Πέμπτη 8 Φεβρουαρίου 2018
Pruritic arthropod bite-like papules in T-cell large granular lymphocytic leukaemia and chronic myelomonocytic leukaemia
Summary
T-cell large granular lymphocytic leukaemia (T-LGLL) is a clinically indolent mature T-cell neoplasm characterized by a monoclonal population of CD3+ CD8+ cytotoxic T cells, which usually presents as neutropenia, anaemia and thrombocytopenia. Chronic myelomonocytic leukaemia (CMML) is a clonal haematopoietic disorder with features of both a myeloproliferative neoplasm and myelodysplastic syndrome (MDS). Patients with CMML exhibit a persistent peripheral blood monocytosis in addition to myelodysplastic features. Because of the rarity of T-LGLL, its cutaneous manifestations are poorly documented, but include vasculitis, vasculopathy, persistent ulcerations, generalized pruritus and disseminated granuloma annulare. Various types of skin lesions have been observed in patients with CMML and reportedly occur in approximately 10% of cases. We report the extraordinary case of a patient with MDS who developed T-LGLL, and subsequently the MDS progressed to CMML. The patient then developed diffuse arthropod bite-like papules and intractable pruritus.
Involvement of spinal cannabinoid receptors in the antipruritic effects of WIN 55,212-2, a cannabinoid receptor agonist
Summary
Background
Cannabinoids have been used for their analgesic and euphoric effects for millennia, but recently the antipruritic effects of cannabis have been discovered. Considering the similarities between pain and itch sensations, we hypothesized that cannabinoid receptors may play a role in the antipruritic effects of cannabinoids.
Aim
To analyse the role of the spinal cannabinoid receptors, CB1 and CB2, in the antipruritic effects of the cannabinoid agonist WIN 55,212-2.
Methods
Male Balb/c mice weighing 20–30 g were used. Scratching behaviour in the mice was produced by injection of serotonin 5 μg/50 μL intradermally into the nape of the neck. Scratching of the site of injection by the hind paws was video-recorded for 30 min. After testing different doses of WIN 55,212-2 [1, 3 and 10 mg/kg intraperitoneally (IP)], the effects of the CB1 receptor antagonist, AM-251 [1 μg/mouse administered intrathecally (IT)] and the CB2 receptor antagonist AM-630 (4 μg/mouse IT) on the antipruritic effects of WIN 55,212-2 were studied using a rotarod apparatus.
Results
WIN 55,212-2 (1, 3 or 10 mg/kg IP) dose-dependently decreased serotonin-induced scratches. The receptor antagonist CB1 partially reversed the effects of WIN 55,212-2 (P < 0.05); whereas CB2 had no statistically significant effect. WIN 55,212-2 impaired motor function only at the highest dose given (10 mg/kg, P < 0.05).
Conclusions
Our findings support prior researches indicating that cannabinoids exert antipruritic effects. Moreover, our results show that the antipruritic effects of cannabinoids are partially mediated by spinal CB1 receptors.
Alternative activation of hedgehog pathway induced by ultraviolet B radiation: preliminary study
Summary
Background
There is still much ambiguity in studies of Sonic hedgehog (Shh) pathways and its dysregulation. Some studies concerning the role of the Shh pathway in basal cell carcinoma (BCC) have been conducted, but there is a lack of studies about Shh pathway dysregulation under the influence of ultraviolet (UV)B radiation.
Aim
To evaluate skin expression of Shh, Ptch1, Ptch2, Smo and Gli1 proteins in BCCs with and without the influence of UVB radiation.
Methods
In total, 34 healthy controls (HCs) and 42 patients with nodular BCC were recruited into the study. Patients were divided into five groups (A–E), depending on UVB dose received and BCC status. In all skin specimens, expression of Shh, Ptch1, Ptch2, Smo and Gli1 protein was evaluated.
Results
Comparing the BCC group with the HC group, there was significantly higher expression of Shh, Ptch1, Ptch2, Smo and Gli1 proteins. Expression of Ptch2, Smo and Gli1 was increased in response to UVB doses of 3 MED (minimal erythema dose), whereas expression of Ptch1 and Shh was unaffected.
Conclusion
The lack of change in expression of Shh and Ptch1 after exposure to UVB suggests that the Shh pathway may be activated through a noncanonical pathway under the influence of strong UVB doses.
Systemic allergic contact dermatitis associated with topical diltiazem and/or cinchocaine
Abstract
Topical anesthetics for the treatment of anal fissures or hemorrhoids are a frequent cause of allergic contact dermatitis (ACD) in the perianal region1. Since 2009, a few cases have been reported also to the calcium channel blocker diltiazem2,3,4 used as a first-line agent in the treatment of anal fissures. We present a case of ACD from diltiazem and/or cinchocaine followed by systemic contact dermatitis (SCD).
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A retrospective case series of referrals to our psychodermatology clinic 2009-2016
Abstract
Psychodermatology is a relatively new subspecialty exploring the interaction between skin and the mind. Managing patients in this cohort can be challenging1,2,3. The aetiology of psychocutaneous disease is often complex, ranging from solely functional skin-directed symptoms (psychogenic pruritis), to thought disorders manifesting in a cutaneous fashion (delusional parasitosis), to factitious disorders with cutaneous consequences (e.g. dermatitis artefacta). In addition, purely psychiatric conditions (i.e. substance misuse, depression or obsessive compulsive disorder), may occur alongside dermatological disease, further complicating successful management.
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High Surface Area SnO2-Ta2O5 Composite for Visible Light Driven Photocatalytic Degradation of an Organic Dye
Abstract
SnO2-Ta2O5 nanocomposite was synthesised by a facile co-precipitation method and further calcined to obtain crystalline powder. Phase formation, morphology, bandgap and photo-catalytic properties were analysed using powder X-ray diffraction, Scanning electron microscopy, UV-Vis diffused reflectance spectroscopy, BET surface area and Raman spectroscopy respectively. Effect of calcination temperature on the crystallinity of the composite was studied. The as prepared samples of SnO2, Ta2O5 and SnO2-10wt%Ta2O5 composite as well as the calcined composite sample were tested for photocatalytic activity for methylene blue dye degradation under visible light. Photocatalytic studies reveal that, the as prepared SnO2-10wt%Ta2O5 composite showed the best photocatalytic activity for the degradation of Methylene Blue (MB) by harvesting visible light radiation efficiently. Further mineralisation of methylene blue, estimated by COD analysis, is found to have degraded with an efficiency of 91.6%. The study demonstrates that heterostructure of SnO2-Ta2O5 nanocomposite could be applied in photocatalytic purification of organic pollutants.
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Anti-photoaging Effect of Prunus yeonesis Blossom Extract via Inhibition of MAPK/AP-1 and Regulation of the TGF-βI/Smad and Nrf2/ARE Signaling Pathways
Abstract
Cherry blossoms have attracted attention as an ingredient with potential for use in skincare products. However, no skin photoaging-related research has been performed with this plant. In the present study, cherry blossom extract (CBE) at 1, 10, and 100 μg/mL was investigated for its skin anti-photoaging effects in UVB-irradiated normal human dermal fibroblasts (NHDF) cells in vitro. Our results showed that CBE markedly increased type I procollagen during UVB exposure via two pathways. Firstly, transcription activator protein-1 expression and MAP kinases were downregulated, consequently reducing the production of matrix metalloproteinase (MMP)-1 and MMP-3. Secondly, transforming growth factor TGF-βI secretion was upregulated by Smads. Application of CBE facilitated the nuclear translocation of Nrf2 against reactive oxygen species (ROS)-induced damage, which is essential for the coordinated induction of cytoptotective enzymes. Together, our findings suggest that CBE may be a promising ingredient for skin aging therapy and provide a novel approach for alleviating cutaneous aging.
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Effects of Repeated UVA Irradiation on Human Skin Fibroblasts Embedded in 3D Tense Collagen Matrix
Abstract
Skin photoaging is caused by cumulative UVA exposure that leads to dermal matrix alterations associated with impaired fibroblast functions. In this study, we evaluated the effects of repeated UVA irradiation on mechanically stressed fibroblasts which were embedded in 3D tense collagen matrix. By comparison to 2D monolayer culture, we investigated the expressions of alpha smooth muscle actin (α-SMA) cytoskeleton and α2 subunit of integrin receptors, as well as the collagen metabolism, focusing to MMP-1 and collagen type I expressions. We found that UVA exposure reduces collagen levels in both culture conditions. However, concerning integrin α2 and α-SMA expression, UVA irradiation had no effect on 2D culture, whereas in tense 3D culture, it had an inhibitory effect. In UVA-irradiated 3D culture, fibroblasts acquired elongated shape and lost their dynamic interaction with collagen fibers through a decrease of integrin α2 and α-SMA. Fibroblast responses to UVA irradiation were different in 2D versus 3D environment, highlighting the importance of collagen environment in the regulation of mechanical activities. The behavior of fibroblast upon mechanical stimulation closely mimics stressed extracellular environment. The model of UVA-irradiated fibroblasts cultured in tense 3D collagen gel illustrated the in vivo situation of both mechanically stressed and photoaged human skin.
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Validation of Questionnaire and Diary Measures of Time Outdoors Against an Objective Measure of Personal Ultraviolet Radiation Exposure
Abstract
Self-reported sun exposure is commonly measured using questionnaires or diaries, but there are limited data on their validity, particularly for population subgroups. This research aimed to compare self-reported sun exposure, measured as 1) habitual time outdoors over the past month on weekends and weekdays, and 2) a four-day diary measure, against objective measurement of personal ultraviolet radiation using polysulfone film dosimeters. From November 2015 to January 2016, 94 people (22-69 years and living in New South Wales, Australia) completed a questionnaire, 4-day diary and 4-day dosimeter measures of overall, weekday and weekend sun exposure. Spearman correlations and Bland-Altman plots were used to measure agreement. The overall weekly correlation was 0.57 (95% confidence interval [CI] 0.44, 0.68) between standard erythemal doses (SEDs) measured by dosimeter and time spent outdoors measured by questionnaire, 0.74 (95% CI 0.66-0.81) between dosimeter and diary, and 0.59 (95% CI 0.48-0.68) between questionnaire and diary measures. Validity was lower for younger people and weekend sun exposure. There was strong correlation between dosimeter and sun diary measures and moderate correlation between dosimeter and questionnaire measures. Daily measurement over a longer period may be required to accurately capture week-long sun exposure in all population subgroups.
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Heat shock protein 90 inhibitor enhances apoptosis by inhibiting the AKT pathway in thermal-stimulated SK-MEL-2 human melanoma cell line
: Heat shock proteins (Hsps) are chaperone proteins, which are upregulated after various stresses. Hsp90 inhibitors have been investigated as adjuvant therapies for the treatment of melanoma. Thermal ablation could be a treatment option for surgically unresectable melanoma or congenital nevomelanocytic nevi, however, there is a limitation such as the possibility of recurrence.
Assessment of progeny concentrations of 222 Rn/ 220 Rn and their related doses using deposition-based direct progeny sensors
Abstract
Indoor radon and thoron concentrations in the domestic environment result in natural radiation exposure to the public due to the inhalation of their short-lived decay products. Keeping this in view, the annual effective dose and other radiation risks due to radon/thoron progenies have been calculated. In this study, newly developed time deposition-based progeny sensors (DTPS/DRPS) were used for long-term passive determination of progeny concentrations in the environment of Jammu and Kashmir, Himalayas, India. The total equilibrium equivalent radon (EECRA + U) and thoron (EECTA + U) concentrations ("A" and "U" referring to attached and unattached fractions) were found to vary from 5 to 38 Bq m−3 with an average value of 18 Bq m−3 and from 0.48 to 5.49 Bq m−3 with an average value of 1.69 Bq m−3, respectively. The aerosol concentration, equilibrium factors, and unattached fractions for radon and thoron progeny have been estimated in normal living conditions and their dependence on each others have also been studied. The annual equilibrium factor for radon and thoron progeny has been determined from the calculated data. The estimated annual effective dose due to radon progeny (0.34 to 2.42 mSv y−1) and thoron progeny (0.13 to 1.54 mSv y−1) is found to be below the world's recommended level. Based on measurements of mean values of the unattached fraction, dose conversion factors (DCFs) in units of mSv per working level month (WLM) has been calculated and the average calculated values of DCFs are 24, 10, and 13 mSv WLM−1. The variability of equilibrium factor and radon/thoron progeny with different seasons, ventilation conditions, and types of houses were also analyzed.
Treatment of soak liquor and bioelectricity generation in dual chamber microbial fuel cell
Abstract
The discharge of untreated soak liquor from tannery industry causes severe environmental pollution. This study is characterizing the soak liquor as a substrate in the microbial fuel cell (MFC) for remediation along with electricity generation. The dual chamber MFC was constructed and operated. Potassium permanganate was used as cathode solution and carbon felt electrode as anodic and cathodic material, respectively. The soak liquor was characterized by electrochemical studies viz., cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS), and polarization studies, respectively. The removal percentage of protein, lipid, and chemical oxygen demand (COD) were measured before and after treatment with MFC. The results of MFC showed a highest current density of 300 mA/cm2 and a power density of 92 mW/m2. The removal of COD, protein, and lipid were noted as 96, 81, and 97% respectively during MFC process. This MFC can be used in tannery industries for treating soak liquor and simultaneous electricity generation.
Probing the toxic mechanism of bisphenol A with acid phosphatase at the molecular level
Abstract
As an endocrine-disrupting chemical, bisphenol A (BPA), can affect normal endocrine function of hormone. This paper studied the toxic effect of BPA on acid phosphatase at the molecular level by multi-spectroscopic measurements, molecular docking, and enzyme activity experiment. BPA could enhance the fluorescence intensity, change the structure, and cause an increased hydrophobicity of acid phosphatase. Hydrogen bond interaction and van der Waals forces were the main forces to generate the BPA-acid phosphatase complex on account of the negative ΔH (− 36.92 kJ mol−1) and ΔS (− 50.78 J mol−1 K−1). BPA led to the loosening and unfolding of protein structure and extending the peptide strands, as revealed by UV-vis absorption and CD spectra. Based on the enzyme activity experiment, BPA could decrease the activity of the acid phosphatase by entering the active site of the enzyme. The molecular docking model showed that BPA could bind into the cavity of acid phosphatase and interact with Tyr A252 and a hydrogen bond (1.47 Å) was formed in the binding process. This work suggested the structures and functions of acid phosphatase were both affected by BPA.
Occurrence and molecular characterization of Giardia duodenalis cysts and Cryptosporidium oocysts in raw water samples from the Rímac River, Peru
Abstract
Giardia and Cryptosporidium are potentially pathogenic protozoa which are ubiquitous in ambient surface water. The present study included 60 samples of surface water from three sampling sites from the Rímac River, Lima and Callao, Peru, to detect the occurrence of Giardia spp. and Cryptosporidium spp. and to perform molecular characterization of specimens found. Water samples were concentrated using the membrane filtration technique, and following elution, cysts and oocysts were visualized by direct immunofluorescence assay (IFA). For molecular characterization, tpi and bg gene fragments and 18S rRNA were amplified by nested PCR for Giardia and Cryptosporidium, respectively, followed by sequencing and phylogenetic analysis. Giardia cysts were found in 93.3% of the analyzed samples, whereas Cryptosporidium oocysts were detected in 15%. The positivity of the Giardia cysts was 86.6% (n = 26) in 2014, while Cryptosporidium oocysts were not detected. In 2015, both protozoa were found in raw water samples, with all 30 samples collected positive for Giardia cysts (100.0%) and 9 positive for Cryptosporidium oocysts (30.0%). Oocysts were detected in 20.0% of water samples from sites 1 (mean 5.25 oocysts/L) and 2 (mean 52.3 oocysts/L), while at site 3, oocysts were detected in 50.0% of raw water samples (mean 193.6 oocysts/L). The presence of Giardia duodenalis assemblage A was confirmed in several samples by the phylogenetic positioning of the bg and tpi genes, and the sub-assemblage AII was predominant (8/9). Sequencing for Cryptosporidium resulted in profiles compatible with Cryptosporidium hominis, Cryptosporidium meleagridis, and Cryptosporidium baileyi. This is the first time that the presence of G. duodenalis assemblage A/sub-assemblage AII and Cryptosporidium species has been reported in surface water samples in Peru. These Cryptosporidium species and the Giardia duodenalis assemblage are associated with human disease which highlights the potential risk to public health and the need to increase environmental monitoring measures to protect this water body.
Antimicrobial Photodynamic Therapy as a Co-adjuvant in Endodontic Treatment of Deciduous Teeth: Case Series
Abstract
To assure the success of endodontic treatment, the root canal must be completely decontaminated. Thus, some methods have been researched in an attempt to effectively eliminate microorganisms from the interior of the root canal system. Among them, is conventional endodontic therapy in conjunction with photodynamic therapy (PDT). Five anterior deciduous teeth were treated endodontically with the conventional technique and PDT. For PDT, 0.005% methylene blue was used as a photosensitizer and a 660nm laser. After the conventional endodontic therapy, the photosensitizer was applied inside the root canal, 3 minutes of pre-irradiation time and then the laser was applied for 40s with an energy of 4J. Afterwards, the canal was irrigated with saline solution and the sealing material of the root canal was placed. The microbiological analysis of the samples were collected before and after the treatments were performed. Observing the results obtained in this case series,which showed a bacterial reduction from 37.57% to 100%, and the clear difficulty in the success of endodontic treatment of deciduous teeth, antimicrobial photodynamic therapy can be considered an alternative of easy application, and that does not generate microbial resistance, to act as a support in the decontamination of the root canals.
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Absorption Characteristics and Quantum Yields of Singlet Oxygen Generation of Thioguanosine Derivatives
Abstract
6–Thioguanine (1a) is considered to be photochemotherapeutic agents due to its specific characteristics of photosensitivity to UVA light and singlet molecular oxygen generation. To extend its phototherapeutic ability, two related thioguanines, 8–thioguanine (2a) and 6,8–dithioguanine (3a), have been designed and explored. Since the solubility of these thioguanines in dehydrated organic solvents is too poor to study, their tri–acetyl–protected ribonucleosides, i.e. 2',3',5'–tri–O–acetyl–6–thioguanosine (1c), 2',3',5'–tri–O–acetyl–8–thioguanosine (2c) and 2',3',5'–tri–O–acetyl–6,8–dithioguanosine (3c) were prepared and investigated. The absorption maxima of 1c, 2c and 3c in acetonitrile were found at longer wavelengths than that of un–thiolated guanosine (4c). Especially, 3c has the longest wavelength for absorption maximum and the highest value in terms of molar absorption coefficient among all thio–nucleobases and thio–nucleosides reported. These absorption properties were also well reproduced by quantum chemical calculations. Quantum yields of singlet oxygen generation of 2c and 3c were determined by near–infrared emission measurements to be as large as that of 1c. These results suggest that the newly synthesized thioguanosines, in particular 3c, can be further developed as a potential photosensitive agent for light–induced therapies.
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Is Antimicrobial Photodynamic Therapy Effective for Microbial Load Reduction in Peri-implantitis Treatment? A Systematic Review and Meta-Analysis
Abstract
The systematic review and meta-analysis were undertaken to evaluate the effectiveness of antimicrobial photodynamic therapy (aPDT) in the microbiological alteration beneficial to peri-implantitis treatment. This study is registered with PROSPERO, number CRD42017064215. Bibliographic databases including Cochrane Library, Web of Science, Scopus and PubMed were searched from inception to January 8, 2017. The search strategy was assembled from the following MeSH-Terms: "Photochemotherapy", "Dental Implants" and "Peri-Implantitis". Unspecific free-text words and related terms were also included. The Cochrane Collaboration's tool were used to evaluate the risk of bias of included studies. The random effect model was chosen and heterogeneity was evaluated using the I2 test. Three studies met the inclusion criteria. Meta-analysis demonstrated an association between aPDT and reduction in viable bacteria counts for: Aggregatibacter actinomycetemcomitans (OR= 1.31; confidence interval= 1.13, 1.49; p<0.00001), Porphyromonas gingivalis (OR= 4.08; confidence interval= 3.22, 4.94; p<0.00001), and Prevotella intermedia (OR= 1.66; confidence interval= 1.06, 2.26; p<0.00001). A aPDT appears to be effective in bacterial load reduction in peri-implantitis and has a positive potential as an alternative therapy for peri-implantitis.
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Societal Identification of Facial Paralysis and Paralysis Location
This observational study examines the ability of casual observers to identify paralysis of varying degrees of severity and to localize the defect on the face.
Attitudes to climate change, perceptions of disaster risk, and mitigation and adaptation behavior in Yunlin County, Taiwan
Abstract
Issues that are associated with climate change have global importance. Most related studies take a national or regional perspective on the impact of climate change. Taiwan is constrained by its geographical conditions, which increase its vulnerability to climate change, especially in its western coastal areas. The county that is most affected by climate change is Yunlin. In 2013–2014, projects that were sponsored by Taiwan's government analyzed the relationship among synthesized vulnerability, ecological footprint (EF) and adaptation to climate change and proposed 15 categories of synthesized vulnerability and EF values. This study further examines the relationship between vulnerability and EF values and examines how residents of four townships—Linnei, Sihu, Mailiao, and Huwei—cope with the effects of climate change. This study investigates whether the residents of the four townships vary in their attitudes to climate change, their perceptions of disaster risk, and their behavioral intentions with respect to coping with climate change. The structural equation model (SEM) is used to examine the relationships among attitudes to climate change, perceptions of disaster risk, and the behavioral intentions of residents in townships with various vulnerabilities to climate change. The results that are obtained using the SEM reveal that climate change mitigation/adaptation behavior is affected by attitudes to climate change and perceptions of disaster risk. However, the effects of attitudes and perceptions on mitigation and adaptation that are mediated by place attachment are not statistically significant.
Assessment of atrazine toxicity to the estuarine phytoplankter, Dunaliella tertiolecta (Chlorophyta), under varying nutrient conditions
Abstract
Anthropogenic inputs of chemical environmental contaminants are frequently associated with developing harmful algal blooms, but little is known about how estuarine phytoplankton assemblages respond to multiple, co-occurring chemical stressors in chronically disturbed habitats. The goals of this research were to establish a robust protocol for testing the effects of atrazine on estuarine phytoplankton, and then to use that protocol to compare the effects of atrazine exposure with and without nutrient enrichment on a cosmopolitan estuarine/marine alga, Dunaliella tertiolecta (Chlorophyta). Atrazine sensitivity in nutrient-replete media (96-h growth inhibition \( \overline{x} \) ) was 159.16 μg l−1, but sensitivity was influenced by exposure duration, and inhibitory effects of herbicide on algal growth decreased under imbalanced nutrient regimes and low nitrogen and phosphorus supplies. These findings advance knowledge about how nutrient regimes and herbicides interact to control estuarine phytoplankton population dynamics.
Toward the full spectrum of genes for human skin colour
Humans across the globe shows a remarkable diversity in colouration of skin, hair and eyes (Jablonski & Chaplin, 2017) reflecting adaption of pigmentation genes within populations to their environment (Sturm & Duffy, 2012), as well as other evolutionary forces. Skin colour is highly correlated with incident levels of solar UV, and this has led to hypotheses that the need for vitamin D synthesis and protection from photolysis of folate are major balancing selective pressures modulating melanogenesis in the epidermis necessary for both healthy bones at high Northern latitudes experiencing low solar irradiance, but also shielding the skin from the high equatorial sun exposure.
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Ablation of colorectal liver metastasis: Interaction of ablation margins and RAS mutation profiling on local tumour progression-free survival
Abstract
Objectives
To investigate effects of ablation margins on local tumour progression-free survival (LTPFS) according to RAS status in patients with colorectal liver metastases (CLM).
Methods
This two-institution retrospective study from 2005–2016 included 136 patients (91 male, median age 60 years) with 218 ablated CLM. LTPFS was performed using the Kaplan–Meier method and evaluated with the log-rank test. Uni/multivariate analyses were performed using Cox-regression models.
Results
Three-year LTPFS rates for CLM with minimal ablation margin ≤10 mm were significantly worse than those with >10 mm in both mutant-RAS (29% vs. 48%, p=0.038) and wild-type RAS (70% vs. 94%, p=0.039) subgroups. Three-year LTPFS rates of mutant-RAS were significantly worse than wild-type RAS in both CLM subgroups with minimal ablation margin ≤10 mm (29% vs. 70%, p<0.001) and >10 mm (48% vs. 94%, p=0.006). Predictors of worse LTPFS were ablation margins ≤10 mm (HR: 2.17, 95% CI 1.2–4.1, p=0.007), CLM size ≥2 cm (1.80, 1.1–2.8, p=0.017) and mutant-RAS (2.85, 1.7–4.6, p<0.001).
Conclusions
Minimal ablation margin and RAS status interact as independent predictors of LTPFS following CLM ablation. While minimal ablation margins >10 mm should be always the procedural goal, this becomes especially critical for mutant-RAS CLM.
Key Points
• RAS and ablation margins are predictors of local tumour progression-free survival.
• Ablation margin >10 mm, always desirable, is crucial for mutant RAS metastases.
• Interventional radiologists should be aware of RAS status to optimize LTPFS.
Subclinical changes in MRI-determined right ventricular volumes and function in subjects with prediabetes and diabetes
Abstract
Objectives
The aim of this study was to assess subclinical changes in right ventricular volumes and function in subjects with prediabetes and diabetes and controls without a history of cardiovascular disease.
Methods
Data from 400 participants in the KORA FF4 study without self-reported cardiovascular disease who underwent 3-T whole-body MRI were obtained. The right ventricle was evaluated using the short axis and a four-chamber view. Diabetes was defined according to WHO criteria. Associations between glucose tolerance and right ventricular parameters were assessed using multivariable adjusted linear regression models.
Results
Data from 337 participants were available for analysis. Of these, 43 (13%) had diabetes, 87 (26%) had prediabetes, and 207 (61%) were normoglycaemic controls. There was a stepwise decrease in right ventricular volumes in men with prediabetes and diabetes in comparison with controls, including right ventricular end-diastolic volume (β = −20.4 and β = −25.6, respectively; p ≤ 0.005), right ventricular end-systolic volume (β = −12.3 and β = −12.7, respectively; p ≤ 0.037) and right ventricular stroke volume (β = −8.1 and β = −13.1, respectively, p ≤ 0.016). We did not observe any association between prediabetes or diabetes and right ventricular volumes in women or between prediabetes or diabetes and right ventricular ejection fraction in men and women.
Conclusions
This study points towards early subclinical changes in right ventricular volumes in men with diabetes and prediabetes.
Key Points
• MRI was used to detect subclinical changes in right ventricular parameters.
• Diabetes mellitus is associated with right ventricular dysfunction.
• Impairment of right ventricular volumes seems to occur predominantly in men.
Normalized STEAM-based diffusion tensor imaging provides a robust assessment of muscle tears in football players: preliminary results of a new approach to evaluate muscle injuries
Abstract
Objectives
To assess acute muscle tears in professional football players by diffusion tensor imaging (DTI) and evaluate the impact of normalization of data.
Methods
Eight football players with acute lower limb muscle tears were examined. DTI metrics of the injured muscle and corresponding healthy contralateral muscle and of ROIs drawn in muscle tears (ROItear) in the corresponding healthy contralateral muscle (ROIhc_t) in a healthy area ipsilateral to the injury (ROIhi) and in a corresponding contralateral area (ROIhc_i) were compared. The same comparison was performed for ratios of the injured (ROItear/ROIhi) and contralateral sides (ROIhc_t/ROIhc_i). ANOVA, Bonferroni-corrected post-hoc and Student's t-tests were used.
Results
Analyses of the entire muscle did not show any differences (p>0.05 each) except for axial diffusivity (AD; p=0.048). ROItear showed higher mean diffusivity (MD) and AD than ROIhc_t (p<0.05). Fractional anisotropy (FA) was lower in ROItear than in ROIhi and ROIhc_t (p<0.05). Radial diffusivity (RD) was higher in ROItear than in any other ROI (p<0.05). Ratios revealed higher MD and RD and lower FA and reduced number and length of fibre tracts on the injured side (p<0.05 each).
Conclusions
DTI allowed a robust assessment of muscle tears in athletes especially after normalization to healthy muscle tissue.
Key Points
• STEAM-based DTI allows the investigation of muscle tears affecting professional football players.
• Fractional anisotropy and mean diffusivity differ between injured and healthy muscle areas.
• Only normalized data show differences of fibre tracking metrics in muscle tears.
• The normalization of DTI-metrics enables a more robust characterization of muscle tears.
Comparison of effectiveness and safety of excimer lamp versus topical calcipotriol-clobetasol propionate combination in the treatment of palmoplantar psoriasis
Abstract
Background
Very few studies have assessed the efficacy of excimer treatment in palmoplantar psoriasis (PPP), and none has compared the excimer with calcipotriol-clobetasol combination.
Purpose
To compare the effectiveness and safety of excimer lamp versus topical ointment containing calcipotriol (0.005% w/w) and clobetasol propionate (0.05% w/w) combination in PPP.
Methods
This right-left randomization trial included 36 patients with PPP, who received treatment with excimer lamp (twice weekly) on one side and calcipotriol-clobetasol combination once daily on another side for 12 weeks, followed by 8 weeks follow-up. Recruitment and response assessment was done by 2 experienced dermatologists (SD and TN) using modified palmoplantar pustular psoriasis area and severity index score (m-PPPASI, originally devised for palmoplantar pustulosis, suitably modified to assess response in PPP).
Primary outcome measure was percentage improvement in mPPPASI at 12 weeks, which was classified as minimal (≤ 25%), mild (>25-50%), moderate (>50-75%) and marked (>75%). The secondary outcome measures were the proportion of patients achieving >75% reduction in m-PPPASI and the time to achieve it.
Results
Of 36 recruited patients, 33 completed treatment and 21 adhered to 8-weeks follow-up. The mean mPPPASI on the excimer treated sides reduced significantly from 7.75 ± 4.62 to 4.01 ± 4.07 (p < 0.001) at 12th week (end of the treatment) and 2.66 ± 3.97 at 20th week (at 8 weeks follow-up). The mean mPPPASI on the calcipotriol-clobetasol treated sides reduced significantly from 7.36 ± 4.46 to 3.55 ± 3.77 (p < 0.001) and 2.70 ± 3.97 at 12th week and 20th week respectively. The reduction was significant for both treatment modalities. The difference between the two modalities was not significant.
Minimal, mild, moderate and marked improvement was seen in 5/33 (15.2%) and 1/33 (3.0%), 6/33 (18.2%) and 8/33 (24.2%), 12/33 (36.4%) and 13/33 (39.4%), and 8/33 (24.2%) and 8/33 (24.2%) sides in the excimer and calcipotriol-clobetasol combination respectively. A total of 8 patients in each group achieved mPPPASI 75 at 12 weeks. The mPPPASI 75 was achieved at 2, 4 and 8 weeks in 1, 2 and 8 patients respectively using either modality. The adverse effects (most commonly hyperpigmentation) were noted more on the excimer-treated sides, however they were well tolerated.
Conclusion
Both excimer lamp and calcipotriol-clobetasol combination are equally effective in treatment of PPP.
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Early laser intervention to reduce scar formation: a systematic review
Abstract
The ability of laser treatment to affect wound healing and subsequently minimize scar formation has been investigated in recent years. However, no systematic review links these clinical trials. The aim of this study is to systematically review and evaluate clinical evidence for early laser intervention to reduce scar formation in studies where laser treatment were introduced less than 3 months after wounding. We searched PubMed using relevant key words in June 2017. Titles, abstracts and articles were sorted according to inclusion and exclusion criteria. Methodological quality was evaluated according to Cochrane Collaborations risk-of-bias assessment guideline by two independent authors. Twenty-five articles met the inclusion criteria. In total 22 of 25 studies were controlled studies and 17 of 25 studies compared laser treatment versus untreated control scars. The following laser devices have been investigated; pulsed-dye laser (PDL) laser, potassium-titanyl-phosphat (KTP) laser, fractional Erbium:Glass 1540 nm/1550 nm, fractional/full-ablation erbium-doped-yttrium-aluminium-garnet (Er:YAG) laser, or fractional CO2-laser. Eighteen studies applied laser treatments 2-4 times with 2-8 weeks intervals, while 7 studies applied only one laser treatment. Follow-up time ranged from 1-12 months with 18 studies using a follow-up time ≤3 months. In general, laser treated wounds and scars showed benefit from laser intervention, though not always reaching significance. Significant scar improvement were found in: 3 of 4 studies using laser treatment in inflammation phase, in 6 of 16 studies with laser initiated in the proliferation phase and in 2 of 5 studies in the remodeling phase. High risk-of- bias were found in randomization and allocation concealment, and low risk-of-bias with regard to blinding of outcome assessment and lost to follow-up. In conclusion, laser intervention when introduced in inflammation, proliferation or remodeling phase has the potential to reduce cutaneous scar formation. Further high quality studies are needed before standard protocols can be implemented in clinical practice.
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Predatory conferences: Caveat emptor!
Abstract
It is a dream of every young researcher or postgraduate student to publish an article in an indexed journal and to present an oral paper or poster at a reputed conference. Unfortunately these young researchers are commonly fallen prey to predatory publications which have become a major hazard in recent years because of their rapid multidisciplinary proliferation. In fact many dermatologists daily come across with such fraudulent journals which have quite matured and rooted and now days, flourished with conference version i.e. 'Predatory conferences'. In the name of greater good of Open Access, these fraudulent journals and organizers are prospering by trading on the naïve doctors and academicians, who look to enhance their academic resume and to earn tenure and promotion.
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Granulomatous Tattoo reaction with Associated Uveitis successfully treated with methotrexate
Abstract
Few reports describe tattoo granulomas with the simultaneous development of intraocular inflammation without any evidence of systemic sarcoidosis at the time of presentation. Here, we present a patient with no prior diagnosis of sarcoidosis who developed inflammation of tattooed skin and shortly after bilateral uveitis.A 52-year-old previously healthy woman presented with a 8 months history of swelling and itching located in all of her 11 black tattoos. Approximately 5 months later she developed complaints of blurred vision, diagnosed as recurrent uveitis anterior by an ophthalmologist.
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Normoglycemic glucagonoma syndrome associated with necrolytic migratory erythema
Abstract
Glucagonoma is an extremely rare tumor of the pancreatic alpha-cells. Its estimated annual incidence is 1 case per 20 million individuals. Necrolytic migratory erythema (NME) is the hallmark clinical sign. We report a patient with normoglycemic glucagonoma and NME.
A 44-year-old male patient presented with a 4-year history of unexplained exanthema and unintentional weight loss. Skin examination revealed a mildly pruritic rash on the trunc, the extremities and the face (fig 1). One found erythematous polycyclic migratory lesions with scaling and crusting margins and central resolution. Histological examination showed parakeratotic epidermis and upper epidermal pallor with vacuolated keratinocytes (fig 2). The glucagon level was elevated at 444,5 pg/mL (normal 5,1-62,3 pg/mL). Fasting blood sugar and HbA1c where within normal range. The insulin level was raised (112 μU/mL, normal 3,21-16,32 μU/mL). CT scan of the abdomen showed two masses in the tail of pancreas, measuring 3,8 cm and 2,6 cm in diameter and thrombosis of the left common femoral vein. In the somatostatin receptor scintigraphy, the pancreatic masses stained positive. Multiple endocrine neoplasia type 1 syndrome (MEN 1) was ruled out by genetic analysis. Surgical resection of the pancreatic tail with local lymphadenectomy and splenectomy was performed. Pathological examination confirmed two low-grade neuroendocrine neoplasms consistent with glucagonoma. Tumor cells were also found in 1 out of 19 removed lymph nodes. After surgery, the patients general condition improved rapidly and the skin lesions completely disappeared.
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Once weekly targeted excimer light produced modest re-pigmentation of vitiligo over a 20-week period
Abstract
Vitiligo is an acquired disorder of depigmentation resulting from the loss of functional epidermal melanocytes. It has a worldwide prevalence of 0.5-2%. Vitiligo can have a major negative impact on patients' quality of life.Current treatments include topical corticosteroids and immunomodulators, systemic immunosuppressants, cosmetic camouflage, ultraviolet radiation and surgical procedures, e.g. punch grafting. Recently, targeted phototherapy using the 308-nm xenon-chloride (XeCl) monochromatic excimer light (MEL) delivered by a laser or a lamp emitting non-coherent monochromatic light has been used.
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The regular use of an emollient improves symptoms of atopic dermatitis in children: a randomized controlled study
Abstract
Background
Emollients are considered as a first-line therapy for the treatment of atopic dermatitis (AD). However, evidence-based proof that the regular use of emollients reduces AD severity is lacking.
Objective
To assess whether the regular use of emollients results in a reduction of AD severity in children with AD.
Methods
In this multicenter randomized, parallel group, open-label study, children with mild to moderate AD were recruited during a flare. After flare resolution with a topical corticosteroid, patients were randomized to V0034CR emollient, reference emollient, or no emollient (1:1:1 ratio), for 12 weeks. AD severity was assessed regularly by physicians (SCORAD and subcomponents, IGA) and by parents (PO-SCORAD and POEM).
Results
335 patients were randomized to V0034CR (n=111), reference emollient (n=116) or no emollient (n=108). After 12 weeks of treatment, SCORAD score was reduced by 5.28 points in the V0034CR group and by 3.36 points in the reference emollient group compared with the no emollient group (+4 points; p<0.001 in both emollient groups vs no emollient group). In a similar manner, PO-SCORAD score was reduced by 4.88 and 2.67 points in the V0034CR and reference emollient groups, respectively, but increased by 2.90 points in the no emollient group (p<0.001). Similar results were observed for POEM. A continuous decrease in all scores was observed over the 12-week treatment period. At the end of the study, the percentage of patients in complete remission (i.e. without a new flare over the treatment period) was higher in the V0034CR (59.5%) and reference emollient (44.3%) groups than in the no emollient group (29.8%) (p<0.001).
Conclusion
These results demonstrate that the regular use of emollients in children with mild to moderate AD reduces the severity of symptoms and, therefore, support their use as a first-line treatment for these patients.
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Variation in the diagnosis and clinical management of Lentigo Maligna across Europe: a survey study among EADV members
Abstract
Background
Lentigo maligna (LM), a form of melanoma in situ, is treated to prevent progression to lentigo maligna melanoma (LMM). Surgical treatment is the gold standard. However, treatment guidelines are based on expert opinion and comparative studies are lacking.
Objective
The objective of this study is to assess the diagnostic methods and clinical management of LM patients among European dermatologists and residents.
Methods
A survey consisting of 29 questions about diagnostic methods and treatment options used for LM patients was sent to 3308 members of the European association of Dermatologists and Venereologists (EADV).
Results
Most questions were multiple choice, and multiple answers could be ticked per question.
A total of N = 415 (12.5%) completed surveys were included into the analyses. A combination of clinical diagnosis 65.7%, dermatoscopy 83.4% and histopathology 88.2% is used by most respondents to diagnose LM. Tissue for histopathological evaluation was collected using most often by a single punch biopsy in 61.0%, The most common treatment for LM patients <60 years of age is surgery (97,6%). For LM patients >70 years of age, 66.8% of the respondents preferred surgical treatment. Non-surgical options such as radiotherapy (17.0%), topical imiquimod (30.6%), watchful waiting (19.6%) or cryotherapy (20.4%) were used in this elderly group. Sub-analysis showed that respondents who take into account patient preference, used topical imiquimod, radiotherapy and watchful waiting more often.
Conclusion
In conclusion, the results of this survey show that there is a variance in the diagnostic methods and treatment modalities used for LM across Europe. Surgery remains the most utilized option. However, non-surgical options, such as topical imiquimod and radiotherapy, are most often used for elderly patients. We recommend that future studies focus on patient preference and compare surgical to non-surgical therapy.
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Autosomal recessive hyper-IgE syndrome in two brothers of a Chinese family with a novel mutation in DOCK8 gene
Abstract
The hyper-IgE syndromes (HIES) are complex primary immunodeficiency disorders, including autosomal dominant form (AD-HIES) and recessive form (AR-HIES). Here we describe two boys with AR-HIES in a Chinese family and a novel mutation of DOCK8 gene was identified.The index patient was an 8-year-old boy. He presented with recurrent flexural skin lesions (similar with atopic dermatitis (AD)) for more than 5 years (Fig. 1a,b), and a 6-months history of severe molluscum contagiosum(Fig. 1c) and verruca plana(Fig. 1d). He had repeated respiratory tract infection, nasosinusitis and otitis media every year, with a history of asthma and peanut allergy.
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Skin manifestations in patients with hcv–related chronic liver disease
Abstract
Hepatitis C virus (HCV) is able to trigger both hepatic and extra-hepatic manifestations (1,2).
Among the latter, the most investigated is mixed cryoglobulinemia vasculitis (MCV), especially of type II (3, 4), usually detected in 40-60% of patients chronically infected with enhanced the risk to develop lymphomas (5). Autoimmune disorders including thyroid disease, and diabetes mellitus have also been associated with chronic HCV infection (6). Skin manifestations may occur in up to 17% of HCV positive patients (7) and are the result of the immuno-mediated damage induced by the virus itself, and/or the associated liver injury (8). Cutaneous palpable purpura is the most frequent (70-90%). Porfiria cutanea tarda (PCT) is detected in 50% of HCV-infected patients (8). Observational and cohort studies described an association between psoriasis and HCV infection independently from exposure to interferon treatments (9). Instead, cutaneous Kaposi's sarcoma was reported only once in association with HCV (10). In this retrospective study, we aimed to evaluate the frequency and clinical features of skin disorders in a large cohort of patients with HCV-related liver disease.
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Cytokeratin 19 expression is a risk factor for metastasis in cutaneous squamous cell carcinoma
Abstract
Cytokeratin 19 (CK19) expression has been reported to be a risk factor for metastasis in oral squamous cell carcinoma. However, the significance of CK19 expression in cutaneous squamous cell carcinoma (cSCC) is unclear. Although some studies have reported CK19 expression in cSCC, no study has focused on the relationship between CK19 expression and metastasis in cSCC. Herein, we evaluate whether CK19 expression is related to metastasis in cSCC.
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Evaluation of T lymphocyte subpopulations in Actinic Keratosis, In Situ and Invasive Squamous Cell Carcinoma of the Skin
Abstract
Background
Tumor infiltrating lymphocytes (TILs) represent important regulators of carcinogenesis. Cutaneous invasive squamous cell carcinoma (inSCC) develops through precursor lesions, namely in situ squamous cell carcinoma (isSCC) and actinic keratosis (AK), representing a natural model of carcinogenesis. The study evaluates TIL subpopulations in inSCC and its precursors by comparing two semi-quantitative scoring systems, and assesses the presence of regulatory T-cells (Tregs) in these lesions.
Methods
Paraffin sections from 33 cases of AK, 19 isSCCs and 34 inSCCs with adjacent precursor lesions or normal skin were immunostained for CD3, CD4, CD8 and Foxp3. TIL subgroups were evaluated by the semi-quantitative Klintrup-Mäkinen score, and by a more detailed modification of this system. Treg counts were assessed by image analysis quantification.
Results
An increase of all TIL subpolulations from precursor lesions towards inSCC was shown by both scoring systems. Treg counts progressively increased from normal skin to AK and isSCC, but decreased in inSCC. Tregs were more numerous in pT2 and around indolent inSCCs compared to T1 and aggressive subtypes.
Conclusions
T-cells and cytotoxic T-cells progressively increase in cutaneous squamous cell carcinogenesis, while Treg counts diminish in inSCC. The K-M score is an appropriate, easily applicable TIL scoring system in cutaneous inSCC.
The vacuolar ATPase is required for ERK-dependent wound healing in the Drosophila embryo
Abstract
Epithelia have the ability to repair injuries through an evolutionary conserved wound healing mechanism. Wound healing events can be classified into the transcription-independent signals involving mobilization of ionic currents and cytoskeletal rearrangements or the transcription-dependent response with activation of repair genes. The vacuolar H+-ATPase (V-ATPase) has been implicated in the regeneration of vertebrate structures, but the underlying cellular mechanisms remain unclear. Here, we use wounding assays on the epidermis of Drosophila embryos to assess the role of the V-ATPase in the healing response. We show that a deficient V-ATPase induces a defective wound healing response by delaying re-epithelialization and preventing the ERK-dependent transcriptional activation of repair around the wound site. Our data suggests that the V-ATPase plays an evolutionary conserved role in the activation of genes necessary for the wound healing response. This article is protected by copyright. All rights reserved.
Constitutive overexpression of periostin delays wound healing in mouse skin
Abstract
Periostin is a matricellular protein involved in development, maintenance and regulation of tissues and organs via by binding to cell surface integrin receptors. Pathologically, periostin plays an important role in the process of wound healing: as a deficiency of the Postn gene delays wound closure and periostin is consistently upregulated in response to injury and skin diseases. However, the functional role of elevated periostin in the process of wound healing has not been tested. In this study, we generated Postn-transgenic mice under the control of the CAG promoter/enhancer to investigate the effects of constitutive overexpression of full length periostin during its pathophysiological roles. Transgenic mice showed significant overexpression of periostin in skin, lung, and heart, but no morphological changes were observed. However, when these transgenic mice were injured, periostin overexpression delayed the closure of excisional wounds. Expression of IL-1β and TNFα, pro-inflammatory cytokines important for wound healing, was significantly decreased in the transgenic mice, prior to delayed healing. Infiltration of neutrophils and macrophages, the main sources of IL-1β and TNFα, was also downregulated in the transgenic wound sites. From these data, we conclude that enforced expression of periostin delays wound closure due to reduced infiltration of neutrophils and macrophages followed by downregulation of IL-1β and TNFα expression. This suggests that regulated spatiotemporal expression of periostin is important for efficient wound healing and that constitutive periostin overexpression interrupts the normal process of wound closure. This article is protected by copyright. All rights reserved.
Molecular diagnosis of skin infections using paraffin-embedded tissue – review and interdisciplinary consensus
Summary
Nucleic acid amplification techniques (NATs), such as PCR, are highly sensitive and specific methods that have become valuable supplements to culture and serology in the diagnosis of infectious disorders. However, especially when using formalin-fixed and paraffin-embedded tissue, these techniques are associated with both false-negative and false-positive results, a pitfall that is frequently misjudged. Representatives of the German Society of Hygiene and Microbiology (DGHM) and the German Society of Dermatology (DDG) therefore set out to develop a consensus – in the form of a review article – on the appropriate indications for NATs using paraffin-embedded tissue, its contraindications, and the key points to be considered in the pre- and post-analytical phase.
Given that fresh, naive tissue is preferably to be used in the workup of a suspected infection, PCR analysis on paraffin sections represents an exception. The latter may be considered if an infection is suspected at a later point in time and fresh tissue has not been preserved or can no longer be obtained. Potential indications include confirmation of histologically suspected infections with Leishmania spp., Bartonella spp., Rickettsia spp., or in case of ecthyma contagiosum. Infections with, for example, mycobacteria or RNA viruses, on the other hand, are not considered useful indications for NATs using paraffin sections.
In order to avoid misinterpretation of test results, it is essential that laboratory reports on NATs using paraffin-embedded tissue contain information on the indication/diagnostic circumstances, the required and chosen pre-analytical steps, the limitations of the method, and on diagnostic alternatives.
Spalthauttransplantation zur Defektdeckung am Ohr: eine statistische Analyse
Zusammenfassung
Hintergrund und Ziele
Die Rekonstruktion nach Entfernung ausgedehnter maligner Hauttumoren am Ohr ist eine Herausforderung. Verschiedene Methoden der Defektdeckung wurden beschrieben. Lappenplastiken, längere Anästhesiezeiten, geringe Compliance und Antikoagulation stellen bei den oft älteren Patienten zusätzliche Risiken dar. Eine rasch, effizient und unkompliziert durchführbare Methode der Defektdeckung ist daher wünschenswert. Ziel der Studie war die Beurteilung des ästhetischen Resultats, des Heilungsprozesses, der Komplikations- und Rezidivrate nach Transplantation ungenetzter Spalthaut (SPHT) zur Defektdeckung nach knorpelerhaltender Resektion maligner Tumoren am Ohr.
Patienten und Methodik
32 Patienten wurden nach Entfernung von Hauttumoren am Ohr einer Defektdeckung mittels SPHT unterzogen.
Ergebnisse
Die durchschnittliche Defektgröße betrug 8,0 cm2. Eine vollständige Einheilung des Transplantates erfolgte in allen Fällen innerhalb von zwei Wochen. Wesentliche Komplikationen traten nicht auf. Das ästhetische Resultat wurde sowohl von den Patienten als auch von einem Dermatochirurgen und zwei plastischen Chirurgen als gut bewertet.
Schlussfolgerungen
Die SPHT am Ohr ist eine zuverlässige Methode zur Deckung ausgedehnter Hautdefekte. Selbst bei großen Tumoren des äußeren Ohres ist der Ohrknorpel nicht immer infiltriert. Eine knorpelschonende Tumorresektion mit anschließender Defektdeckung mittels SPHT ist eine ausgezeichnete und rasch durchführbare Technik mit hoher Patientenzufriedenheit.
Elastolysen und Hauterkrankungen mit Verlust der elastischen Fasern
Zusammenfassung
Die elastischen Fasern sind neben den kollagenen Fasern der wichtigste Bestandteil des Bindegewebsgerüstes der Haut. Eine Verminderung oder ein Verlust der elastischen Fasern ist bei einer Vielzahl von klinisch sich unterschiedlich präsentierenden Erkrankungen, hereditär oder erworben, beschrieben. Bei den Erkrankungen, die mit einer Entzündung einhergehen ist die Elastophagozytose ein wichtiges histologisches Merkmal. Die Therapie der Erkrankungen dieser Gruppe ist grundsätzlich schwierig.
Biosimilars in der Dermatologie – Theorie wird Realität
Zusammenfassung
Biosimilars sind biologische Medikamente, bei denen es sich um Nachbildungen eines spezifischen Referenzprodukts handelt. Biosimilars der Tumornekrosefaktor-alpha-Inhibitoren Infliximab und Etanercept sind bereits zugelassen und stehen für dermatologische Indikationen zur Verfügung. Die Aufsichtsbehörden verlangen eine eingehende Analyse der physikochemischen und funktionellen Eigenschaften dieser hochkomplexen Moleküle sowie klinische Daten hinsichtlich ihrer gleichwertigen Wirksamkeit und Sicherheit anhand mindestens einer klinischen Studie mit einer sensitiven und homogenen Population. Für die Zulassung in einem regulierten Arzneimittelmarkt muss daher nachgewiesen werden, dass die Biosimilars praktisch gleichwertig mit dem jeweiligen Originalpräparat sind. Demzufolge werden diese Daten von einem Molekül (dem Originator) auf das andere (das Biosimilar) extrapoliert und die resultierende Zulassung umfasst die gleichen Indikationen wie beim Originalpräparat. Die Extrapolation ist zwar gut akzeptiert und reguliert, es fehlen jedoch klare Empfehlungen hinsichtlich der Austauschbarkeit von Originator und Biosimilar ebenso wie Daten über mehrmalige aufeinanderfolgende Umstellungen. Die aktuellen wissenschaftlichen Erkenntnisse stehen einer Anwendung von Biosimilars bei dermatologischen Indikationen nicht entgegen. Eine mehrmalige Umstellung der Biosimilars sollte jedoch sorgfältig überdacht werden. Um das Vertrauen in Biosimilars zu festigen und ihre Evidenz zu verbessern, ist es essentiell das spezifische Produkt, das jeder Patient erhält, möglichst genau und möglichst im Rahmen von Patientenregister zu dokumentieren.
Molekulare Diagnostik von Hautinfektionen am Paraffinmaterial – Übersicht und interdisziplinärer Konsensus
Zusammenfassung
Nukleinsäure-Amplifikations-Techniken (NAT), wie die PCR, sind hochsensitiv sowie selektiv und stellen in der mikrobiologischen Diagnostik wertvolle Ergänzungen zur kulturellen Anzucht und Serologie dar. Sie bergen aber gerade bei formalinfixiertem und in Paraffin eingebettetem Gewebe ein Risiko für sowohl falsch negative als auch falsch positive Resultate, welches nicht immer richtig eingeschätzt wird. Daher haben Vertreter der Deutschen Gesellschaft für Hygiene und Mikrobiologie (DGHM) und der Deutschen Dermatologischen Gesellschaft (DDG) einen Konsensus in Form einer Übersichtsarbeit erarbeitet, wann eine NAT am Paraffinschnitt angezeigt und sinnvoll ist und welche Punkte dabei in der Präanalytik und Befundinterpretation beachtet werden müssen.
Da bei Verdacht auf eine Infektion grundsätzlich Nativgewebe genutzt werden soll, ist die PCR am Paraffinschnitt ein Sonderfall, wenn beispielsweise bei erst nachträglichaufgekommenem Verdacht auf eine Infektion kein Nativmaterial zur Verfügung steht und nicht mehr gewonnen werden kann. Mögliche Indikationen sind der histologisch erhobene Verdacht auf eine Leishmaniose, eine Infektion durch Bartonellen oder Rickettsien, oder ein Ecthyma contagiosum. Nicht sinnvoll ist oder kritisch gesehen wird eine NAT am Paraffinschnitt zum Beispiel bei Infektionen mit Mykobakterien oder RNA-Viren.
Die Konstellation für eine NAT aus Paraffingewebe sollte jeweils benannt werden, die erforderliche Prä-Analytik, die jeweiligen Grenzen des Verfahrens und die diagnostischen Alternativen bekannt sein. Der PCR-Befund sollte entsprechend kommentiert werden, um Fehleinschätzungen zu vermeiden.
Water infrastructure and well-being among First Nations, Métis and Inuit individuals in Canada: what does the data tell us?
Abstract
This paper documents the association between water and sanitation infrastructure and health indicators in Canada for First Nations, Métis and Inuit individuals living on and off-reserve in Canada. We use two data sources: the Aboriginal Peoples Survey and a survey conducted in a First Nations community in northern Manitoba—St. Theresa Point First Nation. We find statistically significant relationships between water infrastructure and health status in both sources of data. In particular, among individuals living off-reserve, contaminated water is associated with a 5–7% lower likelihood of reporting good self-rated health and a 4% higher probability of reporting a health condition or stomach problem. Those in St. Theresa Point First Nation without running water are four times more likely to report an illness relative to those with running water. Off-reserve, this likely suggests a need for improved public education on the management of private water supplies and more frequent water testing. Our case study suggests that further investment in water/sanitation infrastructure and housing is needed in the community.
Light-based Methods for Whole Blood Bacterial Inactivation Enabled by a Recirculating Flow System
Abstract
Light of certain wavelengths can be used to inactivate pathogens. Whole blood is opaque, thus the penetration of light is reduced. Here, we overcame this limitation by using a thin transparent tube that is illuminated from all angles. Three light-based techniques were evaluated: photodynamic therapy (PDT) using a 660-nm light and antibody-photosensitizer conjugates, ultraviolet, and violet light. We observed a reduction of 55-71% of Staphylococcus aureus after 5 h of exposure (starting concentration 107 CFU/mL), and an 88-97% reduction in Methicillin-resistant Staphylococcus aureus (MRSA) (starting 104 CFU/mL). An 83-92% decrease for S. aureus and 98-99.9% decrease for MRSA was observed when combined with an immunocapture approach. Complete blood count with differential analysis did not reveal any significant changes in the blood cell numbers. Genotoxicity studies showed that violet and ultraviolet did not induce any significant level of single strand breaks and alkalie labile sites in the peripheral blood mononuclear cells (PBMC). In contrast, ultraviolet did induce a very low level of cyclobutane pyrimidine dimers, a UV damage indicator. PDT generated a significant level of single strand breaks and 8-oxoGua in these cells. The approaches showed promise for whole blood pathogen inactivation with minimal collateral damage to PBMC.
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Evidence for Reverse Hoogsteen Hairpin Intermediates in the Photocrosslinking of Human Telomeric DNA Sequences
Abstract
UVB irradiation of human telomeric (GGGTTA)3GGG sequences in potassium ion solution crosslinks the first and third TTA segments through anti cyclobutane pyrimidine dimer (CPD) formation. The photocrosslinking reaction was first proposed to occur through a form 3 two tetrad G-quadruplex in which the lateral 4-nucleotide GTTA loop can interact with an adjacent TTA loop. Curiously, the reaction does not occur with sodium ion, which was explained by the formation of a basket structure which only has 3-nucleotide TTA loops that cannot interact. Sequences known or expected to favor the two-tetrad basket did not show enhanced photocrosslinking, suggesting that some other structure was the reactive intermediate. Herein, we report that anti CPDs form in human telomeric DNA sequences with lithium ion that is known to disfavor G-quadruplex formation, as well as with potassium ion when the bases are modified to interfere with G-quartet formation. We also show that anti-CPDs form in sequences containing A's in place of G's that cannot form Hoogsteen hairpins, but can form reverse Hoogsteen hairpins. These results suggest that reverse Hoogsteen hairpins may play a hitherto unrecognized role in the biology and photoreactivity of DNA in telomeres, and possibly in other purine-rich sequences found in regulatory regions.
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Long-term distribution and habitat changes of protected wildlife: giant pandas in Wolong Nature Reserve, China
Abstract
Changes in wildlife habitat across space and time, and corresponding changes in wildlife space use, are increasingly common phenomenon. It is critical to study and understand these spatio-temporal changes to accurately inform conservation strategy and manage wildlife populations. These changes can be particularly large and complex in areas that face pressure from human development and disturbance but are also under protection and/or restoration regimes. We analyzed changes in space use and habitat suitability of giant pandas in Wolong Nature Reserve, China, over three decades using kernel density, spatio-temporal analysis of moving polygons (STAMP), and MaxEnt methods, and data from three national censuses. Between 2001 and 2012, there was a slight retraction in total range, and more area of significant space use decreases than increases. Habitat suitability varied spatially and temporally, with a 4.1% decrease in average suitability between 1987 and 2001 and a 3.5% increase in average suitability in between 2001 and 2012. Elevation and bamboo were the most important habitat predictors across the three censuses. Human and natural disturbance variables such as distance to household and the distance to landslide variable in the 4th census were also important predictors, and likely also negatively influenced important habitat variables such as bamboo and forest cover. We were able to measure changes in space utilization and habitat suitability over a large time scale, highlighting the achievements and challenges of giant panda conservation. Long-term monitoring of the changes in distribution and habitat of threatened species, and an analysis of the drivers behind these changes such as undergone here, are important to inform the management and conservation of the world's remaining wildlife populations.
Inverted Follicular Keratoses of the Buttocks
Abstract
Inverted follicular keratosis is a benign follicular tumor. Tumors classically demonstrate lobulated, endophytic growth with squamous eddy formation. The histologic differential diagnosis includes irritated seborrheic keratosis, trichilemmoma, verruca vulgaris, squamous cell carcinoma, and keratoacanthoma. The clinical differential diagnosis includes verruca, molluscum contagiosum, follicular cyst, and squamous cell carcinoma. In the past, a predilection for the head and neck of elderly men has been reported. Our experience is that the age, gender, and anatomic distribution of this lesion are more varied. Herein, we describe five cases of inverted follicular keratoses of the buttocks in middle-aged persons of both genders. These cases highlight the importance of considering inverted follicular keratosis as a possible buttock lesion because of its benign nature, in contrast to its clinical and histologic mimics. In addition, these cases are unique and relevant to the study of dermatopathology because they demonstrate a different age, gender, and anatomic distribution than previously reported.
Quantitative assessment of human-induced impacts based on net primary productivity in Guangzhou, China
Abstract
Urban expansion and land cover change driven primarily by human activities have significant influences on the urban eco-environment, and together with climate change jointly alter net primary productivity (NPP). However, at the spatiotemporal scale, there has been limited quantitative analysis of the impacts of human activities independent of climate change on NPP. We chose Guangzhou city as a study area to analyze the impacts of human activities on NPP, as well as the spatiotemporal variations of those impacts within three segments, using a relative impact index (RII) based on potential NPP (NPPp), actual NPP (NPPact), and NPP appropriation due to land use/land cover change (NPPlulc). The spatial patterns and dynamics of NPPact and NPPlulc were evaluated and the impacts of human activities on NPP during the process of urban sprawl were quantitatively analyzed and assessed using the RII. The results showed that NPPact and NPPlulc in the study area had clear spatial heterogeneity, between 2001 and 2013 there was a declining trend in NPPact while an increasing trend occurred in NPPlulc, and those trends were especially significant in the 10–40-km segment. The results also revealed that more than 91.0% of pixels in whole study region had positive RII values, while the lowest average RII values were found in the > 40-km segment (39.03%), indicating that human activities were not the main cause for the change in NPP there; meanwhile, the average RII was greater than 65.0% in the other two, suggesting that they were subjected to severe anthropogenic disturbances. The RII values in all three segments of the study area increased, indicating an increasing human interference. The 10–40-km buffer zone had the largest slope value (0.5665), suggesting that this segment was closely associated with growing human disturbances. Particularly noteworthy is the fact that the > 40-km segment had a large slope value (0.3323) and required more conservation efforts. Based on the above results, we suggest that continuous efforts may be necessary to improve the intensity of protection and management in the urban environment of Guangzhou.
Onychoscopy of trachyonychia: An analysis of 30 patients and comparison with onychomycosis
The diagnosis of trachyonychia is often challenging, and misdiagnoses, particularly as onychomycosis, are common.1-3 The correct diagnosis of trachyonychia is crucial because treatment options for trachyonychia include observation/active non-intervention, topical and systemic steroids, or immunomodulating agents, while onychomycosis should be treated with antifungal agents1, 2. Onychoscopy (nail dermoscopy) is a useful tool for various nail disorders.4-8 However, a detailed morphologic analysis of trachyonychia has not been performed. Here, we aim to describe the characteristic dermoscopic features of trachyonychia and to explore whether these features are significantly different from those in onychomycosis.
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Exposure to aged crumb rubber reduces survival time during a stress test in earthworms ( Eisenia fetida )
Abstract
Solid waste management struggles with the sustainable disposal of used tires. One solution involves shredding used tires into crumb rubber and using the material as infill for artificial turf. However, crumb rubber contains hydrocarbons, organic compounds, and heavy metals, and it travels into the environment. Earthworms living in soil contaminated with virgin crumb rubber gained 14% less body weight than did earthworms living in uncontaminated soil, but the impact of aged crumb rubber on the earthworms is unknown. Since many athletic fields contain aged crumb rubber, we compared the body weight, survivorship, and longevity in heat and light stress for earthworms living in clean topsoil to those living in topsoil contaminated with aged crumb rubber. We also characterized levels of metals, nutrients, and micronutrients of both soil treatments and compared those to published values for soil contaminated with virgin crumb rubber. Consistent with earlier research, we found that contaminated soil did not inhibit microbial respiration rates. Aged crumb rubber, like new crumb rubber, had high levels of zinc. However, while exposure to aged crumb rubber did not reduce earthworm body weight as did exposure to new crumb rubber, exposure to aged crumb rubber reduced earthworm survival time during a stress test by a statistically significant 38 min (16.2%) relative to the survival time for worms that had lived in clean soil. Aged crumb rubber and new crumb rubber appear to pose similar toxic risks to earthworms. This study suggests an environmental cost associated with the current tire-recycling solution.
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Publication date: Available online 25 July 2018 Source: Journal of Photochemistry and Photobiology B: Biology Author(s): Marco Ballestr...
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Editorial AJR Reviewers: Heartfelt Thanks From the Editors and Staff Thomas H. Berquist 1 Share + Affiliation: Citation: American Journal...
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Publication date: Available online 28 September 2017 Source: Actas Dermo-Sifiliográficas Author(s): F.J. Navarro-Triviño
