPD, Pyridine DRIFT, TEM, CO Chemisorption and XAS were employed to better understand the influencing parameters. High crystallinity, high acidity with a higher proportion of medium acid sites and high metal dispersion were identified as the most important factors influencing aromatization performance. Evidently, the deposition precipitation synthesis technique is effective in obtaining each of these attributes. Additionally, a methane environment increased aromatic production when compared to an inert environment. Methane was found to not only maintain high metal dispersion throughout the reaction, but may participate in the reaction as well. The synthesis technique utilized for the upgrading of glycerol can influence the distribution of products, allowing for increased selectivity of the desired product. The demonstrated feasibility and excellent upgrading performance of the DP synthesized catalyst could make the production of biodiesel more economical and environmentally friendly.

http://ift.tt/2AJoyWd

Prediction of soil parameters using the spectral range between 350 and 15,000nm: A case study based on the Permanent Soil Monitoring Program in Saxony, Germany

Publication date: 1 April 2018
Source:Geoderma, Volume 315
Author(s): Frank Riedel, Michael Denk, Ingo Müller, Natalja Barth, Cornelia Gläßer
In this study, we tested the potential of visible-near infrared (VNIR, 350–2500nm) and mid-infrared spectroscopy (MIR, 2500–15,000nm) for quantification and prediction of soil parameters to support the Saxon Permanent Soil Monitoring Program. As Saxony is characterised by a large variety of soil metal concentrations which can negatively affect essential soil functions, the presented study is strongly focused on the forecast of soil metal contents. As data basis, a total of 203 soil samples of the Saxon Permanent Soil Monitoring Program, collected between 1998 and 2013 at 48 representative locations with respect to soil type, parent material, land use and climate conditions, were used. The chemical analysis provided information regarding total soil organic carbon content (TOC) and pH-value as well as element concentrations (Al, As, Ca, Cu, Fe, K, Mn, Na, Ni, Pb, Zn). VNIR-spectra were collected utilising an ASD FieldSpec Pro FR while an Agilent 4300 Handheld FTIR spectrometer was applied to cover the MIR wavelength region. Spectra pre-processing comprised the application of multi scatter correction (MSC), standard normal variate (SNV), continuum removal (CR) and the first and second derivatives. To model the relationship between soil spectral and chemical properties, and to predict element concentration, the spectra and chemical data were used as input for Partial Least Square Regression (PLSR) models. The definition of training data was realised on Kennard-Stone sampling algorithm and we selected 103 samples for model calibration and 100 samples for model validation. In general, the MIR-spectra and the MSC- and SNV-pre-processing improved the model performance. We obtained promising model results for TOC, Al, Fe, K and Ni with R²-values between 0.70 and 0.88. Moderate results were obtained for Ca (R²=0.61) and Mn (R²=0.43). We conclude that VNIR and MIR spectroscopy has the potential to quickly provide reliable information regarding major soil parameters and metal contents and is thus a promising alternative approach to support soil analysis within the Saxon Permanent Soil Monitoring Program.

http://ift.tt/2AHJkFk

AC impedance spectroscopy on Al/p-Si/ZnTPyP/Au heterojunction for hybrid solar cell applications

Publication date: 5 March 2018
Source:Journal of Alloys and Compounds, Volume 736
Author(s): M.M. Shehata, T.G. Abdel-Malik, K. Abdelhady
A p-Silicon/Zn-tetra pyridyl-porphyrin (ZnTPyP) heterojunction was fabricated by forming a ZnTPyP layer on a p-type Si single crystal substrate using a conventional thermal evaporation technique. Complex impedance measurements of the Al/p-Si/ZnTPyP/Au heterojunction were carried out at applied AC-voltage range from 0.2 V to 1 V, temperature range from 303 K to 353 K and over the frequency range from 100HZ to 2 MHz. Impedance spectra of the heterojunction under the standard illumination ranged from 0 to 40 mW/cm² were reported and analysed.

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Exploiting Metabolic Vulnerabilities of Cancer with Precision and Accuracy

Publication date: Available online 8 December 2017
Source:Trends in Cell Biology
Author(s): Adam J. Wolpaw, Chi V. Dang
Links between oncogenic drivers and cancer cell metabolism have emerged over the past several decades, indicating that constitutive oncogenic growth signaling can render cancers susceptible to metabolic interventions. While significant progress has been achieved in the identification of metabolic vulnerabilities of cancer cells, the complexity of the tumor microenvironment (TME) and the dynamic nature of organismal circadian metabolism challenge the precision of targeting cancer metabolism. Here current progress in the areas of cancer metabolism and TME metabolism is reviewed, highlighting how cancer metabolism can be accurately and precisely targeted.

http://ift.tt/2A8BpQj

A New Textured Polyphosphazene Biomaterial with Improved Blood Coagulation and Microbial Infection Responses

Publication date: Available online 8 December 2017
Source:Acta Biomaterialia
Author(s): Li-Chong Xu, Zhongjing Li, Zhicheng Tian, Chen Chen, Harry R. Allcock, Christopher A. Siedlecki
A new poly[bis(octafluoropentoxy) phosphazene] (OFP) was synthesized for the purpose of blood contacting medical devices. OFP was further either developed into crosslinkable polyphosphazene (X-OFP) or blended with polyurethane (PU) as the mixture (OFP/PU) for improvement of mechanical property of polyphosphazene polymers. All the materials were fabricated as smooth films or further textured with submicron pillars for the assay of antimicrobial and antithrombotic properties. Results showed that crosslinkable OFP (X-OFP) and blends of OFP/PU successfully improved the mechanical strength of OFP and fewer defects of pillars were found on the textured polyphosphazene surfaces. The antithrombotic experiments showed that polyphosphazene OFP materials reduced human Factor XII activation and platelet adhesion, thereby being resistant to plasma coagulation and thrombosis. The bacterial adhesion and biofilm experiments demonstrated that OFP materials inhibited staphylococcal bacterial adhesion and biofilm formation. The surface texturing further reduced the platelet adhesion and bacterial adhesion, and inhibited biofilm formation up to 23 days. The data suggested that textured OFP materials may provide a practical approach to improve the biocompatibility of current biomaterials in the application of blood contacting medical devices with significant reduction in risk of pathogenic infection and thrombosis.Statement of SignificanceThe thromboembolic events and microbial infection have been the significant barriers for the long term use of biomaterials in blood-contacting medical devices. The development of new materials with multiple functions including anti-thrombosis and antibacterial surfaces is a high research priority. This study synthesized new biostable and biocompatible polyphosphazene polymers, poly[bis(octafluoropentoxy)phosphazene] (OFP) and crosslinkable OFP, and successfully improved the mechanical strength of polyphosphazenes. Polymers were fabricated into textured films with submicron pillars on the surfaces. The antimicrobial and antithrombotic assays demonstrated that new materials combined with surface physical modification have significant reduction in risk of pathogenic infection and thrombosis, and improve the biocompatibility of current biomaterials in the application of blood-contacting medical devices. It would be interest to biomaterials and bioengineering related communities.

Graphical abstract

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Fabrication of Hybrid Crosslinked Network with Buffering Capabilities and Autonomous Strengthening Characteristics for Dental Adhesive

Publication date: Available online 8 December 2017
Source:Acta Biomaterialia
Author(s): Linyong Song, Qiang Ye, Xueping Ge, Anil Misra, Candan Tamerler, Paulette Spencer
Ingress of bacteria and fluids at the interfacial gaps between the restorative composite biomaterial and the tooth structure contribute to recurrent decay and failure of the composite restoration. The inability of the material to increase the pH at the composite/tooth interface facilitates the outgrowth of bacteria. Neutralizing the microenvironment at the tooth/composite interface offers promise for reducing the damage provoked by cariogenic and aciduric bacteria. We address this problem by designing a dental adhesive composed of hybrid network to provide buffering and autonomous strengthening simultaneously. Two amino functional silanes, 2-hydroxy-3-morpholinopropyl (3-(triethoxysilyl)propyl) carbamate and 2-hydroxy-3-morpholinopropyl (3-(trimethoxysilyl)propyl) carbamate were synthesized and used as co-monomers. Combining free radical initiated polymerization (polymethacrylate-based network) and photoacid-induced sol-gel reaction (polysiloxane) results in the hybrid network formation. Resulting formulations were characterized with regard to real-time photo-polymerization, water sorption, leached species, neutralization, and mechanical properties. Results from real-time FTIR spectroscopic studies indicated that ethoxy was less reactive than methoxy substituent. The neutralization results demonstrated that the methoxy-containing adhesives have acute and delayed buffering capabilities. The mechanical properties of synthetic copolymers tested in dry conditions were improved via condensation reaction of the hydrolyzed organosilanes. The leaching from methoxy containing copolymers was significantly reduced. The sol-gel reaction provided a chronic and persistent reaction in wet condition-performance that offers potential for reducing secondary decay and increasing the functional lifetime of dental adhesives.Statement of SignificanceThe interfacial gaps between the restorative composite biomaterial and the tooth structure contributes to recurrent decay and failure of the composite restoration. The inability of the material to increase the pH at the composite/tooth interface facilitates the outgrowth of more cariogenic and aciduric bacteria.This paper reports a novel, synthetic resin that provides buffering capability and autonomous strengthening characteristics. In this work, two amino functional silanes were synthesized and the effect of alkoxy substitutions on the photoacid-induced sol-gel reaction was investigated. We evaluated the neutralization capability (monitoring the pH of lactic acid solution) and the autonomous strengthening property (monitoring the mechanical properties of the hybrid copolymers under wet conditions and quantitatively analyzing the leachable species by HPLC). The novel resin investigated in this studyoffersthe potential benefits of reducing the risk of recurrent decay and prolonging the functional lifetime of dental adhesives.

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Acoustic Characterization of Echogenic Polymersomes Prepared From Amphiphilic Block Copolymers

Publication date: Available online 8 December 2017
Source:Ultrasound in Medicine & Biology
Author(s): Lang Xia, Fataneh Karandish, Krishna Nandan Kumar, James Froberg, Prajakta Kulkarni, Kara N. Gange, Yongki Choi, Sanku Mallik, Kausik Sarkar
Polymersomes are a class of artificial vesicles prepared from amphiphilic polymers. Like lipid vesicles (liposomes), they too can encapsulate hydrophilic and hydrophobic drug molecules in the aqueous core and the hydrophobic bilayer respectively, but are more stable than liposomes. Although echogenic liposomes have been widely investigated for simultaneous ultrasound imaging and controlled drug delivery, the potential of the polymersomes remains unexplored. We prepared two different echogenic polymersomes from the amphiphilic copolymers polyethylene glycol–poly-DL-lactic acid (PEG-PLA) and polyethylene glycol–poly-L-lactic acid (PEG-PLLA), incorporating multiple freeze-dry cycles in the synthesis protocol to ensure their echogenicity. We investigated acoustic behavior with potential applications in biomedical imaging. We characterized the polymeric vesicles acoustically with three different excitation frequencies of 2.25, 5 and 10 MHz at 500 kPa. The polymersomes exhibited strong echogenicity at all three excitation frequencies (about 50- and 25-dB enhancements in fundamental and subharmonic, respectively, at 5-MHz excitation from 20 µg/mL polymers in solution). Unlike echogenic liposomes, they emitted strong subharmonic responses. The scattering results indicated their potential as contrast agents, which was also confirmed by clinical ultrasound imaging.

http://ift.tt/2ARk4hY

upper respiratory tract infection; +27 new citations

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

upper respiratory tract infection

These pubmed results were generated on 2017/12/09

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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American Journal of Cancer Research; +19 new citations

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

American Journal of Cancer Research

These pubmed results were generated on 2017/12/09

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The underlying physiological basis of the desert rodent Meriones shawi's survival to prolonged water deprivation: Central vasopressin regulation on peripheral kidney water channels AQPs-2.

The underlying physiological basis of the desert rodent Meriones shawi's survival to prolonged water deprivation: Central vasopressin regulation on peripheral kidney water channels AQPs-2.

Acta Histochem. 2017 Dec 04;:

Authors: Elgot A, El Hiba O, Belkouch M, Gamrani H

Abstract
Meriones shawi (M. shawi) is a particular semi-desert rodent known by its resistance to long periods of thirst. The aim of the present investigation is to clarify the underlying mechanisms allowing M. shawi to resist to hard conditions of dehydration. For this reason we used two different approaches: i) a morphometric study, which consists in measuring the effect of dehydration on body and kidneys weights as well as the report kidney weight/body weight, ii) By immunohistochemistry, we proceed to study the effect of dehydration on the immunoreactivity of central vasopressin (AVP) and the kidney aquaporin-2 (AQP-2) which is a channel protein that allows water to permeate across cell membranes. Our results showed both a body mass decrease accompanied by a remarkable kidneys hypertrophy. The immunohistochemical study showed a significant increase of AQP-2 immunoreactivity in the medullar part of Meriones kidneys allowing probably to Meriones a great ability to water retention. Consistently, we demonstrate that the increased AQP-2 expression occurred together with an increase in vasopressin (AVP) expression in both hypothalamic supraoptic (SON) and paraventricular nucleus (PVN), which are a major hub in the osmotic control circuitry. These various changes seen either in body weight and kidneys or at the cellular level might be the basis of peripheral control of body water homeostasis, providing to M. shawia strong resistance against chronic dehydration.

PMID: 29217107 [PubMed - as supplied by publisher]

http://ift.tt/2Bpns4T

Bilateral sequential peripheral vestibulopathy.

http:--highwire.stanford.edu-icons-exter

Bilateral sequential peripheral vestibulopathy.

Neurology. 2016 04 12;86(15):1454-6

Authors: Young AS, Taylor RL, McGarvie LA, Halmagyi GM, Welgampola MS

PMID: 26968514 [PubMed - indexed for MEDLINE]

http://ift.tt/2jBusBb

Molecular identification of Trichinella species by multiplex PCR: new insight for Trichinella murrelli.

Molecular identification of Trichinella species by multiplex PCR: new insight for Trichinella murrelli.

Parasite. 2017;24:52

Authors: Karadjian G, Heckmann A, Rosa G, Pozio E, Boireau P, Vallée I

Abstract
In order to identify Trichinella at the species level, the commonly used test is a multiplex PCR, allowing the discrimination of nine out of the twelve taxa described so far. This test is based on five primer pairs amplifying fragments of the large subunit rDNA. Each taxon produces one or two bands of different sizes, resulting in a specific band pattern. By multiplex PCR, Trichinella murrelli shows two bands of 127 bp and 316 bp. However, a third band of 256 bp can occur. This band can lead to misidentification, since it is similar to the 253 bp band displayed by Trichinella britovi. BLAST analysis confirmed that the 256 bp band is from T. murrelli. The aim of this short note is to inform analysts that T. murrelli larvae may display either two- or three-band patterns.

PMID: 29219110 [PubMed - in process]

http://ift.tt/2nJISDU

MEK inhibitors under development for treatment of non-small-cell lung cancer.

MEK inhibitors under development for treatment of non-small-cell lung cancer.

Expert Opin Investig Drugs. 2017 Dec 07;:

Authors: Kim C, Giaccone G

Abstract
INTRODUCTION: The mitogen-activated protein kinase (MAPK) pathway is intimately implicated in the molecular pathogenesis of non-small-cell lung cancer (NSCLC). Aberrant MAPK signaling resulting from the upstream activating mutations converges on mitogen-activated protein kinase kinase 1/2 (MEK1/2), making MEK inhibition an attractive strategy for the treatment of NSCLC. Several MEK inhibitors have demonstrated anticancer activity in patients with NSCLC. Areas covered: In this article, we discuss the biological rationale for the use of MEK inhibitors and summarize the clinical experience with MEK1/2 inhibitors for the treatment of NSCLC, from initial phase I studies to phase II/III studies, both as monotherapy or in combination with other anticancer agents. Expert opinion: Trametinib in combination with the BRAF inhibitor dabrafenib represents the first MEK1/2 inhibitor containing regimen that is approved for advanced BRAFV600E-mutant NSCLC. Other MEK1/2 inhibitors that are also in advanced stages of clinical development include selumetinib, cobimetinib, and binimetinib. Several studies of MEK inhibitor combination therapies are underway, including trials using combined MEK inhibition and immune checkpoint blockade. Further research aimed at discovering biomarkers of response and resistance to MEK1/2 inhibitors will be needed to develop rational combination strategies for the treatment of NSCLC driven by aberrant MAPK signaling.

PMID: 29216787 [PubMed - as supplied by publisher]

http://ift.tt/2iIzeMv

Reduced empathic responses for sexually objectified women: an fMRI investigation

Publication date: Available online 8 December 2017
Source:Cortex
Author(s): Carlotta Cogoni, Andrea Carnaghi, Giorgia Silani
Sexual objectification is a widespread phenomenon characterized by a focus on the individual´s physical appearance over his/her mental state. This has been associated with negative social consequences, as objectified individuals are judged to be less human, competent, and moral. Moreover, behavioral responses toward the person change as a function of the degree of the perceived sexual objectification. In the present study, we investigated how behavioral and neural representations of other social pain are modulated by the degree of sexual objectification of the target. Using a within-subject fMRI design, we found reduced empathic feelings for positive (but not negative) emotions toward sexually objectified women as compared to non-objectified (personalized) women when witnessing their participation to a ball-tossing game. At the brain level, empathy for social exclusion of personalized women recruited areas coding the affective component of pain (i.e., anterior insula and cingulate cortex), the somatosensory components of pain (i.e., posterior insula and secondary somatosensory cortex) together with the mentalizing network (i.e., middle frontal cortex) to a greater extent than for the sexually objectified women. This diminished empathy is discussed in light of the gender-based violence that is afflicting the modern society.

http://ift.tt/2Aow8IO

Toxicity trial of canine posterior cricoarytenoid intramuscular vincristine injections.

Toxicity trial of canine posterior cricoarytenoid intramuscular vincristine injections.

Laryngoscope. 2017 Dec 08;:

Authors: Paniello RC, Bhatt NK, Chernock R

Abstract
OBJECTIVES/HYPOTHESIS: In animal studies, intramuscular vincristine injections have been shown to block reinnervation of the denervated target muscle. This application could be used selectively to influence recovery patterns following injury of recurrent laryngeal nerves (RLNs). However, vincristine is currently Food and Drug Administration approved only for intravenous use. A formal toxicity trial of intramuscular injections was performed.
STUDY DESIGN: Animal study.
METHODS: Sixteen female canines underwent direct laryngoscopy with injection of moderate- (0.4 mg, n = 8) or high-dose (0.6 mg, n = 8) vincristine into the posterior cricoarytenoid (PCA) muscles. Plasma samples were collected at various time points postinjection and vincristine levels determined. At 24 hours (n = 7) or 14 days (n = 9) postinjection, animals were anesthetized and videolaryngoscopy documented vocal fold mobility and mucosal appearance. Adductor function was measured during stimulation of the RLN. Larynges were processed for histology.
RESULTS: Fifteen minutes after injection, plasma vincristine levels averaged 10.2% ± 6.7% of the intravenous maximum, suggesting about 90% of the vincristine remained within the PCA muscle. Plasma levels were usually below detectable limits within 24 hours. At the end points, all animals had grossly normal-appearing mucosa and full range of motion. Laryngeal adductor strength was normal in all cases. Histology showed moderate to severe acute inflammation in the submucosa only in the high-dose group at 24 hours. There was no necrosis of muscle or mucosa.
CONCLUSIONS: Intramuscular vincristine injections into the canine PCA muscles resulted in no significant local toxicity, even at the maximum dose. It would be reasonable to evaluate this treatment strategy in a phase I human trial.
LEVEL OF EVIDENCE: NA Laryngoscope, 2017.

PMID: 29219188 [PubMed - as supplied by publisher]

http://ift.tt/2AOdfOw

Αρχειοθήκη ιστολογίου

! # Ola via Alexandros G.Sfakianakis on Inoreader

Η λίστα ιστολογίων μου

Σάββατο 9 Δεκεμβρίου 2017

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