Current Status of HDAC Inhibitors in Cutaneous T-cell Lymphoma

Abstract

Cutaneous T-cell lymphomas (CTCLs) are a heterogeneous group of lymphomas that are characterized by primary skin involvement. Mycosis fungoides (MF) and Sézary syndrome (SS), the two most common subtypes of CTCL, can be difficult to manage clinically as there are few effective treatment options available. Recently, histone deacetylase inhibitors (HDACi) have emerged as promising therapies with favorable adverse effect profiles, compared with traditional chemotherapies. In this article, we review the published literature to evaluate the role of HDACi in the treatment of CTCL. Specifically, we (1) briefly discuss the molecular rationale for the use of HDACi in CTCL; (2) compare the efficacy, tolerability, and adverse effects of HDACi; (3) review the cardiac safety data; and (4) discuss optimization of therapy with HDACi in the treatment of CTCL.

https://ift.tt/2C9ywnZ

Pediatric Onychophagia: A Survey-Based Study of Prevalence, Etiologies, and Co-Morbidities

Abstract

Background

Onychophagia, defined as habitual nail biting, is a common disorder affecting 6–45% of the population and is more prevalent in children.

Objectives

Our primary objective was to determine the prevalence of nail biting in the pediatric population. Secondary objectives were to assess the presence of psychiatric co-morbidities associated with nail biting, and the effect of treatment on nail biting.

Methods

An anonymous voluntary survey was administered to participants at an outpatient academic pediatric clinic at Weill Cornell Medicine. Age, sex, psychiatric diagnosis, treatment sought, family history, and frequency of nail biting were analyzed across 282 enrolled patients aged 3–21 years. One patient was subsequently excluded due to incomplete data.

Results

Of 281 patients, 101 (37%) reported past or present nail biting lasting more than a month. Median age of onset was 5 years old (range 1–13 years). A significantly higher percentage of biters (18%; 19/104) than non-biters (6%; 11/177) were diagnosed with a psychiatric disorder (p < 0.01). Amongst biters, concurrent fingernail and toenail involvement was much less common (12%; 12/104) than that of fingernails alone (88%; 92/104). However, the ratio of fingernail and toenail biters to fingernail biters alone was greater in those with psychiatric diagnosis (0.36) than without (0.09) (p = 0.07).

Conclusions

Our study highlights behavioral patterns as well as familial, psychiatric, and other factors associated with pediatric nail biting. Familiarity with such factors, the clinical presentation of onychophagia, and available treatment options may aid in reducing its severity in affected patients and overall prevalence.

https://ift.tt/2PYzKVZ

Cutaneous Infections Due to Nontuberculosis Mycobacterium: Recognition and Management

Abstract

Nontuberculous mycobacteria (NTM) are a diverse group of organisms that are ubiquitous in the environment, and the incidence of cutaneous infections due to NTM has been steadily increasing. Cutaneous infections due to NTM can be difficult to diagnose, due to their wide spectrum of clinical presentations and histopathological findings that are often nonspecific. A variety of modalities including tissue culture and polymerase chain reaction (PCR) assays may be necessary to identify the organism. Treatment can also be challenging, as it can depend on multiple factors, including the causative organism, the patient's immunological status, and the extent of disease involvement. In this review, we discuss the common presentations of cutaneous NTM infections, diagnostic tools, and treatment recommendations. A multi-disciplinary approach that involves good communication between the clinician, the histopathologist, the microbiologist, and infectious disease specialists can help lead to successful diagnosis and management.

https://ift.tt/2Ca9DIS

Major Comorbidities of Atopic Dermatitis: Beyond Allergic Disorders

Abstract

The consequences of atopic dermatitis reach beyond the skin and past childhood. Patients with atopic dermatitis are at risk of developing allergic comorbidities, but less is known about the associations between atopic dermatitis and non-allergic conditions. Understanding these non-allergic comorbidities has the potential to improve patient outcomes and to help mitigate the cost and burdens associated with these conditions. Atopic dermatitis is associated with cutaneous bacterial infections, more severe forms/courses of cutaneous viral infections, and extra-cutaneous infections. Atopic dermatitis is also associated with several mental health comorbidities particularly attention-deficit hyperactivity disorder, anxiety, and depression. Data are largely inconsistent for specific cancers, but atopic dermatitis appears to protect against malignancy overall; severe long-term atopic dermatitis is associated with adult lymphomas. Atopic dermatitis may also be associated with obesity, cardiovascular disease, and autoimmune disease, particularly alopecia areata and gastrointestinal immune-mediated disorders. Although the causative mechanisms underlying these associations are poorly understood, treating physicians should be aware of associations in seeking to alleviate the burden for patients with atopic dermatitis.

https://ift.tt/2NajrGZ

A Comprehensive Conceptual Model of the Experience of Chronic Itch in Adults

Abstract

Background

Itch is common and often debilitating. Itch is best assessed by self-report, often using patient-reported outcome measures (PROMs). Current PROMs for itch are limited and may not capture its full impact on quality of life (QOL).

Objective

We sought to develop a comprehensive conceptual model of itch to improve the understanding of itch for clinicians and to serve as a framework for development of efficient and valid PROMs of itch.

Methods

Using mixed methods, including systematic review (n = 491 articles), semi-structured interviews (n = 33 adults with chronic itch with multiple etiologies), and grounded theory using a constant comparative approach, we developed a conceptual model of itch.

Results

We found the Wilson and Cleary model to be a reasonable framework for organizing our findings. It includes five primary components: biological and physiological variables, symptom status, functional status, general health perceptions, and QOL. We propose a causal relationship beginning with the biological and physiological driving factors, with direct and indirect impacts of itch and its sequelae, including pain and sleep disturbance. These can impair function, lead to task avoidance, stigma, social life and relationship problems, emotional disturbances, and treatment burden. Together, these sequelae alter one's perceptions of health, QOL, and treatment response.

Conclusions

Our conceptual model demonstrates the profound patient-burden of itch and identifies unmet needs in the evaluation and management of itch.

https://ift.tt/2NHRzXF

Incidence of and Risk Factors for Cutaneous Scarring after Herpes Zoster

Abstract

Background

About 20% of children have cutaneous scars following chickenpox. In contrast, skin scars are not often reported after herpes zoster (HZ). Risk factors for post-HZ scarring remain undetermined.

Objective

Our objective was to prospectively study the incidence of and risk factors for post-HZ scarring.

Methods

This was a 3-year prospective study of patients with HZ attending a tertiary university hospital. Baseline data, including age, sex, immunosuppression, prior history of scarring, severity and extension of HZ, afflicted HZ dermatome, and antiviral treatment received, were recorded. At 1 month after the HZ skin lesions had healed, patients were screened for skin scars at the prior HZ site. These patients were followed every 2 months for 6 months.

Results

At 6 months, 11 (9.7%) of 113 HZ patients still had post-HZ scarring (fair-skinned patients: hypopigmented [n = 3], hyperpigmented [n = 2], atrophic cicatricial [n = 3], and hypertrophic cicatricial [n = 1]; dark-skinned patients: severe hyperpigmented hypertrophic scarring [n = 2]). HZ was extensive and severe in all cases. Nine of the 11 patients were immunocompromised. Three cases had a history of hypertrophic/keloid scarring but no post-varicella scars. The most frequent location was the trunk (n = 5), followed by the cervical region (n = 3) and the face (n = 3). Given the study setting, it is possible that immunocompromized patients with severe HZ were overrepresented in this study.

Conclusions

Scarring after HZ is probably overlooked. The principal risk factors seem to be severe HZ and immunosuppression. Hence, prompt instigation of antiviral treatment for HZ and HZ vaccination could help reduce the incidence of post-HZ scarring.

https://ift.tt/2PYzshR

Reinforcement of barrier function – skin repair formulations to deliver physiological lipids into skin

International Journal of Cosmetic Science, Volume 0, Issue ja, -Not available-.


https://ift.tt/2PoktN5

Consensus research priorities for facial palsy: a Delphi survey of patients, carers, clinicians and researchers

Despite the potential negative impact of facial palsy, major gaps in understanding persist surrounding the treatment and care of those affected. This collaborative three-round Delphi process aimed to identify priorities for future facial palsy research, from the perspective of clinicians, researchers, patients and carers. It also determined whether the research priorities of patients and carers aligned with those of health professionals and researchers.In Round one participants (n=85) were asked to generate research questions via focus groups or an online or postal survey.

https://ift.tt/2NHs5cX

Effect of iron plaque and selenium on mercury uptake and translocation in rice seedlings grown in solution culture

Abstract

A hydroponics experiment was conducted to investigate the effect of iron plaque on root surfaces and selenium (Se) on the uptake and transfer of mercury (Hg) in rice seedlings by adding in the EDTA-Fe (0, 10, 30, 50, 70 mg Fe l⁻¹) into the solution to produce a different amount of iron plaque outside rice root. After 24 h, the red-brown iron plaque was formed on the root surface, and the amount of iron plaques was positively correlated with the amount of Fe in the solution. The iron plaque deposited on the root surface has a strong adsorption effect on the inorganic Hg. The addition of Se could promote the adsorption of Hg²⁺ on the iron plaque of rice, and the introduction of Se could increase the adsorption capacity of Hg on iron plaque on average by 1.42 times. The Hg was extracted by DCB (Dithionite-citrate-bicarbonate) up to between 66.2 and 67.8% of the total Hg when the roots with iron plaque (Fe70) were incubated with the combination of 5 μmol L⁻¹ of HgCl₂ and 5 μmol L⁻¹ of Na₂SeO₃ for an hour. After 3 days, the content of Hg in the iron plaque decreased to 6.3–33.9%, indicating that part of the inorganic Hg adsorbed by the iron plaque could be reabsorbed and used. Besides that, the iron plaque allowed the Hg to stay longer in the iron plaque, which hindered the transfer of Hg to the shoot significantly. Hg adsorbed in the iron plaque can be desorbed by low-molecular-weight organic acids, which was equivalent to desorption of Hg from ferric hydroxide oxides. Hg adsorbed on the iron plaque can be moved back to the rest of the plant. These results suggest that the iron plaque and Se in the root surface might play a role as "physical buffer" in the absorption and transfer of Hg.

https://ift.tt/2ou34aj

Intraoperative intermittent neuromonitoring of inferior laryngeal nerve and staged thyroidectomy: our experience

Abstract

Purpose

To evaluate the reliability of intermittent intraoperative neuromonitoring (I-IONM) through recurrent laryngeal nerve (RLN) stimulation and laryngeal palpation in predicting postoperative vocal cord palsy and to examine the reliability of this technique in providing useful information in the decision to perform a staged surgery in initially planned total thyroidectomy.

Methods

This was a retrospective cohort study of patients who underwent thyroid surgery at the ENT Department of the University of Bologna from January 2014 to June 2017. In all cases, preoperative and postoperative laryngoscopy was performed. All surgeries were conducted with I-IONM and RLN simultaneous laryngeal palpation (NSLP) to detect contraction (laryngeal twitch) of the posterior crico-arytenoid muscle. The incidence of vocal cord palsy was calculated for nerves at risk. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV), positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio were calculated with a confidence interval determined at 95% level.

Results

Seven hundred and sixteen patients were enrolled in the study. The incidence of vocal cord palsy was 3.16%. Specificity of I-IONM in predicting vocal cord paralysis was 99.1% and sensitivity was 90%. The NPV was 99.7% and PPV 78.3%. Two-stage thyroidectomy (ST) was performed in 22 cases (22/570: 3.85%). Six patients (27.3%) were false positive and 16 true positive (72.7%) at I-IONM.

Conclusion

High sensitivity and specificity values confirm the validity of I-IONM with NSLP in predicting postoperative normal vocal cord function. Our results confirm that I-IONM may safely guide an ST overall in benign thyroid diseases and in low-grade malignancies.

https://ift.tt/2otdO8X

Intraoperative intermittent neuromonitoring of inferior laryngeal nerve and staged thyroidectomy: our experience

Abstract

Purpose

To evaluate the reliability of intermittent intraoperative neuromonitoring (I-IONM) through recurrent laryngeal nerve (RLN) stimulation and laryngeal palpation in predicting postoperative vocal cord palsy and to examine the reliability of this technique in providing useful information in the decision to perform a staged surgery in initially planned total thyroidectomy.

Methods

This was a retrospective cohort study of patients who underwent thyroid surgery at the ENT Department of the University of Bologna from January 2014 to June 2017. In all cases, preoperative and postoperative laryngoscopy was performed. All surgeries were conducted with I-IONM and RLN simultaneous laryngeal palpation (NSLP) to detect contraction (laryngeal twitch) of the posterior crico-arytenoid muscle. The incidence of vocal cord palsy was calculated for nerves at risk. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV), positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio were calculated with a confidence interval determined at 95% level.

Results

Seven hundred and sixteen patients were enrolled in the study. The incidence of vocal cord palsy was 3.16%. Specificity of I-IONM in predicting vocal cord paralysis was 99.1% and sensitivity was 90%. The NPV was 99.7% and PPV 78.3%. Two-stage thyroidectomy (ST) was performed in 22 cases (22/570: 3.85%). Six patients (27.3%) were false positive and 16 true positive (72.7%) at I-IONM.

Conclusion

High sensitivity and specificity values confirm the validity of I-IONM with NSLP in predicting postoperative normal vocal cord function. Our results confirm that I-IONM may safely guide an ST overall in benign thyroid diseases and in low-grade malignancies.

https://ift.tt/2otdO8X

ESR1-promoter-methylation status in primary breast cancer and its corresponding metastases

Abstract

The role of ESR1 methylation in breast cancer and its influence on disease progression is not yet fully understood. Healthy breast tissue usually does not show ESR1 promoter methylation, whereas the frequency of ESR1 methylation appears to increase in primary breast cancer and in metastatic disease. Although women with ER positive breast cancer have a good prognosis, some will relapse. We aimed to evaluate the methylation status of ESR1 in primary breast cancer and its corresponding metastases by a methylation-specific real-time PCR and to correlate the methylation status with clinical outcome. Women who were treated for primary and metastatic breast cancer were included in the study. Tumor DNA was isolated from paraffin embedded tissue sections. After bisulfite treatment ESR1 promoter methylation was analyzed by real time-MSP of each tissue sample. Kaplan–Meier–Curves were drawn for survival. In the group of patients with positive ESR1 promoter methylation in the primary breast carcinoma survival was lower compared to the group of patients without methylation (38.1 months vs. 54.3 months, n.s.). Seven out of 19 (37%) of those patients with positive ESR1 promoter methylation developed loss of ER expression in metastatic disease. None of the patients who had primary tumours that were ESR1 methylation negative developed ER expression negative metastatic disease. The results underline the importance of the ESR1 promoter methylation and its potential application as a predictive marker. To improve the clinical outcome of patients with metastatic disease, those with initially positive ESR1 methylation status should undergo a tissue biopsy already at the beginning of metastatic disease to identify those with loss of ER expression and thus resitance to anti-endocrine therapy.

https://ift.tt/2PVryWz

A group-level comparison of volumetric and combined volumetric-surface normalization for whole brain analyses of myelin and iron maps

Publication date: Available online 1 September 2018

Source: Magnetic Resonance Imaging

Author(s): Antonietta Canna, Sara Ponticorvo, Andrea G. Russo, Renzo Manara, Francesco Di Salle, Renato Saponiero, Martina F. Callaghan, Nikolaus Weiskopf, Fabrizio Esposito

Abstract

Quantitative MRI (qMRI) provides surrogate brain maps of myelin and iron content. After spatial normalization to a common standard brain space, these may be used to detect altered myelination and iron accumulation in clinical populations. Here, volumetric and combined volumetric and surface-based (CVS) normalization were compared to identify which procedure would afford the greatest sensitivity to inter-regional differences (contrast), and the lowest inter-subject variability (under normal conditions), of myelin- and iron-related qMRI parameters, in whole-brain group-level studies.

Ten healthy volunteers were scanned twice at 3 Tesla. Three-dimensional T1-weighted, T2-weighted and multi-parametric mapping sequences for brain qMRI were used to map myelin and iron content over the whole brain. Parameter maps were spatially normalized using volumetric (DARTEL) and CVS procedures. Tissue probability weighting and isotropic Gaussian smoothing were integrated in DARTEL for voxel-based quantification (VBQ). Contrasts, coefficients of variations and sensitivity to detecting differences in the parameters were estimated in standard space for each approach on region of interest (ROI) and voxel-by-voxel bases.

The contrast between cortical and subcortical ROIs with respectively different myelin and iron content was higher following CVS, compared to DARTEL-VBQ, normalization. Across cortical voxels, the inter-individual variability of myelin and iron qMRI maps were comparable between CVS (with no smoothing) and DARTEL-VBQ (with smoothing).

CVS normalization of qMRI maps preserves higher myelin and iron contrast than DARTEL-VBQ over the entire brain, while exhibiting comparable variability in the cerebral cortex without extra smoothing. Thus, CVS may prove useful for detecting small microstructural differences in whole-brain group-level qMRI studies.

https://ift.tt/2oxmrPD

Characterization of prostate cancer with MR spectroscopic imaging and diffusion-weighted imaging at 3 Tesla

Publication date: Available online 31 August 2018

Source: Magnetic Resonance Imaging

Author(s): Yousef Mazaheri, Amita Shukla-Dave, Debra A. Goldman, Chaya S. Moskowitz, Toshikazu Takeda, Victor E. Reuter, Oguz Akin, Hedvig Hricak

Abstract

Purpose

To retrospectively measure metabolic ratios and apparent diffusion coefficient (ADC) values from 3-Tesla MR spectroscopic imaging (MRSI) and diffusion-weighted imaging (DWI) in benign and malignant peripheral zone (PZ) prostate tissue, assess the parameters' associations with malignancy, and develop and test rules for classifying benign and malignant PZ tissue using whole-mount step-section pathology as the reference standard.

Methods

This HIPAA-compliant, IRB-approved study included 67 men (median age, 61 years; range, 41–74 years) with biopsy-proven prostate cancer who underwent preoperative 3 T endorectal multiparametric MRI and had ≥1 PZ lesion >0.1 cm³ at whole-mount histopathology. In benign and malignant PZ regions identified from pathology, voxel-based choline/citrate, polyamines/choline, polyamines/creatine, and (choline + polyamines + creatine)/citrate ratios were averaged, as were ADC values. Patients were randomly split into training and test sets; rules for separating benign from malignant regions were generated with classification and regression tree (CART) analysis and assessed on the test set for sensitivity and specificity. Odds ratios (OR) were evaluated using generalized estimating equations.

Results

CART analysis of all parameters identified only ADC and (choline + polyamines + creatine)/citrate as significant predictors of cancer. Sensitivity and specificity, respectively, were 0.81 and 0.82 with MRSI-derived, 0.98 and 0.51 with DWI-derived, and 0.79 and 0.90 with MRSI + DWI-derived classification rules. Areas under the curves (AUC) in the test set were 0.93 (0.87–0.97) with ADC, 0.82 (0.72–0.91) with MRSI, and 0.96 (0.92–0.99) with MRSI + ADC.

Conclusion

We developed statistically-based rules for identifying PZ cancer using 3-Tesla MRSI, DWI, and MRSI + DWI and demonstrated the potential value of MRSI + DWI.

https://ift.tt/2wG4KRY

Cover figure

Publication date: September 2018

Source: Cortex, Volume 106

Author(s):

https://ift.tt/2wzg1nT

Editorial Board

Publication date: September 2018

Source: Cortex, Volume 106

Author(s):

https://ift.tt/2C7xXuQ

First European case of Creutzfeldt-Jakob Disease with a PRNP G114V Mutation

Publication date: Available online 1 September 2018

Source: Cortex

Author(s): Louis Cousyn, David Grabli, Danielle Seilhean, Carole Azuar, Camille Huiban, Stéphane Epelbaum, Elodie Bouaziz-Amar, Jean-Philippe Brandel, Damien Galanaud, Aurélie Méneret

Abstract

Genetic Creutzfeldt-Jakob disease is due to mutations in the PRNP gene. Only two families with a PRNP G114V mutation have been described around the world. We report the first European case, who had no family history and initially presented with isolated deficit in hippocampus-dependent memory. Initial investigations were normal except for elevated total tau protein in the cerebrospinal fluid. He died 4 years after disease onset. This case highlights the diagnostic difficulties posed by genetic Creutzfeldt-Jakob disease, and shows that genetic analyses should be considered even in sporadic cases.

https://ift.tt/2PXUoFw

Scholar : These new articles for Studies in Chinese Religions are available online

The online platform for Taylor & Francis Online content New for Studies in Chinese Religions and online now on Taylor & Francis Online: Book Reviews Buddhism and medicine: an anthology of premodern sources Matthew W. King Pages: 1-2 | DOI: 10.1080/23729988.2018.1488917 Discover Asian Affairs' latest Special Issue: Ghosts from the Past? Assessing Recent Developments in Religious Freedom in South Asia To update which email alerts you receive, manage your alerts within the My Account area. Unsubscribe from new content alerts for this journal (both new issue and latest article notifications) with one click. If you need any further help, please contact us at support@tandfonline.com Please do not reply to this email. To ensure that you receive your alerts and information from Taylor & Francis Online, please add "alerts@tandfonline.com" and "info@tandfonline.com" to your safe senders list. Taylor & Francis, an Informa business. Taylor & Francis is a trading name of Informa UK Limited, registered in England under no. 1072954. Registered office: 5 Howick Place, London, SW1P 1WG.

BLIMP1 transcriptionally induced by EGFR activation and post-translationally regulated by proteasome and lysosome is involved in keratinocyte differentiation, migration and inflammation

Publication date: Available online 31 August 2018

Source: Journal of Dermatological Science

Author(s): Hua-Ching Chang, Duen-Yi Huang, Nan-Lin Wu, Reiji Kannagi, Li-Fang Wang, Wan-Wan Lin

Abstract

Background

B lymphocyte-induced maturation protein-1 (BLIMP1) is a transcriptional repressor, and plays a crucial role in the regulation of development and functions of various immune cells. Currently, there is limited understanding about the regulation of BLIMP1 expression in keratinocytes and crosstalk between EGFR and BLIMP1 in skin homeostasis.

Objective

The aim of the study was to investigate the regulation and functional link between EGFR and BLIMP1 in human epidermal keratinocytes.

Methods

Immunoblotting and Q-PCR were used to determine the molecular mechanism of BLIMP1 expression induced by EGFR in primary human epidermal keratinocytes (NHEK) and HaCaT cells. Effects of BLIMP1 knockdown on EGFR-mediated cytokine production, differentiation, and migration in NHEK were evaluated.

Results

EGFR activation by EGFR ligands could upregulate the protein and mRNA levels of BLIMP1 in NHEK and HaCaT cells. This effect was dependent on PKC, p38, and ERK activation. Additionally, the stability of BLIMP1 protein was under the control of the proteasome and lysosome degradation systems. In addition, BLIMP1 knockdown enhanced the EGFR-mediated IL8, CXCL5 and IL6 gene expression and keratinocyte migration, but reduced the EGFR-mediated suppression of differentiation marker K10.

Conclusions

Our findings shed new insights into the regulation of BLIMP1 expression by EGFR-mediated gene transcription and proteasome/lysosome-mediated degradation in keratinocytes. Functionally, BLIMP1 is a negative regulator of EGF-induced inflammation and migration in keratinocytes, and exerts a gene-specific regulation on keratinocyte differentiation.

https://ift.tt/2PVXvxK

Low-dose UVB therapy is comparable with conventional UVB phototherapy for treatment of vitiligo: A pilot study

Publication date: Available online 31 August 2018

Source: Journal of Dermatological Science

Author(s): Szu-Hao Chiu, I Liang Liu, Yu Wen Chen, Cheng-Che E. Lan

https://ift.tt/2Ca5Xa0