Mental Health in China: Change, Tradition and Therapeutic Governance

China's massive economic restructuring in recent decades has generated alarming incidences of mental disorder affecting over one hundred million people. This timely book provides an anthropological analysis of mental health in China through an exploration of psychology, psychiatry, psychotherapy and psychosocial practices, and the role of the State. The book offers a critical study of new characteristics and unique practices of Chinese psychology and Read More...

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Mental Health in China: Change, Tradition and Therapeutic Governance

China's massive economic restructuring in recent decades has generated alarming incidences of mental disorder affecting over one hundred million people. This timely book provides an anthropological analysis of mental health in China through an exploration of psychology, psychiatry, psychotherapy and psychosocial practices, and the role of the State. The book offers a critical study of new characteristics and unique practices of Chinese psychology and Read More...

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Kit W-sh Mutation Prevents Cancellous Bone Loss during Calcium Deprivation

Abstract

Calcium is essential for normal bone growth and development. Inadequate calcium intake increases the risk of osteoporosis and fractures. Kit ligand/c-Kit signaling plays an important role in regulating bone homeostasis. Mice with c-Kit mutations are osteopenic. The present study aimed to investigate whether impairment of or reduction in c-Kit signaling affects bone turnover during calcium deprivation. Three-week-old male WBB6F1/J-Kit ^W/Kit ^W-v/J (W/W ^v ) mice with c-Kit point mutation, Kit ^W-sh /HNihrJaeBsmJ (W ^sh/W ^sh ) mice with an inversion mutation in the regulatory elements upstream of the c-Kit promoter region, and their wild-type controls (WT) were fed either a normal (0.6% calcium) or a low calcium diet (0.02% calcium) for 3 weeks. μCT analysis indicated that both mutants fed normal calcium diet had significantly decreased cortical thickness and cancellous bone volume compared to WT. The low calcium diet resulted in a comparable reduction in cortical bone volume and cortical thickness in the W/W ^v and W ^sh/W ^sh mice, and their corresponding controls. As expected, the low calcium diet induced cancellous bone loss in the W/W ^v mice. In contrast, W ^sh/W ^sh cancellous bone did not respond to this diet. This c-Kit mutation prevented cancellous bone loss by antagonizing the low calcium diet-induced increase in osteoblast and osteoclast numbers in the W ^sh/W ^sh mice. Gene expression profiling showed that calcium deficiency increased Osx, Ocn, Alp, type I collagen, c-Fms, M-CSF, and RANKL/OPG mRNA expression in controls; however, the W ^sh mutation suppressed these effects. Our findings indicate that although calcium restriction increased bone turnover, leading to osteopenia, the decreased c-Kit expression levels in the W ^sh/W ^sh mice prevented the low calcium diet-induced increase in cancellous bone turnover and bone loss but not the cortical bone loss.

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Management of cervicofacial infections: a survey of current practice in maxillofacial units in the UK

Publication date: Available online 13 October 2017
Source:British Journal of Oral and Maxillofacial Surgery
Author(s): C. McDonald, A. Hennedige, A. Henry, B. Dawoud, R. Kulkarni, K. Gilbert, P. Kyzas, R. Morrison, J.A. McCaul
Cervicofacial infections are common emergency presentations to maxillofacial departments in the UK, there is no consensus about their management and, in particular, the role of corticosteroids is not clear. Our aim was to find out the current practice of UK maxillofacial surgeons in managing these infections using a multicentre questionnaire study. The questionnaire was designed, piloted, and revised before distribution, and questions were asked to assess preoperative, operative, and postoperative management. It was distributed to maxillofacial surgeons throughout the UK through the Maxillofacial Research Trainee Collaborative (MTReC) network, and at the 2016 British Association of Oral and Maxillofacial Surgeons (BAOMS) Junior Trainees Group conference. A total of 350 questionnaires were distributed to 17 maxillofacial units. Eighty-six questionnaires were distributed at the BAOMS Junior Trainee conference. An overall response rate of 92% (n=324) was achieved. The results showed that there were important differences in reported practice between and within maxillofacial units in the UK in managing these infections. The antibiotic regimens and use of steroids varied widely. Twenty-three per cent of respondents had to wait over 24hours for access to emergency theatres. However, these results provide no hard evidence for or against the use of corticosteroids in cervicofacial infections.



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Iatrogenic mandibular fracture after open reduction and internal fixation in a patient with osteogenesis imperfecta

Publication date: Available online 14 October 2017
Source:British Journal of Oral and Maxillofacial Surgery
Author(s): M.-Y. Kim, C.-H. Kim
To the best of our knowledge, this is the first report to discuss the possible mechanisms of an iatrogenic fracture during operation on an original mandibular fracture in a patient with osteogenesis imperfecta.



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Cardiac Macrophage Biology in the Steady State Heart, the Aging Heart, and Following Myocardial Infarction

Publication date: Available online 13 October 2017
Source:Translational Research
Author(s): Yonggang Ma, Alan J. Mouton, Merry L. Lindsey
Macrophages play critical roles in homeostatic maintenance of the myocardium under normal conditions and in tissue repair after injury. In the steady state heart, resident cardiac macrophages remove senescent and dying cells and facilitate electrical conduction. In the aging heart, the shift in macrophage phenotype to a pro-inflammatory subtype leads to inflammaging. Following myocardial infarction (MI), macrophages recruited to the infarct produce both pro- and anti- inflammatory mediators (cytokines, chemokines, matrix metalloproteinases, and growth factors), phagocytize dead cells, and promote angiogenesis and scar formation. These diverse properties are attributed to distinct macrophage subtypes and polarization status. Infarct macrophages exhibit a pro-inflammatory M1 phenotype early and become polarized towards an anti-inflammatory M2 phenotype later post-MI. While this classification system is oversimplified and needs to be refined to accommodate the multiple different macrophage subtypes that have been recently identified, general concepts on macrophage roles are independent of subtype classification. This review summarizes current knowledge about cardiac macrophage origins, roles, and phenotypes in the steady state, with aging, and after MI, as well as highlights outstanding areas of investigation.



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Dynamics of Plasma Cytokines in a Patient with Deficiency of Interleukin-36 Receptor Antagonist Successfully Treated with Anakinra

Generalized pustular psoriasis (GPP) is an autoinflammatory disease characterized by abrupt-onset episodes of erythematous skin plaques with countless pustules, fever, marked neutrophilia and increased acute phase reactants (APR).¹ Loss-of-function mutations in the IL36RN gene, encoding for interleukin (IL)-36 receptor antagonist (IL-36Ra), have been described in a significant proportion of GPP patients.^2,3 Previous studies have shown in vitro and ex vivo enhanced production of pro-inflammatory cytokines (IL-1, IL-6 and IL-8) and successful outcomes with anti-IL-1 drugs in patients carrying IL36RN mutations.^1,2 However, little is known about the correlation of plasma cytokines, inflammatory markers and clinical follow-up, before and after treatment with anti-IL-1 drugs.

This article is protected by copyright. All rights reserved.

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Comment on: A Visual Literacy Course for Dermatology Trainees

We would like to congratulate Griffin and colleagues on their report of an innovative training programme in visual literacy for dermatology registrars (residents).¹ Our experience of visual literacy training for registrars in South London resonates with that of the Manchester group, and we would like to add to this by describing our observation of some additional qualitative benefits which may be derived from such training. Training similar to that described by the Griffin et al was delivered to 10 dermatology registrars at the Dulwich Picture Gallery in London, England from September 2016 – January 2017 in 5 one hour sessions. Baseline and post-course assessments, scored on the unique accurate observations method described by Huang et al,² were carried out and demonstrated an increase in the number of unique accurate observations per image following the course compared to pre-course assessment.

This article is protected by copyright. All rights reserved.

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Representation of environmental shape in the hippocampus of domestic chicks ( Gallus gallus )

Abstract

The hippocampus plays an important role in spatial encoding and memory across various vertebrate species. In rodents, hippocampal neurons are particularly sensitive to a change in environmental geometry. Given the similarities in function between the mammalian and avian hippocampi, we aimed to measure whether enclosures varying in geometric shape (square and rectangle) can differentially activate hippocampal cells in the domestic chick (Gallus gallus domesticus). Chicks exposed to both a square and a rectangular arena exhibited a significantly higher neural activation (as measured by c-Fos expression) than those exposed twice to just the square or just the rectangle (both of which were significantly higher in activation than a one-environment control group). For the first time in an avian species, we show that exposure to two enclosures of different geometric shape activates the hippocampus to a greater degree, suggesting a possible effect of spatial remapping.

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Global gene expression profiles of hematopoietic stem and progenitor cells from patients with chronic myeloid leukemia: the effect of in vitro culture with or without imatinib

Abstract

In this study, we determined the gene expression profiles of bone marrow-derived cell fractions, obtained from normal subjects and Chronic Myeloid Leukemia (CML) patients, that were highly enriched for hematopoietic stem (HSCs) and progenitor (HPCs) cells. Our results indicate that the profiles of CML HSCs and HPCs were closer to that of normal progenitors, whereas normal HSCs showed the most different expression profile of all. We found that the expression profiles of HSCs and HPCs from CML marrow were closer to each other than those of HSCs and HPCs from normal marrow. The major biologic processes dysregulated in CML cells included DNA repair, cell cycle, chromosome condensation, cell adhesion, and the immune response. We also determined the genomic changes in both normal and CML progenitor cells under culture conditions, and found that several genes involved in cell cycle, steroid biosynthesis, and chromosome segregation were upregulated, whereas genes involved in transcription regulation and apoptosis were downregulated. Interestingly, these changes were the same, regardless of the addition of Imatinib (IM) to the culture. Finally, we identified three genes—PIEZO2, RXFP1, and MAMDC2- that are preferentially expressed by CML primitive cells and that encode for cell membrane proteins; thus, they could be used as biomarkers for CML stem cells.

Gene expression profiles of hematopoietic stem and progenitor cells from CML patients have been obtained. The in vitro effect of Imatinib on such gene expression profiles was assessed. Potential leukemic biomarker genes were identified.

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Phosphorylated ERK is a potential prognostic biomarker for Sorafenib response in hepatocellular carcinoma

Abstract

Sorafenib, the only approved drug for hepatocellular carcinoma, acts as a remarkable inhibitor of Raf serine-threonine kinases. However, Sorafenib is expensive, and clinical experience shows that it is not an effective treatment for many patients. Previous study has demonstrated that phosphorylated ERK (pERK) is a key downstream component in the RAF/MEK/ERK signaling pathway. Here, we investigate whether pERK is a useful biomarker for treating HCC with Sorafenib. In vitro cell viability assays showed that the efficacy of Sorafenib was distinctly different according to the level of pERK. Furthermore, in established patient-derived xenografts from HCC specimens, we found that the growth rate of tumors with high levels of pERK was significantly decreased by Sorafenib treatment. Taken together, pERK is a potential biomarker for the sensitivity to Sorafenib in treating HCC.

In hepatocellular carcinoma (HCC), the efficacy of Sorafenib remains moderate and certain patients display a short period of survival following treatment. Our vitro and in vivo results revealed the relationship between the expression of phosphorylated ERK (pERK) and Sorafenib response in HCC. We confirmed that tumors containing higher levels of pERK are more sensitive to Sorafenib. pERK may be a useful biomarker in treating HCC with Sorafenib.

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The role of general psychosocial factors for the use of cancer screening—Findings of a population-based observational study among older adults in Germany

Abstract

Within the framework of the health-belief model, some studies exist investigating the association between illness-specific psychosocial factors and the use of cancer screenings. However, studies investigating the association between general psychosocial factors and the use of cancer screenings are missing. Thus, this study aimed at examining the association between well-established general psychosocial factors and the use of cancer screenings. Data were gathered from a large, population-based sample of community-dwelling individuals aged 40 and above in Germany (n = 7673; in 2014). Loneliness, cognitive well-being, affective well-being (negative and positive affect), optimism, self-efficacy, self-esteem, self-regulation, perceived autonomy, perceived stress, and perceived social exclusion were used as general psychosocial factors. Furthermore, individuals were asked whether they regularly underwent early cancer screening in the past years (yes; no). A total of 65.6% of the individuals used cancer screening. Adjusting for sociodemographic factors, self-rated health, morbidity and lifestyle factors, multiple logistic regressions revealed that the use of cancer screening is positively associated with decreased loneliness, cognitive well-being, optimism, self-efficacy, self-esteem, self-regulation, perceived autonomy, decreased perceived stress, decreased perceived social exclusion, and positive affect, while it is not associated with negative affect. This study stresses the strong association between general psychosocial factors and the use of cancer screening. This knowledge might be fruitful to address individuals at risk for underuse.

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An In Vivo Model of a Mechanically-Induced Bone Marrow Lesion

Publication date: Available online 13 October 2017
Source:Journal of Biomechanics
Author(s): Jonathan B. Matheny, Matthew G. Goff, Sarah L. Pownder, Matthew F. Koff, Kei Hayashi, Xu Yang, Mathias P.G. Bostrom, Marjolein C.H. van der Meulen, Christopher J. Hernandez
Bone marrow lesions (BMLs) are radiologic abnormalities in magnetic resonance images of subchondral bone that are correlated with osteoarthritis. Little is known about the physiologic processes within a BML, although BMLs are associated with mechanical stress, bone tissue microdamage and increased bone remodeling. Here we establish a rabbit model to study the pathophysiology of BMLs. We hypothesized that in vivo loads that generate microdamage in cancellous bone would also create BMLs and increase bone remodeling. In vivo cyclic loading (0.2 to 2.0 MPa in compression for 10,000 cycles at 2 Hz) was applied to epiphyseal cancellous bone in the distal femurs of New Zealand white rabbits (n=3, right limb loaded, left limb controls experienced surgery but no loading). Magnetic resonance images were collected using short tau inversion recovery (STIR) and T1 weighted sequences at 1 and 2 weeks after surgery/loading and histological analysis of the BML was performed after euthanasia to examine tissue microdamage and remodeling. Loaded limbs displayed BMLs while control limbs showed only a small BML-like signal caused by surgery. Histological analysis of the BML at 2 weeks after loading showed increased tissue microdamage (p=0.03) and bone resorption (p=0.01) as compared to controls. The model described here displays the hallmarks of load-induced BMLs, supporting the use of the model to examine changes in bone during the development, progression and treatment of BMLs.



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Tissue viscoelasticity is related to tissue composition but may not fully predict the apparent-level viscoelasticity in human trabecular bone - an experimental and finite element study

Publication date: Available online 13 October 2017
Source:Journal of Biomechanics
Author(s): X. Ojanen, P. Tanska, M.K.H. Malo, H. Isaksson, S.P. Väänänen, A.P. Koistinen, L. Grassi, S.P. Magnusson, S.M. Ribel-Madsen, R.K. Korhonen, J.S. Jurvelin, J. Töyräs
Trabecular bone is viscoelastic under dynamic loading. However, it is unclear how tissue viscoelasticity controls viscoelasticity at the apparent-level. In this study, viscoelasticity of cylindrical human trabecular bone samples (n=11, male, age 18-78 years) from 11 proximal femurs were characterized using dynamic and stress-relaxation testing at the apparent-level and with creep nanoindentation at the tissue-level. In addition, bone tissue elasticity was determined using scanning acoustic microscope (SAM). Tissue composition and collagen crosslinks were assessed using Raman micro-spectroscopy and high performance liquid chromatography (HPLC), respectively. Values of material parameters were obtained from finite element (FE) models by optimizing tissue-level creep and apparent-level stress-relaxation to experimental nanoindentation and unconfined compression testing values, respectively, utilizing the second order Prony series to depict viscoelasticity. FE simulations showed that tissue-level equilibrium elastic modulus (Eeq) increased with increasing crystallinity (r=0.730, p=0.011) while at the apparent-level it increased with increasing hydroxylysyl pyridinoline content (r=0.718, p=0.019). In addition, the normalized shear modulus g1 (r=-0.780, p=0.005) decreased with increasing collagen ratio (amide III/CH2) at the tissue-level, but increased (r=0.696, p=0.025) with increasing collagen ratio at the apparent-level. No significant relations were found between the measured or simulated viscoelastic parameters at the tissue- and apparent-levels nor were the parameters related to tissue elasticity determined with SAM. However, only Eeq, g2 and relaxation time τ1 from simulated viscoelastic values were statistically different between tissue- and apparent-levels (p<0.01). These findings indicate that bone tissue viscoelasticity is affected by tissue composition but may not fully predict the macroscale viscoelasticity in human trabecular bone.



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Analysis of non-Newtonian effects within an aorta-iliac bifurcation region

Publication date: Available online 13 October 2017
Source:Journal of Biomechanics
Author(s): Marcello Iasiello, Kambiz Vafai, Assunta Andreozzi, Nicola Bianco
The geometry of the arteries at or near arterial bifurcation influences the blood flow field, which is an important factor affecting arteriogenesis. The blood can act sometimes as a non-Newtonian fluid. However, many studies have argued that for large and medium arteries, the blood flow can be considered to be Newtonian. In this work a comprehensive investigation of non-Newtonian effects on the blood fluid dynamic behavior in an aorta-iliac bifurcation is presented. The aorta-iliac geometry is reconstructed with references to the values reported in Shah et al. (1978); the 3D geometrical model consists of three filleted cylinders of different diameters. Governing equations with the appropriate boundary conditions are solved with a finite-element code. Different rheological models are used for the blood flow through the lumen and detailed comparisons are presented for the aorta-iliac bifurcation. Results are presented in terms of the velocity profiles in the bifurcation zone and Wall Shear Stress (WSS) for different sides of the bifurcation both for a male and female geometries, showing that the Newtonian fluid assumption can be made without any particular loss in terms of accuracy with respect to the other more complex rheological models.



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Laser Sintering Technology and Balling Phenomenon

Photomedicine and Laser Surgery , Vol. 0, No. 0.


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Identification and characterization of a metastatic suppressor BRMS1L as a target gene of p53

Summary

The tumor suppressor p53 and its family members, p63 and p73, play a pivotal role in the cell fate determination in response to diverse upstream signals. As transcription factors, p53 family proteins regulate a number of genes that are involved in cell-cycle arrest, apoptosis, senescence, and maintenance of genomic stability. Recent studies revealed that p53 family proteins are important for the regulation of cell invasion and migration. Microarray analysis showed that breast cancer metastasis-suppressor 1- like (BRMS1L) is upregulated by p53 family proteins, specifically p53, TAp63γ, and TAp73β. We identified two responsive elements of p53 family proteins in the first intron and upstream of BRMS1L. These response elements are well conserved among mammals. Functional analysis showed that ectopic expression of BRMS1L inhibited cancer cell invasion and migration; knockdown of BRMS1L by siRNA induced the opposite effect. Importantly, clinical databases revealed that reduced BRMS1L expression correlated with poor prognosis in patients with breast and brain cancer. Altogether, these results strongly indicate that BRMS1L is one of the mediators downstream of the p53 pathway, and inhibits cancer cell invasion and migration, which are essential steps in cancer metastasis. Collectively, our results demonstrate that BRMS1L is involved in cancer cell invasion and migration, and may be a therapeutic target for cancer.

This article is protected by copyright. All rights reserved.

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Outpatient parenteral antimicrobial therapy in Enterococcus faecalis infective endocarditis

Summary

What is known and objective

Enterococcus faecalis is the third most common causal agent of infective endocarditis. Currently, the treatment recommended is a combination of ampicillin (2 g/4 h) plus ceftriaxone (2 g/12 h), so patients must remain hospitalized for almost 6 weeks to receive the treatment. They are not generally included in outpatient parenteral antimicrobial therapy programs because 2 different electronic pumps are required to administer these 2 antibiotics. To enable the treatment of patients with E. faecalis IE at home, we designed a continuation combination regimen of ceftriaxone 4 g once daily in a short infusion plus ampicillin 2 g/4 h using a programmable pump.

Methods

We analyzed a cohort of patients attended in an outpatient parenteral antimicrobial therapy program that has been working since 2012 in 2 tertiary hospitals. We selected patients attended in this program for E. faecalis IE treated with a continuation regimen of ampicillin 12 g daily (2 g/4 h) and ceftriaxone 4 g every 24 hours between July 2012 and March 2017.

Results and discussion

Of the 720 patients included in the outpatient parenteral antimicrobial therapy program, 42 had infective endocarditis, and 4 (9.52%) were treated using the combination regimen described above. All patients were men, and all had left-sided native-valve infective endocarditis. All 4 patients received ampicillin 2 g every 4 hours and ceftriaxone 2 g every 12 hours in hospital, for a median duration of 25 days (IQR 15-32). Thereafter, in the program, they received the following regimen: a 30-minute infusion of ceftriaxone 4 g in 250 mL of saline solution, followed by ampicillin 12 g daily in 500 mL of saline solution delivered by a pump programmed to administer 2 g every 4 hours. Patients received this treatment at home for a median of 22.5 days (IQR 13-32). All patients achieved clinical and microbiological cure with no recurrences or complications after a lengthy follow-up period (median 365 days, IQR 221-406). No drug-related adverse events or problems with the pump system were reported.

What is new and conclusions

Use of ceftriaxone 4 g in a single dose yields a mean plasma concentration of 30 μg/mL. Ceftriaxone also has a high plasma protein binding capability, and once this binding is saturated, there is no reason to administer higher doses. Therefore, it seems reasonable to use a dose of 4 g of ceftriaxone once daily to have a synergist effect with ampicillin within the vegetation, and enable the treatment of patients with E. faecalis infective endocarditis at home. In conclusion, the administration of ampicillin (2 g/4 h) plus ceftriaxone (4 g/24 h) as a continuation regimen in an outpatient parenteral antimicrobial therapy program may be as effective and safe as the usual lengthy in-hospital regimen (ampicillin 2 g/4 h and ceftriaxone 2 g/12 h) in patients with E. faecalis infective endocarditis.

One of the most employed treatment for infective endocarditis due to E. faecalis is a combination of ampicillin (2 g/4 h) plus ceftriaxone (2 g/12 h), so patients must remain hospitalized for 6 weeks. We describe four cases treated with a continuation régimen of ampicillin 12 g daily (2 g/4 h) and ceftriaxone 4 g every 24 hours in an OPAT program in two Spanish tertiary hospitals. This strategy seems to be as effective and safe as the classic in-hospital régimen.

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Evaluation of the predictive performance of bleeding risk scores in patients with non-valvular atrial fibrillation on oral anticoagulants

Summary

What is known and objective

Bleeding risk scores (BRSs) aid in the assessment of oral anticoagulant-related bleeding risk in patients with atrial fibrillation. Ideally, the applicability of a BRS needs to be assessed, prior to its routine use in a population other than the original derivation cohort. Therefore, we evaluated the performance of 6 established BRSs to predict major or clinically relevant bleeding (CRB) events associated with the use of oral anticoagulant (OAC) among Malaysian patients.

Methods

The pharmacy supply database and the medical records of patients with non-valvular atrial fibrillation (NVAF) receiving warfarin, dabigatran or rivaroxaban at two tertiary hospitals were reviewed. Patients who experienced an OAC-associated major or CRB event within 12 months of follow-up, or who have received OAC therapy for at least 1 year, were identified. The BRSs were fitted separately into patient data. The discrimination and the calibration of these BRSs as well as the factors associated with bleeding events were then assessed.

Results

A total of 1017 patients with at least 1-year follow-up period, or those who developed a bleeding event within 1 year of OAC use, were recruited. Of which, 23 patients experienced a first major bleeding event, whereas 76 patients, a first CRB event. Multivariate logistic regression results show that age of 75 or older, prior bleeding and male gender are associated with major bleeding events. On the other hand, prior gastrointestinal bleeding, a haematocrit value of less than 30% and renal impairment are independent predictors of CRB events. All the BRSs show a satisfactory calibration for major and CRB events. Among these BRSs, only HEMORR₂HAGES (C-statistic = 0.71, 95% CI 0.60-0.82, P < .001) and ATRIA score (C-statistic = 0.70, 95% CI 0.58-0.82, P < .001) show acceptable discrimination performance for major bleeding events. All the 6 BRSs, however, lack acceptable predictive performance for CRB events.

What is new and conclusion

To the best of our knowledge, this is the first evaluation study of the predictive performance of these 6 BRSs on clinically relevant bleeding events applied to the same cohort consisting of mainly Asian novel oral anticoagulant users. These BRSs show poor to acceptable predictive performance on OAC-induced major or CRB events. An improvement in the existing BRSs for OAC users is warranted.

The performance of mOBRI, CBRM, HEMORR₂HAGES, HAS-BLED, ATRIA and ORBIT bleeding risk scores (BRS) to predict major bleeding (MB) or clinically relevant bleeding (CRB) events associated with the use of oral anticoagulant among Malaysian patients is evaluated. Among these BRSs, only HEMORR₂HAGES and ATRIA score show acceptable discrimination performance for major bleeding events. All the 6 BRSs, however, lack acceptable predictive performance for CRB events.

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Corrigendum to “The influence of different abutment materials on tissue regeneration after surgical treatment of peri-implantitis – A randomized controlled preclinical study” [J Cranio-Maxillo-Facial Surg 45 (2017) 1190–1196]

The authors regret an incorrect approval number of "54-2532.1-45/12" by the Pest county government Department for Food Safety and Animal Health, Hungary. The correct number is "PEI/001/961-2/2013".

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Colchicine is an active treatment for everolimus-induced oral ulcers

Stomatitis (oral ulcers), the dose-limiting toxicity of everolimus [1], occurs in up to 59% of patients [2] and is unpredictably relieved by local treatments [3]. Its clinical presentation is close to that of oral ulcers seen in Behçet's disease [3].

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Codon usage and amino acid usage influence genes expression level

Abstract

Highly expressed genes in any species differ in the usage frequency of synonymous codons. The relative recurrence of an event of the favored codon pair (amino acid pairs) varies between gene and genomes due to varying gene expression and different base composition. Here we propose a new measure for predicting the gene expression level, i.e., codon plus amino bias index (CABI). Our approach is based on the relative bias of the favored codon pair inclination among the genes, illustrated by analyzing the CABI score of the Medicago truncatula genes. CABI showed strong correlation with all other widely used measures (CAI, RCBS, SCUO) for gene expression analysis. Surprisingly, CABI outperforms all other measures by showing better correlation with the wet-lab data. This emphasizes the importance of the neighboring codons of the favored codon in a synonymous group while estimating the expression level of a gene.

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The Effect of a Pediatric Intensive Care Severity-Tiered Pathway for Status Asthmaticus on Quality Measures and Outcomes

Pediatric Allergy, Immunology, and Pulmonology , Vol. 0, No. 0.


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Halofuginone improves caustic-induced oxidative injury of esophagus in rats

Abstract

Background

The aim of this study is to evaluate the anti-inflammatory and anti-fibrotic effects of halofuginone in caustic esophageal burn injury in rats.

Materials and methods

Corrosive esophageal injury (CEI) was produced in male Wistar albino rats by instilling NaOH solution (1 ml, 37.5%) into the distal esophagus. Rats were decapitated on the 3rd day (early group) or 28th day (late group), and treated daily with either saline or halofuginone (100 µg/kg/day; i.p.), continued on alternate days after the third day. Histopathological evaluation and measurement of nitric oxide (NO), peroxynitrite (ONOO-) and oxygen-derived radicals by chemiluminescence (CL) were made in the distal 2 cm of the esophagus. Non-irrigated proximal esophageal samples were assessed for the levels of nuclear factor (NF)-κB, caspase-3, glutathione (GSH), malondialdehyde (MDA) and myeloperoxidase (MPO) activity.

Results

GSH, MDA, NF-κB and caspase-3 levels, and MPO activity in the proximal esophagus were not different among groups. Increased number of TUNEL (+) cells in the irrigated esophagus of the early and late caustic injury groups was reduced by halofuginone treatment. High microscopic damage scores in both early and late CEI groups were decreased with halofuginone treatment. NO, ONOO- and CL levels, which were elevated in the saline-treated early CEI group, were reduced by halofuginone treatment, but reduced NO and ONOO- levels in the late period of saline-treated group were increased by halofuginone.

Conclusion

In addition to its anti-fibrotic effects, current findings demonstrate that halofuginone exerts antioxidant and anti-apoptotic actions and supports therapeutic potential for halofuginone in CEI-induced oxidative stress.

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Antiviral effects of Lactobacillus crispatus against HSV-2 in mammalian cell lines

Herpes simplex virus type 2 (HSV-2) infectious disease is one of the most common viral sexually transmitted diseases. As regards, vaginal lactobacilli play an important role in protecting host against the urogenital pathogens; here we assessed the potential antiviral activity of Lactobacillus crispatus against HSV-2 infection in vitro.

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Implant-oriented navigation in orbital reconstruction. Part 1: technique and accuracy study

Intraoperative navigation is frequently used to assess the position of the implant in orbital reconstruction. Interpretation of the feedback from the navigation system to a three-dimensional position of the implant needs to be done by the surgeon, and feedback is only gathered after the implant has been positioned. An implant-oriented navigation approach is proposed, with real-time intuitive feedback during insertion. A technical framework was set up for implant-oriented navigation, with requirements for planning, implant tracking, and feedback.

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Corrigendum to “The influence of different abutment materials on tissue regeneration after surgical treatment of peri-implantitis – A randomized controlled preclinical study” [J Cranio-Maxillo-Facial Surg 45 (2017) 1190–1196]

The authors regret an incorrect approval number of "54-2532.1-45/12" by the Pest county government Department for Food Safety and Animal Health, Hungary. The correct number is "PEI/001/961-2/2013".

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Colchicine is an active treatment for everolimus-induced oral ulcers

Publication date: Available online 13 October 2017
Source:European Journal of Cancer
Author(s): Stanislas Ropert, Romain Coriat, Benjamin Verret, Audrey Perret, Francesca Lucibello, Ali N. Chamseddine, Jean-Pierre Armand, Angelo Paci, Olivier Mir




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Iatrogenic mandibular fracture after open reduction and internal fixation in a patient with osteogenesis imperfecta

To the best of our knowledge, this is the first report to discuss the possible mechanisms of an iatrogenic fracture during operation on an original mandibular fracture in a patient with osteogenesis imperfecta.

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Review: Diagnosing Common Variable Immunodeficiency Disorder in the Era of Genome Sequencing

Abstract

Common variable immunodeficiency disorders (CVID) are an enigmatic group of often heritable conditions, which may manifest for the first time in early childhood or as late as the eighth decade of life. In the last 5 years, next generation sequencing (NGS) has revolutionised identification of genetic disorders. However, despite the best efforts of researchers around the globe, CVID conditions have been slow to yield their molecular secrets. We have previously described the many clinical advantages of identifying the genetic basis of primary immunodeficiency disorders (PIDs). In a minority of CVID patients, monogenic defects have now been identified. If a causative mutation is identified, these conditions are reclassified as CVID-like disorders. Here we discuss recent advances in the genetics of CVID and discuss how NGS can be optimally deployed to identify the causal mutations responsible for the protean clinical manifestations of these conditions. Diagnostic criteria such as the Ameratunga et al. criteria will continue to play an important role in patient management as well as case selection and sequencing strategy design until the genetic conundrum of CVID is solved.

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Unstable Thyroid Function in Older Adults Is Caused by Alterations in Both Thyroid and Pituitary Physiology and Is Associated with Increased Mortality

Thyroid , Vol. 0, No. 0.


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87th Annual Meeting of the American Thyroid Association

Thyroid Oct 2017, Vol. 27, No. S1: P-1-A-156.


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Short Call Abstracts

Thyroid Oct 2017, Vol. 27, No. S1: A-166-A-188.


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Short Call Author Abstract Index

Thyroid Oct 2017, Vol. 27, No. S1: A-189-A-191.


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Abstract Author Index

Thyroid Oct 2017, Vol. 27, No. S1: A-157-A-165.


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Primary pulmonary leiomyosarcoma: a case report

Abstract

Primary pulmonary leiomyosarcoma (PPL) is a very rare tumour. Presentation depends on the site of origin of tumour. Early detection and complete resection result in long-term survival. Complete surgical resection offers the only chance of cure. The role of radiotherapy or chemotherapy is not established.

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An uneventful life

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Workers laid off, awarded severance at plant

Colwell Systems, a company created in 1928, operated at a plant in Champaign. The business was a division of Patterson Companies, which is based in Minnesota.

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Girl Scout organizes dental project for Gold Award

Shivani Chati with volunteers and pupils at Greenvale School, where she organized a pediatric dental clinic as part of earning her Girl Scout Gold Award.

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Análisis de supervivencia libre de recaída audiométrica en pacientes con hipoacusia inmunomediada tratados exclusivamente con corticoides

Publication date: Available online 13 October 2017
Source:Acta Otorrinolaringológica Española
Author(s): Nieves Mata-Castro, Raimon García-Chilleron, Javier Gavilanes-Plasencia, Rafael Ramírez-Camacho, Alfredo García-Fernández, José Ramón García-Berrocal
ObjetivoDescribir los resultados en términos de supervivencia libre de recaída audiométrica y el ritmo de recaída en pacientes con hipoacusia inmunomediada tratados exclusivamente con corticoides.MétodoEstudio retrospectivo de pacientes, con recaídas audiométricas, en seguimiento desde 1995 hasta 2014, en 2 centros de la Comunidad de Madrid.ResultadosSe evaluaron 31 pacientes con una media de edad de 48,52 años (14,67 DE) de los cuales el 61,3% fueron mujeres. La mayoría de las hipoacusias fueron fluctuantes (48,4%). Solo el 16,1% de los pacientes presentaban enfermedad autoinmune sistémica. Existe una correlación positiva moderada entre ser mujer y presentar afectación sistémica (coeficiente de correlación de Spearman=0,356). La tasa relativa de incidencia de recaída en el primer año en nuestra serie fue de 2,01 recaídas/año con un IC95% (1,32-2,92). El tiempo de supervivencia medio del evento (recaída audiométrica) fue de 5,25 meses (DE 0,756). Con el análisis multivariante, la única variable que consiguió significación estadística fue la edad, con una hazard ratio de 1,032 (IC95%; 1,001-1,063, p=0,043)ConclusionesLa enfermedad inmunomediada del oído interno es una enfermedad crónica con recaídas. La mitad de los pacientes tratados exclusivamente con corticoides recaen antes de los 6 meses de seguimiento. Además, si un paciente no ha presentado recaída, tiene más riesgo de recaer cada año que pasa. El análisis de la supervivencia libre de recaída audiométrica permitirá comparar el efecto de tratamientos futuros y su capacidad para reducir el ritmo de recaídas.ObjectiveTo describe the results in terms of audiometric relapse-free survival and relapse rate in immunomediated hearing loss patients treated exclusively with corticosteroids.MethodRetrospective study of patients with audiometric relapses, monitored from 1995 to 2014, in two centres of the Community of Madrid.ResultsWe evaluated 31 patients with a mean age of 48.52 years (14.67 SD), of which 61.3% were women. Most hearing loss was fluctuating (48.4%). Only 16.1% of patients had systemic autoimmune disease. There is a moderate positive correlation between the sex variable and the systemic involvement variable (Spearman's correlation coefficient=0.356): specifically, between being female and systemic disease. The relative incidence rate of relapse in the first year was 2.01 relapses/year with a 95% CI (1.32 to 2.92). The mean survival time of the event (audiometric relapse) was 5.25 months (SD 0.756). With multivariate analysis, the only variable that achieved statistical significance was age, with a hazard ratio of 1.032 (95% CI; 1.001-1.063, P=.043).ConclusionsImmune-mediated disease of the inner ear is a chronic disease with relapses. Half of the patients with immunomediated hearing loss treated exclusively with corticosteroids relapse before 6 months of follow-up. In addition, if a patient has not relapsed, they are more likely to relapse as each year passes. Analysis of the of audiometric relapse- free survival will enable the effect of future treatments to be compared and their capacity to reduce the rhythm of relapses.



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Carcinoma análogo del secretor mamario de glándulas salivales: a propósito de un caso clínico

Publication date: Available online 13 October 2017
Source:Acta Otorrinolaringológica Española
Author(s): Carlota Rovira, Xavier León, Celina P. Vásquez, Montserrat López




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Vértigo y mareo en el hospital: frecuentación, flujo y características de los pacientes

Publication date: Available online 13 October 2017
Source:Acta Otorrinolaringológica Española
Author(s): Carmen Bécares Martínez, Marta M. Arroyo Domingo, Aurora López Llames, Jaime Marco Algarra, María M. Morales Suárez-Varela
Introducción y objetivosLos síntomas de vértigo y mareo son frecuentes en la población, se presentan como manifestación de un amplio abanico de enfermedades y habitualmente es difícil realizar un diagnóstico de certeza. El objetivo general de este estudio es obtener la información para evaluar estos síntomas en el entorno hospitalario. Los objetivos específicos son: estimar el peso global que representan estos síntomas en las derivaciones al hospital; conocer las características de los pacientes derivados y detallar el flujo de las consultas.MétodosEstudio descriptivo observacional. Se buscaron las propuestas de consulta realizadas en 2011 y 2012 al hospital por el síntoma de vértigo. Se analizaron características demográficas y clínicas de los pacientes, y administrativas de las derivaciones.ResultadosSe analizaron un total de 558 propuestas correspondientes a 494 pacientes. El vértigo supuso el 0,5% del total de las derivaciones realizadas desde Atención Primaria al hospital. El 63% de la muestra han sido mujeres, con una edad media de 58 años. El 88% de los pacientes fue valorado por Otorrinolaringología y el 24% por Neurología. Un 30,8% consultó en 3 o más ocasiones por el síntoma. El 16% fue valorado por enfermedad psiquiátrica en el hospital.ConclusionesEl vértigo como síntoma supone una carga significativa en el ámbito hospitalario. Los pacientes que lo presentan consultan en múltiples ocasiones y son valorados en distintas especialidades. En ciertos casos, el flujo de pacientes puede resultar excesivamente dinámico e ineficaz. En nuestro entorno, Otorrinolaringología es el principal receptor de pacientes con síntomas de vértigo y mareo.Introduction and objectivesVertigo and dizziness as symptoms are frequent in the population. They are present in a wide range of pathologies and it is usually difficult to make an accurate diagnosis. The general objective of this study is to obtain the information to evaluate vertigo and dizziness in the hospital setting. The specific objectives are: to estimate the burden of these symptoms at the hospital; to study patients' conditions and to detail the flow of these patients inside the hospital.MethodsObservational descriptive study. We made a search of the referral proposals made in 2011 and 2012 to the hospital because of vertigo symptoms. The patients' demographic and clinical characteristics, and the administrative details of the referrals were analysed.ResultsA total of 558 proposals were analysed corresponding to 494 patients. Vertigo accounted for 0.5% of all referrals made from Primary Care to the hospital. Sixty-three percent of the sample were women; the average age was 58 years. Eighty-eight percent of the patients were evaluated by Otorhinolaryngology, 24% by Neurology. Thirty point eight percent consulted on 3 or more occasions for the symptom. Sixteen percent were assessed for psychiatric conditions in the hospital.ConclusionsVertigo as a symptom is a significant burden in the hospital setting. The patients who suffer it consult on several occasions and are assessed by different specialties. This implies in some cases an excessive and ineffective flow of patients. In our setting, otorhinolaryngology is the main department to treat vertigo and dizziness patients.



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Significado pronóstico de la extensión extranodal en pacientes con carcinomas escamosos de cabeza y cuello cN0 con metástasis ganglionares ocultas

Publication date: Available online 13 October 2017
Source:Acta Otorrinolaringológica Española
Author(s): Joan Lop, Antoni Rigó, Alberto Codina, Julia de Juan, Miquel Quer, Xavier León
Introducción y objetivosLa presencia de extensión extranodal en adenopatías metastásicas de pacientes con carcinoma escamoso de cabeza y cuello es un reconocido factor de mal pronóstico. Sin embargo, pocos estudios analizan específicamente su significado en pacientes sin evidencia clínica de extensión ganglionar en el momento del diagnóstico inicial.Material y métodosEstudio retrospectivo de 348 pacientes con carcinoma escamoso de cabeza y cuello cN0 tratados con un vaciamiento cervical electivo. Se evaluó la presencia de metástasis ganglionares ocultas con extensión extranodal y se analizó su impacto sobre la supervivencia.ResultadosEl porcentaje de pacientes con metástasis ganglionares ocultas fue del 33%. De estos, un 23,5% presentaron al menos una adenopatía metastásica con extensión extranodal. Existieron diferencias significativas en la supervivencia específica en función del estatus ganglionar. La supervivencia a los 5 años para los pacientes sin afectación ganglionar patológica fue del 90%, para aquellos con metástasis ganglionares ocultas sin extensión extranodal, del 71,2%, y para los pacientes con metástasis ganglionares ocultas con extensión extranodal, del 25,9% (p=0,0001). En un estudio multivariante la presencia de metástasis ganglionares ocultas con extensión extranodal fue el factor relacionado de forma más importante con la supervivencia. La incorporación de la extensión extranodal como criterio de clasificación histopatológico en la octava edición del TNM mejoró la capacidad pronóstica en relación con las ediciones anteriores.ConclusionesLa presencia de adenopatías metastásicas con extensión extranodal es un factor de mal pronóstico en pacientes con carcinoma escamoso de cabeza y cuello sin evidencia clínica de afectación regional en el momento del diagnóstico de la enfermedad.Introduction and objectivesExtranodal extension in nodal metastases is an independent adverse prognostic factor in head and neck squamous cell carcinoma patients. However, few studies specifically address the subgroup of patients with no clinical evidence of nodal disease.Material and methodsWe retrospectively analysed data from 348 head and neck squamous cell carcinoma patients without any previous treatment and lacking clinical or radiological evidence of neck node metastases during the initial workup, treated with an elective neck dissection between 1992-2014. The incidence of occult metastatic neck nodes with extranodal extension and the impact of extranodal extension in survival were evaluated.ResultsThe proportion of patients with occult neck node metastases was 33%. Of these, 23.5% had at least one metastatic neck node with extranodal extension. There were significant differences in the disease-specific survival rate according to neck node status. Five-year disease-specific survival for patients without histopathological metastases was 90%, for patients with occult neck node metastases without extranodal extension it was 71.2%, and for patients with occult neck node metastases with extranodal extension it was 25.9% (P=.0001). The multivariate analysis revealed that the presence of occult node metastases with extranodal extension was the factor with strongest impact on survival. The inclusion of the extranodal extension as a criterion of histopathological evaluation in the 8th TNM classification edition improves the prognostic capacity compared to previous TNM editions.ConclusionsAppearance of metastatic neck nodes with extranodal extension is an adverse prognostic factor in head and neck squamous cell carcinoma patients without clinical evidence of regional disease during the initial workup of the tumour.



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The Effect of Telemedicine on Resource Utilization and Hospital Disposition in Critically Ill Pediatric Transport Patients

Telemedicine and e-Health , Vol. 0, No. 0.


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Initial Assessment, Treatment, and Follow-Up of Minor Pediatric Burn Wounds in Four Patients Remotely: A Preliminary Communication

Telemedicine and e-Health , Vol. 0, No. 0.


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Acceptance of Telemonitoring Among Patients with Obstructive Sleep Apnea Syndrome: How is the Perceived Interest by and for Patients?

Telemedicine and e-Health , Vol. 0, No. 0.


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Accuracy and Reliability of a Handheld, Nonmydriatic Fundus Camera for the Remote Detection of Optic Disc Edema

Telemedicine and e-Health , Vol. 0, No. 0.


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Análisis de supervivencia libre de recaída audiométrica en pacientes con hipoacusia inmunomediada tratados exclusivamente con corticoides

Publication date: Available online 13 October 2017
Source:Acta Otorrinolaringológica Española
Author(s): Nieves Mata-Castro, Raimon García-Chilleron, Javier Gavilanes-Plasencia, Rafael Ramírez-Camacho, Alfredo García-Fernández, José Ramón García-Berrocal
ObjetivoDescribir los resultados en términos de supervivencia libre de recaída audiométrica y el ritmo de recaída en pacientes con hipoacusia inmunomediada tratados exclusivamente con corticoides.MétodoEstudio retrospectivo de pacientes, con recaídas audiométricas, en seguimiento desde 1995 hasta 2014, en 2 centros de la Comunidad de Madrid.ResultadosSe evaluaron 31 pacientes con una media de edad de 48,52 años (14,67 DE) de los cuales el 61,3% fueron mujeres. La mayoría de las hipoacusias fueron fluctuantes (48,4%). Solo el 16,1% de los pacientes presentaban enfermedad autoinmune sistémica. Existe una correlación positiva moderada entre ser mujer y presentar afectación sistémica (coeficiente de correlación de Spearman=0,356). La tasa relativa de incidencia de recaída en el primer año en nuestra serie fue de 2,01 recaídas/año con un IC95% (1,32-2,92). El tiempo de supervivencia medio del evento (recaída audiométrica) fue de 5,25 meses (DE 0,756). Con el análisis multivariante, la única variable que consiguió significación estadística fue la edad, con una hazard ratio de 1,032 (IC95%; 1,001-1,063, p=0,043)ConclusionesLa enfermedad inmunomediada del oído interno es una enfermedad crónica con recaídas. La mitad de los pacientes tratados exclusivamente con corticoides recaen antes de los 6 meses de seguimiento. Además, si un paciente no ha presentado recaída, tiene más riesgo de recaer cada año que pasa. El análisis de la supervivencia libre de recaída audiométrica permitirá comparar el efecto de tratamientos futuros y su capacidad para reducir el ritmo de recaídas.ObjectiveTo describe the results in terms of audiometric relapse-free survival and relapse rate in immunomediated hearing loss patients treated exclusively with corticosteroids.MethodRetrospective study of patients with audiometric relapses, monitored from 1995 to 2014, in two centres of the Community of Madrid.ResultsWe evaluated 31 patients with a mean age of 48.52 years (14.67 SD), of which 61.3% were women. Most hearing loss was fluctuating (48.4%). Only 16.1% of patients had systemic autoimmune disease. There is a moderate positive correlation between the sex variable and the systemic involvement variable (Spearman's correlation coefficient=0.356): specifically, between being female and systemic disease. The relative incidence rate of relapse in the first year was 2.01 relapses/year with a 95% CI (1.32 to 2.92). The mean survival time of the event (audiometric relapse) was 5.25 months (SD 0.756). With multivariate analysis, the only variable that achieved statistical significance was age, with a hazard ratio of 1.032 (95% CI; 1.001-1.063, P=.043).ConclusionsImmune-mediated disease of the inner ear is a chronic disease with relapses. Half of the patients with immunomediated hearing loss treated exclusively with corticosteroids relapse before 6 months of follow-up. In addition, if a patient has not relapsed, they are more likely to relapse as each year passes. Analysis of the of audiometric relapse- free survival will enable the effect of future treatments to be compared and their capacity to reduce the rhythm of relapses.



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Carcinoma análogo del secretor mamario de glándulas salivales: a propósito de un caso clínico

Publication date: Available online 13 October 2017
Source:Acta Otorrinolaringológica Española
Author(s): Carlota Rovira, Xavier León, Celina P. Vásquez, Montserrat López




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Vértigo y mareo en el hospital: frecuentación, flujo y características de los pacientes

Publication date: Available online 13 October 2017
Source:Acta Otorrinolaringológica Española
Author(s): Carmen Bécares Martínez, Marta M. Arroyo Domingo, Aurora López Llames, Jaime Marco Algarra, María M. Morales Suárez-Varela
Introducción y objetivosLos síntomas de vértigo y mareo son frecuentes en la población, se presentan como manifestación de un amplio abanico de enfermedades y habitualmente es difícil realizar un diagnóstico de certeza. El objetivo general de este estudio es obtener la información para evaluar estos síntomas en el entorno hospitalario. Los objetivos específicos son: estimar el peso global que representan estos síntomas en las derivaciones al hospital; conocer las características de los pacientes derivados y detallar el flujo de las consultas.MétodosEstudio descriptivo observacional. Se buscaron las propuestas de consulta realizadas en 2011 y 2012 al hospital por el síntoma de vértigo. Se analizaron características demográficas y clínicas de los pacientes, y administrativas de las derivaciones.ResultadosSe analizaron un total de 558 propuestas correspondientes a 494 pacientes. El vértigo supuso el 0,5% del total de las derivaciones realizadas desde Atención Primaria al hospital. El 63% de la muestra han sido mujeres, con una edad media de 58 años. El 88% de los pacientes fue valorado por Otorrinolaringología y el 24% por Neurología. Un 30,8% consultó en 3 o más ocasiones por el síntoma. El 16% fue valorado por enfermedad psiquiátrica en el hospital.ConclusionesEl vértigo como síntoma supone una carga significativa en el ámbito hospitalario. Los pacientes que lo presentan consultan en múltiples ocasiones y son valorados en distintas especialidades. En ciertos casos, el flujo de pacientes puede resultar excesivamente dinámico e ineficaz. En nuestro entorno, Otorrinolaringología es el principal receptor de pacientes con síntomas de vértigo y mareo.Introduction and objectivesVertigo and dizziness as symptoms are frequent in the population. They are present in a wide range of pathologies and it is usually difficult to make an accurate diagnosis. The general objective of this study is to obtain the information to evaluate vertigo and dizziness in the hospital setting. The specific objectives are: to estimate the burden of these symptoms at the hospital; to study patients' conditions and to detail the flow of these patients inside the hospital.MethodsObservational descriptive study. We made a search of the referral proposals made in 2011 and 2012 to the hospital because of vertigo symptoms. The patients' demographic and clinical characteristics, and the administrative details of the referrals were analysed.ResultsA total of 558 proposals were analysed corresponding to 494 patients. Vertigo accounted for 0.5% of all referrals made from Primary Care to the hospital. Sixty-three percent of the sample were women; the average age was 58 years. Eighty-eight percent of the patients were evaluated by Otorhinolaryngology, 24% by Neurology. Thirty point eight percent consulted on 3 or more occasions for the symptom. Sixteen percent were assessed for psychiatric conditions in the hospital.ConclusionsVertigo as a symptom is a significant burden in the hospital setting. The patients who suffer it consult on several occasions and are assessed by different specialties. This implies in some cases an excessive and ineffective flow of patients. In our setting, otorhinolaryngology is the main department to treat vertigo and dizziness patients.



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Significado pronóstico de la extensión extranodal en pacientes con carcinomas escamosos de cabeza y cuello cN0 con metástasis ganglionares ocultas

Publication date: Available online 13 October 2017
Source:Acta Otorrinolaringológica Española
Author(s): Joan Lop, Antoni Rigó, Alberto Codina, Julia de Juan, Miquel Quer, Xavier León
Introducción y objetivosLa presencia de extensión extranodal en adenopatías metastásicas de pacientes con carcinoma escamoso de cabeza y cuello es un reconocido factor de mal pronóstico. Sin embargo, pocos estudios analizan específicamente su significado en pacientes sin evidencia clínica de extensión ganglionar en el momento del diagnóstico inicial.Material y métodosEstudio retrospectivo de 348 pacientes con carcinoma escamoso de cabeza y cuello cN0 tratados con un vaciamiento cervical electivo. Se evaluó la presencia de metástasis ganglionares ocultas con extensión extranodal y se analizó su impacto sobre la supervivencia.ResultadosEl porcentaje de pacientes con metástasis ganglionares ocultas fue del 33%. De estos, un 23,5% presentaron al menos una adenopatía metastásica con extensión extranodal. Existieron diferencias significativas en la supervivencia específica en función del estatus ganglionar. La supervivencia a los 5 años para los pacientes sin afectación ganglionar patológica fue del 90%, para aquellos con metástasis ganglionares ocultas sin extensión extranodal, del 71,2%, y para los pacientes con metástasis ganglionares ocultas con extensión extranodal, del 25,9% (p=0,0001). En un estudio multivariante la presencia de metástasis ganglionares ocultas con extensión extranodal fue el factor relacionado de forma más importante con la supervivencia. La incorporación de la extensión extranodal como criterio de clasificación histopatológico en la octava edición del TNM mejoró la capacidad pronóstica en relación con las ediciones anteriores.ConclusionesLa presencia de adenopatías metastásicas con extensión extranodal es un factor de mal pronóstico en pacientes con carcinoma escamoso de cabeza y cuello sin evidencia clínica de afectación regional en el momento del diagnóstico de la enfermedad.Introduction and objectivesExtranodal extension in nodal metastases is an independent adverse prognostic factor in head and neck squamous cell carcinoma patients. However, few studies specifically address the subgroup of patients with no clinical evidence of nodal disease.Material and methodsWe retrospectively analysed data from 348 head and neck squamous cell carcinoma patients without any previous treatment and lacking clinical or radiological evidence of neck node metastases during the initial workup, treated with an elective neck dissection between 1992-2014. The incidence of occult metastatic neck nodes with extranodal extension and the impact of extranodal extension in survival were evaluated.ResultsThe proportion of patients with occult neck node metastases was 33%. Of these, 23.5% had at least one metastatic neck node with extranodal extension. There were significant differences in the disease-specific survival rate according to neck node status. Five-year disease-specific survival for patients without histopathological metastases was 90%, for patients with occult neck node metastases without extranodal extension it was 71.2%, and for patients with occult neck node metastases with extranodal extension it was 25.9% (P=.0001). The multivariate analysis revealed that the presence of occult node metastases with extranodal extension was the factor with strongest impact on survival. The inclusion of the extranodal extension as a criterion of histopathological evaluation in the 8th TNM classification edition improves the prognostic capacity compared to previous TNM editions.ConclusionsAppearance of metastatic neck nodes with extranodal extension is an adverse prognostic factor in head and neck squamous cell carcinoma patients without clinical evidence of regional disease during the initial workup of the tumour.



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Measuring ICT orientation: Scale development & validation

Abstract

This paper attempts to measure ICT orientation of higher education teachers in Indian context. The study has identified 4 factors of ICT orientation and examined their impact on Job performance. To generate the items, their purification and validation this study has adopted well accepted and renowned scale development procedures by Churchill (Journal of Marketing Research, 16(1), 64–73, 1979) and Hinkin (Organizational Research Methods, 1(1), 104–121, 1995). A one way ANOVA test is applied to test the relationship between 4 factors of ICT orientation and the demographics of respondents. The findings of this study present a 15 item 4 factor scale measuring ICT orientation of teachers among which "advantage" emerged out to be a significant factor. The study further highlighted that ICT orientation has a direct and positive relationship with job performance. This study is the foremost study, which has developed a valid and reliable scale for measuring the ICT orientation of teachers in Indian context.

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Integrated genomic characterization of cancer genes in glioma

Cancers are caused by the acquisition of somatic mutations. Numerous efforts have been made to characterize the key driver genes and pathways in glioma, however, the etiology of glioma is still not completely ...

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Direct binding to integrins and loss of disulfide linkage in IL-1{beta} are involved in the agonistic action of IL-1{beta} [Immunology]

There is a strong link between integrins and IL-1β, but the specifics of the role of integrins in IL-1β signaling are unclear. We describe that IL-1β specifically bound to integrins αvβ3 and α5β1. The E128K mutation in the IL1R-binding site enhanced integrin binding. We studied if direct integrin binding is involved in IL-1β signaling. We compared sequences of IL-1β and IL-1 receptor antagonist (IL1RN), which is an IL-1β homologue but has no agonistic activity. Several surface-exposed Lys residues are present in IL-1β, but not in IL1RN. A disulfide-linkage is present in IL1RN, but is not in IL-1β due to natural C117F mutation. Substitution of the Lys residues to Glu markedly reduced integrin binding of E128K IL-1β, suggesting that the Lys residues mediate integrin binding. The Lys mutations reduced, but not completely abrogated, agonistic action of IL-1β. We studied if the disulfide linkage plays a role in agonistic action of IL-1β. Re-introduction of the disulfide linkage by the F117C mutation did not affect agonistic activity of WT IL-1β, but effectively reduced the remaining agonistic activity of the Lys mutants. Also, deletion of the disulfide linkage in IL1RN by the C116F mutation did not make it agonistic. We propose that the direct binding to IL-1β to integrins is primarily important for agonistic IL-1β signaling, and that the disulfide linkage indirectly affect signaling by blocking conformational changes induced by weak integrin binding to the Lys mutants. The integrin-IL-1β interaction is a potential target for drug discovery.

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Activating mutations in quorum-sensing regulator Rgg2 and its conformational flexibility in the absence of an intermolecular disulfide bond [Microbiology]

Rap/Rgg/NprR/PlcR/PrgX (RRNPP) quorum-sensing systems use extracellular peptide pheromones that are detected by cytoplasmic receptors to regulate gene expression in firmicute bacteria. Rgg-type receptors are allosterically regulated through direct pheromone binding to control transcriptional activity; however, the receptor activation mechanism remains poorly understood. Previous work has identified a disulfide bond between Cys-45 residues within the homodimer interface of Rgg2 from Streptococcus dysgalactiae (Rgg2Sd). Here, we compared two Rgg2Sd(C45S) X-ray crystal structures with that of wild-type Rgg2Sd and found that in the absence of the intermolecular disulfide, the Rgg2Sd dimer interface is destabilized and Rgg2Sd can adopt multiple conformations. One conformation closely resembled the disulfide-locked Rgg2Sd secondary and tertiary structures, but another displayed more extensive rigid-body shifts as well as dramatic secondary structure changes. In parallel experiments, a genetic screen was used to identify mutations in Rgg2 of Streptococcus pyogenes (Rgg2Sp) that conferred pheromone-independent transcriptional activation of an Rgg2-stimulated promoter. Eight mutations yielding constitutive Rgg2 activity, designated Rgg2Sp*, were identified and five of them clustered in or near an Rgg2 region that underwent conformational changes in one of the Rgg2Sd(C45S) crystal structures. The Rgg2Sp* mutations increased Rgg2Sp sensitivity to pheromone and pheromone variants while displaying decreased sensitivity to the Rgg2 antagonist cyclosporine A. We propose that Rgg2Sp* mutations invoke shifts in free-energy bias to favor the active state of the protein. Finally, we present evidence for an electrostatic interaction between an N-terminal Asp of the pheromone and Arg-153 within the proposed pheromone-binding pocket of Rgg2Sp.

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A retractable lid in lecithin:cholesterol acyltransferase provides a structural mechanism for activation by apolipoprotein A-I [Lipids]

Lecithin:cholesterol acyltransferase (LCAT) plays a key role in reverse cholesterol transport by transferring an acyl group from phosphatidylcholine to cholesterol, promoting the maturation of high density lipoproteins (HDL) from discoidal to spherical particles. LCAT is activated through an unknown mechanism by apolipoprotein A-I (ApoA-I) and other mimetic peptides that form a belt around HDL. Here we report the crystal structure of LCAT with an extended lid that blocks access to the active site, consistent with an inactive conformation. Residues Thr123 and Phe382 in the catalytic domain form a latch-like interaction with hydrophobic residues in the lid. Because these residues are mutated in genetic disease, lid displacement was hypothesized to be an important feature of ApoA-I activation. Functional studies of site-directed mutants revealed that loss of latch interactions or the entire lid enhanced activity against soluble ester substrates, and hydrogen deuterium exchange mass spectrometry (HDX MS) revealed that the LCAT lid is extremely dynamic in solution. Upon addition of a covalent inhibitor that mimics one of the reaction intermediates, there is an overall decrease in HDX in the lid and adjacent regions of the protein, consistent with ordering. These data suggest a model wherein the active site of LCAT is shielded from soluble substrates by a dynamic lid until it interacts with HDL to allow transesterification to proceed.

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Quantitative time-course metabolomics in human red blood cells reveal the temperature dependence of human metabolic networks [Computational Biology]

The temperature dependence of biological processes has been studied at the levels of individual biochemical reactions and organism physiology (e.g., basal metabolic rates) but has not been examined at the metabolic network level. Here, we used a systems biology approach to characterize the temperature dependency of the human red blood cell (RBC) metabolic network between 4C and 37C through absolutely quantified exo- and endo-metabolomics data. We used an Arrhenius-type model (Q10) to describe how the rate of a biochemical process changes with every 10C change in temperature. Multivariate statistical analysis of the metabolomics data revealed that the same metabolic network-level trends previously reported for RBCs at 4C were conserved but accelerated with increasing temperature. We calculated a median Q10 coefficient of 2.89+\-1.03 for 48 individual metabolite concentrations, within the expected range of 2-3 for biological processes. We then integrated these metabolomics measurements into a cell-scale metabolic model to study pathway usage, calculating a median Q10 coefficient of 2.73+\-0.75 for 35 reaction fluxes. The relative fluxes through glycolysis and nucleotide metabolism pathways were consistent across the studied temperature range despite the non-uniform distributions of Q10 coefficients of individual metabolites and reaction fluxes. Together, these results indicate that the rate of change of network-level responses to temperature differences in RBC metabolism is consistent between 4C and 37C. More broadly, we provide a baseline characterization of a biochemical network given no transcriptional or translational regulation that can be used to explore the temperature dependence of metabolism.

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Structural insights into marine carbohydrate degradation by family GH16 kappa-carrageenases [Protein Structure and Folding]

Carrageenans are sulfated α-1,3-β-1,4-galactans found in the cell wall of some red algae that are practically valuable for their gelation and biomimetic properties but also serve as a potential carbon source for marine bacteria. Carbohydrate degradation has been studied extensively for terrestrial plant/bacterial systems, but sulfation is not present in these cases, meaning the marine enzymes used to degrade carrageenans must possess unique features to recognize these modifications. To gain insights into these features, we have focused on κ-carrageenases from two distant bacterial phyla, which belong to glycoside hydrolase family 16 (GH16) and cleave the β-1,4 linkage of κ-carrageenan. We have solved the crystal structure of the catalytic module of ZgCgkA from Zobellia galactanivorans at 1.66 Å resolution, and compared it with the only other structure available, that of PcCgkA from Pseudoalteromonas carrageenovora 9T (ATCC 43555T). We also describe the first substrate complex in the inactivated mutant form of PcCgkA at 1.7 Å resolution. The structural and biochemical comparison of these enzymes suggests key determinants that underlie the functional properties of this subfamily. In particular, we identify several arginine residues that interact with the polyanionic substrate, and confirmed the functional relevance of these amino acids using a targeted mutagenesis strategy. These results give new insight in the diversity of the κ-carrageenase subfamily. The phylogenetic analyses show the presence of several distinct clades of enzymes that relate to differences in modes of action or subtle differences within the same substrate specificity, matching the hybrid character of the κ-carrageenan polymer.

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Molecular insights into the m-AAA protease mediated dislocation of transmembrane helices in the mitochondrial inner membrane [Protein Synthesis and Degradation]

In the mitochondrial inner membrane, many protein complexes involved in respiration, ATP synthesis, and protein import reside, thus proper regulation of these proteins is essential for cell viability. The mAAA protease, a conserved heterohexameric AAA (ATPases associated with diverse cellular activities) protease composed of the Yta10 and Yta12 proteins, regulates mitochondrial proteostasis by mediating protein maturation and degradation. It also recognizes and mediates dislocation of membrane embedded substrates, including foreign transmembrane (TM) segments, yet the molecular mechanism involved in these processes remains elusive. This study investigated the role of the TM domains in the mAAA protease by systematic replacement of one TM domain at a time in yeast. Our data indicated that replacement of the Yta10 TM2 domain abolishes membrane dislocation for only a subset of substrates, whereas replacement of the Yta12 TM2 domain impairs membrane dislocation for all tested substrates, suggesting different roles of the TM domains in each mAAA protease subunit. Furthermore, mAAA protease mediated membrane dislocation was impaired in the presence of a large downstream hydrophilic moiety in a membrane substrate. This finding suggested that the mAAA protease cannot dislocate large hydrophilic domains across the membrane, indicating that the membrane dislocation probably occurs in a lipid environment. In summary, this study highlights previously underappreciated biological roles of TM domains of the mAAA proteases in mediating recognition and dislocation of membrane embedded substrates.

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Robust lysosomal calcium signaling through channel TRPML1 is impaired by lysosomal lipid accumulation [Research]

The transient receptor potential cation channel mucolipin 1 (TRPML1) channel is a conduit for lysosomal calcium efflux, and channel activity may be affected by lysosomal contents. The lysosomes of retinal pigmented epithelial (RPE) cells are particularly susceptible to build-up of lysosomal waste products because they must degrade the outer segments phagocytosed daily from adjacent photoreceptors; incomplete degradation leads to accumulation of lipid waste in lysosomes. This study asks whether stimulation of TRPML1 can release lysosomal calcium in RPE cells and whether such release is affected by lysosomal accumulations. The TRPML agonist ML-SA1 raised cytoplasmic calcium levels in mouse RPE cells, hesRPE cells, and ARPE-19 cells; this increase was rapid, robust, reversible, and reproducible. The increase was not altered by extracellular calcium removal or by thapsigargin but was eliminated by lysosomal rupture with glycyl-l-phenylalanine-β-naphthylamide. Treatment with desipramine to inhibit acid sphingomyelinase or YM201636 to inhibit PIKfyve also reduced the cytoplasmic calcium increase triggered by ML-SA1, whereas RPE cells from TRPML1^–/– mice showed no response to ML-SA1. Cotreatment with chloroquine and U18666A induced formation of neutral, autofluorescent lipid in RPE lysosomes and decreased lysosomal Ca²⁺ release. Lysosomal Ca²⁺ release was also impaired in RPE cells from the ATP-binding cassette, subfamily A, member 4^–/– mouse model of Stargardt's retinal dystrophy. Neither TRPML1 mRNA nor total lysosomal calcium levels were altered in these models, suggesting a more direct effect on the channel. In summary, stimulation of TRPML1 elevates cytoplasmic calcium levels in RPE cells, but this response is reduced by lysosomal accumulation.—Gómez, N. M., Lu, W. Lim, J. C., Kiselyov, K., Campagno, K. E., Grishchuk, Y., Slaugenhaupt, S. A., Pfeffer, B., Fliesler, S. J., Mitchell, C. H. Robust lysosomal calcium signaling through channel TRPML1 is impaired by lysosomal lipid accumulation.

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Analysis of early death in Japanese patients with advanced non-small cell lung cancer treated with nivolumab

In the first 3 months of nivolumab treatment, 38 patients (18.6%) of 201 non-small cell lung cancer patients died (early death). A PS score ≥ 2, pretreatment of CAR > 0.3, and poor response to prior treatment, were risk factors of early death. The major reasons for early death were disease progression and/or immune-related adverse event.

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Costunolide specifically binds and inhibits thioredoxin reductase 1 to induce apoptosis in colon cancer

Colon cancer is one of the leading causes of cancer-related deaths. A natural sesquiterpene lactone, costunolide (CTD), showed inhibition of cancer development. However, the underlying mechanisms are not known. Here, we have examined the therapeutic activity and novel mechanisms of the anti-cancer activities of CTD in colon cancer cells. Using SPR analysis and enzyme activity assay on recombinant TrxR1 protein, our results show that CTD directly binds and inhibits the activity of TrxR1, which caused enhanced generation of ROS and led to ROS-dependent endoplasmic reticulum stress and cell apoptosis in colon cancer cells.

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Advances in mechanisms of allergic disease in 2016

This review highlights advances in mechanisms of allergic disease, particularly type 2 innate lymphoid cells; TH2 lymphocytes; eicosanoid regulation of inflammation; extracellular vesicles in allergic responses; IL-33; microbiome properties, especially as they relate to mucosal barrier function; and a series of findings concerning the allergic inflammatory cells eosinophils, basophils, and mast cells. During the last year, mechanistic advances occurred in understanding type 2 innate lymphoid cells, particularly related to their response to ozone, involvement with experimental food allergy responses, and regulation by IL-33.

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Fibrinogen-cleavage products and TLR4 promote the generation of programmed cell death 1 ligand 2(PD-L2)+ dendritic cells in allergic asthma

Inhaled protease allergens preferentially trigger Th2-mediated inflammation in allergic asthma. The role of dendritic cells (DCs) on the induction of Th2 cell responses in allergic asthma has been well documented; however, the mechanism by which protease allergens induce Th2-favorable DCs in the airway remains unclear.

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Costunolide specifically binds and inhibits thioredoxin reductase 1 to induce apoptosis in colon cancer

Colon cancer is one of the leading causes of cancer-related deaths. A natural sesquiterpene lactone, costunolide (CTD), showed inhibition of cancer development. However, the underlying mechanisms are not known. Here, we have examined the therapeutic activity and novel mechanisms of the anti-cancer activities of CTD in colon cancer cells. Using SPR analysis and enzyme activity assay on recombinant TrxR1 protein, our results show that CTD directly binds and inhibits the activity of TrxR1, which caused enhanced generation of ROS and led to ROS-dependent endoplasmic reticulum stress and cell apoptosis in colon cancer cells.

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Black, White, and Gray: Macrophages in Skin Repair and Disease

Abstract

Purpose of Review

Macrophages alter their responses during the temporal stages of wound healing. During the inflammatory phase, they perform phagocytosis. During neovascularization, they fuse sprouting endothelial cells. In the proliferation phase, they deposit extracellular matrix, and during wound resolution, macrophages phagocytize excessive cellular components. This review addresses how changing macrophage phenotypes affects skin repair and disease.

Recent Findings

Macrophages can determine the outcome of repair and can shift the normal wound healing response into fibrosis or chronic wounds. Emerging single-cell technologies for the first time provide us with tools to uncover macrophage origin, heterogeneity, and function.

Summary

Macrophages may exist as one population where all cells alter their phenotype in response to signals from the microenvironment. Alternatively, macrophages may exist as distinct subsets that can control wound outcomes. A clarified understanding will strengthen our knowledge of skin biology and aid in the development of wound healing therapies.

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Adams-Oliver Syndrome With Moyamoya Disease for Cerebral Revascularisation Surgery.

No abstract available

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BMP-2 plasmid DNA-loaded chitosan films─a new strategy for bone engineering

Bone defects are common in every area of medicine and remain a clinical challenge. Tissue engineering has led to promising new strategies in accelerating bone repair. Bone morphogenetic proteins (BMPs) play crucial roles in bone regeneration, but are required in supra-physiological doses, which are expensive and produce severe side effects.

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Preterm Delivery Trends by Maternal Race/Ethnicity in the United States, 2006-2012

To estimate changes in preterm delivery (PTD) in the United States (US) from 2006 to 2012 by clinical circumstance, timing of delivery, and race/ethnicity.

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Examining Racial Disparities in Colon Cancer Clinical Delay in the Colon Cancer Patterns of Care in Chicago Study

We explored a potential racial disparity in clinical delay among non-Hispanic (nH) Black and White colon cancer patients and examined factors that might account for the observed disparity.

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Preferred Reporting Items for Overviews of systematic reviews including harms checklist: A pilot tool to be used for balanced reporting of benefits and harms

An Overview of Systematic Reviews (OoSRs) is a study designed to synthesize multiple evidence from existing systematic reviews on a specific domain. The aim of this paper was to offer a pilot version checklist with Preferred Reporting Items for OoSRs (PRIO-harms) in order to promote a more balanced reporting of benefits and harms in OoSRs of healthcare interventions.

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Le Morte d’Arthur, A Commentary on Hugo L. Obwegeser

Two years ago this autumn, Hugo Obwegeser embarked on his final adventure on the western shores of the Atlantic when he returned to Washington, D.C. to celebrate his first visit to that city of some fifty years earlier. The course of days has reduced to a skeleton crew those in our ranks who lived those times, but with those lectures Obwegeser initiated an indebtedness in us for all generations that is so enormous as to be beyond reckoning.

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Analysis of facial symmetry after zygomatic bone fracture management

The location of the zygomatic bone plays a significant role in facial symmetry and aesthetics. The aim of this study was to determine and compare the frequency of facial asymmetry in a sample of patients who had undergone treatment of unilateral ZMC fractures (study) and a sample of normal subjects (control).

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Functional Anatomic Computer Engineered Surgery (FACES) Protocol for the Management of Self-Inflicted Gunshot Wounds to the Maxillofacial Skeleton

Self-inflicted gunshot wounds (SIGSW's) to the craniofacial region result in devastating functional disabilities and esthetic deformities, which are further magnified by the associated psychological trauma. [1, 2] Because a substantial number of these patients return to work, return to their pre-injury life style, and have a low rate of suicide recidivism, adequate reconstruction is essential to their comprehensive rehabilitation. Studies suggest that early diagnosis and treatment should be considered to further reduce the risk of suicide attempts.

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Immunohistochemical analysis on cortex-to-cortex healing after mandibular vertical ramus osteotomy: A preliminary study

This study aimed to analyze the expression of specific cytokines among TGF-β superfamily over postoperative periods after mandibular VRO.

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Proteomic analyses of signalling complexes associated with receptor tyrosine kinase identify novel members of fibroblast growth factor receptor 3 interactome

Publication date: Available online 13 October 2017
Source:Cellular Signalling
Author(s): Lukas Balek, Pavel Nemec, Peter Konik, Michaela Kunova Bosakova, Miroslav Varecha, Iva Gudernova, Jirina Medalova, Deborah Krakow, Pavel Krejci
Receptor tyrosine kinases (RTKs) form multiprotein complexes that initiate and propagate intracellular signals and determine the RTK-specific signalling patterns. Unravelling the full complexity of protein interactions within the RTK-associated complexes is essential for understanding of RTK functions, yet it remains an understudied area of cell biology. We describe a comprehensive approach to characterize RTK interactome. A single tag immunoprecipitation and phosphotyrosine protein isolation followed by mass-spectrometry was used to identify proteins interacting with fibroblast growth factor receptor 3 (FGFR3). A total of 32 experiments were carried out in two different cell types and identified 66 proteins out of which only 20 (30.3%) proteins were already known FGFR interactors. Using co-immunoprecipitations, we validated FGFR3 interaction with adapter protein STAM1, transcriptional regulator SHOX2, translation elongation factor eEF1A1, serine/threonine kinases ICK, MAK and CCRK, and inositol phosphatase SHIP2. Further analyses of FGFR3-ICK interaction discovered an unexpected link between the FGF pathway and primary cilia, while elucidation of FGFR3-SHIP2 interaction unraveled a critical role of SHIP2 in regulation of canonical FGF-ERK MAP kinase signalling. We show that unappreciated signalling mediators exist for well-studied RTKs, such as FGFR3, and may be identified via proteomic approaches described here. These approaches are easily adaptable to other RTKs, enabling identification of novel signalling mediators for majority of the 54 known human RTKs.



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BMP-2 plasmid DNA-loaded chitosan films─a new strategy for bone engineering

Bone defects are common in every area of medicine and remain a clinical challenge. Tissue engineering has led to promising new strategies in accelerating bone repair. Bone morphogenetic proteins (BMPs) play crucial roles in bone regeneration, but are required in supra-physiological doses, which are expensive and produce severe side effects.

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Attention deficit hyperactivity disorder symptom severity and sleep problems in adult participants of the Netherlands Sleep Registry

We examined whether current overall attention deficit hyperactivity disorder (ADHD), inattention, or hyperactivity symptom severities are associated with the current presence and persistent history of sleep problems.

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Oliver Borst Dissertation

Christoph Borst, Markus Grebenstein, Oliver Eiberger, and Gerd Hirzinger, The serum- and glucocorticoid-inducible kinase 1 - CiteSeerX Oliver Borst ...

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Liquid Structure with Nano-Heterogeneity Promotes Cationic Transport in Concentrated Electrolytes

ACS Nano

DOI: 10.1021/acsnano.7b05664

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Effect of the ultraviolet light treatment and storage methods on the biological activity of a titanium implant surface

Publication date: Available online 13 October 2017
Source:Dental Materials
Author(s): Sung-Hwan Choi, Won-Seok Jeong, Jung-Yul Cha, Jae-Hoon Lee, Kee-Joon Lee, Hyung-Seog Yu, Eun-Ha Choi, Kwang-Mahn Kim, Chung-Ju Hwang
ObjectiveWe evaluated whether the biological activity of the surface of titanium, when stored in an aqueous solution, in low vacuum, and under ambient conditions after ultraviolet light (UV) treatment is comparable to that of the surface immediately after UV treatment for 15min and that after dielectric barrier discharge (DBD) plasma treatment for 15min.MethodsGrade IV titanium discs with machined surfaces were irradiated with UV and their surface properties were evaluated immediately and after storage for 28days in distilled H2O (dH2O), a vacuum desiccator (31.325kPa), and a sealed container under air. Their surface characteristics were evaluated by atomic force microscopy, X-ray diffraction, contact angle analysis, and X-ray photoelectron spectroscopy. Biological activities were determined by analyzing the albumin adsorption, MC3T3-E1 cell adhesion, and cytoskeleton development.ResultsHydrophilicity of titanium surfaces stored in dH2O was comparable to that immediately after UV treatment and higher than that immediately after DBD plasma treatment (P<0.001). Storage in dH2O and in low vacuum immediately after UV treatment prevented hydrocarbon contamination and maintained elevated amounts of titanium and oxygen. After 28 days, protein adsorption, cellular adhesion, and cytoskeletal development of MC3T3-E1 cells on the titanium surfaces stored in dH2O were significantly enhanced compared to those stored in low vacuum and under ambient conditions while being comparable to those immediately after UV and DBD plasma treatments.SignificanceUV treatment of the titanium implants followed by wet storage is useful for maintaining enhanced biological activity and overcoming biological aging during shelf storage.



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Sanguinarine inhibits pancreatic cancer stem cell characteristics by inducing oxidative stress and suppressing sonic hedgehog-Gli-Nanog pathway

Abstract

Sonic hedgehog pathway is highly activated in pancreatic cancer stem cells (CSC) which play crucial roles in cancer initiation, progression and metastasis. However, the molecular mechanisms by which sanguinarine regulates pancreatic CSC characteristics is not well understood. The objectives of this study were to examine the molecular mechanisms by which sanguinarine regulates pancreatic CSC characteristics. Sanguinarine inhibited cell proliferation and colony formation and induced apoptosis through oxidative damage. Sanguinarine inhibited self-renewal capacity of pancreatic CSCs isolated from human and Kras^G12D mice. Furthermore, sanguinarine suppressed epithelial-mesenchymal transition (EMT) by up-regulating E-cadherin and inhibiting N-cadherin. Significant decrease in expression level of Snail, Slug and Zeb1 corroborated the suppression of EMT in sanguinarine treated pancreatic CSCS. The ability of sanguinarine to inhibit pluripotency maintaining factors and CSC markers suggest that sanguinarine can be an effective agent for inhibiting pancreatic cancer growth and development by targeting CSCs. Furthermore, sanguinarine inhibited Shh-Gli pathway leading to modulation of Gli target genes in pancreatic CSCs. Chromatin immunoprecipitation assay demonstrated that Nanog directly binds to promoters of Cdk2, Cdk6, FGF4, c-Myc and Oct4, and sanguinarine inhibits the binding of Nanog with these genes, suggesting the direct involvement of Nanog in cell cycle, pluripotency and self-renewal. To further investigate the role of Shh-Gli-Nanog pathway, we regulated Shh signaling either by Shh protein or Nanog overexpression. Enforced activation of Shh or overexpression of Nanog counteracted the inhibitory effects of sanguinarine on pancreatic CSC proliferation, suggesting the actions of sanguinarine are mediated, at least in part, through Shh-Gli-Nanog pathway. Our studies suggest that sanguinarine can be used for the treatment and/or prevention of pancreatic cancer by targeting CSCs.

from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2gibZem
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