Head and Neck Diseases by Alexandros G.Sfakianakis: 11/22/17

Τετάρτη 22 Νοεμβρίου 2017

Non-corticosteroid adherence and itch severity influence perception of itch in atopic dermatitis

Abstract

Topical corticosteroid phobia is an important problem in the treatment of atopic dermatitis as it can affect the ability to control disease severity and itch by reducing treatment adherence. Topical corticosteroid phobia often ends up even non-corticosteroid adherence. As such, non-corticosteroid adherence, disease severity and itch are likely to be associated with each other, but their relationship has yet to be thoroughly investigated. Thus, the purpose of this study is to investigate it in atopic dermatitis. Using data from 1190 participants in an Internet survey, we identified 255 non-corticosteroid users and 225 with moderate to severe itch who were defined as non-corticosteroid adherents. Corticosteroid users with the same itch categories (n = 878) served as controls. We also examined how itch severity affects the perception of itch in atopic dermatitis. Unexpectedly, non-corticosteroid adherents were less sensitive to the conditions to elicit itch such as perspiring, commuting homeward, drinking alcohol and wearing woolen clothes compared with the control. We also found that patients with severer itch were more sensitive to itch during/after bathing, when lying in bed, commuting homeward, studying/working, drinking alcohol, undressing, getting up in the morning, after a meal, ingesting piquant foods and when they were unoccupied, angry, busy, nervous, sad or enjoying themselves. In conclusion, we found that non-corticosteroid adherence and itch severity influence perception of itch in atopic dermatitis and discuss possible mechanisms underlying these results. The information obtained in this study may be useful for communication with and education of atopic dermatitis patients and their treatment in outpatient clinics.

http://ift.tt/2zu2d1l

Three cases of Nagashima-type palmoplantar keratosis associated with atopic dermatitis: A diagnostic pitfall

http://ift.tt/2mVqU0E

Waardenburg syndrome type IIE in a Japanese patient caused by a novel non-frame-shift duplication mutation in the SOX10 gene

http://ift.tt/2zvMPRU

Abrupt generalized pustules in patients with rheumatoid arthritis and interstitial lung disease

Abstract

We report a case of a 30-year-old Chinese woman with rheumatoid arthritis and interstitial lung disease who abruptly developed generalized pustules and a high fever for 10 days. She had been taking oral prednisone, iguratimod and total glucosides of peony regularly for 5 months prior. In addition, she had taken metronidazole for 3 days 20 days prior which she had used before with no adverse reaction. She had no history of similar lesions and psoriasis. A biopsy of a pustule on the back showed spongiform pustule of Kogoj. She was suspected of having generalized pustular psoriasis or acute generalized exanthematous pustulosis. Finally, she was diagnosed with generalized pustular psoriasis (von Zumbusch type) considering the characteristics and clinical course of the rash. In addition to the above three drugs, systemic cyclosporin (5 mg/kg per day) was applied, and the lesions and fever resolved within the proceeding 2 months.

http://ift.tt/2mTDvBE

Economic assessment of actual prescription of drugs for treatment of atopic dermatitis: Differences between dermatology and pediatrics in large-scale receipt data

Abstract

Using large-scale receipt data, we analyzed the differences in the prescription of drugs and their costs between dermatology and pediatrics in the treatment of atopic dermatitis (AD) in children. Between August 2010 and July 2011, 50 706 patients were diagnosed as having AD, and the data of 21 075 (15 257 dermatology, 5818 pediatric) patients aged 0–14 years were included in this study. The use of classes I (strongest), II (very strong), and III (strong) topical corticosteroids and tacrolimus was significantly higher in dermatology than in pediatrics (class I, 2.88% vs 0.76%; class II, 27.68% vs 8.32%; class III, 52.53% vs 39.88%; tacrolimus, 5.05% vs 2.82%; all P < 0.05). Although total drug costs were higher in dermatology than in pediatrics, mean drug costs per person were significantly higher in pediatrics. Moisturizers and protective agents had the highest cost (~ ¥690 million). The introduction rate of generic drugs was low at 8.3% among classes I–V. The introduction rate of moisturizers and protective agents, for which costs were the highest, was approximately 9%. The prescription of generic classes II–V topical corticosteroids and moisturizers and protective agents was also significantly higher in dermatology than in pediatrics (P < 0.05). Among patients younger than 2 years, 4405 received drugs for AD; classes I and II topical corticosteroids and tacrolimus (against the guidelines) were administrated in 35 (0.8%), 474 (10.8%) and 29 patients (0.7%), respectively. The introduction of generic drugs is still low, and the use of generic moisturizers and protective agents should be addressed further.

http://ift.tt/2ztvedt

Unusual subcutaneous invasion of myxoid liposarcoma

http://ift.tt/2mTDfma

Transverse nasal crease with milia and comedones: Dermoscopic observation

http://ift.tt/2zvpq3j

Successful treatment of hidradenitis suppurativa with rituximab for a patient with idiopathic carpotarsal osteolysis and chronic active antibody-mediated rejection

http://ift.tt/2mTCYzE

Agranulocytosis associated with voriconazole-induced hypersensitivity syndrome

http://ift.tt/2zuATQo

Effectiveness of Gastrostomy for Improving Nutritional Status and Quality of Life in Patients with Epidermolysis Bullosa: A Systematic Review

Abstract

Inherited epidermolysis bullosa (EB) is a group of rare genetic disorders clinically characterized by a wide range of skin and mucosal blistering after minor trauma¹. This condition is caused by mutations on genes coding for structural proteins of the skin and affects both genders from all ethnic groups, and its estimated prevalence is about 500,000 cases worldwide².

http://ift.tt/2mV7ida

Effectiveness of Gastrostomy for Improving Nutritional Status and Quality of Life in Patients with Epidermolysis Bullosa: A Systematic Review

Abstract

http://ift.tt/2mV7ida

Acknowledgements to Reviewers

http://ift.tt/2jRLdes

Author Guidelines

http://ift.tt/2hXpPnE

Acknowledgements to Reviewers

http://ift.tt/2jRLdes

Author Guidelines

http://ift.tt/2hXpPnE

The COL5A3 and MMP9 genes interact in eczema susceptibility

Abstract

Background

Genetic studies of eczema have identified many genes, which explain only 14% of the heritability. Missing heritability may be partly due to ignored Gene–Gene (G-G) interactions.

Objective

Our aim was to detect new interacting genes involved in eczema.

Methods

The search for G-G interaction in eczema was conducted using a two-step approach, which included as a first step, a biological selection of genes, which are involved either in the skin or epidermis development or in the collagen metabolism, and as a second-step, an interaction analysis of the selected genes. Analyses were carried out at both SNP and gene levels in three asthma-ascertained family samples: the discovery dataset of 388 EGEA (Epidemiological study on the Genetics and Environment of Asthma) families and the two replication datasets of 253 SLSJ (Saguenay-Lac-Saint-Jean) families and 207 MRCA (Medical Research Council) families.

Results

One pair of SNPs, rs2287807 in COL5A3 and rs17576 in MMP9, that were detected in EGEA at P ≤ 10^-5 showed significant interaction by meta-analysis of EGEA, SLSJ and MRCA samples (P=1.1x10^-8 under the significant threshold of 10^-7). Gene-based analysis confirmed strong interaction between COL5A3 and MMP9 (P=4x10^-8 under the significant threshold of 4x10^-6) by meta-analysis of the three datasets. When stratifying the data on asthma, this interaction remained in both groups of asthmatic and non-asthmatic subjects.

Conclusion

This study identified significant interaction between two new genes, COL5A3 and MMP9, which may be accounted for by a degradation of COL5A3 by MMP9 influencing eczema susceptibility.

Further confirmation of this interaction as well as functional studies are needed to better understand the role of these genes in eczema.

http://ift.tt/2AozzyR

Nasal Cytology: a Precision Medicine tool in clinical practice

Abstract

The BSACI guideline for the diagnosis and management of allergic and non-allergic rhinitis represents a precise and accurate document in defining the different sub-groups of patients suffering from allergic rhinitis (AR) and non-allergic rhinitis (NAR). We would like to stimulate the debate about this matter, mainly concerning the definition and classification of NAR. In particular, we would convince the readers that there are different phenotypes/endotypes of NAR in addition to non-allergic rhinitis with eosinophils (NARES). This concept is clinically relevant as deserves an adequate work-up and constitutes the background for the Precision Medicine (PM) approach.

http://ift.tt/2A0KQoc

The COL5A3 and MMP9 genes interact in eczema susceptibility

Abstract

Background

Genetic studies of eczema have identified many genes, which explain only 14% of the heritability. Missing heritability may be partly due to ignored Gene–Gene (G-G) interactions.

Objective

Our aim was to detect new interacting genes involved in eczema.

Methods

Results

Conclusion

This study identified significant interaction between two new genes, COL5A3 and MMP9, which may be accounted for by a degradation of COL5A3 by MMP9 influencing eczema susceptibility.

Further confirmation of this interaction as well as functional studies are needed to better understand the role of these genes in eczema.

http://ift.tt/2AozzyR

Nasal Cytology: a Precision Medicine tool in clinical practice

Abstract

http://ift.tt/2A0KQoc

Characterization of oromotor and limb motor dysfunction in the DJ1 -/- model of Parkinson disease

Publication date: 26 February 2018
Source:Behavioural Brain Research, Volume 339
Author(s): Katie M. Yang, Katherine V. Blue, Haleigh M. Mulholland, Meghna P. Kurup, Cynthia A. Kelm-Nelson, Michelle R. Ciucci
Parkinson disease (PD) is devastating to sensorimotor function that includes cranial/oromotor and limb motor deficits. However, the onset, progression, and neural correlates of PD-related dysfunctions are poorly understood. To address this gap, we used a genetic rat model of PD, DJ1 -/-, and hypothesized that motor deficits would manifest early in the disease process, be progressive in nature, and be related to pathologies in brainstem structures associated with sensorimotor function. The present study compares homozygous DJ1 -/- male rats to age-matched wild type controls. Progressive cranial sensorimotor function (ultrasonic vocalizations and tongue motor performance) and limb motor function (tapered balance beam) was analyzed at 2, 4, 6, and 8 months of age. Additionally, tyrosine hydroxylase cell counts were performed in the locus coeruleus and correlated to behavioral measures. We found that compared to wild type controls, DJ1 -/- show deficits in ultrasonic vocalizations as well as oromotor (tongue) deficits that were progressive. Overtime, DJ1 -/- rats cross a tapered balance beam with significantly decreased speed of traversal. Additionally, in the DJ1 -/-, tyrosine hydroxylase positive cells in the locus coeruleus are significantly reduced and are negatively correlated to oromotor behaviors. Characterizing the DJ1 -/- model of PD provides important foundational work necessary to define behavioral and early-onset biomarkers that parallels early-stage PD pathology in humans.

http://ift.tt/2A04n7L

Inhibition of AMPAR endocytosis alleviates pentobarbital-induced spatial memory deficits and synaptic depression

Publication date: 26 February 2018
Source:Behavioural Brain Research, Volume 339
Author(s): Wei Wang, Tao Tan, Yanzhi Yu, Zhilin Huang, Yehong Du, Huili Han, Zhifang Dong
Our previous study has shown that pentobarbital causes memory deficits and impairs hippocampal synaptic plasticity. The Tat-GluA23Y peptide (GluA23Y) prevents activity-dependent α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor (AMPAR) endocytosis. It enables early-phase long-term potentiation (LTP) to proceed to late-phase LTP allowing short-term memory to convert to long-term memory. The purpose of this study is to explore the potential effects of GluA23Y on pentobarbital-induced memory deficits through behavioral and electrophysiological paradigms. We found that in vivo intrahippocampal infusion of GluA23Y (100μM, 1μl per hippocampus) 30min prior to pentobarbital administration (8mM, 1μl per hippocampus) significantly rescued the pentobarbital-induced deficit of memory retrieval in rats during the Morris water maze test. Pre-incubation of GluA23Y (10μM) partially rescued bath application of pentobarbital-induced synaptic transmission of the CA3-CA1 pathway in hippocampal slices. More importantly, GluA23Y selectively upregulated the synaptic GluA2 expression that was suppressed by pentobarbital. Together, these results suggest that inhibition of GluA2-containing AMPAR endocytosis by GluA23Y increases the pentobarbital-suppressed basal synaptic transmission by upregulating the synaptic GluA2, and then subsequently alleviates spatial memory deficits. Therefore, inhibition of AMPAR endocytosis may be a potential therapeutic way to treat memory disorders caused by anesthetics.

http://ift.tt/2hPdxJX

Brain-derived neurotrophic factor (BDNF) determines a sex difference in cue-conditioned alcohol seeking in rats

Publication date: 26 February 2018
Source:Behavioural Brain Research, Volume 339
Author(s): Samuel J. Hogarth, Emily J. Jaehne, Maarten van den Buuse, Elvan Djouma
Alcohol use disorder is a detrimental addictive disease that develops through prolonged ethanol exposure and regular intoxication. However, the changes in the underlying neurobiology leading to alcohol addiction remain unclear. Brain-Derived Neurotrophic Factor (BDNF) is implicated in substance abuse disorders including alcoholism. As the vast majority of previous animal model studies have concentrated on males only, the aim of this study was to determine whether endogenous BDNF mediates alcohol seeking in a sex-specific manner.We used an operant self-administration paradigm where the animals were trained in operant chambers to self-administer a 10% ethanol solution, and compared male and female BDNF heterozygous (HET) and wildtype (WT) rats. Over several weeks, the animals progressed through acquisition, progressive ratio, extinction, and reinstatement phases.There were no significant sex or genotype differences in the number of alcohol-paired lever presses during acquisition, progressive ratio and extinction. However, a significant difference between male and female WT rats following alcohol-primed reinstatement was completely absent in BDNF HET rats suggesting a role of BDNF in sex differences in alcohol seeking after abstinence. Female BDNF HET rats showed significantly higher number of alcohol-paired lever presses during reinstatement than female WT controls.These findings suggest that BDNF regulatory pathways are involved in sex differences in reinstatement of alcohol intake and emphasize the need to include both male and female animals to explore sex-specific interactions in addiction neurocircuitry.

http://ift.tt/2zZgUIM

Relevance-dependent modulation of tactile suppression during active, passive and pantomime reach-to-grasp movements

Publication date: 26 February 2018
Source:Behavioural Brain Research, Volume 339
Author(s): Damian M. Manzone, J. Timothy Inglis, Ian M. Franks, Romeo Chua
When we move, our ability to detect tactile events on the moving limb is reduced (e.g., movement-related tactile suppression). This process prevents unimportant sensory information from bombarding our central nervous system. This study investigated whether movement-related suppression can be modulated according to task relevance, while introducing a novel motor-driven complex upper limb movement. In three experiments, participants performed volitional self-driven and passive motor-driven reaching and grasping movements. Over the course of the movement, weak electrical stimulation was presented at task-relevant (i.e., index finger) and irrelevant sites (i.e., forearm) on the moving limb. In Experiment 1, participants displayed reduced detectability during movement (90% resting detection). This was true for all locations on the moving limb irrespective of task-relevance and during both self and motor-driven movements. In Experiments 2 and 3 a range of stimulus amplitudes were presented to one task-relevant location during both self and motor-driven movements (Experiment 2A), to a task-relevant and irrelevant site (Experiment 2B) and during a targeted and pantomime/no target reach (Experiment 3). This allowed us to estimate perceptual thresholds and assess the magnitude of movement-related suppression. During both self and motor-driven movements participants exhibited movement-related suppression. Suppression was greater at the irrelevant site (forearm) than at the relevant site (index finger) of the limb. Further, the magnitude of suppression varied with task relevance such that pantomime movements elicited more suppression than targeted movements. Collectively, these experiments suggest that although tactile suppression may be a general consequence of movement, suppression can be modulated in a relevance-dependent manner.

http://ift.tt/2hLPuMd

Leaf saponins of Quillaja brasiliensis enhance long-term specific immune responses and promote dose-sparing effect in BVDV experimental vaccines

Publication date: Available online 23 November 2017
Source:Vaccine
Author(s): Samuel Cibulski, Mariana Rivera-Patron, Norma Suárez, Macarena Pirez, Silvina Rossi, Anna Carolina Yendo, Fernanda de Costa, Grace Gosmann, Arthur Fett-Neto, Paulo Michel Roehe, Fernando Silveira
Saponin-based adjuvants are promising adjuvants that enhance both humoral and T-cell-mediated immunity. One of the most used natural products as vaccine adjuvants are Quillaja saponaria bark saponins and its fraction named Quil A®. Despite that, its use has been restricted for human use due to safety issues. As an alternative, our group has been studying the congener species Quillaja brasiliensis saponins and its performance as vaccine adjuvants, which have shown to trigger humoral and cellular immune responses comparable to Quil A® but with milder side effects. Here, we studied a semi purified aqueous extract (AE) and a previously little characterized saponin-enriched fraction (QB-80) from Q. brasiliensis as vaccine adjuvants and an inactivated virus (bovine viral diarrhea virus, BVDV) antigen co-formulated in experimental vaccines in mice model. For the first time, we show the spectra pattern of the Q. brasiliensis saponins by MALDI-TOF, a novel and cost-effective method that could be used to characterize different batches during saponins production. Both AE and QB-80 exhibited noteworthy chemical similarities to Quil A®. In addition, the haemolytic activity and toxicity were assessed, showing that both AE and QB-80 were less toxic than Quil A®. When subcutaneously inoculated in mice, both fractions promoted long-term strong antibody responses encompassing specific IgG1 and IgG2a, enhanced the avidity of IgG antibodies, induced a robust DTH reaction and significantly increased IFN-ɣ production in T CD4⁺ and T CD8⁺ cells. Furthermore, we have proven herein that AE has the potential to promote dose-sparing, substantially reducing the dose of antigen required for the BVDV vaccines and still eliciting a mixed Th1/Th2 strong immune response. Based on these results, and considering that AE is a raw extract, easier and cheaper to produce than commercially available saponins, this product can be considered as candidate to be escalated from experimental to industrial uses.

http://ift.tt/2zglIGu

Molecular epidemiology of influenza B virus and implications in immunization strategy, Southern Brazil

Publication date: Available online 23 November 2017
Source:Vaccine
Author(s): Bruna Lapinscki, Luciane A. Pereira, Meri B. Nogueira, Luine R. Vidal, Irina Riediger, Maria C. Debur, Mayra Presibella, Sonia M. Raboni
Epidemiological indicators have shown the substantial impact of influenza B (Flu B) on the development of severe acute respiratory infection (SARI) and on mortality rates. In Brazil, the trivalent vaccine, composed of only one Flu B lineage is available. We investigated Flu B infections in clinical samples collected by the epidemiological surveillance service of Paraná State, Brazil, from 2013 to 2016. The Flu B lineages Yamagata- (B/Yam) and Victoria-like (B/Vic) were identified using the qRT-PCR assay, and notification forms were reviewed. Among 379 Flu B positive samples evaluated, 370 (98%) were characterized as B/Yam or B/Vic lineages. Both co-circulated with a frequency of 47% and 53%, respectively. B/Yam infected equally both genders, while B/Vic was more frequent in females (71%). The median age of patients infected by B/Vic (23y; 11–35) was lower than that of patients infected by B/Yam (32y; 12–50). Mismatch between the vaccine and the circulating strain was observed in the 2013 season, with a high number of SARI cases. B/Vic lineage was associated with a larger number of SARI cases (62%), while B/Yam with influenza-like illness (ILI) (61%). Differences were observed in the strains circulating in separate regions of Paraná State. B/Vic was prevalent in the northwestern (67%) and B/Yam in the southeastern region (60%). The unpredictability of Flu B lineage circulation causes a substantial increase in severe disease during epidemics in a vaccine mismatch season. In addition, the differences in the epidemiological profile of the target population of Flu B infections in relation to other respiratory viruses, as well as among the B/Vic and B/Yam lineages may also be associated to an increase in disease burden. These findings have direct consequences on vaccination strategies. Therefore, further molecular epidemiology studies of Flu B in Brazil are required to corroborate these primary results.

http://ift.tt/2BfEDTe

Knowledge, attitudes, and practices of private sector immunization service providers in Gujarat, India

Publication date: Available online 23 November 2017
Source:Vaccine
Author(s): José E. Hagan, Narayan Gaonkar, Vikas Doshi, Anas Patni, Shailee Vyas, Vihang Mazumdar, J.K. Kosambiya, Satish Gupta, Margaret Watkins
BackgroundIndia is responsible for 30% of the annual global cohort of unvaccinated children worldwide. Private practitioners provide an estimated 21% of vaccinations in urban centers of India, and are important partners in achieving high vaccination coverage.MethodsWe used an in-person questionnaire and on-site observation to assess knowledge, attitudes, and practices of private immunization service providers regarding delivery of immunization services in the urban settings of Surat and Baroda, in Gujarat, India. We constructed a comprehensive sampling frame of all private physician providers of immunization services in Surat and Baroda cities, by consulting vaccine distributors, local branches of physician associations, and published lists of private medical practitioners. All providers were contacted and asked to participate in the study if they provided immunization services. Data were collected using an in-person structured questionnaire and directly observing practices; one provider in each practice setting was interviewed.ResultsThe response rate was 82% (121/147) in Surat, and 91% (137/151) in Baroda. Of 258 participants 195 (76%) were pediatricians, and 63 (24%) were general practitioners. Practices that were potential missed opportunities for vaccination (MOV) included not strictly following vaccination schedules if there were concerns about ability to pay (45% of practitioners), and not administering more than two injections in the same visit (60%). Only 22% of respondents used a vaccination register to record vaccine doses, and 31% reported vaccine doses administered to the government. Of 237 randomly selected vaccine vials, 18% had expired vaccine vial monitors.ConclusionsQuality of immunization services in Gujarat can be strengthened by providing training and support to private immunization service providers to reduce MOVs and improve quality and safety; other more context specific strategies that should be evaluated may involve giving feedback to providers on quality of services delivered and working through professional societies to adopt standards of practice.

http://ift.tt/2zg6otn

Impact of measles supplementary immunization activities on reaching children missed by routine programs

Publication date: Available online 23 November 2017
Source:Vaccine
Author(s): Allison Portnoy, Mark Jit, Stéphane Helleringer, Stéphane Verguet
BackgroundMeasles supplementary immunization activities (SIAs) are vaccination campaigns that supplement routine vaccination programs with a recommended second dose opportunity to children of different ages regardless of their previous history of measles vaccination. They are conducted every 2–4 years and over a few weeks in many low- and middle-income countries. While SIAs have high vaccination coverage, it is unclear whether they reach the children who miss their routine measles vaccine dose. Determining who is reached by SIAs is vital to understanding their effectiveness, as well as measure progress towards measles control.MethodsWe examined SIAs in low- and middle-income countries from 2000 to 2014 using data from the Demographic and Health Surveys. Conditional on a child's routine measles vaccination status, we examined whether children participated in the most recent measles SIA.ResultsThe average proportion of zero-dose children (no previous routine measles vaccination defined as no vaccination date before the SIA) reached by SIAs across 14 countries was 66%, ranging from 28% in São Tomé and Príncipe to 91% in Nigeria. However, when also including all children with routine measles vaccination data, this proportion decreased to 12% and to 58% when imputing data for children with vaccination reported by the mother and vaccination marks on the vaccination card across countries. Overall, the proportions of zero-dose children reached by SIAs declined with increasing household wealth.ConclusionsSome countries appeared to reach a higher proportion of zero-dose children using SIAs than others, with proportions reached varying according to the definition of measles vaccination (e.g., vaccination dates on the vaccination card, vaccination marks on the vaccination card, and/or self-reported data). This suggests that some countries could improve their targeting of SIAs to children who miss other measles vaccine opportunities. Across all countries, SIAs played an important role in reaching children from poor households.

http://ift.tt/2zgxf8L

Stereoselective and domain-specific effects of ibuprofen on the thermal stability of human serum albumin

Publication date: 15 January 2018
Source:European Journal of Pharmaceutical Sciences, Volume 112
Author(s): Alexa Guglielmelli, Bruno Rizzuti, Rita Guzzi
Ibuprofen is one of the most used anti-inflammatory drugs, and it is transported in the blood by human serum albumin, a major plasmatic protein with a peculiar adaptability in the binding of several different ligands. We have characterized the interaction between albumin and ibuprofen, either in racemic mixture, or in the S(+) and R(−) enantiomeric forms, by using differential scanning calorimetry, attenuated total reflectance Fourier transform infrared spectroscopy, and molecular dynamics simulation. The results show that increasing concentrations of ibuprofen (up to sixfold drug/protein molar ratio) improve the protein resistance to thermal unfolding without altering the secondary structure. Deconvolution of the calorimetric thermal profiles at different albumin/ibuprofen molar ratios demonstrates a selective stability of the protein domains where the binding sites of the drug are localized. At the highest ibuprofen concentration, the melting temperature increased by about 10°C with respect to the drug-free protein, whereas the unfolding enthalpy maintains an almost constant value. Furthermore, the degree of protein stabilization depends upon the chirality of the drug, and the R(−) enantiomer is more effective compared to the S(+) form. The stability is supported by molecular dynamics simulations, showing that ibuprofen maintains a stable coordination in the most favorable binding sites, leading to a more compact protein structure at high temperature. The overall results attest that the binding of ibuprofen determines on albumin a stereoselective and domain-specific stabilization with a predominantly entropic character, contributing to clarify significant aspects of the molecular mechanism of protein/drug interaction.

Graphical abstract

http://ift.tt/2hYutBs

Synergistic inhibition of cell proliferation by combined targeting with kinase inhibitors and dietary xanthone is a promising strategy for melanoma treatment

Summary

α-Mangostin is a dietary xanthone that displays various biological activities, and numerous reports have shown its efficacy in cancer prevention and inhibition. As most agents have been shown to be ineffective as single-agent therapy for malignant melanoma (MM), the principle of targeted chemotherapy for MM is to use effective inhibitors and combination methods. In this study, we tested the cytotoxicity of several kinase inhibitors, including the glycogen synthase kinase (GSK)-3 inhibitor CHIR99021, and rapamycin, in combination with a dietary xanthone, α-mangostin, by screening from a kinase inhibitor library for melanogenesis in SK-MEL-2 MM cells, and verified these by clone formation efficiency, terminal dUTP nick end labelling, and expression of apoptosis-related proteins. We also explored the molecular mechanisms for the apoptosis-inducing effects reported. We found a marked synergistic effect of CHIR99021 or rapamycin in combination with α-mangostin, which we verified through apoptosis-related methods. These data provide a strong rationale for the use of α-mangostin as an adjunct to GSK-3 inhibitor or mammalian target of rapamycin inhibitor treatment. The intrinsic mechanism behind α-mangostin might be inhibition of phosphatidylinositol 3-kinase/AKT signalling and autophagy, and induction of reactive oxygen species generation.

http://ift.tt/2hMhOxS

Synergistic inhibition of cell proliferation by combined targeting with kinase inhibitors and dietary xanthone is a promising strategy for melanoma treatment

Summary

http://ift.tt/2hMhOxS

Dose warping uncertainties for the accumulated rectal wall dose in cervical cancer brachytherapy

Publication date: Available online 22 November 2017
Source:Brachytherapy
Author(s): Laura E. van Heerden, Niek van Wieringen, Kees Koedooder, Coen R.N. Rasch, Bradley R. Pieters, Arjan Bel
PurposeStructure-based deformable image registration (DIR) can be used to calculate accumulated dose volume histogram parameters for cervical cancer brachytherapy (BT). The purpose of this study is to investigate dose warping uncertainties for the accumulated dose to the 2 cm³ receiving the highest dose (D2cm3) in the rectal wall, using a physically realistic model (PRM) describing rectal wall deformation.Methods and materialsFor 10 patients, treated with MRI-guided pulsed dose rate BT (two times 24 × 0.75 Gy, given in two applications BT1 and BT2), the planning images were registered with structure-based DIR. The resulting transformation vectors were used to accumulate the total rectum dose from BT. To investigate the dose warping uncertainty, a PRM describing rectal deformation was used. For point pairs on rectumBT1 and rectumBT2 that were at the same location according to the PRM, the dose for BT1 and BT2 was added (DPRM) and compared to the DIR-accumulated dose (DDIR) in the BT2 point. The remaining distance after DIR between corresponding point pairs, defined as the residual distance, was calculated.ResultsFor points within the D2cm3 volume, more than 75% was part of the D2cm3 volume according to both PRM and DIR. The absolute dose difference was <7.3 GyEQD2, and the median (95th percentile) of the residual distance was 8.7 (22) mm.ConclusionsDIR corresponded with the PRM for on average 75% of the D2cm3 volume. Local absolute dose differences and residual distances were large. Care should therefore be taken with DIR for dose-warping purposes in BT.

http://ift.tt/2zhm141

Reduction of MRI signal distortion from titanium intracavitary brachytherapy applicator by optimizing pulse sequence parameters

Publication date: Available online 22 November 2017
Source:Brachytherapy
Author(s): Thomas P. Sullivan, Matthew M. Harkenrider, Murat Surucu, Abbie M. Wood, Joseph H. Yacoub, Steven M. Shea
PurposeTo demonstrate that optimized pulse sequence parameters for a T2-weighted (T2w) fast spin echo acquisition reduced artifacts from a titanium brachytherapy applicator compared to conventional sequence parameters.Methods and materialsFollowing Institutional Review Board approval and informed consent, seven patients were successfully imaged with both standard sagittal T2w fast spin echo parameters (voxel size of 0.98 × 0.78 × 4.0 mm³; readout bandwidth of 200 Hz/px; repetition time of 2800 ms; echo time of 91 ms; echo train length of 15; 36 slices; and imaging time of 3:16 min) and an additional optimized T2w sequence (voxel size of 0.98 × 0.98 × 4.0 mm³; readout bandwidth of 500 Hz/px; repetition time of 3610 ms; echo time of 91 ms; echo train length of 25; 18–36 slices; and imaging time of 1:15–2:30 min), which had demonstrated artifact reduction in prior phantom work. Visualized intracavitary tandem was hand-segmented by two of the authors. Three body imaging radiologists assessed image quality and intraobserver agreement scores were analyzed.ResultsThe average segmented volume of the intracavitary applicator significantly (p < 0.05) decreased with the experimental pulse sequence parameters as compared to the standard pulse sequence. Comparison of experimental and standard T2w sequence qualitative scores for each reviewer showed no significant differences between the two techniques.ConclusionsThis study demonstrated that pulse sequence parameter optimization can significantly reduce distortion artifact from titanium applicators while maintaining image quality and reasonable imaging times.

http://ift.tt/2BhEsqy

The administration of surfactant decreased oxidative stress in lungs of mice exposed to cigarette smoke

Publication date: January 2018
Source:International Immunopharmacology, Volume 54
Author(s): Dafne Fernandes Machado, Keila Karine Duarte Campos, Natália Pereira da Silva, Camila de Oliveira Ramos, Sílvia Dantas Cangussú, Guilherme de Paula Costa, André Talvani, Frank Silva Bezerra
The alveolar surfactant, which composition consists of a unique and complex mixture of lipids and proteins, has immunomodulatory action. This study aimed to evaluate the effects of exogenous surfactant on pulmonary inflammatory response in mice exposed to cigarette smoke (CS). Twenty-four mice C57BL/6 were divided into four groups: control group exposed to ambient air (CG); surfactant treated group (SG); CS exposed group (CSG) and CS exposed group treated with surfactant (CSSG). For five days, CSG and CSSG were exposed to 12 commercial cigarettes/day and SG and CSSG received the surfactant by intranasal instillation. At the end of the experiment, the animals were euthanatized for the collection of bronchoalveolar lavage fluid (BALF) and lungs. The total number of leukocytes in BALF increased in CSG compared to CG, however, there was a decrease in CSSG compared to CSG. There was an increase in lipid peroxidation in SG and CSG compared to CG while there was a decrease in CSSG compared to CSG. Regarding the antioxidant enzymes, the catalase (CAT) activity increased in all groups compared to CG and the superoxide dismutase (SOD) activity decreased in CSG compared to the CG and SG. There was an increase in TNF in SG, CSG and CSSG compared to CG. There was an increase in IL-17 in CSSG compared to CG. There was an increase in CCL5 in SG and CSSG compared to CG. Therefore, our results demonstrated that the administration of exogenous surfactant was able to decrease the oxidative processes in the lungs of mice induced by short-term exposure to CS.

http://ift.tt/2mUFbuK

Response Regarding Surgical Techniques for Retrograde Parotidectomy

Publication date: Available online 22 November 2017
Source:American Journal of Otolaryngology
Author(s): Maxwell Kligerman, Uchechukwu Megwalu, Davud Sirjani

http://ift.tt/2iJ0BpX

How does the endophytic fungus Mucor sp. improve Arabidopsis arenosa vegetation in the degraded environment of a mine dump?

Publication date: March 2018
Source:Environmental and Experimental Botany, Volume 147
Author(s): P. Rozpądek, A. Domka, R. Ważny, M. Nosek, R. Jędrzejczyk, K. Tokarz, K. Turnau
The endophytic fungus Mucor sp. was isolated from Arabidopsis arenosa inhabiting post mining wastes lands. Its role in plant adaptation to toxic metal enriched environment was evaluated. Plants inoculated with the fungus yielded significantly more biomass. Their growth response was correlated with significant elongation of root hairs, an improved water and P status and a significant upregulation of the expression of genes associated with nutrient uptake. The mechanism of root hair elongation was investigated with auxin and ethylene insensitive Arabidopsis thaliana mutants. The results clearly indicate that the root hair elongation phenotype results from fungi induced alterations in ethylene metabolism. The upregulation of close to 50 genes associated with ethylene biosynthesis and signaling confirm these results. The accumulation of Zn and Fe was lower in endophyte inoculated plants. Additionally, root to shoot translocation of Fe, Cd and Zn was improved. The expression of metal transporters associated with metal influx, efflux and distribution within the plant corresponded with altered metal homeostasis. The results of this study clearly show that the endophytic fungus plays an important role in the adaptation of the non-mycorrhizal A. arenosa to metal toxicity.

http://ift.tt/2BeG9F2

A new three-dimensional zinc-based metal-organic framework as a fluorescent sensor for detection of cadmium ion and nitrobenzene

Publication date: 1 March 2018
Source:Journal of Colloid and Interface Science, Volume 513
Author(s): Yanan Pan, Jundong Wang, Xiumei Guo, Xiaoyan Liu, Xiaoliang Tang, Haixia Zhang
In this study, a novel three-dimensional zinc-based metal-organic framework (Zn-MOF), i.e., {Zn2(L)2(DMF)2H2O}n (L = 2,5-bis(phenylamino)-1,4-benzenedicarboxylic acid) was designed and developed under solvothermal condition. As a proof-of-principle, a π-conjugated framework of carboxylate ligand capable of "bottom up" synthesis was integrated with metal ion to construct a novel MOF for sensing applications. As expected, the synthesized Zn-MOF exhibited fluorescence enhancement for cadmium ion (Cd²⁺) and sensing of nitrobenzene (NB) through fluorescence quenching. The detection limits were calculated to be 0.12 μM for Cd²⁺ and 1.19 μg mL⁻¹ for NB based on signal-to-noise ratio of 3:1. Moreover, various techniques and density functional theory investigations verified that the possible sensing mechanisms for Cd²⁺ and NB included ion exchange and photoinduced electron transfer, respectively. Finally, their practical applications on real samples also demonstrated that the Zn-MOF-based sensor can be effectively utilized for detection and imaging of Cd²⁺ present in the real water samples and living cells. This study may inspire future research and design of target fluorescent MOFs with specific functions.

Graphical abstract

http://ift.tt/2zf7Z2E

Noise exposure while commuting in Toronto - a study of personal and public transportation in Toronto

Abstract

Background

With an increasing proportion of the population living in cities, mass transportation has been rapidly expanding to facilitate the demand, yet there is a concern that mass transit has the potential to result in excessive exposure to noise, and subsequently noise-induced hearing loss.

Methods

Noise dosimetry was used to measure time-integrated noise levels in a representative sample of the Toronto Mass Transit system (subway, streetcar, and buses) both aboard moving transit vehicles and on boarding platforms from April – August 2016. 210 measurements were conducted with multiple measurements approximating 2 min on platforms, 4 min within a vehicle in motion, and 10 min while in a car, on a bike or on foot. Descriptive statistics for each type of transportation, and measurement location (platform vs. vehicle) was computed, with measurement locations compared using 1-way analysis of variance.

Results

On average, there are 1.69 million riders per day, who are serviced by 69 subway stations, and 154 streetcar or subway routes. Average noise level was greater in the subway and bus than in the streetcar (79.8 +/− 4.0 dBA, 78.1 +/− 4.9 dBA, vs 71.5 +/−1.8 dBA, p < 0.0001). Furthermore, average noise measured on subway platforms were higher than within vehicles (80.9 +/− 3.9 dBA vs 76.8 +/− 2.6 dBA, p < 0.0001). Peak noise exposures on subway, bus and streetcar routes had an average of 109.8 +/− 4.9 dBA and range of 90.4–123.4 dBA, 112.3 +/− 6.0 dBA and 89.4–128.1 dBA, and 108.6 +/− 8.1 dBA and 103.5–125.2 dBA respectively. Peak noise exposures exceeded 115 dBA on 19.9%, 85.0%, and 20.0% of measurements in the subway, bus and streetcar respectively.

Conclusions

Although the mean average noise levels on the Toronto transit system are within the recommended level of safe noise exposure, cumulative intermittent bursts of impulse noise (peak noise exposures) particularly on bus routes have the potential to place individuals at risk for noise induced hearing loss.

http://ift.tt/2zdA9v4

Noise exposure while commuting in Toronto - a study of personal and public transportation in Toronto

Abstract

Background

Methods

Results

Conclusions

http://ift.tt/2zdA9v4

Constitutively Active SMAD2/3 Are Broad-Scope Potentiators of Transcription-Factor-Mediated Cellular Reprogramming

Publication date: Available online 22 November 2017
Source:Cell Stem Cell
Author(s): Tyson Ruetz, Ulrich Pfisterer, Bruno Di Stefano, James Ashmore, Meryam Beniazza, Tian V. Tian, Daniel F. Kaemena, Luca Tosti, Wenfang Tan, Jonathan R. Manning, Eleni Chantzoura, Daniella Rylander Ottosson, Samuel Collombet, Anna Johnsson, Erez Cohen, Kosuke Yusa, Sten Linnarsson, Thomas Graf, Malin Parmar, Keisuke Kaji
Reprogramming of cellular identity using exogenous expression of transcription factors (TFs) is a powerful and exciting tool for tissue engineering, disease modeling, and regenerative medicine. However, generation of desired cell types using this approach is often plagued by inefficiency, slow conversion, and an inability to produce mature functional cells. Here, we show that expression of constitutively active SMAD2/3 significantly improves the efficiency of induced pluripotent stem cell (iPSC) generation by the Yamanaka factors. Mechanistically, SMAD3 interacts with reprogramming factors and co-activators and co-occupies OCT4 target loci during reprogramming. Unexpectedly, active SMAD2/3 also markedly enhances three other TF-mediated direct reprogramming conversions, from B cells to macrophages, myoblasts to adipocytes, and human fibroblasts to neurons, highlighting broad and general roles for SMAD2/3 as cell-reprogramming potentiators. Our results suggest that co-expression of active SMAD2/3 could enhance multiple types of TF-based cell identity conversion and therefore be a powerful tool for cellular engineering.

Graphical abstract

Teaser

Ruetz et al. show that constitutively active SMAD2/3 has a surprising ability to boost the efficiency of cell reprogramming both to iPSCs and across lineages and may therefore be a general factor that can enhance transcription-factor-mediated reprogramming in a variety of contexts.

http://ift.tt/2zZNwT7

Injury Activates Transient Olfactory Stem Cell States with Diverse Lineage Capacities

Publication date: Available online 22 November 2017
Source:Cell Stem Cell
Author(s): Levi Gadye, Diya Das, Michael A. Sanchez, Kelly Street, Ariane Baudhuin, Allon Wagner, Michael B. Cole, Yoon Gi Choi, Nir Yosef, Elizabeth Purdom, Sandrine Dudoit, Davide Risso, John Ngai, Russell B. Fletcher
Tissue homeostasis and regeneration are mediated by programs of adult stem cell renewal and differentiation. However, the mechanisms that regulate stem cell fates under such widely varying conditions are not fully understood. Using single-cell techniques, we assessed the transcriptional changes associated with stem cell self-renewal and differentiation and followed the maturation of stem cell-derived clones using sparse lineage tracing in the regenerating mouse olfactory epithelium. Following injury, quiescent olfactory stem cells rapidly shift to activated, transient states unique to regeneration and tailored to meet the demands of injury-induced repair, including barrier formation and proliferation. Multiple cell fates, including renewed stem cells and committed differentiating progenitors, are specified during this early window of activation. We further show that Sox2 is essential for cells to transition from the activated to neuronal progenitor states. Our study highlights strategies for stem cell-mediated regeneration that may be conserved in other adult stem cell niches.

Graphical abstract

Teaser

Gadye et al. use multiple single-cell techniques to identify the cell state transitions underlying the stem cell self-renewal and differentiation during injury-induced regeneration of the olfactory epithelium. Olfactory stem cells shift en masse to a transient cell state unique to regeneration in which diverse fates are specified.

http://ift.tt/2A1lpTm

Injury Induces Endogenous Reprogramming and Dedifferentiation of Neuronal Progenitors to Multipotency

Publication date: Available online 22 November 2017
Source:Cell Stem Cell
Author(s): Brian Lin, Julie H. Coleman, Jesse N. Peterson, Matthew J. Zunitch, Woochan Jang, Daniel B. Herrick, James E. Schwob
Adult neurogenesis in the olfactory epithelium is often depicted as a unidirectional pathway during homeostasis and repair. We challenge the unidirectionality of this model by showing that epithelial injury unlocks the potential for Ascl1+ progenitors and Neurog1+ specified neuronal precursors to dedifferentiate into multipotent stem/progenitor cells that contribute significantly to tissue regeneration in the murine olfactory epithelium (OE). We characterize these dedifferentiating cells using several lineage-tracing strains and single-cell mRNA-seq, and we show that Sox2 is required for initiating dedifferentiation and that inhibition of Ezh2 promotes multipotent progenitor expansion. These results suggest that the apparent hierarchy of neuronal differentiation is not irreversible and that lineage commitment can be overridden following severe tissue injury. We elucidate a previously unappreciated pathway for endogenous tissue repair by a highly regenerative neuroepithelium and introduce a system to study the mechanisms underlying plasticity in the OE that can be adapted for other tissues.

Graphical abstract

Teaser

Lin et al. demonstrate that Ascl1+ and Neurog1+ neuronal progenitors can acquire cell fate plasticity after injury using genetic lineage trace and transplantation assays. Injury-induced multipotency occurs through a developmentally reminiscent endogenous upregulation of Sox2, KLF4, and Pax6, and dedifferentiation efficiency can be enhanced by Ezh2 inhibition.

http://ift.tt/2A1NxpI

Impact of carrier gas flow rate on the synthesis of nanodiamonds via microplasma technique

Publication date: February 2018
Source:Materials Science in Semiconductor Processing, Volume 74
Author(s): Saman Iqbal, Muhammad Shahid Rafique, Muhammad Zahid, Shazia Bashir, Muhammad Ashfaq Ahmad, Rabia Ahmad
Nanodiamonds (NDs) have been fabricated utilizing micro plasma facility. The mixture of argon as carrier gas and ethanol as precursor has been dissociated in micro plasma. The argon flow rate was varied from 4 to 9l/min. The influence of argon gas flow rates on structural, surface and optical properties of NDs was compared. An increased amount of diamond has been reported with the increase in flow rate, obtaining the maximum value at 6l/min. Further increase in flow rate starts decreasing the quality of NDs. Raman and XRD confirm that the smallest size and stress free NDs are obtained at 6l/min argon flow rate. AFM micrograph also reveals the smallest size of NDs ~27nm for 6l/min argon flow rate. The hydrophobicity of NDs increases with increasing argon flow rate as confirmed by FTIR. Photoluminescence indicates the presence of nitrogen vacancy defect centers such as N3, H3 and NV for all the flow rates. The smallest PL peak intensity at 6l/min argon flow rate indicates the lowest density of vacancy defects in the diamond. UV–Visible spectroscopy indicates the presence of nitrogen-hydrogen defect and nitrogen vacancy defect centers (N4 and N5). The largest band gap at 6l/min argon flow rate also confirms the highest quality of NDs. The centers offer promising applications as, active laser material, fluorescent markers, quantum information, nanoscale magnetic and electric filed sensors.

http://ift.tt/2mVgH4o

Influence of shape and dispersion media of titanium dioxide nanostructures on microvessel network and ossification

Publication date: Available online 23 November 2017
Source:Colloids and Surfaces B: Biointerfaces
Author(s): Verónica Freyre-Fonseca, Estefany I. Medina-Reyes, Darío I. Téllez-Medina, Gloria L. Paniagua-Contreras, Erick Monroy-Pérez, Felipe Vaca-Paniagua, Norma L. Delgado-Buenrostro, José O. Flores-Flores, Edgar O. López-Villegas, Gustavo F. Gutiérrez-López, Yolanda I. Chirino
Titanium dioxide nanoparticles (TiO2 NPs) production has been used for pigment, food and cosmetic industry and more recently, shaped as belts for treatment of contaminated water, self-cleaning windows and biomedical applications. However, the toxicological data have demonstrated that TiO2 NPs inhalation induce inflammation in in vivo models and in vitro exposure leads to cytotoxicity and DNA damage. Dermal exposure has limited adverse effects and the possible risks for implants used for tissue regeneration is still under research. Then, it has been difficult to establish a straight statement about TiO2 NPs toxicity since route of exposure and shapes of nanoparticles play an important role in the effects. In this study we aimed to investigate the effect of three different types of TiO2 NPs (industrial, food-grade and belts) dispersed in fetal bovine serum (FBS) and saline solution (SS) on microvessel network, angiogenesis gene expression and femur ossification using a chick embryo model after an acute exposure of NPs on the day 7 after eggs fertilization. Microvascular density of chorioallantoic membrane (CAM) was analyzed after 7days of NPs injection and vehicles induced biological effects per se. NPs dispersed in FBS or SS have slight differences in microvascular density, mainly opposite effect on angiogenesis gene expression and no effects on femur ossification for NPs dispersed in SS. Interestingly, NPs shaped as belts dramatically prevented the alterations in ossification induced by FBS used as vehicle.

Graphical abstract

http://ift.tt/2zuHZod

Leveraging Mega-trends in Medicine Today to Enhance Patient Care in Radiology Tomorrow

Publication date: Available online 22 November 2017
Source:Academic Radiology
Author(s): Andrew B. Rosenkrantz

http://ift.tt/2A1cdOQ

Shear Wave Elastography (SWE) for Monitoring of Treatment of Tendinopathies

Publication date: Available online 16 November 2017
Source:Academic Radiology
Author(s): Timm Dirrichs, Valentin Quack, Matthias Gatz, Markus Tingart, Björn Rath, Marcel Betsch, Christiane K. Kuhl, Simone Schrading
Rationale and ObjectivesWe aimed to investigate the diagnostic accuracy with which shear wave elastography (SWE) can be used to monitor response to treatment of tendinopathies, and to compare it to conventional ultrasound (US)-imaging methods (B-mode US (B-US) and power Doppler US (PD-US)).Materials and MethodsA prospective Institutional Review Board-approved longitudinal study on 35 patients with 47 symptomatic tendons (17 Achilles-, 15 patellar-, and 15 humeral-epicondylar) who underwent standardized multimodal US and standardized clinical assessment before and after 6 months of treatment (tailored stretching exercise, sport break, and local Polidocanol) was carried out. All US studies were performed by radiologists blinded to the clinical symptoms on both tendon sides to avoid biased interpretations, by B-US, PD-US, and SWE, conducted in the same order, using a high-resolution linear 15 MHz probe (Aixplorer). Orthopedic surgeons who were in turn blinded to US imaging results used established orthopedic scores (Victorian Institute of Sports Assessment questionnaire for Achilles, Victorian Institute of Sports Assessment questionnaire for patellar tendons, and Disability Arm Shoulder Hand scoring system) to rate presence, degree, and possible resolution of symptoms. We analyzed the diagnostic accuracy with which the different US imaging methods were able to detect symptomatic tendons at baseline as well as treatment effects, with orthopedic scores serving as reference standard.ResultsB-US, PD-US, and SWE detected symptomatic tendons with a sensitivity of 66% (31 of 47), 72% (34 of 47), and 87.5% (41 of 47), respectively. Positive predictive value was 0.67 for B-US, 0.87 for PD-US, and 1 for SWE. After treatment, clinical scores improved in 68% (32 of 47) of tendons. Treatment effects were observable by B-US, PD-US, and SWE with a sensitivity of 3.1% (1 of 32), 28.1% (9 of 32), and 81.3% (26 of 32), respectively. B-US was false-positive in 68.8% (20 of 32), PD-US in 46.9% (15 of 32), and SWE in 12.5% (4 of 32) (SWE). Clinical scores and B-US, PD-US, and SWE findings correlated poorly (r = 0.24), moderately (r = 0.59), and strongly (r = 0.80).ConclusionUnlike B-US or PD-US, SWE is able to depict processes associated with tendon healing and may be a useful tool to monitor treatment effects.

http://ift.tt/2zYTLXg

The Current State of Radiology Call Assistant Triage Programs Among US Radiology Residency Programs

Publication date: Available online 22 November 2017
Source:Academic Radiology
Author(s): Jennifer Shaffer Ngo, Charles M. Maxfield, Gary R. Schooler
Rationale and ObjectivesGiven increasing volume and workflow interruptions in radiology, we sought to identify and characterize radiology call assistant triage (RCAT) programs among US radiology residency programs.Materials and MethodsA survey was created using Qualtrics survey software and emailed to all members of the Association of Program Directors in Radiology listserv. A total of 296 active members belong to this listserv, including program directors and assistant program directors. The survey included questions about the existence and specifics of a call triage assistant program.ResultsData were obtained from 88 active members of the Association of Program Directors in Radiology (30% response rate). Of those, 20 programs (23%) have an RCAT program. Triage assistant staffing includes nonmedical or clerical staff (60%), medical students (30%), first-year radiology residents (5%), and technologists (5%). All respondents with RCAT programs report satisfaction with their program and plan to continue. A significant majority (75%) have no plans to change, whereas the remaining 25% are considering program expansion and pay increases. Among residency programs without RCAT programs, none reported termination of their triage program. The most common reasons for not having triage assistants include cost, lack of awareness, differing opinions on utility, and the presence of 24/7 attending coverage.ConclusionTwenty US radiology residency programs report having an RCAT program. All report satisfaction with their program despite different staffing models. RCAT programs may represent an effective measure in limiting interruptions and potentially decreasing interpretative errors made by residents on call.

http://ift.tt/2ApWzNZ

Design, synthesis and pharmacological evaluation of some novel indanone derivatives as acetylcholinesterase inhibitors for the management of cognitive dysfunction.

Publication date: Available online 22 November 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Poonam Piplani, Ankit Jain, Dhiksha Devi, Anjali, Anuradha Sharma, Pragati Silakari
The present study reports the effect of indanone derivatives on scopolamine induced deficit cholinergic neurotransmission serving as promising leads for the therapeutics of cognitive dysfunction. Eleven compounds 54 - 64 have been designed, synthesised and evaluated against behavioural alterations using step down passive avoidance protocol at a dose of 0.5 mg/kg with Donepezil (1) as the reference standard. All the synthesised compounds were evaluated for their in vitro acetylcholinesterase (AChE) inhibition at five different concentrations using mice brain homogenate as the source of the enzyme. Compounds 54, 56, 59 and 64 displayed appreciable activity with an IC50 value of 14.06 µM, 12.30 µM, 14.06 µM and 12.01 µM, respectively towards acetylcholinesterase inhibition. The molecular docking study performed to predict the binding mode of the compounds suggested that these compounds could bind appreciably to the amino acids present at the active site of recombinant human acetylcholinesterase (rhAChE). The behavioral, biochemical and in silico pharmacokinetic studies were in concordance with each other.

Graphical abstract

http://ift.tt/2hV4Y49

7-methylguanosine monophosphate analogues with 5′-(1,2,3-triazoyl) moiety: synthesis and evaluation as the inhibitors of cNIIIB nucleotidase

Publication date: Available online 22 November 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Mateusz Kozarski, Dorota Kubacka, Blazej A. Wojtczak, Renata Kasprzyk, Marek R. Baranowski, Joanna Kowalska
The hydrolysis of nucleoside 5′-monophosphates to the corresponding nucleosides and inorganic phosphate is catalysed by 5′-nucleotidases, thereby contributing to the control of endogenous nucleotide turnover and affecting the fate of exogenously delivered nucleotide- and nucleoside-derived therapeutics in cells. A recently identified nucleotidase cNIIIB shows preference towards 7-methylguanosine monophosphate (m⁷GMP) as a substrate, which suggests its potential involvement in mRNA degradation. However, the extent of biological functions and the significance of cNIIIB remains to be elucidated. Here, we synthesised a series of m⁷GMP analogues carrying a 1,2,3-triazole moiety at the 5′ position as the potential inhibitors of human cNIIIB. The compounds were synthesised by using the copper-catalysed azide-alkyne cycloaddition (CuAAC) between 5′-azido-5′-deoxy-7-methylguanosine and different phosphate or phosphonate derivatives carrying terminal alkyne. The analogues were evaluated as cNIIIB inhibitors using HPLC and malachite green assays, demonstrating that compound 1a, carrying a 1,2,3-triazoylphosphonate moiety, inhibits cNIIIB activity at micromolar concentrations (IC50 87.8 ± 7.5 µM), while other analogues showed no activity. In addition, compound 1d was identified as an artifical substrate for ^HscNIIIB. Further characterization of inhibitor 1a revealed that it is poorly recognised by other m⁷G-binding proteins, eIF4E and DcpS, indicating its selectivity towards cNIIIB. The first inhibitor (1a) and unnatural substrate (1d) of cNIIIB, identified here, can be used as molecular probes for the elucidation of biological roles of cNIIIB, including the verification of its proposed function in mRNA metabolism.

Graphical abstract

http://ift.tt/2hV6GT0

Lead identification and optimization of bacterial Glutamate racemase inhibitors

Publication date: Available online 21 November 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Prasanthi Malapati, Vagolu Siva Krishna, Radhika Nallangi, Nikhila Meda, Rudraraju Reshma Srilakshmi, Dharmarajan Sriram
Mycobacterium tuberculosis glutamate racemase is an essential enzyme involved in peptidoglycan synthesis and conserved in most bacteria. Small molecule inhibitors were reported on other bacterial species whereas in M. tuberculosis it wasn't explored much. In this study we have screened in house compound library using fluorescence thermal shift assay and enzyme inhibition assay, form this (1-(3-(benzo[d]thiazol-2-yl)phenyl)-3-(p-tolyl)thiourea) was identified as lead compound with IC50 19.47±0.81 μM. Further lead optimization by synthesis resulted in twenty-three compounds, of which Compound 25 has shown more efficacy compared to lead 1 showing non- competitive mode of inhibition with IC50 1.32±0.43 μM. It also showed significant activity (represented in log reduction) in nutrient starved dormant M. tuberculosis model (2.1), M. tuberculosis biofilm assay (2.0) and in vivo M. marinum infected zebrafish model (3.5).

Graphical abstract

http://ift.tt/2hV4PO9

Pre-diagnostic dynamic HPV16 IgG seropositivity and risk of oropharyngeal cancer: Methodological issues

We were interested to read the paper authored by Anderson and colleagues that was published in the journal of Oral Oncology in October 2017 [1]. The authors aimed to examine the association of HPV16 antibodies (Abs) and oropharyngeal cancer (OPC) risk in sera obtained prior to clinical diagnosis. They found that Abs to E2 were strongly associated with cases 0–2 years pre- diagnosis (odds ratio (OR): 150.1; 95% confidence interval (CI): 27.4–1040.0) and HPV status (OR: 35.6; 95% CI: 8.7–200.0). Although their study makes valuable contribution to the area, some methodological issues need to be taken into account.

http://ift.tt/2mUOsTl

Applicability of energy-positive net-zero water management in Alaska: technology status and case study

Abstract

Challenges of water and wastewater management in Alaska include the potential need for above-grade and freeze-protected piping, high unit energy costs and, in many rural areas, low population density and median annual income. However, recently developed net-zero water (NZW), i.e., nearly closed-loop, direct potable water reuse systems, can retain the thermal energy in municipal wastewater, producing warm treated potable water without the need for substantial water re-heating, heat pumping or transfer, or additional energy conversion. Consequently, these systems are projected to be capable of saving more energy than they use in water treatment and conveyance, in the temperate USA. In this paper, NZW technology is reviewed in terms of potential applicability in Alaska by performing a hypothetical case study for the city of Fairbanks, Alaska. Results of this paper study indicate that in municipalities of Alaska with local engineering and road access, the use of NZW systems may provide an energy-efficient water service option. In particular, case study modeling suggests hot water energy savings are equivalent to five times the energy used for treatment, much greater savings than in mid-latitudes, due largely to the substantially higher energy needed for heating water from a conventional treatment system and lack of need for freeze-protected piping. Further study of the applicability of NZW technology in cold regions, with expanded evaluation in terms of system-wide lifecycle cost, is recommended.

http://ift.tt/2BfkJYk

Small-diameter compression screws completely embedded in bone for rigid internal fixation of the condylar head of the mandible

Complications after open reduction and internal fixation of the condylar head include irritation of the sensitive soft tissues surrounding the temporomandibular joint (TMJ) caused by permanent friction from the screw head,1 and resorption beneath the screw heads because of bony remodelling around the lateral pole.1,2 However, a second operation can risk damage to the facial nerve.

http://ift.tt/2A3HM8o

Demonstration of analgesic effect of intranasal ketamine and intranasal fentanyl for postoperative pain after pediatric tonsillectomy

Tonsillectomy is one of the oldest and most commonly performed surgical procedure in otolaryngology. Postoperative pain management is still an unsolved problem. In this study, our aim is to demonstrate the efficacy of intranasal ketamine and intranasal fentanyl for postoperative pain relief after tonsillectomy in children.

http://ift.tt/2BhbzuC

Childhood hearing loss is a key feature of CAPOS syndrome: A case report

CAPOS syndrome (cerebellar ataxia, areflexia, pes cavus, optic atrophy, and sensorineural hearing loss) is a rare neurological disorder, recently associated with the c.2452G > A hotspot mutation in the ATP1A3 gene, with sensorineural hearing loss as a prominent feature. We herein report on a girl who has experienced hearing loss for three years following an initial encephalitic episode when aged 15 months old. CAPOS was diagnosed only when she was six years old by targeted testing whilst she displayed optic atrophy, cerebellar signs and areflexia.

http://ift.tt/2zdgGuu

Identification of two novel pathogenic compound heterozygous MYO7A mutations in Usher syndrome by whole exome sequencing

The current study aims to identify the pathogenic sites in a core pedigree of Usher syndrome (USH). A core pedigree of USH was analyzed by whole exome sequencing (WES). Mutations were verified by polymerase chain reaction (PCR) amplification and Sanger sequencing. Two pathogenic variations (c.849+2T>C and c.5994G>A) in MYO7A were successfully identified and individually separated from parents. One variant (c.849+2T>C) was nonsense mutation, causing the protein terminated in advance, and the other one (c.5994G>A) located near the boundary of exon could cause aberrant splicing.

http://ift.tt/2BflJMm

Spontaneous retropharyngeal and mediastinal thoracic duct cyst in an infant with respiratory distress

Thoracic duct cysts (TDC) within the retropharyngeal space and mediastinum are exceeding rare lesions, with the majority related to trauma or neoplasm. We describe a case of an otherwise healthy 8-month-old boy who presented with severe respiratory distress, which was found to be caused by a large, spontaneous TDC occupying most the retropharyngeal and mediastinal space. To our knowledge, this is the youngest patient to date presenting with TDC. Ultimately, his TDC was completely resolved with sclerotherapy, however the patient's age and size presented unique challenges to his medical management, which we describe below.

http://ift.tt/2zdKE1a

Cataplexy plus presence of HLA-DQB1*0602 allele can predict Hypocretin-1 deficiency

Currently, narcolepsy patients are treated with stimulants and other drugs for cataplexy.[1] However, emerging therapies focus on hypocretin-1 "replacement" and immunotherapy.[2] Unfortunately, the hypocretin-1 levels in CSF analysis depend on a lumbar puncture and radioimmunoassay, which are not available for the most part in sleep centers. Thus/Therefore, we studied the areas under the ROC curve of clinical or/and electrophysiology methods to predict Hypocretin-1 deficiency.

http://ift.tt/2ApcNXk

Willis-Ekbom disease/restless legs syndrome in patients with opioid withdrawal

Many patients with opioid use disorder report symptoms similar to restless legs syndrome (RLS) during withdrawal. However, whether these symptoms are true RLS, their predictors and effect of treatment with pregabalin are still unknown.

http://ift.tt/2zYMNRZ

Work-Related Musculoskeletal Disorders among Plastic Surgeons: A Systematic Review

J reconstr Microsurg
DOI: 10.1055/s-0037-1608680

Background To date, no review has been conducted on the growing body of literature describing various work-related musculoskeletal disorders (MSDs), ergonomic hazards, and potential interventions relevant to plastic surgeons. This systematic review sought to (1) define the scope of coverage of this important issue in the peer-reviewed literature; (2) critically assess the evidence; and (3) provide recommendations for future directions. Methods We conducted a literature search of MEDLINE, Embase, Web of Science, and PubMed from the inception of each database until 2016. All articles reporting on work-related MSDs or ergonomics among plastic surgeons were reviewed, summarized, and assessed for trends. Results Sixteen articles met our inclusion criteria including five expert opinions, four cross-sectional studies and case reports/series, one review, and six experimental studies. Four articles presented evidence on disease burden. The most commonly described work-related MSD was cervical spine disease, for which one study reported a career prevalence of 24.7% (point prevalence in the general population: 0.1–0.4%); three studies reported 64 cases of surgeon work-related MSD resulting in surgical intervention, decreased productivity, or involuntary early retirement. Eight studies described interventions, most of which aimed to improve the ergonomics of microsurgery. Conclusion This review found low-level evidence of plastic surgeons' vulnerability to a work-related MSD at times severe enough to end careers. Further investigation is needed to clearly define this important problem in plastic surgery. Specifically, future directions should include more methodologically rigorous epidemiologic studies evaluating disease burden.
[...]

Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Article in Thieme eJournals:
Table of contents | Abstract | Full text

http://ift.tt/2hWvbzu

Food Allergy in the developing world

http://ift.tt/2zYFBVZ

Pesticide residues in muscles of some marine fish species and seaweeds of Iskenderun Bay (Northeastern Mediterranean), Turkey

Abstract

Pesticide residues in muscles of nine marine fish and four seaweed species of Iskenderun Bay (Northeastern Mediterranean) have been investigated. In sampled fish species, two herbicides, three insecticides, two fungicides, and one synergist were identified and quantified. Metribuzin DADK, propamocarb HCl, and piperonyl butoxide (PBO) were detected in all the muscles of sampled fish species. Metribuzin DADK was the most abundant pesticide residue in fish muscles and the highest metribuzin DADK concentration was found in sardine (311.20 μg/kg). Propamocarb HCl concentrations varied greatly among species; from 0.530 ± 0.020 μg/kg in striped sea bream to 34.170 μg/kg in sea bass. The level of PBO ranged from 0.001 μg/kg for fourlined terapon to 0.013 μg/kg for sardine. No measurable oxamyl residue was found in any of the muscles of sampled fish species (except sardine). In seaweeds, two herbicides and two insecticides were identified and quantified. Metribuzin DADK was the most abundant and found in Cystoseira corniculata (5.01 mg/kg), Corallina elongata (0.703 mg/kg), and Jania rubens (3.85 mg/kg). Molinate was a minor contaminant and only found in Corallina elongata (0.002 mg/kg). Pyrethrin I was determined only in Padina pavonia to be 0.567 mg/kg. Pyrethrine II was found in Padina pavonia and Corallina elongate to be 1.214 and 0.229 mg/kg, respectively. The most hazardous pesticide residues of organochlorines and organophosphorus were not detected in both sampled fish muscles and seaweeds. There are no clear maximum residue limits for the detected eight pesticide residues declared for fish muscle by European Union MRL (2017). In conclusion, it can be considered that observed concentrations of pesticides in sampled nine marine fish species do not have a potential health risk for consumers. Some of the detected pesticide residues can be toxic for algae and aquatic life and regular monitoring studies are therefore essential to control the pesticide concentrations of aquatic biota in the region.

http://ift.tt/2mRYqF0

Metabolomic analysis of the toxic effect of chronic exposure of cadmium on rat urine

Abstract

This study aimed to assess the toxic effect of chronic exposure to cadmium through a metabolomic approach based on ultra-performance liquid chromatography/mass spectrometry (UPLC–MS). Forty male Sprague–Dawley rats were randomly assigned to the following groups: control, low-dose cadmium chloride (CdCl₂) (0.13 mg/kg body weight (bw)), middle-dose CdCl₂ (0.8/kg bw), and high-dose CdCl₂ (4.9 mg/kg bw). The rats continuously received CdCl₂ via drinking water for 24 weeks. Rat urine samples were then collected at different time points to establish the metabolomic profiles. Multiple statistical analyses with principal component analysis and partial least squares–discriminant analysis were used to investigate the metabolomic profile changes in the urine samples and screen for potential biomarkers. Thirteen metabolites were identified from the metabolomic profiles of rat urine after treatment. Compared with the control group, the treated groups showed significantly increased intensities of phenylacetylglycine, guanidinosuccinic acid, 4-pyridoxic acid, 4-aminohippuric acid, 4-guanidinobutanoic acid, allantoic acid, dopamine, LysoPC(18:2(9Z,12Z)), and L-urobilinogen. By contrast, the intensities of creatinine, L-carnitine, taurine, and pantothenic acid in the treated groups were significantly decreased. These results indicated that Cd disrupts energy and lipid metabolism. Meanwhile, Cd causes liver and kidney damage via induction of oxidative stress; serum biochemical indices (e.g., creatinine and urea nitrogen) also support the aforementioned results.

http://ift.tt/2ztDnhW

Does the proposed removal of mitotic count as a prognostic indicator in melanoma, accurately reflect the risk profile for metastasis in UK patients?

We of the Newcastle upon Tyne Hospitals NHS Foundation Trust Specialist Skin Cancer MDT, write with concern regarding the most recently published AJCC 8th edition staging system for malignant melanoma 1 (proposed to be implemented in the UK in January 2018) and its possible implications for accurate risk stratification and prognostic forecasting.

http://ift.tt/2iGHNaL

The effect of supragingival biofilm re-development on the subgingival microbiota in chronic periodontitis

Publication date: January 2018
Source:Archives of Oral Biology, Volume 85
Author(s): Fátima Aparecida Rocha Resende Hartenbach, Carina Maciel Silva-Boghossian, Ana Paula Vieira Colombo
ObjectiveIn this study, we hypothesized that in the absence of oral hygiene, re-growth of the climax microbial communities of supra and subgingival biofilm happens in a faster and more intense fashion in individuals with chronic periodontitis (CP) compared to periodontally healthy controls (PH).DesignThirty patients (PH=15 and CP=15) received professional supragingival prophylaxis, and were asked to refrain from oral hygiene for 7days. Supra and subgingival biofilm samples and GCF were collected from randomly selected quadrants at baseline (before prophylaxis), immediately after prophylaxis, 2h, 6h, 24h, and 7days after prophylaxis. The composition of the biofilm was determined by the checkerboard method.ResultsAll subjects developed gingivitis at the end of 7days without oral hygiene. GCF mean volumes were significantly higher in CP than PH patients at baseline, but they started decreasing 2h after prophylaxis, returning to baseline levels after 24h in both groups. Significant increases in mean counts for most of the species evaluated were observed in both groups and biofilms over time (p<0.05). Few hours after prophylaxis, a more marked reduction in microbial counts happened in the supragingival biofilm of the CP group, and re-development of biofilm started later than in the PH group. At 7days, no differences were seen between groups. Significant differences in kinetics of re-colonization between groups were observed only in the subgingival biofilm for T. denticola and F. nucleatum ss vicentii (increased in the CP), and N. mucosa (increased in the PH group; p<0.05).ConclusionsBiofilm re-development was very similar between CP and PH individuals, although microbial re-growth occurred few hours earlier in PH than PC. Only 3 species in the subgingival biofilm differed in re-colonization between groups. Thus, we reject the hypothesis that re-colonization of biofilm in CP patients is more intense and faster than in individuals with PH.

http://ift.tt/2A3x9SV

Aims & Scope/Editorial board

Publication date: January 2018
Source:Archives of Oral Biology, Volume 85

http://ift.tt/2jeYPw8

Homeobox genes and tooth development: Understanding the biological pathways and applications in regenerative dental science

Publication date: January 2018
Source:Archives of Oral Biology, Volume 85
Author(s): Anand Ramanathan, Thekkeparambil Chandrabose Srijaya, Prema Sukumaran, Rosnah Binti Zain, Noor Hayaty Abu Kasim
ObjectivesHomeobox genes are a group of conserved class of transcription factors that function as key regulators during the embryonic developmental processes. They act as master regulator for developmental genes, which involves coordinated actions of various auto and cross-regulatory mechanisms. In this review, we summarize the expression pattern of homeobox genes in relation to the tooth development and various signaling pathways or molecules contributing to the specific actions of these genes in the regulation of odontogenesis.Materials and methodsAn electronic search was undertaken using combination of keywords e.g. Homeobox genes, tooth development, dental diseases, stem cells, induced pluripotent stem cells, gene control region was used as search terms in PubMed and Web of Science and relevant full text articles and abstract were retrieved that were written in English. A manual hand search in text books were also carried out. Articles related to homeobox genes in dentistry and tissue engineering and regenerative medicine of odontogenesis were selected.ResultsThe possible perspective of stem cells technology in odontogenesis and subsequent analysis of gene correction pertaining to dental disorders through the possibility of induced pluripotent stem cells technology is also inferred.ConclusionsWe demonstrate the promising role of tissue engineering and regenerative medicine on odontogenesis, which can generate a new ray of hope in the field of dental science.

http://ift.tt/2A3skJq

Novel methodology for determining the effect of adsorbates on human enamel acid dissolution

Publication date: January 2018
Source:Archives of Oral Biology, Volume 85
Author(s): N. Pechlivani, D.A. Devine, P.D. Marsh, A. Mighell, S.J. Brookes
ObjectiveThe effect of various interventions on enamel demineralisation can be determined by chemically measuring mineral ions dissolved by the attacking acid. Results are usually expressed as mineral loss per surface area of enamel exposed. Acid resistant varnish or adhesive tape are typically used to delineate an area of enamel. However, enamel surface curvature, rugosity and porosity reduce the reliability of simple area measurements made at the macro scale. Our aim was to develop a simple method for investigating the effect of adsorbates on enamel demineralisation that does not rely on knowing the area of enamel exposed. As an exemplar we have used salivary proteins as a model adsorbate.DesignNatural human tooth enamel surfaces were subjected to five sequential acid challenges and then incubated in adsorbate (whole clarified saliva) followed by a further 15 acid challenges. Demineralisation was determined by measuring the phosphate released into the acid during each exposure by a spectrophotometric assay. The initial five challenges established a mean baseline mineral loss for each tooth against which the effect of subsequently adsorbed proteins could be compared.ResultsSalivary proteins significantly reduced the acid demineralisation of human enamel by 43% (p<0.01). Loss of proteins during each challenge corresponded to a gradual reduction in the degree of protection afforded.ConclusionsThe methodology provides a simple and flexible means to investigate the effect of any adsorbate on enamel acid dissolution. Knowledge of the area of exposed enamel is irrelevant as each tooth acts as its own negative control.

http://ift.tt/2jf1Pcd

Raloxifene reduces the risk of local alveolar bone destruction in a mouse model of periodontitis combined with systemic postmenopausal osteoporosis

Publication date: January 2018
Source:Archives of Oral Biology, Volume 85
Author(s): Ryota Ichimaru, Tsukasa Tominari, Shosei Yoshinouchi, Chiho Matsumoto, Kenta Watanabe, Michiko Hirata, Yukihiro Numabe, Gillian Murphy, Hideaki Nagase, Chisato Miyaura, Masaki Inada
OBJECTIVEPeriodontitis is characterized by local inflammation leading to tooth loss and severe destruction of alveolar bone. Raloxifene is a selective estrogen receptor modulator (SERM) that halts estrogen deficiency-induced systemic bone loss in postmenopausal osteoporosis without the side effects of cancer in breast and uterus. In this study, we examined the effects of raloxifene on alveolar bone mass in a mouse model with estrogen deficiency-induced periodontitis.METHODSPeriodontitis was induced by the injection of lipopolysaccharide (LPS) into the lower gingiva in ovariectomized (OVX) mice, and the alveolar bone and femur bone mineral density (BMD) were analyzed by dual-energy X-ray absorptiometry. To explore the direct osteoclast inhibitory effect of raloxifene, a co-culture system for osteoclast formation and organ culture of alveolar bone was established.RESULTSWhen OVX mice were treated with raloxifene, the bone loss in both alveolar bone and femur were abrogated. Interleukin 1 and/or LPS stimulated the osteoclast formation and bone-resorbing activity; however, raloxifene did not show any inhibitory effect on the osteoclast formation or function. In vivo local injection of raloxifene also did not prevent bone resorption in a mouse model of periodontitis. However, the systemic treatment of raloxifene using a mini-osmotic pump did prevent the loss of BMD of alveolar bone induced by LPS.CONCLUSIONThese results suggest that the SERM raloxifene systemically maintain alveolar bone mass in a mouse model of periodontitis with osteoporosis. Increasing the alveolar bone mass by SERMs treatment in patients with postmenopausal osteoporosis may be a useful approach to preventing the destruction of alveolar bone in late-onset periodontitis.

http://ift.tt/2A4xqFo

Cdc42 is essential for the polarized movement and adhesion of human dental pulp stem cells

Publication date: January 2018
Source:Archives of Oral Biology, Volume 85
Author(s): Mingwei Li, Liang Ma, Bing Song, Dingyi Yu, Min Xiao, Xiaohan Mei, Huihui Guo, Qing Yu
ObjectiveStem cell-based tissue repair and regeneration require the regulation of cell migration and adhesion. As a regulator of cell polarization, Cdc42 (cell division control protein 42) plays a basic role at the initial stage of cell migration and adhesion. This study explores the effect of Cdc42 on the polarized migration and adhesion of hDPSCs (human dental pulp stem cells).DesignHDPSCs were isolated from extracted third molars and transfected with siRNA targeted against Cdc42. Scratch wound assays and transwell assays were performed to detect the migration of human dental pulp stem cells. Polarization assays were applied to explore the polarized movement of Golgi bodies and nuclei.Western blot was used to examine the expression of related proteins.ResultsThe expression of Cdc42 was knocked down by siRNA transfection, which inhibited the migration of hDPSCs in both the scratch wound assays and transwell assays. Meanwhile, the proportion of polarized hDPSCs during migration was also decreased, and the adhesion ability of hDPSCs was downregulated. Western blot demonstrated that these effects were dependent on FAK (focal adhesion kinase), β-catenin and GSK3β (Glycogen synthase kinase-3β).ConclusionOur study demonstrates that Cdc42 plays an essential role during the polarized movement and adhesion of hDPSCs.

http://ift.tt/2jfOqQW

Inhibitory effect of probiotic lactobacilli supernatants on single and mixed non-albicans Candida species biofilm

Publication date: January 2018
Source:Archives of Oral Biology, Volume 85
Author(s): Yulong Tan, Matthias Leonhard, Doris Moser, Su Ma, Berit Schneider-Stickler
ObjectivesOral candidiasis is one of the most common human fungal infections. While most cases of the Candida species isolated from the oral cavity are Candida albicans, a large number of candidiasis is attributed to non-albicans Candida species. In this study, we aim to evaluate the in vitro inhibition of supernatants of Lactobacillus gasseri and Lactobacillus rhamnosus on the single and mixed species biofilm of non-albicans Candida species, including Candida tropicalis, Candida krusei and Candida parapsilosis.DesignCell-free supernatants of Lactobacillus gasseri and Lactobacillus rhamnosus were prepared. Single and mixed non-albicans Candida species biofilm were formed in the 96-well microplate and on the surfaces of medical grade silicone. Biomass and cell viability were tested with crystal violet and cell counting kit-8. In order to examine the ability of the supernatant to disrupt pre-formed biofilm, supernatant was added to 24h-old biofilms. Biofilm architecture on silicone was investigated by scanning electron microscopy and confocal laser scanning microscopy was used to examine live/dead organisms within biofilm.ResultsSingle and mixed species biofilms and cell viability of non-albicans Candida biofilms were inhibited by probiotic lactobacilli supernatants. Matrue biofilm formation was disrupted by lactobacilli supernatants added at 24h after biofilm initiation. Examination with confocal laser scanning microscopy and scanning electron microscopy confirmed that lactobacilli supernatants inhibited the mixed biofilms and damaged the cells.ConclusionsOur data elucidate the inhibitory activity of probiotic lactobacilli on non-albicans Candida biofilm, so as to support their utility as an adjunctive therapeutic mode against oral candida infections.

http://ift.tt/2A5s38S

Colonization of oropharynx and lower respiratory tract in critical patients: Risk of ventilator-associated pneumonia

Publication date: January 2018
Source:Archives of Oral Biology, Volume 85
Author(s): Ivany Machado de Carvalho Baptista, Frederico Canato Martinho, Gustavo Giacomelli Nascimento, Carlos Eduardo da Rocha Santos, Renata Falchete do Prado, Marcia Carneiro Valera
ObjectiveTo investigate the microbial diversity existing in oral cavity and respiratory tract samples (from mini-bronchoalveolar lavage (BAL), endotracheal aspirate, and orotracheal tube) of patients on mechanical ventilation by using the checkerboard DNA-DNA hybridisation. Also, the study aimed to evaluate whether the microbial profile in the oral cavity is found in respiratory tract samples, at different periods of mechanical ventilation time (12h, 48h, 96h) in attempt to identification of relationship between VAP (ventilator-associated pneumonia) and bacterial species studied. The last objective was to analyses correlation between blood cultures and VAP.DesignThe samples were collected from ten patients in intensive care unit with medical prescription of orotracheal intubation and mechanical ventilation. Clinical data were tabulated and blood cultures were performed according medical indication. For checkerboard samples collection, chosen sites were the dorsal side of the tongue and gingival sulcus at 12h, 48h, 96h, BAL, at 12h, endotracheal aspirate at 48 and 96h, and orotracheal tube at extubation time, when feasible.ResultsIt was possible to identify the presence of bacterial species in mouth and in the BAL/endotracheal aspirate. The data demonstrated an increase in the quantity of bacterial associated with prolonged use of mechanical ventilation (48 and 96h).ConclusionsBacterial species may migrate rapidly from mouth and upper airways during orotracheal intubation which contributes to the pathogenesis of VAP. There were associations between VAP and Enterococcus faecalis, Fusobacterium periodonticum, Gemella morbillorum, Neisseria mucosa, Propionibacterium acnes, Prevotella melaninogenica, Streptococcus oralis, Streptococcus sanguinis, Treponema denticola, Treponema socransckii, and Veillonella parvula.

http://ift.tt/2jgn3pQ

Probiotic intervention influences the salivary levels of Matrix Metalloproteinase (MMP)-9 and Tissue Inhibitor of metalloproteinases (TIMP)-1 in healthy adults

Publication date: January 2018
Source:Archives of Oral Biology, Volume 85
Author(s): Heli Jäsberg, Taina Tervahartiala, Timo Sorsa, Eva Söderling, Anna Haukioja
ObjectiveTo study the effect of orally administered Bifidobacterium animalis subsp. lactis BB-12 and Lactobacillus rhamnosus GG on the salivary levels of Matrix Metalloproteinases (MMP)-8, MMP-9 and of Tissue Inhibitor of Metalloproteinases (TIMP)-1 in healthy adults. Furthermore, the correlations between MMP-8, MMP-9 and TIMP-1 and plaque and gingival indices, salivary mutans streptococci and lactobacilli counts, and stimulated saliva secretion rate were analysed.DesignThe salivary samples originated from a randomized controlled trial where healthy student volunteers consumed probiotic or placebo lozenges twice a day for four weeks. The saliva samples were collected and clinical parameters measured at the baseline and at the end of the original study. For this study, the salivary levels of MMP-8, MMP-9 and TIMP-1 were analysed with immunofluorometric assay (IFMA) and enzyme-linked immunosorbent assay (ELISA).ResultsIn the probiotic group (n=29), salivary MMP-9 levels increased (p<0.01) and TIMP-1 levels decreased (p<0.01) significantly during the intervention. Furthermore, MMP-9/TIMP-1 ratio differed significantly from the baseline level (p<0.01). These changes were not observed in the control group (n=31). In the whole data, salivary MMP-9 and gingival index correlated (r=0.260, p<0.05 at baseline and r=0.354, p<0.01 at the end of the study). Intergroup differences or correlations with other clinical parameters were not found. Probiotic consumption did not affect the saliva flow rate.ConclusionsIncreased MMP-9 and decreased TIMP-1 levels in saliva may indicate that probiotics have immunomodulatory effects in the oral cavity. Furthermore, increased salivary MMP-9 levels may be an indication of the defensive potential of matrix metalloproteinases.

http://ift.tt/2A4BmG9

Reactivation of peroxidase activity in human saliva samples by polyphenols

Publication date: January 2018
Source:Archives of Oral Biology, Volume 85
Author(s): Jana Gau, Jürgen Arnhold, Jörg Flemmig
ObjectivesThe enzyme lactoperoxidase (LPO), which is released into several body fluids like saliva, is an essential part to maintain the oral bacterial homeostasis by catalysing the oxidation of thiocyanate (SCN⁻) to hypo-thiocyanite (⁻OSCN). The formation of unreactive redox intermediates (like Compound II) leads to a decreased pseudo-halogenating enzyme activity, which is associated with a higher risk for oral infections. According to former studies with bovine LPO selected flavonoids were tested in respect to their potential to reactivate the enzymatic activity in a more physiological, human salivary system.DesignSaliva samples from healthy donors were collected and characterized by using several gel staining methods and immunoblotting. Afterwards kinetic measurements were performed by applying the TNB-assay to evaluate the pseudo-halogenating salivary peroxidase (SAPX) activity. The measurements were performed in the presence of excess H2O2 to simulate pro-inflammatory conditions. Moreover selected flavonoids or an ethanolic extract of Tormentillae rhizoma were applied to test their regenerating effect on the LPO-derived ⁻OSCN production.ResultsDespite the complex protein composition of the collected saliva samples, an SAPX-derived pseudo-halogenating activity could be identified. The ⁻OSCN regenerating effects of the tested polyphenols were completely comparable to previous in vitro experiments with bovine LPO. Thus, we could show that phenolic substances are suitable to regenerate the peroxidase activity in human saliva samples after H2O2-induced inactivation.ConclusionThe studies provide new insights into the effect of pharmaceutical relevant polyphenols on salivary peroxidase activity and thus, suggest this enzyme as a new target for the prevention and therapy of oral inflammatory diseases.

http://ift.tt/2jhtjO7

Patterns of gray matter atrophy in genetic frontotemporal dementia: results from the GENFI study

Publication date: February 2018
Source:Neurobiology of Aging, Volume 62
Author(s): David M. Cash, Martina Bocchetta, David L. Thomas, Katrina M. Dick, John C. van Swieten, Barbara Borroni, Daniela Galimberti, Mario Masellis, Maria Carmela Tartaglia, James B. Rowe, Caroline Graff, Fabrizio Tagliavini, Giovanni B. Frisoni, Robert Laforce, Elizabeth Finger, Alexandre de Mendonça, Sandro Sorbi, Martin N. Rossor, Sebastien Ourselin, Jonathan D. Rohrer
Frontotemporal dementia (FTD) is a highly heritable condition with multiple genetic causes. In this study, similarities and differences of gray matter (GM) atrophy patterns were assessed among 3 common forms of genetic FTD (mutations in C9orf72, GRN, and MAPT). Participants from the Genetic FTD Initiative (GENFI) cohort with a suitable volumetric T1 magnetic resonance imaging scan were included (319): 144 nonmutation carriers, 128 presymptomatic mutation carriers, and 47 clinically affected mutation carriers. Cross-sectional differences in GM volume between noncarriers and carriers were analyzed using voxel-based morphometry. In the affected carriers, each genetic mutation group exhibited unique areas of atrophy but also a shared network involving the insula, orbitofrontal lobe, and anterior cingulate. Presymptomatic GM atrophy was observed particularly in the thalamus and cerebellum in the C9orf72 group, the anterior and medial temporal lobes in MAPT, and the posterior frontal and parietal lobes as well as striatum in GRN. Across all presymptomatic carriers, there were significant decreases in the anterior insula. These results suggest that although there are important differences in atrophy patterns for each group (which can be seen presymptomatically), there are also similarities (a fronto-insula-anterior cingulate network) that help explain the clinical commonalities of the disease.

http://ift.tt/2mTRCXI

Αρχειοθήκη ιστολογίου

! # Ola via Alexandros G.Sfakianakis on Inoreader

Η λίστα ιστολογίων μου

Τετάρτη 22 Νοεμβρίου 2017

Abstract

Abstract

Abstract

Abstract

Abstract

Abstract

Background

Objective

Methods

Results

Conclusion

Abstract

Abstract

Background

Objective

Methods

Results

Conclusion

Abstract

Graphical abstract

Summary

Summary

Graphical abstract

Abstract

Background

Methods

Results

Conclusions

Abstract

Background

Methods

Results

Conclusions

Graphical abstract

Teaser

Graphical abstract

Teaser

Graphical abstract

Teaser

Graphical abstract

Graphical abstract

Graphical abstract

Graphical abstract

Abstract

Abstract

Abstract

Αρχειοθήκη ιστολογίου