Head and Neck Diseases by Alexandros G.Sfakianakis: 01/16/17

Δευτέρα 16 Ιανουαρίου 2017

Current and future management of the young child with early onset wheezing.

Purpose of review: In this review, we discuss current thinking in relation to available guidelines for the care of preschool-aged children with recurrent wheezing, while highlighting the gaps in our knowledge and discussing changes that could occur over the next 5 years. Recent findings: The Asthma Predictive Index as well as allergen-specific IgE, peripheral eosinophil count and exhaled nitric oxide are perhaps underutilized sources of information that can assist in predicting progression to asthma and response to therapies. Inhaled corticosteroids and leukotriene receptor antagonists decrease impairment and exacerbation frequency in wheezing children but are not disease modifying. Macrolides may be useful during acute wheezing episodes for preventing progression to more severe symptoms. Monoclonal antibodies targeting IgE and TH2 cytokines have been successful in trials of adults and older children with asthma, but trials in younger children are needed. Summary: Establishing the phenotype and endotype of young wheezing children can be useful for prognostication of future asthma risk as well as for selection of the most appropriate treatment. Primary asthma prevention strategies are needed during the critical developmental window in early life prior to the onset of irrecoverable loss of lung function. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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Adaptive cone-beam CT planning improves long-term biochemical disease-free survival for 125I prostate brachytherapy

Publication date: Available online 16 January 2017
Source:Brachytherapy
Author(s): M. Peters, D.A. Smit Duijzentkunst, H. Westendorp, S.M.G. van de Pol, R. Kattevilder, A. Schellekens, J.R.N. van der Voort van Zyp, M.A. Moerland, M. van Vulpen, C.J. Hoekstra
PurposeDetermining the independent effect of additional intraoperative adaptive C-arm cone-beam CT (CBCT) planning vs. transrectal ultrasound (TRUS)-guided interactive planning alone in ¹²⁵I brachytherapy for prostate cancer (PCa) on biochemical disease-free survival (BDFS).Methods and materialsT1/T2-stage PCa patients receiving TRUS-guided brachytherapy from 2000 to 2014 were analyzed. From October 2006, patients received additional intraoperative adaptive CBCT planning for dosimetric evaluation and subsequent remedial seed placement in underdosed areas. Patients were stratified according to the National Comprehensive Cancer Network (NCCN) risk classification. Kaplan–Meier analysis was used to estimate BDFS (primary outcome), overall survival, and PCa-specific survival (secondary outcomes). Cox regression was used to assess the relation between CBCT use and biochemical failure (BF) and overall mortality.ResultsIn all, 1623 patients were included. Median followup was 99 months (interquartile range 70–115) for TRUS patients (n = 613) and 51 months (interquartile range 29–70) for CBCT patients (n = 1010). BF occurred 203 times and 206 patients died, 26 from PCa. For TRUS and CBCT patients, 7-year BDFS was 87.2% vs. 93.5% (log rank: p = 0.04) for low, 75.9% vs. 88.5% (p < 0.001) for intermediate, and 57.1% vs. 85.0% for high-risk patients (p < 0.001). For TRUS and CBCT patients, 7-year PCa-specific survival was 96.0% vs. 100% (p < 0.0001). After Cox regression, CBCT patients had lower hazard of BF: hazard ratio (HR) 0.25 (95% confidence interval [CI]: 0.18–0.33; p < 0.0001). Corrected for confounders, CBCT remained a predictor of BF: HR 0.51 (95% CI: 0.31–0.86; p = 0.01) but not for overall mortality: HR 0.66 (95% CI: 0.40–1.07; p = 0.09).ConclusionsAdditional intraoperative adaptive CBCT planning in ¹²⁵I prostate brachytherapy leads to a significant increase in BDFS in all NCCN risk groups.

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Cosmetics, Vol. 4, Pages 6: Acknowledgement to Reviewers of Cosmetics in 2016

The editors of Cosmetics would like to express their sincere gratitude to the following reviewers for assessing manuscripts in 2016. [...]

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American Brachytherapy Society Task Group Report: Use of androgen deprivation therapy with prostate brachytherapy—A systematic literature review

Publication date: Available online 16 January 2017
Source:Brachytherapy
Author(s): M. Keyes, G. Merrick, S.J. Frank, P. Grimm, M.J. Zelefsky
PurposeProstate brachytherapy (PB) has well-documented excellent long-term outcomes in all risk groups. There are significant uncertainties regarding the role of androgen deprivation therapy (ADT) with brachytherapy. The purpose of this report was to review systemically the published literature and summarize present knowledge regarding the impact of ADT on biochemical progression-free survival (bPFS), cause-specific survival (CSS), and overall survival (OS).Methods and MaterialsA literature search was conducted in Medline and Embase covering the years 1996–2016. Selected were articles with >100 patients, minimum followup 3 years, defined risk stratification, and directly examining the role and impact of ADT on bPFS, CSS, and OS. The studies were grouped to reflect disease risk stratification. We also reviewed the impact of ADT on OS, cardiovascular morbidity, mortality, and on-going brachytherapy randomized controlled trials (RCTs).ResultsFifty-two selected studies (43,303 patients) were included in this review; 7 high-dose rate and 45 low-dose rate; 25 studies were multi-institutional and 27 single institution (retrospective review or prospective data collection) and 2 were RCTs. The studies were heterogeneous in patient population, risk categories, risk factors, followup time, and treatment administered, including ADT administration and duration (median, 3–12 months);71% of the studies reported a lack of benefit, whereas 28% showed improvement in bPFS with addition of ADT to PB. The lack of benefit was seen in low-risk and favorable intermediate-risk (IR) disease and most high–dose rate studies. A bPFS benefit of up to 15% was seen with ADT use in patients with suboptimal dosimetry, those with multiple adverse risk factors (unfavorable IR [uIR]), and most high-risk (HR) studies. Four studies reported very small benefit to CSS (2%). None of the studies showed OS advantage; however, three studies reported an absolute 5–20% OS detriment with ADT. Literature suggests that OS detriment is more likely in older patients or those with pre-existing cardiovascular disease. Four RCTs with an adequate number of patients and well-defined risk stratification are in progress. One RCT will answer the question regarding the role of ADT with PB in favorable IR patients and the other three RCTs will focus on optimal duration of ADT in the uIR and favorable HR population.ConclusionsPatients treated with brachytherapy have excellent long-term disease outcomes. Existing evidence shows no benefit of adding ADT to PB in low-risk and favorable IR patients. UIR and HR patients and those with suboptimal dosimetry may have up to 15% improvement in bPFS with addition of 3–12 months of ADT, with uncertain impact on CSS and a potential detriment on OS. To minimize morbidity, one should exercise caution in prescribing ADT together with PB, in particular to older men and those with existing cardiovascular disease. Due to the retrospective nature of this evidence, significant selection, and treatment bias, no definitive conclusions are possible. RCT is urgently needed to define the potential role and optimal duration of ADT in uIR and favorable HR disease.

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Application of autologous hematopoietic stem cell transplantation for pemphigus

Abstract

Background

Pemphigus is a rare and fatal autoimmune disease for which the treatment options are limited. This study aimed to evaluate the efficacy of autologous peripheral hematopoietic stem cell transplantation (APHSCT) for pemphigus.

Methods

We conducted APHSCT for 12 pemphigus patients (seven males and five females, mean age 23.8 years) with life-threatening complications or who responded poorly to conventional therapy. Peripheral blood stem cells were mobilized with cyclophosphamide, granulocyte colony-stimulating factor, and rituximab, and purified autologous CD34⁺ stem cells were infused. Overall survival rate, progression-free survival, and adverse events were recorded.

Results

With a mean follow-up period of 80.3 months, overall survival and complete clinical remission rates were 92% (11/12) and 75% (9/12), respectively. Adverse effects included pyrexia, allergy, infection, and elevation of enzymes. Only one patient died of severe sepsis and multiple organ failure 2 months after APHSCT.

Conclusion

Overall APHSCT is a promising therapeutic option for pemphigus.

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Syphilitic chancre and condylomata lata possibly coexisting with neurosyphilis

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Tumor necrosis factor alpha gene promoter −238G/A polymorphism increases the risk of psoriasis vulgaris in Indian patients

Abstract

Background

Tumor necrosis factor alpha (TNFα) gene −238G/A polymorphism (rs361525) is associated with psoriasis in several populations worldwide. To the best of our knowledge, there is no information about this polymorphism in Indian psoriatic patients. This study was undertaken to fill the gap in knowledge.

Methods

This case–control study involved 72 patients with psoriasis vulgaris (PsV) and 72 age and gender matched healthy individuals. TNFα −238G/A polymorphism was genotyped by PCR-RFLP method.

Results

TNFα −238A allele was 5 times commoner in PsV patients than in the control group (P = 4.1 × 10⁻⁷; odds ratio [OR] = 6.5 [0.95 CI: 2.9–14.6]). Distribution of the genotypes in the two groups showed statistically significant difference in dominant genetic model (P = 2.3 × 10⁻⁷) and not in recessive genetic model (P = 2.5 × 10⁻¹). Odds ratio for the occurrence of −238A genotype in PsV patients was 8.8 (0.95 CI: 3.5–20.2). The association showed no major difference when PsV patients were subgrouped into type I and type II categories and tested separately. Subgroup analysis on the basis of disease severity showed higher association with the moderate-severe subgroup (P = 2.4 × 10⁻⁹, OR 15.4 [0.95 CI: 5.8–41.0]) than with mild subgroup (P = 1.3 × 10⁻², OR 3.8 [0.95 CI: 1.3–10.9]).

Conclusions

Our results indicate that TNFα gene −238G/A polymorphism increases the risk of developing psoriasis vulgaris among Indians. Also, the data show that severity and not the type affects the strength of association in this population.

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Knowledge about, attitude toward, and practice of skin lightening products use and its social correlates among university students in five Association of Southeast Asian Nations (ASEAN) countries

Abstract

Background

The aim of this study was to investigate the knowledge about, attitude toward, and use of skin lightening products (SLP) and its social and psychological correlates among university students from five Association of Southeast Asian Nations (ASEAN) countries.

Methods

In a cross sectional survey, 3259 undergraduate university students (Mean age = 20.5 years, SD = 1.6) from five ASEAN countries responded to an anonymous questionnaire. Multivariate logistic regression analysis was used to identify associations between sociodemographic characteristics, knowledge, attitude, poor mental health, and SLP use.

Results

Overall, 79.1% of the students were aware that the use of SLP can harm the skin, and 30.1% knew the active ingredients of SLP. Most students had a positive perception of having a lighter skin tone and SLP. Overall, the prevalence of SLP use over the past 12 months was 30.7%, 16.7% of male, and 30.0% of female students, ranging from 13.4% in Myanmar to 69.4% in Thailand. In multivariate logistic regression analysis, among women, older age, coming from a poorer family, residing in an upper middle income country, awareness of active skin lightening ingredients, and poor mental health were associated with SLP, while among men, not aware of the negative effects of SLP and awareness of active skin lightening ingredients and poor mental health were associated with SLP use.

Conclusion

A high prevalence of SLP use was found in a large sample of ASEAN university students, and several social and mental health-related risk factors were found that may help in guiding interventions.

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Aims and Scope and Editorial Board

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Effects of neuromuscular electrical stimulation during hemodialysis on peripheral muscle strength and exercise capacity: a randomized clinical trial

Publication date: Available online 16 January 2017
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Ana Karla Vieira Brüggemann, Carolina Luana Mello, Tarcila Dal Pont, Deborah de Camargo Hizume Kunzler, Daniel Fernandes Martins, Franciane Bobinski, Wellington Pereira Yamaguti, Elaine Paulin
ObjectiveTo evaluate the effects of neuromuscular electrical stimulation of high and low frequency and intensity, performed during hemodialysis (HD), on physical function and inflammation markers in patients with chronic kidney disease (CKD).DesignRandomized clinical trialSettingHemodialysis clinic.Participants51 CKD patients were randomized into blocks of four by means of opaque envelopes. They were divided into a group of high frequency and intensity neuromuscular electrical stimulation (HG) and a group of low frequency and intensity neuromuscular electrical stimulation (LG).InterventionHG was submitted to neuromuscular electrical stimulation with 50Hz and medium intensity of 72.90mA, and LG used 5Hz and medium intensity of 13.85mA, 3 times per week for one hour, during 12 sessions.Main Outcome MeasuresPeripheral muscle strength, exercise capacity, levels of muscle trophism marker [growth factor similar to insulin type 1 (IGF-1)] and levels of pro- inflammatory [tumor necrosis factor (TNF-alpha)] and anti-inflammatory [Interleukin 10 – (IL-10)] cytokines.ResultsHG showed significant increase in right peripheral muscle strength (155.35±65.32Nm versus 161.60±68.73Nm; p=0.01) and left peripheral muscle strength (156.60±66.51Nm versus 164.10±69.76Nm, p=0.02) after training, which did not occur with LG for both right muscle strength (109.40±32.08Nm versus 112.65±38.44Nm, p=0.50) and left muscle strength (113.65±37.79Nm versus 116.15±43.01Nm; p=0.61). The distance of the 6-minute walk test (6MWTD) increased in both groups: HG (435.55±95.81m versus 457.25±90.64m; p=0.02) and LG (403.80±90.56m versus 428.90±87.42m, p=0.007). The groups did not differ in peripheral muscle strength and in the 6MWTD after the training protocol. In HG, a correlation was observed between initial and final values for 6MWTD and muscle strength. In LG, correlations occurred only between the 6MWTD and the initial muscle strength. Only LG increased levels of IGF-1 (252.38±156.35pg/ml versus 336.97±207.34 pg/ml; p=0.03) and only HG reduced levels of IL-10 (7.26±1.81 pg/ml versus 6.32±1.54 pg/ml; p=0.03). The groups showed no differences in the TNF-alpha concentrations.ConclusionCKD patients on HD improve exercise capacity after peripheral neuromuscular electrical stimulation of high and low frequency and intensity. However, the benefits on muscle and inflammatory outcomes seem to be specific for the adopted strategy.

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Intermediate outcomes of a transcutaneous bone conduction hearing device in a paediatric population

Publication date: Available online 16 January 2017
Source:International Journal of Pediatric Otorhinolaryngology
Author(s): Panagiotis A. Dimitriadis, Suzanne Carrick, Jaydip Ray
ObjectiveThe aim of this study was to review the outcomes of Bone Anchored Hearing Aid (BAHA®) Attract implantation in a cohort of paediatric patients.MethodsProspective data collection and case review were undertaken in apaediatric tertiary referral centre. We have included patients under the age of 16 years with unilateral or bilateral hearing loss that met the criteria for BAHA^® Attract implantation. The main outcome measures were surgical complications and Patient Reported Outcomes including the 'Speech, Spatial and Qualities of Hearing scale' (SSQ-12) and 'Qualitative Feedback for BAHA^® 5 Hearing Aids'.ResultsTwenty-five paediatric patients were implanted with the BAHA^® Attract between June 2014 and July 2016. Nine of them had a conversion from a percutaneous Bone Conduction Hearing Device (BCHD). Four children had minor skin problems that settled with conservative measures. Two children with a previous percutaneous BCHD developed skin dehiscence over the magnet after conversion to the transcutaneous version. The SSQ-12 was completed by 6 children and an improvement of 22% was noted between the unaided and aided condition. The patients and their parents were generally satisfied with the BAHA^® Attract.ConclusionsThe BAHA^® Attract offers a good solution for hearing rehabilitation in appropriately selected and counseled patients. The complication rate was low for primary surgery but higher in cases of conversion from a percutaneous device. Large, prospective data is needed to evaluate the relative risks and benefits of this BCHD.

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Early childhood otitis media and later school performance – A prospective cohort study of associations

Publication date: Available online 16 January 2017
Source:International Journal of Pediatric Otorhinolaryngology
Author(s): Vincent Fougner, Asbjørn Kørvel-Hanquist, Anders Koch, Jesper Dammeyer, Janni Niclasen, Jørgen Lous, Preben Homøe
IntroductionOtitis media (OM) is a common disease in childhood and hearing loss (HL) is the most common complication. Prolonged HL may lead to language delay and cognitive difficulties. However, the consequences of HL due to OM are not fully understood.The aim of this study was to determine the possible association between number of OM episodes in childhood and self-rated school performance controlling for potential confounders.MethodsProspectively gathered systematic interview data on OM episodes in early childhood and school performance at 11 years of age were obtained from The Danish National Birth Cohort, involving >100 000 individual pregnancies and their offspring. We defined four exposure groups (0, 1–3, 4–6 and ≥7 OM episodes) and assessed general school performance, mathematics and literacy. Possible confounders were recognized à priori and associations were determined using proportional odds regression.ResultsOut of 94 745 successful pregnancies, 35,946 children without malformations and their parents completed a questionnaire at age 11 years. No associations were observed between number of OM episodes and school performance, even in children with ≥7 OM episodes.ConclusionThis national birth-cohort study did not support the hypothesis that the number of OM episodes in childhood is associated with reduced self-reported school performance in children at 11 years of age.

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The Temporoparietal Fascia Flap for Coverage of Cochlear Reimplantation Following Extrusion

Publication date: Available online 16 January 2017
Source:International Journal of Pediatric Otorhinolaryngology
Author(s): Kaveh Karimnejad, Asad Shahab Akhter, Scott Gregory Walen, Anthony Alan Mikulec
The management of cochlear implant extrusion (CIE) can be challenging, particularly in the pediatric population in whom reconstructive options are limited. We describe the use of the temporoparietal fascia flap (TPFF) for this purpose due to its ease of use and limited morbidity. We present a case series of two pediatric patients who underwent explantation of their devices, followed by reimplantation with TPFF coverage. Our experience provides evidence that the TPFF can be used to prevent further CIE through a postauricular incision following cochlear reimplantation with successful long-term results.

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The effects of cochlear implantation on vestibular function in 1–4 years old children

Publication date: Available online 16 January 2017
Source:International Journal of Pediatric Otorhinolaryngology
Author(s): Mohammad Ajalloueyan, Masoumeh Saeedi, Mohammad Sadeghi, Farzaneh Zamiri
ObjectivesAlthough cochlear implants offer an effective hearing restoration option in children with severe to profound hearing loss, concern continues to exist regarding the possible effects of cochlear implantation on the vestibular system and balance.MethodsIn a prospective cohort study, 27 children with bilateral profound hearing loss (all candidates for cochlear implantation) were evaluated for their vestibular function before and after cochlear implantation. Vestibular evaluations consisted of Vestibular Evoked Myogenic Potentials, caloric testing and the Head-Impulse Test.ResultsMean age at the time of cochlear implantation was 27.19 months. Without considering vestibular evaluation results, one of the ears was selected for surgery. Vestibular tests after surgery were not indicative of any statistically significant change in vestibular system or balance.ConclusionThis limited data shows that cochlear implantation did not impair the vestibular system of these patients. By the results of our study we may conclude that round window implantation does not have any disturbing impact on vestibular function in children. The generalization of this result needs further research.

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Bromodomain and Extraterminal Protein Inhibitor JQ1 Suppresses Thyroid Tumor Growth

http://ssccancermelanoma.blogspot.com/2017/01/bromodomain-and-extraterminal-protein_16.html

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

6948891480

alsfakia@gmail.com

Production of renewable aromatic hydrocarbons via conversion of canola oil methyl ester (CME) over zinc promoted HZSM-5 catalysts

Publication date: June 2017
Source:Renewable Energy, Volume 106
Author(s): A. Bayat, S.M. Sadrameli
The conversion of canola oil methyl ester (CME) to aromatics was studied over Zn-modified HZSM-5 catalysts. The catalysts were prepared by incipient wetness impregnation method. Several techniques were used in characterization of the catalysts: X-ray diffraction, scanning electron microscopy, transmission electron microscopy, N2 adsorption-desorption and ammonia temperature-programmed desorption. The effects of reaction temperature and Weight Hourly Space Velocity (WHSV) on the aromatics yields were investigated. The reactor was operated at atmospheric pressure, temperatures of 400 and 450 °C and space velocities of 2 and 4 hr⁻¹. The main products were liquid hydrocarbon product (LHP), gases and water. Gas Chromatography (GC) analysis was applied to determine the BTX content of the LHP. Similar aromatic products distributions were obtained in the presence of unpromoted as well as Zn-promoted HZSM-5 catalysts. Toluene was the major aromatic compound followed by para-meta xylenes and benzene. The addition of zinc species to HZSM-5 catalyst promoted the aromatization capacity of the catalyst. The maximum aromatic yield of 42.6% was achieved at 450 °C and 2 h⁻¹ over 4Zn/ZS catalyst.

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Synthesis, structure, spectroscopic properties and DFT studies on some 7-hydroxy-4-methyl-8-(arylazo)-2H-1-benzopyran-2-one and their complexes with some divalent transition metal ions

Publication date: 15 April 2017
Source:Journal of Molecular Structure, Volume 1134
Author(s): Samir A. Abdel-Latif, Adel A. Mohamed
A novel 7-hydroxy-4-methyl-8-(p-tolylazo)-2H-1-benzopyran-2-one (coumarin) (L1) and 7-hydroxy-4-methyl-8-(p-anisylazo)-2H-1-benzopyran-2-one (coumarin) (L2) and their metal complexes with Mn(II), Co(II), Ni(II) Cu(II) and Zn(II) have been prepared and characterized by elemental analysis, infrared (IR), proton nuclear magnetic resonance (¹H NMR) and mass spectra. The solid complexes have been also characterized by thermal analyses (TG and DTA), magnetic measurements, electronic transition, molar conductance; mass spectra, and electron spin resonance (ESR). The molecular orbital calculations of the complexes have been performed using the density functional theory (DFT) method and the basis sets 6-31G* and 6-311G**. The computational results revealed that the proposed geometrical structures for the investigated metal complexes suggest trigonal bipyramid for 1:1 and tetrahedral geometry for 1:2 complexes. The 1:1 complexes contain coordinated and lattice held water molecules whereas 1:2 complexes contain only lattice water molecules. The complexes behave as non-electrolytes in dimethyl formamide (DMF).

Graphical abstract

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A Zn-Ni coating with both high electrical conductivity and infrared emissivity prepared by hydrogen evolution method

Publication date: 30 April 2017
Source:Applied Surface Science, Volume 402
Author(s): Jiacheng Guo, Xingwu Guo, Wenbin Xu, Zhicheng Zhang, Jie Dong, Liming Peng, Wenjiang Ding
A Zn-Ni coating with both high electrical conductivity and infrared emissivity was prepared by hydrogen evolution method in order to satisfy the demand of thermal control in space. The maximum infrared emissivity of 0.91 was obtained, meanwhile the electrical resistivity is lower than 0.01mΩ/cm. The infrared emissivity of the coating obtained from the experimental result is proportional to the projected area of pores per unit area in the coating. The addition of NH4SCN in the bath can obviously increase the projected area of pores per unit area in the coating and lead to the formation of NiO and ZnO compounds, which further increase the infrared emissivity of the coating. The porous hierarchical structure of Zn-Ni coating can further improve the infrared emissivity, and the infrared emissivity can be tuned by changing the projected area of pores in the coating. Based on the experimental results, a mathematical relationship between infrared emissivity and the projected area of pores per unit area is established. The bond strength and the mass of volatiles of the design of coatings satisfy the technical standard demanded by the satellites in space.

Graphical abstract

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Magnetic losses versus sintering treatment in Mn-Zn ferrites

Publication date: 1 May 2017
Source:Journal of Magnetism and Magnetic Materials, Volume 429
Author(s): Cinzia Beatrice, Vasiliki Tsakaloudi, Samuel Dobák, Vassilios Zaspalis, Fausto Fiorillo
Mn-Zn ferrites prepared by different sintering schedules at 1325°C, 1340°C, and 1360°C, have been characterized from the structural, electrical, and magnetic viewpoint. Magnetic losses and complex permeability have been, in particular, measured and analyzed from quasi-static excitation up to 1GHz. It is observed that lower sintering temperatures and shorter treatment times lead to more homogeneous grain structure and better soft magnetic response at all frequencies. It is shown, however, that, once the contribution by eddy currents is singled out, the energy losses tend to coincide beyond a few MHz in the differently treated samples. The interpretative approach consists in separating the contributions by the domain wall displacements and the magnetization rotations to complex permeability and losses as a function of frequency. This can be accomplished in a relatively simple way in the low induction region described by the Rayleigh law, where these quantities can be quantitatively related and the linear Landau-Lifshitz-Gilbert equation applies, account being taken of the distribution in amplitude and orientation of the local anisotropy fields.

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16 novel mutations in PNPLA1 in patients with autosomal recessive congenital ichthyosis reveal the importance of an extended patatin domain in PNPLA1 that is essential for proper human skin barrier function

Abstract

Background

Autosomal recessive congenital ichthyosis (ARCI) is a genetically heterogeneous group of rare Mendelian skin disorders characterized by cornification and differentiation defects of keratinocytes. Mutations in nine genes including PNPLA1 are known to cause non-syndromic forms of ARCI. To date, only ten distinct pathogenic mutations in PNPLA1 have been reported.

Objectives

To identify new causative PNPLA1 mutations, we screened genetically unresolved cases including our ARCI collection comprising more than 700 families. Here, we report on 16 novel mutations present in patients from 17 families.

Methods

The screening for mutations was performed either by direct Sanger sequencing or in combination with a multi gene panel, followed by sequence and mutation analysis.

Results

While all previously reported mutations and most of our novel mutations are located within the core patatin domain, here we report on five novel PNPLA1 mutations, which are downstream of this domain. Thus, as recently described for PNPLA2, we hypothesize that a region larger than core domain is required for full enzymatic activity of PNPLA1 in human skin barrier formation.

Conclusions

We estimate the frequency of PNPLA1 mutations amongst ARCI patients to around 3%. Most of our patients were born as collodion babies and showed a relatively mild ichthyosis phenotype. In four unrelated patients we observed a cyclic scaling course, which seems to be a potential phenotype variation in a small percentage of patients with PNPLA1 mutations.

The variability of the clinical manifestations as well as the lack of typical clinical features are specific for patients with PNPLA1 mutations, and emphasize the importance of DNA sequencing for differential diagnosis of ARCIs.

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16 novel mutations in PNPLA1 in patients with autosomal recessive congenital ichthyosis reveal the importance of an extended patatin domain in PNPLA1 that is essential for proper human skin barrier function

Abstract

Background

Objectives

Methods

The screening for mutations was performed either by direct Sanger sequencing or in combination with a multi gene panel, followed by sequence and mutation analysis.

Results

Conclusions

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A Reviewers Guide to an Evaluation of the Scientific Literature

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

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Low-Level Laser Therapy in Enhancing Wound Healing and Preserving Tissue Thickness at Free Gingival Graft Donor Sites: A Randomized, Controlled Clinical Study

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

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Temperature Development on the External Root Surface During Laser-Assisted Endodontic Treatment applying a Microchopped Mode of a 980 nm Diode Laser

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

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Photodynamic Inactivation of Cariogenic Pathogens Using Curcumin as Photosensitizer

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

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Cell proliferation and differentiation during the three dimensional reconstitution of eccrine sweat glands

Abstract

The aim of this study is to characterize the cell proliferation and proliferating cell types during three-dimensional reconstitution of eccrine sweat glands. Eccrine sweat gland cells suspended in Matrigel were injected subcutaneously into the inguinal regions of nude mice. At 1, 2, 4, 6, 8, 14, 21, 28, 35 and 42 days post-implantation, Matrigel plugs were immunostained for Ki67, to detect cycling cells, and the Ki67 labeling index at different time points was calculated. Three pairs of antibodies, Ki67/K7, Ki67/K14 and Ki67/α-SMA, were used to identify proliferating cell types in the plugs, on days 28, 35 and 42, by immunofluorescence double staining. The Ki67 labeling index on the first day of implantation was 30.53%, rapidly reached a peak value of 81.43% at 2 days post-implantation, and then decreased gradually to a low of 2.87% at 42 days. Double immunofluorescence staining showed that K14/Ki67 double-stained cells accounted for 80% of the Ki67-positive cells, whereas K7/Ki67 and α-SMA/Ki67 double-stained cells each accounted for 10% of the Ki67-positive population on days 28, 35, or 42 post-implantation. We conclude that eccrine sweat gland cells rapidly enter the cell cycle after implantation, but quickly show decreased cell proliferation and increased cell differentiation.

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IL-15-deficient mice develop enhanced allergic responses to airway allergen exposure

Abstract

Background

Interleukin-15 is a pleiotropic cytokine that is critical for the development and survival of multiple hematopoietic lineages. Mice lacking IL-15 have selective defects in populations of several pro-allergic immune cells including natural killer (NK) cells, NKT cells, and memory CD8⁺T cells. We therefore hypothesized that IL-15^-/- mice will have reduced inflammatory responses during the development of allergic airway disease (AAD).

Objective

To determine whether IL-15^-/- mice have attenuated allergic responses in a mouse model of AAD.

Methods

C57BL/6 wild-type (WT) and IL-15^-/- mice were sensitized and challenged with ovalbumin (OVA) and the development of AAD was ascertained by examining changes in airway inflammatory responses, Th2 responses, and lung histopathology.

Results

Here we report that IL-15^-/- mice developed enhanced allergic responses in an OVA-induced model of AAD. In the absence of IL-15, OVA-challenged mice exhibited enhanced bronchial eosinophilic inflammation, elevated IL-13 production, and severe lung histopathology in comparison with WT mice. In addition, increased numbers of CD4⁺T and B cells in the spleens and broncholaveolar lavage (BAL) were also observed. Examination of OVA-challenged IL-15Rα^-/- animals revealed a similar phenotype resulting in enhanced airway eosinophilia compared to WT mice. Adoptive transfer of splenic CD8⁺T cells from OVA-sensitized WT mice suppressed the enhancement of eosinophilia in IL-15^-/- animals to levels observed in WT mice, but had no further effects.

Conclusion and Clinical Relevance

These data demonstrate that mice with an endogenous IL-15 deficiency are susceptible to the development of severe, enhanced Th2-mediated AAD, which can be regulated by CD8⁺T cells. Furthermore, the development of disease as well as allergen-specific Th2 responses occurs despite deficiencies in several IL-15-dependent cell types including NK, NKT, and γδ T cells, suggesting that these cells or their subsets are dispensable for the induction of AAD in IL-15-deficient mice.

http://ift.tt/2j3fmC4

IL-15-deficient mice develop enhanced allergic responses to airway allergen exposure

Abstract

Background

Objective

To determine whether IL-15^-/- mice have attenuated allergic responses in a mouse model of AAD.

Methods

Results

Conclusion and Clinical Relevance

http://ift.tt/2j3fmC4

Retro-Auricular Thyroidectomy: An Open Approach

Abstract

Distant access robot-assisted thyroidectomy has gained popularity in recent years. Adoption of distant access procedures has been limited by cost, need for specialized training and expertise. We report our preliminary clinical experience with our modification of the retro-auricular thyroidectomy approach that allows adequate exposure for thyroid lobectomy without robotic or endoscopic assistance. This is a retrospective chart review of ten patients who have undergone retro-auricular thyroidectomies in the absence of robotic or endoscopic assistance. Ten patients were identified to have undergone this procedure over an 18-month period. All patients were female with average age 36 years (range 27–52). Six were right sided and 4 were left sided procedures. The average gland size was 4.2 cm (range 3.7–6 cm). The average nodule size was 2.1 cm (range 1.1–3.5 cm). The average operative time was 91 min (range 76–114 min). All patients had benign pathology on final histopathology. There were no conversions to open cervical thyroidectomy. Two patients had vocal cord paresis that resolved spontaneously. The average postoperative follow up was 3 months (range 1–7 months). Our technique for retro-auricular thyroidectomy is a safe, reproducible, and cost effective option for remote access thyroidectomy.

http://ift.tt/2iyCV4U

Postoperative Pain in Adult Tonsillectomy: Is There Any Difference Between the Technique?

Abstract

Tonsillectomy is one of the most common surgical procedures performed worldwide. Several techniques have been developed to reduce morbidity and enhance recovery after tonsillectomy. Our study was designed to compare post-operative pain with three different techniques: cold dissection (CD), monopolar–bipolar dissection (MBD) and coblation dissection (CBD). 103 adults were scheduled for elective tonsillectomy from September 2014 to December 2015, and were randomized to CD, MBD and CBD. Post-operative pain was assessed using visual analogue scale (VAS) and Lattinen Test (LT). We did not find significant differences between the groups in the VAS pain scores (p > 0.05), except for the first day, when CBD tonsillectomy showed a higher pain score (p < 0.05). The differences in LT scores between the three techniques were not statistically significant (p > 0.05). Comparison of analgesic consumption between CD, MBD and CBD did not found any significant differences irrespective of the technique used. When first and second week after surgery were compared, differences in analgesics requirements were statistically significant (p < 0.05). Seventeen cases (16.5%) of secondary haemorrhage were reported, but there were no statistical differences in the rate of postoperative bleeding between the three groups (p > 0.05). We conclude that in our study comparison of the three techniques, CD, MBD and CBD, did not show significant differences in the post-tonsillectomy pain scores and bleeding rate.

http://ift.tt/2iDRS8S

Erratum

In the article entitled "Immunodominance in allergic T-cell reactivity to Japanese cedar in different geographic cohorts" (Ann Allergy Asthma Immunol 2016;117:680-689), acknowledgment of funding sources was inadvertently omitted from the article. Funding for the article was provided in part by ALK-Abello A/S (Horsholm, Denmark) and with federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, under grant number U19 AI100275.

http://ift.tt/2jE6Dr1

Erratum

Complications associated with the treatment of fractures of the dentate portion of the mandible in paediatric patients: a systematic review

This study aimed to answer the following question: What is the best treatment option for fractures of the dentate portion of the mandible in paediatric patients when considering the occurrence of postoperative complications? A systematic literature review was done using the PubMed, Scopus, and Cochrane Library databases, and 1186 articles on the topic were found. Twelve of these articles were included in the final review after the full texts had been read. A sample of 178 paediatric patients was obtained.

http://ift.tt/2iG3dp8

Acoustic Analyses of the Singing Vibrato in Traditional Peking Opera

China's traditional Peking Opera has four standard categories of roles: Sheng, Dan, Jing, and Chou, the singing vibrato of each displaying a different auditory effect. The audio and respiratory signals were recorded for two performers of the Qing Yi role, one of the Jing role, one of the Chou role, one of the Lao Sheng role, one of the Xiao Sheng role, and one of the Lao Dan role. The recordings gained eventually consisted of 24 representative songs from six roles. The rates and extents of vibrato, fundamental frequency, and rib cage signals were analyzed.

http://ift.tt/2iG0zj5

A Surgeon's View on the Pathogenesis of Atherosclerosis.

Author: Haverich, Axel MD

Page: 205-207

http://ift.tt/2jE3tDF

Wide Variation in Reported Rates of Stroke Across Cohorts of Patients With Atrial Fibrillation.

Author: Quinn, Gene R. MD, MS; Severdija, Olivia N. MD; Chang, Yuchiao PhD; Singer, Daniel E. MD

Page: 208-219

http://ift.tt/2jtJw4L

Adding Rigor to Stroke Rate Investigations in Patients With Atrial Fibrillation.

Author: Nielsen, Peter Bronnum PhD; Lip, Gregory Y. H. MD

Page: 220-223

http://ift.tt/2jDRmWQ

Heart Failure Stages Among Older Adults in the Community: The Atherosclerosis Risk in Communities Study.

Author: Shah, Amil M. MD, MPH; Claggett, Brian PhD; Loehr, Laura R. MD, PhD; Chang, Patricia P. MD, MHS; Matsushita, Kunihiro MD, PhD; Kitzman, Dalane MD; Konety, Suma MD; Kucharska-Newton, Anna PhD, MPH; Sueta, Carla A. MD, PhD; Mosley, Thomas H. PhD; Wright, Jacqueline D. DrPH; Coresh, Joseph MD, PhD; Heiss, Gerardo MD, PhD; Folsom, Aaron R. MD, MPH; Solomon, Scott D. MD

Page: 224-240

http://ift.tt/2jtPWkr

Ticagrelor Compared With Clopidogrel in Patients With Prior Lower Extremity Revascularization for Peripheral Artery Disease.

Author: Jones, W. Schuyler MD; Baumgartner, Iris MD; Hiatt, William R. MD; Heizer, Gretchen MS; Conte, Michael S. MD; White, Christopher J. MD; Berger, Jeffrey S. MD, MS; Held, Peter MD, PhD; Katona, Brian G. PharmD; Mahaffey, Kenneth W. MD; Norgren, Lars MD, PhD; Blomster, Juuso MD; Millegard, Marcus MSc; Reist, Craig PhD; Patel, Manesh R. MD; Fowkes, F. Gerry R. MD; On behalf of the International Steering Committee and Investigators of the EUCLID Trial

Page: 241-250

http://ift.tt/2jDYra2

LPA Gene, Ethnicity, and Cardiovascular Events.

Author: Lee, Sang-Rok MD, PhD; Prasad, Anand MD; Choi, Yun-Seok MD, PhD; Xing, Chao PhD; Clopton, Paul MS; Witztum, Joseph L. MD; Tsimikas, Sotirios MD

Page: 251-263

http://ift.tt/2jtQQ01

Prognostic Value of N-Terminal Pro-B-Type Natriuretic Peptide, Troponin-T, and Growth-Differentiation Factor 15 in Adult Congenital Heart Disease.

Author: Baggen, Vivan J.M. MD; van den Bosch, Annemien E. MD, PhD; Eindhoven, Jannet A. MD, PhD; Schut, Anne-Rose W. BSc; Cuypers, Judith A.A.E. MD, PhD; Witsenburg, Maarten MD, PhD; de Waart, Monique; van Schaik, Ron H.N. PhD; Zijlstra, Felix MD, PhD; Boersma, Eric MSc, PhD; Roos-Hesselink, Jolien W. MD, PhD

Page: 264-279

http://ift.tt/2jDRW7f

Endothelial Microparticles From Acute Coronary Syndrome Patients Induce Premature Coronary Artery Endothelial Cell Aging and Thrombogenicity: Role of the Ang II/AT1 Receptor/NADPH Oxidase-Mediated Activation of MAPKs and PI3-Kinase Pathways.

Author: Abbas, Malak PhD; Jesel, Laurence MD, PhD; Auger, Cyril PhD; Amoura, Lamia; Messas, Nathan MD; Manin, Guillaume MD; Rumig, Cordula PhD; Leon-Gonzalez, Antonio J. PhD; Ribeiro, Thais P. PhD; Silva, Grazielle C. PhD; Abou-Merhi, Raghida PhD; Hamade, Eva PhD; Hecker, Markus PhD; Georg, Yannick MD; Chakfe, Nabil MD, PhD; Ohlmann, Patrick MD, PhD; Schini-Kerth, Valerie B. PhD; Toti, Florence PhD; Morel, Olivier MD, PhD

Page: 280-296

http://ift.tt/2jtDMYs

Exercise Dynamics in Secondary Mitral Regurgitation: Pathophysiology and Therapeutic Implications.

Author: Bertrand, Philippe B. MD, MSc, PhD; Schwammenthal, Ehud MD, PhD; Levine, Robert A. MD; Vandervoort, Pieter M. MD

Page: 297-314

http://ift.tt/2jDUFh4

Effect of Clopidogrel by Smoking Status on Secondary Stroke Prevention.

Author: Ovbiagele, Bruce MD; Wang, Jing MD; Johnston, S. Claiborne MD, PhD; Wang, Anxin MS; Wang, David DO; Wang, Yongjun MD; Zhao, Xingquan MD, PhD; Wang, Yilong MD, PhD

Page: 315-316

http://ift.tt/2jtKkGR

Letter by Colli and Gerosa Regarding Article, "Transapical Beating-Heart Mitral Valve Repair With an Expanded Polytetrafluoroethylene Cordal Implantation Device: Initial Clinical Experience".

Author: Colli, Andrea MD, PhD; Gerosa, Gino MD

Page: e16-e17

http://ift.tt/2jDRoxW

Response by Gammie et al to Letter Regarding Article, "Transapical Beating-Heart Mitral Valve Repair With an Expanded Polytetrafluoroethylene Cordal Implantation Device: Initial Clinical Experience".

Author: Gammie, James S. MD; Wilson, Peter BSMET; Bartus, Krzysztof MD, PhD; Gackowski, Andrzej MD, PhD; Hung, Judy MD; D'Ambra, Michael N. MD; Kolsut, Piotr MD, PhD; Bittle, Gregory J. MD; Szymanski, Piotr MD, PhD; Sadowski, Jerzy MD, PhD; Kapelak, Boguslaw MD, PhD; Bilewska, Agata MD, PhD; Kusmierczyk, Mariusz MD; Ghoreishi, Mehrdad MD

Page: e18-e19

http://ift.tt/2jtO0IB

Letter by Dhruva and Redberg Regarding Article, "Sex and Race/Ethnicity Differences in Implantable Cardioverter-Defibrillator Counseling and Use Among Patients Hospitalized With Heart Failure: Findings From the Get With The Guidelines-Heart Failure Program".

Author: Dhruva, Sanket S. MD; Redberg, Rita F. MD, MSc

Page: e20-e21

http://ift.tt/2jDV7fe

Response by Hess et al to Letter Regarding Article, "Sex and Race/Ethnicity Differences in Implantable Cardioverter-Defibrillator Counseling and Use Among Patients Hospitalized With Heart Failure: Findings From the Get With The Guidelines-Heart Failure Program".

Author: Hess, Paul L. MD, MHS; Hernandez, Adrian F. MD, MHS; Bhatt, Deepak L. MD, MPH; Hellkamp, Anne S. MS; Yancy, Clyde W. MD, MSc; Schwamm, Lee H. MD; Peterson, Eric D. MD, MPH; Schulte, Phillip J. PhD; Fonarow, Gregg C. MD; Al-Khatib, Sana M. MD, MHS

Page: e22-e23

http://ift.tt/2jZ5HRc

pH/thermo-responsive poly(N-isopropylacrylamide-co-maleic acid) hydrogel with a sensor and an actuator for biomedical applications

Publication date: 10 February 2017
Source:Polymer, Volume 110
Author(s): Gheorghe Fundueanu, Marieta Constantin, Sanda Bucatariu, Paolo Ascenzi
Poly(N-isopropylacrylamide-co-maleic acid) (poly(NIPAAm-co-MAc)) with an appropriate comonomer ratio was designed and synthesized as an appealing pH/thermo-responsive copolymer. In simulated physiological fluids (phosphate buffer solution (PBS) at pH = 7.4 and T = 36 °C), both carboxylic groups of MAc in copolymer (pKa1 = 3.45, pKa2 = 6.09) are in the ionized form, more hydrophilic and consequently the copolymer loses the thermosensitive properties. However, when the carboxylate groups present in the copolymer are protonated or interact ionically with positively-charged compounds with hydrophobic character (e.g. diphenhydramine, DPH), the copolymer takes back the thermosensitive properties at the physiological pH and temperature. Therefore, microgels obtained from poly(NIPAAm-co-MAc) are in the swollen state in PBS at T = 36 °C, i.e. they are in the "inactive" state. However, after ionic interactions with hydrophobic compounds, taken as triggering agents, the microgels become "activated" and collapse. Therefore, the triggering agent is the key factor controlling the thermosensitivity of the hydrogel.

Graphical abstract

http://ift.tt/2jZ5pK8

Endonasal septal perforation repair using posterior and inferiorly based mucosal rotation flaps

Repair of nasal septal perforations is challenging regardless of surgical technique due to their location and the health of surrounding tissue. There is currently no surgical procedure which is completely effective in the treatment of anteriorly located perforations.

http://ift.tt/2jqfSxu

Endonasal septal perforation repair using posterior and inferiorly based mucosal rotation flaps

Trouble sleeping inside: a cross-sectional study of the prevalence and associated risk factors of insomnia in adult prison populations in England

To investigate the prevalence of insomnia and identify associated demographic, clinical and forensic risk factors in adult prisoners in England.

http://ift.tt/2jYQNdF

Germinal centers: programmed for affinity maturation and antibody diversification

Oliver Bannard | Jason G Cyster

http://ift.tt/2j2Ix8i

DNA sensing and immune responses in cancer therapy

Jian Qiao | Haidong Tang | Yang-Xin Fu

http://ift.tt/2j2GKQJ

Früherkennung bei Brustkrebs

Zusammenfassung

Brustkrebs ist die häufigste Krebserkrankung und auch die häufigste krebsbedingte Todesursache von Frauen in Deutschland. Die Früherkennung für Frauen mit normalem Brustkrebsrisiko beginnt in Deutschland mit dem 30. Lebensjahr. Seit 2004 können Frauen zwischen 50 und 69 Jahren im Rahmen der Früherkennung an einem systematischen und bevölkerungsbezogenen Mammografiescreening teilnehmen. Dessen Nutzen und Schaden werden aktuell kontrovers diskutiert. Ergebnisse zur Mortalitätsreduktion aus dem deutschen Screeningprogramm sind erst ab 2018 zu erwarten. Zukünftig ist als Weiterentwicklung der Mammografie v. a. mit der Anwendung der Tomosynthese zu rechnen. Für Frauen mit erhöhtem Brustkrebsrisiko aufgrund entsprechender Genveränderungen (Mutationen in den BRCA1- und BRCA2-Genen) stehen ab dem 25. Lebensjahr oder 5 Jahre vor dem frühesten Erkrankungsalter der betroffenen Angehörigen intensivierte Früherkennungsmaßnahmen (Sonografie, Magnetresonanztomografie, Mammografie) zur Verfügung.

http://ift.tt/2j20BiZ

Profound Loss of Esophageal Tissue Differentiation in Eosinophilic Esophagitis

There is a profound impairment of esophageal tissue differentiation including a loss of tissue identity genes in eosinophilic esophagitis, providing potential value for predictive medicine, diagnostics and treatment of this emerging disease.

http://ift.tt/2jqkJip

Corrigendum to “Molecules in seminal plasma related to platelets in preeclampsia” [Med. Hypotheses 93 (2016) 27–29]

Publication date: March 2017
Source:Medical Hypotheses, Volume 100
Author(s): Iván Antonio García-Montalvo, Gabriel Mayoral Andrade, Laura Perez-Campos Mayoral, Socorro Pina Canseco, Ruth Martinez Cruz, Margarito Martínez-Cruz, Edgar Zenteno, Eduardo Perez-Campos Mayoral, Itandehui Gallegos Velasco, Maria Teresa Hernandez-Huerta, Diana Matias-Perez, Eduardo Pérez-Campos

http://ift.tt/2iAKfNr

Primary trigeminal neuralgia and the role of pars oralis of the spinal trigeminal nucleus

Publication date: Available online 16 January 2017
Source:Medical Hypotheses
Author(s): Selcuk Peker, Alperen Sirin
Trigeminal neuralgia is a painful condition that causes great discomfort. Although this disease has been known for more than 1,000 years, there is still no consensus on its underlying mechanism or treatment. Many hypotheses have been reported to explain the cause and nature of trigeminal neuralgia. These include theories about peripheral mechanisms and central mechanisms. We put forward a new hypothesis that trigeminal neuralgia is associated with the pars oralis of the spinal trigeminal nucleus (POSTN). The main basis for this is the close similarity between trigger point distribution and the area of influence of the POSTN. We also highlight that the areas of influence for the trigeminal nerve divisions do not match the trigger point distribution; therefore, peripheral theories should be further investigated.

http://ift.tt/2iFGVno

Impaired Illness Awareness and Leftward Visuospatial Inattention in Schizophrenia Are Attributable to a Common Neural Deficit – Posterior Parietal Hemispheric Imbalance

Publication date: Available online 16 January 2017
Source:Medical Hypotheses
Author(s): Julia Kim, Eric Plitman, Shinichiro Nakajima, Jun Ku Chung, Youssef Alshehri, Yusuke Iwata, Fernando Caravaggio, Bruce G. Pollock, Dave Pothier, Ariel Graff-Guerrero, Philip Gerretsen

http://ift.tt/2iFQFy1

The effects of cochlear implantation on vestibular function in 1–4 years old children

Although cochlear implants offer an effective hearing restoration option in children with severe to profound hearing loss, concern continues to exist regarding the possible effects of cochlear implantation on the vestibular system and balance.

http://ift.tt/2jqemf2

Intermediate outcomes of a transcutaneous bone conduction hearing device in a paediatric population

The aim of this study was to review the outcomes of Bone Anchored Hearing Aid (BAHA®) Attract implantation in a cohort of paediatric patients.

http://ift.tt/2jSkKbv

The Temporoparietal Fascia Flap for Coverage of Cochlear Reimplantation Following Extrusion

The management of cochlear implant extrusion (CIE) can be challenging, particularly in the pediatric population in whom reconstructive options are limited. We describe the use of the temporoparietal fascia flap (TPFF) for this purpose due to its ease of use and limited morbidity. We present a case series of two pediatric patients who underwent explantation of their devices, followed by reimplantation with TPFF coverage. Our experience provides evidence that the TPFF can be used to prevent further CIE through a postauricular incision following cochlear reimplantation with successful long-term results.

http://ift.tt/2jqi3RE

Identification of allosteric binding sites for PI3Kα oncogenic mutant specific inhibitor design

Publication date: Available online 16 January 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Michelle S. Miller, Sweta Maheshwari, Fiona M. McRobb, Kenneth W. Kinzler, L. Mario Amzel, Bert Vogelstein, Sandra B. Gabelli
PIK3CA, the gene that encodes the catalytic subunit of phosphatidylinositol 3-kinase α (PI3Kα), is frequently mutated in breast and other types of cancer. A specific inhibitor that targets the mutant forms of PI3Kα could maximize treatment efficiency while minimizing side-effects. Herein we describe the identification of novel binding pockets that may provide an opportunity for the design of mutant selective inhibitors. Using a fragment-based approach, we screened a library of 352 fragments (MW <300 Da) for binding to PI3Kα by X-ray crystallography. Five novel binding pockets were identified, each providing potential opportunities for inhibitor design. Of particular interest was a binding pocket near Glu542, which is located in one of the two most frequently mutated domains.

Graphical abstract

http://ift.tt/2ivIbLe

Identification of Novel Inverse Agonists of Estrogen-Related Receptors ERRγ and ERRβ

Publication date: Available online 16 January 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Donna D. Yu, Janice M. Huss, Hongzhi Li, Barry M. Forman
Estrogen-related receptors (ERRs, α, β, and γ) are orphan nuclear receptors most closely related in sequence to estrogen receptors (ERα and ERβ). Much attention has been paid recently to the functions of ERRs for their potential roles as new therapeutic targets implicated in the etiology of metabolic disorders. While no endogenous ligand has been identified for any of the ERR isoforms to date, the potential for using synthetic small molecules to modulate their activity has been demonstrated. In the present study, a series of novel inverse agonists of ERRγ and ERRβ were synthesized using regio- and stereo-specific direct substitution of triarylethylenes. These compounds were evaluated for their ability to modulate the activities of ERRs. The rational directed substitution approach and extensive SAR studies resulted in the discovery of compound 4a (DY40) as the most potent ERRγ inverse agonist described to date with mixed ERRγ/ERRβ functional activities, which potently suppressed the transcriptional functions of ERRγ with IC50 = 0.01 μM in a cell-based reporter gene assay and antagonized ERRγ with a potency approximately 60 times greater than its analog Z-4-OHT (Z-4-hydroxytamoxifen). In addition, compound 3h (DY181) was identified as the most potent synthetic inverse agonist for the ERRβ that exhibited excellent selectivity over ERRα/γ in functional assays. This selectivity was also supported by computational docking models that suggest DY181 forms more extensive hydrogen bound network with ERRβ which should result in higher binding affinity on ERRβ over ERRγ.

Graphical abstract

http://ift.tt/2ivDukM

Synthesis of new spirooxindole-pyrrolothiazoles derivatives: Anti-cancer activity and molecular docking

Publication date: Available online 16 January 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Gehad Lotfy, Mohamed M. Said, El Sayed H. El Ashry, El Sayed H. El Tamany, Abdullah Al-Dhfyan, Yasmine M. Abdel Aziz, Assem Barakat
The 1,3-dipolar cycloadditions of an azomethine ylide generated from isatin and thiazolidinecarboxylic acid to a series of 2,6-bis[(E)-arylmethylidene]cyclohexanones afforded new di-spiro heterocycles incorporating pyrrolidine and oxindole rings in quantitative yields and chemo-, regio-, and stereoselectively. The newly synthesized compounds were characterized using spectroscopic techniques. Furthermore, the molecular structures of 4a, 4e, and 4n were confirmed by X-ray crystallography. These newly synthesized compounds were screened for their in vitro activity against breast cancer cell line MCF-7 and K562-leukemia. 4k was found to be the most potent compound of this series in targeting MCF-7 breast cancer cells and K562-leukemia, with IC50 values of 15.32 ± 0.02 and 14.74 ± 0.7 μM, respectively. The molecular studies of the synthesized compounds were investigated.

Graphical abstract

http://ift.tt/2ivEp4v

Chiral resolution of serial potent and selective σ1 ligands and biological evaluation of (-)-[18F]TZ3108 in rodent and the nonhuman primate brain

Publication date: Available online 16 January 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Xuyi Yue, Hongjun Jin, Zonghua Luo, Hui Liu, Xiang Zhang, Ethan D. McSpadden, Linlin Tian, Hubert P. Flores, Joel S. Perlmutter, Stanley M. Parsons, Zhude Tu
Twelve optically pure enantiomers were obtained using either crystallization or chiral high performance liquid chromatography (HPLC) separation methodologies to resolve six racemic sigma-1 (σ1) receptor ligands. The in vitro binding affinities of each enantiomer for σ1, σ2 receptors and vesicular acetylcholine transporter (VAChT) were determined. Out of the 12 optically pure enantiomers, five displayed very high affinities for σ1 (Ki < 2 nM) and high selectivity for σ1 versus σ2 and VAChT (>100-fold). The minus enantiomer, (-)-14a ((-)-TZ3108)) (Ki-σ1 = 1.8 ± 0.4 nM, Ki-σ2 = 6960 ± 810 nM, Ki-VAChT = 980 ± 87 nM), was chosen for radiolabeling and further in vivo evaluation in rodents and nonhuman primates (NHPs). A biodistribution study in Sprague Dawley rats showed brain uptake (%ID/gram) of (-)-[¹⁸F]TZ3108 reached 1.285 ± 0.062 at 5 min and 0.802 ± 0.129 at 120 min. NHP microPET imaging studies revealed higher brain uptake of (-)-[¹⁸F]TZ3108 and more favorable pharmacokinetics compared to its racemic counterpart. Pretreatment of the animal using two structurally different σ1 ligands significantly decreased accumulation of (-)-[¹⁸F]TZ3108 in the brain. Together, our in vivo evaluation results suggest that (-)-[¹⁸F]TZ3108 is a promising positron emission tomography (PET) tracer for quantifying σ1 receptor in the brain.

Graphical abstract

http://ift.tt/2ivyix4

Design, synthesis, molecular modeling and anti-hyperglycemic evaluation of novel quinoxaline derivatives as potential PPARγ and SURs agonists

Publication date: Available online 16 January 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Mohamed.K. Ibrahim, Ibrahim H. Eissa, AbdallahE. Abdallah, Ahmed M. Metwaly, M.M. and M.A. Radwan ElSohly
In our effort to develop potent anti-hyperglycemic agents with potential agonistic activities toward PPARγ and SURs, three novel series of quinoxaline derivatives bearing sulfonylurea or sulfonylthiourea moieties with different linkers were designed and synthesized. Some of the newly synthesized compounds were evaluated in vivo for their anti-hyperglycemic activities in STZ-induced hyperglycemic rats. Compounds 15a, 15e, 19b and 24a exhibited the highest anti-hyperglycemic activities with% reduction in blood glucose level of (50.58, 43.84, 45.10 and 49.62, respectively). Additionally, eight compounds revealed potent anti-hyperglycemic activities were further evaluated in vitro for their PPARγ binding affinity and insulin-secreting ability as potential mechanisms for anti-hyperglycemic activity. Four compounds (15a, 15b, 15d and 15e) significantly bound to PPARγ with IC50 values of 0.482, 0.491, 0.350 and 0.369 μM, respectively. Moreover, Compounds 15a and 15b have demonstrated induction of insulin-secretion with EC50 values of 0.92 and 0.98 μM, respectively. Furthermore, molecular docking and pharmacophore generation techniques were carried out to investigate binding patterns and fit values of the designed compounds with PPARγ and SUR, respectively.

Graphical abstract

http://ift.tt/2ivCMnw

Strategy for constructing vascularized adipose units in poly(L-glutamic acid) hydrogel porous scaffold through inducing in-situ formation of ASCs spheroids

Publication date: Available online 16 January 2017
Source:Acta Biomaterialia
Author(s): Kunxi Zhang, Li Song, Jia Wang, Shifeng Yan, Guifei Li, Lei Cui, Jingbo Yin
Vascularization is of great importance to adipose tissue regeneration. Here we introduced a paradigm that using scaffold to induce ASC spheroids, so to promote vascularized adipose tissue regeneration. Poly (L-glutamic acid) (PLGA) was activated by EDC, followed by being cross-linked by Adipic dihydrazide (ADH) to form a homogeneous hydrogel. Lyophilization was then carried out to create porous structure. The PLGA hydrogel scaffold possessed a significant swollen hydrophilic network to weaken cell-scaffold adhesion but drive ASCs to aggregate to form spheroids. Increase of seeding cell density was proved to result in the increase of spheroid size, upregulating angiogenic genes (VEGF and FGF-2) expression by enhancing the hypoxia-induced paracrine secretion. Also, the adipogenic differentiation of ASCs was achieved in spheroids in vitro. Moreover, the in vivo vascularized adipose tissue regeneration was evaluated in the dorsum of nude mice. After 12 weeks post-implantation, the significant angiogenesis was found in both adipogenic induced and non-induced engineered tissue. In adipogenic induced group, the clear ring-like morphology, the large vacuole in the middle of the cell and the Oil red O staining demonstrated adipose tissue formation.Statement of SignificanceVascularization is of great importance to adipose tissue regeneration. Adipose derived stem cell (ASC) spheroids possessed not only the high efficiency of vascularization, but also the improved differentiation ability. Several research works have illustrated the advantage of ASC spheroids in vascularization. However, in adipose regeneration, ASC spheroid was rarely used. Even so, it is reasonable to believe that ASC spheroids hold a great promise in vascularized adipose tissue engineering. Thus in the present study, we introduced a method to create lots of ASC spheroids that acted as lots of individual adipogenesis and angiogenesis units inside of a porous hydrogel scaffold. Then, the scaffold carrying ASC spheroids was implanted subcutaneously in nude mice to preliminarily evaluate the adipose tissue generation and blood vessel formation.

Graphical abstract

http://ift.tt/2jikB1W

Immune-mediated processes implicated in chemotherapy-induced peripheral neuropathy

Publication date: March 2017
Source:European Journal of Cancer, Volume 73
Author(s): Justin G. Lees, Preet G.S. Makker, Ryan S. Tonkin, Munawwar Abdulla, Susanna B. Park, David Goldstein, Gila Moalem-Taylor
Chemotherapy-induced peripheral neuropathy (CIPN) and associated neuropathic pain are challenging complications of cancer treatment. Many of the major classes of chemotherapeutics can cause neurotoxicity and significantly modulate the immune system. There is ongoing investigation regarding whether reciprocal crosstalk between the nervous and immune systems occurs and, indeed, contributes to neuropathic pain during treatment with chemotherapeutics. An emerging concept is that neuroinflammation is one of the major mechanisms underlying CIPN. Here, we discuss recent findings, which provide insight into this complex process of neuroimmune interactions. Findings show limited infiltration of leukocytes into the nervous system of CIPN animals and varying degrees of peripheral and central glial activation depending on the chemotherapeutic drug, dose, schedule, and timing. Most evidence suggests an increase in pro-inflammatory cytokine expression and changes in immune signalling pathways. There is, however, limited evidence available from human studies and it remains unclear whether neuroinflammatory responses are the cause of neuropathy or a bystander effect of the chemotherapy treatment.

http://ift.tt/2jq3D42

Fabrication of nanofibrous electrospun scaffolds from a heterogeneous library of co- and self-assembling peptides

Publication date: Available online 16 January 2017
Source:Acta Biomaterialia
Author(s): Mahboubeh Maleki, Antonino Natalello, Raffaele Pugliese, Fabrizio Gelain
Self-assembling (SAPs) and co-assembling peptides (CAPs) are driving increasing enthusiasm as synthetic but biologically inspired biomaterials amenable of easy functionalization for regenerative medicine. On the other hand, electrospinning (ES) is a versatile technique useful for tailoring the nanostructures of various biomaterials into scaffolds resembling the extracellular matrices found in organs and tissues. The synergistic merging of these two approaches is a long-awaited advance in nanomedicine that has not been deeply documented so far. In the present work, we describe the successful ES of a library of diverse SAPs and CAPs into biomimetic nanofibrous mats. Our results suggest that suitable ES solutions are characterized by high concentrations of peptides, providing backbone physical chain entanglements, and by random coil/α-helical conformations while β-sheet aggregation may be detrimental to spinnability. The resulting peptide fibers feature interconnected seamless mats with nanofibers average diameters ranging from ∼100 nm to ∼400 nm. Also, peptide chemical nature and ES set up parameters play pivotal roles in determining the conformational transitions and morphological properties of the produced nanofibers. Far from being an exhaustive description of the just-opened novel field of ES-assembled peptides, this seminal work aims at shining a light on a still missing general theory for the production of electrospun peptidic biomaterials bringing together the spatial, biochemical and biomimetic of these two techniques into unique scaffolds for tissue engineering.Statement of SignificanceConstruction of peptide hydrogels has received considerable attention due to their potential as nanostructures amenable of easy functionalization and capable of creating microenvironments suited for culturing cells and triggering tissue regeneration. They display a superior biocompatibility unmatched by other known synthetic biomaterials so far. However, their applications are confined to body fillers because most of them do spontaneously form hydrogels, while effective tissue regeneration often requires well-defined fibrous scaffolds. In this work, we developed electrospun fibers of various peptides (cross-beta self-assembling, hierarchically assembling, functionalized, co-assembling) and we provided a deep understanding of the crucial phenomena to be taken into account when peptides fibers fabrication. These results open new venues for exploring novel regenerative applications of peptide nanofibrous scaffolds.

Graphical abstract

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Composite material consisting of microporous β-TCP ceramic and alginate for delayed release of antibiotics

Publication date: Available online 16 January 2017
Source:Acta Biomaterialia
Author(s): Michael Seidenstuecker, Juergen Ruehe, Norbert P. Suedkamp, Annerose Serr, Annette Wittmer, Marc Bohner, Anke Bernstein, Hermann O. Mayr
ObjectiveThe aim of this study was to produce a novel composite of microporous β-TCP filled with alginate and Vancomycin (VAN) to prolong the release behavior of the antibiotic for up to 28 days.Material and MethodsUsing the flow chamber developed by the group, porous ceramics in a directional flow were filled with alginates of different composition containing 50 mg/mL of antibiotics. After cross-linking the alginate with calcium ions, incubation took place in 10 mL double-distilled water for 4 weeks at 37 °C. At defined times (1, 2, 3, 6, 9, 14, 20 and 28 days), the liquid was completely exchanged and analyzed by capillary zone electrophoresis and microtiter trials. For statistical purposes, the mean and standard deviation were calculated and analyzed by ANOVA.ResultsThe release of VAN from alginate was carried out via an external calcium source over the entire period with concentrations above the minimal inhibitory concentration (MIC). The burst release measured 35.2 ± 1.5%. The release of VAN from alginate with an internal calcium source could only be observed over 14 days. The burst release here was 61.9 ± 4.3%. The native alginate's burst release was 54.1 ± 7.8%; that of the sterile alginate 40.5 ± 6.4%. The microtiter experiments revealed efficacy over the entire study period for VAN. The MIC value was determined in the release experiments as well in a range of 0.5-2.0 μg/mL against Staphylococcus aureus.Statement of SignificanceDrug release systems based on β-TCP and hydrogels are well documented in literature. However, in all described systems the ceramic, as granule or powder, is inserted into a hydrogel. In our work, we do the opposite, a hydrogel which acts as reservoir for antibiotics is placed into a porous biodegradable ceramic. Eventually, this system should be applied as treatment of bone infections. Contrary to the "granule in hydrogel" composites it has the advantage of mechanical stability. Thus, it can take over functions of the bone during the healing process. For a quicker translation from our scientific research into clinical use, only FDA approved materials were used in this work.

Graphical abstract

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Alignment of collagen fiber in knitted silk scaffold for functional massive rotator cuff repair

Publication date: Available online 16 January 2017
Source:Acta Biomaterialia
Author(s): Zefeng Zheng, Jisheng Ran, Weishan Chen, Yejun Hu, Ting Zhu, Xiao Chen, Zi Yin, Boon Chin Heng, Gang Feng, Huihui Le, Chenqi Tang, Jiayun Huang, Yangwu Chen, Yiting Zhou, Pioletti Dominique, Weiliang Shen, Hong-wei Ouyang
Rotator cuff tear is one of the most common types of shoulder injuries, often resulting in pain and physical debilitation. Allogeneic tendon-derived decellularized matrices do not have appropriate pore size and porosity to facilitate cell infiltration, while commercially-available synthetic scaffolds are often inadequate at inducing tenogenic differentiation. The aim of this study is to develop an advanced 3D aligned collagen/silk scaffold (ACS) and investigate its efficacy in a rabbit massive rotator cuff tear model. ACS has similar 3D alignment of collagen fibers as natural tendon with superior mechanical characteristics. Based on ectopic transplantation studies, the optimal collagen concentration (10mg/ml), pore diameter (108.43 ± 7.25 μm) and porosity (97.94 ± 0.08%) required for sustaining a stable macro-structure conducive for cellular infiltration was determined. Within in vitro culture, tendon stem/progenitor cells (TSPCs) displayed spindle-shaped morphology, and were well-aligned on ACS as early as 24 hours. TSPCs formed intercellular contacts and deposited extracellular matrix after 7 days. With the in vivo rotator cuff repair model, the regenerative tendon of the ACS group displayed more conspicuous native microstructures with larger diameter collagen fibrils (48.72 ± 3.75 vs. 44.26 ± 5.03 nm) that had better alignment and mechanical properties (139.85 ± 49.36 vs. 99.09 ± 33.98 N) at 12 weeks post-implantation. In conclusion, these findings demonstrate the positive efficacy of the macroporous 3D aligned scaffold in facilitating rotator cuff tendon regeneration, and its practical applications for rotator cuff tendon tissue engineering.Statement of SignificanceMassive rotator cuff tear is one of the most common shoulder injuries, and poses a formidable clinical challenge to the orthopedic surgeon. Tissue engineering of tendon can potentially overcome the problem. However, more efficacious scaffolds with good biocompatibility, appropriate pore size, favorable inductivity and sufficient mechanical strength for repairing massive rotator cuff tendon injuries need to be developed. In this study, we developed a novel macroporous 3D aligned collagen/silk scaffold, and demonstrated that this novel scaffold enhanced the efficacy of rotator cuff tendon regeneration by inducing aligned supracellular structures similar to natural tendon, which in turn enhanced cellular infiltration and tenogenic differentiation of stem/progenitor cells from both the tendon itself and surrounding tissues. Hence, it can potentially be a clinically useful application for tendon tissue engineering.

Graphical abstract

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Effect of construction of TiO2 nanotubes on platelet behaviors: Structure-property Relationships

Publication date: Available online 16 January 2017
Source:Acta Biomaterialia
Author(s): Qiaoling Huang, Yun Yang, Dajiang Zheng, Ran Song, Yanmei Zhang, Pinliang Jiang, Erwin A. Vogler, Changjian Lin
Blood compatibility of TiO2 nanotubes (TNTs) has been assessed in rabbit platelet-rich plasma (PRP), which combines activation of both blood plasma coagulation and platelets. We find that (i) amorphous TiO2 nanotubes (TNTs) with relatively larger outer diameters led to reduced platelet adhesion/activation, (ii) TNTs with relatively smaller outer diameters in a predominately rutile phase also inhibited platelet adhesion and activation, and (iii) a pervasive fibrin network formed on larger outer diameter TNTs in a predominately anatase phase. Thus, this study suggests that combined effect of crystalline phase and surface chemistry controls blood-contact behavior of TNTs. A more comprehensive mechanism is proposed for understanding hemocompatibility of TiO2 which might prove helpful as a guide to prospective design of TiO2-based biomaterials.Statement of SignificanceTo realize optimal design and construction of biomaterials with desired properties for blood contact materials, a comprehensive understanding of structure-property relationships is required. In the existing literature, TiO2 nanotube has been reported to be a good candicate for biomedical applications. However, it is noticeable that the blood compatibility of TiO2 nanotubes (TNTs) remains obscure or even inconsistent in the previously published works. The inconsistency could derive from different research protocols, material properties or blood sources. Thus, a thorough investigation of the effect of suface properties on blood compatibility is crucial to the development of titanium based materials. In this paper, we explored the effect of surface properties on the response of platelet-rich plasma, especially surface morphology, chemistry, wettability and crystalline phase. The results indicated that cyrstalline phase was a dominant factor in platelet behaviors. Reduced adhesion and activation of platelets were observed on amorphous and rutile dominated TNTs, whereas anatase dominated TNTs activated the formation of fibrin network. We further proposed a hypothetical mechanism for better understanding of how surface properties affect the response of platelet-rich plasma. Therefore, this study expands the fundamental understanding of the structure-property relationships of titanium based materials.

Graphical abstract

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Surface Modification of PDLLGA Microspheres with Gelatine Methacrylate: Evaluation of Adsorption, Entrapment, and Oxygen Plasma Treatment Approaches

Publication date: Available online 16 January 2017
Source:Acta Biomaterialia
Author(s): Abdulrahman Baki, Cheryl V. Rahman, Lisa J. White, David J. Scurr, Omar Qutachi, Kevin M. Shakesheff
Injectable poly (DL-lactic-co-glycolic acid) (PDLLGA) microspheres are promising candidates as biodegradable controlled release carriers for drug and cell delivery applications; however, they have limited functional groups on the surface to enable dense grafting of tissue specific biocompatible molecules. In this study we have evaluated surface adsorption, entrapment and oxygen plasma treatment as three approaches to modify the surfaces of PDLLGA microspheres with gelatine methacrylate (gel-MA) as a biocompatible and photo cross-linkable macromolecule. Time of flight secondary ion mass spectroscopy (TOF SIMS) and X-ray photoelectron spectroscopy (XPS) were used to detect and quantify gel-MA on the surfaces. Fluorescent and scanning electron microscopies (SEM) were used to image the topographical changes. Human mesenchymal stem cells (hMSCs) of immortalised cell line were cultured on the surface of gel-MA modified PDLLGA microspheres and Presto-Blue assay was used to study the effect of different surface modifications on cell proliferation. Data analysis showed that the oxygen plasma treatment approach resulted in the highest density of gel-MA deposition. This study supports oxygen plasma treatment as a facile approach to modify the surface of injectable PDLLGA microspheres with macromolecules such as gel-MA to enhance proliferation rate of injected cells and potentially enable further grafting of tissue specific molecules.Statement of SignificancePoly (DL lactic-co-glycolic) acid (PDLLGA) microspheres offer limited functional groups on their surface to enable proper grafting of tissue specific bioactive molecules. To overcome this limitation, previous approaches have suggested using alkaline solutions to introduce active groups to the surface; however, they may compromise surface topography and lose any potential surface patterns. Plasma polymerisation of bioactive monomers has been suggested to enhance surface biocompatibility; however, it is not applicable on low vapour pressure macromolecules such as most extracellular matrix (ECM) proteins and growth factors. This study aims to evaluate three different approaches to modify the surface of PDLLGA microspheres with gelatine-methacrylate (gel-MA) to enable further grafting of cross-linkable biomolecules without compromising the surface topography or the biocompatibility of the system.

Graphical abstract

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Vitamin B3 metal-organic frameworks as potential delivery vehicles for therapeutic nitric oxide

Publication date: Available online 16 January 2017
Source:Acta Biomaterialia
Author(s): Rosana V. Pinto, Fernando Antunes, João Pires, Vanessa Graça, Paula Brandão, Moisés L. Pinto
The synthesis and structural characterization of two isostructural metal (M=Ni, Co) 3D framework structure that integrate vitamin B3 building blocks with NO delivery capabilities and low toxicity is presented. The compounds with a formula [M2(μ2-H2O)(μ-vitamin B3)4]·2H2O contain two crystallographic distinct divalent metal centers connected by a bridging water and carboxylate group from vitamin B3. The porous compounds have the capability of storing and releasing nitric oxide (NO) in a slow and reversible manner, with released amounts of 2.6 and 2.0 μmol NO mgsolid^-1, on the Ni and Co compound, respectively. The NO release followed a convenient slow release kinetic profile in both gas and liquid phases. Hemoglobin tests demonstrated that NO is released to the medium in a biologically active form, thus suitable to trigger the desired response in biological systems. The toxicity of the samples with and without loaded NO was evaluated from cytotoxicity tests in HeLa and HEKn cells, showing low toxicity of the compounds at concentrations below 180 μg cm^-3. The overall results indicate that these bio based MOFs are of interest for therapeutic applications related with NO delivery.Significance statementThe synthesis and characterization of new vitamin B3 porous metal-organic frameworks (MOFs) is presented in this work for the first time. Few other examples of porous MOFs build up of vitamin exist in the literature with adsorbing capacity like our materials.The ligand (vitamin B3) in these MOFs is much more biocompatible than the usual ligands like, for example, benzene carboxylic acids (terephthalic acid or trimesic acid) and imidazole based ligands.No other vitamin based MOFs have been studied for NO storage.The effects on cell cultures of the materials loaded with NO are studied for the first time and the cell line used is a human primary cell line representative of the human skin. This is relevant for future applications related to wound healing.

Graphical abstract

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The Effectiveness of Free Vascularized Fibular Flaps in Osteonecrosis of the Femoral Head and Neck: A Systematic Review

J reconstr Microsurg
DOI: 10.1055/s-0036-1594294

Background Free vascularized fibular flaps (FVFFs) are accepted surgical options to treat osteonecrosis of the femoral head and neck (ONFHN) to prevent conversion to total hip replacement (THR), yet many studies are single institution cohorts, with little generalizability. Purpose The purpose of this study was to perform a systematic review examining the comparative effectiveness of FVFF to treat ONFHN, particularly preventing conversion to a THR and improving hip function/symptoms. Methods We searched PubMed and EMBASE databases using femoral head, free fibula, and femoral neck keywords. Articles were excluded if not translated into English, n < 10 hips, article was a compilation/review, outcomes were not relevant, or prior to 1994. If from the same institution, we included the largest cohort and excluded others within the same timeline. Two investigators independently reviewed articles and reported number of patients/hips, average age/follow-up time/graft survival before THR, Harris hip score, THR rate, complications, and radiographic progression rates. Results We identified 128 and 157 articles from PubMed and EMBASE. After screening/duplicate removal, 21 studies were included from 14 institutions in 9 countries. Overall, 71% were level IV evidence. The average patient number was 129, number of hips was 166, age at surgery was 34 years, and follow-up time was 92 months. HHS improved on average 21.7 points, with the number of patients requiring THR being 19.4%. Graft survival before THR was 5.2 years, and 47.7% of hips had radiographic progression. Conclusions There is a significant amount of level IV evidence describing the favorable role of FVFF to treat ONFHN. Although efficacious, there is a need for higher level evidence. The level of evidence is 3.
[...]

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Article in Thieme eJournals:
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The Impact of Changes in Distress Tolerance on PTSD Symptom Severity Post-Treatment among Veterans in Residential Trauma Treatment

Publication date: Available online 16 January 2017
Source:Journal of Anxiety Disorders
Author(s): Anne N. Banducci, Kevin M. Connolly, Anka A. Vujanovic, Jennifer Alvarez, Marcel O. Bonn-Miller
Given that rates of PTSD, particularly among military populations, are increasing, it is critical to gain a better understanding of factors associated with treatment response. Low distress tolerance (DT), conceptualized as the perceived or actual inability to tolerate negative emotional states, may impacts veterans' responses to PTSD treatment. Low DT has been associated with more severe PTSD symptoms in clinical and non-clinical samples; however, its impact on PTSD symptomatology across treatment has yet to be assessed. We examined the impact of changes in DT, from intake to discharge, on post-treatment PTSD symptom severity within two samples of veterans recruited from Veterans Affairs residential PTSD treatment facilities in the northwestern and southern United States (Total N=86; 87% male; 46% White, 39% Black, 9% Latino, 6% Other). Veterans completed the Distress Tolerance Scale and PTSD Checklist (PCL) at intake and discharge from residential PTSD treatment. Regression analyses revealed that, within each veteran sample, those with the greatest improvements in DT had the lowest PCL total and subscale scores at discharge after controlling for respective intake PCL scores. This suggests increases in DT across treatment help explain the degree of benefits experienced by veterans following PTSD treatment.

http://ift.tt/2jt33SQ

Heroin use is associated with lower levels of restriction factors and type I interferon expression and facilitates HIV-1 replication

Publication date: Available online 16 January 2017
Source:Microbes and Infection
Author(s): Jia-Wu Zhu, Feng-Liang Liu, Dan Mu, De-Yao Deng, Yong-Tang Zheng
Heroin use is associated with increased incidence of infectious diseases such as HIV-1 infection, as a result of immunosuppression to a certain extent. Host restriction factors are recently identified cellular proteins with potent antiviral activities. Whether heroin use impacts on the in vivo expression of restriction factors that result in facilitating HIV-1 replication is poorly understood. Here we recruited 432 intravenous drug users (IDUs) and 164 non-IDUs at high-risk behaviors. Based on serological tests, significantly higher prevalence of HIV-1 infection was observed among IDUs compared with non-IDUs. We included those IDUs and non-IDUs without HIV-1 infection, and found IDUs had significantly lower levels of TRIM5α, TRIM22, APOBEC3G, and IFN-α, -β expression than did non-IDUs. We also directly examined plasma viral load in HIV-1 mono-infected IDUs and non-IDUs and found HIV-1 mono-infected IDUs had significantly higher plasma viral load than did non-IDUs. Moreover, intrinsically positive correlation between type I interferon and TRIM5α or TRIM22 was observed, however, which was dysregulated following heroin use. Collectively, heroin use benefits HIV-1 replication that may be partly due to suppression of host restriction factors and type I interferon expression.

http://ift.tt/2jpZ5e0

Assessing the progression of chronic periodontitis using subgingival pathogen levels: a 24-month prospective multicenter cohort study

Abstract

Background

The diagnosis of the progression of periodontitis presently depends on the use of clinical symptoms (such as attachment loss) and radiographic imaging. The aim of the multicenter study described here was to evaluate the diagnostic use of the bacterial content of subgingival plaque recovered from the deepest pockets in assessing disease progression in chronic periodontitis patients.

Methods

This study consisted of a 24-month investigation of a total of 163 patients with chronic periodontitis who received trimonthly follow-up care. Subgingival plaque from the deepest pockets was recovered and assessed for bacterial content of Porphyromonas gingivalis, Prevotella intermedia, and Aggregatibacter actinomycetemcomitans using the modified Invader PLUS assay. The corresponding serum IgG titers were measured using ELISA. Changes in clinical parameters were evaluated over the course of 24 months. The sensitivity, specificity, and prediction values were calculated and used to determine cutoff points for prediction of the progression of chronic periodontitis.

Results

Of the 124 individuals who completed the 24-month monitoring phase, 62 exhibited progression of periodontitis, whereas 62 demonstrated stable disease. The P. gingivalis counts of subgingival plaque from the deepest pockets was significantly associated with the progression of periodontitis (p < 0.001, positive predictive value = 0.708).

Conclusions

The P. gingivalis counts of subgingival plaque from the deepest pockets may be associated with the progression of periodontitis.

http://ift.tt/2jt0eRD

Do children’s previous dental experience and fear affect their perceived oral health-related quality of life (OHRQoL)?

Abstract

Background

Oral health-related quality of life (OHRQoL) has been used to describe the consequences of oral health conditions and treatments in children. A better understanding of OHRQoL and its relationship with dental fear and previous dental experience is necessary to improve children's oral health status. The aim of this study was to investigate the association of dental history and experience with dental fear and the OHRQoL of children aged 11 to 14 years.

Methods

A cross-sectional study was conducted using a multi-stage stratified sample of 1,312 middle school children. Information regarding OHRQoL was collected from the children using the Child Perceptions Questionnaire (CPQ_11–14), and information regarding dental fear was collected using the Children's Fear Survey Schedule-Dental Subscale (CFSS-DS). Information on past dental experiences and sociodemographic data were collected from the parents using self-administered questionnaires. Dental examinations were performed to assess caries experience.

Results

The multivariable model indicated that dental fear was the strongest predictor of OHRQoL as the fearful children had on average CPQ_11–14 scores that were 10 units higher than those of the non-fearful children. Regarding past dental experience, pain as the reason for the most recent dental visit was associated with poor OHRQoL, while receiving a filling during the previous dental visits was significantly associated with better OHRQoL. In addition, a larger number of siblings, a lower family income, a lower paternal education level, health problems and prior hospitalization were significantly associated with poor OHRQoL.

Conclusion

This study identified that dental fear and some factors related to previous dental experience are associated with OHRQoL. In dental practice, children with dental fear should be identified, guided and treated early to avoid deterioration of their OHRQoL.

http://ift.tt/2jDi1U2

In vitro effects of hyaluronic acid on human periodontal ligament cells

Abstract

Background

Hyaluronic acid (HA) has been reported to have a positive effect on periodontal wound healing following nonsurgical and surgical therapy. However, to date, a few basic in vitro studies have been reported to investigating the potential of HA on human periodontal ligament (PDL) cell regeneration. Therefore, the aim of this study was to investigate the effect of HA on PDL cell compatibility, proliferation, and differentiation in vitro.

Methods

Either non-cross-linked (HA_ncl) or cross-linked (HA_cl) HA was investigated. Human PDL cells were seeded in 7 conditions as follows (1) Control tissue culture plastic (TCP) (2) dilution of HA_ncl (1:100), (3) dilution of HA_ncl (1:10), 4) HA_ncl directly coated onto TCP, (5) dilution of HA_cl (1:100), 6) dilution of HA_cl (1:10) and (7) HA_cl directly coated onto TCP. Samples were then investigated for cell viability using a live/dead assay, an inflammatory reaction using real-time PCR and ELISA for MMP2, IL-1 and cell proliferation via an MTS assay. Furthermore, the osteogenic potential of PDL cells was assessed by alkaline phosphatase(ALP) activity, collagen1(COL1) and osteocalcin(OCN) immunostaining, alizarin red staining, and real-time PCR for genes encoding Runx2, COL1, ALP, and OCN.

Results

Both HA_ncl and HA_cl showed high PDL cell viability (greater than 90%) irrespective of the culturing conditions. Furthermore, no significant difference in both mRNA and protein levels of proinflammatory cytokines, including MMP2 and IL-1 expression was observed. Both diluted HA_ncl and HA_cl significantly increased cell numbers compared to the controlled TCP samples at 3 and 5 days. HA_ncl and HA_cl in standard cell growth media significantly decreased ALP staining, COL1 immunostaining and down-regulated early osteogenic differentiation, including Runx2, COL1, and OCN mRNA levels when compared to control samples. When osteogenic differentiation medium (ODM) was added, interestingly, the expression of early osteogenic markers increased by demonstrating higher levels of COL1 and ALP expression; especially in HA 1:10 diluted condition. Late stage osteogenic markers remained inhibited.

Conclusions

Both non-cross-linked and cross-linked HA maintained high PDL cell viability, increased proliferation, and early osteogenic differentiation. However, HA was consistently associated with a significant decrease in late osteogenic differentiation of primary human PDL cells. Future in vitro and animal research is necessary to further characterize the effect of HA on periodontal regeneration.

http://ift.tt/2jDm0Qi

Less extrusion debris during the retreatment of curved canals using twisted files with higher rotational speeds: an ex vivo study

Abstract

Background

Debris extrusion from the apical foramen can be problematic in severely curved canals. This study aimed to assess the use of Twisted Files (TF) at different rotational speeds during retreatment, compared with manual technique using Triple-Flex Files (TFF).

Methods

Forty-eight mesiobuccal root canals were randomized to four groups (n = 12 per group). In groups A, B, and C, gutta-percha was removed using TF at 500, 1000, and 1500 rpm, respectively, while it was removed using TFF in group D. Apical debris was collected in a pre-weighed centrifuge tube. The weight of dry debris was assessed by comparing the pre- and post-instrumentation weight for each group.

Results

Instrumentation in group D (0.69 ± 0.04 mg) extruded significantly more debris than any of the TF groups (A: 0.54 ± 0.05 mg; B: 0.48 ± 0.04 mg; C: 0.42 ± 0.03 mg; all P < 0.001). In addition, increasing the rotational speed of TF decreased the amount of extruded debris (A vs. B: P = 0.006; B vs. C: P < 0.001; A vs. C: P < 0.001).

Conclusions

TF at 1500 rpm produced less apical extrusion debris than other TF operating speeds and TFF.

http://ift.tt/2jtiBWK

Thyroid High-Impact Articles

FREE ACCESS through January 30, 2017.
Read now:

Latest Impact Factor: 3.784
The Official Journal of: American Thyroid Association

3-Iodothyronamine Decreases Expression of Genes Involved in Iodide Metabolism in Mouse Thyroids and Inhibits Iodide Uptake in PCCL3 Thyrocytes
Nancy Schanze, Simon Friedrich Jacobi, Eddy Rijntjes, Stefan Mergler, Marta del Olmo, Carolin Stephanie Hoefig, Noushafarin Khajavi, Ina Lehmphul, Heike Biebermann, Jens Mittag, Josef Köhrle

Differences in Brain Glucose Metabolism During Preparation for ¹³¹I Ablation in Thyroid Cancer Patients: Thyroid Hormone Withdrawal Versus Recombinant Human Thyrotropin
Hyeonseok S. Jeong, Eun Kyoung Choi, In-Uk Song, Yong-An Chung, Jong-Sik Park, Jin Kyoung Oh

RAS Mutations, and RET/PTC and PAX8/PPAR-gamma Chromosomal Rearrangements Are Also Prevalent in Benign Thyroid Lesions: Implications Thereof and A Systematic Review
Alireza Najafian, Salem Noureldine, Faris Azar, Chady Atallah, Gina Trinh, Eric B. Schneider, Ralph P. Tufano, Martha A. Zeiger

Thyroglobulin Liquid Chromatography—Tandem Mass Spectrometry Has a Low Sensitivity for Detecting Structural Disease in Patients with Antithyroglobulin Antibodies
Umal Azmat, Kyle Porter, Leigha Senter, Matthew D. Ringel, Fadi Nabhan

Lessons Learned After 1000 Cases of Transcutaneous Laryngeal Ultrasound (TLUSG) with Laryngoscopic Validation: Is There a Role of TLUSG in Patients Indicated for Laryngoscopic Examination Before Thyroidectomy?
Kai-Pun Wong, Kin-Pan Au, Shi Lam, Brian Hung-Hin Lang

The post Thyroid High-Impact Articles appeared first on American Thyroid Association.

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Thyroid High-Impact Articles

FREE ACCESS through January 30, 2017.
Read now:

Latest Impact Factor: 3.784
The Official Journal of: American Thyroid Association

The post Thyroid High-Impact Articles appeared first on American Thyroid Association.

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Αρχειοθήκη ιστολογίου

! # Ola via Alexandros G.Sfakianakis on Inoreader

Η λίστα ιστολογίων μου

Δευτέρα 16 Ιανουαρίου 2017

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