Reproducibility of measurement of skin melanin, total hemoglobin, and oxygen saturation

http://ift.tt/2hY8Uxb

Spread of fluid: Role of tip configurations in needles

Abstract

Background/purpose

During the injection of a fluid in a tissue model, the fluid might be affected by the needle tip configuration and the number of channels. Thus, the objective of the present work is to observe the influence of different needle tips and number of channels on the spread of a fluid.

Methods

Fluid distribution data were obtained after injecting 0.3 mL of fluid into a foamed polymer model with a velocity of 2 mm/s. The spread area and the depth were determined for 3 different types of hypodermic needles: Single channel needles with bevel tip and blunt tip and a needle with conical tip and 3 internal channels.

Results

The bevel tip provides a higher spread in the direction where the bevel points and reaches larger depths than the other two needles. The spread for the blunt tip and the polymer needle is equally distributed on both sides of the needle. The largest horizontal area around the tip is achieved by the 3-channel needle.

Conclusion

The tip configuration and number of channels have an influence on the distribution of fluid. The bevelled needle directs the fluid and reaches larger depths compared with the 3-channel needle that gets more horizontal spread.

http://ift.tt/2gwsFvu

A feature fusion system for basal cell carcinoma detection through data-driven feature learning and patient profile

Abstract

Background

Basal cell carcinoma (BCC) is the most common skin cancer, which is highly damaging in its advanced stages. Computer-aided techniques provide a feasible option for early detection of BCC. However, automated BCC detection techniques immensely rely on handcrafting high-level precise features. Such features are not only computationally complex to design but can also represent a very limited aspect of the lesion characteristics. This paper proposes an automated BCC detection technique that directly learns the features from image data, eliminating the need for handcrafted feature design.

Methods

The proposed method is composed of 2 parts. First, an unsupervised feature learning framework is proposed which attempts to learn hidden characteristics of the data including vascular patterns directly from the images. This is done through the design of a sparse autoencoder (SAE). After the unsupervised learning, we treat each of the learned kernel weights of the SAE as a filter. Convolving each filter with the lesion image yields a feature map. Feature maps are condensed to reduce the dimensionality and are further integrated with patient profile information. The overall features are then fed into a softmax classifier for BCC classification.

Results

On a set of 1199 BCC images, the proposed framework achieved an area under the curve of 91.1%, while the visualization of learned features confirmed meaningful clinical interpretation of the features.

Conclusion

The proposed framework provides a non-invasive fast BCC detection tool that incorporates both dermoscopic lesional features and clinical patient information, without the need for complex handcrafted feature extraction.

http://ift.tt/2hYudi5

Validation of digital photographic reference scales for evaluating facial aging signs

Abstract

Background

Validated tools are essential to evaluate facial skin aging for both dermatological and cosmetic investigations. While many visual aging scales have been developed, few have been validated and none in terms of degree of distinguishability (DD). We developed and validated a series of visual scales using a novel digital interface for scoring facial skin aging in Caucasian women.

Materials and methods

Three dermatologists independently established scales for 12 distinct aging signs from high-definition facial photographs of 400 adult women (Fitzpatrick phototypes I-IV) taken under standardized conditions. They then selected a consensus scale for each individual sign with a representative photo per grade. Scales were integrated into a digital interface allowing simultaneous viewing of all grades of each scale alongside the photograph of a test subject. Next, scales were validated by a different dermatologist, a general practitioner and a non-medical expert skin evaluator using photos of 350 women which had not been used for establishing the scales.

Results

Kappa estimates showed almost perfect agreement for wrinkle and skin aging scales (≥0.85) and moderate to substantial agreement for scales relating to color irregularities (telangiectasia, solar lentigines, freckles) for both inter- and intra-observer reproducibility. Intra-observer DD estimates were mostly high. Non-dermatologists performed well on reproducibility for both Kappa (from 0.6 to 0.9) and DD estimates.

Conclusion

Our work demonstrates that the digital interface scales for 12 distinct aging features are highly suitable for use in clinical and epidemiological studies on skin aging by both dermatologists and non-dermatologists.

http://ift.tt/2gxuzM1

Spectrophotometer is useful for assessing vitiligo and chemical leukoderma severity by quantifying color difference with surrounding normally pigmented skin

Abstract

Background

Acquired skin hypopigmentation has many etiologies, including autoimmune melanocyte destruction, skin aging, inflammation, and chemical exposure. Distinguishing lesions from normally pigmented skin is clinically important to precisely assess disease severity. However, no gold standard assessment method has been reported. We aimed to investigate whether spectrophotometers are useful for assessing vitiligo and rhododendrol (4-(4-hydroxyphenol)-2-butanol) (Rhododenol^®)-induced leukoderma disease severity by quantifying skin color.

Methods

Mexameter^® MX18 and CM-700d spectrophotometer were used for assessing vitiligo/leukoderma by measuring melanin index, L*a*b* color space, and ΔE*ab value, which represents the color difference between two subjects and is calculated by the values of L*a*b*.

Results

MX18 and CM-700d can quantitatively distinguish vitiligo/leukoderma from normally pigmented skin based on melanin index. CM-700d consistently quantified the color of vitiligo/leukoderma lesions and surrounding normally pigmented skin in L*a*b* color spaces and ΔE*ab. ΔE*ab is well correlated with melanin index and clinical appearance.

Conclusion

ΔE*ab has been frequently used in aesthetic dentistry; however, current study is the first to use it in the measurement of skin color. ΔE*ab seems to be a useful parameter to evaluate the color contrast between vitiligo/leukoderma and surrounding normally pigmented skin and can be used to evaluate disease severity and patient's quality of life.

http://ift.tt/2i0oGY2

Reply to correspondence ‘Topical ionic contra viral therapy comprised of digoxin and furosemide as a potential novel treatment approach for common warts’

We appreciate Dr Abdelmaksoud's thorough review of our manuscript (1) and would like to reply to the comments that were raised with this letter. First, it appears that the understanding is that the study describes the 'clinical response of common warts to a topical application of a fixed dose of 980 mg of the ICVT gel on the patients' lower back. It should be clarified that the main objective of this first-in-man study was evaluate the systemic exposure, safety and tolerability of ionic-contra-viral therapy (ICVT) (2).

This article is protected by copyright. All rights reserved.

http://ift.tt/2l83hkB

Activity in LIP, But not V4, Matches Performance When Attention is Spread

Abstract

The enhancement of neuronal responses in many visual areas while animals perform spatial attention tasks has widely been thought to be the neural correlate of visual attention, but it is unclear whether the presence or absence of this modulation contributes to our striking inability to notice changes in change blindness examples. We asked whether neuronal responses in visual area V4 and the lateral intraparietal area (LIP) in posterior parietal cortex could explain the limited ability of subjects to attend multiple items in a display. We trained animals to perform a change detection task in which they had to compare 2 arrays of stimuli separated briefly in time and found that each animal's performance decreased as function of set-size. Neuronal discriminability in V4 was consistent across set-sizes, but decreased for higher set-sizes in LIP. The introduction of a reward bias produced attentional enhancement in V4, but this could not explain the vast improvement in performance, whereas the enhancement in LIP responses could. We suggest that behavioral set-size effects and the marked improvement in performance with focused attention may not be related to response enhancement in V4 but, instead, may occur in or on the way to LIP.

http://ift.tt/2gA97tw

Ventromedial Frontal Lobe Damage Alters how Specific Attributes are Weighed in Subjective Valuation

Abstract

The concept of subjective value is central to current neurobiological views of economic decision-making. Much of this work has focused on signals in the ventromedial frontal lobe (VMF) that correlate with the subjective value of a variety of stimuli (e.g., food, monetary gambles), and are thought to support decision-making. However, the neural processes involved in assessing and integrating value information from the attributes of such complex options remain to be defined. Here, we tested the necessary role of VMF in weighting attributes of naturalistic stimuli during value judgments. We asked how distinct attributes of visual artworks influenced the subjective value ratings of subjects with VMF damage, compared to healthy participants and a frontal lobe damaged control group. Subjects with VMF damage were less influenced by the energy (emotion, complexity) and color radiance (warmth, saturation) of the artwork, while they were similar to control groups in considering saliency, balance and concreteness. These dissociations argue that VMF is critical for allowing certain affective content to influence subjective value, while sparing the influence of perceptual or representational information. These distinctions are important for better defining the often-underspecified concept of subjective value and developing more detailed models of the brain mechanisms underlying decision behavior.

http://ift.tt/2hZgBmw

Task-Modulated Cortical Representations of Natural Sound Source Categories

Abstract

In everyday sound environments, we recognize sound sources and events by attending to relevant aspects of an acoustic input. Evidence about the cortical mechanisms involved in extracting relevant category information from natural sounds is, however, limited to speech. Here, we used functional MRI to measure cortical response patterns while human listeners categorized real-world sounds created by objects of different solid materials (glass, metal, wood) manipulated by different sound-producing actions (striking, rattling, dropping). In different sessions, subjects had to identify either material or action categories in the same sound stimuli. The sound-producing action and the material of the sound source could be decoded from multivoxel activity patterns in auditory cortex, including Heschl's gyrus and planum temporale. Importantly, decoding success depended on task relevance and category discriminability. Action categories were more accurately decoded in auditory cortex when subjects identified action information. Conversely, the material of the same sound sources was decoded with higher accuracy in the inferior frontal cortex during material identification. Representational similarity analyses indicated that both early and higher-order auditory cortex selectively enhanced spectrotemporal features relevant to the target category. Together, the results indicate a cortical selection mechanism that favors task-relevant information in the processing of nonvocal sound categories.

http://ift.tt/2gA96Wu

Fall 2017 - Introduction to Tempus

A review of the technological advancements of Unitron's Tempus™ platform, new rechargeable solutions, and new features in Unitron TrueFit fitting software.

http://ift.tt/2gZJKhO

Angiolymphoid hyperplasia with eosinophilia: report of nine cases

Abstract

Background

Angiolymphoid hyperplasia with eosinophilia (ALHE) is a benign vascular proliferation characterized by dermal or subcutaneous red or brown papules or nodules, most commonly on the head and neck.

Objective

The aim of this study was to review the epidemiological and clinical characteristics of ALHE, focusing particularly on the histological and therapeutic features.

Methods

We performed a retrospective study of all cases of ALHE diagnosed in our dermatology and pathology departments between 2004 and 2015.

Results

Over 12 years, we collected nine cases of ALHE (0.75 case/year). There were four men and five women. The mean age was 43 years. Lesions presented as erythematous or violaceous papules or nodules in all cases, multiple in five cases, and localized on the head in eight cases or other sites in four cases. The diagnosis of ALHE was clinically suspected in only two cases. The histopathological findings showed an ill-circumscribed, intradermal slightly lobular proliferation of capillary-sized vessels around several central vessels. In all cases, the blood vessels were lined by large endothelial cells. An inflammatory infiltrate around the vessels was formed mainly of lymphocytes and eosinophils with isolated plasma cells and histiocytes. Surgery was the most common treatment in our series. Other local or general treatment has also been used with varying responses.

Conclusion

Angiolymphoid hyperplasia with eosinophilia is a rare epithelioid vascular tumor with a challenging clinical and histological diagnosis. Despite its benign nature, ALHE causes a therapeutic dilemma.

http://ift.tt/2l6zYPv

ALK-positive primary cutaneous anaplastic large cell lymphoma: a case report and review of the literature

Abstract

Anaplastic large cell lymphoma (ALCL) limited to the skin is a distinct disease that is designated primary cutaneous ALCL (pcALCL). It has an indolent course with a significantly better prognosis compared to systemic ALCL (sALCL). Anaplastic lymphoma kinase (ALK) expression in lesions of cutaneous ALCL is classically considered to be a marker for skin involvement by sALCL. However, recent reports of patients with ALK-positive pcALCL challenge this concept and raise prognostic and therapeutic dilemmas. Herein, we report a case of ALK-positive pcALCL in a 45-year-old woman who was treated with local radiotherapy. We review previously reported cases in the literature to better characterize this rare variant. Overall, the rates of cutaneous recurrence, systemic dissemination, and disease-related mortality in ALK-positive pcALCL do not differ from those previously reported in pcALCL. ALK-positive pcALCL is diagnosed at younger age and has a better disease course in children compared to adults with lower incidences of skin recurrence and progression to systemic disease. We conclude that ALK-positivity in cutaneous ALCL does not necessarily imply systemic disease. ALK-positive pcALCL has an excellent prognosis and should be treated by excision and/or radiotherapy. However, patients must remain under close long-term follow-up as recurrence and progression to systemic disease may occur.

http://ift.tt/2xXw6Xc

Unusual location of a common dermatosis

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Novel Double-Needle System That Can Prevent Intravascular Injection of Any Filler

Summary: A new type of needle system combines 2 parts, an inner needle and an outer needle. The inner needle is used for filler injection and the outer needle acts as a guiding needle that can observe blood reflow when inserting into the vessel lumen during injection process. This new needle system can be used for all kinds of filler, providing real time monitoring for physician and preventing intravascular injection of any filler.

http://ift.tt/2xYcqlQ

Prepectoral Implant-Based Breast Reconstruction

Background: The development of acellular dermal matrices (ADMs) has facilitated single-stage implant breast reconstruction (IBR) following skin-sparing mastectomy. The conventional approach of postpectoral implant placement with lower pole ADM confers a good cosmetic result by improving lower pole projection and control, while minimizing issues of implant visibility, palpability, and rippling. This is balanced with potential disadvantages including pain, disruption of pectoral muscle function, and animation. We report the results of a prospective study of prepectoral IBR with total ADM coverage. Methods: Prepectoral IBR with total ADM coverage was performed in 106 patients (166 breasts) in our institution from 2013 to 2017. The cohort included patients undergoing immediate IBR (113 breasts) and revision of existing submuscular IBR (53 breasts). Patient demographics, surgical complications, and outcomes from a prospective database were analyzed. Results: At a mean follow-up of 485 days, patient satisfaction and cosmetic outcomes have been good, with no significant capsular contractures or animation deformity. Minor complications including delayed healing, red breast, or seroma occurred in 14 breasts (8.4%). Major complications including necrosis and implant loss occurred in 5 breasts (3 patients), with a total explantation rate of 3%. No patients required more than an overnight stay in hospital, and there were no delays to adjuvant treatment in therapeutic cases. Conclusion: Prepectoral implant placement with ADM cover is emerging as an alternative approach for IBR. This method facilitates breast reconstruction with a good cosmetic outcome for patients who want a quick recovery without potential compromise of pectoral muscle function and associated problems.

http://ift.tt/2ztcRSt

Q-switched Nd: YAG laser alone or with modified Jessner chemical peeling for treatment of mixed melasma in dark skin types: A comparative clinical, histopathological, and immunohistochemical study

Summary

Backgrounds

Treatment of mixed melasma remains challenging. Promising results have been achieved with low-fluence 1064-nm Q-switched Nd-YAG laser; however, multiple sessions are necessary with occurrence of complications especially in dark skin types. So, combination methods may be recommended.

Aims

To compare efficacy of Q-switched Nd-YAG laser alone or with modified Jessner's peel in mixed melasma in dark skin.

Patients/Methods

Nineteen patients with mixed melasma received 6 sessions of laser on left side of face and alternating laser and modified Jessner on right side. Evaluation was carried out clinically through modified melasma area and severity index at 1 month after last session. Using histopathological, immunohistochemical, and computerized morphometric analysis, objective evaluation of melanin particle surface area and MART-1-positive cells was performed for pre- and post-treated skin biopsies.

Results

There was significant clinical improvement on both sides of face (P < .001), without significant difference (P > .05). At the sixth laser session on left side of face, ill-defined mottled hypopigmentation was observed in 21.05% of patients. Histopathologically, melanin particle surface area and number of MART-1-positive cells (total, epidermal, and dermal) were significantly decreased after two treatment modalities (P < .001), without significant difference in their reduction percentage between both sides of face (P > .05).

Conclusion

Low-fluence Q-switched Nd-YAG laser alone and with modified Jessner's peel are equally effective regimens for mixed melasma clinically, histopathologically, and immunohistochemically. However, combined method is preferred, especially in dark skin, for obtaining better cosmetic result with fewer side effects of multiple laser sessions and decreasing cost rate of laser.

http://ift.tt/2l80d8b

Q-switched Nd: YAG laser alone or with modified Jessner chemical peeling for treatment of mixed melasma in dark skin types: A comparative clinical, histopathological, and immunohistochemical study

Summary

Backgrounds

Treatment of mixed melasma remains challenging. Promising results have been achieved with low-fluence 1064-nm Q-switched Nd-YAG laser; however, multiple sessions are necessary with occurrence of complications especially in dark skin types. So, combination methods may be recommended.

Aims

To compare efficacy of Q-switched Nd-YAG laser alone or with modified Jessner's peel in mixed melasma in dark skin.

Patients/Methods

Nineteen patients with mixed melasma received 6 sessions of laser on left side of face and alternating laser and modified Jessner on right side. Evaluation was carried out clinically through modified melasma area and severity index at 1 month after last session. Using histopathological, immunohistochemical, and computerized morphometric analysis, objective evaluation of melanin particle surface area and MART-1-positive cells was performed for pre- and post-treated skin biopsies.

Results

There was significant clinical improvement on both sides of face (P < .001), without significant difference (P > .05). At the sixth laser session on left side of face, ill-defined mottled hypopigmentation was observed in 21.05% of patients. Histopathologically, melanin particle surface area and number of MART-1-positive cells (total, epidermal, and dermal) were significantly decreased after two treatment modalities (P < .001), without significant difference in their reduction percentage between both sides of face (P > .05).

Conclusion

Low-fluence Q-switched Nd-YAG laser alone and with modified Jessner's peel are equally effective regimens for mixed melasma clinically, histopathologically, and immunohistochemically. However, combined method is preferred, especially in dark skin, for obtaining better cosmetic result with fewer side effects of multiple laser sessions and decreasing cost rate of laser.

http://ift.tt/2l80d8b

Science as momentary truth

Publication date: Available online 19 October 2017
Source:Brazilian Journal of Otorhinolaryngology
Author(s): Leonardo Silva




http://ift.tt/2xZoVJ6

Side effects of intraoral devices for OSAS treatment

Publication date: Available online 14 October 2017
Source:Brazilian Journal of Otorhinolaryngology
Author(s): Andressa Otranto de Britto Teixeira, Ana Luiza Ladeia Andrade, Rhita Cristina da Cunha Almeida, Marco Antonio de Oliveira Almeida
IntroductionIntraoral devices have increasingly assumed a key role in the treatment of Obstructive Sleep Apnea Syndrome, but there are limitations to their indication and side effects that result from their continuous use, as well as the use of the Continuous Positive Airway Pressure (CPAP) device.ObjectivesTo evaluate the changes in dental positioning caused by the continuous use of mandibular advancement devices.MethodsA prospective longitudinal study with a sample of 15 patients, with evaluation of complete documentation after a mean time of 6.47 months, assessed changes in dental positioning due to the use of the Twin Block oral device for the treatment of patients with apnea. The following variables were evaluated: overjet, overbite, upper and lower intermolar distances, upper and lower intercanine distances, Little's irregularity index and the incisor mandibular plane angle (IMPA). An intraclass correlation test was performed and a correlation index>0.08 was accepted. After verifying the normal sample distribution (Shapiro-Wilks), a parametric test was used (t Test), with a significance level set at 5%.ResultsThere was a decrease in the values of overjet, overbite and Little's irregularity index, whereas there was an increase in the lower intercanine distance and IMPA values. All these variables are influenced, at different levels, by the forward inclination of the lower incisors, an action that can be expected due to the force applied by the device on the dentition. The other variables did not show statistically significant differences.ConclusionAfter a mean time of 6.47 months of use of the mandibular advancement device, there were statistically significant changes in the dental positioning, but they were not clinically relevant. However, it is relevant that this device is commonly in use over long periods of time, making the monitoring of these patients of the utmost importance for the duration of their therapy.



http://ift.tt/2yHNvBL

Neutrophil–lymphocyte ratios in the prognostication of primary non-metastatic Nasopharyngeal Carcinoma

Publication date: Available online 19 October 2017
Source:Brazilian Journal of Otorhinolaryngology
Author(s): Kong Yew Liew, Abu Bakar Zulkiflee
IntroductionNasopharyngeal Carcinoma is a geographically and racially variable disease which has a high incidence in Malaysia. Based on current concepts in tumour related inflammation the inflammatory marker, Neutrophil–Lymphocyte Ratio was tested to find its relationship with prognosis in Nasopharyngeal Carcinoma.ObjectiveTo investigate the effect of the Neutrophil–Lymphocyte Ratio on prognosis in non-metastatic primary Nasopharyngeal Carcinoma patients and to further refine the cut off between high and low Neutrophil–Lymphocyte Ratio values.MethodsThe medical charts of patients with histologically confirmed Nasopharyngeal Carcinoma from 1st January 2005 until 31st December 2009 were reviewed retrospectively and the Neutrophil–Lymphocyte Ratio was calculated to see if there was any association between their higher values with higher failure rates.ResultsRecords of 98 patients (n=98) were retrieved and reviewed. Only Neutrophil–Lymphocyte Ratio (p=0.004) and TMN staging (p=0.002) were significantly different between recurrent and non-recurrent groups, with the Neutrophil–Lymphocyte Ratio being independent of TNM staging (p=0.007). Treatment failure was significantly higher in the high Neutrophil–Lymphocyte Ratio group (p=0.001). Disease Free Survival was also significantly higher in this group (p=0.000077).ConclusionHigh Neutrophil–Lymphocyte Ratio values are associated with higher rates of recurrence and worse Disease Free Survival in non-metastatic Nasopharyngeal Carcinoma patients undergoing primary curative treatment.



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Strain rate-induced plasticity in bcc β-Ti alloy single crystal micropillars containing brittle ω-precipitates

Publication date: 5 January 2018
Source:Materials & Design, Volume 137
Author(s): Wei Chen, Zaiwang Huang, Shuo Cao, Yan Pan, Mingda Huang, Qingmiao Hu, Ding Xu, Qiaoyan Sun, Lin Xiao, Jun Sun
Brittle ω-precipitates in bcc β-Ti alloys are well known to dramatically degrade material plasticity and even trigger macroscopic premature fracture, posing an obstacle for structural applications. The embrittlement mechanism is intimately related to dislocation pile-up at the ω/β interface that leads to stress concentration and undesirable failure. The underlying physics of improving ductility remains to be further uncovered. Here we report a new finding in β-Ti alloy single crystal micropillar compression that the plasticity can be substantially improved by means of increasing strain rate, while mechanical strength simultaneously exhibits striking "faster is stronger" fashion. The results reveal that the improvement of micropillar plasticity upon higher loading rate can be ascribed to the wider deformation band, in contrast to equivalents under quasi-static mode. The microscopic examination shows that cross slip induced by screw dislocations governs the plasticity improvement, which is further validated by crystallographic analysis and first principle energy landscape calculations. This "dynamic self-toughening" behavior advances our fundamental understanding to the plastic deformation mechanism of ω-precipitate contained bcc β-Ti alloys.

Graphical abstract

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Materials selection of flexible open-cell foams in energy absorption applications

Publication date: 5 January 2018
Source:Materials & Design, Volume 137
Author(s): Evan T. Bird, Anton E. Bowden, Matthew K. Seeley, David T. Fullwood
Foam must be engineered to absorb a particular range of energy in various impact-related applications. Since energy absorption is dependent upon the unique stress-strain response of each foam specimen, it is difficult to quantify analytically; thus, energy absorption cannot be easily compared across materials. Current methods accomplish this using an experimental approach, individually testing foam materials, densities, and geometries to quantify how each influences energy absorption. Such methods require large amounts of time and money to characterize a narrow range of foams. This paper facilitates foam selection by deriving generalized energy absorption material indices. Assuming Euler buckling of columns in the open-cell foam structure, this paper applies equations derived by Maiti et al. to a typical impact scenario wherein the indices are extracted. Using existing Ashby charts, these indices allow polymers to be ranked by the mass and cost each would require as a foamed structure to satisfy specific energy absorption constraints. The presented method allows the energy absorption of a wide range of flexible foams to be compared and relieves the need for extensive factor-specific testing. This method is applied to football helmet foam selection; however, it can be used for many applications where energy absorption is of interest.

Graphical abstract

http://ift.tt/2yGu3Uu

Joint groupwise registration and ADC estimation in the liver using a B-value weighted metric

Publication date: February 2018
Source:Magnetic Resonance Imaging, Volume 46
Author(s): Santiago Sanz-Estébanez, Iñaki Rabanillo-Viloria, Javier Royuela-del-Val, Santiago Aja-Fernández, Carlos Alberola-López
PurposeThe purpose of this work is to develop a groupwise elastic multimodal registration algorithm for robust ADC estimation in the liver on multiple breath hold diffusion weighted images.MethodsWe introduce a joint formulation to simultaneously solve both the registration and the estimation problems. In order to avoid non-reliable transformations and undesirable noise amplification, we have included appropriate smoothness constraints for both problems. Our metric incorporates the ADC estimation residuals, which are inversely weighted according to the signal content in each diffusion weighted image.ResultsResults show that the joint formulation provides a statistically significant improvement in the accuracy of the ADC estimates. Reproducibility has also been measured on real data in terms of the distribution of ADC differences obtained from different b-values subsets.ConclusionsThe proposed algorithm is able to effectively deal with both the presence of motion and the geometric distortions, increasing accuracy and reproducibility in diffusion parameters estimation.



http://ift.tt/2yMmxcu

Multi-echo reconstruction from partial K-space scans via adaptively learnt basis

Publication date: January 2018
Source:Magnetic Resonance Imaging, Volume 45
Author(s): Jyoti Maggu, Prerna Singh, Angshul Majumdar
In multi-echo imaging, multiple T1/T2 weighted images of the same cross section is acquired. Acquiring multiple scans is time consuming. In order to accelerate, compressed sensing based techniques have been proposed. In recent times, it has been observed in several areas of traditional compressed sensing, that instead of using fixed basis (wavelet, DCT etc.), considerably better results can be achieved by learning the basis adaptively from the data. Motivated by these studies, we propose to employ such adaptive learning techniques to improve reconstruction of multi-echo scans. This work will be based on two basis learning models – synthesis (better known as dictionary learning) and analysis (known as transform learning). We modify these basic methods by incorporating structure of the multi-echo scans. Our work shows that we can indeed significantly improve multi-echo imaging over compressed sensing based techniques and other unstructured adaptive sparse recovery methods.



http://ift.tt/2yHqE7E

Diffusion tensor imaging and tractography of the white matter in normal aging: The rate-of-change differs between segments within tracts

Publication date: January 2018
Source:Magnetic Resonance Imaging, Volume 45
Author(s): J. Mårtensson, J. Lätt, F. Åhs, M. Fredrikson, H. Söderlund, H.B. Schiöth, J. Kok, B. Kremer, Danielle van Westen, E.-M. Larsson, M. Nilsson
Knowledge concerning the normal aging of cerebral white matter will improve our understanding of abnormal changes in neurodegenerative diseases. The microstructural basis of white matter maturation and aging can be investigated using diffusion tensor imaging (DTI). Generally, diffusion anisotropy increases during childhood and adolescence followed by a decline in middle age. However, this process is subject to spatial variations between tracts. The aim of this study was to investigate to what extent age-related variations also occur within tracts. DTI parameters were compared between segments of two white matter tracts, the cingulate bundle (CB) and the inferior fronto-occipital fasciculus (IFO), in 257 healthy individuals between 13 and 84years of age. Segments of the CB and the IFO were extracted and parameters for each segment were averaged across the hemispheres. The data was analysed as a function of age. Results show that age-related changes differ both between and within individual tracts. Different age trajectories were observed in all segments of the analysed tracts for all DTI parameters. In conclusion, aging does not affect white matter tracts uniformly but is regionally specific; both between and within white matter tracts.



http://ift.tt/2yLbksL

Validation of diffusion measurements obtained on a 0.35T MR in Malawi: Important insights for radiologists in low income settings with low field MRI

Publication date: January 2018
Source:Magnetic Resonance Imaging, Volume 45
Author(s): Yuchuan Zhuang, Michael J. Potchen, Samuel D. Kampondeni, Madalina Tivarus, Gretchen L. Birbeck, Jianhui Zhong
PurposeTo investigate the reliability of diffusion weighted image (DWI) measurements obtained on a 0.35T MR scanner in Malawi for malaria research.Materials and methodsThe same healthy volunteers (n=6) were scanned on a 0.35T MR scanner in Malawi and a 3T scanner in the US. Three subjects had two repeated DWI scans at 0.35T. Due to scanner constraints, only three diffusion gradient directions for DWI on 0.35T could be obtained. An apparent diffusion coefficient (ADC) map was reconstructed from the 0.35T and the result was compared to standard DWI acquisition on the 3T scanner. The mean ADC from 15 different regions and the voxel-wise coefficient of variation (CV) were calculated to investigate the intra-scanner and inter-scanner variability. Reproducibility was calculated using intra-class correlation coefficient (ICC).ResultsThe 0.35T intra-scanner ADC repeatability was high for all three subjects with repeated scans (ICC>0.7). The intra-scanner correlation between repeated scans was also high (r>0.67, p< 0.01). Comparing the ADC findings from the 0.35T and 3T MRs, the high inter-scanner correlation suggested that the 0.35T ADC results were valid (ICC>0.7, r>0.5, p<0.01). Voxel-wise CV revealed a few regions with larger variation (CV>20%), which were primarily located in peripheral regions and the boundary of lateral ventricles, and likely due to partial volume effects in low field scans.ConclusionThese findings support the validity of DWI obtained from low field MR scanners used in many low income countries.



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Addressing Professionalism, Social, and Communication Competencies in Surgical Residency Via Integrated Humanities Workshops: A Pilot Curriculum

Publication date: Available online 20 October 2017
Source:Journal of Surgical Education
Author(s): Jennifer Colvin, Judith French, Allan Siperstein, Tony R. Capizzani, Vikram D. Krishnamurthy
ObjectiveWe aimed to conduct professionalism and social competencies (PSC) training by integrating humanities into structured workshops, and to assess reception of this curriculum by first-year surgical residents.DesignAn IRB-approved, pilot curriculum consisting of 4 interactive workshops for surgical interns was developed. The workshops were scheduled quarterly, often in small group format, and supplemental readings were assigned. Humanities media utilized to illustrate PSC included survival scenarios, reflective writing, television portrayals, and social media. Emphasis was placed on recognizing personal values and experiences that influence judgment and decision-making, using social media responsibly, identifying and overcoming communication barriers related to generational changes in training (especially technology and work-life balance), and tackling stereotypes of surgeons. Anonymous and voluntary pre- and postcurriculum surveys were administered. Univariate analysis of responses was performed with JMP Pro v12 using Fisher's exact, χ², and Students' t-tests for categorical and continuous variables.SettingThe study took place at the Cleveland Clinic in Cleveland, OH, within the general surgery program.ParticipantsSurgical interns at the Cleveland Clinic were included in the study. A total of 16 surgical interns completed the curriculum.ResultsSixteen surgical interns participated in the curriculum: 69% were domestic medical school graduates (DG) and 31% were international medical school graduates (IMG). Overall, the majority (81%) of residents had received PSC courses during medical school: 100% of DG compared to 40% of IMG (p = 0.02). Before beginning the curriculum, 86% responded that additional PSC training would be useful during residency, which increased to 94% upon completion (p = 0.58). Mean number of responses supporting the usefulness of PSC training increased from 1.5 ± 0.2 before the curriculum to 1.75 ± 0.2 upon completion (p = 0.4). When describing public and medical student perceptions of surgeons, 60% and 83% of adjectives used were negative, respectively. When describing perceptions of female surgeons, 88% of adjectives used were negative.ConclusionsMost interns received prior PSC coursework; however, the majority still desired additional training during residency. After completion, a greater percentage of interns responded that PSC training was important and choose more reasons in favor of the curriculum. Formalized didactics should be strongly considered, especially in programs with IMG. Future areas of investigation include expanding the cohort to additional years of residency; potentially identifying unique PSC needs for each postgraduate year.



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The Effect of Formal Robotic Residency Training on the Adoption of Minimally Invasive Surgery by Young Colorectal Surgeons

Publication date: Available online 18 October 2017
Source:Journal of Surgical Education
Author(s): David E. Disbrow, Stephanie M. Pannell, Beth-Ann Shanker, Jeremy Albright, Juan Wu, Amir Bastawrous, Mark Soliman, Jane Ferraro, Robert K. Cleary
ObjectiveThe minimally invasive approach to colorectal surgery is still underused. Only 50% to 60% of colectomies and 10% to 20% of rectal resections for cancer are performed laparoscopically. The increasing adoption of the robotic platform for colorectal surgery warrants re-evaluation of minimally invasive surgery (MIS) training techniques. Although considering lessons learned from past laparoscopic training, a standardized national robotic training program for colon and rectal surgery residents was developed and implemented in 2011. The objective of this study was to assess the effect of this program on the usage of MIS in practice following residency training.DesignAn internet-based 18 question survey was sent to all colon and rectal surgeons who graduated from ACGME-approved colon and rectal surgery residencies from 2013 to 2016. The survey questions were designed to determine MIS practice patterns for young colon and rectal surgeons after residency training for those who participated in the standardized national robotics training course when compared to those who did not participate. Grouped bar charts with error bars are presented along with summary statistics to offer a descriptive overview of training experiences by cohort.Setting/ParticipantsThis study is a survey of colon and rectal surgeons who completed colon and rectal surgery residencies to include all 52 programs across the United States.ResultsThe overall survey response rate was 37.2% (109 of 293). Most (79.8%) of the colon and rectal surgery resident respondents participated in the formal robotic training course. The average respondent reported that 84% of colectomy cases and 74.8% of rectal resections done after residency training by all respondents were by the MIS approach. The laparoscopic approach was most prevalent for colectomies for both course participants (laparoscopic 55.1%, hand assisted lap 14.5%, and robotic 15.7%) and nonparticipants (laparoscopic 53.8%, hand assisted lap 12.3%, and robotic 15.9%). For rectal resections, the robotic approach was the preferred option for course participants (laparoscopic 24.5%, hand assist lap 14.0%, and robotic 39.2%) whereas laparoscopic and open approaches were used more often by nonparticipants (laparoscopic 36.8%, hand assist lap 8.0%, robotic 26.8%, and open 28.4%). Barriers to robotic implementation included lack of robotic mentors, inadequate robotic assistance, and the preference for the laparoscopic approach.ConclusionThe usage of MIS by young recently fellowship-trained colorectal surgeons is higher than previously reported. The proportion of rectal cases done robotically is higher compared to colon cases and with an apparent decrease in open rather than laparoscopic surgery, suggesting selective usage of robotic surgery for more challenging cases in the pelvis. Methods to more effectively increase the usage of minimally invasive approaches in colorectal surgery warrant further evaluation.



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The ACGME Case Log System May Not Accurately Represent Operative Experience Among General Surgery Interns

Publication date: Available online 18 October 2017
Source:Journal of Surgical Education
Author(s): Nimesh D. Naik, Eduardo F. Abbott, Johnathon M. Aho, T.K. Pandian, Cornelius A. Thiels, Stephanie F. Heller, David R. Farley
ObjectiveTo assess if the Accreditation Council for Graduate Medical Education (ACGME) case log system accurately captures operative experience of our postgraduate year 1 (PGY-1) residents.DesignACGME case log information was retrospectively obtained for 5 cohorts of PGY-1 residents (2011-2015) and compared to the number of operative cases captured by an institutional automated operative case report system, Surgical Access Utility System (SAUS). SAUS automatically captures all surgical team members who are listed in the operative dictation for a given case, including interns. A paired t-test analysis was used to compare number of cases coded between the 2 systems.SettingAcademic, tertiary care referral center with a large general surgery training program.ParticipantsPGY-1 general surgery trainees (interns) from the years 2011-2015.ResultsForty-nine PGY-1 general surgery residents were identified over a 5-year period. Mean operative case volume per intern, per year, captured by the automated SAUS was 176.5 ± 28.1 (SD) compared to 126.3 ± 58.0 ACGME cases logged (mean difference = 50.2 cases, p < 0.001).ConclusionsACGME case log data may not accurately reflect the actual operative experience of our PGY-1 residents. If such data holds true for other general surgery training programs, the true impact of duty hour regulations on operative volume may be unclear when using the ACGME case log data. This current standard approach for using ACGME case logs as a representation of operative experience requires further scrutiny and potential revision to more accurately determine operative experience for accreditation purposes.



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Am I Cut Out for This? Transitioning From Surgical Trainee to Attending

Publication date: Available online 18 October 2017
Source:Journal of Surgical Education
Author(s): Sandra de Montbrun, Priyanka Patel, Melanie Hammond Mobilio, Carol-Anne Moulton
ObjectiveProgressing from trainee to attending surgeon is arguably one of the most significant transitions in a surgeon's career. Despite this, little is known about this critical period. The purpose of this study was to develop a framework for understanding the phenomenon of the transition from trainee to attending surgeon.DesignA constructivist grounded theory methodology was used to explore the experience of new attending surgeons as they transition into practice. A purposeful sampling strategy was used to conduct 13 semistructured interviews with surgeons from various specialties. Data collection and analysis were performed simultaneously as part of the iterative process. Themes were identified and informed the development of the conceptual framework.SettingThe setting included 4 separate Canadian urban, academic health centers.ParticipantsA total of 13 surgeons in their first 5 years of practice from 6 separate departments were included.ResultsParticipants described 4 phases that marked their transition from trainee to attending surgeon. In the initial phase (getting undressed), participants shared vivid moments where they realized they no longer fit their trainee identity, but did not yet belong to the attending group. An intense phase of vulnerability and self-doubt (exposed and vulnerable), which was associated with building a new reputation and identity, followed. In the next phase (suiting up), surgeons began to project the image associated with their new role to others. With the passage of time and accumulation of successful cases, participants began to internalize their new identity in the final phase (tailoring the fit).ConclusionsThe transition from trainee to attending surgeon is a critical time during which new surgeons experience an identity shift. The conceptual framework presented contributes to a deeper understanding of the experience of this transition in order to help new surgeons transition successfully into independent practice.



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Surgery Website as a 24/7 Adjunct to a Surgical Curriculum

Publication date: Available online 21 October 2017
Source:Journal of Surgical Education
Author(s): Apram Jyot, Mohamed S. Baloul, Eric J. Finnesgard, Samuel J. Allen, Nimesh D. Naik, Miguel A. Gomez Ibarra, Eduardo F. Abbott, Becca Gas, Francisco J. Cardenas-Lara, Muhammad H. Zeb, Rachel Cadeliña, David R. Farley
ObjectiveSuccessfully teaching duty hour restricted trainees demands engaging learning opportunities. Our surgical educational website and its associated assets were assessed to understand how such a resource was being used.DesignOur website was accessible to all Mayo Clinic employees via the internal web network. Website access data from April 2015 through October 2016 were retrospectively collected using Piwik.SettingAcademic, tertiary care referral center with a large general surgery training program. Mayo Clinic, Rochester, MN.ParticipantsA total of 257 Mayo Clinic employees used the website.ResultsThe website had 48,794 views from 6313 visits by 257 users who spent an average of 14 ± 11 minutes on the website. Our website houses 295 videos, 51 interactive modules, 14 educational documents, and 7 flashcard tutorials. The most popular content type was videos, with a total of 30,864 views. The most popular visiting time of the day was between 8 pm and 9 pm with 6358 views (13%), and Thursday was the most popular day with 17,907 views (37%).  A total of 78% of users accessed content beyond the homepage. Average visits peaked in relation to 2 components of our curriculum: a 240% increase one day before our biannual intern simulation assessments, and a 61% increase one day before our weekly conducted Friday simulation sessions. Interns who rotated on the service of the staff surgeon who actively endorses the website had 93% more actions per visit as compared to other users. The highest clicks were on the home banner for our weekly simulation session pre-emptive videos, followed by "groin anatomy," and "TEP hernia repair" videos.ConclusionsOur website acted as a "just-in-time" accessible portal to reliable surgical information. It supplemented the time sensitive educational needs of our learners by serving as a heavily used adjunct to 3 components of our surgical education curriculum: weekly simulation sessions, biannual assessments, and clinical rotations.



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Discourse production of mandarin-speaking children with high-functioning autism: The effect of mental and action verbs’ semantic-pragmatic features

Publication date: November–December 2017
Source:Journal of Communication Disorders, Volume 70
Author(s): Yiqi Song, Zhongheng Jia, Shunhua Liu, Dandan Liang
The present study investigated the syntactic and pragmatic performance of children with high-functioning autism (HFA) during a discourse production task with mental verbs. Children with HFA and typically developing (TD) children were matched by chronological age, verbal IQ (VIQ) and full-scale IQ (FIQ). We found that children with HFA tended to select a nominal object given a mental verb with either a nominal or clausal object. They committed few syntactic errors but generated syntactic stereotypes with mental verbs. However, this behavior was not observed with action verbs. Thus, children with HFA were specifically impaired in the argument structures of mental verbs. In pragmatic performance, children with HFA produced significantly fewer clauses or sentences with lower syntactic complexity for mental verbs than TD controls. This result might be due to the semantic-pragmatic impairment of children with HFA in the use of mental verbs. This study concludes that children with HFA were able to acquire the syntactic frames of mental verbs but were nevertheless impaired in the acquisition of pragmatic information inherent in those verbs.



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Issue Information

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Note

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Molecular control of regulatory T cell development and function

Yohko Kitagawa | Shimon Sakaguchi

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Insights into immune tolerance from AIRE deficiency

Irina Proekt | Corey N Miller | Michail S Lionakis | Mark S Anderson

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Restless legs syndrome is highly prevalent in patients with postpolio syndrome

We read with great interest the recent article by Marin et al. (1) about the prevalence of restless legs syndrome (RLS) in post-polio syndrome (PPS). The authors reported RLS as highly prevalent (36%) in a large sample of PPS patients (n=119) with a marked disease severity, as measured by IRLSSS score, and identified lower educational level and depression as predictive factors for RLS risk.

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Simultaneous Reconstruction of Columella and Philtrum Using Prolabial Flap Combined with Abbe Flap in Secondary Bilateral Cleft Lip and Nasal Deformity

Open rhinoplasty and Abbe flap techniques are traditionally useful tools for the reconstruction of secondary bilateral cleft lip nasal (BCLN) deformity. We aimed to investigate the long-term outcomes of simultaneous columella and philtrum reconstruction using prolabial flap combined with Abbe flap in secondary BCLN deformity.From January 2009 to July 2014, 26 patients (17 males and 9 females; mean age 21 years) with secondary BCLN deformity were recruited. All patients had severe short columella and philtrum deficiency.

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Luminescence analysis of Mn4+,Zn2+: Li2TiO3 red phosphors

Publication date: February 2018
Source:Journal of Luminescence, Volume 194
Author(s): Fugui Yang, Liang Qiao, Haike Ren, Fengpo Yan
The Mn⁴⁺,Zn²⁺:Li2TiO3red phosphors are synthesized through the high temperature solid state reaction method. The XRD, SEM, ICP, absorption spectra, excitation and emission spectra are described. The Zn²⁺ acts as the luminescence adjustment ion to enhance the red emission efficiency. The phosphors have the crystal structure consisting of [TiO6] and [LiO6] octahedral sites and the Zn-O-Zn bonds. Concentration dependence on Zn²⁺ in Mn⁴⁺,Zn²⁺: Li2TiO3 is presented. Results indicate the suitable concentration of Zn²⁺ can enhance the emission efficiency. In the region of 682–697nm when excited by 475nm, the external quantum efficiency are obtained to be 18%, correlative with the transition of ²Eg (²T1)→⁴A2g of Mn⁴⁺. The crystal field strength (Dq) and the Racah parameters (B and C) are estimated to evaluate the nephelauxetic effect of Mn⁴⁺. The white-LED performances and thermal stability are also presented.



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Reconstruction after salvage laryngectomy

Publication date: December 2017
Source:Oral Oncology, Volume 75
Author(s): David H. Yeh, Axel Sahovaler, Kevin Fung
Both early and advanced stage laryngeal cancers are treated with organ-preserving strategies including radiation alone or concurrent chemoradiotherapy. While organ-preserving modalities have proven effective in eradicating cancer while also preserving laryngeal function, there remains a proportion of cases where residual or recurrent cancer prevails, or conversely, where radiotherapy renders a larynx dysfunctional. In these circumstances, salvage total laryngectomy is often the surgical treatment. The effects of radiotherapy to the neck, amplified by chemotherapy, can create an inhospitable surgical environment, making the salvage laryngectomy an operation fraught with the potential for major complications such as the dreaded pharyngocutaneous fistula.The introduction of vascularized tissue from outside the irradiated field decreases the risk of major wound complications. Free tissue transfer, with a variety of donor sites available, is commonly employed to reconstruct either a patch or a circumferential segment of the pharynx. When there is enough pharyngeal mucosa for primary closure, a vascularized onlay graft or a pharyngeal interposition graft can be used to reinforce the closure. This has been demonstrated to both reduce the severity of pharyngocutaneous fistula and decrease the risk of developing a pharyngocutaneous fistula compared to primary closure alone.Beyond mitigating the risk for perioperative complications, flap selection may have implications on the long-term outcomes after salvage total laryngectomy and these must be considered preoperatively. The purpose of this review is to examine the various options for reconstruction after salvage total laryngectomy and to examine some of their advantages and disadvantages in the short and long-term.



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Outcome by treatment modality in sinonasal undifferentiated carcinoma (SNUC): A case-series, systematic review and meta-analysis

Publication date: December 2017
Source:Oral Oncology, Volume 75
Author(s): Grégoire B. Morand, Nanina Anderegg, Domenic Vital, Kristian Ikenberg, Gerhard F. Huber, Michael B. Soyka, Matthias Egger, David Holzmann
ObjectiveSinonasal undifferentiated carcinoma (SNUC) is an aggressive malignancy first described by Frierson et al. in 1986. As the tumor is very rare, current treatment recommendations are based on institutional case reports. We thus felt the need to perform a comprehensive systematic review and meta-analysis to investigate how treatment modalities are associated with survival.DesignCase-series, systematic review and meta-analysisMethodsWe searched the OvidMedline, OvidEmbase, Web of Science, Biosis, Scopus and the Cochrane Library database libraries. We extracted aggregate and individual patient data for statistical analysis. To study the association between treatment modalities and survival, we used random-effects meta-regression for the aggregate- and cox mixed-effects models.Results379 citations were found; 29 case series could be included in the final analysis, including a total number of 390 single patients (34.6% female). Median age at diagnosis was 52 years. 80.9% of patients presented with a T4 tumor and 16.0% with nodal metastasis at diagnosis. In individual patient data (IPD) meta-analysis, single modality (surgery alone or radiation alone) treatment was associated with reduced survival compared to double modality (surgery & radiation or chemoradiation) treatment (adjusted Hazard Ratio [aHR] 2.97, 95% ConfidenceInterval [1.41–6.27]) and compared to triple modality (surgery & radiation & chemotherapy) treatment (aHR 2.80 95%-CI 1.29–6.05 for triple vs. single modality). Triple modality treatment was not superior to double modality treatment. (aHR 1.06, 95%-CI 0.59–1.92).ConclusionDouble and triple modality treatment are associated with improved survival over single modality but there is no evidence that triple modality is superior to double modality treatment.



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Adoption in Pakistan: Stigma around a Noble Deed?

Giving a child your name and shelter over their heads, by way of legal adoption is a noble gesture. I fail to understand why it is a stigmatized phenomenon in Pakistan to this day. No ...

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Delineating the relationship between Point A prescription dose and pelvic lymph node doses in intracavitary high-dose-rate brachytherapy treatment of cervical cancer for use in low- and middle-income countries

Publication date: Available online 21 October 2017
Source:Brachytherapy
Author(s): John Weaver, Grant Harmon, Matthew M. Harkenrider, Murat Surucu, Abbie Wood, Fiori Alite, William Small
PurposeTo define the relationship between the Point A prescription dose and the dose delivered to various pelvic lymph node groups during high-dose-rate (HDR) brachytherapy treatment of cervical cancer. In less developed countries, brachytherapy is often done without three-dimensional image guidance, instead relying on plain radiography and prescription to Point A. A defined relationship between Point A dose and lymph node doses would help physicians in these health care settings to more accurately estimate nodal doses.Methods AND MATERIALSTreatment data from 50 fractions of HDR brachytherapy of cervical cancer were reviewed, the pelvic lymph nodes were contoured, and dose–volume histogram parameters were obtained. Dose–volume histogram parameters for each contour were normalized as a percentage of the corresponding Point A dose. All nodal groups were divided into left and right sides, except the presacral nodal group.Results AND CONCLUSIONSMean Point A doses were bilateral (Bil) 5.92 Gy ± 0.58, left (L) 5.93 ± 0.59, and right (R) 5.92 ± 0.59. Mean normalized D90 values for the various lymph node groups were as follows—obturator: Bil 20.3% ± 4.5, L 20.5% ± 4.4, and R 20.2% ± 5.2; external iliac: Bil 9.5% ± 2.9, L 10.0% ± 3.1, and R 9.5% ± 3.0; internal iliac: Bil 12.2% ± 3.5, L 12.1% ± 3.4, and R 12.9% ± 4.7; common iliac: Bil 4.3% ± 1.6, L 4.3% ± 1.6, and R 4.3% ± 1.7; and presacral: 8.7% ± 3.4. These relationships can serve as a useful tool for evaluating lymph node doses during HDR brachytherapy of cervical cancer in facilities performing two-dimensional treatment planning and those with limited resources.



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Interferon regulatory factor 6 variants affect nasolabial morphology in East Asian populations

Publication date: January 2018
Source:Archives of Oral Biology, Volume 85
Author(s): Daisuke Tomita, Tetsutaro Yamaguchi, Takatoshi Nakawaki, Yu Hikita, Mohamed Adel, Yong-Il Kim, Shugo Haga, Masahiro Takahashi, Akira Kawaguchi, Mutsumi Isa, Soo-Byung Park, Hajime Ishida, Koutaro Maki, Ryosuke Kimura
ObjectiveThe interferon regulatory factor 6 gene (IRF6) is one of the most conspicuous genes among a large number of candidate risk genes for non-syndromic cleft lip with or without cleft palate, which is considered to be a multifactorial defect. Variants of IRF6 are also suggested to affect normal craniofacial variations, especially in the area of the nose and the upper lip. In the present study, we used lateral cephalograms to establish the relationship between IRF6 and sagittal nasolabial morphology in healthy East Asian subjects.DesignGenomic DNA was extracted from 215 Japanese and 226 Korean individuals, and genotyped for five IRF6 single nucleotide polymorphisms (SNPs): rs17389541, rs642961, rs2013162, rs2235371, and rs7802. These SNPs were tested by multiple regression analyses for their association with craniofacial measurements obtained from lateral cephalometrics.ResultsWe detected a significant association between the derived variants, rs2013162 and rs2235371 and the distances between a facial bone plane indicated by distance from Nasion and Point A (NA plane) to soft tissue landmarks; the Subalare (NA-Sbal) and the Subnasale (NA-Sn) in the sagittal plane.ConclusionOur results indicate that IRF6 variants play an important role in the normal range of variation in nasolabial soft-tissue morphology.



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Vertebral Cement Leak: How Far Will It Go…?

Publication date: Available online 22 October 2017
Source:European Journal of Vascular and Endovascular Surgery
Author(s): Maxime Elens, Frédéric Lecouvet




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Neuroimaging Findings in Normocephalic Newborns with Intrauterine Zika Virus Exposure

Publication date: Available online 19 October 2017
Source:Pediatric Neurology
Author(s): Sarah B. Mulkey, Gilbert Vezina, Dorothy I. Bulas, Zarir Khademian, Anna Blask, Youssef Kousa, Caitlin Cristante, Lindsay Pesacreta, Adre J. du Plessis, Roberta L. DeBiasi
BackgroundCongenital Zika infection can result in a spectrum of neurologic abnormalities in the newborn. Newborns exposed to Zika virus in utero have neuroimaging as part of their clinical evaluation.MethodsThrough a Congenital Zika Program at Children's National Health System in Washington D.C., we performed fetal and/or neonatal neuroimaging, including magnetic resonance imaging and ultrasound on over 70 fetuses and/or neonates with intrauterine Zika exposure. Novel findings on neonatal brain magnetic resonance imaging were described in two cases. Results: Gadolinium-contrast magnetic resonance imaging showed enhancement of multiple cranial nerves at three days of age on one infant. Another infant had magnetic resonance imaging at sixteen days of age and found chronic ischemic cerebral infarction. This infant had previously normal fetal magnetic resonance imaging.ConclusionCranial nerve enhancement and cerebral infarction may be among the expanding list of neurologic findings in congenital Zika infection. Postnatal brain MRI should be considered for newborns exposed to Zika virus in utero.



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Clinical Considerations Derived from the Administration of Melatonin to Children with Sleep Disorders

Publication date: Available online 18 October 2017
Source:Pediatric Neurology
Author(s): Ana Checa-Ros, Antonio Muñoz-Gallego, María de los Ángeles Muñoz-Gallego, Antonio Molina-Carballo, Susana Narbona-Galdó, Antonio Jeréz-Calero, María del Carmen Augustín-Morales, Antonio Muñoz-Hoyos
Background and ObjectivesDespite the numerous investigations carried out in relation to melatonin, there is a lack of knowledge about the specific melatonin secretion patterns in the diverse primary sleep disturbances. The objective of this study was to analyze the plasma melatonin concentrations in children with primary sleep disorders and the effects of melatonin therapy on their serum levels and their actigraphic sleep parameters.MethodsFourteen participants (9 girls; 7-14 years old) diagnosed with diverse primary sleep disorders were recruited. Four different melatonin secretion patterns were identified: low plasma melatonin levels, absence of a circadian rhythm, advanced acrophase and delayed acrophase. A placebo (one week) was administered followed by three months of melatonin therapy (3mg/night). Urinary 6-sulphatoxymelatonin (aMT6s) levels, 24-hour plasma melatonin concentrations and a seven-day actigraphic record were collected after both treatments.ResultsAfter melatonin therapy, a significant increase (p < 0.001) of urinary aMT6s excretion with a clear circadian variation was observed. Plasma melatonin concentrations were also significantly higher with a recovery in the circadian rhythm. Actual sleep time was significantly longer, with a substantial reduction in the sleep onset latency and night awakenings. No severe side effects were reported.ConclusionsThe main clinical implication of this study is to demonstrate the efficacy of melatonin in three main circumstances: an insufficient hormone production, a disturbed circadian rhythm and an advanced / delayed acrophase. As ongoing work, we are exploring the effect of different doses of melatonin on the regulation of its concentrations and of its secretion rhythm.



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Chasing Zebras: a Child with Skin Stripes and Whorls

Publication date: Available online 20 October 2017
Source:Pediatric Neurology
Author(s): Matthew Z. Dawson, Debabrata Ghosh




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Effect of stem cell niche elasticity/ECM protein on the self-beating cardiomyocyte differentiation of inducedpluripotent stem (iPS) cells at different stages

Publication date: Available online 21 October 2017
Source:Acta Biomaterialia
Author(s): Mitsuhi Hirata, Tetsuji Yamaoka
Stem cell-based myocardial regeneration therapies have emerged as alternative strategies to heart transplantation for serious heart diseases, but autologous beating mature cardiomyocytes are not available. Here we investigated the effect of culture substrates on the cardiomyocyte differentiation of induced pluripotent stem cells (iPSs) in vitro by separately evaluating the following continuous three steps: (1) cardiac marker gene expression, (2) contractile gene expression and self-beating, and (3) beating duration. To this end, we used iPS cells to study the cardiac differentiation, and neonatal rat cardiomyocytes (NCMs) to study beating behavior. These cells were cultured on substrates with different natures, i.e., an elastic substrate (Es) with the modulus of 9, 20, or 180 kPa, and hard tissue culture polystyrene dishes (TCPS) coated with collagen type I (Col), gelatin (Gel), or fibronectin (FN). The results revealed that the effective niches in each step were very different. The cardiac marker gene (GATA4, Tbx5, MEF2C) expression of iPSs at the 1st step was very high on the TCPS coated with FN or Gel, whereas on the FN-coated Es (especially with the 9 kPa modulus), the undifferentiated marker gene (Nanog) expression of iPSs was maintained. The expression of the contractile genes α-MHC, TnC1, and TnT2 and the self-beating (the 2nd step) of the NCMs were high on FN-coated TCPS and Col-coated Es. The 3rd step (beating duration) of the NCMs was effective on the Es, and at 21 days both the iPSs and NCMs stopped beating on the TCPS but were still beating on the Es. Overall, cardiac differentiation 'preferred' ECM-rigid culture substrates, and beating-behavior 'preferred' Col-soft culture substrates. These results are important for understanding and designing cardiac differentiation niches for regenerative medicine, and they suggest that a single culture substrate is not suitable for preparing self-beating cardiomyocytes.Statement of SignificanceThe transplantation of beating cardiomyocytes (BCMs) is expected to be made more effective for serious heart diseases. The identification of the appropriate engineering processes and suitable culture substrates for inducing stem cell differentiation into BCMs is thus indispensable. The differentiation can be divided into three major processes, the cardiac differentiation step, the beating-induction step and the beating-duration step. A protocol with the higher efficiency in all of the steps must be useful. In this study, we separately evaluated the effect of culture substrates at each three step. We clarified that the biological and the physical properties of the culture substrates required at these steps were different. We found useful criteria for effective cardiac cell niche systems design.

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Cu-doping of calcium phosphate bioceramics: from mechanism to the control of cytotoxicity

Publication date: Available online 21 October 2017
Source:Acta Biomaterialia
Author(s): Sandrine Gomes, Charlotte Vichery, Stéphane Descamps, Hervé Martinez, Amandeep Kaur, Aurélie Jacobs, Jean-Marie Nedelec, Guillaume Renaudin
In this study, the Cu-doping mechanism of Biphasic Calcium Phosphate (BCP) was thoroughly investigated, as was its ionic release behavior, in order to elucidate cytotoxicity features of these bioceramics. BCP are composed of hydroxyapatite (Ca10(PO4)6(OH)2) and β-TCP (Ca3(PO4)2). The two phases present two different doping mechanisms. Incorporation into the β-TCP structure is achieved at around 700°C thanks to a substitution mechanism leading to the Cu-doped Ca3-xCux(PO4)2 compound. Incorporation into the HAp structure is achieved thanks to an interstitial mechanism that is limited to a Cu-poor HAp phase for temperatures below 1100°C (Ca10Cux(PO4)6(OH)2-2xO2x with x < 0.1). Above 1100°C, the same interstitial mechanism leads to the formation of a Cu-rich HAp mixed-valence phase (Ca10Cu²⁺xCu⁺y(PO4)6(OH)2-2x-yO2x+y with x+y ∼ 0.5). The formation of both high-temperature Cu-doped α-TCP and Cu3(PO4)2 phases above 1100°C induces a transformation into the Cu-rich HAp phase on cooling. The linear O-Cu-O oxocuprate entity was confirmed by EXAFS spectroscopy, and the mixed Cu⁺/Cu²⁺ valence was evidenced by XPS analyses. Ionic releases (Cu⁺/Cu²⁺, Ca²⁺, PO4^2- and OH^-) in water and in simulated body media were investigated on as-synthesized ceramics to establish a pretreatment before biological applications. Finally the cytotoxicity of pretreated disks was evaluated, and results confirm that Cu-doped BCP samples are promising bioceramics for bone substitutes and/or prosthesis coatings.Statement of significanceBiphasic Calcium Phosphates (BCP) are bioceramics composed of hydroxyapatite (HAp, Ca10(PO4)6(OH)2) and beta-Tricalium Phosphate (β-TCP, Ca3(PO4)2). Because their chemical and mineral composition closely resembles that of the mineral component of bone, they are potentially interesting candidates for bone repair surgery. Doping can advantageously be used to improve their biological behaviors; however, it is important to describe the doping mechanism of BCP thoroughly in order to fully appraise the benefit of the doping process.The present paper scrutinizes in detail the incorporation of copper cation in order to correctly interpret the behavior of the Cu-doped bioceramic in biological fluid. The understanding of the copper doping mechanism, related to doping mechanism of others 3d-metal cations, makes it possible to explain the rates and kinetic of release of the dopant in biological medium. Finally, the knowledge of the behavior of the copper doped ceramic in biological environment allowed the tuning of its cytotoxicity properties. The present study resulted on pre-treated ceramic disks which have been evaluated as promising biocompatible ceramic for bone substitute and/or prosthesis coating: good adherence of bone marrow cells with good cell viability.

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Photodynamic therapy of human biliary cancer cell line using combination of phosphorus porphyrins and light emitting diode

Publication date: Available online 21 October 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Jin Matsumoto, Kou Suzuki, Masahide Yasuda, Yuya Yamaguchi, Yoshitaka Hishikawa, Naoya Imamura, Atsushi Nanashima
A series of phosphorus porphyrin complexes ([(RO)2P(tpp)]Cl, tpp = tetraphenylporphyrinato group, R = −(CH2CH2O)m(CH2)nH; 1a: m = 2, n = 2; 1b: m = 2, n = 4; 1c: m = 2, n = 6; 1d: m = 3, n = 6) were used for the photodynamic therapy (PDT) of human biliary cancer cell line (NOZ) when exposed to the irradiation of light emitting diodes (LEDs). A Dulbecco's modified Eagle's medium (DMEM) containing NOZ cells (2000 cell well⁻¹) and 1 (0–100 nM) was introduced into a 96-well microplate and incubated for 24 h to accumulate 1 into the NOZ cells and to multiply the NOZ cells until the cell number reached 10⁴ cells well⁻¹. After replacing the DMEM medium containing 1 with a fresh DMEM medium without 1, the plates were irradiated for 30 min at 610 nm. After incubation was performed for 24 h in dark conditions, the cell viability of the NOZ cells was determined using the MTT assay. The half maximum inhibitory concentrations 50 (IC50) of 1a–1d were found to be in the range of 33.7−58.7 nM for NOZ. These IC50 values for the NOZ were one hundredth the IC50 value (7.57 μM) for mono-L-aspartyl chlorin e6 (laserphyrin®). Thus, it was found that the PDT activity of 1a–1d was much higher than the mono-L-aspartyl chlorin e6. Similarly, IC50 vales of 1a–1d for HeLa cells were found to be 27.8−52.5 nM. This showed that 1a–1d had high photodynamic activity in cancer cells. At the same time, it was speculated that an LED is a useful light source for deactivating the cancer cells because it can excite the sensitizers with peak width in their absorption spectra using the light of the specified wave length with band width of 10–20 nm; LEDs provide a homogeneous light distribution for the target cells.

Graphical abstract

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Synthesis, antifungal and antitumor activity of two new types of imidazolin-2-ones

Publication date: Available online 21 October 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Shaopeng Wei, Li Li, Yaping Shu, Kun Zhao, Zhiqin Ji
Thirty-six imidazolin-2-ones, including ten pairs of benzimidazolones and sixteen imidazopyridines, were synthesized and subjected for the evaluation of antifungal and antitumor activity. Compounds 4a-01, 6-01, 6-04 and 6-06 could effectively inhibit the spore germination and mycelium growth of Botrytis cinerea. The relationship between structure and antifungal activity revealed that the introducing short-chain aliphatic acyl groups at the moiety of imidazopyridines is favorable for the antifungal activity, whereas aromatic acyl groups are much better than aliphatic acyl groups for the activity of benzimidazolones except for acetyl. Preliminary SRB assay indicated that 6-01 exerted strong antiproliferative effect against Hela and NCM460 cell lines. Further kinases assay revealed that 6-01 could specially inhibit mTOR among 114 human cancer related kinases. Elisa and Western blot analysis testified that 6-01 simultaneously inhibits the phosphorylation of Akt and 4E-BP1, and 6-01 is a novel mTOR inhibitor which targets on both mTORC1 and mTORC2. This investigation provided a valuable chemical structure for the development of antitumor drugs.

Graphical abstract

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Trisubstituted purine inhibitors of PDGFRα and their antileukemic activity in the human eosinophilic cell line EOL-1

Publication date: Available online 21 October 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Veronika Malínková, Eva Řezníčková, Radek Jorda, Tomáš Gucký, Vladimír Kryštof
Inhibition of protein kinases is a validated concept for pharmacological intervention in cancers. Many kinase inhibitors have been approved for clinical use, but their practical application is often limited. Here, we describe a collection of 23 novel 2,6,9-trisubstituted purine derivatives with nanomolar inhibitory activities against PDGFRα, a receptor tyrosine kinase often found constitutively activated in various tumours. The compounds demonstrated strong and selective cytotoxicity in the human eosinophilic leukemia cell line EOL-1, whereas several other cell lines were substantially less sensitive. The cytotoxicity in EOL-1, which is known to express the FIP1L1‐PDGFRA fusion gene encoding an oncogenic kinase, correlated significantly with PDGFRα inhibition. EOL-1 cells treated with the compounds also exhibited dose-dependent inhibition of PDGFRα autophosphorylation and suppression of its downstream signaling pathways with concominant G1 phase arrest, confirming the proposed mechanism of action. Our results show that substituted purines can be used as platforms for preparing tyrosine kinase inhibitors with specific activity towards eosinophilic leukemia.

Graphical abstract

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Influence of hydrocarbon-stapling on membrane interactions of synthetic antimicrobial peptides

Publication date: Available online 21 October 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Tracy A. Stone, Gregory B. Cole, Huong Q. Nguyen, Simon Sharpe, Charles M. Deber
Cyclization has sbeen recognized as a valuable technique for increasing the efficacy of small molecule and peptide therapeutics. Here we report the application of a hydrocarbon staple to a rationally-designed cationic antimicrobial peptide (CAP) that acquires increased membrane targeting and interaction vs. its linear counterpart. The previously-described CAP, 6K-F17 (KKKKKK-AAFAAWAAFAA-NH2) was used as the backbone for incorporation of an i to i+4 helical hydrocarbon staple through olefin ring closing metathesis. Stapled versions of 6K-F17 showed an increase in non-selective membrane interaction, where the staple itself enhances the degree of membrane interaction and rate of cell death while maintaining high potency against bacterial membranes. However, the higher averaged hydrophobicity imparted by the staple also significantly increases toxicity to mammalian cells. This deleterious effect is countered through stepwise reduction of the stapled 6K-F17's backbone hydrophobicity through polar amino acid substitutions. Circular dichroism assessment of secondary structure in various bacterial membrane mimetics reveals that a helical structure may improve - but is not an absolute requirement for - antimicrobial activity of 6K-F17. Further, phosphorus-31 static solid state NMR spectra revealed that both non-toxic stapled and linear peptides bind bacterial membranes in a similar manner that does not involve a detergent-like mechanism of lipid removal. The overall results suggest that the technique of hydrocarbon stapling can be readily applied to membrane-interactive CAPs to modulate how they interact and target biological membranes.

Graphical abstract

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Cyclic Perylene diimide: Selective ligand for tetraplex DNA binding over double stranded DNA

Publication date: Available online 21 October 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Suresh Vasimalla, Shinobu Sato, Fuminori Takenaka, Yui Kurose, Shigeori Takenaka
Synthesized cyclic perylene diimide, cPDI, showed the binding constant of 6.3×106 M-1 with binding number of n=2 with TA-core as a tetraplex DNA in 50 mM Tris-HCl buffer (pH=7.4) containing 100 mM KCl using Schatchard analysis and showed a higher preference for tetraplex DNA than for double stranded DNA with over 103 times. CD spectra showed that TA-core induced its antiparallel conformation upon addition of cPDI in the absence or presence of K+ or Na+ ions. The cPDI inhibits the telomerase activity with IC50 of 0.3 µM using TRAP assay which is potential anti-cancer drug with low side effect.

Graphical abstract

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Vaccine wastage in Nigeria: An assessment of wastage rates and related vaccinator knowledge, attitudes and practices

Publication date: Available online 21 October 2017
Source:Vaccine
Author(s): Aaron S. Wallace, Fred Willis, Eric Nwaze, Boubacar Dieng, Naawa Sipilanyambe, Danni Daniels, Emmanuel Abanida, Alex Gasasira, Mustapha Mahmud, Tove K. Ryman
IntroductionThe introduction of new vaccines highlights concerns about high vaccine wastage, knowledge of wastage policies and quality of stock management. However, an emphasis on minimizing wastage rates may cause confusion when recommendations are also being made to reduce missed opportunities to routinely vaccinate children. This concern is most relevant for lyophilized vaccines without preservatives [e.g. measles-containing vaccine (MCV)], which can be used for a limited time once reconstituted.MethodsWe sampled 54 health facilities within 11 local government areas (LGAs) in Nigeria and surveyed health sector personnel regarding routine vaccine usage and wastage-related knowledge and practices, conducted facility exit interviews with caregivers of children about missed opportunities for routine vaccination, and abstracted vaccine stock records and vaccination session data over a 6-month period to calculate wastage rates and vaccine vial usage patterns.ResultsNearly half of facilities had incomplete vaccine stock data for calculating wastage rates. Among facilities with sufficient data, mean monthly facility-level wastage rates were between 18 and 35% across all reviewed vaccines, with little difference between lyophilized and liquid vaccines. Most (98%) vaccinators believed high wastage led to recent vaccine stockouts, yet only 55% were familiar with the multi-dose vial policy for minimizing wastage. On average, vaccinators reported that a minimum of six children must be present prior to opening a 10-dose MCV vial. Third dose of diphtheria-tetanus-pertussis vaccine (DTP3) was administered in 84% of sessions and MCV in 63%; however, the number of MCV and DTP3 doses administered were similar indicating the number of children vaccinated with DTP3 and MCV were similar despite less frequent MCV vaccination opportunities. Among caregivers, 30% reported being turned away for vaccination at least once; 53% of these children had not yet received the missed dose.DiscussionOur findings show inadequate implementation of vaccine management guidelines, missed opportunities to vaccinate, and lyophilized vaccine wastage rates below expected rates. Missed opportunities for vaccination may occur due to how the health system's contradicting policies may force health workers to prioritize reduced wastage rates over vaccine administration, particularly for multi-dose vials.



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Historical Case of Cervical Penetrating Wound: From First Aid to Surgical Intervention

Objective. We report a case of cervical penetrating wound by posing the problem of its support and by analyzing the chain of survival of a patient to human sacrifice. Case Report. It was an 11-year-old boy admitted to the hosting service of cervical penetrating wound emergency occurring in a context of human sacrifice by weapon (knife). On admission, the conscious patient had a left cervical hematoma at the level of the cervical zone II and severe signs of acute anemia. The exploratory cervicotomy, carried out 12 hours after the trauma under transfusion, allowed us to highlight a section of the front edge of the sternocleidomastoid and previous jugular muscles under hyoid. We noted the presence of a linear wound of 1 cm at the level of the left internal jugular vein. The wound of the internal jugular vein has been repaired with the Prolene 4.O. The outcome was good, allowing the exit 10 days after cervicotomy. Conclusion. The causal circumstances of cervical penetrating wounds are diverse. Their importance or their severity depends on the causative circumstances dominated by aggression and attempts to autolysis. Human sacrifice, with use of the weapon, is an exceptional circumstance.

http://ift.tt/2yB9f2W

Lingual Osseous Choristoma of the Tongue Base: Unusual Presentation of a Rare Entity

Osseous lesions of the tongue, also referred to as osseous choristomas, are benign growths of bony tissue. These lesions are not true neoplasms but rather represent growth of normal tissue at an abnormal location. Clinically, they appear as exophytic masses of the tongue, and they are treated by surgical excision. Lingual osseous choristomas are rare entities, with only 71 reported cases in the literature. We present the case of a lingual osseous choristoma of the tongue base in a 21-year-old female. Of the cases of lingual osseous choristoma reported in the literature, ours is only the fifth case to involve this location.

http://ift.tt/2irQ3ye

Historical Case of Cervical Penetrating Wound: From First Aid to Surgical Intervention

Objective. We report a case of cervical penetrating wound by posing the problem of its support and by analyzing the chain of survival of a patient to human sacrifice. Case Report. It was an 11-year-old boy admitted to the hosting service of cervical penetrating wound emergency occurring in a context of human sacrifice by weapon (knife). On admission, the conscious patient had a left cervical hematoma at the level of the cervical zone II and severe signs of acute anemia. The exploratory cervicotomy, carried out 12 hours after the trauma under transfusion, allowed us to highlight a section of the front edge of the sternocleidomastoid and previous jugular muscles under hyoid. We noted the presence of a linear wound of 1 cm at the level of the left internal jugular vein. The wound of the internal jugular vein has been repaired with the Prolene 4.O. The outcome was good, allowing the exit 10 days after cervicotomy. Conclusion. The causal circumstances of cervical penetrating wounds are diverse. Their importance or their severity depends on the causative circumstances dominated by aggression and attempts to autolysis. Human sacrifice, with use of the weapon, is an exceptional circumstance.

http://ift.tt/2yB9f2W

Lingual Osseous Choristoma of the Tongue Base: Unusual Presentation of a Rare Entity

Osseous lesions of the tongue, also referred to as osseous choristomas, are benign growths of bony tissue. These lesions are not true neoplasms but rather represent growth of normal tissue at an abnormal location. Clinically, they appear as exophytic masses of the tongue, and they are treated by surgical excision. Lingual osseous choristomas are rare entities, with only 71 reported cases in the literature. We present the case of a lingual osseous choristoma of the tongue base in a 21-year-old female. Of the cases of lingual osseous choristoma reported in the literature, ours is only the fifth case to involve this location.

http://ift.tt/2irQ3ye

Drug monitoring of sunitinib in patients with advanced solid tumors: a monocentric observational French study.

Drug monitoring of sunitinib in patients with advanced solid tumors: a monocentric observational French study.

Fundam Clin Pharmacol. 2017 Oct 21;:

Authors: Cabel L, Blanchet B, Thomas-Schoemann A, Huillard O, Bellesoeur A, Cessot A, Giroux J, Boudou-Rouquette P, Coriat R, Vidal M, Saidu NEB, Golmard L, Alexandre J, Goldwasser F

Abstract
Therapeutic drug monitoring (TDM) could be helpful in oral targeted therapies. Data are sparse to evaluate its impact on treatment management. This study aimed to determine a threshold value of plasma drug exposure associated with the occurrence of grade 3-4 toxicity, then the potential impact of TDM on clinical decision. Consecutive outpatients treated with sunitinib were prospectively monitored between days 21-28 of the first cycle, then monthly until disease progression. At each consultation, the composite AUCƬ,ss (sunitinib + active metabolite SU12662) was assayed. The decisions taken during each consultation were matched with AUCƬ,ss and compared to the decisional algorithm based on TDM. 105 cancer patients and 288 consultations were matched with the closest AUCƬ,ss measurement. The majority (60%) of the patients had metastatic renal clear-cell carcinoma (mRCC). Fifty-five (52%) patients experienced grade 3-4 toxicity. Multivariate analysis identified composite AUCƬ,ss as a parameter independently associated with grade 3-4 toxicity (p<0.0001). Using the ROC curve, the threshold value of composite AUCƬ,ss predicting grade ≥ 3 toxicity was 2150 ng/mL.h (CI 95%, 0.6-0.79%; p<0.0001). At disease progression in mRCC patients, AUCƬ,ss tended to be lower than the one assayed during the first cycle (1678 vs 2004 ng/mL.h, respectively, p=0.072). TDM could have changed the medical decision for sunitinib dosing in 30% of patients at the first cycle of treatment, and in 46% of the patients over the whole treatment course. TDM is routinely feasible, and may both contribute to improve toxicity management and to identify sunitinib under-exposure at the time of disease progression. This article is protected by copyright. All rights reserved.

PMID: 29055166 [PubMed - as supplied by publisher]

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Novel p-carborane-containing multitarget anticancer agents inspired by the metabolism of 17β-estradiol.

Related Articles

Novel p-carborane-containing multitarget anticancer agents inspired by the metabolism of 17β-estradiol.

Bioorg Med Chem. 2017 Oct 12;:

Authors: Kaise A, Ohta K, Endo Y

Abstract
The female hormone 17 β-estradiol (E2) is synthesized from estrone by steroid sulfatase (STS), and metabolized into 2-methoxyestradiol (2-ME), whereby the biological activity of the latter is substantially different from that of E2. Based on the metabolic pathways of E2, a carborane-containing 2-ME mimic (1c) and its derivatives (1 and 2) were designed and synthesized as novel multitarget anticancer agents. Bissulfamate 1f exhibited potent STS-inhibitory activity and tubulin-polymerization-inhibitory activity. Moreover, the cell-growth-inhibitory (CGI) activity of 1f was similar to that of 2-ME in a panel screening against 39 human cancer cell lines. Accordingly, 1f should be a promising perspective therapeutic agent for hormone-dependent breast tissue.

PMID: 29054710 [PubMed - as supplied by publisher]

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Selenocompounds in Cancer Therapy: An Overview.

Related Articles

Selenocompounds in Cancer Therapy: An Overview.

Adv Cancer Res. 2017;136:259-302

Authors: Bartolini D, Sancineto L, Fabro de Bem A, Tew KD, Santi C, Radi R, Toquato P, Galli F

Abstract
In vitro and in vivo experimental models clearly demonstrate the efficacy of Se compounds as anticancer agents, contingent upon chemical structures and concentrations of test molecules, as well as on the experimental model under investigation that together influence cellular availability of compounds, their molecular dynamics and mechanism of action. The latter includes direct and indirect redox effects on cellular targets by the activation and altered compartmentalization of molecular oxygen, and the interaction with protein thiols and Se proteins. As such, Se compounds interfere with the redox homeostasis and signaling of cancer cells to produce anticancer effects that include alterations in key regulatory elements of energy metabolism and cell cycle checkpoints that ultimately influence differentiation, proliferation, senescence, and death pathways. Cys-containing proteins and Se proteins involved in the response to Se compounds as sensors and transducers of anticancer signals, i.e., the pharmacoproteome of Se compounds, are described and include critical elements in the different phases of cancer onset and progression from initiation and escape of immune surveillance to tumor growth, angiogenesis, and metastasis. The efficacy and mode of action on these compounds vary depending on the inorganic and organic form of Se used as either supplement or pharmacological agent. In this regard, differences in experimental/clinical protocols provide options for either chemoprevention or therapy in different human cancers.

PMID: 29054421 [PubMed - in process]

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A Case of Nivolumab-Induced Severe Mononeuropathy Multiplex and Rhabdomyolysis

We report an 81-year-old man with multiple liver metastases after tumorectomy for primary mediastinal malignant melanoma, who experienced limb weakness and sensory disturbance after nivolumab monotherapy. He was diagnosed with nivolumab-induced mononeuropathy multiplex and rhabdomyolysis based on serologic examination, muscle biopsy, magnetic resonance imaging of the limbs, and a nerve conduction study. A course of intravenous methylprednisolone (mPSL) was initiated at 1 g/day for 3 days. After that, oral prednisolone (PSL) was started at 1 mg/kg/day and gradually tapered. Limb muscle strength improved, but when PSL was reduced to 0.3 mg/kg/day, the weakness recurred, and a nerve conduction study showed exacerbation of mononeuropathy multiplex. The patient was again administered intravenous mPSL (0.5 g/day for 3 days) followed by oral PSL at 0.5 mg/kg/day, and his neurological symptoms improved. Nivolumab, an immune checkpoint inhibitor, is used for the treatment of advanced melanoma and other cancers and causes various immune-related adverse events (irAEs). However, neurological irAEs related to nivolumab are rare. Furthermore, there are no reports of simultaneous nerve and muscle impairment. Unexpected irAEs affecting various organs should be recognized and treated appropriately.

http://ift.tt/2ir9RSp

Reconstruction after salvage laryngectomy

Publication date: December 2017
Source:Oral Oncology, Volume 75
Author(s): David H. Yeh, Axel Sahovaler, Kevin Fung
Both early and advanced stage laryngeal cancers are treated with organ-preserving strategies including radiation alone or concurrent chemoradiotherapy. While organ-preserving modalities have proven effective in eradicating cancer while also preserving laryngeal function, there remains a proportion of cases where residual or recurrent cancer prevails, or conversely, where radiotherapy renders a larynx dysfunctional. In these circumstances, salvage total laryngectomy is often the surgical treatment. The effects of radiotherapy to the neck, amplified by chemotherapy, can create an inhospitable surgical environment, making the salvage laryngectomy an operation fraught with the potential for major complications such as the dreaded pharyngocutaneous fistula.The introduction of vascularized tissue from outside the irradiated field decreases the risk of major wound complications. Free tissue transfer, with a variety of donor sites available, is commonly employed to reconstruct either a patch or a circumferential segment of the pharynx. When there is enough pharyngeal mucosa for primary closure, a vascularized onlay graft or a pharyngeal interposition graft can be used to reinforce the closure. This has been demonstrated to both reduce the severity of pharyngocutaneous fistula and decrease the risk of developing a pharyngocutaneous fistula compared to primary closure alone.Beyond mitigating the risk for perioperative complications, flap selection may have implications on the long-term outcomes after salvage total laryngectomy and these must be considered preoperatively. The purpose of this review is to examine the various options for reconstruction after salvage total laryngectomy and to examine some of their advantages and disadvantages in the short and long-term.



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