Inherited epidermolysis bullosa (EB) is a group of rare genetic disorders clinically characterized by a wide range of skin and mucosal blistering after minor trauma1. This condition is caused by mutations on genes coding for structural proteins of the skin and affects both genders from all ethnic groups, and its estimated prevalence is about 500,000 cases worldwide2.
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Publication date: Available online 23 November 2017
Source:Vaccine
Author(s): Allison Portnoy, Mark Jit, Stéphane Helleringer, Stéphane Verguet
BackgroundMeasles supplementary immunization activities (SIAs) are vaccination campaigns that supplement routine vaccination programs with a recommended second dose opportunity to children of different ages regardless of their previous history of measles vaccination. They are conducted every 2–4 years and over a few weeks in many low- and middle-income countries. While SIAs have high vaccination coverage, it is unclear whether they reach the children who miss their routine measles vaccine dose. Determining who is reached by SIAs is vital to understanding their effectiveness, as well as measure progress towards measles control.MethodsWe examined SIAs in low- and middle-income countries from 2000 to 2014 using data from the Demographic and Health Surveys. Conditional on a child's routine measles vaccination status, we examined whether children participated in the most recent measles SIA.ResultsThe average proportion of zero-dose children (no previous routine measles vaccination defined as no vaccination date before the SIA) reached by SIAs across 14 countries was 66%, ranging from 28% in São Tomé and Príncipe to 91% in Nigeria. However, when also including all children with routine measles vaccination data, this proportion decreased to 12% and to 58% when imputing data for children with vaccination reported by the mother and vaccination marks on the vaccination card across countries. Overall, the proportions of zero-dose children reached by SIAs declined with increasing household wealth.ConclusionsSome countries appeared to reach a higher proportion of zero-dose children using SIAs than others, with proportions reached varying according to the definition of measles vaccination (e.g., vaccination dates on the vaccination card, vaccination marks on the vaccination card, and/or self-reported data). This suggests that some countries could improve their targeting of SIAs to children who miss other measles vaccine opportunities. Across all countries, SIAs played an important role in reaching children from poor households.
http://ift.tt/2zgxf8L
Publication date: 15 January 2018
Source:European Journal of Pharmaceutical Sciences, Volume 112
Author(s): Alexa Guglielmelli, Bruno Rizzuti, Rita Guzzi
Ibuprofen is one of the most used anti-inflammatory drugs, and it is transported in the blood by human serum albumin, a major plasmatic protein with a peculiar adaptability in the binding of several different ligands. We have characterized the interaction between albumin and ibuprofen, either in racemic mixture, or in the S(+) and R(−) enantiomeric forms, by using differential scanning calorimetry, attenuated total reflectance Fourier transform infrared spectroscopy, and molecular dynamics simulation. The results show that increasing concentrations of ibuprofen (up to sixfold drug/protein molar ratio) improve the protein resistance to thermal unfolding without altering the secondary structure. Deconvolution of the calorimetric thermal profiles at different albumin/ibuprofen molar ratios demonstrates a selective stability of the protein domains where the binding sites of the drug are localized. At the highest ibuprofen concentration, the melting temperature increased by about 10°C with respect to the drug-free protein, whereas the unfolding enthalpy maintains an almost constant value. Furthermore, the degree of protein stabilization depends upon the chirality of the drug, and the R(−) enantiomer is more effective compared to the S(+) form. The stability is supported by molecular dynamics simulations, showing that ibuprofen maintains a stable coordination in the most favorable binding sites, leading to a more compact protein structure at high temperature. The overall results attest that the binding of ibuprofen determines on albumin a stereoselective and domain-specific stabilization with a predominantly entropic character, contributing to clarify significant aspects of the molecular mechanism of protein/drug interaction.
α-Mangostin is a dietary xanthone that displays various biological activities, and numerous reports have shown its efficacy in cancer prevention and inhibition. As most agents have been shown to be ineffective as single-agent therapy for malignant melanoma (MM), the principle of targeted chemotherapy for MM is to use effective inhibitors and combination methods. In this study, we tested the cytotoxicity of several kinase inhibitors, including the glycogen synthase kinase (GSK)-3 inhibitor CHIR99021, and rapamycin, in combination with a dietary xanthone, α-mangostin, by screening from a kinase inhibitor library for melanogenesis in SK-MEL-2 MM cells, and verified these by clone formation efficiency, terminal dUTP nick end labelling, and expression of apoptosis-related proteins. We also explored the molecular mechanisms for the apoptosis-inducing effects reported. We found a marked synergistic effect of CHIR99021 or rapamycin in combination with α-mangostin, which we verified through apoptosis-related methods. These data provide a strong rationale for the use of α-mangostin as an adjunct to GSK-3 inhibitor or mammalian target of rapamycin inhibitor treatment. The intrinsic mechanism behind α-mangostin might be inhibition of phosphatidylinositol 3-kinase/AKT signalling and autophagy, and induction of reactive oxygen species generation.
Publication date: January 2018
Source:International Immunopharmacology, Volume 54
Author(s): Dafne Fernandes Machado, Keila Karine Duarte Campos, Natália Pereira da Silva, Camila de Oliveira Ramos, Sílvia Dantas Cangussú, Guilherme de Paula Costa, André Talvani, Frank Silva Bezerra
The alveolar surfactant, which composition consists of a unique and complex mixture of lipids and proteins, has immunomodulatory action. This study aimed to evaluate the effects of exogenous surfactant on pulmonary inflammatory response in mice exposed to cigarette smoke (CS). Twenty-four mice C57BL/6 were divided into four groups: control group exposed to ambient air (CG); surfactant treated group (SG); CS exposed group (CSG) and CS exposed group treated with surfactant (CSSG). For five days, CSG and CSSG were exposed to 12 commercial cigarettes/day and SG and CSSG received the surfactant by intranasal instillation. At the end of the experiment, the animals were euthanatized for the collection of bronchoalveolar lavage fluid (BALF) and lungs. The total number of leukocytes in BALF increased in CSG compared to CG, however, there was a decrease in CSSG compared to CSG. There was an increase in lipid peroxidation in SG and CSG compared to CG while there was a decrease in CSSG compared to CSG. Regarding the antioxidant enzymes, the catalase (CAT) activity increased in all groups compared to CG and the superoxide dismutase (SOD) activity decreased in CSG compared to the CG and SG. There was an increase in TNF in SG, CSG and CSSG compared to CG. There was an increase in IL-17 in CSSG compared to CG. There was an increase in CCL5 in SG and CSSG compared to CG. Therefore, our results demonstrated that the administration of exogenous surfactant was able to decrease the oxidative processes in the lungs of mice induced by short-term exposure to CS.
http://ift.tt/2mUFbuK
Publication date: March 2018
Source:Environmental and Experimental Botany, Volume 147
Author(s): P. Rozpądek, A. Domka, R. Ważny, M. Nosek, R. Jędrzejczyk, K. Tokarz, K. Turnau
The endophytic fungus Mucor sp. was isolated from Arabidopsis arenosa inhabiting post mining wastes lands. Its role in plant adaptation to toxic metal enriched environment was evaluated. Plants inoculated with the fungus yielded significantly more biomass. Their growth response was correlated with significant elongation of root hairs, an improved water and P status and a significant upregulation of the expression of genes associated with nutrient uptake. The mechanism of root hair elongation was investigated with auxin and ethylene insensitive Arabidopsis thaliana mutants. The results clearly indicate that the root hair elongation phenotype results from fungi induced alterations in ethylene metabolism. The upregulation of close to 50 genes associated with ethylene biosynthesis and signaling confirm these results. The accumulation of Zn and Fe was lower in endophyte inoculated plants. Additionally, root to shoot translocation of Fe, Cd and Zn was improved. The expression of metal transporters associated with metal influx, efflux and distribution within the plant corresponded with altered metal homeostasis. The results of this study clearly show that the endophytic fungus plays an important role in the adaptation of the non-mycorrhizal A. arenosa to metal toxicity.
http://ift.tt/2BeG9F2
Publication date: 1 March 2018
Source:Journal of Colloid and Interface Science, Volume 513
Author(s): Yanan Pan, Jundong Wang, Xiumei Guo, Xiaoyan Liu, Xiaoliang Tang, Haixia Zhang
In this study, a novel three-dimensional zinc-based metal-organic framework (Zn-MOF), i.e., {Zn2(L)2(DMF)2H2O}n (L = 2,5-bis(phenylamino)-1,4-benzenedicarboxylic acid) was designed and developed under solvothermal condition. As a proof-of-principle, a π-conjugated framework of carboxylate ligand capable of "bottom up" synthesis was integrated with metal ion to construct a novel MOF for sensing applications. As expected, the synthesized Zn-MOF exhibited fluorescence enhancement for cadmium ion (Cd2+) and sensing of nitrobenzene (NB) through fluorescence quenching. The detection limits were calculated to be 0.12 μM for Cd2+ and 1.19 μg mL−1 for NB based on signal-to-noise ratio of 3:1. Moreover, various techniques and density functional theory investigations verified that the possible sensing mechanisms for Cd2+ and NB included ion exchange and photoinduced electron transfer, respectively. Finally, their practical applications on real samples also demonstrated that the Zn-MOF-based sensor can be effectively utilized for detection and imaging of Cd2+ present in the real water samples and living cells. This study may inspire future research and design of target fluorescent MOFs with specific functions.
Publication date: Available online 22 November 2017
Source:Cell Stem Cell
Author(s): Tyson Ruetz, Ulrich Pfisterer, Bruno Di Stefano, James Ashmore, Meryam Beniazza, Tian V. Tian, Daniel F. Kaemena, Luca Tosti, Wenfang Tan, Jonathan R. Manning, Eleni Chantzoura, Daniella Rylander Ottosson, Samuel Collombet, Anna Johnsson, Erez Cohen, Kosuke Yusa, Sten Linnarsson, Thomas Graf, Malin Parmar, Keisuke Kaji
Reprogramming of cellular identity using exogenous expression of transcription factors (TFs) is a powerful and exciting tool for tissue engineering, disease modeling, and regenerative medicine. However, generation of desired cell types using this approach is often plagued by inefficiency, slow conversion, and an inability to produce mature functional cells. Here, we show that expression of constitutively active SMAD2/3 significantly improves the efficiency of induced pluripotent stem cell (iPSC) generation by the Yamanaka factors. Mechanistically, SMAD3 interacts with reprogramming factors and co-activators and co-occupies OCT4 target loci during reprogramming. Unexpectedly, active SMAD2/3 also markedly enhances three other TF-mediated direct reprogramming conversions, from B cells to macrophages, myoblasts to adipocytes, and human fibroblasts to neurons, highlighting broad and general roles for SMAD2/3 as cell-reprogramming potentiators. Our results suggest that co-expression of active SMAD2/3 could enhance multiple types of TF-based cell identity conversion and therefore be a powerful tool for cellular engineering.
Publication date: Available online 22 November 2017
Source:Cell Stem Cell
Author(s): Levi Gadye, Diya Das, Michael A. Sanchez, Kelly Street, Ariane Baudhuin, Allon Wagner, Michael B. Cole, Yoon Gi Choi, Nir Yosef, Elizabeth Purdom, Sandrine Dudoit, Davide Risso, John Ngai, Russell B. Fletcher
Tissue homeostasis and regeneration are mediated by programs of adult stem cell renewal and differentiation. However, the mechanisms that regulate stem cell fates under such widely varying conditions are not fully understood. Using single-cell techniques, we assessed the transcriptional changes associated with stem cell self-renewal and differentiation and followed the maturation of stem cell-derived clones using sparse lineage tracing in the regenerating mouse olfactory epithelium. Following injury, quiescent olfactory stem cells rapidly shift to activated, transient states unique to regeneration and tailored to meet the demands of injury-induced repair, including barrier formation and proliferation. Multiple cell fates, including renewed stem cells and committed differentiating progenitors, are specified during this early window of activation. We further show that Sox2 is essential for cells to transition from the activated to neuronal progenitor states. Our study highlights strategies for stem cell-mediated regeneration that may be conserved in other adult stem cell niches.
Publication date: Available online 22 November 2017
Source:Cell Stem Cell
Author(s): Brian Lin, Julie H. Coleman, Jesse N. Peterson, Matthew J. Zunitch, Woochan Jang, Daniel B. Herrick, James E. Schwob
Adult neurogenesis in the olfactory epithelium is often depicted as a unidirectional pathway during homeostasis and repair. We challenge the unidirectionality of this model by showing that epithelial injury unlocks the potential for Ascl1+ progenitors and Neurog1+ specified neuronal precursors to dedifferentiate into multipotent stem/progenitor cells that contribute significantly to tissue regeneration in the murine olfactory epithelium (OE). We characterize these dedifferentiating cells using several lineage-tracing strains and single-cell mRNA-seq, and we show that Sox2 is required for initiating dedifferentiation and that inhibition of Ezh2 promotes multipotent progenitor expansion. These results suggest that the apparent hierarchy of neuronal differentiation is not irreversible and that lineage commitment can be overridden following severe tissue injury. We elucidate a previously unappreciated pathway for endogenous tissue repair by a highly regenerative neuroepithelium and introduce a system to study the mechanisms underlying plasticity in the OE that can be adapted for other tissues.
Publication date: February 2018
Source:Materials Science in Semiconductor Processing, Volume 74
Author(s): Saman Iqbal, Muhammad Shahid Rafique, Muhammad Zahid, Shazia Bashir, Muhammad Ashfaq Ahmad, Rabia Ahmad
Nanodiamonds (NDs) have been fabricated utilizing micro plasma facility. The mixture of argon as carrier gas and ethanol as precursor has been dissociated in micro plasma. The argon flow rate was varied from 4 to 9l/min. The influence of argon gas flow rates on structural, surface and optical properties of NDs was compared. An increased amount of diamond has been reported with the increase in flow rate, obtaining the maximum value at 6l/min. Further increase in flow rate starts decreasing the quality of NDs. Raman and XRD confirm that the smallest size and stress free NDs are obtained at 6l/min argon flow rate. AFM micrograph also reveals the smallest size of NDs ~27nm for 6l/min argon flow rate. The hydrophobicity of NDs increases with increasing argon flow rate as confirmed by FTIR. Photoluminescence indicates the presence of nitrogen vacancy defect centers such as N3, H3 and NV for all the flow rates. The smallest PL peak intensity at 6l/min argon flow rate indicates the lowest density of vacancy defects in the diamond. UV–Visible spectroscopy indicates the presence of nitrogen-hydrogen defect and nitrogen vacancy defect centers (N4 and N5). The largest band gap at 6l/min argon flow rate also confirms the highest quality of NDs. The centers offer promising applications as, active laser material, fluorescent markers, quantum information, nanoscale magnetic and electric filed sensors.
http://ift.tt/2mVgH4o
Publication date: Available online 23 November 2017
Source:Colloids and Surfaces B: Biointerfaces
Author(s): Verónica Freyre-Fonseca, Estefany I. Medina-Reyes, Darío I. Téllez-Medina, Gloria L. Paniagua-Contreras, Erick Monroy-Pérez, Felipe Vaca-Paniagua, Norma L. Delgado-Buenrostro, José O. Flores-Flores, Edgar O. López-Villegas, Gustavo F. Gutiérrez-López, Yolanda I. Chirino
Titanium dioxide nanoparticles (TiO2 NPs) production has been used for pigment, food and cosmetic industry and more recently, shaped as belts for treatment of contaminated water, self-cleaning windows and biomedical applications. However, the toxicological data have demonstrated that TiO2 NPs inhalation induce inflammation in in vivo models and in vitro exposure leads to cytotoxicity and DNA damage. Dermal exposure has limited adverse effects and the possible risks for implants used for tissue regeneration is still under research. Then, it has been difficult to establish a straight statement about TiO2 NPs toxicity since route of exposure and shapes of nanoparticles play an important role in the effects. In this study we aimed to investigate the effect of three different types of TiO2 NPs (industrial, food-grade and belts) dispersed in fetal bovine serum (FBS) and saline solution (SS) on microvessel network, angiogenesis gene expression and femur ossification using a chick embryo model after an acute exposure of NPs on the day 7 after eggs fertilization. Microvascular density of chorioallantoic membrane (CAM) was analyzed after 7days of NPs injection and vehicles induced biological effects per se. NPs dispersed in FBS or SS have slight differences in microvascular density, mainly opposite effect on angiogenesis gene expression and no effects on femur ossification for NPs dispersed in SS. Interestingly, NPs shaped as belts dramatically prevented the alterations in ossification induced by FBS used as vehicle.
Publication date: Available online 22 November 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Poonam Piplani, Ankit Jain, Dhiksha Devi, Anjali, Anuradha Sharma, Pragati Silakari
The present study reports the effect of indanone derivatives on scopolamine induced deficit cholinergic neurotransmission serving as promising leads for the therapeutics of cognitive dysfunction. Eleven compounds 54 - 64 have been designed, synthesised and evaluated against behavioural alterations using step down passive avoidance protocol at a dose of 0.5 mg/kg with Donepezil (1) as the reference standard. All the synthesised compounds were evaluated for their in vitro acetylcholinesterase (AChE) inhibition at five different concentrations using mice brain homogenate as the source of the enzyme. Compounds 54, 56, 59 and 64 displayed appreciable activity with an IC50 value of 14.06 µM, 12.30 µM, 14.06 µM and 12.01 µM, respectively towards acetylcholinesterase inhibition. The molecular docking study performed to predict the binding mode of the compounds suggested that these compounds could bind appreciably to the amino acids present at the active site of recombinant human acetylcholinesterase (rhAChE). The behavioral, biochemical and in silico pharmacokinetic studies were in concordance with each other.
Publication date: Available online 22 November 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Mateusz Kozarski, Dorota Kubacka, Blazej A. Wojtczak, Renata Kasprzyk, Marek R. Baranowski, Joanna Kowalska
The hydrolysis of nucleoside 5′-monophosphates to the corresponding nucleosides and inorganic phosphate is catalysed by 5′-nucleotidases, thereby contributing to the control of endogenous nucleotide turnover and affecting the fate of exogenously delivered nucleotide- and nucleoside-derived therapeutics in cells. A recently identified nucleotidase cNIIIB shows preference towards 7-methylguanosine monophosphate (m7GMP) as a substrate, which suggests its potential involvement in mRNA degradation. However, the extent of biological functions and the significance of cNIIIB remains to be elucidated. Here, we synthesised a series of m7GMP analogues carrying a 1,2,3-triazole moiety at the 5′ position as the potential inhibitors of human cNIIIB. The compounds were synthesised by using the copper-catalysed azide-alkyne cycloaddition (CuAAC) between 5′-azido-5′-deoxy-7-methylguanosine and different phosphate or phosphonate derivatives carrying terminal alkyne. The analogues were evaluated as cNIIIB inhibitors using HPLC and malachite green assays, demonstrating that compound 1a, carrying a 1,2,3-triazoylphosphonate moiety, inhibits cNIIIB activity at micromolar concentrations (IC50 87.8 ± 7.5 µM), while other analogues showed no activity. In addition, compound 1d was identified as an artifical substrate for HscNIIIB. Further characterization of inhibitor 1a revealed that it is poorly recognised by other m7G-binding proteins, eIF4E and DcpS, indicating its selectivity towards cNIIIB. The first inhibitor (1a) and unnatural substrate (1d) of cNIIIB, identified here, can be used as molecular probes for the elucidation of biological roles of cNIIIB, including the verification of its proposed function in mRNA metabolism.
Publication date: Available online 21 November 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Prasanthi Malapati, Vagolu Siva Krishna, Radhika Nallangi, Nikhila Meda, Rudraraju Reshma Srilakshmi, Dharmarajan Sriram
Mycobacterium tuberculosis glutamate racemase is an essential enzyme involved in peptidoglycan synthesis and conserved in most bacteria. Small molecule inhibitors were reported on other bacterial species whereas in M. tuberculosis it wasn't explored much. In this study we have screened in house compound library using fluorescence thermal shift assay and enzyme inhibition assay, form this (1-(3-(benzo[d]thiazol-2-yl)phenyl)-3-(p-tolyl)thiourea) was identified as lead compound with IC50 19.47±0.81 μM. Further lead optimization by synthesis resulted in twenty-three compounds, of which Compound 25 has shown more efficacy compared to lead 1 showing non- competitive mode of inhibition with IC50 1.32±0.43 μM. It also showed significant activity (represented in log reduction) in nutrient starved dormant M. tuberculosis model (2.1), M. tuberculosis biofilm assay (2.0) and in vivo M. marinum infected zebrafish model (3.5).
Challenges of water and wastewater management in Alaska include the potential need for above-grade and freeze-protected piping, high unit energy costs and, in many rural areas, low population density and median annual income. However, recently developed net-zero water (NZW), i.e., nearly closed-loop, direct potable water reuse systems, can retain the thermal energy in municipal wastewater, producing warm treated potable water without the need for substantial water re-heating, heat pumping or transfer, or additional energy conversion. Consequently, these systems are projected to be capable of saving more energy than they use in water treatment and conveyance, in the temperate USA. In this paper, NZW technology is reviewed in terms of potential applicability in Alaska by performing a hypothetical case study for the city of Fairbanks, Alaska. Results of this paper study indicate that in municipalities of Alaska with local engineering and road access, the use of NZW systems may provide an energy-efficient water service option. In particular, case study modeling suggests hot water energy savings are equivalent to five times the energy used for treatment, much greater savings than in mid-latitudes, due largely to the substantially higher energy needed for heating water from a conventional treatment system and lack of need for freeze-protected piping. Further study of the applicability of NZW technology in cold regions, with expanded evaluation in terms of system-wide lifecycle cost, is recommended.
J reconstr Microsurg
DOI: 10.1055/s-0037-1608680
Background To date, no review has been conducted on the growing body of literature describing various work-related musculoskeletal disorders (MSDs), ergonomic hazards, and potential interventions relevant to plastic surgeons. This systematic review sought to (1) define the scope of coverage of this important issue in the peer-reviewed literature; (2) critically assess the evidence; and (3) provide recommendations for future directions. Methods We conducted a literature search of MEDLINE, Embase, Web of Science, and PubMed from the inception of each database until 2016. All articles reporting on work-related MSDs or ergonomics among plastic surgeons were reviewed, summarized, and assessed for trends. Results Sixteen articles met our inclusion criteria including five expert opinions, four cross-sectional studies and case reports/series, one review, and six experimental studies. Four articles presented evidence on disease burden. The most commonly described work-related MSD was cervical spine disease, for which one study reported a career prevalence of 24.7% (point prevalence in the general population: 0.1–0.4%); three studies reported 64 cases of surgeon work-related MSD resulting in surgical intervention, decreased productivity, or involuntary early retirement. Eight studies described interventions, most of which aimed to improve the ergonomics of microsurgery. Conclusion This review found low-level evidence of plastic surgeons' vulnerability to a work-related MSD at times severe enough to end careers. Further investigation is needed to clearly define this important problem in plastic surgery. Specifically, future directions should include more methodologically rigorous epidemiologic studies evaluating disease burden.
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Pesticide residues in muscles of nine marine fish and four seaweed species of Iskenderun Bay (Northeastern Mediterranean) have been investigated. In sampled fish species, two herbicides, three insecticides, two fungicides, and one synergist were identified and quantified. Metribuzin DADK, propamocarb HCl, and piperonyl butoxide (PBO) were detected in all the muscles of sampled fish species. Metribuzin DADK was the most abundant pesticide residue in fish muscles and the highest metribuzin DADK concentration was found in sardine (311.20 μg/kg). Propamocarb HCl concentrations varied greatly among species; from 0.530 ± 0.020 μg/kg in striped sea bream to 34.170 μg/kg in sea bass. The level of PBO ranged from 0.001 μg/kg for fourlined terapon to 0.013 μg/kg for sardine. No measurable oxamyl residue was found in any of the muscles of sampled fish species (except sardine). In seaweeds, two herbicides and two insecticides were identified and quantified. Metribuzin DADK was the most abundant and found in Cystoseira corniculata (5.01 mg/kg), Corallina elongata (0.703 mg/kg), and Jania rubens (3.85 mg/kg). Molinate was a minor contaminant and only found in Corallina elongata (0.002 mg/kg). Pyrethrin I was determined only in Padina pavonia to be 0.567 mg/kg. Pyrethrine II was found in Padina pavonia and Corallina elongate to be 1.214 and 0.229 mg/kg, respectively. The most hazardous pesticide residues of organochlorines and organophosphorus were not detected in both sampled fish muscles and seaweeds. There are no clear maximum residue limits for the detected eight pesticide residues declared for fish muscle by European Union MRL (2017). In conclusion, it can be considered that observed concentrations of pesticides in sampled nine marine fish species do not have a potential health risk for consumers. Some of the detected pesticide residues can be toxic for algae and aquatic life and regular monitoring studies are therefore essential to control the pesticide concentrations of aquatic biota in the region.
This study aimed to assess the toxic effect of chronic exposure to cadmium through a metabolomic approach based on ultra-performance liquid chromatography/mass spectrometry (UPLC–MS). Forty male Sprague–Dawley rats were randomly assigned to the following groups: control, low-dose cadmium chloride (CdCl2) (0.13 mg/kg body weight (bw)), middle-dose CdCl2 (0.8/kg bw), and high-dose CdCl2 (4.9 mg/kg bw). The rats continuously received CdCl2 via drinking water for 24 weeks. Rat urine samples were then collected at different time points to establish the metabolomic profiles. Multiple statistical analyses with principal component analysis and partial least squares–discriminant analysis were used to investigate the metabolomic profile changes in the urine samples and screen for potential biomarkers. Thirteen metabolites were identified from the metabolomic profiles of rat urine after treatment. Compared with the control group, the treated groups showed significantly increased intensities of phenylacetylglycine, guanidinosuccinic acid, 4-pyridoxic acid, 4-aminohippuric acid, 4-guanidinobutanoic acid, allantoic acid, dopamine, LysoPC(18:2(9Z,12Z)), and L-urobilinogen. By contrast, the intensities of creatinine, L-carnitine, taurine, and pantothenic acid in the treated groups were significantly decreased. These results indicated that Cd disrupts energy and lipid metabolism. Meanwhile, Cd causes liver and kidney damage via induction of oxidative stress; serum biochemical indices (e.g., creatinine and urea nitrogen) also support the aforementioned results.
We of the Newcastle upon Tyne Hospitals NHS Foundation Trust Specialist Skin Cancer MDT, write with concern regarding the most recently published AJCC 8th edition staging system for malignant melanoma 1 (proposed to be implemented in the UK in January 2018) and its possible implications for accurate risk stratification and prognostic forecasting.
http://ift.tt/2iGHNaL
No abstract available
Abstract: Primary cutaneous anaplastic large cell lymphoma (ALCL), similar to systemic ALCL, has as its histomorphologic hallmarks cohesive sheets of large lymphoid cells expressing CD30. Several morphologic variants of systemic ALCL have been reported, including the common (classic) type, lymphohistiocytic, and small cell variants. The small cell variant of ALCL is characterized by a predominant cytomorphology which is unexpected for ALCL, being in the context of a small- to medium-sized hyperchromatic atypical lymphocyte. Although well recognized in its systemic form including cases with secondary cutaneous involvement, it is less well characterized as a form of primary cutaneous ALCL. In this study, we collected 8 cases of primary cutaneous small cell variant of ALCL and examined their clinical, histologic, and phenotypic features. All patients were middle aged to older adult men; the youngest patient was a 46-year-old man with underlying hepatitis C. In one case, there was a history of lymphomatoid papulosis. In all patients, the disease was in the context of a local regional presentation. Patients were treated with complete excision and/or radiation except in one in whom chemotherapy was administered. In all but one patient, the cutaneous presentation was a regionally confined process; however, in 2 cases, recurrent disease occurred, and in 25% of cases, extracutaneous dissemination specifically to regional lymph nodes was observed. Although there was nodal involvement, there was no dissemination to bone marrow or peripheral blood; no patient has died because of disseminated lymphoma. In all cases, there was a predominance of small atypical hyperchromatic cells with a variable background of larger hallmark cells typical of ALCL. Epidermotropism was seen in half of the cases, and in one case, there was striking pseudoepitheliomatous hyperplasia. The smaller cells demonstrated CD30 positivity, and the neoplastic cells showed a CD4-positive phenotype with a variable expression of cytotoxic proteins in about half of the cases, whereas in the remaining cases, a double negative phenotype was observed. Epithelial membrane antigen expression was observed in the cases tested. In our literature review, similar demographics were observed with a comparable percent of cases with extracutaneous dissemination; one case manifested an aggressive clinical course eventuating in death. In summation, the small cell variant of primary cutaneous ALCL exhibits distinctive features clinically and histologically. While exhibiting an overall higher incidence of extracutaneous dissemination, the prognosis fairs better compared with other forms of cutaneous T-cell lymphoma associated with extracutaneous dissemination, an event that defines a harbinger of aggressive disease.
Background: Histopathology plays an important role in the diagnosis of cutaneous leishmaniasis (CL) but Leishman–Donovan (LD) bodies may not always be discernible. Recently, anti–CD1a antibody (Ab), clone MTB1, was found to decorate LD bodies immunohistochemically. Objective: Can histopathology without discernible LD bodies be used to diagnose CL, and can immunohistochemistry using anti–CD1a Ab, clone MTB1, detect LD bodies in these cases. Methods: Suspected CL lesions were studied histopathologically and immunohistochemically, and the patients' clinical files were reviewed. Results: Of the 196 patients with suspected CL, direct smear demonstrated LD bodies in 50 (25.5%). Of the remaining 146 patients, 118 underwent biopsy. In 56 (47.5%) patients, the hematoxylin-eosin–stained sections revealed LD bodies. In 47 (39.8%) patients, LD bodies were not discerned but the histopathology demonstrated histiocytic infiltrates with varying numbers of plasma cells along with other inflammatory cells, and negative Ziehl–Neelsen and periodic acid–Schiff stains. This pattern was termed "histopathology consistent with leishmaniasis." The history, clinical findings, and response to anti–leishmania therapy supported the diagnosis of CL in all of them, and immunostains for CD1a, clone MTB1, detected LD bodies in 11 (23.4%) of these 47 patients. Conclusions: "Histopathology consistent with CL" along with appropriate clinical findings supports the diagnosis of CL in an endemic area, and immunostains with CD1a Ab, clone MTB1, may help in the minority of the cases.
No abstract available
Abstract: Primary skin adnexal tumors can be challenging to classify and must be discerned from cutaneous adenocarcinoma metastases from various sites. We evaluated expression of Sox10 and DOG1 in normal cutaneous adnexa and in 194 primary skin adnexal tumors, and compared their performance in discriminating primary skin adnexal tumors from cutaneous metastatic adenocarcinomas with that of p40 and p63. In normal skin adnexa, we noted Sox10 expression in both the secretory and myoepithelial cells in eccrine glands, but only in myoepithelial cells in apocrine glands. DOG1 demonstrated canalicular expression in eccrine glands, and weak expression in myoepithelial cells of apocrine glands, germinative cells of sebaceous glands, and outer root sheath of follicular infundibulum. Sox10 was expressed in 100% of cylindromas and spiradenomas, and in variable frequency in other benign and malignant tumors of sweat glands. DOG1 was positive in most cylindromas (87.5%), in only 10.5% of spiradenomas, and was variably expressed in other benign and malignant tumors of sweat glands. All syringomas (n = 20) were negative for Sox10 and DOG1. One out of the 33 follicular neoplasms was positive for Sox10 and DOG1 (3%). All sebaceous neoplasms were negative for Sox10, and 28.1% of them were positive for DOG1. Sox10 was specific (91.9%) but not sensitive (28.4%) for primary skin origin, and was far less accurate (38.5%) than p63 or p40 (95.5% accuracy). Combining Sox10 with p63 or p40 showed only very minimal gain in accuracy (96%). DOG1 expression in tumors showed low sensitivity and specificity for skin adnexal origin.
Abstract: Transient reactive aquagenic pseudokeratoderma is characterized by transient whitish and translucent papules after water exposure in palms and soles. We report 5 additional cases and their histopathologic features. Patient 5 showed a topography that had not been reported before; this demonstrates that it is not an exclusive condition of palms and soles. Patient 2 presents very subtle clinical findings, making difficult the diagnosis. And the other 3 patients have a typical presentation. Transient reactive aquagenic pseudokeratoderma has heterogeneous clinical features; in some cases, histopathologic findings, although subtle, help to confirm the diagnosis.
Abstract: Melanocytic matrical carcinoma is a very uncommon malignant neoplasm with follicular differentiation. The lesion often presents as a solitary nodule on sun-exposed skin of elderly patients. Histopathologically, it is characterized by proliferation of atypical matrical cells admixed with an increased number of melanocytes, and some atypical matrical cells may have cytoplasmic pigment. When melanocytic proliferation or melanin pigment is prominent, melanocytic metrical carcinoma can mimic melanoma. Here, we present a novel case of melanocytic matrical carcinoma mimicking melanoma in an 80-year-old man with our findings in histopathologic and immunohistochemical study.
No abstract available
Abstract: Melanocytic matricoma is a recently described cutaneous adnexal tumor composed of matrical and supramatrical cells admixed with pigmented dendritic melanocytes, thought to recapitulate the anagen bulb of the hair follicle. We report a case of a 75-year-old white man, which demonstrates consumption of the epidermis that is defined as thinning of the epidermis with attenuation of the basal and suprabasal layers and loss of the normal rete architecture in areas of direct contact with neoplastic cells. It has been associated with aggressive histologic features in melanoma and likely represents an early phase of ulceration due to attenuation. Epidermal consumption has not been previously reported in nonmelanocytic tumors and it is uncertain whether this atypical histologic feature represents a sign of malignant behavior in this rare tumor.
No abstract available
Abstract: Cutaneous chronic graft-versus-host disease (GvHD) has a broad spectrum of clinicopathological presentations, the most common ones being poikiloderma, lichen planus–like eruptions, lichen sclerosus–like lesions, morphea-like plaques, and deep sclerosis. New forms of chronic cutaneous GvHD with different clinicopathological characteristics have been described, most of them mimicking cutaneous manifestations of autoimmune diseases. We report the case of a 35-year-old man who underwent allogenic stem cell transplantation for a therapy-associated acute myeloid leukemia and developed an acute GvHD with involvement of skin and gastrointestinal tract. He subsequently presented with chronic sclerodermatous cutaneous GvHD, followed by the appearance of indurated erythematous papules and plaques located on his back, resembling the nodular/keloidal form of cutaneous scleroderma on both clinical and histopathological grounds. This peculiar clinicopathologic presentation of chronic cutaneous GvHD was never described previously.
Abstract: Direct immunofluorescence (DIF) using frozen section material from a fresh/preserved perilesional biopsy is the gold standard for the immunopathologic diagnosis of bullous pemphigoid (BP). DIF in BP shows linear dermoepidermal junction (DEJ) staining for C3, with or without staining for IgG. In some situations, only a formalin-fixed lesional biopsy is obtained (with no fresh/preserved perilesional biopsy for DIF). In this setting, paraffin section C4d immunohistochemistry has proven to be diagnostically useful, demonstrating linear DEJ positivity for C4d. We present a novel use of C4d staining for the diagnosis of BP, specifically analyzing C4d perilesional frozen section DIF in a case where standard perilesional frozen section DIF for IgG/C3 was available, but was negative. An 80-year-old woman presented with a pruritic bullous lesion on her left upper extremity, clinically thought to represent BP. Lesional histologic findings were typical for BP, but perilesional frozen section DIF staining was negative for IgG and C3. A second set of biopsies processed at a different laboratory yielded the same result. A diagnosis of bullous scabies was considered. Subsequently, perilesional frozen section DIF for C4d was obtained, which showed strong linear DEJ positivity, confirming the diagnosis of BP. DIF for C4d is widely used in transplant pathology, since C4d is persistent in tissue, versus C3. Our case demonstrates that perilesional frozen section DIF staining for C4d may be positive and diagnostic in BP, even when conventional DIF staining for IgG and C3 is negative.
Abstract: Annular lichenoid dermatitis of youth (ALDY), a dermatosis with peculiar clinical and pathological features, represents still a debated entity, given its similarity, among others, with mycosis fungoides. A case of ALDY in a 50-year-old male patient is reported. Clinically, the patient presented an oval scleroderma-like plaque on the right flank. Histology and immunohistochemistry showed the classic appearance described in ALDY. T-cell receptor rearrangement was absent. Interestingly, a focus consistent with lichen planus was observed. The lesion resolved with topical steroids and at a follow-up of 24 months no recurrence has been registered. The case described herein supports the hypothesis that ALDY is a reactive lichenoid dermatosis, closely related to lichen planus.
Abstract: Minocycline is a derivative of tetracycline. It has been widely used in dermatology for the treatment of acne and rosacea. One of its adverse effects is pigmentation of various body tissues. Clinically, 3 main distinct types of hyperpigmentation by minocycline have been distinguished: type I, with blue-gray to black pigment on the face in areas of scarring or inflammation; type II, with blue-gray pigment on normal skin of the legs, forearms and on the shins; and type III, with a diffuse muddy-brown discoloration in areas of sun exposure. In the current report, we present the case of a 50-year old man with a history of severe acne treated with minocycline in the past, who currently complained about discoloration of his face. He had also taken colloidal silver supplements for "good health" about 16 years ago. Physical examination revealed gray-blue discoloration on the face, sclera, hard palate and back. Histologic examination showed intracellular pigment deposits in macrophages of the superficial dermis in a perivascular and an interstitial distribution. The pigment stained with Fontana-Masson and von Kossa, whereas it was Perls' iron negative. This case does not fit well into any of the previously described patterns of minocycline-related hyperpigmentation.
Abstract: Syringotropic mycosis fungoides (STMF) is a very rare variant of cutaneous T-cell lymphoma. It follows a much milder disease course than its clinically indistinguishable adnexal counterpart, folliculotropic mycosis fungoides (FMF). We report a case of a 36-year-old man who presented with erythematous, studded papules and plaques on the left upper extremity and right anterior thigh diagnosed as mycosis fungoides (MF) Stage 1A on initial superficial shave biopsy. Lesions recurred after initial improvement with narrow-band ultraviolet light therapy demonstrating a concentration of abnormal lymphocytes around eccrine sweat glands on repeat biopsy consistent with STMF. Although the deeper, periadnexal infiltrate found in both STMF and FMF confers increased resistance to skin-directed therapies effective in classic MF, these entities diverge with respect to their clinical behavior. Syringotropism is a marker for increased disease-specific survival, whereas even FMF carries a prognosis worse than conventional MF. Increased awareness among the dermatopathology community of the histopathologic distinction between STMF and FMF is essential to guide treatment type, duration, and intensity in adnexal disease.
No abstract available
Abstract: The histopathological features of cutaneous hyperpigmentation in Addison disease have very occasionally been reported, and they include acanthosis, hyperkeratosis, focal parakeratosis, spongiosis, superficial perivascular lymphocytic infiltrate, basal melanin hyperpigmentation, and superficial dermal melanophages. We present a study on 2 biopsies from the arm and the thigh in a 77-year-old woman with a long clinical history of Addison disease as well as senile purpura and alopecia of female pattern. The patient presented diffuse hyperpigmentation of the skin, more pronounced on her face, and left upper forehead. The skin biopsies showed no remarkable dermal inflammatory infiltrate with melanocytic hyperpigmentation of the basal layer of the epidermis as well as a mild amount of melanophages in the papillary dermis. In addition, we found lipofuscin in the luminal pole of the secretory epithelium of the eccrine glands. In the perieccrine areas, there was Perls-positive pigment in the cytoplasm of macrophages most likely related to the senile purpura. An immunohistochemical study with Melan-A showed a melanocyte/keratinocyte ratio of 1:20 (5%) in the arm and of less than 1:50 (only 2 melanocytes in the whole section;Publication date: Available online 22 November 2017
Source:Materials Today
Author(s): Bao Dong Chen, Wei Tang, Chuan He, Chao Ran Deng, Lei Jing Yang, Lai Pan Zhu, Jian Chen, Jia Jia Shao, Long Liu, Zhong Lin Wang
Due to the natural working mechanism of triboelectric nanogenerators (TENGs), potential energy stored by elastic materials may not be effectively converted into electric power, post mechanical triggering. Here, we report a practical bionic-jellyfish triboelectric nanogenerator (bjTENG) with polymeric thin film as the triboelectric material, which is shape-adaptive, with a hermetic package and a unique elastic resilience structure, similar to the behavior of a jellyfish. The charge separation in the elastic resilience of this bionic-structure is based on the liquid pressure-induced contact-separation of the triboelectric layers. On the basis of the conjunction of the triboelectrification and the electrostatic induction, a sustainable and enhanced output performance of 143 V, 11.8 mA/m2 and 22.1 μC/m2 under a low frequency of 0.75 Hz and at a water depth of 60 cm is produced, which can be used to supply power for dozens of green LEDs or a temperature sensor directly. More significantly, bjTENG is believed to be a priority technology which is attributable to its highly sensitivity, portability, and suitability for continuous detection of water level and fluctuation. Furthermore, a wireless self-powered fluctuation sensor early-warning system, which provides exact and wireless monitoring of fluctuation of a liquid surface, is also successfully developed.
Publication date: Available online 22 November 2017
Source:Materials Today
Author(s): Hao Li, Kecheng Wang, Yujia Sun, Christina T. Lollar, Jialuo Li, Hong-Cai Zhou
Gas storage and separation are closely associated with the alleviation of greenhouse effect, the widespread use of clean energy, the control of toxic gases, and various other aspects in human society. In this review, we highlight the recent advances in gas storage and separation using metal-organic frameworks (MOFs). In addition to summarizing the gas uptakes of some benchmark MOFs, we emphasize on the desired chemical properties of MOFs for different gas storage/separation scenarios. Greenhouse gases (CO2), energy-related gases (H2 and CH4), and toxic gases (CO and NH3) are covered in the review.
