Cosmetics, Vol. 5, Pages 67: Evaluation of the Transepidermal Penetration of a Carnosine Complex in Gel Formulation by 3D Skin Models

Cosmetics, Vol. 5, Pages 67: Evaluation of the Transepidermal Penetration of a Carnosine Complex in Gel Formulation by 3D Skin Models

Cosmetics doi: 10.3390/cosmetics5040067

Authors: Valeria Dissette Carlo Alberto Bignozzi Giuseppe Valacchi Alessandra Pecorelli Stefano Manfredini Silvia Vertuani

Carnosine has several physiological roles, from intracellular pH buffering to antioxidant activities, which all depend on bioavailability. This study was conducted in a human skin 3D model and focuses on the effects of the topical delivery of carnosine, from a dermo-cosmetic gel, through the stratum corneum in the presence of a magnesium ion as a complexing agent. To evaluate possible enhancement for small peptide delivery to the skin from simple cosmetic formulations, we discovered that complexation was able to improve the delivery of carnosine into human skin 3D models by application in gel formulation. The concentrations of carnosine released in the underlying media and those that remained in the reconstructed human epidermis (RHE) tissues after 24 and 48 h exposure were measured. Moreover, the influence of magnesium ions was also evaluated comparing the same formulation with and without the salt. The results obtained in this study support hypothesis that magnesium can influence the delivery of small peptides and that the gel formulation based on the carnosine-magnesium complex allows for superior delivery of carnosine in the lower skin layer at a concentration up to 60% more than carnosine alone.

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Pollutants from fish feeding recycled for microalgae production as sustainable, renewable and valuable products

Abstract

Trash fish feeding of cage fish can result in marine pollution. Whole and chopped trash fish can leach pollutants such as ammonia, phosphate and protein into surrounding waters. Reduction of pollution can be achieved by recycling the wastewater generated from trash fish feeding for cultivation of microalgae. Microalgae are potent candidates for the production of renewable and sustainable products such as feed and food, health and pharmaceutical, cosmeceutical, industrial products, and biofuel. Two microalgae, Chlorella saccharophila and Nannochloropsis sp., have the potential to produce high amounts of polyunsaturated fatty acids. Furthermore, high oil content ranging from 10.7 to 13.6% is found in Chlorella saccharophila and up to 9.3% for Nannochloropsis sp. Moreover, these microalgae can also be utilized as a biofuel to give a mean calorific value of 5364 Cal/g which is higher than that of wood for Chlorella saccharophila and 6132 Cal/g which is equivalent to that of coal for Nannochloropsis sp. An alternative biofuel derived from microalgae is feasible due to the fact that they do not compete for arable land for cultivation and land crops for feed and food. This study discusses the synergistic coupling of microalgae mass production with wastewater treatment and carbon sequestration potential for mitigation of environmental impacts and a technically viable alternative energy resource. Additionally, the de-oiled biomass byproduct after oil extraction or its whole biomass can be converted into sustainable and renewal industrial products such as bioplastic, biopaint, bioasphalt, and biobuilding components.

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Statistical assessment of nonpoint source pollution in agricultural watersheds in the Lower Grand River watershed, MO, USA

Abstract

The water quality in many Midwestern streams and lakes is negatively impacted by agricultural activities. Although the agricultural inputs that degrade water quality are well known, the impact of these inputs varies as a function of geologic and topographic parameters. To better understand how a range of land use, geologic, and topographic factors affect water quality in Midwestern watersheds, we sampled surface water quality parameters, including nitrate, phosphate, dissolved oxygen, turbidity, bacteria, pH, specific conductance, temperature, and biotic index (BI) in 35 independent sub-watersheds within the Lower Grand River Watershed in northern Missouri. For each sub-watershed, the land use/land cover, soil texture, depth to bedrock, depth to the water table, recent precipitation area, total stream length, watershed shape/relief ratio, topographic complexity, mean elevation, and slope were determined. Water quality sampling was conducted twice: in the spring and in the late summer/early fall. A pairwise comparison of water quality parameters acquired in the fall and spring showed that each of these factors varies considerably with season, suggesting that the timing is critical when comparing water quality indicators. Correlation analysis between water quality indicators and watershed characteristics revealed that both geologic and land use characteristics correlated significantly with water quality parameters. The water quality index had the highest correlation with the biotic index during the spring, implying that the lower water quality conditions observed in the spring might be more representative of the longer-term water quality conditions in these watersheds than the higher quality conditions observed in the fall. An assessment of macroinvertebrates indicated that the biotic index was primarily influenced by nutrient loading due to excessive amounts of phosphorus (P) and nitrogen (N) discharge from agricultural land uses. The PCA analysis found a correlation between turbidity, E. coli, and BI, suggesting that livestock grazing may adversely affect the water quality in this watershed. Moreover, this analysis found that N, P, and SC contribute greatly to the observed water quality variability. The results of this study can be used to improve decision-making strategies to improve water quality for the entire river basin.

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Composition, mixing state, and size distribution of single submicron particles during pollution episodes in a coastal city in southeast China

Abstract

Size-resolved particle composition, size distribution, and mixing state were characterized at the single-particle level during two air pollution episodes during 12–25 January, 2016 in a coastal city in southeast China. The two pollution episodes occurred under distinct meteorological conditions (i.e., different wind speeds, relative humidity, and backward trajectories); thus, they were assigned to stagnation and transport episodes, respectively. Single-particle data, obtained from single-particle aerosol mass spectrometry (SPAMS), showed that carbonaceous particles were the predominant particles during the whole study period, accounting for more than 60% of the total particles. However, the number fractions of carbonaceous particles and nitrate-containing particles significantly increased in the stagnation episode, while the number fractions of sulfate- and ammonium-containing particles both increased in the transport episode compared to the levels over the whole study period. The potassium-rich (K-rich) particle class was more abundant and more strongly mixed with sulfate in the transport episode, which indicates the impact of biomass burning emissions and the subsequent aging process by acquiring sulfate during transport. The particle classes (e.g., carbonaceous and K-rich classes) had a broader size distribution during the pollution episodes than during the clean episode. The diameters of the size distribution peak for all particle classes (except for dust class) were observed to be larger in the transport episode than in the stagnation episode. This suggests that the particles underwent an extensive aging process through the addition of sulfate and ammonium during transport, leading to the growth of particles.

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aCGH Analysis of Predictive Biomarkers for Response to Bevacizumab plus Oxaliplatin‐ or Irinotecan‐Based Chemotherapy in Patients with Metastatic Colorectal Cancer

AbstractBackground.The randomized phase III study (WJOG4407G) showed equivalent efficacy between FOLFOX and FOLFIRI in combination with bevacizumab as the first‐line treatment for metastatic colorectal cancer (mCRC). We studied whole genome copy number profiles using array‐based comparative genomic hybridization (aCGH) analysis of tumor tissue samples obtained in this study. The aim of this study was to identify gene copy number alterations that could aid in selecting either FOLFOX or FOLFIRI in combination with bevacizumab for patients with mCRC.Materials and Methods.DNA was purified from 154 pretreatment formalin‐fixed paraffin‐embedded tissue samples (75 from the FOLFOX arm and 79 from the FOLFIRI arm) of 395 patients enrolled in the WJOG4407G trial and analyzed by aCGH. Genomic regions greater than 1.2‐fold were regarded as copy number gain (CNG).Results.Patient characteristics between the treatment arms were well balanced except for tumor laterality (left side; 64% in FOLFOX arm and 80% in FOLFIRI arm, p = .07). FOLFIRI showed a trend toward better response rate (RR), progression‐free survival (PFS) and overall survival (OS) than FOLFOX in the patients with CNG of chromosome 8q24.1 (Fisher's exact test, p = .134 for RR; interaction test, p = .102 for PFS and p = .003 for OS) and 8q24.2 (Fisher's exact test, p = .179 for RR; interaction test, p = .144 for PFS and p = .002 for OS).Conclusion.Chromosome 8q24.1–q24.2 may contain genes that could potentially serve as predictive markers for selecting either FOLFOX or FOLFIRI in combination with bevacizumab for treatment of patients with mCRC.Implications for Practice.Bevacizumab has been used as a standard first‐line treatment for patients with metastatic colorectal cancer (mCRC) in combination with either oxaliplatin‐based or irinotecan‐based chemotherapy. Until now, there has been no predictive marker to choose between the two combination chemotherapies. This array‐based comparative genomic hybridization analysis revealed that the difference in therapeutic effect between the two combination chemotherapies is prominent in patients with mCRC with gene copy number gain in chromosome 8p24.1–p24.2. Such patients showed more favorable response and survival when treated with irinotecan‐based combination chemotherapy. Overlapping genes commonly found in this region may be predictive biomarkers of the efficacy of the combination chemotherapy with bevacizumab.

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How Does a Supervised Exercise Program Improve Quality of Life in Patients with Cancer? A Concept Mapping Study Examining Patients' Perspectives

AbstractBackground.Previous systematic reviews and meta‐analyses demonstrated beneficial effects of exercise during or following cancer treatment on quality of life (QoL). Aiming to understand how exercise contributes to a patient's QoL, we examined patients' perspectives via a process called concept mapping. This unique method provides structure and objectivity to rich qualitative data.Methods.Patients with cancer who were participating in an exercise program were invited to enroll. Eleven meetings with 3–10 patients were organized in which patients generated ideas in response to the question "How has participating in a supervised exercise program contributed positively to your QoL?" Next, patients individually clustered (based on similarity) and rated (based on importance) the ideas online. The online assessments were combined, and one concept map was created, visualizing clusters of ideas of how patients perceive that participating in a supervised exercise program improved their QoL. The research team labelled the clusters of ideas, and physiotherapists reflected on the clusters during semistructured interviews.Results.Sixty patients attended the meetings; of these, one patient was not able to generate an idea in response to the statement. Forty‐four patients completed the online clustering and rating of ideas. The resulting concept map yielded six clusters: personalized care, coaching by a physiotherapist, social environment, self‐concept, coping, and physical fitness and health. Personalized care was rated as most important. Overall, physiotherapists recognized these clusters in practice.Conclusion.Patients with cancer reported that participating in a supervised exercise program improved their physical fitness and influenced social, mental, and cognitive factors, resulting in improvements in QoL. These results can be used to increase the awareness of the importance of supervised exercise programs for the QoL of patients with cancer.Implications for Practice.According to patients, a supervised exercise program contributes positively to their quality of life by improving physical fitness and health and providing personalized care, coaching by a physiotherapist, and improved social environment, self‐concept, and coping. This knowledge could help to increase physicians' and patients' awareness of the importance of an exercise program during or following cancer treatment, possibly improving referral, participation, and adherence rates to these programs. Furthermore, patients' perspectives may be used to improve supervised exercise programs, taking into account the importance of personalized care, the supervision of a physiotherapist, the social environment, self‐concept, and coping.

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Association between hidradenitis suppurativa and hospitalization for psychiatric disorders: A cross‐sectional analysis of the National Inpatient Sample

Abstract

Background

Hidradenitis suppurativa (HS) is associated with pain, disfigurement, psychosocial distress and poor quality of life, all of which may lead to higher likelihood of mental health (MH) disorders. However, little is known about the MH comorbidities of HS.

Objectives

to determine the MH disorders and cost‐burden associated with HS.

Methods

Data were examined from the 2002‐2012 National Inpatient Sample, comprising a ~20% sample of all US pediatric and adult hospitalizations (n=87,053,155 admissions).

Results

MH disorders were much more common in inpatients with vs. without HS (34·27% vs. 20·05%). In multivariable logistic regression models controlling for gender, age, race/ethnicity, and insurance status, HS was associated with significantly higher odds of a MH disorder (adjusted odds ratio [95% confidence interval]: 2·53 [2·42‐2·63]), including 10 of 15 MH disorders examined. In contrast, HS was not associated with primary hospitalization for a MH disorder overall (0·95 [0·84‐1·07]), but was associated with primary hospitalization for 8 of 15 MH disorders examined. Among inpatients with HS, primary admission for a MH disorder was associated with female sex, public or no insurance, more chronic diseases, but inversely associated with older age, female sex, and non‐white race/ethnicity. HS was associated with >$38 million of excess mean annual costs of hospitalization for MH disorders.

Conclusions

Inpatients with HS had increased odds of comorbid mental health disorders, overall, and multiple primary mental health admissions, in particular, which were associated with considerable excess costs.

This article is protected by copyright. All rights reserved.

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Association between hidradenitis suppurativa and hospitalization for psychiatric disorders: A cross‐sectional analysis of the National Inpatient Sample

Abstract

Background

Hidradenitis suppurativa (HS) is associated with pain, disfigurement, psychosocial distress and poor quality of life, all of which may lead to higher likelihood of mental health (MH) disorders. However, little is known about the MH comorbidities of HS.

Objectives

to determine the MH disorders and cost‐burden associated with HS.

Methods

Data were examined from the 2002‐2012 National Inpatient Sample, comprising a ~20% sample of all US pediatric and adult hospitalizations (n=87,053,155 admissions).

Results

MH disorders were much more common in inpatients with vs. without HS (34·27% vs. 20·05%). In multivariable logistic regression models controlling for gender, age, race/ethnicity, and insurance status, HS was associated with significantly higher odds of a MH disorder (adjusted odds ratio [95% confidence interval]: 2·53 [2·42‐2·63]), including 10 of 15 MH disorders examined. In contrast, HS was not associated with primary hospitalization for a MH disorder overall (0·95 [0·84‐1·07]), but was associated with primary hospitalization for 8 of 15 MH disorders examined. Among inpatients with HS, primary admission for a MH disorder was associated with female sex, public or no insurance, more chronic diseases, but inversely associated with older age, female sex, and non‐white race/ethnicity. HS was associated with >$38 million of excess mean annual costs of hospitalization for MH disorders.

Conclusions

Inpatients with HS had increased odds of comorbid mental health disorders, overall, and multiple primary mental health admissions, in particular, which were associated with considerable excess costs.

This article is protected by copyright. All rights reserved.

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Interaction of the mycotoxin metabolite dihydrocitrinone with serum albumin

Abstract

Citrinin (CIT) is a nephrotoxic mycotoxin produced by Penicillium, Monascus, and Aspergillus species. CIT appears as a contaminant in cereals, cereal-based products, fruits, nuts, and spices. During the biotransformation of CIT, its major urinary metabolite dihydrocitrinone (DHC) is formed. Albumin interacts with several compounds (including mycotoxins) affecting their tissue distribution and elimination. CIT-albumin interaction is known; however, the complex formation of DHC with albumin has not been reported previously. In this study, we aimed to investigate the interaction of DHC with albumin, employing fluorescence spectroscopy, circular dichroism, and molecular modeling studies. Furthermore, species differences and thermodynamics of the interaction as well as the effects of albumin on the acute in vitro toxicity of DHC and CIT were also tested. Our main observations/conclusions are as follows: (1) Fluorescence signal of DHC is strongly enhanced by albumin. (2) Formation of DHC-albumin complexes is supported by both fluorescence spectroscopic and circular dichroism studies. (3) DHC forms similarly stable complexes with human albumin (K~10⁵ L/mol) as CIT. (4) DHC-albumin interaction did not show significant species differences (tested with human, bovine, porcine, and rat albumins). (5) Based on modeling studies and investigations with site markers, DHC occupies the Heme binding site (subdomain IB) on human albumin. (6) The presence of albumin significantly decreased the acute in vitro cytotoxic effects of both DHC and CIT on MDCK cell line.

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Natural disasters, climate change, and their impact on inclusive wealth in G20 countries

Abstract

This paper uses the 1990–2010 natural disaster and carbon emission data of G20 countries to examine the impact of natural disasters and climate change on the natural capital component of inclusive wealth. Our study shows that climate change and GDP have no positive impacts on the growth of natural capital. By contrast, trade openness and natural disaster frequency contribute to the accumulation of natural capital in G20 countries. There is an inverted U-shaped relationship between the growth of natural capital and the magnitude of natural disaster. Natural capital growth is not affected very much by small disasters. By contrast, large disasters tend to make the growth of natural capital fall sharply.

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Multi-criteria decision approach for evaluation, ranking, and selection of remediation options: case of polluted groundwater, Kuwait

Abstract

Freshwater groundwater resources at north Kuwait were contaminated by infiltrated oil as well as sea water that was used to fight the oil-well fires during the liberation of Kuwait in 1991. This paper investigates the feasibility of five remediation options to restore the polluted aquifers. These options include: (i) pump and treat of contaminated groundwater; (ii) cleaning the aquifer formation; (iii) construction of additional desalination plant; (iv) constructing additional storage tanks, and (v) development of artificial aquifer recharge schemes. The basis for this assessment study is to supply minimum basic drinking water to Kuwait City at a total rate of 50,000 m³/day in an emergency for up to one year based on essential basic need of 32 liters per capita per day. To compare these options, a decision matrix to select suitable remediation options using Multiple Criteria Decision Analysis (MCDA) approach is developed. The cost was given a relative weight of 20 whereas other criteria are given weight of 10. Based on these MCDA scores, it was found that option 3, namely, establishing an additional water desalination plant, is the most feasible option followed by option 5, artificial recharge of aquifers.

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Cyhalothrin biodegradation in Cunninghamella elegans

Abstract

The insecticide λ-cyhalothrin was incubated with planktonic and biofilm cultures of the fungus Cunninghamella elegans. ¹⁹F nuclear magnetic resonance spectroscopy demonstrated that the compound was initially biosorbed to the biomass and more slowly degraded by the fungus. Furthermore, the presence of trifluoromethyl-containing metabolites was observed. Analysis of culture extracts by gas chromatography-mass spectrometry (GC-MS) identified non-fluorinated metabolites that suggested the likely catabolic pathway. The hydroxylated metabolites were probably generated from the action of cytochromes P450 (CYPs), as the presence of CYP inhibitors resulted in the absence of biodegradation. Planktonic cells were measurably faster at degrading the pesticide compared with biofilm.

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Effective degradation of Orange G and Rhodamine B by alkali-activated hydrogen peroxide: roles of HO 2 − and O 2 ·−

Abstract

Advanced oxidation processes offer effective solutions in treating wastewater from various industries. The process of alkali-activated hydrogen peroxide (H₂O₂) was superior for the treatment of alkaline dye wastewater because no additional reagents were required except H₂O₂. However, an important and interesting phenomenon had been observed that the primary reactive species were found different for degrading organic pollutants with the process of alkali-activated H₂O₂. Azo dye of Orange G (OG) and triphenylmethane dye of Rhodamine B (RhB) were chosen as the target organic pollutants. The influences of various parameters on OG and RhB degradation by alkali-activated H₂O₂ were evaluated. Furthermore, different scavengers, including ascorbic acid, methanol, t-butanol, isopropyl alcohol, furfuryl alcohol, and nitro blue tetrazolium, have been tested to identify the active species involved in dye degradation, and it was found that O₂^·− was mainly responsible for degrading OG, while HO₂⁻ anion was the primary oxidant for degrading RhB.

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In situ genotoxicity assessment in freshwater zooplankton and sediments from different dams, ponds, and temporary rivers in Tunisia

Abstract

Tunisia water resources are limited. The country currently has 29 large dams, more than 1000 hill lakes, and 220 small dams which are essential for economic and social development given their contribution to irrigation, drinking water consumption, flooding protection, production of electrical energy, groundwater recharge, and industrial uses. Given the scarcity of these resources, it is crucial to be able to ensure the quality of freshwater environments, particularly those intended for human consumption. In this study, we meant to assess the health status of various freshwater ecosystems in different regions of Tunisia (north and center west) in order to detect genotoxic components in sediments and their potential effect on zooplankton (cladocerans). Sediment and cladoceran species were collected from dams, ponds, and temporary rivers in Tunisia. For each collection site, micronucleus (MN) assay was performed, in triplicates, using a pool of ten specimens of the same cladoceran species. MN occurrence in cladocerans varied from one site to another and MN frequencies varied between 0.67 and 22‰, suggesting the presence of genotoxic substances in certain sites. Sediment genotoxicity and mutagenicity were assessed using the SOS Chromotest and the Ames test. Sediment results showed that genotoxicity varies from one site to another displaying a quantitative and a qualitative variation of pollutant among the sites. These results suggest an urgent need for continuous monitoring of freshwater environments in Tunisia, particularly those intended for drinking water.

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Evaluation of efficacy of the essential oil from Ostericum viridiflorum (Turcz.) Kitagawa in control of stored product insects

Abstract

The natural and ecologically safe control of stored product insects has gained considerable attention in modern society. In this study of further searching for botanical pesticides from wild-growing plant, the contact toxicity and repellency towards Tribolium castaneum and Liposcelis bostrychophila were assessed for the essential oil (EO) from Ostericum viridiflorum. The EO was distilled from aboveground parts of O. viridiflorum and checked by gas chromatography-mass spectrometry. Twenty-two compounds were identified and the main components were β-caryophyllene (24.3%), α-humulene (21.0%), apiol (10.2%), and carotol (2.5%). For bioactivity tests, results indicated that the EO and its two main compounds (β-caryophyllene and α-humulene) all showed potent contact toxicity towards L. bostrychophila with LD₅₀ values of 44.52 μg/cm², 74.11 μg/cm², and 118.56 μg/cm², respectively. The EO and the two main compounds also exhibited comparable repellency towards T. castaneum and L. bostrychophila. The results evidenced the EO of O. viridiflorum aboveground parts and its major compounds could be considered for the development of eco-friendly botanical insecticides and repellents in controlling stored product insects.

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The relative role of spatial and environmental processes on seasonal variations of phytoplankton beta diversity along different anthropogenic disturbances of subtropical rivers in China

Abstract

The phytoplankton community structure is potentially influenced by both environmental and spatial processes. In addition, the relative importance of these two processes to phytoplankton assemblage will be affected by hydrological connectivity. However, the impacts of anthropogenic activities on phytoplankton beta diversity and the relative importance of these two processes to phytoplankton are still poorly understood, especially in water conservation areas. Here, we examined the relative importance of local and regional environmental control and spatial structuring of phytoplankton communities in five rivers with different degrees of disturbance during wet and dry seasons. We found that community structure and local environmental conditions varied greatly in seasons and rivers. The reference river (with minimum disturbance) had the highest homogeneity of environmental conditions and phytoplankton assemblage, while the excessive disturbance rivers (sand mining activities) had the greatest environmental heterogeneity and species dissimilarity between sites. Variation partitioning analysis showed that the phytoplankton community variation was mainly explained by the spatial variables in the wet season (summer and autumn) and winter, while the local environmental variables explained the largest variation of phytoplankton community in the dry season (spring). However, broad-scale variables were selected by redundancy analysis in both dry and wet seasons, which indicates that long-distance scales always have low river connectivity, regardless of whether the river is overflowing or drying up. Local environmental processes explained the most variation in phytoplankton community within all of the rivers, suggesting that deterministic processes usually work on relatively small spatial scales. However, this effect would be weakened by anthropogenic activities, especially sand mining activities. We inferred that sand mining activities increased the environmental heterogeneity and species dissimilarity between sites by causing watercourse habitat patches and obstructing river connectivity. On the other hand, as the excessive disturbance, sand mining activities significantly reduced the species richness and abundance of phytoplankton.

https://ift.tt/2qSI1Q9

Thyroid® High-Impact Articles

FREE ACCESS through November 27, 2018.
Latest Impact Factor: 7.557
The Official Journal of: American Thyroid Association^®

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Immune-Related Thyroiditis with Immune Checkpoint Inhibitors
Priyanka C. Iyer, Maria E. Cabanillas, Steven G. Waguespack, Mimi I. Hu, Sonali Thosani, Victor R. Lavis, Naifa L. Busaidy, Sumit K. Subudhi, Adi Diab, and Ramona Dadu

Patients with Benign Thyroid Diseases Experience an Impaired Sex Life
Nadia Sawicka-Gutaj, Marek Ruchala, Ulla Feldt-Rasmussen, Åse Krogh Rasmussen, Laszlo Hegedüs, Steen Joop Bonnema, Mogens Groenvold, Jakob Bue Bjorner, and Torquil Watt

Thyroid Cancer Treatment Choice: A Pilot Study of a Tool to Facilitate Conversations with Patients with Papillary Microcarcinomas Considering Treatment Options
Juan P. Brito, Jae Hoon Moon, Rebecca Zeuren, Sung Hye Kong, Yeo Goon Kim, Nicole M. Iñiguez-Ariza, June Young Choi, Kyu Eun Lee, Ji-hoon Kim, Ian Hargraves, Victor Bernet, Victor M. Montori, Young Joo Park, and R. Michael Tuttle

Association of Thyroid Function and Autoimmunity with Ovarian Reserve in Women Seeking Infertility Care
Tim I.M. Korevaar, Lidia Mínguez-Alarcón, Carmen Messerlian, Ralph A. de Poortere, Paige L. Williams, Maarten A. Broeren, Russ Hauser, and Irene C. Souter  

Hyperthyroidism and Papillary Thyroid Carcinoma in Thyrotropin Receptor D633H Mutant Mice
Holger Jaeschke, Henriette Undeutsch, Konrad Patyra, Christoffer Löf, Markus Eszlinger, Moosa Khalil, Meeri Jännäri, Kristiina Makkonen, Jorma Toppari, Fu-Ping Zhang, Matti Poutanen, Ralf Paschke, and Jukka Kero  

The post <i>Thyroid^®</i> High-Impact Articles appeared first on American Thyroid Association.

https://ift.tt/2T7j00i

Thyroid® High-Impact Articles

FREE ACCESS through November 27, 2018.
Latest Impact Factor: 7.557
The Official Journal of: American Thyroid Association^®

Read now:

Immune-Related Thyroiditis with Immune Checkpoint Inhibitors
Priyanka C. Iyer, Maria E. Cabanillas, Steven G. Waguespack, Mimi I. Hu, Sonali Thosani, Victor R. Lavis, Naifa L. Busaidy, Sumit K. Subudhi, Adi Diab, and Ramona Dadu

Patients with Benign Thyroid Diseases Experience an Impaired Sex Life
Nadia Sawicka-Gutaj, Marek Ruchala, Ulla Feldt-Rasmussen, Åse Krogh Rasmussen, Laszlo Hegedüs, Steen Joop Bonnema, Mogens Groenvold, Jakob Bue Bjorner, and Torquil Watt

Thyroid Cancer Treatment Choice: A Pilot Study of a Tool to Facilitate Conversations with Patients with Papillary Microcarcinomas Considering Treatment Options
Juan P. Brito, Jae Hoon Moon, Rebecca Zeuren, Sung Hye Kong, Yeo Goon Kim, Nicole M. Iñiguez-Ariza, June Young Choi, Kyu Eun Lee, Ji-hoon Kim, Ian Hargraves, Victor Bernet, Victor M. Montori, Young Joo Park, and R. Michael Tuttle

Association of Thyroid Function and Autoimmunity with Ovarian Reserve in Women Seeking Infertility Care
Tim I.M. Korevaar, Lidia Mínguez-Alarcón, Carmen Messerlian, Ralph A. de Poortere, Paige L. Williams, Maarten A. Broeren, Russ Hauser, and Irene C. Souter  

Hyperthyroidism and Papillary Thyroid Carcinoma in Thyrotropin Receptor D633H Mutant Mice
Holger Jaeschke, Henriette Undeutsch, Konrad Patyra, Christoffer Löf, Markus Eszlinger, Moosa Khalil, Meeri Jännäri, Kristiina Makkonen, Jorma Toppari, Fu-Ping Zhang, Matti Poutanen, Ralf Paschke, and Jukka Kero  

The post <i>Thyroid^®</i> High-Impact Articles appeared first on American Thyroid Association.

https://ift.tt/2T7j00i

Physical Activity, Functional Ability, and Quality of Life after Breast Cancer Surgery

This cross-sectional study aimed to assess the influence of different surgical treatment modalities on the level of physical activity, functional capacity and quality of life of breast cancer survivors. One hundred and eighty women aged 30 to 60 years old were selected and allocated to control (CG, women without breast cancer, n=45), breast-conserving surgery (BCG, n=45), mastectomy (MG, n=45) and breast reconstruction (BRG, n=45) groups. Physical activity, functional capacity and quality of life were assessed, respectively, by using the following self-report questionnaires validated for use in Brazil: International Physical Activity Questionnaire (IPAQ), Stanford Health Assessment Questionnaire (HAQ-20) and Medical Outcomes Study 36-item Short-Form Health Survey (SF-36).

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Title: Microscope Assisted Surgery for Dupuytrens Disease

The traditional surgical management for Dupuytrens Disease (DD) is a limited fasciectomy.1 Surgeons will often use magnification in the form of surgical loupes to dissect out the fibrous cord from the neurovascular structures in the palm and digit. Authors have described an up to 7.8% risk of neurovascular injury in DD.2 This can be higher in recurrent disease as often the neurovascular structures are encased in scar tissue and surgical planes are hard to determine.

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USE OF INNOVATIVE NEGATIVE PRESSURE THERAPY FOR CARTILAGE EXPOSURE IN MICROTIA RECONSTRUCTION

Complications of autologous cartilage staged microtia reconstruction are multiple with a variable incidence; nevertheless, delayed wound healing leading to skin necrosis and cartilage exposure is among the most frequent. Although in most cases of framework exposure flap coverage is needed, we report a case in which portable negative pressure therapy was used achieving complete and definitive coverage of the defect.

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Referral of patients to Plastic Surgeons following self-harm: Opportunities for suicide prevention

Self-harm is a common source of referral to plastic and hand surgery services. Appropriate management of these patients is complex and includes the need for close liaison with mental health services. Self-harm is the single biggest risk factor for completed suicide, increasing the risk by a factor of 66.1 This study aimed to analyse the clinical pathway and demographics of patients referred to plastic surgeons following self-harm.This 6-year retrospective series captured patients referred to plastic surgeons following self-harm within the Galway University Hospital group.

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Perioperative intralesional injection of fibrin glue for extirpation of oral haemangioma: A technical note

Ethical approval: Not required

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Microvascular Anastomosis with Fish-Mouth Suturing and Adhesive Sealants

The primary drive in microvascular surgery is to ensure reliability of patency and flow. Conventional interrupted suturing (CIS) is the current gold standard, despite the known complication of intimal damage and exposure of the media layer1. Numerous techniques have been described to remove suture dependency and reduce vessel trauma, including vessel clips, stents, and laser-assisted bonding with no clinical success.

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Reduction mammaplasty technique. The core and the master key of oncoplastic breast surgery.

Dear Sir,

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Shear wave elastography of median nerve at wrist and forearm. Heterogeneity of normative values – response to authors

We read with interest the letter of Abdelmohsen Bedewi, et al. concerning the heterogeneity of the normative values of the median nerve in shear wave elastography.1 The authors investigated 20 wrists of healthy patients of Asian ethnicity with an average age of 31. The mean value of nerve elasticity at the wrist was 20.78 kPa which was lower than the normal wrist values observed by Kantarci, et al. (31 - 32 kPa)2 and much lower than the normal values observed by our group (43.6 kPa)3. There may be several reasons for these discrepancies, although we believe that it probably results from two main differences.

https://ift.tt/2K1O79l

Should we be imaging soft tissue masses of the hand and wrist?

We examined the relationship between pre-operative clinical diagnosis, radiological diagnosis (ultrasonography (US) and magnetic resonance imaging (MRI)) and histopathological findings of soft tissue lesions of the hand. A retrospective review of 62 patients undergoing excision of soft tissue masses of the hand between 2015 and 2018 was conducted. The most common diagnoses were: ganglion (n=23), fibroma (n=8), giant cell tumour (GCT) (n=6) and vascular malformation (n=4). 31 patients underwent pre-operative imaging with US and/or MRI.

https://ift.tt/2B3s92O

Single use negative-pressure wound therapy: Are we being sucked in?

Single use negative pressure wound therapy (NPWT) devices (PICOTM Smith and Nephew and PrevenaTM Acelity,) have been marketed as a significant advancement in wound care providing a more comfortable and user-friendly experience than their cumbersome re-usable competitors.1 A small, light weight pump, powered by batteries, and small enough to fit easily into a pocket, unobtrusively delivers 80mmHg (PICOTM) or 125mmHg (PrevenaTM) of continuous negative pressure.

https://ift.tt/2K1O1P1

The Evolving Role of the Chaperone in Medicine-Protection and Training: A plastic Surgery Perspective

The role of the chaperone is integral in clinical examination and with this short communication aim to highlight the evolving role of the chaperone as a "witness" who with the appropriate training and standardised documentation can act as an observer of the behaviour of all parties during the consultation.

https://ift.tt/2B2GMDx

The Plastic Surgeon as Employee: Survey of the American Society of Plastic Surgeons

None of the authors have received funding for this manuscript.

https://ift.tt/2K3bUpw

Achieving clear margins: Review of techniques to more accurately delineate basal cell carcinoma (BCC) macroscopic border prior to excision biopsy

Basal cell carcinoma (BCC) is the most common skin cancer worldwide, and a large proportion are amenable to removal by excision biopsy under local anaesthetic with predetermined margins. This article reviews the techniques reported in the literature to assist surgeons in achieving this aim (Table 1).

https://ift.tt/2B62wyz

Immediate Breast Reconstruction in High Risk Cases Using an Anatomical Shaped Permanent Expandable Implant

Anatomically shaped permanent expandable implants are dual-chambered devices, which allow their postoperative expansion for adjustment of the volume. Their use is optional when 1-stage immediate breast reconstruction (IBR) direct to permanent implant is not feasible. The aim of this study is to present one center's long-term experience with the anatomical Becker expandable implant in a large series of patients who underwent either IBR or a salvage procedure for IBR with the device.

https://ift.tt/2K5bFug

ALT vs. Jejunum: Have We Found the Ideal Flap for Circumferential Pharyngoesophageal Reconstruction? A Meta-analysis of Comparative Studies

Free flap reconstruction has become the preferred procedure for circumferential pharyngoesophageal defect. Among the free flaps used, free anterolateral thigh (ALT) flap and free jejunal flap are the two most popularly used flaps. The choice of flap usually depends on the surgeon's training and experience. There are limited studies that directly compared the clinical and functional outcomes with these two flaps. We conduct a systematic review and meta-analysis to compare the postoperative complications and the functional outcomes after reconstruction of circumferential pharyngoesophageal defects using free ALT flap versus free jejunal flap.

https://ift.tt/2B3s5QC

Shear wave elastography of median nerve at wrist and forearm. Heterogeneity of normative values

we have read the Letter by Paluch and collaborators about the potential usefulness of wrist-forearm ratio of the median nerve stiffness measured by shear wave elastography (SWE).1 The paper is very interesting and we completely agree with the authors about the use of relative values instead of absolute ones to increase the diagnostic meaning of the SWE findings. A similar approach of ratio between two segment of the same nerve has shown high usefulness in other measurements, like nerve cross sectional area.

https://ift.tt/2K1NXPh

Altered Lymphatic Drainage in Malignant Melanoma after previous Sentinel Node Biopsy in the Same Nodal Drainage Basin

We would like to present the case of a melanoma patient with altered sentinel lymph node drainage on repeat sentinel lymph node biopsy (SNB) subsequent to previous breast cancer. A 53-year-old lady underwent a wide local excision (WLE) of a melanoma scar from her right breast with lymphoscintigraphy. She had a completely excised superficial spreading malignant melanoma (SSMM) of Breslow thickness (BT) 3.7mm with ulceration. She had a history of right breast carcinoma diagnosed in 2009, treated with lumpectomy and radiotherapy, and had undergone a previous negative sentinel lymph node biopsy of the right axilla.

https://ift.tt/2B3MNzU

Fast and inexpensive production of "homemade" PRP: a simple method

Platelet-rich plasma (PRP) is increasingly used to improve wound healing in plastic surgery, orthopaedic surgery or maxillofacial surgery, and as a tissue inducer in skin, muscles, tendons, cartilage and bone.

https://ift.tt/2K1LDI4

Wound healing after cultured epithelial autografting in patients with massive burn injury: a cohort study

Last century, our laboratory produced Cultured Epithelial Autograft (CEA) for clinical use by the affiliated adult burn service and other burn units across the country. Production of CEA for clinical use was discontinued after several years because of a low success rate and subsequent low demand. Recently at our burns unit, a cell culture program was re-introduced as a direct response to the need for improvement in ongoing deficiencies and clinical requirements in burn wound closure. The aim of this study was to validate the laboratory processes and clinical algorithms established and share our recent clinical experiences involving CEA.

https://ift.tt/2DkwqAI

Video-recording a surgical procedure

Funding: None

https://ift.tt/2PV3KVn

Long‐term quality of life in older patients with HPV‐related oropharyngeal cancer

Abstract

Background

We explored if age affects quality of life (QOL) in survivors of locally advanced human papillomavirus (HPV)‐related oropharyngeal squamous cell carcinoma (SCC).

Methods

In a cross‐sectional survey of 185 patients, at least 12 months from radiation, we evaluated generic (EuroQOL‐5D questionnaire [EQ‐5D]) and head and neck specific (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire‐Head and Neck 35‐questions [EORTC‐QLQ‐H&N35]) QOL questionnaires and compared differences between younger (<65) and older (≥65) patients.

Results

The median age was 57.0 years (range 25‐77 years), and 31 patients (16.8%) were ≥65 years old. There was no significant difference in EQ‐5D global QOL scores by age (P = .53). Patients ≥65 years reported more immobility (P < .01), problems with social eating (P < .0001), and coughing (P < .01). Patients ≥65 years were not more likely to ever require a gastrostomy (P = .24) but were more likely to remain gastrostomy‐dependent at the time of the survey (P = .02).

Conclusion

Despite similar generic QOL, older survivors may have more mobility problems and issues with social eating compared with younger survivors deserving of further evaluation.

https://ift.tt/2zOGhv1

Patterns of failure after postoperative intensity‐modulated radiotherapy for locally advanced buccal cancer: Initial masticator space involvement is the key factor of recurrence

Abstract

Background

The purpose of this study was to determine failure patterns and clinicopathologic prognostic factors in patients with locally advanced buccal cancer after postoperative intensity‐modulated radiotherapy (IMRT).

Methods

Eighty‐two patients with locally advanced (American Joint Committee on Cancer [AJCC] stage III/IV) buccal cancer who underwent surgery followed by postoperative IMRT between January 2007 and October 2012 were retrospectively analyzed.

Results

Eighteen patients had local recurrences as the first recurrent site and 11 had supramandibular notch recurrences; the majority of recurrences were classified as marginal failures. The median time from the first local or regional recurrence to death was 5.9 months. In multivariate analyses of survivals, the initial masticator space involvement was the most important prognostic factor. Masticator space involvement, N classification, and maxillectomy were the significant prognostic predictors for supramandibular notch recurrences.

Conclusion

Postoperative IMRT for buccal cancer should not include the surgical beds alone, rather, it should be based on the potential patterns of spread.

https://ift.tt/2Tc2Ti4

Pattern of planned systemic therapy usage in newly diagnosed, nonmetastatic squamous cell carcinoma of the head and neck in a commercially insured population in the United States

Abstract

Background

We analyzed systemic therapy plans submitted for commercially insured patients with untreated, newly diagnosed squamous cell carcinoma of the head and neck (SCCHN) to investigate patterns of practice.

Methods

Consecutive chemotherapy treatment plans were submitted using Eviti Connect (https://www.marylandphysicianscare.com/content/dam/centene/maryland/pdfs/evitiConnectFactSheet.pdf) portal for preauthorization between June 1, 2011, and June 30, 2015, were analyzed.

Results

A total of 387 treatment plans were submitted for 340 patients; 68 and 272 patients were from academic centers and community practices, respectively. Single agent cisplatin (57%), cetuximab (18%), and carboplatin (9%) were the most commonly proposed regimens concurrent with definitive radiotherapy (RT). The frequency of cetuximab use was not significantly different between academic centers and community practices. A clinical trial was proposed in only 15% of patients.

Conclusion

Among commercially insured patients with newly diagnosed, nonmetastatic SCCHN, the choice of systemic therapy in initial treatment plans was not significantly different between academic centers and community practices. Clinical trials are underutilized and should be encouraged.

https://ift.tt/2zPWcct

The red leg dilemma: a scoping review of the challenges of diagnosing lower limb cellulitis

Abstract

Background

Suspected lower limb cellulitis presentations are commonly misdiagnoses, resulting in avoidable antibiotic prescribing or hospital admissions. Understanding the challenges posed in diagnosing cellulitis may help enhance future care.

Objectives

To examine and map out the challenges and facilitators identified by patients and health professionals in diagnosing lower limb cellulitis.

Methods

A scoping systematic review was performed in MEDLINE and Embase in October 2017. Thematic analysis was used to identify key themes. Quantitative data was summarised by narrative synthesis.

Results

Three themes were explored: (i) clinical case reports of misdiagnosis, (ii) service development and (iii) diagnostic aids. Forty‐seven different pathologies were misdiagnosed, including seven malignancies. Two different services have been piloted to reduce the misdiagnosis rates of lower limb cellulitis and save costs. Four studies have looked at biochemical markers, imaging and a scoring tool to aid diagnosis.

Conclusions

This review highlights the range of alternative pathologies that can be misdiagnosed as cellulitis, and emerging services and diagnostic aids developed to minimise misdiagnosis. Future work should focus on gaining a greater qualitative understanding of the diagnostic challenges from the perspective of patients and clinicians.

This article is protected by copyright. All rights reserved.

https://ift.tt/2qIreij

The red leg dilemma: a scoping review of the challenges of diagnosing lower limb cellulitis

Abstract

Background

Suspected lower limb cellulitis presentations are commonly misdiagnoses, resulting in avoidable antibiotic prescribing or hospital admissions. Understanding the challenges posed in diagnosing cellulitis may help enhance future care.

Objectives

To examine and map out the challenges and facilitators identified by patients and health professionals in diagnosing lower limb cellulitis.

Methods

A scoping systematic review was performed in MEDLINE and Embase in October 2017. Thematic analysis was used to identify key themes. Quantitative data was summarised by narrative synthesis.

Results

Three themes were explored: (i) clinical case reports of misdiagnosis, (ii) service development and (iii) diagnostic aids. Forty‐seven different pathologies were misdiagnosed, including seven malignancies. Two different services have been piloted to reduce the misdiagnosis rates of lower limb cellulitis and save costs. Four studies have looked at biochemical markers, imaging and a scoring tool to aid diagnosis.

Conclusions

This review highlights the range of alternative pathologies that can be misdiagnosed as cellulitis, and emerging services and diagnostic aids developed to minimise misdiagnosis. Future work should focus on gaining a greater qualitative understanding of the diagnostic challenges from the perspective of patients and clinicians.

This article is protected by copyright. All rights reserved.

https://ift.tt/2qIreij

Arthrocentesis in the management of internal derangement of the temporomandibular joint

Abstract

Background

Temporomandibular disorders (TMD) cover a wide spectrum of disorder; myalgic, arthralgic and psychogenic. The procedure of TMJ arthrocentesis has a role in managing patients with arthralgic pain and limitation if they fail to respond to non‐surgical therapy.

Method

The patient records of a single private specialist OMS were searched over the nine year period of 2006‐2014 to identify patients who had arthrocentesis as part of their multidisciplinary management. The detailed demographic, diagnosis, pre and post arthrocentesis procedure were identified and put on a database. Appropriate statistics were performed.

Results

Seventy six patients had 115 arthrocentesis procedures performed in the study period. Fifty of 76 had improvement in their pain and 16 of 41 had an increased jaw opening of more than 10mm. There was no complications or morbidity. Analysis of patient variables generally showed no correlations.

Conclusions

Temporomandibular joint arthrocentesis has a role in the multidisciplinary, multimodality treatment of arthralgic TMD.

This article is protected by copyright. All rights reserved.

https://ift.tt/2QFHgVy

Assessment of the content, occurrence, and leachability of arsenic, lead, and thallium in wastes from coal cleaning processes

Abstract

The aim of the study was to evaluate the content, occurrence, and leachability of arsenic (As), lead (Pb), and thallium (Tl) in wastes from coal cleaning processes with respect to the safe management of this waste. The study focused on wastes resulting from the wet gravitation and flotation processes employed for the purposes of coking coal cleaning in four coal mines situated in the Upper Silesian Coal Basin (Poland). The scope of the study included (i) determination of the content of these elements in the investigated wastes using atomic absorption spectrometry, (ii) evaluation of their mode of occurrence using electron microprobe analysis, and (iii) preliminary assessment of their leachability in deionized water. The content of the analyzed elements in the examined samples of coal waste was twice as high as the average content of these elements in the Earth's crust. The contents of As and Pb, however, did not exceed their permissible contents in inert waste in accordance with Polish legal regulations based on EU directives. The limit on the content of Tl is not specified by these regulations, but its amount in the examined samples was similar to that occurring in the soils. Moreover, leaching tests have shown that these elements are hardly eluted from the analyzed material. Their content in the water leachates was generally lower than the detection limit of the analytical method, complying with the standards for good and very good water quality. Low leachability of these elements most probably results from their mode of occurrence in the investigated wastes. The chemical analysis using an electron microprobe and the analysis of the correlation between these elements, e.g., total and pyritic sulfur, have shown that Pb, As, and Tl are mainly found in sulfide minerals which are characterized by negligible solubility. In conclusion, the investigated hard coal processing waste does not constitute a threat to the environment and can be commercially used or safely neutralized, e.g., by landfilling.

https://ift.tt/2Tdt9c3

Inflammatory and oxidative stress biomarkers at protein and molecular levels in workers occupationally exposed to crystalline silica

Abstract

Workers chronically exposed to respirable crystalline silica (CS) are susceptible to adverse health effects like silicosis and lung cancer. This study aimed to investigate potential early peripheral biomarkers of inflammation and oxidative stress in miners. The subjects enrolled in this study were occupationally unexposed workers (OUW, n = 29) and workers exposed to crystalline silica (WECS), composed by miners, which were divided into two subgroups: workers without silicosis (WECS I, n = 39) and workers diagnosed with silicosis, retired from work (WECS II, n = 42). The following biomarkers were evaluated: gene expression of L-selectin, CXCL2, CXCL8 (IL-8), HO-1, and p53; malondialdehyde (MDA) plasma levels and non-protein thiol levels in erythrocytes. Additionally, protein expression of L-selectin was evaluated to confirm our previous findings. The results demonstrated that gene expression of L-selectin was decreased in the WECS I group when compared to the OUW group (p < 0.05). Regarding gene expression of CXCL2, CXCL8 (IL-8), HO-1, and p53, significant fold change decreases were observed in workers exposed to CS in relation to unexposed workers (p < 0.05). The results of L-selectin protein expression in lymphocyte surface corroborated with our previous findings; thus, significant downregulation in the WECS groups was observed compared to OUW group (p < 0.05). The MDA was negatively associated with the gene expression of CXCL-2, CXCL8 (IL-8), and p53 (p < 0.05). The participants with silicosis (WECS II) presented significant increased non-protein thiol levels in relation to other groups (p < 0.05). Taken together, our findings may contribute to help the knowledge about the complex mechanisms involved in the silicosis pathogenesis and in the risk of lung cancer development in workers chronically exposed to respirable CS.

https://ift.tt/2zSLDFx

Issue Information

https://ift.tt/2zPWq3z

Issue Information

https://ift.tt/2PnNI7c

Issue Information

https://ift.tt/2PnNI7c

Low-Level Laser in Treatment of Head and Neck Lymphedema: A Pilot Study

Conditions:   Head and Neck Cancer;   Lymphedema;   Fibrosis
Intervention:   Device: Low-Level Laser
Sponsor:   University of Pennsylvania
Recruiting

https://ift.tt/2FwJSEr

Low-Level Laser in Treatment of Head and Neck Lymphedema: A Pilot Study

Conditions:   Head and Neck Cancer;   Lymphedema;   Fibrosis
Intervention:   Device: Low-Level Laser
Sponsor:   University of Pennsylvania
Recruiting

https://ift.tt/2FwJSEr

Window of Opportunity Trial of Durvalumab (MEDI4736) or Durvalumab/Tremelimumab as Neoadjuvant Chemotherapy to Identify Immune Dynamics in Surgically Resectable Head and Neck Cancer Patients.

Conditions:   Stage II-IVB Operable HNSCC Oral Cavity;   Hypopharynx;   Oropharynx;   Larynx
Interventions:   Drug: Durvalumab;   Drug: durvalumab + tremelimumab
Sponsor:   Yonsei University
Not yet recruiting

https://ift.tt/2qL8jn4

Window of Opportunity Trial of Durvalumab (MEDI4736) or Durvalumab/Tremelimumab as Neoadjuvant Chemotherapy to Identify Immune Dynamics in Surgically Resectable Head and Neck Cancer Patients.

Conditions:   Stage II-IVB Operable HNSCC Oral Cavity;   Hypopharynx;   Oropharynx;   Larynx
Interventions:   Drug: Durvalumab;   Drug: durvalumab + tremelimumab
Sponsor:   Yonsei University
Not yet recruiting

https://ift.tt/2qL8jn4

Study on the Occurrence of Head and Neck Cancers During Pregnancy

Conditions:   Head and Neck Cancer;   Pregnancy Related
Intervention:  
Sponsors:   Centre Francois Baclesse;   French scientific group REFCOR
Not yet recruiting

https://ift.tt/2FjdIvR

Study on the Occurrence of Head and Neck Cancers During Pregnancy

Conditions:   Head and Neck Cancer;   Pregnancy Related
Intervention:  
Sponsors:   Centre Francois Baclesse;   French scientific group REFCOR
Not yet recruiting

https://ift.tt/2FjdIvR

Gustatory Function Following Radiotherapy to the Head and Neck

Condition:   Head and Neck Cancer
Interventions:   Other: Olfactory screening;   Other: Quantative Gustatory Testing using Taste Strips
Sponsor:   Royal Marsden NHS Foundation Trust
Recruiting

https://ift.tt/2OJdMEC

Gustatory Function Following Radiotherapy to the Head and Neck

Condition:   Head and Neck Cancer
Interventions:   Other: Olfactory screening;   Other: Quantative Gustatory Testing using Taste Strips
Sponsor:   Royal Marsden NHS Foundation Trust
Recruiting

https://ift.tt/2OJdMEC

Strahlentherapie bei Gliomen

Zusammenfassung

Hintergrund

Die Strahlentherapie (RT) ist eine der wichtigen Säulen der Behandlung von Gliomen. Ständig werden neue Studien zum optimalen Bestrahlungszeitpunkt, der Dosierung und Fraktionierung und zur optimalen Kombination mit anderen Therapieformen publiziert.

Ziel

Die aktuellen Leitlinien und Studienergebnisse werden dargestellt und für die klinische Praxis zusammengefasst.

Material und Methode

Eine Literaturrecherche wurde durchgeführt, und die wichtigsten Publikationen und Leitlinien wurden als Grundlage der Empfehlungen für die klinische Praxis genommen.

Ergebnisse

Für die RT von Low-grade-Gliomen (WHO II) beim Erwachsenen ist das individuelle Risikoprofil entscheidend. Für die Patienten mit erhöhtem Rezidivrisiko ist eine frühe adjuvante RT mit 45–54 Gy empfohlen. Patienten mit High-grade-Gliomen sollten dagegen alle eine adjuvante RT mit einer Dosis von 59,4–60 Gy erhalten. Die Zielvolumendefinition und ob eine konkomittante oder adjuvante Chemotherapie notwendig ist, richtet sich nach dem WHO-Grad und der molekularen Diagnostik. Für Patienten in hohem Alter, mit reduziertem Allgemeinzustand und im Fall von Rezidiven gibt es immer mehr gute strahlentherapeutische Optionen.

Schlussfolgerungen

Die RT von Gliomen ist hinsichtlich der Zielvolumendefinition, Dosis und der Kombination mit Chemotherapie maßgeblich auf die WHO-Klassifikation, die molekulare Diagnostik und den klinischen Allgemeinzustand des Patienten ausgerichtet.

https://ift.tt/2z4SJY8

Radiotherapy of epicondylitis humeri

Abstract

Background

Epicondylitis humeri is a common disease with a prevalence of 1.7%. One of the treatment options is radiotherapy. Most published cases were treated with the orthovoltage technique or with a telecobalt device. Many radiotherapy institutions are nowadays using linear accelerators for treatment of epicondylitis humeri. There is a discussion whether the treatment results with linear accelerators are comparable to the orthovoltage technique. The aim of this study was to analyze the results of radiotherapy with a linear accelerator for epicondylitis humeri.

Material and methods

The analysis was performed on patients of 2 German radiotherapy institutions and included 138 irradiated elbows. Pain was documented with the numeric rating scale (NRS). Evaluation of the NRS was done before and directly after each radiation therapy course as well as for the follow-up of 24 months. The median age of the patients was 49 years with 48.4% male and 51.6% female. In all, 81.0% were suffering from from epicondylitis humeri radialis while 16.7% were treated because of epicondylitis humeri ulnaris. In 65.4% the dominant arm was treated.

Results

A significant response to radiotherapy could be found. For the whole sample the median pain was 7 on the NRS before radiotherapy, 4 after 6 weeks and 0 after 12 and 24 months. The percentage of patients with 0 or 1 on the NRS was 64.6% 12 months after radiotherapy. All subgroups, notably those with epicondylitis humeri radialis and epicondylitis humeri ulnaris had a significant reduction of pain.

Conclusion

Radiotherapy of epicondylitis humeri with a linear accelerator is an effective treatment without showing side effects. All analyzed subgroups showed a good response to radiotherapy for at least 24 months.

https://ift.tt/2z6Zicw

Polychlorinated biphenyls (PCBs) in commonly consumed seafood from the coastal area of Bangladesh: occurrence, distribution, and human health implications

Abstract

Dietary intake is the most important route of polychlorinated biphenyls (PCBs) exposure and seafood is the major dietary component for the coastal populations. It is, therefore, an urgent need to assess the levels of PCBs in seafood. A comprehensive congener-specific evaluation of PCBs was carried out for the first time in Bangladesh. All 209 congeners of PCBs in 48 seafood samples (5 finfish and 2 shellfish species) collected in winter and summer of 2015 were measured by GC-MS/MS. Regardless of season and site, the ∑PCBs (ng/g wet weight) in finfish and shellfish were in the range of 6.4–86.2 and 3.8–37.7, respectively. The results were comparable to or higher than those observed in other studies worldwide, particularly from Spain, China, Korea, Thailand, and Hong Kong. No significant seasonal variation was observed in the levels of ∑PCBs in the examined seafood (p > 0.05); however, interspecies differences were significant (p < 0.05). Nonetheless, spatial distribution revealed seafood collected from the areas with recent urbanization and industrialization (Chittagong, Cox's Bazar, and Sundarbans) were more contaminated with PCBs than the area unaffected by industries (Meghna Estuary). Moderately chlorinated (4–6 Cl) homologs dominated the PCB profiles. The congener profile and homolog composition revealed that the source origin of PCBs in the Bangladeshi seafood was related to mixtures of technical PCBs formulations. The dietary exposure assessment revealed that the coastal residents are sufficiently exposed to the dietary PCBs through seafood consumption which may cause severe health risk including dioxin-like toxic effects.

https://ift.tt/2FjxVl7

Pollutant source analysis and tempo-spatial analysis of pollutant discharge intensity in a transboundary river basin

Abstract

From the perspective of river basin refined management and pollution control of water bodies, a transboundary river basin and its regional pollutant sources are identified and the typical status of discharging processes of different pollutant sources are screened. Then organic connection which can comprehensively reflect and dynamically characterize the discharge of transboundary water pollutants is constructed. In addition, the integrated prediction (IP) model of the transboundary river basin and its regional water pollutants discharge is established. Finally, the dynamic simulation of typical status characteristics of the transboundary river basin and its regional pollutant sources discharge as well as the tempo-spatial changing pattern of pollutant discharge intensity is conducted in this paper. This paper selected the Songhua River basin as an example where planting, industry, household (urban living and rural living), and livestock and poultry are the main pollutant sources. The dynamic simulation of water pollution discharge in Songhua River basin during the 13th Five-year Plan and its tempo-spatial changing trend analysis are conducted by employing the established IP model of transboundary river basin water pollution discharge. The results show that during the 13th Five-year Plan, through comprehensive management and control of pollutant sources in Songhua River basin, the discharge amounts of different pollutant sources (planting, industry, household, livestock, and poultry) present an overall decreasing trend and the main pollutants discharge intensity decreases significantly year by year. It is demonstrated that pollution discharge in Songhua River basin is controlled effectively.

https://ift.tt/2qI9oMn

No evidence of the role of early chemical exposure in the development of β-cell autoimmunity

Abstract

Exposure to environmental chemicals can modulate the developing immune system, but its role in the pathogenesis of type 1 diabetes is largely unexplored. Our objective was to study the levels of circulating concentrations of environmental pollutants during the first years of life and their associations with the later risk of diabetes-predictive autoantibodies. From two birth-cohort studies including newborn infants with HLA-conferred susceptibility to type 1 diabetes (FINDIA and DIABIMMUNE), we identified case children with at least one biochemical diabetes-associated autoantibody (n = 30–40) and from one to four autoantibody-negative controls per each case child matched for age, gender, diabetes-related HLA-risk, delivery hospital, and, in FINDIA, also dietary intervention group. Plasma levels of 13 persistent organic pollutants and 14 per- and polyfluorinated substances were analyzed in cord blood and plasma samples taken at the age of 12 and 48 months. Both breastfeeding and the geographical living environment showed association with circulating concentrations of some of the chemicals. Breastfeeding-adjusted conditional logistic regression model showed association between decreased plasma HBC concentration at 12-month-old children and the appearance of diabetes-associated autoantibodies (HR, 0.989; 95% Cl, 0.978–1.000; P = 0.048). No association was found between the plasma chemical levels and the development of clinical type 1 diabetes. Our results do not support the view that exposure to the studied environmental chemicals during fetal life or early childhood is a significant risk factor for later development of β-cell autoimmunity and type 1 diabetes.

https://ift.tt/2FhwhQU

The suitability of growing mulberry ( Morus alba L.) on soils consisting of urban sludge composted with garden waste: a new method for urban sludge disposal

Abstract

Efficient disposal of urban sewage sludge, material that typically contains high concentrations of heavy metals, has become a significant concern worldwide. The empirical purpose of the current study is to investigate physical and chemical parameters of composted sludge and garden waste at different ratios. Results reveal that nutrient content has significantly increased after the application of composts as compared to the controlled sample. Composting garden waste with sewage sludge at a 1:1 ratio promoted plant growth and gradually showed superiority in the later period. The maximum plant height, total biomass, and crown width of mulberry trees increased by 12.1, 33.5, and 45.7%, respectively, compared with the control treatment. The bound to organic matter of Hg, Cr, and Pb in the sewage sludge increased after composting with garden waste, and the mulberry exhibited a high ability to accumulate Ni and Cd from the soil. Conclusively, compared to using the two soil mediums separately, composting garden waste and sewage sludge together is beneficial for soil improvement and vegetation growth.

https://ift.tt/2qHJyIm

CORRECTION

Publication date: Available online 13 November 2018

Source: Journal of the American Academy of Dermatology

Author(s):

https://ift.tt/2PTosoN

Salivary duct carcinoma: A prospective multicenter study of 61 cases of the Réseau d'Expertise Français des Cancers ORL Rares

Abstract

Background

The purposes of this study were to describe the characteristics of a prospective multicenter series of patients with salivary duct carcinoma and to investigate prognostic factors.

Methods

Patients included for salivary duct carcinoma between 2009 and 2016 in the Réseau d'Expertise Français des Cancers ORL Rares (REFCOR) database were selected. Immunohistochemical analyses were performed.

Results

Sixty‐one patients were included in this study. The primary site was the parotid gland in 90% of the cases. Fifty‐seven percent of the tumors were stage IV, 65% of patients had lymph node involvement, and 10% had metastases. Tumors showed androgen receptor (89%) and human epidermal growth factor receptor 2 (HER2)/neu (36%). Ninety‐four percent of patients underwent surgery and 86% had postoperative radiotherapy. Six patients were treated with targeted therapies. The 3‐year overall survival (OS) was 74% and the 3‐year disease‐free survival (DFS) was 44%. Tumor stages III to IV reduced DFS (hazard ratio [HR] 4.3; P = .04). The N2/3 class reduced distant metastasis‐free survival (HR 7.3; P = .007).

Conclusion

Salivary duct carcinoma prognosis is poor and is correlated with tumor stage and lymph node classification. Androgen receptor and HER2/neu should be tested as they offer the possibility of targeted therapies.

https://ift.tt/2qLimJ4

Sensing Mitochondrial Acetyl-CoA to Tune Respiration

Publication date: Available online 12 November 2018

Source: Trends in Endocrinology & Metabolism

Author(s): Christine A. Mills, Alec G. Trub, Matthew D. Hirschey

Fatty acid synthesis (FAS) in mitochondria produces a key metabolite called lipoic acid. However, a new study by Van Vranken et al.[1] (Mol. Cell 2018;71:567–580) shows that mitochondrial FAS regulates the assembly of oxidative phosphorylation complexes, thereby functioning as a nutrient sensor for mitochondrial respiration.

https://ift.tt/2PrUYic

Food OIT is Superior to Food Avoidance

Publication date: Available online 13 November 2018

Source: Annals of Allergy, Asthma & Immunology

Author(s): J. Andrew Bird

https://ift.tt/2FjMhSu

An Ounce of Caution: Superparamagnetic Iron Oxide Nanoparticle Based MRI Contrast Associated Anaphylaxis

Publication date: Available online 13 November 2018

Source: Annals of Allergy, Asthma & Immunology

Author(s): Alexander J. Heckman, Anjali Agarwal, Keith A. Sacco, Brett T. Hiroto, Pramod K. Guru

https://ift.tt/2qKctMg

The Effect of Delayed and Early Diagnosis in Siblings, and Importance of Newborn Screening for SCID

Publication date: Available online 12 November 2018

Source: Annals of Allergy, Asthma & Immunology

Author(s): Matthew S. Krantz, Cosby A. Stone, James A. Connelly, Allison E. Norton, Yasmin W. Khan

https://ift.tt/2FjM7KS

6-MOMIPP, a novel brain-penetrant anti-mitotic indolyl-chalcone, inhibits glioblastoma growth and viability

Abstract

Purpose

3-(6-Methoxy-2-methyl-1H-indol-3-yl)-1-(4-pyridinyl)-2-propene-1-one (6-MOMIPP) is a novel indole-based chalcone that disrupts microtubules. The present study aims to define the mechanism through which 6-MOMIPP induces cell death and to evaluate the efficacy of the compound in penetrating the blood–brain barrier and inhibiting growth of glioblastoma xenografts.

Methods

The effects of 6-MOMIPP were evaluated in cultured U251 glioblastoma cells, using viability, flow cytometry, and tubulin polymerization assays. Scintillation proximity and tubulin crosslinking methods were used to identify the binding site of 6-MOMIPP on tubulin, and western blots were performed to define the signaling pathways that contribute to cell death. LC/MS assays were used to study the pharmacokinetic behavior of 6-MOMIPP in mice. Subcutaneous and intracerebral xenograft models were utilized to assess the effects of 6-MOMIPP on growth of U251 glioblastoma in vivo.

Results

The findings indicate that 6-MOMIPP targets the colchicine site on β-tubulin. At concentrations ≥ 250 nm, 6-MOMIPP induces mitotic arrest, caspase activation and loss of cell viability. Cells are protected by caspase inhibitors, pointing to an apoptotic mechanism of cell death. Loss of cell viability is preceded by activation of Cdk1(Cdc2) and phosphorylation of Bcl-2 and Bcl-xL. Inhibition of both events with a Cdk1 inhibitor prevents cell death. 6-MOMIPP has broad activity against the viability of multiple glioblastoma, melanoma and lung carcinoma cell lines. Viability of normal cells, including differentiated neurons, is not significantly affected at a drug concentration (1 µM) that reduces viability in most cancer lines. Pharmacokinetic studies in mice show that concentrations of 6-MOMIPP in the brain mirror those in the plasma, indicating that 6-MOMIPP readily penetrates the blood–brain barrier. Studies with mice bearing human U251 glioblastoma xenografts demonstrate that 6-MOMIPP is effective in suppressing growth of subcutaneous and intracerebral tumors without causing general toxicity.

Conclusions

The results indicate that 6-MOMIPP is a novel microtubule disruptor that targets the colchicine binding site on β-tubulin to induce mitotic arrest and cell death. The ability of 6-MOMIPP to penetrate the blood–brain barrier and inhibit growth of glioblastoma xenografts suggests that it warrants further preclinical evaluation as potential small-molecule therapeutic that may have advantages in treating primary and metastatic brain tumors.

https://ift.tt/2PXsrAF

Celastrol antagonizes high glucose-evoked podocyte injury, inflammation and insulin resistance by restoring the HO-1-mediated autophagy pathway

Publication date: December 2018

Source: Molecular Immunology, Volume 104

Author(s): Xiaojiang Zhan, Caixia Yan, Yanbing Chen, Xin Wei, Jun Xiao, Lijuan Deng, Yuting Yang, Panlin Qiu, Qinkai Chen

Abstract

Diabetic nephropathy (DN) contributes to end-stage renal disease and kidney dysfunction with a proverbial feature of podocyte injury. Inflammation and insulin resistance is recently implicated in the pathogenesis of diabetic kidney injury. Celastrol exerts critical roles in inflammatory diseases and injury progression. However, its function and mechanism in DN remains elusive. Here, celastrol dose-dependently restored podocyte viability under high glucose (HG) conditions, but with little cytotoxicity in podocyte. Preconditioning with celastrol counteracted HG-evoked cell apoptosis, LDH release, ROS production and podocyte depletion. Additionally, HG-elevated high transcripts and secretions of pro-inflammatory cytokines were reversed following celastrol treatment, including IL-1β, TNF-α, IL-6. Simultaneously, the inhibitory effects of HG on insulin-triggered glucose uptake and nephrin expression were overturned after celastrol exposure. Intriguingly, celastrol restored HG-induced deficiency of autophagy pathway. Nevertheless, blocking the autophagy signaling by its antagonist 3-MA muted celastrol-protected against HG-evoked cell injury, inflammation and insulin resistance. Importantly, celastrol enhanced heme oxygenase-1 (HO-1) expression in HG-stimulated podocytes. Notably, HO-1 cessation depressed autophagy pathway activation and subsequently blunted beneficial effects of celastrol on HG-exposed podocytes. These finding suggest that celastrol may protect against HG-induced podocyte injury, inflammation and insulin resistance by restoring HO-1-mediated autophagy pathway, implying a promising therapeutic strategy against DN.

https://ift.tt/2QJFPWs

Detection and location of second mesiobuccal canal in permanent maxillary teeth: a cone-beam computed tomography analysis in a Taiwanese population

Publication date: Available online 12 November 2018

Source: Archives of Oral Biology

Author(s): Chi-Chun Su, Ren-Yeong Huang, Yu-Chiao Wu, Wan-Chien Cheng, Ho-Sheng Chiang, Ming-Pang Chung, Yi-Wen Cathy Tsai, Chi-Hsiang Chung, Yi-Shing Shieh

Abstract

Objectives

The aim of this study was to analyze the incidence, symmetry, concurrence of second mesiobuccal canal (MB2) and determine geometric relationships between each orifice of maxillary first and second molars by cone-beam computed tomography (CBCT) analysis.

Methods

A total of 216 qualified individuals' (503 teeth) CBCT image were enrolled in the present study. The consistency of bilateral symmetry and concurrent appearance of MB2 canals were analyzed among individuals with contralateral and adjacent molar teeth. The inter-orifice distances and angulations of first and second molars were also measured.

Results

The overall incidence of MB2 canal of maxillary molars was 39.2%, in which 45.9% and 32.3% in the first and second molars, respectively. The distribution of MB2 canal in contralateral molar teeth has significant gender difference in second molars (p = 0.024) while analyzing the frequency of MB2 canal appearing in contralateral molar pairs. The simultaneous occurrence of MB2 canal was 22.4% for contralateral molars, and the prevalence of concurrent appearance of MB2 canal in the adjacent molars was 43.4%. After adjusting for gender, age, and tooth type, the inter-orifice distances of mesiobuccal to palatal (odds ratios = 1.891) and to distobuccal (odds ratios = 1.448) canals, demonstrated significant differences between molars with and without MB2 canals.

Conclusions

The clinical significance of the results presents critical information on the geometric features, including inter-orifice distances and angulations between each orifice in maxillary molar teeth. Further studies should be conducted to investigate the exact anatomic coordination between each orifice and its impact on access preparation and external crown morphology.

https://ift.tt/2OEDutP

PERIODONTAL MECHANORECEPTORS AND BRUXISM AT LOW BITE FORCES

Publication date: Available online 12 November 2018

Source: Archives of Oral Biology

Author(s): Gizem Yilmaz, Christopher Laine, Neslihan Tinastepe, M. Gorkem Ozyurt, Kemal S. Türker

Abstract

Objective

In this study, we examined if 6–9 Hz jaw tremor, an indirect indicator of Periodontal Mechanoreceptor (PMR) activity, is different in bruxists compared to healthy participants during production of a low-level constant bite force.

Methods

Bite force and surface EMG from the masseter muscle were recorded simultaneously as participants (13 patients, 15 controls) held a force transducer between the upper and lower incisors very gently.

Results

Tremor in 6–9 Hz band for bruxists was greater on average compared to controls, but the difference was not significant, both for force recordings and EMG activity.

Conclusions

The low effect sizes measured with the current protocol contrast highly with those of our previous study, where larger, dynamic bite forces were used, and where jaw tremor was markedly different in bruxists compared with controls.

Significance

We have now gained important insight into the conditions under which abnormal jaw tremor can be elicited in bruxism. From a scientific standpoint, this is critical for understanding the 'abnormality' of PMR feedback in bruxism. From a clinical perspective, our results represent progress towards the development of an optimal protocol in which jaw tremor can serve as a biological marker of bruxism.

https://ift.tt/2z4Lgs4

Development and use of a mouth gag for oral experiments in rats

Publication date: Available online 12 November 2018

Source: Archives of Oral Biology

Author(s): Ryutaro Kuraji, Shuichi Hashimoto, Hiroshi Ito, Katsuhisa Sunada, Yukihiro Numabe

ABSTRACT

Objective

Rodent models such as mice and rats are often used in investigations of the oral cavity in the fields of periodontology and dental anesthesiology. When various treatments are performed in the oral cavity, it is very important to secure the visual field while keeping the animal's mouth fully opened, in order to ensure the consistency of experimental procedures. Therefore, we developed a standardized gag conforming to various degrees of oral cavity size of different aged rats.

Design

The gag was composed of a rectangular incisor-opening frame constructed from a stainless steel wire with retractors and a dial to alter the opening amounts. Wistar rats (n = 5) aged 4, 8, and 12 weeks were used to evaluate the suitability of the gag in oral cavity. As tests for application of gag in intraoral experiments, the ligature placement around the molars, drug injection into the gingiva, measurement of gingival blood flow rate, and installation of stimulation an electrode for somatosensory-evoked potentials into the molar were performed.

Results

Adjusting the opening dial enabled both the maintenance of open state and more favorable intraoral observation compared with tweezers as a control device in all different types of rats. Furthermore, our gag made it possible to facilitate the insertion of diverse instruments into the oral cavity and to achieve various experimental purposes. The stainless-steel gag can also be autoclaved and dry-heat sterilized.

Conclusion

It was revealed that our mouth gag can be widely applied to various oral experiments in different old aged rats.

https://ift.tt/2OJ3tQW

Loss of an IgG plasma cell checkpoint in lupus

Publication date: Available online 13 November 2018

Source: Journal of Allergy and Clinical Immunology

Author(s): Jolien Suurmond, Yemil Atisha-Fregoso, Emiliano Marasco, Ashley N. Barlev, Naveed Ahmed, Silvia A. Calderon, Mei Yin Wong, Meggan C. Mackay, Cynthia Aranow, Betty Diamond

Abstract

Background

IgG anti-nuclear antibodies (ANA) are a feature of several autoimmune diseases. These antibodies arise through defects in central or peripheral tolerance checkpoints. The specific checkpoints breached in autoimmune disease are not fully understood.

Objectives

To study whether autoreactive plasma cells in lupus models and SLE patients arise as a consequence of defective antigen-specific selection or a global enhancement of IgG PC differentiation.

Methods and Results

We optimized and validated a novel technique to detect naturally occurring ANA+ B cells and PC. We observed a major checkpoint for generation of ANA+ IgG+ PC in both non-autoimmune mice and healthy human subjects. Interestingly, we observed increased numbers of ANA+ IgG+ PC despite normal tolerance checkpoints in immature and naïve B cells in lupus-prone MRL/lpr and NZB/W mice as well as patients with systemic lupus erythematosus (SLE). This increase was due to increased numbers of total IgG+ PC rather than lack of selection against ANA+ PC.

Conclusion

Using a method that permits quick and accurate quantification of autoreactive B cells and PC in vivo within a native B cell repertoire in mice and humans, we demonstrate the importance of a checkpoint that restricts the generation of IgG plasma cells and protects against IgG ANA. Our observations suggest a fundamentally revised understanding of SLE: that it is a disease of aberrant B cell differentiation rather than a defect in antigen-specific B cell tolerance.

Clinical implication

Therapies for SLE might need to be targeted at IgG plasma cell differentiation rather than antigen-specific tolerance.

Graphical abstract

https://ift.tt/2Qzm43r

Exosome swarms eliminate airway pathogens and provide passive epithelial immunoprotection through nitric oxide

Publication date: Available online 12 November 2018

Source: Journal of Allergy and Clinical Immunology

Author(s): Angela L. Nocera, Sarina K. Mueller, Jules R. Stephan, Loretta Hing, Philip Seifert, Xue Han, Derrick T. Lin, Mansoor M. Amiji, Towia Libermann, Benjamin S. Bleier

Background

Nasal mucosa–derived exosomes (NMDEs) harbor immunodefensive proteins and are capable of rapid interepithelial protein transfer.

Objectives

We sought to determine whether mucosal exposure to inhaled pathogens stimulates a defensive swarm of microbiocidal exosomes, which also donate their antimicrobial cargo to adjacent epithelial cells.

Methods

We performed an institutional review board–approved study of healthy NMDE secretion after Toll-like receptor (TLR) 4 stimulation by LPS (12.5 μg/mL) in the presence of TLR4 inhibitors. Interepithelial transfer of exosomal nitric oxide (NO) synthase and nitric oxide was measured by using ELISAs and NO activity assays. Exosomal antimicrobial assays were performed with Pseudomonas aeruginosa. Proteomic analyses were performed by using SOMAscan.

Results

In vivo and in vitro LPS exposure induced a 2-fold increase in NMDE secretion along with a 2-fold increase in exosomal inducible nitric oxide synthase expression and function through TLR4 and inhibitor of nuclear factor κB kinase activation. LPS stimulation increased exosomal microbiocidal activity against P aeruginosa by almost 2 orders of magnitude. LPS-stimulated exosomes induced a 4-fold increase in NO production within autologous epithelial cells with protein transfer within 5 minutes of contact. Pathway analysis of the NMDE proteome revealed 44 additional proteins associated with NO signaling and innate immune function.

Conclusions

We provide direct in vivo evidence for a novel exosome-mediated innate immunosurveillance and defense mechanism of the human upper airway. These findings have implications for lower airway innate immunity, delivery of airway therapeutics, and host microbiome regulation.

Graphical abstract

https://ift.tt/2Pqa0oY

Mast Cell CRF2 Suppresses Mast Cell Degranulation and Limits the Severity of Anaphylaxis and Stress-Induced Intestinal Permeability

Publication date: Available online 12 November 2018

Source: Journal of Allergy and Clinical Immunology

Author(s): Susan D'Costa, Saravanan Ayyadurai, Amelia J. Gibson, Emily Mackey, Mrigendra Rajput, Laura J. Sommerville, Neco Wilson, Yihang Li, Eric Kubat, Ananth Kumar, Hariharan Subramanian, Aditi Bhargava, Adam J. Moeser

Abstract

Background

Psychological stress and heightened MC activation are linked with important immunological disorders including allergy, anaphylaxis, asthma, and functional bowel diseases, but the mechanisms remain poorly defined. We have previously demonstrated that activation of the corticotropin releasing factor (CRF) system potentiates MC degranulation responses during IgE-mediated anaphylaxis and psychological stress, via CRF receptor subtype 1 (CRF₁) expressed on MCs.

Objective

In this study, we investigated the role of CRF receptor subtype 2 (CRF₂) as a modulator of stress-induced MC degranulation and associated disease pathophysiology.

Methods

In vitro MC degranulation assays were performed with bone marrow derived MCs (BMMCs) derived from WT and CRF₂-deficient (CRF₂^-/-) mice and RBL-2H3 MCs transfected with CRF₂-overexpressing plasmid or CRF₂-siRNA. In vivo MC responses and associated pathophysiology in IgE-mediated passive systemic anaphylaxis (PSA) and acute psychological restraint stress were measured in WT, CRF₂^-/-, and MC-deficient Kit^W-sh/W-sh knock-in mice.

Results

Compared with WT mice, CRF2-/- exhibited heightened serum histamine levels and exacerbated PSA-induced anaphylactic responses and colonic permeability. In addition, CRF₂^-/- mice exhibited increased serum histamine and colonic permeability following acute restraint stress. Experiments with BMMCs and RBL-2H3 MCs demonstrated that CRF₂ expressed on MCs suppresses store-operated Ca²⁺ entry (SOCE) signaling and MC degranulation induced by diverse MC stimuli. Experiments with MC-deficient Kit^W-sh/W-sh mice systemically engrafted with WT and CRF₂^-/- BMMCs demonstrated the functional importance of MC-CRF₂ in modulating stress-induced pathophysiology.

Conclusions

MC CRF₂ is a negative, global modulator of stimuli-induced MC degranulation and limits the severity of IgE-mediated anaphylaxis and stress-related disease pathogenesis.

Graphical abstract

https://ift.tt/2QFQMZ4

Cochlear implantation after canal wall down mastoidectomy — Outcomes after partial mastoid obliteration

Publication date: Available online 12 November 2018

Source: Auris Nasus Larynx

Author(s): Matthias Balk, David Schwarz, Philipp Wolber, Andreas Anagiotos, Antoniu-Oreste Gostian

Abstract

Objective

To describe and evaluate the partial mastoid obliteration of the so-called radical mastoid cavity after canal-wall down mastoidectomy (CWD) for cochlear implantation (CI) compared to overclosure of the external ear canal as two stage procedures.

Methods

Out of 1020 patients undergoing cochlear implantation between January 1st, 2003 and June 15th, 2016 at the Department of Otolaryngology, Head & Neck Surgery, University Hospital Cologne, eight patients underwent obliteration of the radical cavity prior to cochlear implantation. In four additional patients, the external ear canal was overclosed prior to cochlear implantation.

Results

Patients undergoing partial mastoid obliteration (five ♀, 4 left ears) and overclosure of the external ear canal (one ♀, 3 left ears) averaged 56 years and 61 years, respectively. The radical cavities had been present for 21.8 years on average before partial obliteration and for 19.5 years before overclosure. Cochlear implantation following mastoid obliteration was performed after a mean period of 5.1 months and 3.8 months after overclosure. After partial mastoid obliteration, complete insertion of all electrodes was achieved and the clinical courses were uneventful for all patients. Likewise, no patient revealed any complications after overclosure of the external ear canal.

Conclusion

Partial mastoid obliteration with bone paté and cartilage after canal wall down mastoidectomy can be advocated as a feasible alternative technique that allows for a safe subsequent cochlear implantation.

https://ift.tt/2QDa6pD

Efficacy of anti-PD-1 therapy in a patient with brain metastasis of parotid carcinoma: A case report

Publication date: Available online 12 November 2018

Source: Auris Nasus Larynx

Author(s): Kota Takemoto, Nobuyuki Miyahara, Nobuyuki Chikuie, Takao Hamamoto, Takashi Ishino, Tsutomu Ueda, Sachio Takeno

Abstract

CheckMate 141, an open-label, randomized phase III trial of nivolumab, indicated that treatment with nivolumab prolonged overall survival of patients with platinum-refractory, recurrent head and neck squamous cell carcinoma. Herein, we describe a case of brain metastasis of parotid carcinoma in which a good response was achieved after nivolumab treatment. The patient was a 67-year-old woman with parotid carcinoma (cT4bN0M0) who received induction chemotherapy followed by chemoradiation. Computed tomography and magnetic resonance imaging performed 10 weeks after the primary treatment revealed a residual tumor and brain and lung metastases. Thereafter, chemotherapy comprising cisplatin, 5-FU, and cetuximab was performed. Unfortunately, the tumor volume increased 5 months after chemotherapy, after which she received immunotherapy with biweekly nivolumab. After six cycles of nivolumab administration, the brain and lung metastases shrank markedly. Nivolumab had an intracranial effect in the patient with brain metastases of parotid carcinoma. This case report highlights the efficacy of nivolumab in the management of head and neck cancer with brain metastasis.

https://ift.tt/2qLeMyA

Effects of l-carnitine administration on health-related quality of life during cisplatin-based chemoradiotherapy in patients with head and neck squamous cell carcinoma

Publication date: Available online 12 November 2018

Source: Auris Nasus Larynx

Author(s): Kazuhira Endo, Takayoshi Ueno, Kazuya Ishikawa, Yosuke Nakanishi, Satoru Kondo, Naohiro Wakisaka, Tomokazu Yoshizaki

Abstract

Objectives

Cancer-related fatigue impairs daily functioning and negatively impacts health-related quality of life (HRQoL). Our previous study revealed that cisplatin-based chemoradiotherapy (CRT) impairs the carnitine system and carnitine deficiency leads to poor physical functioning. This open label, randomized, controlled prospective study investigated the effects of l-carnitine administration on plasma carnitine concentration, CRT-induced fatigue, and decline in HRQoL in patients with head and neck squamous cell carcinoma (HNSCC).

Methods

Patients were divided into experimental group (received 1000 mg of oral liquid l-carnitine once daily for 8 weeks) and control group. The primary and secondary endpoints were the change in HRQoL scores and the change in carnitine levels, respectively, from baseline (pre-CRT) to after CRT.

Results

The mean total plasma carnitine concentration in the control group decreased significantly, 2 weeks after the end of chemotherapy, while no significant differences were seen in the l-carnitine group. l-carnitine administration, therefore, kept the physical functioning score unchanged.

Conclusion

Our study shows that patients who receive CRT experience chemotherapy-induced damage of carnitine homeostasis leading to deficiency of carnitine and impairment of HRQoL. l-carnitine administration is beneficial in improving the HRQoL in patients with HNSCC.

https://ift.tt/2QCGhp7

Curcumin gum formulation for prevention of oral cavity head and neck squamous cell carcinoma

Objectives/Hypothesis

Head and neck squamous cell carcinoma represents the sixth most common cancer. As a result of field cancerization, second primaries and recurrences are high. Hence, research has focused on chemoprevention. Curcumin, a polyphenol compound with anticarcinogenic properties, is one such promising nutraceutical. As poor bioavailability limits curcumin's use, a novel gum formulation was tested allowing for direct mucosal absorption into the bloodstream. This preliminary study validates curcumin gum efficacy by assessing release and transmucosal absorption, along with measuring its effects on serum cytokine levels.

Study Design

Clinical trial.

Methods

Protocols consisting of initial chew (chewing gum for 30 minutes) and revised chew (alternating chewing and parking gum against buccal mucosa for 30 minutes) were tested in healthy volunteers. High‐performance liquid chromatography measured remnant curcumin in chewed gum, serum, and saliva. Serum levels were assayed for 15 proinflammatory cytokines via multiplex analysis.

Results

Revised chew samples demonstrated significantly higher curcumin release and absorption (P = .0078). Curcumin serum levels were significantly higher at 4 hours in samples > 2.0 g of curcumin release (P = .01). As saliva levels decreased, a concurrent increase in serum levels was observed, with no significance in the inverse relationship (P = .1423). When evaluating differences between gender, race, and age, the Asian population showed significantly lower curcumin release and serum levels (P = .009). CXCL1 (GRO‐α) and TNF‐α were significantly decreased in serum after chewing the gum (P = .036, P < .001, respectively).

Conclusions

Enhanced mucosal contact appears critical in improving curcumin release and absorption. CXCL1 and TNF‐α both represent potential biomarkers for the future study of curcumin chemoprevention.

Level of Evidence

2b Laryngoscope, 2018

https://ift.tt/2QE7YOB

Quantification of injection force mechanics during injection laryngoplasty

Objectives

In‐office or operative injection laryngoplasty requires needle stability for accurate material placement. To date, no reports compare injection forces based on needle gauge, bends, length, or material type or temperature. We hypothesize these factors alter injection forces and could impact clinical use.

Methods

Swine larynges were placed in a compression testing machine. Syringes were affixed to a stabilizing crossbeam. Straight needles (25G 1.5‐inch; 27G 1.25‐inch; or 9.8‐inch malleable shaft 16G per oral with 24G tapered needle tip) were inserted into the swine vocal folds to simulate realistic tissue resistance pressure. Compressive loading was conducted at 40 mm/minute until steady‐state force was achieved. Tests were completed with calcium hydroxylapatite (CaHa), carboxymethylcellulose, and hyaluronic acid at various temperatures and CaHa with various bends in the needles (n = 3 per group, comparisons performed by two‐way analysis of variance (ANOVA), Tukey's post‐hoc).

Results

Needle size, shape, and temperature altered injection force. Steady‐state force was highest with the per‐oral needle at a mean of 44.55N compared to 26.44N and 29.77N in the 25G and 27G percutaneous needles, respectively (P < 0.001). Stiffness rate (initial increasing force vs. distance to initiate injection) ranged from 19.75N/mm (per oral) to 22.06N/mm (25G) to 24.56N/mm (27G), (P = 0.875). Adding multiple bends to the per‐oral needle increased stiffness rate to 24.99N/mm (P = 0.035), whereas the 25G needle stiffness rate remained unchanged (P = 0.941), with the stiffness rate decreasing in the 27G needle with increasing bends (P = 0.033). Increased temperature decreased injection forces across all materials.

Conclusion

Needle caliber, length, and bends impact steady‐state forces and stiffness rates during vocal fold injection.

Level of Evidence

NA. Laryngoscope, 2018

https://ift.tt/2PpLbJv

Gamification as a tool for resident education in otolaryngology: A pilot study

https://ift.tt/2QCope3

T‐Helper 2 Lymphocyte Immunophenotype Is Associated With Iatrogenic Laryngotracheal Stenosis

Objective/Hypothesis

This prospective controlled human and murine study assessed the presence of inflammatory cells and cytokines to test the hypothesis that immune cells are associated with fibroproliferation in iatrogenic laryngotracheal stenosis (iLTS).

Methods

Inflammation was assessed by histology and immunofluorescence (IF), quantitative real‐time polymerase chain reaction (qRT‐PCR), and flow cytometry of cricotracheal resections of iLTS patients compared to normal controls. An iLTS murine model assessed the temporal relationship between inflammation and fibrosis.

Results

iLTS specimens showed increased inflammation versus normal controls (159/high power field [hpf] vs. 119/hpf, P = 0.038), and increased CD3 + T‐cells, CD4 + cells, and CD3+/CD4 + T‐helper (T_H) cells (all P < 0.05). The inflammatory infiltrate was located immediately adjacent to the epithelial surface in the superficial aspect of the thickened lamina propria. Human flow cytometry and qRT‐PCR showed a significant increase in interleukin (IL)‐4 gene expression, indicating a T_H2 phenotype. Murine IF revealed a dense CD4 + T‐cell inflammatory infiltrate on day 4 to 7 postinjury, which preceded the development of fibrosis. Murine flow cytometry and qRT‐PCR studies mirrored the human ones, with increased T‐helper cells and IL‐4 in iLTS versus normal controls.

Conclusion

CD3/CD4 + T‐helper lymphocytes and the proinflammatory cytokine IL‐4 are associated with iLTS. The association of a T_H2 immunophenotype with iLTS is consistent with findings in other fibroinflammatory disorders. The murine results reveal that the inflammatory infiltrate precedes the development of fibrosis. However, human iLTS specimens with well‐developed fibrosis also contain a marked chronic inflammatory infiltrate, suggesting that the continued release of IL‐4 by T‐helper lymphocytes may continue to propagate iLTS.

Level of Evidence

NA. Laryngoscope, 2018

https://ift.tt/2Pq9siU