Τρίτη 29 Ιανουαρίου 2019
Ingestion of plastic fragments by the Guri sea catfish Genidens genidens (Cuvier, 1829) in a subtropical coastal estuarine system
Abstract
One of the most recognized anthropogenic impacts in marine environments is solid waste pollution, especially plastic, which can be ingested by fish, thus interfering with their health. In this context, the aim of this study is to describe the ingestion of plastic fragments and to identify the possible effect of this contamination in the condition factor of Genidens genidens in the Laguna Estuarine System. The stomach contents of 92 G. genidens (26 juveniles and 66 adults) were analyzed. The Index of Relative Importance was performed to identify the contribution of each prey item. Condition factor (CF) was used to analyze the effect of plastic ingestion on the fish's body condition (by comparing individuals in the same ontogenetic phase). For the juveniles, eight items were observed, the most important of which were Penaeidae, followed by Portunidae and plastic. For the adults, 12 items were observed, the most important of which were Penaeidae, Portunidae, Polychaeta, and plastic. The analysis of CF demonstrated higher values for individuals without plastic in the stomach, which indicated a better health condition. The CF of a fish may be affected by variations in the physiological condition, environmental stresses, and nutritional and biological variations, and could be used to compare the body condition or health of a fish species. The ingestion of plastic could significantly influence the worst body condition of the individuals that were analyzed in the present study. The plastic pollution in marine coastal waters is associated with the appropriate waste management levels.
http://bit.ly/2Wt6VEp
Tanycytes: a rich morphological history to underpin future molecular and physiological investigations
Abstract
Tanycytes are located at the base of the brain and retain characteristics from their developmental origins – as radial glial cells ‐ throughout their life span. With transport mechanisms and modulation of tight junction proteins, tanycytes form a bridge connecting the cerebrospinal fluid with the external limiting basement membrane. They also retain the powers of self‐renewal and can differentiate to generate neurons and glia. Like radial glia, they are a heterogeneous family with distinct phenotypes. Although the four subtypes so far distinguished display distinct characteristics, further research is likely to reveal new subtypes. In preparation for this review we re‐visited the work of the pioneers in the field revealing forgotten work waiting to inspire new research with today's cutting‐edge technologies. We have conducted a systematic ultrastructural study of α‐tanycytes that resulted in a wealth of new information, generating numerous questions for future study. We also consider median eminence pituicytes, a closely‐related cell type to tanycytes, and attempt to relate pituicyte fine morphology to molecular and functional mechanism. Our rationale was that future research should be guided by a better understanding of the early pioneering work in the field, which may currently be overlooked when interpreting newer data or designing new investigations.
This article is protected by copyright. All rights reserved.
http://bit.ly/2G7V74O
M1b Disease in the 8th Edition of TNM Staging of Lung Cancer: Pattern of Single Extrathoracic Metastasis and Clinical Outcome
AbstractBackground.The 8th edition of TNM staging of non‐small cell lung cancer (NSCLC) has revised M classification and defined M1b disease with single extrathoracic metastasis, which is distinguished from M1c with multiple extrathoracic metastases. We investigated the prevalence, characteristics, and overall survival (OS) of M1b disease in patients with stage IV NSCLC.Methods.The study reviewed the medical records and imaging studies of 567 patients with stage IV NSCLC to determine M stage using the 8th edition of TNM staging. Clinical characteristics and OS were compared according to M stages.Results.Among 567 patients, 57 patients (10%) had M1b disease, whereas 119 patients (21%) had M1a disease and 391 patients (69%) had M1c disease. Squamous histology was more common in M1b (16%) than in M1a (6%) and M1c (6%; p = .03). The median OS of patients with M1b disease was 14.8 months, compared with 22.6 months for patients with M1a and 13.4 months for those with M1c disease (p < .0001). Significant OS differences of M1b compared with single‐organ M1c and multiorgan M1c groups were noted (single‐organ M1c vs. M1b: hazard ratio [HR], 1.49; p = .02; multiorgan M1c vs. M1b: HR, 1.57; p = .01) in multivariable analyses adjusting for smoking and systemic therapy types. Among patients with M1b disease, the brain was the most common site of single metastasis (28/57; 49%), followed by bone (16/57; 28%). Single brain metastasis was more frequently treated with local treatment (p < .0001).Conclusion.M1b disease was noted in 10% of patients with stage IV NSCLC. Squamous histology was more common in M1b group than others. The brain was the most common site of single metastasis and was often treated locally.Implications for Practice.The newly defined group of M stage consists of a unique subset among patients with stage IV non‐small cell lung cancer that can be studied further to optimize treatment approaches.
http://bit.ly/2WvUNlQ
Refining the Use of Adjuvant Oxaliplatin in Clinical Stage II or III Rectal Adenocarcinoma
AbstractBackground.Current guidelines include the use of adjuvant oxaliplatin in clinical stage II or III rectal adenocarcinoma. However, its efficacy is supported by a single phase II trial. We aimed to examine whether oxaliplatin confers survival benefit in this patient population.Methods.Using the National Cancer Database (2006–2013) we identified 6,868 individuals with clinical stage II or III rectal adenocarcinoma treated with neoadjuvant chemoradiotherapy, surgery, and adjuvant chemotherapy. We used multivariate Cox regression to evaluate survival differences according to treatment intensity and change from clinical to pathological stage.Results.We demonstrated an association with improved overall survival with the use of doublet adjuvant chemotherapy in pathological stage III rectal adenocarcinoma (hazard ratio [HR], 0.78; 95% confidence interval [CI], 0.67–0.92). This association was confirmed in patients with clinical stage III and subsequent pathological stage III disease (HR, 0.69; 95% CI, 0.57–0.83) and was not observed in patients who progressed from clinical stage II to pathological stage III disease. Doublet adjuvant chemotherapy was not associated with improved overall survival in patients with pathological stage 0 or I disease, regardless of their clinical stage.Conclusion.Adjuvant oxaliplatin following neoadjuvant chemoradiotherapy in rectal adenocarcinoma was confirmed in patients with clinical stage III and subsequent pathological stage III disease. Omission of oxaliplatin can be considered in pathological complete response or pathological stage I disease.Implications for Practice.Current guidelines include the use of oxaliplatin as part of adjuvant chemotherapy (AC) in patients with clinical stage II or III rectal adenocarcinoma (RAC). However, its efficacy is supported only by a single phase II trial. This study found an association with improved overall survival with the use of doublet AC in patients diagnosed with clinical stage III and subsequent pathological stage III, and not in patients with pathological stage 0 or I, regardless of their clinical stage. Therefore, omission of oxaliplatin can be considered in patients with either pathological complete response or pathological stage I RAC, thereby avoiding oxaliplatin‐induced neuropathy.
http://bit.ly/2RmirOd
Bridge: Person‐Centered Collaborative Care for Patients with Serious Mental Illness and Cancer
AbstractBackground.Individuals with serious mental illness (SMI) experience increased cancer mortality due to inequities in cancer treatment. Psychiatric care at cancer diagnosis may improve care delivery, yet models for integrating psychiatry and cancer care are lacking. We assessed the feasibility and acceptability of a person‐centered collaborative care trial for SMI and cancer.Subjects, Materials, and Methods.We developed the Bridge intervention for patients with SMI (schizophrenia, bipolar disorder, and severe major depression) and cancer. Bridge includes proactive identification of SMI, person‐centered care from a psychiatrist and case manager, and collaboration with oncology. We conducted a 12‐week, single‐group trial in patients with SMI and a new breast, gastrointestinal, lung, or head/neck cancer. We assessed the feasibility of patient identification, enrollment and study completion; evaluated acceptability and perceived benefit with exit interviews with patients, caregivers, and oncology clinicians; and examined change in psychiatric symptoms with the Brief Psychiatric Rating Scale (BPRS).Results.From November 2015 to April 2016, 30/33 eligible patients (90.9%) enrolled, and 25/29 (86.2%) completed assessments at all timepoints, meeting feasibility criteria. Of 24 patients, 23 (95.8%) found meeting with the psychiatrist helpful; 16/19 caregivers (84.2%) shared that Bridge addressed key caregiving challenges. Oncology clinicians evaluated Bridge as "very" or "most" useful for 94.3% of patients. Exit interviews with all participant groups suggested that Bridge fostered patient‐clinician trust, increased access to psychiatric treatment, and enabled patients to initiate and complete cancer treatment. Psychiatric symptoms on the BPRS improved from baseline to 12 weeks.Conclusion.Bridge is a feasible and acceptable care delivery model for patients with SMI, their caregivers, and oncology clinicians. Randomized trials are warranted to assess the efficacy of improving cancer outcomes in this underserved population.Implications for Practice.Serious mental illness affects 13 million U.S. adults who experience increased cancer mortality. To improve outcomes, new models of integrated oncology and mental health care are urgently needed. This study found that it was feasible to identify, enroll, and retain patients with serious mental illness and a new cancer in a trial of integrated mental health and cancer care (Bridge). Patients, caregivers, and oncologists reported that Bridge facilitated the initiation and completion of cancer care. Randomized trials are warranted to investigate the impact on cancer outcomes. Trial procedures may inform consent, engagement, and trial retention for patients with mental illness.
http://bit.ly/2WsCdeI
Clinicopathological and Preclinical Findings of NUT Carcinoma: A Multicenter Study
AbstractBackground.NUT carcinoma is a rare aggressive disease caused by BRD4/3‐NUT fusion, and C‐MYC upregulation plays a key role in the pathogenesis. Here, we report on the clinicopathological characteristics of Korean patients with NUT carcinoma and the in vitro efficacy of MYC‐targeting agents against patient‐derived NUT carcinoma cell lines.Materials and Methods.Thirteen patients with NUT carcinoma were evaluated for p53, C‐MYC, epidermal growth factor receptor (EGFR), HER2, and programmed cell death ligand 1 (PD‐L1) by immunohistochemistry. The half maximal inhibitory concentration (IC50) values of NUT carcinoma cell lines (SNU‐2972‐1, SNU‐3178S, HCC2429, and Ty‐82) were determined using MYC‐targeting agents, including bromodomain and extraterminal (BET) inhibitors (I‐BET, OTX‐015, AZD5153) and histone deacetylase (HDAC) inhibitors (vorinostat, romidepsin, panobinostat, CUDC‐907).Results.Primary tumor sites included head and neck (n = 9) and lung (n = 4). The patient age ranged from 8 to 73 years with the male/female ratio of 1.2:1. Nine patients died at 3–23.6 months (median, 10.6) after diagnosis. Eight patients had been misdiagnosed initially with other diseases. One patient with metastatic NUT carcinoma who received mass excision plus metastasectomy followed by chemoradiotherapy was a long‐term survivor (>27 months). Although expressions of C‐MYC (8/12, 73%) and p53 (12/12, 100%) were commonly observed, EGFR, HER2, and PD‐L1 expressions were observed in 2 of 7 (29%), 2 of 8 (25%), and 1 of 12 (8.3%) patients, respectively. BET and HDAC inhibitors showed variable but limited in vitro efficacy. However, a dual HDAC/PI3K inhibitor, CUDC‐907, was most potent against NUT carcinoma cells, with an IC50 of 5.5–9.0 pmol/L. Consistent with these findings, kinome short interfering RNA screening showed a positive hit for PI3KCA in NUT carcinoma cells. Panobinostat (IC50, 0.4–1.3 nmol/L) and a bivalent BET inhibitor, AZD5153 (IC50, 3.7–8.2 nmol/L), also showed remarkable efficacies.Conclusion.East Asian patients with NUT carcinoma showed dismal survival outcomes like Western patients, and CUDC‐907 might be promising in NUT carcinoma treatment.Implications for Practice.NUT carcinoma (NC) is a disease caused by BRD‐NUT fusion leading to C‐MYC upregulation. NC is often misdiagnosed and very aggressive, requiring development of effective therapeutic strategy. This article presents the clinicopathological features of the largest series of NCs in East Asians and preclinical sensitivities to MYC‐targeting agents in NC cell lines. Patients with NC had grave outcomes and poor response to treatment. Among MYC‐targeting agents, including BET and HDAC inhibitors, CUDC‐907 (a dual PI3K/HDAC inhibitor) was most effective against NC cells, followed by panobinostat (an HDAC inhibitor) and AZD5153 (a bivalent BET inhibitor). CUDC‐907 might be promising in NC treatment.
http://bit.ly/2Ru5y4M
Preoperative Angiography for Free Fibula Flap Harvest: A Meta-Analysis
J reconstr Microsurg
DOI: 10.1055/s-0038-1677012
Background The necessity for routine preoperative imaging for free fibula harvest is controversial. The primary objective of this meta-analysis is to determine if lower extremity angiography is necessary to detect abnormalities that may alter flap selection. The secondary objective is to determine if physical examination alone is sufficient to predict these abnormalities. Methods A literature search was performed using Cochrane, CENTRAL, MEDLINE, CINAHL, and EMBASE. Studies were selected for inclusion if they included patients undergoing free fibula flap harvest with preoperative imaging, with or without physical examination findings. Data extraction was performed independently and in duplicate, including a change in flap selection and the level of agreement between physical examination and imaging. Pooled proportions were calculated using a random-effects model and 95% confidence intervals (CI). Results Sixteen studies were included for analysis. Mean sample size was 42 patients (range: 5–123). Included studies were of low methodologic quality. Pooled proportion of patients who had flap selection change secondary to abnormalities identified on preoperative angiography was 20.1% (95% CI: 9.6–33.2%). A pooled proportion of 71.5% (95% CI: 5–88.7%) of cases requiring change in flap selection was missed by physical examination findings alone. Conclusions There is low-quality evidence suggesting a necessity for routine preoperative angiography for all patients undergoing free fibula flap harvest. Physical examination alone is insufficient in detecting vascular abnormalities that may result in limb compromise or an inability to successfully harvest a free fibula. Further investigation is warranted for cost-effectiveness of preoperative imaging protocols.
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Dissemination of resistance genes in duck/fish polyculture ponds in Guangdong Province: correlations between Cu and Zn and antibiotic resistance genes
Abstract
Duck/fish polyculture farming is a typical farming model in the Pearl River delta in southern China. We examined soil, water, and sediment samples from three duck-fish farms in Guangdong Province in September and December 2014. We determined the abundance of three metal resistance genes, 16S rDNA, and 23 antibiotic resistance genes encoding resistance to tetracycline, sulfonamides, quinolones, chloramphenicol, and β-lactamases. Microbial community structure was quantified by Illumina high-throughput sequencing of 16S rDNA genes. We found a prevalence of antibiotic resistance genes and the sul1, sul2, tetA, tetM, aac(6′)-Ib, and floR genes were the most abundant. Levels of Cu and Zn were significantly correlated with numerous ARG types and sul2, floR, and tetM were identified as potential antibiotic resistance gene indicators. Cu levels were significantly and positively correlated with the relative abundance of sul3, tetT, tetW, qnrB, qnrS, fexB, sul1, sul2, tetM, and qnrA. Zn was significantly correlated to relative abundance of sul2, sul3, tetM, tetA, tetT, tetW, qnrA, qnrB, qnrS, aac(6′)-Ib, qepA, blaSHV, cmlA, floR, fexA, cfr, and fexB. The levels of Acinetobacter, Brevibacillus, and Wautersiella showed significant positive correlations with metal resistance genes as well as qnrB, oqxA, oqxB, and blaSHV (p > 0.8). Sphingobacterium, Flavobacterium, Acidothermus, and Corynebacterium had significant correlations with abundance of tetracycline resistance genes, sulfonamide resistance genes, blaTEM, blaCTX, and cfr (p > 0.8). Sphingobacterium, Flavobacterium, Acidothermus, and Corynebacterium were most abundant in soil samples while Acinetobacter, Brevibacillus, and Wautersiella were most abundant in water samples. Dissemination of antibiotic resistance genes in aquaculture environments is extensive and tracing their origins is necessary to establish risk assessment methods required for aquatic environmental protection.
http://bit.ly/2UoUAiB
Electrokinetic remediation of antibiotic-polluted soil with different concentrations of tetracyclines
Abstract
This study investigated the efficacy of electrokinetic remediation of soils polluted with different concentrations of tetracyclines (TCs). Three widely used TCs (oxytetracycline, chlortetracycline, and tetracycline) were selected, and concentrations of 0, 5, 10, 20, and 50 mg/kg (C0, C5, C10, C20, C50) were selected for comparison. Antibiotic-polluted soils with no electric field served as controls. The average removal rates of TCs in different treatments ranged from 25 to 48% after 7-day remediation. The contributing ratios of electrokinetics to TCs removal varied from 22 to 84%. The concentrations of NH4+ increased in soils and electrolytes, which indicated the decomposition of TCs in the electric field. The highest removal amount of TCs was obtained in the C50 treatment, due to efficient reactions of TCs with oxidative radicals generated during the electrolysis. The fluctuant range of pH in the electrolytes was decreased with increasing concentration of TCs, while the soil pH was increased. The removal rate of antibiotic-resistant bacteria (ARB) in the C5 treatment was significantly higher than that in other treatments. The abundance of antibiotic resistance genes (ARGs) increased with the concentrations of TCs in soils. It might result from the induction of increasing selective pressure of antibiotics. Significant removal of ARGs occurred in the C50 treatment (38–60%). In terms of controlling ARB and ARGs, which were more resistant, the electrokinetic technology showed advantageous effects. Above all, electrokinetic technology provides an effective remediation method, especially for TC-polluted soil with a concentration of 20–50 mg/kg.
http://bit.ly/2B7Gjje
Plasma TNF‐α and adiponectin levels differentiate psoriatic arthritis from psoriasis patients
Abstract
Psoriasis (PsO) and psoriatic arthritis (PsA) are inflammatory disorders. Circulating biomarkers of inflammation such as interleukin‐6 (IL‐6), Tumor Necrosis Factor‐α (TNF‐α), and C‐reactive protein (CRP) have been associated with disease severity and progression of PsO and PsA. Adiponectin and leptin are adipose derived cytokines, recognized as key regulator of body weight and metabolism2. Whether circulating levels of these inflammatory and metabolic biomarkers may predict the risk of PsA in psoriasis populations remains unclear.
This article is protected by copyright. All rights reserved.
http://bit.ly/2sTKgnh
Physician Perceptions of Primary Care‐based Skin Cancer Screening in a Veterans Affairs Pilot Study
Abstract
Understanding primary care practitioner (PCP) barriers and facilitators to performing clinical skin examination (CSE) for skin cancer screening is necessary before widespread implementation. Time constraints, competing comorbidities, and patient embarrassment have been reported as obstacles. In 2016, the United States Preventative Services Task Force deemed the worldwide evidence as insufficient to assess the balance of benefits versus harms of skin cancer screening (I statement), neither recommending for nor against CSE. While the impact of primary care‐based skin cancer screening on melanoma incidence and mortality has been investigated, qualitative studies describing PCP feedback and diverse contextual factors that may help or hinder program implementation are lacking.
This article is protected by copyright. All rights reserved.
http://bit.ly/2MEgtYK
Protective effects of quercetin supplementation against short-term toxicity of cadmium-induced hematological impairment, hypothyroidism, and testicular disturbances in albino rats
Abstract
The aim of this study was to evaluate the probable protective effect of quercetin (QUE) against cadmium (Cd)-induced sub-chronic toxicity in rats. Adult male rats were given either Cd (as cadmium chloride; 5 mg/kg) alone or in combination with QUE (50 mg/kg) daily for 4 weeks by oral gavage. At the end of the experimental period, Cd accumulation, and selected hematological, thyroid, and reproductive markers were assessed. Results revealed that Cd treatment significantly increased Cd concentrations in blood, thyroid gland, and testicular tissue of rats. Cd also caused a decline in hemoglobin content, hematocrit value, and total erythrocyte and leucocyte counts. Further, significant suppressions in the blood levels of hormones related to thyroid gland function, and male reproductive hormones (i.e., testosterone, luteinizing hormone and follicle-stimulating hormone), were observed in Cd-treated rats compared to the control. In parallel, low sperm count and sperm motility, increased sperm abnormalities, and marked pathology occurred in testis. Combination with QUE recorded amelioration of the deleterious effects of Cd, involving regulation of hematological toxicity and thyroid hormonal levels and subsequently modulation of testicular function. In conclusion, it appears that dietary QUE can rescue from Cd-induced hematological dysfunctions and testicular damage by reversing the hypothyroid state.
http://bit.ly/2FVfG53
Revisiting the Significance of Prominent C Cells in the Thyroid
Abstract
C cell hyperplasia is considered a precursor lesion for hereditary forms of medullary thyroid carcinoma. It has therefore been suggested as a morphological marker to distinguish hereditary from sporadic medullary thyroid carcinoma and to triage genetic testing in resource poor settings. However, numerous definitions for C cell hyperplasia have been suggested, and there is surprisingly little data regarding the number of C cells present in thyroid glands removed for conditions other than medullary carcinoma. We therefore sought to investigate the specificity of different criteria for C cell hyperplasia. We examined the number of C cells and solid cell nests (ultimobranchial body remnants) present in 118 completion thyroidectomy specimens from patients without medullary carcinoma and with no risk factors for MEN2. Morphological review was performed on all H&E-stained slides, and immunohistochemistry for calcitonin was performed on one block from each case. Solid cell nests were found in 4 (3.3%) of thyroids. Increased numbers of C cells sufficient to fulfil criteria for C cell hyperplasia were found in 5 (4.2%) to 36 (30.5%) cases depending on the criteria used. We conclude that large numbers of C cells are commonly found in thyroids not associated with medullary carcinoma. Therefore, regardless of which criteria are used, the presence of C cell hyperplasia is not a specific marker for hereditary medullary thyroid carcinoma.
http://bit.ly/2MEImjj
Spatiotemporal variability of heavy metals and identification of potential source tracers in the surface water of the Lhasa River basin
Abstract
The Lhasa River basin is the economic and population center of Tibet and has abundant resources. Due to its harsh weather condition, high elevation, and inconvenient accessibility, few studies have focused on heavy metal distributions in this region. In the present study, to investigate the dissolved trace metal pollution and its controlling factors, 57 water samples from the Lhasa River and its tributaries were collected during three water flow regimes in 2016. The data on the dissolved fraction revealed that the Lhasa River basin appeared to have no to low pollution levels. However, the Lhasa River water showed alkaline characteristics which may affect the presence of heavy metal elements in a dissolved fraction. The concentration of heavy metal elements in colloidal or particulate matter therefore needs attention. Multivariate analyses were performed to determine the significant relationship between the data and to identify controlling factors for dissolved heavy metals in the study area. The results suggested that Mn, Cd, Cu, and Zn originated from a natural geological background, whereas Pb originated from mining drainage and As was influenced by geothermal flows. The concentration of dissolved heavy metals in the Meldromarchu tributary was greatly affected by the mining drainage water, while that in the Tölungchu tributary was greatly influenced by the geothermal water sources. This paper provides the first comprehensive analysis of dissolved heavy metal pollution characteristics and the controlling factors of pollution during the three different water flow regimes of the Lhasa River basin.
http://bit.ly/2CQev2W
Previous, current, and cumulative dose effect of waterpipe smoking on LDL and total cholesterol
Abstract
The popularity of waterpipe smoking is dramatically increasing in Lebanon, reaching 36.9%, the highest among countries in the region. To the best of our knowledge, no studies have assessed the impact of waterpipe smoking on lipid levels in the Lebanese population. Therefore, the objective of the study was to evaluate the correlation between waterpipe smoking and LDL-C and total cholesterol levels in exclusive Lebanese waterpipe smokers compared to non-smokers. This cross-sectional study was conducted between October 2016 and February 2017, enrolling 308 patients (156 non-smokers and 147 waterpipe smokers) from four laboratories. Current and previous WS (beta = 66.64 and beta = 71.49) were significantly associated with higher LDL scores. Current WS was significantly associated with and total cholesterol levels (beta = 34.12). Cumulative WS (number of waterpipes per week × duration in years) was significantly associated with higher LDL-C and total cholesterol levels respectively (p < 0.001 for all 3 variables). The university level of education (beta = 8.89) and current alcohol drinking (beta = 8.81) were significantly associated with higher LDL scores. Our study demonstrated an association between previous or current waterpipe smoking and lipid level. Future research are needed to detect the direct cause of the relation between waterpipe smoking and CVD. Concerned authorities should set up awareness campaigns to increase alertness on dangers of WS and dependence, and encourage these young adults to embrace health-promoting behaviors.
http://bit.ly/2RYXfmz
Comparative evaluation of neuroendocrine dysfunction in children with craniopharyngiomas before and after mass effects are removed
Journal Name: Journal of Pediatric Endocrinology and Metabolism
Issue: Ahead of print
http://bit.ly/2CP9Nm6
Metabolic Disease Epidemics: Emerging Challenges in Regenerative Medicine
Publication date: Available online 29 January 2019
Source: Trends in Endocrinology & Metabolism
Author(s): Raquel Costa-Almeida, Rui L. Reis, Manuela E. Gomes
The interplay between cell/tissue damage caused by metabolic dysfunction and regenerative potential remains elusive. The tissue engineering and regenerative medicine (TERM) field is now facing a worldwide epidemic of obesity. This Forum article uncovers prospective questions to be addressed in TERM toward the development of effective regenerative therapies adjusted to these new demands.
http://bit.ly/2sST50p
Cosmetics, Vol. 6, Pages 8: Design Methodology for the Development of a New Cosmetic Active Based on Prunus domestica L. Leaves Extract
Cosmetics, Vol. 6, Pages 8: Design Methodology for the Development of a New Cosmetic Active Based on Prunus domestica L. Leaves Extract
Cosmetics doi: 10.3390/cosmetics6010008
Authors: Hortense Plainfossé Pauline Burger Grégory Verger-Dubois Stéphane Azoulay Xavier Fernandez
When it comes to the development of new active ingredients for cosmetics, biodiversity is a rich source for inspiration that must be tapped in a sustainable manner to cause no social nor ecological damage. Agri-food by-products are therefore more and more considered as available biomass that can be reused to extract their maximum value to produce new cosmetic ingredients before returning to the biosphere. The process to transform plant waste materials into powerful cosmetic actives is thoroughly described in the present paper via the example of the design of a liquid anti-aging ingredient based on a Prunus domestica L. extract obtained by maceration of plums’ dried leaves in propylene glycol. The subsequent development of an SPE (solid-phase extraction) methodology used to remove the propylene glycol to get access to the extracted molecules is thoroughly described as a means to follow the stability of the ingredient over time once formulated into a finished product.
http://bit.ly/2B4S6P5
Dopamine effects on frontal cortical blood flow and motor inhibition in parkinson’s disease
Publication date: Available online 29 January 2019
Source: Cortex
Author(s): Paula Trujillo, Nelleke C. van Wouwe, Ya-Chen Lin, Adam J. Stark, Kalen J. Petersen, Hakmook Kang, David H. Zald, Manus J. Donahue, Daniel O. Claassen
Abstract
Parkinson's disease (PD) is characterized by dysfunction in frontal cortical and striatal networks that regulate action control. We investigated the pharmacological effect of dopamine agonist replacement therapy on frontal cortical activity and motor inhibition. Using Arterial Spin Labeling MRI, we examined 26 PD patients in the off- and on-dopamine agonist medication states to assess the effect of dopamine agonists on frontal cortical regional cerebral blood flow. Motor inhibition was measured by the Simon task in both medication states. We applied the dual process activation suppression model to dissociate fast response impulses from motor inhibition of incorrect responses. General linear regression model analyses determined the medication effect on regional cerebral blood flow and motor inhibition, and the relationship between regional cerebral blood flow and motor inhibitory proficiency. We show that dopamine agonist administration increases frontal cerebral blood flow, particularly in the pre-supplementary motor area (pre-SMA) and the dorsolateral prefrontal cortex (DLPFC). Higher regional blood flow in the pre-SMA, DLPFC and motor cortex was associated with better inhibitory control, suggesting that treatments which improve frontal cortical activity could ameliorate motor inhibition deficiency in PD patients.
http://bit.ly/2Sh3l0I
Contributions of left frontal and temporal cortex to sentence comprehension: Evidence from simultaneous TMS-EEG
Publication date: Available online 28 January 2019
Source: Cortex
Author(s): Leon O.H. Kroczek, Thomas C. Gunter, Anna U. Rysop, Angela D. Friederici, Gesa Hartwigsen
Abstract
Sentence comprehension requires the rapid analysis of semantic and syntactic information. These processes are supported by a left hemispheric dominant fronto-temporal network, including left posterior inferior frontal gyrus (pIFG) and posterior superior temporal gyrus/sulcus (pSTG/STS). Previous electroencephalography (EEG) studies have associated semantic expectancy within a sentence with a modulation of the N400 and syntactic gender violations with increases in the LAN and P600. Here, we combined focal perturbations of neural activity by means of short bursts of transcranial magnetic stimulation (TMS) with simultaneous EEG recordings to probe the functional relevance of pIFG and pSTG/STS for sentence comprehension. We applied 10 Hz TMS bursts of three pulses at verb onset during auditory presentation of short sentences. Verb-based semantic expectancy and article-based syntactic gender requirement were manipulated for the sentence final noun. We did not find any TMS effect at the noun. However, TMS had a short-lasting impact at the mid-sentence verb that differed for the two stimulation sites. Specifically, TMS over pIFG elicited a frontal positivity in the first 200 ms post verb onset whereas TMS over pSTG/STS was limited to a parietal negativity at 200-400 ms post verb onset. This indicates that during verb processing in sentential context, frontal brain areas play an earlier role than temporal areas in predicting the upcoming noun. The short-living perturbation effects at the mid-sentence verb suggest a high degree of online compensation within the language system since the sentence final noun processing was unaffected.
http://bit.ly/2HBNmGD
Statistical learning of speech regularities can occur outside the focus of attention
Publication date: Available online 28 January 2019
Source: Cortex
Author(s): Laura J. Batterink, Ken A. Paller
Abstract
Statistical learning, the process of extracting regularities from the environment, plays an essential role in many aspects of cognition, including speech segmentation and language acquisition. A key component of statistical learning in a linguistic context is the perceptual binding of adjacent individual units (e.g., syllables) into integrated composites (e.g., multisyllabic words). A second, conceptually dissociable component of statistical learning is the memory storage of these integrated representations. Here we examine whether these two dissociable components of statistical learning are differentially impacted by top-down, voluntary attentional resources. Learners' attention was either focused towards or diverted from a speech stream made up of repeating nonsense words. Building on our previous findings, we quantified the online perceptual binding of individual syllables into component words using an EEG-based neural entrainment measure. Following exposure, statistical learning was assessed using offline tests, sensitive to both perceptual binding and memory storage. Neural measures verified that our manipulation of selective attention successfully reduced limited-capacity resources to the speech stream. Diverting attention away from the speech stream did not alter neural entrainment to the component words or post-exposure familiarity ratings, but did impact performance on an indirect reaction-time based memory test. We conclude that theoretically dissociable components of statistically learning are differentially impacted by attention and top-down processing resources. A reduction in attention to the speech stream may impede memory storage of the component words. In contrast, the moment-by-moment perceptual binding of speech regularities can occur even while learners' attention is focused on a demanding concurrent task, and we found no evidence that the concentration of attention modulates this process. These results suggest that learners can acquire basic statistical properties of language without directly focusing on the speech input, potentially opening up previously overlooked opportunities for language learning, particularly in adult learners.
http://bit.ly/2SjTwiV
Neutrophil extracellular traps exert both pro- and anti-inflammatory actions in rheumatoid arthritis that are modulated by C1q and LL-37
Publication date: Available online 28 January 2019
Source: Journal of Autoimmunity
Author(s): Matthieu Ribon, Sarra Seninet, Julie Mussard, Mireille Sebbag, Cyril Clavel, Guy Serre, Marie-Christophe Boissier, Luca Semerano, Patrice Decker
Abstract
Objective
Neutrophil extracellular traps (NET), produced by activated polymorphonuclear neutrophils (PMN), are supposed to play a role in the pathogenesis of rheumatoid arthritis (RA), a chronic inflammatory autoimmune disease characterized by anti-citrullinated protein antibodies (ACPA). Indeed, NET contain citrullinated autoantigens and some RA autoantibodies recognize NET. However, the mechanisms by which NET trigger or perpetuate the inflammatory process in RA are hitherto not elucidated. We hypothesized that, in addition to citrullination, NET might also contain stimulatory proteins and directly activate inflammatory target cells, as PMN and macrophages.
Methods
NET antigenic and inflammatory properties were analyzed in 157 healthy donors (HD) and RA patients, the largest analysis reported so far. Primary PMN and monocyte-derived macrophages were isolated and immunoglobulin G (IgG) purified. NET were induced (NETosis), isolated and quantified. NET antigenicity was analyzed by fluorescence microscopy. PMN and macrophages were stimulated with NET with/without ACPA, C1q, LL-37 or lipopolysaccharide (LPS) and cell activation was estimated by flow cytometry and ELISA.
Results
PMN from RA patients produced more NET than HD PMN. We next dissected how NET mechanistically affect inflammatory cells. Particularly, we show for the first time that RA and HD NET activated both resting macrophages and PMN, but importantly RA NET were more stimulatory, leading to secretion of inflammatory cytokines and up-regulation of HLA/CD86/CD11b. IgG from ACPA-positive RA patients specifically recognized RA and even HD NET. Nevertheless, NET-induced cell activation occurs independently of immune complex formation with ACPA. Likewise, endosomal acidification was not required. Notably, we also report that complement C1q increased the NET stimulatory activity on macrophages only, due to higher expression of C1q receptors, which was further supported by the LL-37 antimicrobial peptide. In contrast, NET specifically inhibited interleukin (IL)-6 secretion by LPS-activated macrophages and not PMN, especially with C1q/LL-37. This inhibition was not mediated by NET-derived proteases or LPS neutralization and was associated with the simultaneous induction of IL-10 secretion.
Conclusion
We show that NET possess both pro- and anti-inflammatory properties depending on target cells, their activation levels and C1q/LL-37. Thus, independently of ACPA, NET modulate RA chronic inflammation via this new dual activity we identified. In addition, NET may trigger autoimmunity in RA as ACPA recognize NET antigens but not non-activated PMN. Therefore, we conclude that excess of NETosis together with enhanced NET activity participate to RA pathogenesis at different levels.
Graphical abstract
Dual activity of NET. Activated PMN enter NETosis in response to some stimuli. In RA, PMN are significantly more sensitive to NETosis triggering. These NET directly activate (pink arrows) steady state PMN (left) and macrophages (MΦ, right), leading to strong IL-8, TNF and IL-6 secretion (three important cytokines in RA) but low IL-10 induction, i.e. a pro-inflammatory profile. In addition, RA NET are significantly more stimulatory than normal NET. Although NET are recognized by ACPA, the resulting immune complexes do not clearly enhance PMN and MΦ response to NET. Likewise, endosomal TLR are probably not involved in NET sensing. Regarding MΦ, NET-induced activation is specifically increased in the presence of DNA-binding molecules like C1q and LL-37 (blue arrows). C1q in combination with LL-37 carry NET to PMN and MΦ which express surface C1q and LL-37 receptors (C1qR, LL-37-R). Because MΦ express much more C1qR than PMN, MΦ (and not PMN) activation by NET is enhanced by C1q or C1q/LL-37. On the contrary, NET induce an anti-inflammatory profile in strongly-activated MΦ but not PMN (green arrows). Indeed, NET specifically (partly) inhibit secretion of the pro-inflammatory cytokine IL-6 by MΦ in response to LPS, especially in the presence of both C1q and LL-37, and inversely enhance IL-10 secretion by those MΦ.
http://bit.ly/2DFZ2Uy
The microbiome and immunodeficiencies: Lessons from rare diseases
Publication date: Available online 28 January 2019
Source: Journal of Autoimmunity
Author(s): M. Pellicciotta, R. Rigoni, E.L. Falcone, S.M. Holland, A. Villa, B. Cassani
Abstract
Primary immunodeficiencies (PIDs) are inherited disorders of the immune system, associated with a considerable increase in susceptibility to infections. PIDs can also predispose to malignancy, inflammation and autoimmunity. There is increasing awareness that some aspects of the immune dysregulation in PIDs may be linked to intestinal microbiota. Indeed, the gut microbiota and its metabolites have been shown to influence immune functions and immune homeostasis both locally and systemically. Recent studies have indicated that genetic defects causing PIDs lead to perturbations in the conventional mechanisms underlying homeostasis in the gut, resulting in poor immune surveillance at the intestinal barrier, which associates with altered intestinal permeability and bacterial translocation. Consistently, a substantial proportion of PID patients presents with clinically challenging IBD-like pathology. Here, we describe the current body of literature reporting on dysbiosis of the gut microbiota in different PIDs and how this can be either the result or cause of immune dysregulation. Further, we report how infections in PIDs enhance pathobionts colonization and speculate how, in turn, pathobionts may be responsible for increased disease susceptibility and secondary infections in these patients. The potential relationship between the microbial composition in the intestine and other sites, such as the oral cavity and skin, is also highlighted. Finally, we provide evidence, in preclinical models of PIDs, for the efficacy of microbiota manipulation to ameliorate disease complications, and suggest that the potential use of dietary intervention to correct dysbiotic flora in PID patients may hold promise.
http://bit.ly/2UqOwGt
Optimum wavelength characteristics for phototherapy utilizing deep ultraviolet light-emitting diodes
Publication date: Available online 29 January 2019
Source: Journal of Dermatological Science
Author(s): Hideyuki Masuda, Makoto Kimura, Akimichi Morita
http://bit.ly/2MFnB6U
Patient Satisfaction with the Veteran’s Administration Teledermatology Service
Publication date: Available online 29 January 2019
Source: Journal of the American Academy of Dermatology
Author(s): Marissa L.H. Baranowski, Vijay Balakrishnan, Suephy C. Chen
Abstract
Background
Teledermatology is comparable to face-to-face visits in providing accurate diagnoses and effective treatments. However, there are limited data regarding patient satisfaction with teledermatology models that more directly convey provider recommendations to patients.
Objective
To assess patient satisfaction with the teledermatology service at the Atlanta Veterans Affairs Medical Center (AVAMC).
Methods
A cross-sectional, phone-based questionnaire study of 175 AVAMC teledermatology patients was performed to investigate patient satisfaction. Phase One (n=100) compared teleconsultative and models. Phase Two (n=75) compared patients who received one of three possible consult outcomes: (1) reassurance, (2) appointment for biopsy, or (3) appointment for face-to-face evaluation.
Results
There were no statistically significant differences in satisfaction between patients who were seen with the telemedicine and teleconsultative models. Patients who received appointments for face-to-face evaluation or biopsy were more satisfied than patients who received reassurance only. Both phases were remarkable for high patient satisfaction among all cohorts.
Limitations
This study was performed at a single VA medical center and is vulnerable to both non-response bias and recall bias.
Conclusion
Overall, patients are satisfied with teledermatology services at the AVAMC. Strong partnership with referring primary care providers and clear delineation of responsibilities is vital to the teledermatology process.
http://bit.ly/2WqSyAA
Age as key factor for pattern, timing and extent of distant metastasis in patients with cutaneous melanoma. A study of the German Central Malignant Melanoma Registry
Publication date: Available online 29 January 2019
Source: Journal of the American Academy of Dermatology
Author(s): Maximilian Gassenmaier, Ulrike Keim, Ulrike Leiter, Thomas K. Eigentler, Martin Röcken, Anja Gesierich, Rose K.C. Moritz, Lucie Heinzerling, Thomas Tüting, Uwe Wollina, Claus Garbe
Abstract
Background
Melanoma incidence rates rise as people age but the impact of aging on distant metastasis is unclear.
Objective
To investigate how timing, pattern and extent of distant metastasis is influenced by age.
Methods
Analysis of a single-center cohort of 1.457 patients of the German Central Malignant Melanoma Registry with prospectively documented follow-up. Findings were compared with those of 1.682 patients from five different institutions. All patients presented initially with stage IA – IIC and developed distant metastasis in their further course.
Results
The number of metastatic sites decreased with increasing age at melanoma diagnosis (p < 0.001). The rate of stage M1d decreased from 50.2% in patients ≤ 50 years to 30.1% in patients > 70 years and the rate of stage M1b increased from 5.8% to 21.5%. The rate of lung metastases remained stable in all investigated age groups (p = 0.54). Distant metastases occurred earlier and more synchronized in patients > 70 years compared with patients ≤ 50 years. The age-dependent decrease of metastatic sites and stable rate of lung metastasis were confirmed by the multi-institutional cohort.
Limitations
The study was not population-based.
Conclusion
Pattern, timing and extent of distant metastasis changes as people age. These findings may be considered when treating melanoma patients of different age.
http://bit.ly/2Rl7mN7
Patient-Reported Outcomes are Important Elements of Psoriasis Treatment Decision Making: A Discrete Choice Experiment Survey of Dermatologists in the United States
Publication date: Available online 29 January 2019
Source: Journal of the American Academy of Dermatology
Author(s): Steven R. Feldman, Stephane A. Regnier, Alexandra Chirilov, Felix Hey, Isabelle Gilloteau, David Cella
Abstract
Background
Psoriasis Area and Severity Index (PASI) response rates have been the benchmark for evaluating treatment efficacy in moderate-to-severe psoriasis trials.
Objective
Understand how dermatologists assess biologics and what trade-off rules they apply when planning psoriasis treatment.
Methods
Two online surveys of 130 and 129 U.S. dermatologists (Survey 1 and 2, respectively) were conducted using direct and indirect elicitation via discrete-choice experiment. Respondents were asked to choose hypothetical biologics based on six attributes (PASI 75 or 90 response rate, infection risk, dosing frequency, and three patient-reported outcomes [PROs] [relief of depression and itching, impact on usual activities]).
Results
Most dermatologists (Survey 1: 74%, Survey 2: 76%) reported using both PASI and PROs when selecting a biologic. PASI response rate was the most important attribute (35–38% of overall decision weight), while combined PRO attributes had similar importance (36% of decision weight). Infection risk and dosing frequency influenced the decision to a lesser extent.
Limitations
Potential bias in considering three PROs versus one PASI rate and one safety attribute.
Conclusion
PASI is most important for dermatologists selecting biologics, but PROs are also considered, especially when PASI response rate is similar between treatments. PRO data should be collected in moderate-to severe-psoriasis trials.
http://bit.ly/2WrNCLB
Fractionated de-volumizing Keloid tissue - The ‘pop’ method- A novel technique to facilitate administration of intralesional corticosteroid in difficult keloids
Publication date: Available online 29 January 2019
Source: Journal of the American Academy of Dermatology
Author(s): Rachita Dhurat, Sanober B. Daruwalla, Aseem Sharma
http://bit.ly/2RsdpQk
Treatment and survival of Merkel cell carcinoma since 1993: a population-based cohort study in the Netherlands
Publication date: Available online 29 January 2019
Source: Journal of the American Academy of Dermatology
Author(s): Sanne E. Uitentuis, Marieke W.J. Louwman, Alexander C.J. van Akkooi, Marcel Bekkenk
Abstract
Background
Merkel cell carcinoma (MCC) is a rare and potentially lethal skin-cancer. MCC is known for its potential rapid growth and its propensity to metastasise.
Objective
To describe the incidence, treatment and survival of MCC in a population-based setting.
Methods
All MCC's diagnosed in the Netherlands between 1993 and 2016 were selected from the Netherlands Cancer Registry. Patient and tumour characteristics, therapy and vital status were obtained. Cox' proportional hazards were computed and relative survival analyses were performed.
Results
Our cohort included 1977 patients with MCC. Incidence increased from 0.17/100,000 personyears in 1993 to 0.59/100,000 in 2016. The mean age at diagnosis was 75.5. Most MCC's (59.8%), were treated with surgery alone. Relative five-year survival was low (63.0%) and did not improve. Mortality was higher among males (HR: 1.24, 95%CI: 1.11-1.39), higher age (HR 1.07, 95%CI: 1.06-1.07) and nodal (HR1.26, 95%CI: 1.08-1.48) and distant spread of disease (HR2.44, 95%CI: 1.99-2.99).
Limitations
We lacked data on cause of death, comorbidity and pathological margins, which may have led to misinterpretation of the data.
Conclusion
This study shows continuously increasing incidence rates of MCC in the Netherlands. Survival after MCC diagnosis remained low. Our results emphasise the need for implementation of new therapies.
http://bit.ly/2WtJmLt
Corrigendum to 'Injection technique in neurotoxins and fillers: Indications, products, and outcomes' [J Am Acad Dermatol 79 (2018) 423–435]
Publication date: Available online 29 January 2019
Source: Journal of the American Academy of Dermatology
Author(s):
http://bit.ly/2RscRtK
“A Reliability Study Using Network-Oriented Research Assistant (NORA®) to Evaluate the Use of Digital Photographs in the Assessment of Atopic Dermatitis”
Publication date: Available online 29 January 2019
Source: Journal of the American Academy of Dermatology
Author(s): Meagan E. Hughes, Hilary Aralis, Kevin W. Bruhn, Jonathan Cotliar, Noah Craft, Ilana J. DeLuca, Reyhaneh Hamidi, Kathy Nguyen, Mayha Patel, Vishal A. Patel, Howard Sofen, Belinda H. Tan, Consuelo V. David
http://bit.ly/2Wo2nzf
Treatment of Morphea With Hydroxychloroquine: A Retrospective Review of 84 Patients at Mayo Clinic, 1996-2013
Publication date: Available online 29 January 2019
Source: Journal of the American Academy of Dermatology
Author(s): Anagha Bangalore Kumar, Elizabeth K. Blixt, Lisa A. Drage, Rokea A. el-Azhary, David A. Wetter
Abstract
Background
Few studies support treating morphea (localized scleroderma) with hydroxychloroquine.
Objective
To assess the efficacy of hydroxychloroquine treatment of morphea.
Methods
We conducted a retrospective study of 84 patients who had morphea and were treated with hydroxychloroquine monotherapy for at least 6 months at our institution from 1996 through 2013. The median times to initial and maximal responses were assessed.
Results
Of 84 patients (median age at diagnosis, 29.5 years), 65 (77.4%) were female; 36 (42.9%) had a complete response to hydroxychloroquine; 32 (38.1%) had a partial response greater than 50%; 10 (11.9%) had a partial response less than or equal to 50%; and 6 (7.1%) had no response. The median time to initial response was 4 months; the median time to maximal response was 12 months. Ten patients (11.9%) experienced adverse effects from hydroxychloroquine; the most common was nausea (6 patients).
Limitations
Retrospective study.
Conclusions
Hydroxychloroquine is a valuable treatment for morphea because of its high response rate and low rate of adverse effects; however, prospective studies are needed to determine its true efficacy.
http://bit.ly/2Rscmjm
Risk Factors for Keratinocyte Carcinoma Skin Cancer In Nonwhite Individuals: A Retrospective Analysis
Publication date: Available online 29 January 2019
Source: Journal of the American Academy of Dermatology
Author(s): Kumar S. Nadhan, Christina L. Chung, Erin M. Buchanan, Christine Shaver, Scott Shipman, Rina M. Allawh, Melissa L. Hoffman, Geoffrey Lim, Mark Abdelmalek, Carrie Ann Cusack
Abstract
Background
As the majority of the U.S. population will consist of nonwhite individuals by the year 2043, it is essential that both physicians and patients are educated about skin cancer in nonwhite individuals.
Objective
To update the epidemiology, investigate specific risk factors, and facilitate earlier diagnosis and intervention of KC in nonwhite individuals
Methods
IRB-approved retrospective chart review of all non-white individuals who had received a biopsy-proven diagnosis of skin cancer at Drexel Dermatology from June 2008 to June 2015.
Results
Squamous cell carcinoma (SCC) was the most commonly diagnosed skin cancer in Black and Asian populations, while basal cell carcinoma (BCC) was the most common skin cancer in Hispanics. Blacks exhibited the majority of their SCC lesions in sun-protected areas, particularly the anogenital area. On average, current smokers were diagnosed with skin cancer 12.27 years earlier than former smokers and 9.36 years earlier than nonsmokers.
Limitations
Single-center design and inter-practitioner variability of skin examination
Conclusions
The importance of photoprotection in nonwhite individuals should not go overlooked. However, emphasis should also be placed on active examination of sun-protected areas in nonwhites and recognition of the relationship between HPV and genital SCC lesions. Smoking cessation should be integrated in dermatologic counseling of all patients. Interventions tailored to each of these ethnic groups are needed.
http://bit.ly/2WrNI64
Telementoring and Smart-Phone-Based Answering Systems to Optimize Dermatology Resident Dermoscopy Education
Publication date: Available online 29 January 2019
Source: Journal of the American Academy of Dermatology
Author(s): Kelly C. Nelson, Jeffrey E. Gershenwald, Stephanie A. Savory, Janice M. Wilson, Julie M. Simon, Elizabeth M. Burton, Lauren E. Haydu
http://bit.ly/2RkuEms
Predictors of time to relapse following ustekinumab withdrawal in patients with psoriasis who had responded to therapy: An eight-year multicenter study
Publication date: Available online 29 January 2019
Source: Journal of the American Academy of Dermatology
Author(s): Hsien-Yi Chiu, Rosaline Chung-yee Hui, Tsen-Fang Tsai, Yang-Ching Chen, Nien-Feng Chang Liao, Po-Hua Chen, Po-Ju Lai, Ting-Shun Wang, Yu-Huei Huang
Abstract
Background
Data on predictors and time to relapse in psoriasis patients discontinuing therapy in a real world setting are scarce.
Objective
To investigate predictors of relapse after withdrawal of ustekinumab in psoriasis patients.
Method
This study screened 500 psoriasis patients who received ustekinumab (669 treatment episodes (TEs)) between 2011 and 2018. Overall, 202 patients (304 TEs), who had responded to therapy and were withdrawn from ustekinumab treatment, were included.
Results
The cumulative probabilities of relapse-free at 6 months, 12 months, 18 months, 24 months and 36 months of withdrawal from ustekinumab treatment was 49.3%, 12.6%, 5.3%, 4.7% and 1.6%, respectively. Multivariate regression analyses with a generalized estimating equation showed that after adjustments, biologics-naive, the maximum Psoriasis Area and Severity Index (PASI) improvement on ustekinumab, time to achieve PASI-50 after initiation of ustekinumab, family history of psoriasis, chronic kidney disease, and immunosuppressants use while off ustekinumab were significant predictors of time to relapse following ustekinumab discontinuation.
Limitation
Non-randomized allocation of duration of treatment and follow-up.
Conclusion
Given high rates of relapse, withdrawal of ustekinumab from patients with well-controlled psoriasis cannot be recommended.
http://bit.ly/2WsZTPP
Role of imaging in low grade cutaneous B-cell lymphoma presenting in the skin
Publication date: Available online 29 January 2019
Source: Journal of the American Academy of Dermatology
Author(s): M.K. Kheterpal, J. Dai, S. Geller, M. Pulitzer, Andy Ni, P.L. Myskowski, A. Moskowitz, J. Kim, E.K. Hong, S. Fong, R.T. Hoppe, Y.H. Kim, S.M. Horwitz
Abstract
Background
Whole body imaging is current standard of care for staging all patients presenting with skin lesion(s) of B-cell lymphomas (BCL), regardless of skin disease extent, however supporting data are lacking.
Objective
To determine the clinical utility of imaging in detection of systemic involvement in low grade cutaneous B-cell lymphoma presenting in the skin.
Methods
Retrospective cohort analysis of patients presenting with cutaneous lesions of BCLs at Memorial Sloan Kettering Cancer Center (MSKCC) and Stanford University (SU) from 1997-2016.
Results
At initial staging, of the 522 patients (306 marginal zone and 216 follicle-center cell histology), extracutaneous disease was noted in 3.6% and 8.8% of patients with MZL and FCL histology respectively. In patients with systemic involvement, imaging alone identified 81.8% (9/11) of MZL and 89.4% of follicular lymphoma (FL) cases. In primary cutaneous MZL (pc-MZL) and primary cutaneous follicle center lymphoma (pc-FCL), 1.7% and 3.0% subsequently developed extracutaneous involvement (median follow-up of 45 and 47 months respectively).
Limitations
Retrospective nature of this study.
Conclusions
Imaging is effective in identifying the patients with systemic involvement in indolent BCLs presenting in the skin, however incidence is low. After negative initial staging, pc-MZL patients may be followed clinically without routine imaging.
http://bit.ly/2ME9gI5
Investigation of the Skin Microbiome: Swabs vs Biopsies
Abstract
Background
Human skin is populated by diverse bacteria and there is increasing evidence that resident bacteria play a key role initiating immune responses in cutaneous diseases such as atopic dermatitis, psoriasis and hidradenitis suppurativa. Bacteria are present at all layers of the skin but many studies have relied on swabs to profile the skin microbiota. As the pathogenesis of many skin conditions is dermal, we wished to compare the microbiota obtained in swabs (surface) and biopsies (dermis).
Using 16S rRNA gene sequencing we established the microbial profiles of skin swabs and skin biopsies in sixteen subjects. We found differences in both diversity and taxonomic composition of the microbiome obtained from swabs and biopsies of the same individual. Several taxa were found to be more abundant in the swabs, which displayed significantly higher community richness, but Clostridiales and Bacteroidetes were significantly enriched in the biopsies.
The majority of published research on cutaneous microbiota has been based on skin swabs, which represent the surface of the skin. Our study demonstrated a clear difference between the microbiome observed in skin swabs and skin biopsies. These findings may be highly relevant in disorders such as psoriasis where pathogenesis arises in the dermis.
This article is protected by copyright. All rights reserved.
http://bit.ly/2CNq4I6
Inter‐Relater Reliability of Phenotypes, and Exploratory Genotype‐ Phenotype Analysis in Inherited Hidradenitis Suppurativa
Abstract
Background
Genotype‐phenotype correlation is a statistical relationship that measures correlation between the presence of a physical trait with a group of similar mutations but is dependent upon reliable phenotyping. It can provide information regarding disease pathogenesis, future disease progression, severity or activity. Such indicators would be valuable in Hidradenitis Suppurativa.
Aims and Methods
This study aimed to assess the inter‐rater reliability of hidradenitis suppurativa clinical phenotypes and perform exploratory genotype‐phenotype correlation in cases of hidradenitis suppurativa with identified sequence variants. Linkage disequilibrium between variants was assessed. Genotype‐Phenotype correlations were explored using Spearman correlation coefficients. Inter‐rater reliability was calculated using Cohen's kappa. Correlation between phenotype classifications was assessed using χ2 statistic.
Results
43 sequence variants with clinical information were identified. Clinical phenotypes were classified as LC2 (n=29, 67.4%), Scarring Folliculitis (n=18, 41.8%), atypical (n=38, 88.3%) and nodular (n=26, 60.5%). LC1 phenotype was associated with Regular (χ2=41.289, p<0.0001) and Typical (χ2=29.013, p<0.0001) phenotypes. Cohen's kappa was highest for Van der Zee (0.815), followed by Martorell (0.813), Naasan (0.774) and Canoui (0.435) classifications. High linkage disequilibrium was seen between variants of Han Chinese pedigrees. No significant genotype‐phenotype correlations were identified.
Conclusions
These findings may be influenced by selection, publication bias and the assumption that HS is a monogenic disorder. The poor inter‐rater reliability of existing phenotype measures suggests limited utility of existing measures. Further investigations into the correlation of clinical phenotypes with inflammatory biomarkers may aid in prognostic efforts for this disease.
This article is protected by copyright. All rights reserved.
http://bit.ly/2RV6eoS
Understanding economic evidence for the prevention and treatment of atopic eczema
Abstract
Background
Atopic eczema is an inflammatory skin condition, with a similar impact on health‐related quality‐of‐life as other chronic diseases. Increasing pressures on resources within the NHS increase the importance of having good economic evidence to inform their allocation. This paper aims to educate dermatologists about economic methods with illustration to currently available economic evidence on eczema.
Methods/design
The type and role of different types of economic evidence is illustrated by evidence found in a systematic literature search conducted across 12 online databases published until 22nd May 2017. Primary empirical studies either reporting the results of a cost of illness study or evaluating the cost, utility or full economic evaluation of interventions for preventing or treating eczema were included. Two reviewers independently assessed studies for eligibility and performed data abstraction, with disagreements resolved by a third reviewer. Evidence tables of results were produced for narrative discussion. The reporting quality of economic evaluations was assessed.
Results
78 studies (described in 80 papers) were deemed eligible. 33 (42%) were judged to be economic evaluations, 12 (15%) cost analyses, 6 (8%) utility analyses, 26 (34%) cost‐of‐illness studies and 1 feasibility study (1%). The calcineurin inhibitors: tacrolimus and pimecrolimus, as well as barrier creams had most economic evidence available. Partially hydrolysed infant formula was the most commonly evaluated prevention.
Conclusions
The current level of economic evidence for interventions aimed at preventing and treating eczema is limited compared to that available for clinical outcomes suggesting that greater collaboration between clinicians and economists might be beneficial.
This article is protected by copyright. All rights reserved.
http://bit.ly/2CNqoXk
Indirect immunofluorescence in mucous membrane pemphigoid: which substrate should be used?
Abstract
detection of circulating autoantibodies in mucous membrane pemphigoid (MMP) is challenging. Kamaguchi et al showed that using normal human oral mucosa (NHOM) as a substrate for indirect immunofluorescence (IIF) instead of normal human skin (NHS) or salt‐split‐skin (SSS) resulted in increased sensitivity.1 We recently conducted a similar study in our department.
We collected serum samples from 22 patients with oral MMP. Diagnosis was made upon histopathology consistent with a subepithelial blistering process and direct immunofluorescence (DIF) showing linear IgG, IgA and/or C3 deposits at the basement membrane zone (BMZ). Serum levels of anti‐BP180 NC16A and BP230 autoantibodies were assessed by Enzyme‐Linked‐Immunosorbent‐Assay. IIF was performed on monkey oesophagus (MO), on SSS and NHOM as previously described.
This article is protected by copyright. All rights reserved.
http://bit.ly/2RTb99E
Fibroblasts activation and abnormal extracellular matrix remodelling as common hallmarks in three cancer‐prone genodermatoses
Summary
Background
Recessive dystrophic epidermolysis bullosa (RDEB), Kindler syndrome (KS) and Xeroderma pigmentosum C (XPC) are three cancer‐prone genodermatoses whose causal genetic mutations cannot fully explain, on their own, the array of associated phenotypic manifestations. Recent evidence highlights the role of the stromal microenvironment in the pathology of these disorders.
Objectives
To investigate, by means of comparative gene expression analysis, the role played by dermal fibroblasts in the pathogenesis of RDEB, KS and XPC.
Methods
We conducted RNA‐Seq analysis that included a thorough examination of the differentially expressed genes, a functional enrichment analysis and a description of affected signalling circuits. Transcriptomic data were validated at the protein level in cell cultures, serum samples and skin biopsies.
Results
Inter‐disease comparisons against control fibroblasts revealed a unifying signature of 186 differentially expressed genes and 4 signalling pathways in the three genodermatoses. Remarkably, some of the uncovered expression changes suggest a synthetic fibroblast phenotype characterized by the aberrant expression of extracellular matrix (ECM) proteins. Western blot and immunofluorescence in situ analysis validated the RNA‐Seq data. In addition, enzyme‐linked immunosorbent assay (ELISA) revealed increased circulating levels of periostin in RDEB patients.
Conclusions
Our results suggest that the different causal genetic defects converge into common changes in gene expression, possibly due to injury‐sensitive events. These, in turn, trigger a cascade of reactions involving the abnormal ECM deposition and under‐expression of antioxidant enzymes. The elucidated expression signature provides new potential biomarkers and common therapeutic targets in RDEB, XPC and KS.
This article is protected by copyright. All rights reserved.
http://bit.ly/2CRMKXz
Sonic Hedgehog Pathway Inhibitors: from Clinical Trials to Clinical Practice
Abstract
Basal cell carcinoma (BCC) is the most common malignancy. It can rarely become locally advanced (laBCC) or metastasize (mBCC). For recurrent, inoperable, laBCC and/or mBCC, Sonic Hedgehog (Shh) pathway inhibitors, vismodegib and sonidegib, are treatment options. This case series evaluates limitations surrounding their use in clinical practice.
This was an IRB‐approved retrospective case series of BCC treatment with vismodegib and/or sonidegib at our institution between January 2006 and March 2017, with follow‐ up through August 2018. Patients receiving concurrent Shh inhibitors and radiotherapy were excluded. The examined outcomes included clinical response, progression free survival (PFS), drug holidays (DH), and adverse effects (AE).
This article is protected by copyright. All rights reserved.
http://bit.ly/2RV5XSS
Screening for hepatitis B virus and tuberculosis infection in patients with moderate‐to‐severe psoriasis recruiting for biologic therapy in China
Abstract
Biologics have greatly advanced the therapy of moderate‐to‐severe psoriasis. Screening for Hepatitis B virus (HBV) and tuberculosis (TB) infection is mandatory before biologic therapy to avoid the risk of active infection, which is more likely to be disseminated, fulminant and fatal. Testing and treatment for latent TB infection (LTBI) in at‐risk populations is strongly recommended by recent WHO's guidelines.1 Both HBV and TB infection are endemic in China and also represent important issues for global public health. The purpose of this study was to describe the screening results of HBV and TB infection in patients with moderate‐to‐severe psoriasis in China, which has not been reported.
This article is protected by copyright. All rights reserved.
http://bit.ly/2CTHyCR
Experience of skin disease and relationships with healthcare providers: a qualitative study of Traveller women in Ireland
Abstract
Background
Significant health disparities exist between members of the Travelling community and that of the general population. Barriers to Traveller engagement with health services include the experience or perception of discrimination, cultural and health literacy barriers. Experience of skin disease and interactions with healthcare providers has not been widely explored among this ethnic minority. The formation of positive relationships between the Travelling community and healthcare providers is important in the promotion of treatment adherence and improving health outcomes.
Objectives
We aimed to investigate Travellers' experience of skin disease and their relationships with healthcare providers.
Methods
Focus groups were conducted with a purposive sample of female members of the Irish Travelling community with experience of skin health issues, between January 2018 and April 2018. Three focus groups were conducted at three separate locations with ten participants in each group. Themes were identified from the focus group transcripts using an inductive thematic analysis framework.
Results
Emergent themes surrounding relationships between Travellers and healthcare providers included health literacy, discrimination, information inconsistency, trust and communication. Factors that were valued in the creation of positive relationships included an appreciation of varying degrees of health literacy, the provision of sufficient information tailored to an individual's needs and a demonstration of cultural competence.
Conclusion
Dermatologists are well placed to provide practical, customised, treatment guidance and engage patients while integrating their culturally based beliefs.
This article is protected by copyright. All rights reserved.
http://bit.ly/2RTb9qa
ERYTHEMA MULTIFORME: DIFFERENCES BETWEEN HSV‐1 AND HSV‐2 AND MANAGEMENT OF THE DISEASE ‐ A CASE REPORT AND MINI REVIEW
ABSTRACT
Erythema multiforme (EM) is an immune‐mediated reaction characterized by target lesions and with possible mucosal involvement. Its most frequent cause is HSV, with HSV‐1 more common than ‐2. It is usually self‐limited but it can show recurrences. We report a peculiar case of recurrent herpes‐associated erythema multiforme (HAEM) in a 35‐year old man. The patient was affected by both herpes labialis and genitalis, but the typical target lesions were only associated with recurrent herpes labialis. Here we hypothesize about the pathogenic differences between HSV‐1 and ‐2 and discuss the therapeutic management of HAEM.
This article is protected by copyright. All rights reserved.
http://bit.ly/2FVsRTK
Complete resolution of cutaneous larva migrans with topical ivermectin: A case report
Abstract
Cutaneous larva migrans (CLM) (also called creeping eruption) is a cutaneous ectoparassitosis commonly observed in tropical countries. It is characterized by an erythematous, pruritic, and raised lesion with linear or serpiginous distribution, typically localized at the lower extremities. Oral ivermectin represents the most recommended current treatment, with important adverse effects associated. We report the clinical case of a 52‐year old with CLM, successfully treated with topical ivermectin.
This article is protected by copyright. All rights reserved.
http://bit.ly/2FWEbP8
THE ANALYSIS OF THE THERAPEUTIC POTENTIAL OF USTEKINUMAB IN PSORIASIS VULGARIS TREATMENT
Abstract
The molecular mechanism of ustekinumab action involves an interruption of signaling pathways activated by IL‐12/23.
The aim of this paper was to evaluate the efficacy of the anti‐IL12/23 therapy in 7 psoriatic patients by assessing changes in the values of PASI, DLQI, BSA indexes, and an analysis of changes in the mRNA expression profile of genes IL12A, IL12B, IL23A during three 40‐week long observation periods.
The clinical (PASI, DLQI, BSA indexes) and molecular (RTqPCR for IL12A, IL12B, IL23A) analyses were performed on the day of ustekinumab therapy initiation, 4 weeks post first administration, and every 12 weeks thereafter. The statistically significant differences were observed only during stage I for values of PASI (p=0.0134), DLQI (p=0.01299), BSA (p=0.0355). During the subsequent stages, we observed lower values of PASI, BSA indexes, which suggests that the lesions are less intensified than at the moment of the therapy commencing. The relationship between the selected genes was observed: IL23A>IL12A>IL12B.
In conclusion, the aforementioned clinical and molecular analysis suggests the efficacy of ustekinumab therapy in patients with psoriasis vulgaris can be analyzed with the PASI, BSA, DLQI indexes, and changes in the expression of selected genes. The analysis of IL12A, IL12B, IL23A expression may serve as a valuable supplementation for the therapeutic methods currently used to evaluate the degree of disease progression and treatment efficacy.
This article is protected by copyright. All rights reserved.
http://bit.ly/2FVnfsn
Treatment of Telogen Effluvium using a dietary supplement containing Boswellia serrata, Curcuma longa and Vitis Vinifera: results of an observational study
Abstract
Telogen effluvium (TE) is a diffuse hair loss characterized by shortening of the anagen phase and precipitation of the telogen phase, with consequent reduction of the total hair volume. Many supplements are used in order to counteract TE but a definitive therapy is still unavailable.
27 patients, 4 males and 23 females, aged between 19 and 76 have been enrolled in this open study. All were diagnosed with telogen effluvium hair loss pattern. They were asked to take a supplement containing Boswellia Serrata, Curcuma Longa and Vitis Vinifera for a period of 3 months. The aim of the study was to evaluate the synergistic effect of these plant extracts in the treatment of TE.
The results obtained, although non statistically significant, show an overall improvement of clinical and subjective evaluations of the disease, although a larger study with a bigger sample may be required to better understand the real effects of this plant extracts in TE
The results obtained in this study suggest that the products tested have an eutrophic effect on scalp hair, and we believe that this supplement may determine anti‐oxydant, angiogenic and hair stimulating properties.
This article is protected by copyright. All rights reserved.
http://bit.ly/2G4ZHAK
Hidradenitis Suppurativa and Botulinum Toxin Type a Therapy: Two Cases
Abstract
Hidradenitis suppurativa is a chronic skin disease with an intense inflammatory activation. It typically affects the intertriginous areas with cysts, fistulae and scarring extremely painful. Patients suffer from severe psychological impact. HS still results in a high unmet medical need with several underdiagnosed cases, probably due to the incomplete knowledge of the pathogenesis of HS. The use of botulinum toxin a has recently been proposed as an effective therapy for HS.
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http://bit.ly/2FVUDz9
Current and Emerging Therapies for Hand Eczema
Abstract
Purpose
Though hand eczema (HE) and chronic hand eczema (CHE) are common conditions with significant disease burden, they traditionally have had limited treatment options beyond topical and short‐term systemic corticosteroids. We reviewed published and preliminary evidence on the current and emerging topical and systemic therapeutic agents for HE and CHE. The etiologies of various HE subtypes are discussed, and remaining knowledge and practice gaps are highlighted to encourage further investigations.
Material and Methods
A comprehensive search of ClinicalTrials.gov and PubMed was completed for clinical trials that utilized known and emerging treatment options for HE and CHE.
Results
Several agents that target IL‐4 and IL‐13 signaling, keratinocyte proliferation, inflammatory cytokine production, bacterial protein synthesis, and inflammatory mediator (TNF‐ α, JAK1, JAK2, JAK3) proliferation are shown to be involved in the pathogenesis of CHE. Systemic agents include dupilumab, alitretinoin, acitretin, cyclosporine, azathioprine, and probiotics. Topical agents include delgocitinib, retapamulin, halometasone/triclosan, calcipotriol/betamethasone, tacrolimus, and pimecrolimus. These modalities have demonstrated varying degrees of clinical efficacy, evaluated by subjective assessments and scoring indexes.
Conclusions
Targeted therapies are emerging for HE, but options are still limited, partially due to our narrow understanding of this heterogeneous condition. Additional and targeted therapeutic options are needed to match the rising prevalence and burden of HE.
This article is protected by copyright. All rights reserved.
http://bit.ly/2Gdg2DF
Treatment resistant impetigo herpetiformis treated with infliximab
Abstract
Impetigo herpetiformis is a rare disease of pregnancy with the onset being in the second half of pregnancy and resolution after delivery. It is associated with a high rate of perinatal mortality and fetal abnormalities. Clinical and histological features of the disease are consistent with pustuler psoriasis. We reported a case of 25‐year‐old female gravida 1 para 0, who responded poorly to consecutively treatments with systemic steroids, cyclosporine, intravenous immunoglobulin, and acitretin. Good response was obtained with adding infliximab to the treatment.
This article is protected by copyright. All rights reserved.
http://bit.ly/2FUQsng
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