Polymer structure-property requirements for stereolithographic 3D printing of soft tissue engineering scaffolds

Publication date: September 2017
Source:Biomaterials, Volume 140
Author(s): Ryan J. Mondschein, Akanksha Kanitkar, Christopher B. Williams, Scott S. Verbridge, Timothy E. Long
This review highlights the synthesis, properties, and advanced applications of synthetic and natural polymers 3D printed using stereolithography for soft tissue engineering applications. Soft tissue scaffolds are of great interest due to the number of musculoskeletal, cardiovascular, and connective tissue injuries and replacements humans face each year. Accurately replacing or repairing these tissues is challenging due to the variation in size, shape, and strength of different types of soft tissue. With advancing processing techniques such as stereolithography, control of scaffold resolution down to the μm scale is achievable along with the ability to customize each fabricated scaffold to match the targeted replacement tissue. Matching the advanced manufacturing technique to polymer properties as well as maintaining the proper chemical, biological, and mechanical properties for tissue replacement is extremely challenging. This review discusses the design of polymers with tailored structure, architecture, and functionality for stereolithography, while maintaining chemical, biological, and mechanical properties to mimic a broad range of soft tissue types.



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Investigation of itraconazole ternary amorphous solid dispersions based on povidone and Carbopol

Publication date: 30 August 2017
Source:European Journal of Pharmaceutical Sciences, Volume 106
Author(s): Fan Meng, Jordan Meckel, Feng Zhang
We investigate a ternary system that consists of itraconazole (ITZ) and two polymers: povidone K12 and Carbopol 907. The interactions between these two polymers and their effects on the properties of ternary ITZ amorphous solid dispersions (ASDs) are studied. These two polymers can form a water-insoluble complex in acidic aqueous media. The critical pH is determined to be 4.17. The weight percentage of Carbopol 907 in the interpolymer complex range from 59 to 70%, depending on the initial ratios between these two polymers in the starting solutions. This complexation is driven by a negative enthalpy change from the H-bonding between the two polymers and a positive entropy change from the freed water molecules. Due to the slow precipitation of the interpolymer complex in aqueous media, the attempt to prepare ternary ASD using solvent-controlled coprecipitation is not successful. Melt extrusion is identified to be the only viable method to prepare this ternary ASD. We find that interpolymer complex–based ASDs are physically less stable and demonstrate the poorest drug-release properties when compared to individual polymer-based binary ASDs. This study illustrates that the too strong interaction between polymers in ternary ASDs is detrimental to their performance.

Graphical abstract

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Influence of the drug distribution in electrospun gliadin fibers on drug-release behavior

Publication date: 30 August 2017
Source:European Journal of Pharmaceutical Sciences, Volume 106
Author(s): Ying Xu, Jiao-Jiao Li, Deng-Guang Yu, Gareth R. Williams, Jun-He Yang, Xia Wang
Drug distribution within its carrier in a solid dosage form often generates a profound influence on its release profile, particularly when the physicochemical properties of the carrier are exploited to manipulate drug release behavior. In this job, two different types of distributions of a model drug ibuprofen (IBU) within a protein gliadin in their electrospun nanofibers were intentionally created. One was homogeneous distribution in the monolithic fibers fabricated using a modified coaxial process, and the other one was heterogeneous distribution in the core/shell fibers prepared through a traditional coaxial process. SEM observations clearly demonstrated the different distributions of IBU within gliadin in the two kinds of nanofibers although both of them had smooth surfaces and linear morphology. XRD results showed that IBU was amorphously distributed in the monolithic fibers, but that some IBU crystalline lattices presented in the core/shell fibers. FTIR and RM spectra suggested that gliadin had good compatibility with IBU. In vitro dissolution tests verified that the gliadin nanofibers with a heterogeneous drug distribution could provide a better sustained release profile than its counterpart in terms of initial burst release and sustained release time period. Both the fiber formation and drug-controlled release mechanisms are suggested. The present study demonstrated a concept that drug distribution with the medicated nanomaterials can be exploited as a tool to optimize the drug sustained release profile.



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Improved anticancer effects of albumin-bound paclitaxel nanoparticle via augmentation of EPR effect and albumin-protein interactions using S-nitrosated human serum albumin dimer

Publication date: September 2017
Source:Biomaterials, Volume 140
Author(s): Ryo Kinoshita, Yu Ishima, Victor T.G. Chuang, Hideaki Nakamura, Jun Fang, Hiroshi Watanabe, Taro Shimizu, Keiichiro Okuhira, Tatsuhiro Ishida, Hiroshi Maeda, Masaki Otagiri, Toru Maruyama
In the latest trend of anticancer chemotherapy research, there were many macromolecular anticancer drugs developed based on enhanced permeability and retention (EPR) effect, such as albumin bound paclitaxel nanoparticle (nab- PTX, also called Abraxane^®). However, cancers with low vascular permeability posed a challenge for these EPR based therapeutic systems. Augmenting the intrinsic EPR effect with an intrinsic vascular modulator such as nitric oxide (NO) could be a promising strategy. S-nitrosated human serum albumin dimer (SNO-HSA Dimer) shown promising activity previously was evaluated for the synergistic effect when used as a pretreatment agent in nab-PTX therapy against various tumor models. In the high vascular permeability C26 murine colon cancer subcutaneous inoculation model, SNO-HSA Dimer enhanced tumor selectivity of nab-PTX, and attenuated myelosuppression. SNO-HSA Dimer also augmented the tumor growth inhibition of nab-PTX in low vascular permeability B16 murine melanoma subcutaneous inoculation model. Furthermore, nab-PTX therapy combined with SNO-HSA Dimer showed higher antitumor activity and improved survival rate of SUIT2 human pancreatic cancer orthotopic model. In conclusion, SNO-HSA Dimer could enhance the therapeutic effect of nab-PTX even in low vascular permeability or intractable pancreatic cancers. The possible underlying mechanisms of action of SNO-HSA Dimer were discussed.

Graphical abstract

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Low expression of long noncoding RNA CASC2 indicates a poor prognosis and promotes tumorigenesis in thyroid carcinoma

Publication date: September 2017
Source:Biomedicine & Pharmacotherapy, Volume 93
Author(s): Xiangqing Xiong, Hua Zhu, Xiangjian Chen
Recently, long noncoding RNAs (lncRNAs) have been shown to be linked to regulate different biological processes, such as cell growth, differentiation and tumorigenesis. LncRNAs have been identified to be promising clinical biomarkers in various tumors. Long noncoding RNAs cancer susceptibility candidate 2 (CASC2) has recently been demonstrated to be correlated to tumorigenesis in renal cell carcinoma, lung carcinoma, glioma, and gastric carcinoma. Nevertheless, the research on the biological function and clinical significance of CASC2 in thyroid carcinoma are still unclear. In this research, we focused on the relationship between CASC2 expression and clinicopathological factors in thyroid cancer. We found that the low expression of CASC2 correlated with multifocality and advanced tumor-node-metastasis (TNM) stage. Kaplan-Meier survival analysis and multivariate analysis showed that CASC2 expression may be an independent prognostic factor in human thyroid carcinoma. Moreover, the area under the receiver operating characteristic (ROC) curve of CASC2 indicated that its diagnostic value in thyroid carcinoma. Additionally, overexpression of CASC2 significantly inhibited the proliferation of thyroid carcinoma cells and arrested cell cycle at G0/G1 stage in thyroid cancer cells. Our findings showed that CASC2 may be a potential prognostic marker and therapeutic target.



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The impact of gut microbiota on kidney function and pathogenesis

Publication date: September 2017
Source:Biomedicine & Pharmacotherapy, Volume 93
Author(s): Fariba Mahmoodpoor, Yalda Rahbar Saadat, Abolfazl Barzegari, Mohammadreza Ardalan, Sepideh V Zununi Vahed
Chronic kidney diseases (CKDs) are a global health problem. Besides diverse leading reasons in initiation and progression of CKDs, it is evident that they might largely originate from changes in the gut microbial community (microbiota). Mounting evidence indicates that a bidirectional relationship exists between host and microbiome in humans and animals with CKDs. Changes in the microbiota composition and structure (dysbiosis) produce excessive amounts of uremic toxins (e.g. indoxyl sulfate, p-cresyl sulfate and trimethylamine-N-oxide) but less reno-protective metabolites that are implicated in oxidative stress, uremia, inflammation, deterioration of kidney function, kidney diseases progression, a higher prevalence of cardiovascular risk, and mortality in patients with CKD. The present review focuses on the pathogenic association between gut microbiota and kidney diseases like CKD, IgA nephropathy, and kidney stone disease. Certainly, novel insights into the impact of the gut microbiota in kidney diseases can be helpful to develop therapeutic strategies in order to avoid and/or treat aforementioned conditions.



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Pure total flavonoids from citrus improve non-alcoholic fatty liver disease by regulating TLR/CCL signaling pathway: A preliminary high-throughput ‘omics’ study

Publication date: September 2017
Source:Biomedicine & Pharmacotherapy, Volume 93
Author(s): Liyan Wu, Maoxiang Yan, Jianping Jiang, Beihui He, Wei Hong, Zhiyun Chen
ObjectiveThis study investigated the possible molecular mechanisms of pure total flavonoids from citrus (PTFC) for the treatment of non-alcoholic fatty liver disease (NAFLD) via toll-like receptor/C-C chemokine ligand (TLR/CCL) signaling pathways by monitoring the changes in gene expression profile in liver tissues induced by high-fat diet.MethodsWe performed systematical analyses on hepatic expression profiles of mRNAs in a high-fat diet (HFD)-induced steatotic animal model with or without PTFC treatment. The study was conducted by using MouseOneArray^® v2 gene chip, and analyzed by bioinformatics tools for differential gene expression. Real time-PCR, Western blot and liquid suspension array analysis were used to validate specific genes in the NAFLD liver expression profile in which PTFC plays a role in the TLR/CCR pathway.ResultsWe found that a total of 562 genes showed varying degrees of reversal after PTFC intervention. Pathway analysis of the differential gene expression in the HFD group and the normal diet group (ND group) revealed six signaling pathways related to inflammatory responses in the top ten results. Comparison of genes between the HFD+PTFC and the HFD groups indicated seven signaling pathways correlated with inflammatory response in the top ten results of the pathway analysis. The TLR/CCL inflammatory signaling pathways played an essential role during liver inflammation in NAFLD mice induced by high-fat diet. Real-time PCR, Western blot and liquid suspension array analysis of the differential gene expression involving the TLR/CCL signaling pathways validated the results of microarray detection.ConclusionPTFC may improve NAFLD by regulating TLR/CCL signaling pathways. Genomic studies provide additional evidence supporting the role of PTFC in the treatment of NAFLD.



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Simvastatin prevents morphine-induced tolerance and dependence in mice

Publication date: September 2017
Source:Biomedicine & Pharmacotherapy, Volume 93
Author(s): Nasim Sadat Pajohanfar, Ehsan Mohebbi, Ahmad Hosseini-Bandegharaei, Mohamadraza Amin, Golnaz Vaseghi, Bahareh Amin
BackgroundTolerance to analgesic effects of opioids and dependence to them are main concerns in the treatment of chronic pain conditions, limiting clinical application of these drugs. This study aimed to evaluate the effect of simvastatin on the morphine-induced tolerance and dependence in mice.Material and methodsFor this purpose, mice were treated with either daily morphine (20 mg/kg, s.c.) alone, or in combination with simvastatin (2.5, 5 and 10mg/kg, i.p.), for 9 continuous days. Antinociceptive effect of morphine was assessed through measuring latency time withdrawal of paw exposed to thermal stimulus, in the hot plate test. Naloxone-precipitated morphine withdrawal (5mg/kg, i.p.), was used for dependence evaluation. Changes in brain gene expression levels of induced nitric oxide synthase (iNOS), astroglia marker, glial fibrillary acidic protein (GFAP), ionized calcium-binding protein (Iba1) a microglia activation marker, a pro-inflammatory mediator and tumor necrosis alpha (TNF-α) were measured after withdrawal by real-time polymerase chain reaction (RT-PCR).ResultsBehavioral tests indicated that latency time increased after morphine treatment in the hot plate test. However, this effect decreased on day 7, demonstrating tolerance to antinociceptive effect of morphine. Reduced anti-nociceptive effect of morphine was returned in animals treated with simvastatin (5 and 10mg/kg) in combination with morphine. Simvastatin (5 and 10mg/kg) attenuated morphine dependence as indicated by a less severe antagonist-precipitated withdrawal syndrome. Administration of naloxone was associated with the increased expression of TNF-α, GFAP, Iba1 and iNOS in the brain samples of morphine dependent mice, while the nine days treatment with both 5 and 10mg/kg simvastatin reduced such changes.ConclusionThe obtained results showed that the protective effects of simvastatin against both tolerance to nociceptive effects of morphine as well as withdrawal-induced behavioral profile are meaningful. Inhibition of glia activity as well as antioxidant effects of pharmaceutical simvastatin further proves its neuroprotective property.

Graphical abstract

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Preclinical evidence of the anxiolytic and sedative-like activities of Tagetes erecta L. reinforces its ethnobotanical approach

Publication date: September 2017
Source:Biomedicine & Pharmacotherapy, Volume 93
Author(s): Gimena Pérez-Ortega, Guadalupe Esther Angeles-López, Arturo Argueta-Villamar, María Eva González-Trujano
Morelos State is one of the regions of Mexico where several plant species are used in traditional medicine. Species from Tagetes genus (Asteraceae) are reported as useful in infusion to treat stomachache and intestinal diseases, but also as tranquilizers. In this study, medicinal uses of T. erecta including its depressant effect on the central nervous system (CNS) were explored by interviewing healers and merchants of local markets of Morelos State, and by investigation of the phytochemical and pharmacological tranquilizing properties. Specific anxiolytic and/or sedative-like responses of different doses of T. erecta (10, 30 and 100 or 300mg/kg, i.p.) were investigated using experimental models in mice such as: open-field, exploration cylinder, hole-board, and the barbituric-induced hypnosis potentiation. The possible anxiolytic mechanism of action was assessed in the presence of WAY100635 (0.32mg/kg, i.p.) and flumazenil (10mg/kg, i.p.), antagonists of 5-HT1A and GABA/BDZs receptors, respectively. Individual flavonoids reported in this species were also evaluated in these experimental models. As a result of this study, healers and merchants from ten local regions of Morelos State recommended T. erecta flowers as an infusion or as a tincture for several culture-bound syndromes associated with CNS, among others. Anxiolytic and sedative-like activities of the T. erecta aqueous and organic polar extracts were corroborated in these models associated to a participation of rutin, kaempferol, quercetin, kaempferitrin, and β-sitosterol constituents; where 5-HT1A, but not BDZs, receptors were involved as anxiolytic mechanism of action. These data support the anxiolytic and sedative-like properties of T. erecta in traditional medicine by involving mainly serotonergic neurotransmission because of the presence in part of flavonoids and the terpenoid β-sitosterol.



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SRPX2, an independent prognostic marker, promotes cell migration and invasion in hepatocellular carcinoma

Publication date: September 2017
Source:Biomedicine & Pharmacotherapy, Volume 93
Author(s): Xiaobo Lin, Weiping Chang, Yuan Wang, Ming Tian, Zhaoxiang Yu
Sushi repeat-containing protein X-linked 2 (SRPX2), a novel chondroitin sulfate proteoglycan, is overexpressed in human cancer. Recent studies have reported that SRPX2 overexpression is observed in gastrointestinal cancer, and promotes migration and invasion of cancer cells. While, the clinical significance and biological function of SRPX2 remain rarely known in hepatocellular carcinoma (HCC). Here, we found that the levels of SRPX2 in HCC tissues were notably overexpressed compared to non-cancerous specimens. Accordingly, the levels of SRPX2 were obviously up-regulated in HCC cells compared with LO2 cells. The positive expression of SRPX2 was prominently correlated with venous infiltration and advanced TNM tumor stage. Furthermore, SRPX2 expression acted as an independent prognostic marker for HCC patients. SRPX2 knockdown prominently inhibited the invasion and migration of HCCLM3 cells, while SRPX2 restoration enhanced these cellular biological behaviors of Hep3B cells in vitro. Moreover, SRPX2 knockdown suppressed pulmonary metastasis of HCCLM3 cells in nude mice. Mechanically, SRPX2 knockdown reduced the levels of phosphorylated focal adhesion kinase (p-FAK), p-AKT, matrix metallopeptidase 2 (MMP2) and MMP9 in HCCLM3 cells. In turn, SRPX2 overexpression promoted the activation of FAK/AKT pathway and increased MMP2/9 expression in Hep3B cells. Thus, SRPX2 contributes to migration and invasion of HCC cells probably by targeting FAK/AKT pathway-mediated MMP2/9 expression. SRPX2 potentially acts as an independent prognostic predictor and a drug-target for HCC patients.



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Chronic pramipexole treatment induces compulsive behavior in rats with 6-OHDA lesions of the substantia nigra and ventral tegmental area

Publication date: 14 August 2017
Source:Behavioural Brain Research, Volume 332
Author(s): D. Dardou, L. Reyrolle, C. Chassain, F. Durif
Dopamine replacement therapy (DRT) reduces motor symptoms in Parkinson's disease (PD), but also induces impulsive–compulsive behavior (ICB) in up to 25% of PD patients. These non-motor side effects of DRT generally follow a gradual transition from impulsive to compulsive-like—i.e. repetitive, compelled, and non-pleasurable—behavior. Here, we investigated the effect of chronic pramipexole (PPX) treatment on the onset of compulsive-like behavior, measured via the post-training signal attenuation (PTSA) procedure, in rats with dopaminergic lesions. Accordingly, we aimed to mimic chronic DRT in a PD context, and obtain data on the brain regions that potentially sustain this type of compulsive behavior pattern in rats. We observed that the lesion or treatment alone did not induce compulsive lever pressing in rats. However, rats with lesions of the substantia nigra and ventral tegmental area as well as with chronic PPX treatment developed strong compulsive lever-pressing behavior, as measured via PTSA. Furthermore, when chronic PPX treatment was discontinued before the PTSA test, the lesioned rats showed the same level of compulsive behavior as sham-operated rats. In fact, lesioned, treated, and compulsive-like rats showed significantly higher Fos expression in the orbitofrontal cortex and dorsal striatum. Thus, chronic PPX treatment in PD rats induced a strong compulsive-like behavior. Furthermore, Fos expression mapping suggests that the behavior was sustained via the activation of the orbitofrontal cortex and dorsal striatum.



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Features of emotional and social behavioral phenotypes of calsyntenin2 knockout mice

Publication date: 14 August 2017
Source:Behavioural Brain Research, Volume 332
Author(s): S.V. Ranneva, K.S. Pavlov, A.V. Gromova, T.G. Amstislavskaya, T.V. Lipina
Calsyntenin-2 (Clstn2) is the synaptic protein that belongs to the super family of cadherins, playing an important role in learning and memory. We recently reported that Clstn2 knockout mice (Clstn2-KO) have a deficit of GABAergic interneurons coupled with hyperactivity and deficient spatial memory. Given, that impaired functioning of GABA receptors is linked to several psychopathologies, including anxiety and autism, we sought to further characterize Clstn2-KO mice with respect to emotional and social behavior. Clstn2-KO males and females were tested in the elevated plus-maze (EPM), open field (OF), forced swim test, social affiliation and recognition test, social transmission of food preference (STFP), dyadic social interactions and marble burying test. Clstn2-KO mice demonstrated high exploration and hyperactivity in the dimly lit EPM that affect anxiety parameters. In contrast, in a more adverse situation in the OF have increased emotionality in Clstn2-KO males, not females. Assessment of hyperactivity for prolong period in the OF showed that Clstn2-KO animals were able to decline their hyperactivity, but their ambulation still remained higher than in WT littermates. Additionally, Clstn2-KO mice expressed stereotyped behavior. Strikingly, analysis of social behavior identified deficient social motivation and social recognition only in Clstn2-KO males, but not in females. Further analysis of social communication in the STFP and direct observation of agonistic interactions confirmed the reduced social behavior in Clstn2-KO males. Altogether, current results showed Clstn2 gene and sex interactions on socio-emotional performance in mice, suggesting a possible role of calsyntenin2 in psychopathological mechanisms of autism.



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Pharmacological inhibition of Anaplastic Lymphoma Kinase rescues spatial memory impairments in Neurofibromatosis 1 mutant mice

Publication date: 14 August 2017
Source:Behavioural Brain Research, Volume 332
Author(s): Joseph B. Weiss, Sydney Weber, Tessa Marzulla, Jacob Raber
Heterozygous Neurofibromatosis 1 (NF1) loss of function mutations are found in 90% of patients with neurofibromatosis, a syndrome associated with disabling cognitive impairment. Drosophila studies have demonstrated a genetic interaction between Anaplastic Lymphoma Kinase (Alk) and NF1 in cognitive performance. In addition, pharmacologic inhibition of Alk improves cognitive performance in heterozygous NF1 mutant flies. In this study, we tested whether pharmacological inhibition of Alk in heterozygous NF1 mutant mice attenuates or rescues cognitive impairments. Cognitive impairment of spatial memory retention observed in heterozygous NF1 mutant mice was rescued by the Alk inhibitor. These data support the hypothesis that inhibition of Alk may cognitively benefit patients with Neurofibromatosis 1.



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Caloric restriction protects livers from ischemia/reperfusion damage by preventing Ca2+-induced mitochondrial permeability transition

Publication date: September 2017
Source:Free Radical Biology and Medicine, Volume 110
Author(s): Sergio L. Menezes-Filho, Ignacio Amigo, Fernanda M. Prado, Natalie C. Ferreira, Marcia K. Koike, Isabella F.D. Pinto, Sayuri Miyamoto, Edna F.S. Montero, Marisa H.G. Medeiros, Alicia J. Kowaltowski
Caloric restriction (CR) promotes lifespan extension and protects against many pathological conditions, including ischemia/reperfusion injury to the brain, heart and kidney. In the liver, ischemia/reperfusion damage is related to excessive mitochondrial Ca²⁺ accumulation, leading to the mitochondrial permeability transition. Indeed, liver mitochondria isolated from animals maintained on CR for 4 months were protected against permeability transition and capable of taking up Ca²⁺ at faster rates and in larger quantities. These changes were not related to modifications in mitochondrial respiratory activity, but rather to a higher proportion of ATP relative to ADP in CR liver mitochondria. Accordingly, both depletion of mitochondrial adenine nucleotides and loading mitochondria with exogenous ATP abolished the differences between CR and ad libitum (AL) fed groups. The prevention against permeability transition promoted by CR strongly protected against in vivo liver damage induced by ischemia/reperfusion. Overall, our results show that CR strongly protects the liver against ischemia/reperfusion and uncover a mechanism for this protection, through a yet undescribed diet-induced change in liver mitochondrial Ca²⁺ handling related to elevated intramitochondrial ATP.

Graphical abstract

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Qualitative and quantitative analysis of peanut adulteration in almond powder samples using multi-elemental fingerprinting combined with multivariate data analysis methods

Publication date: December 2017
Source:Food Control, Volume 82
Author(s): Mahnaz Esteki, Yvan Vander Heyden, Bahman Farajmand, Yadollah Kolahderazi
In this study, adulteration of almond powder samples with peanut was analyzed using multi-elemental fingerprinting based on inductively coupled plasma optical emission measurements (ICP-OES) combined with chemometric methods. The ability of multivariate data analysis approaches, such as principal component analysis (PCA) and principal component analysis-linear discriminant analysis (PCA-LDA), to achieve differentiation of samples and as partial least squares (PLS) and least squares support vector machine (LS-SVM), to quantify the adulteration based on the elemental contents has been investigated. Ten variables i.e. the contents of B, Na, Mg, K, Ca, Fe, Cu, Cu, Zn and Sr at μg g⁻¹ level, determined by ICP-OES were used. Different almond and peanut samples were then mixed at various ratios to obtain mixtures ranging from 95/5 to 5/95 w/w and PCA-LDA was applied to classify the almonds, peanuts and adulterated samples. This method was able to differentiate peanut and almond samples from the adulterated samples. PLS and LS-SVM models were developed to quantify the adulteration ratios of almond using a training set and the constructed models were evaluated using a validation set. The root mean squared error of prediction (RMSEP) and the coefficient of determination (R²) of the validation set for PLS and LS-SVM were 3.81, 0.986 and 1.66, 0.997, respectively, which demonstrates the superiority of the LS-SVM model. The results show that the combination of multi-elemental fingerprinting with multivariate data analysis methods can be applied as an effective and feasible method for testing almond adulteration.



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Adsorption behavior of formaldehyde on ZnO (101¯0) surface: A first principles study

Publication date: 30 November 2017
Source:Applied Surface Science, Volume 423
Author(s): Wentao Jin, Guangde Chen, Xiangyang Duan, Yuan Yin, Honggang Ye, Dan Wang, Jinying Yu, Xuesong Mei, Yelong Wu
In a first principles study of the formaldehyde adsorption on ZnO surface, we found a novel chain adsorption structure on ZnO (101¯0) plane. This adsorption structure results from the electrostatic interactions between those adsorbed formaldehyde molecules and the unique arrangement of Zn-O surface dimers on (101¯0) plane. This adsorption mechanism has the potential to extend to other wurtzite materials' (101¯0) plane and other similar cases. As the physical adsorption configurations are unstable, the chemical adsorption has to happen. The electronic properties show that the CO double bond in CH2O turns into CO single bond and the highest occupied molecule orbital (HOMO) of formaldehyde is lifted into ZnO band gap becoming the hole trapping center. These results may be meaningful for formaldehyde degradation and detection.

Graphical abstract

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Instantaneous voltage as an alternative to power- and phase-based interpretation of oscillatory brain activity

Publication date: 15 August 2017
Source:NeuroImage, Volume 157
Author(s): Gerwin Schalk, Joshua Marple, Robert T. Knight, William G. Coon
For decades, oscillatory brain activity has been characterized primarily by measurements of power and phase. While many studies have linked those measurements to cortical excitability, their relationship to each other and to the physiological underpinnings of excitability is unclear. The recently proposed Function-through-Biased-Oscillations (FBO) hypothesis (Schalk, 2015a, 2015b) addressed these issues by suggesting that the voltage potential at the cortical surface directly reflects the excitability of cortical populations, that this voltage is rhythmically driven away from a low resting potential (associated with depolarized cortical populations) towards positivity (associated with hyperpolarized cortical populations). This view explains how oscillatory power and phase together influence the instantaneous voltage potential that directly regulates cortical excitability. This implies that the alternative measurement of instantaneous voltage of oscillatory activity should better predict cortical excitability compared to either of the more traditional measurements of power or phase. Using electrocorticographic (ECoG) data from 28 human subjects, the results of our study confirm this prediction: compared to oscillatory power and phase, the instantaneous voltage explained 20% and 31% more of the variance in broadband gamma, respectively, and power and phase together did not produce better predictions than the instantaneous voltage. These results synthesize the previously separate power- and phase-based interpretations and associate oscillatory activity directly with a physiological interpretation of cortical excitability. This alternative view has implications for the interpretation of studies of oscillatory activity and for current theories of cortical information transmission.



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Evaluating fibre orientation dispersion in white matter: Comparison of diffusion MRI, histology and polarized light imaging

Publication date: 15 August 2017
Source:NeuroImage, Volume 157
Author(s): Jeroen Mollink, Michiel Kleinnijenhuis, Anne-Marie van Cappellen van Walsum, Stamatios N. Sotiropoulos, Michiel Cottaar, Christopher Mirfin, Mattias P. Heinrich, Mark Jenkinson, Menuka Pallebage-Gamarallage, Olaf Ansorge, Saad Jbabdi, Karla L. Miller
Diffusion MRI is an exquisitely sensitive probe of tissue microstructure, and is currently the only non-invasive measure of the brain's fibre architecture. As this technique becomes more sophisticated and microstructurally informative, there is increasing value in comparing diffusion MRI with microscopic imaging in the same tissue samples. This study compared estimates of fibre orientation dispersion in white matter derived from diffusion MRI to reference measures of dispersion obtained from polarized light imaging and histology.Three post-mortem brain specimens were scanned with diffusion MRI and analyzed with a two-compartment dispersion model. The specimens were then sectioned for microscopy, including polarized light imaging estimates of fibre orientation and histological quantitative estimates of myelin and astrocytes. Dispersion estimates were correlated on region – and voxel-wise levels in the corpus callosum, the centrum semiovale and the corticospinal tract.The region-wise analysis yielded correlation coefficients of r = 0.79 for the diffusion MRI and histology comparison, while r = 0.60 was reported for the comparison with polarized light imaging. In the corpus callosum, we observed a pattern of higher dispersion at the midline compared to its lateral aspects. This pattern was present in all modalities and the dispersion profiles from microscopy and diffusion MRI were highly correlated. The astrocytes appeared to have minor contribution to dispersion observed with diffusion MRI.These results demonstrate that fibre orientation dispersion estimates from diffusion MRI represents the tissue architecture well. Dispersion models might be improved by more faithfully incorporating an informed mapping based on microscopy data.



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The neural basis of form and form-motion integration from static and dynamic translational Glass patterns: A rTMS investigation

Publication date: 15 August 2017
Source:NeuroImage, Volume 157
Author(s): Andrea Pavan, Filippo Ghin, Rita Donato, Gianluca Campana, George Mather
A long-held view of the visual system is that form and motion are independently analysed. However, there is physiological and psychophysical evidence of early interaction in the processing of form and motion. In this study, we used a combination of Glass patterns (GPs) and repetitive Transcranial Magnetic Stimulation (rTMS) to investigate in human observers the neural mechanisms underlying form-motion integration. GPs consist of randomly distributed dot pairs (dipoles) that induce the percept of an oriented stimulus. GPs can be either static or dynamic. Dynamic GPs have both a form component (i.e., orientation) and a non-directional motion component along the orientation axis. GPs were presented in two temporal intervals and observers were asked to discriminate the temporal interval containing the most coherent GP. rTMS was delivered over early visual area (V1/V2) and over area V5/MT shortly after the presentation of the GP in each interval. The results showed that rTMS applied over early visual areas affected the perception of static GPs, but the stimulation of area V5/MT did not affect observers' performance. On the other hand, rTMS was delivered over either V1/V2 or V5/MT strongly impaired the perception of dynamic GPs. These results suggest that early visual areas seem to be involved in the processing of the spatial structure of GPs, and interfering with the extraction of the global spatial structure also affects the extraction of the motion component, possibly interfering with early form-motion integration. However, visual area V5/MT is likely to be involved only in the processing of the motion component of dynamic GPs. These results suggest that motion and form cues may interact as early as V1/V2.

Graphical abstract

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Molecular composition of organic aerosol over an agricultural site in North China Plain: Contribution of biogenic sources to PM2.5

Publication date: September 2017
Source:Atmospheric Environment, Volume 164
Author(s): Xingru Li, Yusi Liu, Dong Li, Guoan Wang, Yu Bai, Heling Diao, Rongrong Shen, Bo Hu, Jinyuan Xin, Zirui Liu, Yuesi Wang, Xueqing Guo, Lili Wang
Sugars and biogenic secondary organic aerosols (BSOAs) are substantial components of particulate organic matter, which affects regional and global air quality and climate. Fine particulate matter (PM2.5) samples were collected from 20 June to 30 July 2015 on a diurnal/nocturnal cycle in Yucheng, China in the North China Plain. The PM2.5 samples were analyzed for sugars and SOA tracers derived from biogenic volatile organic compounds (BVOCs) and other compounds, such as water soluble ions, element carbon (EC), organic carbon (OC) and water soluble organic carbon (WSOC). The quantified organic components accounted for 4.7% and 0.4% of the OC and PM2.5, respectively. SOA tracer concentrations were weakly higher during the day (101.6 ± 61.7 ng m⁻³) than at night (90.2 ± 41.5 ng m⁻³)(t = 0.610, P > 0.05), whereas sugar showed higher concentrations at night (227.0 ± 196.9 ng m⁻³) than during the day (177.9 ± 145.4 ng m⁻³)(t = −1.329, P > 0.05). Anhydro sugar (mannosan, galactosan, and levoglucosan) were the main components of the measured sugars and accounted for 58.5% and 75.6% of the daytime and nighttime measurements. The levoglucosan/mannosan ratios were 20.2 ± 12.9 and 17.6 ± 9.1 for the daytime and nighttime samples, respectively, indicating that crop residues, herbaceous plants and hardwood were the dominant types of biomass burned in the Yucheng region. Isoprene SOA tracers exhibited the highest levels among the measured SOA tracers, followed by α-pinene SOA tracers. The concentration of BSOC estimated using the tracer method was 3.9–1817.5 ng C m⁻³ and accounted for 0.1–26.0% of the OC. A clear negative correlation (r = 0.53) between isoprene-derived SOA and in-situ pH demonstrated that acid-catalyzed heterogeneous reactions can significantly enhance SOA mass. In addition, isoprene-derived SOA increased with the relative humidity (RH) when the RH was lower than 50%, whereas it decreased when the RH was higher than 50%.



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Ultra-sensitive suspended atomically thin-layered black phosphorus mercury sensors

Publication date: 15 December 2017
Source:Biosensors and Bioelectronics, Volume 98
Author(s): Peng Li, Dongzhi Zhang, Chuanxing Jiang, Xiaoqi Zong, Yuhua Cao
The extraordinary properties of black phosphorus (BP) make it a promising candidate for next-generation transistor chemical sensors. However, BP films reported so far are supported on substrate, and substrate scattering drastically deteriorates its electrical properties. Consequentially, the potential sensing capability of intrinsic BP is highly underestimated and its sensing mechanism is masked. Additionally, the optimum sensing regime of BP remains unexplored. This article is the first demonstration of suspended BP sensor operated in subthreshold regime. BP exhibited significant enhancement of sensitivity for ultra-low-concentration mercury detection in the absence of substrate, and the sensitivity reached maximum in subthreshold regime. Without substrate scattering, the suspended BP device demonstrated 10 times lower 1/f noise which contributed to better signal-to-noise ratio. Therefore, rapid label-free trace detection of Hg²⁺ was achieved with detection limit of 0.01 ppb, lower than the world health organization (WHO) tolerance level (1 ppb). The time constant for ion detection extracted was 3s. Additionally, experimental results revealed that good stability, repeatability, and selectivity were achieved. BP sensors also demonstrated the ability of detecting mercury ions in environment water samples. The underling sensing mechanism of intrinsic BP was ascribed to the carrier density variation resulted from surface charge gating effect, so suspended BP in subthreshold regime with optimum gating effect demonstrated the best sensitivity. Our results show the prominent advantages of intrinsic BP as a sensing material.



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Bimetallic Pt–Au nanocatalysts electrochemically deposited on boron-doped diamond electrodes for nonenzymatic glucose detection

Publication date: 15 December 2017
Source:Biosensors and Bioelectronics, Volume 98
Author(s): Siriwan Nantaphol, Takeshi Watanabe, Naohiro Nomura, Weena Siangproh, Orawon Chailapakul, Yasuaki Einaga
The enormous demand for medical diagnostics has encouraged the fabrication of high- performance sensing platforms for the detection of glucose. Nonenzymatic glucose sensors are coming ever closer to being used in practical applications. Bimetallic catalysts have been shown to be superior to single metal catalysts in that they have greater activity and selectivity. Here, we demonstrate the preparation, characterization, and electrocatalytic characteristics of a new bimetallic Pt/Au nanocatalyst. This nanocatalyst can easily be synthesized by electrodeposition by sequentially depositing Au and Pt on the surface of a boron-doped diamond (BDD) electrode. We characterized the nanocatalyst by scanning electron microscopy (SEM), X-ray diffraction (XRD), and voltammetry. The morphology and composition of the nanocatalyst can be easily controlled by adjusting the electrodeposition process and the molar ratio between the Pt and Au precursors. The electrocatalytic characteristics of a Pt/Au/BDD electrode for the nonenzymatic oxidation of glucose were systematically investigated by cyclic voltammetry. The electrode exhibits higher catalytic activity for glucose oxidation than Pt/BDD and Au/BDD electrodes. The best catalytic activity and stability was obtained with a Pt:Au molar ratio of 50:50. Moreover, the presence of Au can significantly enhance the long-term stability and poisoning tolerance during the electro-oxidation of glucose. Measurements of glucose using the Pt/Au/BDD electrode were linear in the range from 0.01 to 7.5mM, with a detection limit of 0.0077mM glucose. The proposed electrode performs selective electrochemical analysis of glucose in the presence of common interfering species (e.g., acetaminophen, uric and ascorbic acids), avoiding the generation of overlapping signals from such species.



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Glucose oxidase-initiated cascade catalysis for sensitive impedimetric aptasensor based on metal-organic frameworks functionalized with Pt nanoparticles and hemin/G-quadruplex as mimicking peroxidases

Publication date: 15 December 2017
Source:Biosensors and Bioelectronics, Volume 98
Author(s): Xingxing Zhou, Shijing Guo, Jiaxi Gao, Jianmin Zhao, Shuyan Xue, Wenju Xu
Based on cascade catalysis amplification driven by glucose oxidase (GOx), a sensitive electrochemical impedimetric aptasensor for protein (carcinoembryonic antigen, CEA as tested model) was proposed by using Cu-based metal-organic frameworks functionalized with Pt nanoparticles, aptamer, hemin and GOx (Pt@CuMOFs-hGq-GOx). CEA aptamer loaded onto Pt@CuMOFs was bound with hemin to form hemin@G-quadruplex (hGq) with mimicking peroxidase activity. Through sandwich-type reaction of target CEA and CEA aptamers (Apt1 and Apt2), the obtained Pt@CuMOFs-hGq-GOx as signal transduction probes (STPs) was captured to the modified electrode interface. When 3,3-diaminobenzidine (DAB) and glucose were introduced, the cascade reaction was initiated by GOx to catalyze the oxidation of glucose, in situ generating H2O2. Simultaneously, the decomposition of the generated H2O2 was greatly promoted by Pt@CuMOFs and hGq as synergistic peroxide catalysts, accompanying with the significant oxidation process of DAB and the formation of nonconductive insoluble precipitates (IPs). As a result, the electron transfer in the resultant sensing interface was effectively hindered and the electrochemical impedimetric signal (EIS) was efficiently amplified. Thus, the high sensitivity of the proposed CEA aptasensor was successfully improved with 0.023pgmL⁻¹, which may be promising and potential in assaying certain clinical disease related to CEA.



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Cellular Mechanisms of Peroxynitrite-Induced Neuronal Death

Publication date: Available online 24 June 2017
Source:Brain Research Bulletin
Author(s): Kristina Ramdial, Maria Clara Franco, Alvaro G. Estevez
Peroxynitrite (ONOO⁻) is a strong biological oxidant formed by the diffusion-limited reaction of nitric oxide (NO⁻) and superoxide anion (O2⁻). It has long been theorized that peroxynitrite generation could be the cause in a number of pathological conditions ranging from atherosclerosis to inflammatory, autoimmune, heart and neurodegenerative diseases. Its relatively long biological half-life and high reactivity allows peroxynitrite to oxidize a number of different targets in the cell. In physiologically relevant conditions peroxynitrite can directly react with thiols, or the radical products of peroxynitrite decomposition may indirectly oxidize other cellular components such as lipids, proteins and DNA. Downstream, oxidative modifications caused by peroxynitrite trigger cell death by a variety of mechanisms depending on the concentration of the oxidant. Peroxynitrite stimulates necrosis, apoptosis, autophagy, parthanatos and necroptosis. Here we review the mechanisms activated by peroxynitrite to cause neuronal death.



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The effect of monascin on hematoma clearance and edema after intracerebral hemorrhage in rats

Publication date: Available online 24 June 2017
Source:Brain Research Bulletin
Author(s): Juan Wang, Gaiqing Wang, Jinying Yi, Yi Xu, Shuna Duan, Tong Li, Xin-gang Sun, Liang Dong
Background and PurposeIntracerebral hemorrhage (ICH) is a particularly devastating form of stroke with high mortality and morbidity. Hematomas are the primary cause of neurologic deficits associated with ICH. The products of hematoma are recognized as neurotoxins and the main contributors to edema formation and tissue damage after ICH. Finding a means to efficiently promote absorption of hematoma is a novel clinical challenge for ICH. Peroxisome proliferator-activated receptor gamma (PPARγ) and nuclear factor erythroid 2-related factor 2 (Nrf2), had been shown that, can take potential roles in the endogenous hematoma clearance. However, monascin, a novel natural Nrf2 activator with PPARγ agonist, has not been reported to play a role in ICH. This study was designed to evaluate the effect of monascin on neurological deficits, hematoma clearance and edema extinction in a model of ICH in rats.Methods164 adult male Sprague-Dawley (SD) rats were randomly divided into sham; vehicle; monascin groups with low dosages (1mg/kg/day), middle dosages (5mg/kg/day) and high dosages (10mg/kg/day) respectively. Animals were euthanized at 1, 3 and 7days following neurological evaluation after surgery. We examined the effect of monascin on the brain water contents, blood brain barrier (BBB) permeability and hemoglobin levels, meanwhile reassessed the volume of hematoma and edema around the hematoma by Magnetic Resonance Imaging (MRI) in each group.ResultsThe high dosage of monascin significantly improved neurological deficits, reduced the volume of hematoma in 1–7days after ICH, decreased BBB permeability and edema formation in 1–3days following ICH.ConclusionOur study demonstrated that the high dosage of monascin played a neuroprotective role in ICH through reducing BBB permeability, edema and hematoma volume.



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Health Anxiety and Medical Utilization: The Moderating Effect of Age among Patients in Primary Care

Publication date: Available online 24 June 2017
Source:Journal of Anxiety Disorders
Author(s): Thomas A. Fergus, Jackson O. Griggs, Scott C. Cunningham, Lance P. Kelley
Health anxiety is commonly seen in medical clinics and is related to the overutilization of primary care services, but existing studies have not yet considered the possible moderating effect of age. We examined if age moderated the association between health anxiety and medical utilization. A secondary aim was to examine potential racial/ethnic differences in health anxiety. An ethnoracially diverse group of patients (N=533) seeking treatment from a primary care clinic completed a self-report measure of health anxiety. Three indices of medical utilization were assessed using medical records, including the number of: (a) clinic visits over the past two years, (b) current medications, and (c) lab tests over the past two years. Age moderated the effect of health anxiety on multiple indices of medical utilization. Supplemental analyses found that the moderating effect of age was specific to a somatic/body preoccupation, rather than health worry, dimension of health anxiety. Mean-level differences in health anxiety were either not supported (health anxiety composite, somatic/body preoccupation) or were small in magnitude (health worry) among self-identifying Black, Latino, and White participants. Results indicate that assessing for health anxiety could be particularly important for older adult patients who frequently seek out medical services.



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The Emerging Zika Virus Threat: A Guide for Dermatologists

What should dermatologists be alert for when encountering patients with a rash and clinical history suggestive of Zika virus infection?
American Journal of Clinical Dermatology

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Leaching of phthalate esters from different drinking stuffs and their subsequent biodegradation

Abstract

Phthalate esters (PAEs) are mainly used as plasticizers, and their release in the environment during the manufacturing, use, and disposal has caused serious environmental health concerns, since some of them are suspected to be mutagens, hepatotoxic agents, and carcinogens. In the present study, leaching of PAEs from different drinking stuffs (water cooler, mineral water bottles) exposed to sunlight and baby feeders subjected to different heating treatments (boiling, autoclave and oven) was studied. Results showed that a total of 10 PAEs were leached and identified. Among them, dimethyl phthalate, bis(2-methoxyethyl) phthalate, diethyl phthalate, and dibutyl phthalate were the major leached PAEs found in the range 9–112.50 μg L⁻¹. Boiling treatment was found safer for baby feeders as PAE leaching was ~26–54% less as compared to other two treatments. The leached PAEs in water samples were then subjected to biodegradation experiment with Bacillus thuringiensis strain at optimized conditions (time 72 h and 30 °C). Hence, leaching of hazardous PAEs from different water stuffs is alarming and needs immediate attention. Moreover, B. thuringiensis strain was found effective for PAE remediation (75–96% degradation) at neutral pH.

Graphical abstract

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A large choledochocystolithiasis mimicking Mirizzi syndrome

An 18-year-old man presented with spontaneous severe epigastric pain, progressing and radiating to back since 3 days. It was associated with epigastric tenderness, bilious vomiting and jaundice. He had been intermittently experiencing these symptoms for the last 1 year. No known comorbid. Ultrasound showed a poorly visualised heterogeneous focus at porta hepatis; considering poor visualisation, this might represent an enlarged calcified lymph node or cystic duct calculus causing extrinsic compression or a large sludge ball within the common bile duct (CBD), leading to dilatation of common hepatic duct and intrahepatic biliary system. Subsequent magnetic resonance cholangiopancreatography revealed a focal saccular dilatation of middle part of CBD, a type I-B choledochal cyst, large heterogeneous focus seen within it representing choledochocystolithiasis. Later, CT was performed for further characterisation of surrounding anatomy and pathology, which confused the appearance of choledochocystolithiasis for Mirizzi syndrome. Later, surgery and histopathology confirmed type I-B choledochocystolithiasis and chronic cholecystitis.

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Bilateral recurrent pyosalpinx in a sexually inactive 12-year-old girl secondary to rare variant of Mullerian duct anomaly

Pyosalpinx is a severe sequel of chronic pelvic inflammatory disease, whereby the fallopian tubes become filled with pus.^{1 2} Pyosalpinx often affects sexually active women and rarely is seen in celibate adolescent girls.³ We report a case of a 12-year-old girl with no prior sexual history who presented to our emergency department with complaints of severe right lower quadrant pain of 1-day duration. Ultrasonography and CT scan of the abdomen and pelvis revealed free fluid collections in the pelvis without visualisation of the appendix. A preoperative diagnosis of acute ruptured appendicitis was given and she was taken to the operating room. Peroperative findings included bilaterally distended, pus-filled pyosalpinges. A definitive diagnosis of bilateral pyosalpinx was then made. Two-week antibiotic therapy was successful but the patient returned with recurrent pyosalpinx and a pelvic abscess 9 weeks later.

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Paget's Disease of the Temporal Bone: A Single-Institution Contemporary Review of 27 Patients

Objectives: To report a contemporary review from a single-institution series on Paget's disease of the temporal bone (PDTB). Study Design: Retrospective chart review of patients evaluated from 1998 to 2016. Setting: Quaternary referral center. Patients: Patients with radiographically confirmed PDTB. Main Outcome Measures: Clinical, audiological, and radiological features and management strategies of PDTB. Results: A total of 50 temporal bones in 27 patients (15 men) were diagnosed with PDTB. Symptoms at presentation included hearing loss (n = 23, 85%), headache (n = 18, 67%), dizziness (n = 14, 52%), tinnitus (n = 5, 19%), chronic otitis media (n = 2, 7%), hemifacial spasm without facial paralysis (n = 1, 4%), multiple cranial neuropathies (n = 1, 4%), and neoplastic transformation (n = 1, 4%). Of the 23 ears with audiometric data available for review, 65% exhibited sensorineural hearing loss, and 35% mixed hearing loss. Long-term audiometric follow-up was available on two patients, both of whom demonstrated hearing loss at a rate greater than would be expected for normal aging. Two patients underwent successful cochlear implantation, achieving open-set speech recognition. Radiographic features of temporal bone involvement are reviewed and illustrated. Conclusion: This is the largest single-institution clinical series examining patients with PDTB in the English literature. Variable patterns of temporal bone involvement by Paget's disease are observed leading to a diverse set of clinical symptoms, including slowly progressive hearing loss, tinnitus, compressive cranial neuropathies, and benign or malignant tumorigenesis. Involvement typically begins in the petrous apex and progresses laterally. Otic capsule bone demineralization occurs late in the disease process. Cochlear implantation appears to be an effective management strategy for patients with severe-to-profound hearing loss.

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The Normal Adult Human Internal Auditory Canal: A Volumetric Multidetector Computed Tomography Study

Objective: The purpose of this study was to demonstrate that volumetric analysis of multidetector computed tomography (CT) images can be used to calculate the volume of the adult human internal auditory canal (IAC) reproducibly, and to describe the range of normal IAC volumes in the adult population with subgroup analysis of sex, age, and laterality. Background: Previous studies of the IAC have typically used measurements in two dimensions or by using casts of cadavers to measure IAC volumes. This study is the first to report the normal ranges of IAC volumes measured by CT. Methods: Two hundred eighty-one CT scans were assessed. Of the CT scans that met the inclusion criteria, a software package was used to manually contour the IACs in each subject to calculate the volumes in cubic millimeters. Subgroup analysis of laterality, sex, and age was evaluated. Interobserver agreement was calculated for the first 59 patients (118 canals). Results: Two hundred fifty-nine scans (518 canals) met the inclusion criteria. The volumes ranged from 74 to 502 mm3, with no statistically significant difference between left and right (p value = 0.69). In males, the range of volumes measured 74 to 502 mm3 while in females it ranged from 78 to 416 mm3. Males had larger IAC volumes than females (Wilcoxon rank-sum test: S = 14,845.0, p value = 0.01 on the right, and S = 14,646, p value = 0.004 on the left). No correlation was found with age (Spearman: −0.10, p value = 0.09 on the right and −0.04, p value = 0.50 on the left). Excellent interobserver agreement was found. Conclusion: IAC volumes of normal adult subjects, measured by CT, were larger in males and not significantly different with respect to age or laterality.

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Surgical Management of a Persistent Stapedial Artery: A Review

Objective: To evaluate the outcome and per- and postoperative complications of the surgical management of patients with a persistent stapedial artery (PSA). Methods: A systemic literature search for reports on patients treated for pulsatile tinnitus and/or conductive hearing loss caused by a PSA was conducted of the PubMed and Embase databases using the terms "stapedial" and "artery." Inclusion criteria were adequate description of the intervention and pre- and postoperative signs and symptoms. In addition, one case of a PSA, treated at VU University Medical Center Amsterdam, The Netherlands, was included in this series. Intervention: Middle ear surgery consisting of stapedotomy or stapedectomy, and/or transection of the PSA. Main Outcome Measures: Pre- and postoperative hearing levels, pre- and postoperative pulsatile tinnitus, and per- and postoperative complications. Results: Seventeen patients and 18 operated ears were evaluated (16 patients described in 14 articles and our case). Twelve out of 14 ears in which a stapedotomy or stapedectomy was initiated experienced improvement in hearing. In four cases pulsatile tinnitus was described pre- and postoperatively. In all four, pulsatile tinnitus subsided after transection of the PSA. Peroperative bleeding from the PSA was described in four patients, which could be controlled during the procedure. No significant postoperative sequelae were reported. Conclusions: In case of a PSA, improvement of conductive hearing loss is best achieved by stapes surgery, while pulsatile tinnitus is effectively treated with transection of the PSA. To date no long-term postoperative complications have been reported.

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Preliminary Model for the Design of a Custom Middle Ear Prosthesis

Hypothesis: Custom prostheses could be used to recreate the ossicular chain and improve hearing. Background: Ossicular discontinuity or fixation occurs in 55% of cases of conductive hearing loss, with most cases involving the incus. Reconstruction has been achieved by a variety of methods; however, there has been little improvement in hearing outcomes in decades. Methods: Precise measurements of anatomic dimensions, weight, and center of gravity were taken from 19 cadaveric incudes. These measurements were combined with measurements from the medical literature and micro-computed tomography (micro-CT) of cadaveric temporal bones to generate a rasterizable incus model. As a proof of concept, incudal replacements including possible anatomic variations were then three-dimensionally (3-D) printed and inserted into a cadaveric temporal bone. Results: Our measurements of cadaveric incudes corresponded well with those from the medical literature. These measurements were combined with anatomical information from micro-CT allowing identification of critical features of the incus, which remained constant. Other model features were modified to increase stability and facilitate synthesis, including broadening and thickening of the lenticular process and the incudomalleolar articulation. 3-D printed incudal replacements based on this model readily fit into a cadaveric temporal bone and successfully bridged the gap between malleus and incus. Conclusion: We have generated a model for custom 3-D synthesis of incudal prostheses. While current 3-D printing in biocompatible materials at the size required is limited, the technology is rapidly advancing, and 3-D printing of incudal replacements with polylactic acid (PLA) is of the correct size and shape.

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Intra- and Interobserver Variability of Cochlear Length Measurements in Clinical CT

Hypothesis: The cochlear A-value measurement exhibits significant inter- and intraobserver variability, and its accuracy is dependent on the visualization method in clinical computed tomography (CT) images of the cochlea. Background: An accurate estimate of the cochlear duct length (CDL) can be used to determine electrode choice, and frequency map the cochlea based on the Greenwood equation. Studies have described estimating the CDL using a single A-value measurement, however the observer variability has not been assessed. Methods: Clinical and micro-CT images of 20 cadaveric cochleae were acquired. Four specialists measured A-values on clinical CT images using both standard views and multiplanar reconstructed (MPR) views. Measurements were repeated to assess for intraobserver variability. Observer variabilities were evaluated using intra-class correlation and absolute differences. Accuracy was evaluated by comparison to the gold standard micro-CT images of the same specimens. Results: Interobserver variability was good (average absolute difference: 0.77 ± 0.42 mm) using standard views and fair (average absolute difference: 0.90 ± 0.31 mm) using MPR views. Intraobserver variability had an average absolute difference of 0.31 ± 0.09 mm for the standard views and 0.38 ± 0.17 mm for the MPR views. MPR view measurements were more accurate than standard views, with average relative errors of 9.5 and 14.5%, respectively. Conclusion: There was significant observer variability in A-value measurements using both the standard and MPR views. Creating the MPR views increased variability between experts, however MPR views yielded more accurate results. Automated A-value measurement algorithms may help to reduce variability and increase accuracy in the future.

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Imaging Criteria to Predict Surgical Difficulties During Stapes Surgery

Background and Purpose: Stapes surgery for otosclerosis can be challenging if access to the oval window niche is restricted. The aim of this study was to determine the accuracy of the computed tomographic (CT) scan in the evaluation of anatomical distances, and to analyze its reliability in predicting surgical technical difficulties. Material and Methods: A total of 96 patients (101 ears) were enrolled in a prospective study between 2012 and May 2015. During surgery, we evaluated the distance D1 between the stapes and the facial nerve, distance D2 between the promontory and the facial nerve after ablation of the superstructure, and the intraoperative discomfort of the surgeon. On preoperative CT scans, we measured the width and depth of the oval window niche, and the angle formed by two axes starting from the center-point of the footplate, the first tangential to the superior wall of the promontory, and the second tangential to the inferior wall of the fallopian canal. Results: Intraoperative distances D1 and D2 were correlated with the width of the oval window and with the facial-promontory angle measured on imaging. CT scan measurements of the facial-promontory angle and width of the oval window were associated with the degree of discomfort of the surgeon. The cut-off threshold for intraoperative subjective discomfort was computed as 1.1 mm for the width of the oval window niche, with a sensibility of 71% and a specificity of 84%. Conclusion: Preoperative imaging analysis of the oval window width and the facialpromontory angle can predict operative difficulty in otosclerosis surgery.

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Pilot Electroacoustic Analyses of a Sample of Direct-to-Consumer Amplification Products

Objective: Recent national initiatives from the White House and Institute of Medicine have focused on strategies to increase the accessibility and affordability of hearing loss treatment given the average cost of $4700 for bilateral hearing aids. More affordable direct-to-consumer hearing technologies are increasingly gaining recognition, but the performance of these devices has been poorly studied. We investigated the technical and electroacoustic capabilities of several direct-to-consumer hearing devices to inform otolaryngologists who may be asked by patients to comment on these devices. Patients/Intervention: Nine direct-to-consumer hearing devices ranging in retail cost from $144.99 to $395.00 and one direct-to-consumer hearing device with a retail cost of $30.00. Main Outcome Measure: Electroacoustic results and simulated real-ear measurements. Main electroacoustic measures are frequency response, equivalent input noise, total harmonic distortion, and maximum output sound pressure level at 90 dB. Results: Five devices met all four electroacoustic tolerances presented in this study, two devices met three tolerances, one device met two tolerances, one device met one tolerance, and one device did not meet any tolerances. Nine devices were able to approximate five of nine National Acoustics Laboratories (NAL) targets within 10 dB while only three devices were able to approximate five of nine NAL targets within a more stringent 5 dB. Conclusion: While there is substantial heterogeneity among the selection of devices, certain direct-to-consumer hearing devices may be able to provide appropriate amplification to persons with mild-to-moderate hearing loss and serve as alternatives for hearing aids in specific cases.

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Transcanal Endoscopic Ear Surgery for Excision of a Facial Nerve Venous Malformation With Interposition Nerve Grafting: A Case Report

Objective: To illustrate a novel approach for the surgical management of a venous malformation of the facial nerve, including interposition nerve grafting, via an exclusively transcanal endoscopic ear surgery (TEES) approach. Patient: Thirty nine-year-old woman with a preoperative House–Brackmann (HB) grade IV facial paresis secondary to a facial nerve tumor. Intervention(s): Surgical excision and interposition nerve graft via a transcanal endoscopic approach. Main Outcome Measure(s): Completeness of resection, approach morbidities, and facial nerve outcome. Results: The TEES approach provided wide exposure of the facial nerve from the geniculate ganglion through the mastoid segment. This visualization facilitated gross total tumor resection, incus interposition ossicular reconstruction, and placement of an interposition nerve graft. The nerve graft was positioned in the fallopian canal and was secured at both ends with surgicel. The patient had no postoperative complications. At 11-month follow-up her facial function had returned to HB grade IV. Conclusions: This is the first report of resecting a venous malformation of the facial nerve with concomitant interposition nerve graft reconstruction via an exclusively endoscopic approach. This report adds to the growing body of evidence that TEES can manage diverse middle ear and lateral skull base pathology. Additional studies are needed to fully elucidate the risk-benefit profile of this technique.

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Endoscopic Infracochlear Approach for Drainage of Petrous Apex Cholesterol Granulomas: A Case Series

Objective: To describe the feasibility and technical nuances of a transcanal endoscopic infracochlear approach for drainage of petrous apex cholesterol granulomas. Study Design: Retrospective case review. Setting: Tertiary care university hospital. Patients: A 32-year-old man with bilateral petrous apex cholesterol granulomas and a 54-year-old man with a left-sided petrous apex granuloma each with symptoms necessitating surgical intervention. Interventions: Transcanal endoscopic infracochlear approach for drainage of the cholesterol granulomas. Main Outcome Measures: Operation efficacy, corridor size, and perioperative morbidity. Results: All three cholesterol granulomas were successful drained without violating the cochlea, jugular bulb, or carotid artery. The dimensions of the infracochlear surgical corridor measured 5 mm × 6 mm, 3.5 mm × 3.5 mm, and 6 mm × 4 mm, respectively. All corridors facilitated visualization within the cyst and allowed lyses of adhesions for additional cyst content eradication. All patients had resolution of their acute symptoms. Two of the three subjects had serviceable hearing before and after their procedures. One patient required revision surgery 2-months after their initial procedure secondary to recurrent symptoms from acute hemorrhage within the cyst cavity. The infracochlear tract in this patient was noted to be patent. Conclusions: A transcanal endoscopic infracochlear approach is feasible for the management of cholesterol granuloma. The surgical access was wide enough to introduce the endoscope into the petrous apex cavity in each case. Further studies are needed to compare the efficacy and perioperative morbidity versus the traditional postauricular transtemporal approaches.

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Epidemiology of Dizzy Patient Population in a Neurotology Clinic and Predictors of Peripheral Etiology

Objective: To compare the proportion of peripheral versus nonperipheral dizziness etiologies among all patients, inclusive of those presenting primarily or as referrals, to rank diagnoses in order of frequency, to determine whether or not age and sex predict diagnosis, and to determine which subgroups tended to undergo formal vestibular testing. Study Design: Retrospective cohort. Setting: Academic neurotology clinic. Patients: Age greater than 18 neurotology clinic patients with the chief complaint of dizziness. Intervention(s): None. Main Outcome Measure(s): Age, sex, diagnosis, record of vestibular testing. Results: Two thousand seventy-nine patients were assigned 2,468 diagnoses, of which 57.7 and 42.3% were of peripheral and nonperipheral etiologies, respectively. The most common diagnoses were Ménière's (23.0%), vestibular migraine (19.3%), benign paroxysmal positional vertigo (BPPV) (19.1%), and central origin, nonmigraine (16.4%). Peripheral diagnoses are more likely to be found in men than in women (odds ratio [OR] 1.59). Peripheral diagnoses were most likely to be found in the 60 to 69 age group (OR 3.82). There was not a significant difference in rate of vestibular testing between women and men. Among patients with two diagnoses, the most common combinations were vestibular migraine and BPPV then vestibular migraine and Ménière's. Conclusions: A large proportion of patients seen for the chief complaint of dizziness in the neurotology clinic were found not to have a peripheral etiology of their symptoms. These data challenge a prevalent dogma that the most common causes of dizziness are peripheral: BPPV, vestibular neuritis, and Ménière's disease. Age and sex are statistically significant predictors of peripheral etiology of dizziness.

http://ift.tt/2rHFJo6

Progression of Unilateral Hearing Loss in Children With and Without Ipsilateral Cochlear Nerve Canal Stenosis: A Hazard Analysis

Objective: To investigate the risk of hearing loss progression in each ear among children with unilateral hearing loss associated with ipsilateral bony cochlear nerve canal (BCNC) stenosis. Setting: Tertiary pediatric referral center. Patients: Children diagnosed with unilateral hearing loss who had undergone temporal bone computed tomography imaging and had at least 6 months of follow-up audiometric testing were identified from a prospective audiological database. Interventions: Two pediatric radiologists blinded to affected ear evaluated imaging for temporal bone anomalies and measured bony cochlear canal width independently. All available audiograms were reviewed, and air conduction thresholds were documented. Main Outcome Measure: Progression of hearing loss was defined by a 10 dB increase in air conduction pure-tone average. Results: One hundred twenty eight children met inclusion criteria. Of these, 54 (42%) had a temporal bone anomaly, and 22 (17%) had ipsilateral BCNC stenosis. At 12 months, rates of progression in the ipsilateral ear were as follows: 12% among those without a temporal bone anomaly, 13% among those with a temporal bone anomaly, and 17% among those with BCNC stenosis. Children with BCNC stenosis had a significantly greater risk of progression in their ipsilateral ear compared with children with no stenosis: hazard ratio (HR) 2.17, 95% confidence interval (CI) (1.01, 4.66), p value 0.046. When we compared children with BCNC stenosis to those with normal temporal bone imaging, we found that the children with stenosis had nearly two times greater risk estimate for progression, but this difference did not reach significance, HR 1.9, CI (0.8, 4.3), p = 0.1. No children with BCNC stenosis developed hearing loss in their contralateral year by 12 months of follow-up. Conclusion: Children with bony cochlear nerve canal stenosis may be at increased risk for progression in their ipsilateral ear. Audiometric and medical follow-up for these children should be considered.

http://ift.tt/2rSL22k

Single-Center Study Investigating Foreign Language Acquisition at School in Children, Adolescents, and Young Adults With Uni- or Bilateral Cochlear Implants in the Swiss German Population

Objective: To evaluate foreign language acquisition at school in cochlear implant patients. Study Design: Cohort study. Setting: CI center. Patients: Forty three cochlear implants (CI) patients (10–18 yr) were evaluated. CI nonusers and patients with CI-explantation, incomplete datasets, mental retardation, or concomitant medical disorders were excluded. Intervention(s): Additional data (type of schooling, foreign language learning, and bilingualism) were obtained with questionnaires. German-speaking children with foreign tuition language (English and/or French) at school were enrolled for further testing. Main Outcome Measure(s): General patient data, auditory data, and foreign language data from both questionnaires and tests were collected and analyzed. Results: Thirty seven out of 43 questionnaires (86%) were completed. Sixteen (43%) were in mainstream education. Twenty-seven CI users (73%) have foreign language learning at school. Fifteen of these were in mainstream education (55%), others in special schooling. From 10 CI users without foreign language learning, one CI user was in mainstream education (10%) and nine patients (90%) were in special schooling. Eleven German-speaking CI users were further tested in English and six additionally in French. For reading skills, the school objectives for English were reached in 7 of 11 pupils (64%) and for French in 3 of 6 pupils (50%). For listening skills, 3 of 11 pupils (27%) reached the school norm in English and none in French. Conclusions: Almost 75% of our CI users learn foreign language(s) at school. A small majority of the tested CI users reached the current school norm for in English and French in reading skills, whereas for hearing skills most of them were not able to reach the norm.

http://ift.tt/2rU6cgu

Cochlear Implantation in Adults With Asymmetric Hearing Loss: Benefits of Bimodal Stimulation

Objective: This study addresses the outcome of cochlear implantation in addition to hearing aid use in patients with asymmetric sensorineural hearing loss. Study Design: Prospective longitudinal study. Setting: Tertiary referral center. Patients: Seven adults with asymmetric sensorineural hearing loss, i.e., less than 30% aided speech recognition in their worst hearing ear and 60 to 85% speech recognition in their best hearing ear. All patients had a postlingual onset of their hearing loss and less than 20 years of auditory deprivation of their worst hearing ear. Intervention: Cochlear implantation in the functionally deaf ear. Main Outcome Measures: Speech recognition in quiet, speech recognition in noise, spatial speech recognition, localization abilities, music appreciation, and quality of life. Measurements were performed before cochlear implantation and 3, 6, and 12 months after cochlear implantation. Results: Before cochlear implantation, the average speech recognition of the ear fitted with a hearing aid was 74%. Cochlear implantation eventually resulted in an average speech recognition of 75%. Bimodal stimulation yielded speech recognition scores of 82, 86, and 88% after 3, 6, and 12 months, respectively. At all time intervals, bimodal stimulation resulted in a significantly better speech recognition as compared with stimulation with only hearing aid or only cochlear implant (CI). Speech recognition in noise and spatial speech recognition significantly improved as well as the ability to localize sounds and the quality of life. Conclusion: This study demonstrated that patients are able to successfully integrate electrical stimulation with contralateral acoustic amplification and benefit from bimodal stimulation. Therefore, we think that cochlear implantation should be considered in this particular group of patients, even in the presence of substantial residual hearing on the contralateral side.

http://ift.tt/2rStdR8

Alterations in soil microbial communities caused by treatments with penicillin or neomycin

Abstract

Antibiotic residues in soils can lead to serious health risk and ecological hazards. In this study, the effects of penicillin and neomycin, two antibiotics widely used in animal production, were investigated on soil bacterial communities. Changes in the community structure were monitored using three 16S ribosomal DNA (rDNA) polymerase chain reaction-based approaches, including denaturing gradient gel electrophoresis (DGGE), amplified rDNA restriction analysis (ARDRA), and terminal-restriction fragment length polymorphism (T-RFLP) analysis. The prominent DGGE bands were excised from gels and sequenced, and the data indicated the prevalence of Gammaproteobacteria in the soils. The total soil bacterial community, including uncultured bacteria, exhibited a higher diversity than that of cultured bacteria. Some microbial strains were capable of surviving and even subsisting on penicillin or neomycin. We also observed toxic effects of the antibiotics on the indigenous soil bacterial communities since some genotypes disappeared after the treatments (e.g., Pseudomonas sp., Stenotrophomonas sp., Salinimonas, and uncultured Acinetobacter sp.). The implications of these findings are that the functions of soil bacterial communities may be negatively affected if key microbial community members are lost.

http://ift.tt/2s8WTrv

Disposal of household pharmaceuticals in insular communities: social attitude, behaviour evaluation and prevention activities

Abstract

The increase in medicine and drug consumption have resulted in identifying these emerging pollutants in all aquatic compartments, ranging from surface water and groundwater resources to the marine environment. Pharmaceuticals are an indispensable part of life today. A large number of pharmaceuticals are used in a daily basis in the treatment, prevention, cure or diagnosis of diseases or to otherwise enhance people's physical or mental well-being. This paper focuses on the evaluation of the attitude of citizens in Cyprus regarding the disposal of pharmaceuticals as well as to identify the main reasons why pharmaceutical wastes are produced. The result indicted that in Cyprus, there is lack of data regarding the amount of pharmaceutical wastes that are discarded into household waste and sinks. The survey audit showed that 86.6% of men's and 83.3% of women's used pharmacy with or without doctor's recipe. Social behaviour is considered to be the most significant reason that pharmaceutical are produced. The results indicated that, citizens mainly keep unused medicines and drugs at home in case they are needed again as well as patients use to cut-off or to reduce their treatment in case that on the first 3–6 days they feel better. The survey indicated that the main disposal method of unused or expired medicines and drugs is in household waste followed from the sink and the toilet. Furthermore, the main disposal solution of unused or expired medicines and drugs remain the household bin as well as the sewage system (sink or toilet), while a percentage more than 55% of the participants indicated that they will follow a specific waste management program if existing in place. Moreover, in order to reduce the production of pharmaceutical wastes, specific prevention activities must be considered.

http://ift.tt/2sDGkrp

Selective removal and preconcentration of triclosan using a water-compatible imprinted nano-magnetic chitosan particles

Abstract

A water-compatible magnetic triclosan (TCS) imprinted material (TCS-CTS-Fe⁰-MIPs) was synthesized for selective enrichment and detection of TCS in real complex water samples. The material was synthesized by using chitosan (CTS) as functional monomer, which has rich surface O- and N-containing functional groups. The TCS imprinted CTS was coated on Fe⁰ surface and then cross-linked with glutaraldehyde. Scanning electron microscopy suggested that the imprinted material was covered with a layer of imprinted film, Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy confirmed that the imprinted material had more functional groups (amino and hydroxyl groups) than that of non-imprinted material. The TCS imprinted and non-imprinted materials used in each adsorption experiments were 0.1 mg mL⁻¹. The maximum adsorption capacity of the TCS imprinted material and non-TCS imprinted material were 20.86 and 15.11 mg g⁻¹, respectively. The adsorption results showed that selectivity coefficient was 10.151, 1.353, and 8.271 in the presence of p-chlorophenol, 2,4,6-trichlorophenol, and bisphenol-A, respectively. The recoveries of river water and lake water samples were 92.8, 91.3, 92.4, and 81.4, 82.3, 82.1%, respectively, when the samples were spiked with 4, 6, and 8 μg L⁻¹ of TCS with the imprinted material. The adsorption capacity of the TCS imprinted material and non-TCS imprinted material lost 5.2 and 6.2% after six times of recycling. The high selectivity and excellent adsorption capacity of the imprinted material can be attributed to the presence of sterically complementary imprinted sites and high surface, which would also made it more accessible to TCS than that of non-imprinted material. The present study would provide an environmental friendly and convenient method for the removal and the monitoring of TCS in environmental water samples.

http://ift.tt/2s8z0AC

Selection of Zygosaccharomyces rouxii strains resistant to cadmium with improved removal abilities through ultraviolet-diethyl sulfate cooperative mutagenesis

Abstract

Cd²⁺ resistance and bioaccumulation capacity were selected from parental Zygosaccharomyces rouxii (CRZ-0) while maintaining NaCl tolerance using protoplast mutagenesis technology. Ultraviolet-diethyl sulfate (UV-DES) cooperative mutagenesis, followed by preliminary screening and rescreening, was used to select the mutant strain CRZ-9. CRZ-9 grew better than CRZ-0 in YPD medium with 20 or 50 mg L⁻¹ of Cd²⁺. Scanning electron microscopy observations and flow cytometry tests indicated that CRZ-9 was more effective at eliminating reactive oxygen species (ROS) generated by Cd²⁺, which led to less cellular structural damage and lower lethality. Furthermore, compared with CRZ-0, CRZ-9 exhibited increased potential for application with higher Cd²⁺ removal ratio, wider working pH range, and lower biomass dosage in Cd²⁺ bioaccumulation. The mutant strain CRZ-9 possessed improved Cd²⁺ resistance and bioaccumulation capacity and therefore is a promising strain to remove Cd²⁺ from wastewater.

http://ift.tt/2sDpU28

Analysis of Newly Identified and Rare Synonymous Genetic Variants in the RET Gene in Patients with Medullary Thyroid Carcinoma in Polish Population

Abstract

Gain-of-function germline mutations of the RET proto-oncogene are responsible for initiation of carcinogenesis within the thyroid gland and development of hereditary form of medullary thyroid carcinoma and MEN2 syndrome. Genotype-phenotype correlations are established for most RET mutations, but the importance of the synonymous changes in this gene remains debatable. We aimed to analyze RET gene variants in Polish population. Genetic testing for the RET gene variants was performed with standard methods in 585 people aged 1–85, including 448 patients with medullary thyroid carcinoma and 131 of their first- and second-degree relatives, as well as six patients suspected of MTC/MEN2. Besides the most frequent synonymous changes, p.Leu769Leu, p.Ser836Ser, and p.Ser904Ser, four rare changes—c.1827C>T (p.Cys609Cys), c.2364C>T (p.Ile788Ile), c.2418C>T (p.Tyr806Tyr), and c.2673G>A (p.Ser891Ser)—were found in the RET gene, in the Polish population. Two of the rare changes, p.Cys609Cys and p.Ile788Ile, had not been previously described. The frequency of molecular synonymous variants in the general population was evaluated by testing 400 anonymous blood samples of neonates. Our findings may contribute to a better understanding of the genetic diversity of the RET gene and the involvement of synonymous variants in this diversity.

http://ift.tt/2sOhHqq

Transmission analysis of TGFB1 gene polymorphisms in non-syndromic cleft lip with or without cleft palate

Publication date: September 2017
Source:International Journal of Pediatric Otorhinolaryngology, Volume 100
Author(s): Ginila T. Raju, Bhaskar V.K.S. Lakkakula, Jyotsna Murthy, Munirajan Arasambattu Kannan, Solomon F.D. Paul
ObjectivesTransforming growth factor beta1 (TGF-β1) plays a significant role in craniofacial development. Previous linkage studies reported that the TGF-β1-locus at 19q13.1 harbour predisposing genes for non-syndromic oral clefts. In the present study case parents triads were evaluated to find the transmission effects of genetic variants in TGF- β1 towards non-syndromic cleft lip or palate (NSCL/P).MethodsUsing allelic discrimination method148 families (case-parent triads) were assessed for single nucleotide polymorphisms (SNPs) in TGF-β1 gene. The SNPs were checked for mendelian errors and Hardy-Weinberg equilibrium (HWE). Transmission disequilibrium test and haplotype frequencies were estimated.ResultsThe TGF-β1 SNPs showed very low minor allele frequencies (MAFs) and observed heterozygosity (Hobs). The transmission disequilibrium test (TDT) and parent-of-origin likelihood ratio tests (PO-LRT) were not significant for any of the SNPs tested. Strong linkage disequilibrium (r² = 0.722) was found between rs1800469 and rs1800470 SNPs. Haplotype analysis ignoring parent of origin showed strong evidence of excess transmission but it is not significant (p-value = 0.293).ConclusionTransmission of minor alleles were not observed from either parent indicating that the TGF-β1 gene polymorphisms by themselves do not confer risk for non-syndromic oral clefts but, rather, modify the stability and the activation process of TGF-β1. As the number of families included in the study are less, results must be considered still preliminary and require replication using more families.



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Study of the effects of hearing on static and dynamic postural function in children using cochlear implants

Publication date: September 2017
Source:International Journal of Pediatric Otorhinolaryngology, Volume 100
Author(s): Malihah Mazaheryazdi, Abdollah Moossavi, Javad Sarrafzadah, Saeed Talebian, Shohreh Jalaie
ObjectiveThe present study aimed to evaluate the postural control perturbations by the center of pressure parameters in two main approaches, cochlear implant turned "on" and "off".MethodsWe included 25 children aged 8–10 years with unilateral cochlear implants and bilateral vestibular hypofunction deficit. To evaluate the postural function, each children was asked to stand on the force plate under 3 different conditions and cochlear implant turned "on" and "off": Condition (A) double stance from open eyes to closed eyes, Condition (B) double stance with open eyes engaging in the dual task and Condition (C) From double leg stance to one leg stance with open eyes for assessment of dynamic postural control. Also to calculate the center of pressure parameters, we designed new software for the force plateResultsIn condition A: although the results demonstrated an overall reduction in the mean of center of pressure parameters when the cochlear implant was "on", only the significant differences were seen in mean and standard deviations for anterior-posterior displacement, mediolateral displacement, area and mean velocity (P =0.00, P=0.04, P=0.02 and P=0.00, respectively) in open eyes In condition B: no significant difference was found between "on" and "off" cochlear implant in single or dual-task situations. In condition C: mean velocity variable demonstrated a significant difference (P=0.00) in the cochlear implant "on" condition in double leg stance only. Also, anterior-posterior displacement demonestrated a significant difference (P=0.00) when the cochlear implant was turned "on" in one leg stance situation.ConclusionThe results of our study show that auditory information can improve postural stability and reduce body sways in different situations as an underlying system for reinforcement of the postural control in children without complete normal balance subsystems.



http://ift.tt/2s8O6G6

Auditory, visual and auditory-visual memory and sequencing performance in typically developing children

Publication date: September 2017
Source:International Journal of Pediatric Otorhinolaryngology, Volume 100
Author(s): Roshni Pillai, Asha Yathiraj
ObjectiveThe study evaluated whether there exists a difference/relation in the way four different memory skills (memory score, sequencing score, memory span, & sequencing span) are processed through the auditory modality, visual modality and combined modalities.MethodsFour memory skills were evaluated on 30 typically developing children aged 7 years and 8 years across three modality conditions (auditory, visual, & auditory-visual). Analogous auditory and visual stimuli were presented to evaluate the three modality conditions across the two age groups.ResultsThe children obtained significantly higher memory scores through the auditory modality compared to the visual modality. Likewise, their memory scores were significantly higher through the auditory-visual modality condition than through the visual modality. However, no effect of modality was observed on the sequencing scores as well as for the memory and the sequencing span. A good agreement was seen between the different modality conditions that were studied (auditory, visual, & auditory-visual) for the different memory skills measures (memory scores, sequencing scores, memory span, & sequencing span). A relatively lower agreement was noted only between the auditory and visual modalities as well as between the visual and auditory-visual modality conditions for the memory scores, measured using Bland-Altman plots.ConclusionsThe study highlights the efficacy of using analogous stimuli to assess the auditory, visual as well as combined modalities. The study supports the view that the performance of children on different memory skills was better through the auditory modality compared to the visual modality.



http://ift.tt/2sDxKZM

Absence of KCNQ4 mutation in Bengali families with ADNSHL originated from West Bengal, India

Publication date: September 2017
Source:International Journal of Pediatric Otorhinolaryngology, Volume 100
Author(s): Bidisha Adhikary, Biswabandhu Bankura, Subhradev Biswas, Silpita Paul, Madhusudan Das
ObjectiveAutosomal Dominant Non-Syndromic Hearing Loss (ADNSHL) is extremely heterogeneous in nature. More than 60 loci with 30 different genes have been identified linked to ADNSHL. Mutation in KCNQ4 is considered as one of the most common causative factor responsible for ADNSHL. No study focused on the genetic alteration of KCNQ4 gene among hearing loss patients in India. The present study for the first time was carried out to determine the mutation spectrum of KCNQ4 gene in ADNSHL patients of West Bengal state, India.MethodTwenty nine individuals from 10 independent ADNSHL family (with two or more generation affected) were studied both clinically and genetically. Most of the patients showed moderate progressive sensorineural hearing loss. Mutation analysis was conducted for KCNQ4 gene using polymerase chain reaction followed by direct sequencing.ResultsNeither any reported nor a novel pathogenic mutation in KCNQ4was detected in our studied group, in contrast to the findings among East Asians.ConclusionThe result of the present study suggests that mutations in KCNQ4 gene are unlikely to be a major causative factor of ADNSHL in our studied patients from West Bengal, India, pointing to other genes might be responsible for ADNSHL in our studied patients.



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Bilateral congenital cholesteatoma: Surgical treatment and considerations

Publication date: August 2017
Source:International Journal of Pediatric Otorhinolaryngology, Volume 99
Author(s): Daniele Marchioni, Alessia Rubini, Mauricio Gonzalez-Navarro, Matteo Alicandri-Ciufelli, Adrian James, Livio Presutti
ObjectivesTo describe a multicenter study regarding surgical management of bilateral congenital cholesteatoma (BCC) and underline the importance of endoscopes in the management of this condition. In BCC, hearing preservation is more crucial than in unilateral cases. The endoscopic approach allows complete removal of cholesteatoma via a minimally invasive technique offering low residual disease rates while preserving the normal physiology of the middle ear and possibly the ossicular chain.Study designRetrospective chart and surgical video review of patients with BCC who underwent surgery at Otolaryngology Department of Modena and Verona University Hospitals and the Hospital for Sick Children, Toronto.MethodsFrom 2002 to November 2016, six patients were identified with bilateral congenital cholesteatoma and included in this study. Pre-operative assessments, surgical treatments and outcomes were collected and described.ResultsThe median age at presentation was 4 years (range 2–7 years). A microscopic post auricular tympanoplasty was performed in two ears, four underwent a canal wall up mastoidectomy procedure and in the other six a transcanal endoscopic approach (TEA) was used. No intra- or post-operative complications were observed in any patients. The mean follow up period was 54.5 months.ConclusionsWhen both ears are involved with congenital cholesteatoma, it is particularly important to use a minimally invasive technique that preserves normal ossicular and mastoid structure and function whenever possible. In many cases this can be achieved with TEA, even in young children. In addition the endoscope allows good surgical control of cholesteatoma removal from hidden recesses.



http://ift.tt/2s8GgfN

Volatile organic compounds (VOCs) during non-haze and haze days in Shanghai: characterization and secondary organic aerosol (SOA) formation

Abstract

To better understand the characterization and secondary organic aerosol (SOA) formation of volatile organic compounds (VOCs) during non-haze and haze days, ambient VOCs were continuously measured by a vehicle-mounted online thermal desorption system coupled with a gas chromatography–mass spectrometry (TD–GC/MS) system in Shanghai, China. The average concentrations of VOCs in haze episodes (193.2 μg m⁻³) were almost 50% higher than in non-haze periods (130.8 μg m⁻³). VOC concentrations exhibited a bi-modal pattern in the morning and evening rush hour periods on both non-haze and haze days. The ratios of toluene to benzene (T/B) and m,p-xylene to ethylbenzene (X/E) indicated that VOCs were aged air mass transported from nearby areas. The estimated SOA yields were 12.6 ± 5.3 and 16.7 ± 6.7 μg m⁻³ for non-haze and haze days, respectively, accounting for 9.6 and 8.7% of the corresponding PM_2.5 concentrations, which were slightly underestimated. VOCs–sensitivity (VOCs–S) based on a PM_2.5-dependent model was used to investigate the variation between VOCs and PM_2.5 concentrations in the morning rush hour. It was found that VOCs were more sensitive to PM_2.5 on clean days than during periods of heavy particulate pollution. VOCs–sensitivity was significantly correlated with the ratio of specific PM_2.5 to background PM_2.5, with a simulated equation of y = 0.84x^−0.62 (r ² = 0.93, p < 0.001). Our findings suggest that strategies to mitigate VOC emissions and further alleviate haze episodes in Shanghai based on reducing gasoline vehicle-related sources would be very efficient.

http://ift.tt/2t4c4X7

Cutting-edge Perspectives in Genomic Maintenance IV

Publication date: Available online 24 June 2017
Source:DNA Repair
Author(s): Philip C. Hanawalt, Samuel H. Wilson




http://ift.tt/2s4655l

Deletion of RDINK4/ARF enhancer: a novel mutation to “inactivate” the INK4-ARF locus

Publication date: Available online 24 June 2017
Source:DNA Repair
Author(s): Ming J. Poi, Thomas J. Knobloch, Junan Li
The presence of an enhancer element, RD^INK4/ARF (RD), in the prominent INK4-ARF locus provides a novel en bloc mechanism to simultaneously regulate the transcription of the p15^INK4B (p15), p16^INK4A (p16), and p14^ARF tumor suppressor genes. While genetic inactivation of p15, p16, and p14^ARF in human cancers has been extensively studied, little is known about RD alteration and its potential contributions to cancer progression. In this review, we discuss recent developments in RD alteration and its association with p15, p16, and p14^ARF alterations in human cancers, and demonstrate that RD deletion may represent a novel mechanism to simultaneously down-regulate p15, p16, and p14^ARF, thus promoting carcinogenesis.



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The role of anti-NHba antibody in bactericidal activity elicited by the meningococcal serogroup B vaccine, MenB-4C

Publication date: Available online 23 June 2017
Source:Vaccine
Author(s): Elizabeth Partridge, Eduardo Lujan, Serena Giuntini, David M. Vu, Dan M. Granoff
BackgroundMenB-4C (Bexsero®) is a multicomponent serogroup B meningococcal vaccine. For vaccine licensure, efficacy was inferred from serum bactericidal antibody (SBA) against three antigen-specific indicator strains. The bactericidal role of antibody to the fourth vaccine antigen, Neisserial Heparin binding antigen (NHba), is incompletely understood.MethodsWe identified nine adults immunized with two or three doses of MenB-4C who had sufficient volumes of sera and >3-fold increases in SBA titer against a strain with high NHba expression, which was mismatched with the other three MenB-4C antigens that elicit SBA. Using 1month-post-immunization sera we measured the effect of depletion of anti-NHba and/or anti-Factor H binding protein (FHbp) antibodies on SBA.ResultsAgainst three strains matched with the vaccine only for NHba, depletion of anti-NHba decreased SBA titers by an average of 43–79% compared to mock-adsorbed sera (P<0.05). Despite expression of sub-family A FHbp (mismatched with the sub-family B vaccine antigen), depletion of anti-FHbp antibodies also decreased SBA by 45–64% (P<0.05). Depletion of both antibodies decreased SBA by 84–100%. Against a strain with sub-family B FHbp and expression of NHba with 100% identity to the vaccine antigen, depletion of anti-NHba decreased SBA by an average of 26%, compared to mock-adsorbed sera (P<0.0001), and depletion of anti-FHbp antibody decreased SBA by 92% (P<0.0001).ConclusionsAnti-NHba antibody can contribute to SBA elicited by MenB-4C, particularly in concert with anti-FHbp antibody. However, some high NHba-expressing strains are resistant, even with an exact match between the amino acid sequence of the vaccine and strain antigens.



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Severe underestimation of pertussis related hospitalizations and deaths in the Netherlands: A capture-recapture analysis

Publication date: Available online 23 June 2017
Source:Vaccine
Author(s): N.A.T. van der Maas, J. Hoes, E.A.M. Sanders, H.E. de Melker
OjectiveDespite vaccination, pertussis has remained endemic, sometimes leading to severe disease. We aimed to quantify the completeness of reporting (CoR) of pertussis hospitalizations and deaths in the Netherlands.Study designCoR was estimated using capture-recapture analyses. Hospitalizations (2007–2014) from the National Registration Hospital Care (hospital data) were matched to the notifiable Infectious Disease case registry (notifications) providing (month and) year of birth, gender and postal code. Deaths (1996–2014) from Statistics Netherlands (death registry) were matched to notifications using gender, age, year of death and notification date. Cases <2years (y) and ≥2y were analysed separately. Chao's estimator estimated the total population, which was used to calculate CoR.ResultsUsing strict matching criteria, we found 461 matches among 876 (hospital data) and 757 (notifications) hospitalizations <2y. The population estimate of hospitalized infants was 1446, resulting in CoR between 52% and 61%. For hospitalizations ≥2y (246; hospital data and 264; notifications) 43 matches were found, with a population estimate of 1512 and CoR between 16.5% and 22%.Among thirteen (death registry) and eight (notifications) deaths <2y, seven cases overlapped. The population estimate was 16. CoR of the two sources was 50–81%. With two (death registry) and eight (notifications) deaths ≥2y without overlap, the population estimate was 26 and CoR 8–31%.ConclusionResults showed substantial underestimation of pertussis hospitalizations and deaths. This has to be taken into account in evaluation of current and future immunization programs.



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