Τρίτη 17 Οκτωβρίου 2017
An Efficient, Large-Scale Survey of Hepatitis C Viremia in the Democratic Republic of the Congo Using Dried Blood Spots
Abstract
Background
Efficient viral load testing is needed for hepatitis C (HCV) surveillance and diagnosis. HCV viral load testing using dried blood spots (DBSs), made with a single drop of finger-prick whole blood on filter paper, is a promising alternative to traditional serum- or plasma-based approaches. Methods
We adapted the Abbott Molecular m2000 instrument for high-throughput HCV viremia testing using DBSs with simple specimen processing and applied these methods to estimate the national burden of infection in the Democratic Republic of the Congo (DRC). We tested DBSs collected during the 2013–2014 DRC Demographic and Health Survey, including 1309 adults ≥40 years of age. HCV-positive samples underwent targeted sequencing, genotyping, and phylogenetic analyses. Results
This high-throughput screening approach reliably identified HCV RNA extracted from DBSs prepared using whole blood, with a 95% limit of detection of 1196 (95% confidence interval [CI], 866–2280) IU/mL for individual 6-mm punches and 494 (95% CI, 372–1228) IU/mL for larger 12-mm punches. Fifteen infections were identified among samples from the DRC Demographic and Health Survey; the weighted country-wide prevalence of HCV viremia was 0.9% (95% CI, 0.3%–1.6%) among adults ≥40 years of age and 0.7% (95% CI, .6%–.8%) among human immunodeficiency virus–infected subjects. All successfully genotyped cases were due to genotype 4 infection. Conclusions
DBS-based HCV testing represents a useful tool for the diagnosis and surveillance of HCV viremia and can easily be incorporated into specimen referral systems. Among adults ≥40 years of age in the DRC, 100000–200000 may have active infection and be eligible for treatment.Increases in Neisseria gonorrhoeae with Reduced Susceptibility to Azithromycin among Men who have sex with Men (MSM), in Seattle, King County, Washington: 2012 – 2016
Abstract
Background
Antimicrobial-resistant Neisseria gonorrhea is a major public health threat. The CDC recommends that clinicians treat gonorrhea with ceftriaxone 250mg plus azithromycin 1g. Resistance to azithromycin could affect gonorrhea control efforts. Methods
We evaluated antimicrobial susceptibility profiles and clinical data of gonococcal isolates collected at the Public Health–Seattle & King County (PHSKC) STD Clinic from 2012–2016, focusing on 2014–2016. We compared cases with CDC azithromycin (AZM) alert value MIC (MIC ≥2 µg/mL) to those with AZM MIC ≤1 µg/mL, and evaluated clinical outcomes. Results
In 2012 and 2013, none of the 263 patients from whom we isolated N. gonorrhoeae were infected with organisms with an AZM MIC ≥2 µg/mL. Between 2014–2016, 4.4% of 926 gonorrhea cases demonstrated reduced susceptibility to AZM; 93% of these cases occurred among men who have sex with men (MSM). Among MSM, 5.4%, 4.8% and 4.6% of cases from 2014, 2015, and 2016, respectively, and 5.0% cumulatively, demonstrated reduced susceptibility to AZM. No AZM alert value isolates had concomitant cephalosporin resistance. There were 2 potential treatment failures: one pharyngeal infection treated with azithromycin 2g alone, and one pharyngeal infection that persisted after a study drug. Conclusions
Among MSM with gonorrhea in Seattle, 5% have gonorrhea with reduced susceptibility to AZM. The World Health Organization recommends changing treatment guidelines when >5% of isolates are resistant to a recommended drug. The emergence of potentially resistant AZM gonorrhea should prompt reconsideration of current treatment recommendations, and highlights the need to develop new therapies for gonorrhea.Diagnostics for yaws eradication: insights from direct next generation sequencing of cutaneous strains of Treponema pallidum
Abstract
Background
Yaws-like chronic ulcers can be caused by Treponema pallidum subsp. pertenue, Haemophilus ducreyi, or other still-undefined bacteria. To permit accurate evaluation of yaws elimination efforts programmatic use of molecular diagnostics is required. The accuracy and sensitivity of current tools remains unclear because our understanding of T. pallidum diversity is limited by the low number of sequenced genomes. Methods
We tested samples from patients with suspected yaws collected in previous studies in the Solomon Islands and Ghana. All samples were from patients whose lesions had previously tested negative using the current CDC diagnostic assay in widespread use. However, some of these patients had positive serological assays for yaws on blood. We used direct whole genome sequencing to identify T.p subsp. pertenue strains missed by the current assay. Results
From 45 Solomon Islands and 27 Ghanaian samples, 11 were positive for T. pallidum DNA using the species-wide qPCR, from which we obtained 6 previously undetected T. p. subsp. pertenue whole genome sequences. These sequences show that Solomon Islands sequences represent distinct T. p. subsp. pertenue clades. These isolates were invisible to the CDC diagnostic PCR assay in widespread current use, due to sequence variation in the primer binding site. Conclusion
Our data double the number of published T. p. subsp. pertenue genomes. We show that Solomon Islands strains are undetectable by the PCR used in many studies and by health ministries. This assay is therefore not adequate for the eradication programme. Next-generation genome sequence data are essential for these efforts.Impact of HIV on the burden and severity of influenza illness in Malawian adults: a prospective cohort and parallel case-control study
Abstract
Background
The impact of HIV infection on influenza incidence and severity in adults in sub-Saharan Africa is unclear. Seasonal influenza vaccination is recommended for HIV-infected persons in developed settings, but is rarely implemented in Africa. Methods
We conducted a prospective cohort study to compare the incidence of laboratory-confirmed influenza illness between HIV-infected and HIV-uninfected adults in Blantyre, Malawi. In a parallel case-control study, we explored risk factors for severe influenza presentation of severe (hospitalized lower respiratory tract infection (LRTI)), and mild influenza (influenza-like illness (ILI)). Results
The cohort study enrolled 608 adults (360 (59%) HIV-infected). Between April 2013 and March 2015, 24/229 (10.5%) ILI episodes in HIV-infected and 5/119 (4.2%) in HIV-uninfected adults were influenza PCR positive (incidence rates 46.0 vs. 14.5 per 1000 person years, incidence rate ratio 2.75; 95% confidence interval [CI] 1.02-7.44; p=0.03, adjusted for age, gender, household crowding and food security). In the case control study, influenza was identified in 56/518 (10.8%) patients with hospitalized LRTI, and 88/642 (13.7%) with ILI. HIV prevalence among influenza-positive cases and controls were 69.6% and 29.6% respectively. HIV was a significant risk factor for severe influenza (odds ratio 4.98, 95%CI 2.09-11.88, p<0.001; population attributable fraction 57%, adjusted for season, sanitation facility and food security). Conclusions
HIV is an important risk factor for influenza-associated ILI and severe presentation in this high HIV prevalence African setting. Targeted influenza vaccination of HIV-infected African adults should be re-evaluated and the optimal mechanism for vaccine introduction in overstretched health systems needs to be determined.Clinical and laboratory features of Group B Streptococcus meningitis in infants and newborns: study of 848 cases in France from 2001-2014
Abstract
Background
Group B Streptococcus (GBS) disease is the leading cause of neonatal bacterial meningitis despite women receiving an intravenous antibiotic prophylaxis (IAP) during labor. We aimed to describe GBS meningitis in children less than 1 year old in France during 2001-2014. Methods
Clinical and biological data of GBS meningitis gathered by ACTIV/GPIP and the French National Reference Center for Streptococci were analyzed. The cases were classified by age: 0 to 6 days old (early-onset disease [EOD]), newborns and infants 7 to 89 days old (late-onset disease [LOD]: LOD1, 7–26 days; LOD2, 27–89 days to 3 months) and infants 3 months to 1 year old (infant disease [ID]). Results
Among 848 GBS meningitis cases from 2001-2014, the incidence of EOD decreased by 63.3% (95% confidence interval [95% CI] [43.9; 80.1], p<0.001) and that of LOD increased by 58.1% 95% CI [39.1; 75.5] p<0.001 (52.9% and 64.3% for LOD1 and LOD2). The mean gestational age (GA) decreased significantly for EOD, LOD1, LOD2 and ID cases, respectively: 38.7, 38.6, 37.3 and 34 weeks. Serotype III accounted for 83.9% of cases, with no significant difference among the four groups or by GA. The frequency of GBS belonging to the clonal complex 17 did not differ among the four groups. Case mortality was 11.4%. Conclusions
In the era of IAP, we found decreased incidence of early-onset GBS meningitis, but unexpectedly, increased incidence of LOD. These data underline the interest in the development of effective GBS vaccines for pregnant women.Desmoplastic Small Round Cell Tumor Presenting as an Ocular Mass: Unusual Localization and Remarkable Surgical Approach
Abstract
Desmoplastic small round cell tumor (DSRCT) is a rare tumor that was first described by Gerald and Rosai in 1989 as a mesenchymal entity. This tumor has a unique translocation t (11:22) (p:13, q:12) resulting in EWS/WT1 gene fusion that is diagnostic for DSCRT. The overall prognosis for desmoplastic small round cell tumor remains extremely poor, with reported rates of death as high as 90%. Although the majority of patients undergo chemotherapy following surgery, the prognosis has been shown to be independent of whether the surgical process preceded or followed chemotherapy. In this review, we provide insights for the management of DSCRT that requires aggressive multimodality therapy.
Extensive nail changes in a toddler with multisystemic Langerhans cell histiocytosis
Abstract
Langerhans cell histiocytosis (LCH) is a multisystem disorder involving various organs. Nail changes in LCH are extremely rare. We present this case report of extensive nail changes in an 18-month-old child with multisystem LCH.
Methotrexate treatment in a case of juvenile pityriasis rubra pilaris
Abstract
An 8-year-old boy who was initially diagnosed with plaque psoriasis failed management with topical therapies and skin biopsy confirmed the suspected diagnosis of juvenile pityriasis rubra pilaris (PRP). Pityriasis rubra pilaris is a rare inflammatory disorder of the skin characterized by follicular keratotic papules coalescing into plaques, along with palmoplantar keratoderma. Treatment modalities include topical and systemic therapies, although previous studies have not shown much benefit with methotrexate in children. We present a case in which methotrexate led to significant improvement of the skin findings in a child with type IV juvenile pityriasis rubra pilaris.
Latent Autoimmune Diabetes in Adults in North Indian Region: Assessment of β-Cell Function, Metabolic and Immunological Features
Metabolic Syndrome and Related Disorders , Vol. 0, No. 0.
Alternaria alternata (Fr.) Keissl with mutation G143A in the Cyt b gene is the source of a difficult-to-control allergen
Abstract
The saprotrophic fungus Alternaria alternata is widespread in the agro-environment and produces more than ten allergenic proteins, mostly protein Alt a 1. The frequency of the Alt a 1 gene was analyzed in a group of A. alternata isolates from winter wheat kernels obtained in Poland, and the effectiveness of various fungicides targeting the pathogen was evaluated. The Alt a 1 gene was identified in four of the seven tested isolates. A. alternata colonized 35.67% kernels on average, but its frequency increased in stored grain where the presence of epiphytes was noted on 23.09 to 51.38% kernels, and endophytes—in 26.21 to 42.01% of kernels. The efficacy of field-applied fungicides did not exceed 50%, despite the fact that A. alternata is highly sensitive to propiconazole, fenpropimorph, and tebuconazole under in vitro conditions. The analyzed isolates were characterized by limited sensitivity to azoxystrobin (EC50 ranged from 0.505 to 1.350 μg cm−3) due to a mutation at codon 143 of the CYT b gene, responsible for resistance to quinone outside inhibitor fungicides, which was noted in all isolates. The spread of A. alternata can be effectively controlled with suitable fungicides and by monitoring the prevalence of pathogenic isolates in the environment.
Multi-site lymphatic venous anastomosis using echography to detect suitable subcutaneous vein in severe lymphedema patients
The method of lymphatic venous anastomosis (LVA), including its indications or pre-operative examinations, has not been established. The purpose of this study is to reveal the possible application of pre-operative echography in surgical LVA outcome.
Three-stage folded forehead flap for nasal reconstruction: objective and subjective measurements of aesthetic and functional outcomes.
This three-stage folded forehead flap (FFF) proved to be a simple and readily available method of lining replacement. To date, no clinical trial has evaluated the outcomes of the FFF the nose shape and function.
Investigating the pros and cons of browns gas and varying EGR on combustion, performance, and emission characteristics of diesel engine
Abstract
The significance of mileage to the fruitful operation of a trucking organization cannot be downplayed. Fuel is one of the biggest variable expenses in a trucking wander. An attempt is made in this research to improve the combustion efficiency of a diesel engine for better fuel economy by introducing hydroxy gas which is also called browns gas or HHO gas in the suction line, without compromising performance and emission. Brown's gas facilitates the air-fuel mixture to ignite faster and efficient combustion. By considering safety and handling issues in automobiles, HHO gas generation by electrolysis of water in the presence of sodium bicarbonate electrolytes (NaHCO3) and usage was explored in this research work over compressed pure hydrogen, due to generation and capacity of immaculate hydrogen as of now confines the application in diesel engine operation. Brown's gas was utilized as a supplementary fuel in a single-cylinder, four-stroke compression ignition (CI) engine. Experiments were carried out on a constant speed engine at 1500 rpm, result shows at constant HHO flow rate of 0.73 liter per minute (LPM), brake specific fuel consumption (BSFC) decreases by 7% at idle load to 16% at full load, and increases brake thermal efficiency (BTE) by 8.9% at minimum load to 19.7% at full load. In the dual fuel (diesel +HHO) operation, CO emissions decreases by 19.4, 64.3, and 34.6% at 25, 50, and 75% load, respectively, and unburned hydrocarbon (UHC) emissions decreased by 11.3% at minimum load to 33.5% at maximum load at the expense of NOx emission increases by 1.79% at 75% load and 1.76% at full load than neat diesel operation. The negative impact of an increase in NOx is reduced by adding EGR. It was evidenced in this experimental work that the use of Brown's gas with EGR in the dual fuel mode in a diesel engine improves the fuel efficiency, performance, and reduces the exhaust emissions.
Determination of element composition and extraterrestrial material occurrence in moss and lichen samples from King George Island (Antarctica) using reactor neutron activation analysis and SEM microscopy
Abstract
Seven lichens (Usnea antarctica and U. aurantiacoatra) and nine moss samples (Sanionia uncinata) collected in King George Island were analyzed using instrumental neutron activation analysis, and concentration of major and trace elements was calculated. For some elements, the concentrations observed in moss samples were higher than corresponding values reported from other sites in the Antarctica, but in the lichens, these were in the same range of concentrations. Scanning electron microscopy (SEM) and statistical analysis showed large influence of volcanic-origin particles. Also, the interplanetary cosmic particles (ICP) were observed in investigated samples, as mosses and lichens are good collectors of ICP and micrometeorites.
Adsorption and desorption for dynamics transport of hexavalent chromium (Cr(VI)) in soil column
Abstract
Batch experiments have been carried out to study the adsorption of heavy metals in soils, and the migration and transformation of hexavalent chromium (Cr(VI)) in the soil of a vegetable base were studied by dynamic adsorption and desorption soil column experiments. The aim of this study was to investigate the effect of initial concentration and pH value on the adsorption process of Cr(VI). Breakthrough curve were used to evaluate the capacity of Cr(VI) adsorption in soil columns. The results show that the higher the initial concentration, the worse the adsorption capacity of Cr(VI). The adsorption of Cr(VI) was strongly sensitive to pH value. The capacity of Cr(VI) adsorption is maximized at very low pH value. This may be due to changes in pH that cause a series of complex reactions in Cr(VI). In a strongly acidic environment, the reaction of Cr(VI) with hydrogen ions is accompanied by the formation of Cr3+, which reacts with the soil free iron-aluminum oxide to produce hydroxide in the soil. The results of the desorption experiments indicate that Cr(VI) is more likely to leach from this soil, but if the eluent is a strong acid solution, the leaching process will be slow and persistent. During the experiment, the pH value of the effluent was in the range of 7–8.5, which tends to the original pH value of the soil. It is indicating that the soil has a strong buffer on the acid liquid. The program CXTFIT was used to fit the breakthrough curve to estimate parameters. The results of the calculation of the dispersion coefficient (D) can be obtained by this program. The two-site model fit the breakthrough curve data of Cr(VI) well, and the parameters calculated by the CXTFIT can be used to explain the behavior of Cr(VI) migration and transformation in soil columns. When pH = 2, the retardation factor (R) reach at 79.71 while the value of the R is generally around 10 in other experiments. The partitioning coefficient β shows that more than half of the adsorption sites are instantaneous in this adsorption process and non-equilibrium affects the Cr(VI) transport process in this soil.
Assessment of filtration efficiency and physiological responses of selected plant species to indoor air pollutants (toluene and 2-ethylhexanol) under chamber conditions
Abstract
Three common plant species (Dieffenbachia maculata, Spathiphyllum wallisii, and Asparagus densiflorus) were tested against their capacity to remove the air pollutants toluene (20.0 mg m−3) and 2-ethylhexanol (14.6 mg m−3) under light or under dark in chamber experiments of 48-h duration. Results revealed only limited pollutant filtration capabilities and indicate that aerial plant parts of the tested species are only of limited value for indoor air quality improvement. The removal rate constant ranged for toluene from 3.4 to 5.7 L h−1 m−2 leaf area with no significant differences between plant species or light conditions (light/dark). The values for 2-ethylhexanol were somewhat lower, fluctuating around 2 L h−1 m−2 leaf area for all plant species tested, whereas differences between light and dark were observed for two of the three species. In addition to pollutant removal, CO2 fixation/respiration and transpiration as well as quantum yield were evaluated. These physiological characteristics seem to have no major impact on the VOC removal rate constant. Exposure to toluene or 2-ethylhexanol revealed no or only minor effects on D. maculata and S. wallisii. In contrast, a decrease in quantum yield and CO2 fixation was observed for A. densiflorus when exposed to 2-ethylhexanol or toluene under light, indicating phytotoxic effects in this species.
Breast Reduction: Decreasing Complications and Improving Long-Term Aesthetic Results with Parenchymal Sutures
Background: The inverted T/keyhole pattern is commonly used for large breast reductions. This technique relies on the breast skin to retain the shape. With the passage of time "fallout" (pseudoptosis) occurs impairing the cosmetic result. A technique is described that uses parenchymal sutures and inframammary fold (IMF) reinforcement sutures to maintain the intraoperative shape. Methods: A retrospective study of 25 consecutive patients (50 breasts) where the IMF was reinforced and parenchymal sutures were inserted. The patients were followed up and the nipple to notch and nipple to IMF distance was measured and compared with that marked preoperatively and set intraoperatively. Complications, especially T junction breakdown, were also recorded. Results: The mean age was 38 years (range, 16–62 years) with a mean follow-up of 12 months. The mean body mass index was 31 (range, 22–41). The mean mass of tissue excised was 925 g (range, 340–1,800 g) per side. The distance from the suprasternal notch to the nipple remained unchanged. The distance from the nipple to the IMF remained the same as that marked preoperatively except in 3 patients who developed pseudoptosis. Only 3 patients had wound dehiscence. Conclusion: Parenchymal and superficial fascial system sutures combined with IMF reinforcement contributes to maintaining the aesthetic result and decreasing complications, in weight stable patients.Characterization of Surgical Procedures in the Spanish Mohs Surgery Registry (REGESMOHS) for 2013-2015
Publication date: Available online 17 October 2017
Source:Actas Dermo-Sifiliográficas (English Edition)
Author(s): E. de Eusebio Murillo, A. Martín Fuentes, V. Ruiz-Salas, J.R. Garcés, R. Miñano Medrano, J.L. López-Estebaranz, T. Alonso-Alonso, M.Á. Rodríguez-Prieto, Y. Delgado Jiménez, V. Morales, P. Redondo Bellón, E. Manubens-Mercadé, O. Sanmartín-Jiménez, C. Guillén Barona, R. Cabeza, N. Cano, A. Toll-Abelló, R. Navarro Tejedor, J.L. Artola Igarza, I. Allende Markixana, A. Alfaro Rubio, C. Ciudad Blanco, H. Vázquez-Veiga, L. Barchino Ortiz, M.A. Descalzo, I. García-Doval
IntroductionThe Spanish Mohs Surgery Registry is used to collect data on the use and outcomes of Mohs micrographic surgery (MMS) in Spain. The aim of this study was to describe perioperative and intraoperative data recorded for MMS procedures performed between July 2013 (when the registry started) and January 2016.Material and methodsProspective cohort study of data from 18 hospitals. The data collected included type of anesthesia, surgical technique, hospital admission, number of Mohs stages, management of preoperative risk factors, additional treatments, previous treatments, type of tumor, operating time, and complications.ResultsData were available for 1796 operations. The most common tumor treated by MMS was basal cell carcinoma (85.96%), followed by squamous cell carcinoma (6.18%), lentigo maligna (2.81%), and dermatofibrosarcoma protuberans (1.97%). Primary tumors accounted for 66.9% of all tumors operated on; 19.2% of tumors were recurrent and 13.9% were persistent. The most common previous treatment was surgical. MMS was mostly performed under local anesthesia (86.7% of cases) and as an outpatient procedure (71.8%). The frozen section technique was used in 89.5% of cases. One stage was needed to achieve tumor-free margins in 56.45% of patients; 2 stages were required in 32.1% of patients, 3 in 7.1%%, 4 in 2.7%, and 5 or more in 1.8%. The defect was reconstructed by the dermatologist in 98% of patients and the most common technique was flap closure (47.2%). Intraoperative complications were recorded for just 1.62% of patients and the median (interquartile range) duration of surgery was 75 (60-100) minutes.ConclusionThe characteristics of the patients and tumors treated by MMS are similar to those reported for similar studies in other geographic areas. Lentigo maligna and dermatofibrosarcoma protuberans accounted for a higher proportion of cases in our series, and repair of the surgical defect by a dermatologist was also more common. Operating times in MMS are not much longer than those reported for other procedures and the rate of intraoperative complications is very low.
Beyond Genes: Treating Memory Loss with Minimum Adverse Effects
By Jamshed Arslan Pharm.D.
Research Associate, University of Alabama, Birmingham
Alzheimer's disease (AD) robs people of their memory and identity. One characteristic feature of AD is the increased expression of the enzyme, histone deacetylase-2 (HDAC-2). This protein stops the expression of some memory-forming genes by condensing them. So, memory can be enhanced by inhibiting HDAC-2. However, this approach is dangerous since HDAC-1, a close family member of HDAC-2, would also become inhibited, resulting in neuronal death and other toxic effects. New research,[1] led by Li-Huei Tsai at the Massachusetts Institute of Technology, Cambridge, suggests a novel way to specifically repress HDAC-2 by targeting the domain of HDAC-2 that makes a complex with the transcription factor, Sp3.
HDACs interact with different binding partners to regulate gene expression. Tsai's team sought to identify specific proteins that recruit HDAC-2 to memory-related genes. Researchers identified these proteins through weighted gene co-expression network analysis (WGCNA), which detects genetic correlational patterns across microarray samples. Binding of candidate proteins (co-regulators) to HDAC-2 was confirmed via immunoprecipitation assays. Knockdown of identified co-regulators in cultured mouse neurons was then used to elucidate their role in regulating synaptic function. It turns out that only the knockdown of Sp3 produced a synaptic effect similar to that seen with Hdac-2-knockdown, resulting in improved synaptic plasticity and memory.
Tsai's team had previously shown[2] that inhibiting Hdac-2 in the hippocampi of mice with AD-like symptoms improved synaptic transmission. In the current study,[1] RNA sequence analysis from mice neurons revealed that knockdown of Sp3 upregulates virtually the same memory-related genes that are targeted for inhibition by Hdac-2. Chromatin immunoprecipitation assays indicated that Sp3 knockdown reduces recruitment of Hdac-2 to the promoters of synaptic genes. Reversing the upregulation of Sp3 inhibited Hdac-2 in AD model mice, restoring the expression of Hdac-2 target genes. In line with these findings, the hippocampi of AD patients were found to have increased expression of both Sp3 and HDAC-2. Together, these studies on mice and humans show that Sp3 recruits HDAC-2 to the promoters of genes involved in memory, where HDAC-2 inhibits their expression.
Once it was clear that HDAC-2 and Sp3 co-regulate the same genes implicated in AD, researchers generated a peptide inhibitor that could disrupt the HDAC-2-Sp3 complex formation. Successful inhibition of the complex enhanced synaptic function in neurons, and improved memory in mice without damaging vital cell functions. Only the future will tell if this peptide-inhibitor approach would be effective at the clinic. However, the discovery of a clear role of Sp3 in cognition opens new avenues for drug targeting with minimal side effects.
This is the first study to use WGCNA to detect co-regulators of HDAC-2. In this way, Tsai's team has paved the way for applying bioinformatics and functional assays to other epigenetic regulators and tissues.
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References
- Yamakawa, Hidekuni, et al. "The Transcription Factor Sp3 Cooperates with HDAC2 to Regulate Synaptic Function and Plasticity in Neurons." Cell Reports, vol. 20, no. 6, 2017, pp. 1319–1334.
- Gräff, Johannes, et al. "An epigenetic blockade of cognitive functions in the neurodegenerating brain." Nature, vol. 483, no. 7388, 2012, pp. 222–226.
The pedicled posteromedial thigh (pPMT) perforator flap and its application in loco-regional soft tissue reconstructions
Source:Journal of Plastic, Reconstructive & Aesthetic Surgery
Author(s): Mario F. Scaglioni, Alberto Franchi, Pietro Giovanoli
IntroductionThe posteromedial thigh (PMT) perforator flap is a valuable reconstructive option. In its pedicled form the experience is currently limited to a few case reports. The purpose of this article is to describe various clinical applications of the pedicled posteromedial thigh flap (pPMT) for reconstruction of loco-regional soft tissue defects.Patients and MethodsFrom 2014 to 2016, 15 patients underwent reconstruction with 15 pedicled PMT (pPMT) flaps. The locations of the defects included: the inguinal region (4 cases), the perineal and genital region (3 cases), the proximal and distal medial thigh (3 and 2 cases, respectively) and the popliteal fossa (3 cases). The perforator selected was a branch of the profunda femoris artery (PFA) in 12 cases and the medial circumflex fermoral artery (MCFA) in 3 cases. In all cases the flap was harvested as a perforator-based island flap while the mechanism of flap transfer varied between V-Y advancement, interpolation or different degrees of axial pivoting around the skeletonised perforator (propeller flap design).ResultsThe flap sizes varied from 5 × 4 cm2 to 29 × 8 cm2 and the pedicle could be skeletonised for up to 13 cm. All of the flaps survived after surgery without complication. The donor sites were all primarily closed with minimal morbidity. Follow-up observations were conducted for 6 to 14 months, and all patients had good functional recovery.ConclusionThe pedicled PMT (pPMT) perforator flap is a reconstructive option that can be considered when dealing with soft tissue defects located in body regions ranging from the groin down to the popliteal fossa. It avoids the need for a microsurgical transfer and easily fulfils the dictum of replacing "like tissue with like tissue".
Three-stage folded forehead flap for nasal reconstruction: objective and subjective measurements of aesthetic and functional outcomes.
Source:Journal of Plastic, Reconstructive & Aesthetic Surgery
Author(s): Warren Noel, Jean-Brice Duron, Samer Jabbour, Marc Revol, Sarra Mazouz-Dorval
BackgroundThis three-stage folded forehead flap (FFF) proved to be a simple and readily available method of lining replacement. To date, no clinical trial has evaluated the outcomes of the FFF the nose shape and function.MethodsPatients undertaking a full thickness unilateral alar reconstruction with a forehead flap between January of 2010 and December of 2015 were included for analysis. Patients were divided into two groups: The FFF group included patients that had a unilateral alar reconstruction using a three-stage folded forehead flap; the standard forehead flap (SFF) group included patients that had a reconstruction using a two-stage forehead flap in combination with another method for lining reconstruction. The following objective measurements were done: The alar thickness, the nostril and hemi-nose areas and the nostril height. Subjective evaluation of the results was assessed using the NAFEQ score. Independent raters also evaluated the appearance of the nose.Results31 patients were included: 15 in FFF group and 16 in the SFF group. In both groups, the reconstructed ala was thicker than the normal side, the reconstructed nostril was smaller than the normal nostril and the reconstructed hemi-nose was bigger than the normal side. 84% of patients were satisfied with their total nasal functioning. All the patients were satisfied with their total nasal appearance.ConclusionThe FFF showed objective, subjective, aesthetic and functional results comparable to other lining reconstruction techniques.
Multi-site lymphatic venous anastomosis using echography to detect suitable subcutaneous vein in severe lymphedema patients
Source:Journal of Plastic, Reconstructive & Aesthetic Surgery
Author(s): Makoto Mihara, Hisako Hara, Yoshihisa Kawakami, Hang Peng Zhou, Shuichi Tange, Kazuki Kikuchi, Takuya Iida
BackgroundThe method of lymphatic venous anastomosis (LVA), including its indications or pre-operative examinations, has not been established. The purpose of this study is to reveal the possible application of pre-operative echography in surgical LVA outcome.MethodsWe performed a retrospective case-control study on patients with lower limb lymphedema who underwent LVA between August 15, 2013 and August 15, 2014. As a pre-operative examination, we introduced venous echography to identify subcutaneous veins in the echo group, and we only used Accuvein visualizing system in the control group. The operation time, number of anastomoses, and limb circumference were compared between the two groups.ResultsSeventeen patients (34 limbs) were included in the echo group, and 21 patients (42 limbs) were included in the control group. The average follow-up period was 11.9 (6-16) and 12.4 (6-27) months, respectively. The average operation time in the echo group was 258.6 minutes, and that in the control group was 216.5 minutes. The average number of anastomoses was 9.8 in the echo group and 7.0 in the control group. The average time per anastomosis in each group was 27.4 and 32.6 minutes, respectively. The diameter of the vein had a tendency to be larger in the echo group than in the control group. In 5.8 % of the echo group, we observed a circumference increase, compared with 23.8 % in the control group.ConclusionsPreoperative venous echography allowed surgeons to increase the number of anastomoses performed within the operating time, resulting in improvement of surgical outcomes.
Perspectives on Integrating Genetic and Physical Explanations of Evolution and Development: An Introduction to the Symposium
Abstract
In the 20th century, genetic explanatory approaches became dominant in both developmental and evolutionary biological research. By contrast, physical approaches, which appeal to properties such as mechanical forces, were largely relegated to the margins, despite important advances in modeling. Recently, there have been renewed attempts to find balanced viewpoints that integrate both biological physics and molecular genetics into explanations of developmental and evolutionary phenomena. Here we introduce the 2017 SICB symposium "Physical and Genetic Mechanisms for Evolutionary Novelty" that was dedicated to exploring empirical cases where both biological physics and developmental genetic considerations are crucial. To further contextualize these case studies, we offer two theoretical frameworks for integrating genetic and physical explanations: combining complementary perspectives and comprehensive unification. We conclude by arguing that intentional reflection on conceptual questions about investigation, explanation, and integration is critical to achieving significant empirical and theoretical advances in our understanding of how novel forms originate across the tree of life.Genetic Decoupling of Thermal Hardiness across Metamorphosis in Drosophila melanogaster
Abstract
As organisms age the environment fluctuates, exerting differential selection across ontogeny. In particular, highly seasonal environments expose life stages to often drastically different thermal environments. This developmental variation is particularly striking in organisms with complex life cycles, wherein life history stages also exhibit distinct morphologies, physiologies, and behaviors. Genes acting pleiotropically on thermal responses may produce genetic correlations across ontogeny, constraining the independent evolution of each life stage to their respective thermal environments. To investigate whether developmental genetic correlations constrain the evolution thermal hardiness of the fly Drosophila melanogaster, we applied quantitative genetic analyses to cold hardiness measured in both larvae and adults from isogenic lines of the Drosophila Genetic Reference Panel (DGRP), using survival at stressful low temperatures as the phenotypic metric. Using full genome resequencing data for the DGRP, we also implemented genome-wide association (GWA) analysis using Bayesian Sparse Linear Mixed Models (BSLMMs) to estimate associations between naturally segregating variation and cold hardiness for both larvae and adults. Quantitative genetic analyses revealed no significant genetic correlation for cold hardiness between life stages, suggesting complete genetic decoupling of thermal hardiness across the metamorphic boundary. Both quantitative genetic and GWA analyses suggested that polygenic variation underlies cold hardiness in both stages, and that associated loci largely affected one stage or the other, but not both. However, reciprocal enrichment tests and correlations between BSLMM parameters for each life stage support some shared physiological mechanisms that may reflect common cellular thermal response pathways. Overall, these results suggest no developmental genetic constraints on cold hardiness across metamorphosis in D. melanogaster, an important consideration in evolutionary models of responses to changing climates. Genetic correlations for environmental sensitivity across ontogeny remains largely unexplored in other organisms, thus assessing the generality of genetic decoupling will require further quantitative or population genetic analysis in additional species.Green synthesis, characterization and catalytic degradation studies of gold nanoparticles against Congo Red and Methyl Orange
Publication date: Available online 16 October 2017
Source:Journal of Photochemistry and Photobiology B: Biology
Author(s): C. Umamaheswari, A. Lakshmanan, N.S. Nagarajan
The present study reports, novel and greener method for synthesis of gold nanoparticles (AuNPs) using 5,7-dihydroxy-6-metoxy-3',4'methylenedioxyisoflavone (Dalspinin), isolated from the roots of Dalbergia coromandeliana was carried out for the first time. The synthesized gold nanoparticles were characterized by UV–Vis spectroscopy, high resolution transmission electron microscopy (HR-TEM), selected area electron diffraction (SAED), Fourier transform infrared spectroscopy (FT-IR) and X-ray diffraction (XRD). The observed surface plasmon resonance (SPR) at 532nm in the UV–Vis absorption spectrum indicates the formation of gold nanoparticles. The powder XRD and SAED pattern for synthesized gold nanoparticles confirms crystalline nature. The HR-TEM images showed that the AuNPs formed were small in size, highly monodispersed and spherical in shape. The average particle sizes of the AuNPs are found to be ~10.5nm. The prepared AuNPs were found to be stable for more than 5months without any aggregation. The catalytic degradation studies of the synthesized AuNPs towards degradation of Congo red and Methyl orange, showed good catalytic in the complete degradation of both the dyes. The reduction catalyzed by gold nanoparticles followed the pseudo-first order kinetics, with a rate constant of 4.5×10−3S−1 (R2=0.9959) and 1.7×10−3S−1 (R2=0.9918) for Congo red (CR) and Methyl orange (MO), respectively.
Graphical abstract
Real world treatment patterns and outcomes among metastatic cutaneous melanoma patients treated with ipilimumab
Abstract
Background
There is a scarcity of real-world data on treatment patterns and outcomes among advanced melanoma patients treated with immunotherapies including ipilimumab, an anti-CTLA-4 antibody approved since 2011.
Objective
To evaluate ipilimumab and post-ipilimumab treatment patterns and outcomes among patients with advanced melanoma in Australia, Germany, Italy and Spain following regulatory approval.
Methods
Retrospective multicentre, multinational, observational chart review study. Data were extracted from the start of ipilimumab therapy until the end of at least 40 weeks of follow-up, or death.
Results
Data from 371 patients (Australia, 103; Germany, 152; Italy, 76; Spain, 40) were analysed. Mean age was 65 years; 62% were male. Eastern Cooperative Oncology Group performance status (ECOG PS) was 0 or 1 for 94%. In 67%, ipilimumab was initially received as second-line or later therapy. Patients received on average 3.4 ipilimumab doses. The ipilimumab-refractory cohort comprised of 226 patients. Of these, 17% in Australia, 47% in Germany, 29% in Italy and 14% in Spain received another anti-melanoma treatment after ipilimumab including chemotherapy in 26% and BRAF/other kinase inhibitors in 11%. Ipilimumab-refractory patients who received post-ipilimumab treatment showed a 40% reduced hazard of dying than those not receiving treatment after ipilimumab (HR 0.60; 95% CI 0.43-0.83), after adjustment for potential confounders.
Conclusion
During the time observed, ipilimumab was mainly used as second-line or later therapy. A significant proportion of patients received post-ipilimumab therapy, most of which was chemotherapy. Nevertheless, overall survival following progression on ipilimumab treatment remained poor, highlighting the need for research to develop more effective end-of-life treatment options.
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Retraction: Common superficial fungal infections in the pediatric age group
Indian Journal of Paediatric Dermatology 2017 18(4):353-353
Determination of the impact of melanoma surgical timing on survival using the National Cancer Database
The ideal timing for melanoma treatment, predominantly surgery, remains undetermined. Patient concern for receiving immediate treatment often exceeds surgeon or hospital availability, requiring establishment of a safe window for melanoma surgery.
Is there a relationship between melanocytes and sensorineural hearing loss? clinical evaluation of fifthy-one alopecia areata patients
Abstract
Melanocytes are located in both the cochlea and vestibular organ of the inner ear. They are present in the hearing organ, in the intermediate layer of stria vascularis in the cochlea.
The most important task of the stria vascularis is to provide the endolymph production necessary for normal hearing levels, especially high K+ concentration, and to protect the positive endocochlear potential.
Specifically, intermediate layer melanocytes express ionic channels, such as inwardly rectifying K+ channels and voltage-dependent outwardly rectifying K+.
The underlying mechanisms of the damage to melanocytes in the skin can also affect other organs, including inner ear.
Coexistence of cochlear dysfunction in alopecia areata patients suggest that presumed autoimmunity against follicular melanocytes in AA might also effect the melanocytes in the inner ear. This could strengthen the relationship between sensorineural hearing loss and autoimmunity.
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Aretrospective review of six-hundred nineteen cases to determine the prevalence and factors associated with revision endoscopic sinus surgery in AFRS vs non-AFRS patients
Abstract
Patients undergoing revision functional endoscopic sinus surgery (rFESS) for refractory chronic rhinosinusitis (CRS) are more likely to be older, have worse pre-operative Lund-Mackay CT scores, and poorer quality-of-life scores than primary FESS patients.
Patients with more aggressive forms of CRS such as CRS with nasal polyposis (CRSwNP) or allergic fungal rhinosinusitis (AFRS) may fare worse in the long term with residual disease and be more likely to seek out tertiary institutions for treatment including rFESS.
Computed tomography (CT) findings most frequently associated with failure of primary FESS were frontal sinus/recess residual bony partitions (91.8%), remnant ethmoid sinus shelves (88.2%) and unopened pneumatized ethmoid cells (77.7%).
Patients with a diagnosis of allergic fungal rhinosinusitis (AFRS) who required rFESS presented with significantly fewer frontal sinus residual bony partitions, residual uncinate process, and ethmoid sinus residual unopened pneumatized cells, than non-AFRS patients, suggesting that intrinsic biological factors were the major contributors to failure of primary FESS.
The factors associated with rFESS are numerous and should be explored further. Other factors that may be important to consider when assessing causes of primary FESS failure may include surgeon skill level as well as the availability of proper instrumentation and support staff in the setting in which the procedure is performed (e.g. tertiary vs community level hospital).
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Does omalizumab modify a course of recalcitrant chronic spontaneous urticaria?: A retrospective study in Asian patients
Abstract
Omalizumab has been approved for the treatment of recalcitrant chronic spontaneous urticaria (CSU). However, it remains unanswered whether omalizumab modifies a CSU course. We aimed to study a course of CSU after omalizumab treatment in an Asian population. Medical records of recalcitrant CSU patients who attended Siriraj Hospital between 2013 and 2017 were reviewed. All patients receiving omalizumab treatment were followed after the first injection for at least 1 year. Of 15 patients receiving omalizumab treatment, 11 patients (73.3%) responded well to 150 mg while the rest required 300 mg. The median follow-up period was 18 months (range, 13.5–25.3). Three patterns of response were proposed and measured: excellent (disease remission over than 6 months) was found in 20%; good (injection interval extended longer than 6 months) was found in 27%; and modest (frequently required injections) was found in 53%. The mean duration of complete remission was 33 weeks (range, 26–38). Two-thirds of patients had disease relapse and required omalizumab injections to control symptoms. The other third did not show relapses for at least 69 weeks of the follow-up period. After 1 year of treatment, Kaplan–Meier curves estimated that a higher percentage (86.7%) of recalcitrant CSU patients receiving omalizumab treatment would be free of symptoms (weekly Urticaria Activity Score = 0) without prednisolone and/or cyclosporin as compared with 42% of patients not receiving omalizumab treatment. In conclusion, patients seem to be easily and safely manageable with omalizumab. Prednisolone and cyclosporin could be discontinued in all patients. Further studies are needed to conclude whether omalizumab can exactly modify CSU.
Possible pro-inflammatory role of heparin-binding epidermal growth factor-like growth factor in the active phase of systemic sclerosis
Abstract
Heparin-binding epidermal growth factor (EGF)-like growth factor (HB-EGF) is a member of the EGF family growth factors, which affects multiple aspects of the wound healing process such as epithelialization, wound contraction and angiogenesis. In our study, we measured the serum HB-EGF levels of 51 systemic sclerosis (SSc) patients, which showed a significant increase compared with those of 20 normal subjects. Further analysis revealed a positive correlation between the HB-EGF level and pulmonary ground-glass score but no correlation between the former and pulmonary fibrosis score. Other findings include: a significant increase of serum sialylated carbohydrate antigen KL-6 levels and significant shortness of disease duration in the diffuse cutaneous SSc patients with elevated HB-EGF levels; and significantly higher HB-EGF levels in the presence of Raynaud's phenomenon, in that of telangiectasia, and in the absence of contracture of phalanges in all SSc patients. We then evaluated HB-EGF mRNA levels of fibroblasts harvested from skin samples of the SSc patients and those of foreskin-derived fibroblasts treated with transforming growth factor-β, both of which were significantly higher than each control. In conclusion, we speculate that HB-EGF plays a pro-inflammatory role in the active skin and lung lesions of SSc.
Between quality of life and hope. Attitudes and beliefs of Muslim women toward withholding and withdrawing life-sustaining treatments
Abstract
The technological advances in medicine, including prolongation of life, have constituted several dilemmas at the end of life. In the context of the Belgian debates on end-of-life care, the views of Muslim women remain understudied. The aim of this article is fourfold. First, we seek to describe the beliefs and attitudes of middle-aged and elderly Moroccan Muslim women toward withholding and withdrawing life-sustaining treatments. Second, we aim to identify whether differences are observable among middle-aged and elderly women's attitudes toward withholding and withdrawing life-sustaining treatments. Third, we aim to explore the role of religion in their attitudes. Fourth, we seek to document how our results are related to normative Islamic literature. Qualitative empirical research was conducted with a sample of middle-aged and elderly Moroccan Muslim women (n = 30) living in Antwerp (Belgium) and with experts in the field (n = 15). We found an unconditional belief in God's sovereign power over the domain of life and death (cf. determined lifespan by God) and in God's almightiness (cf. belief in a miracle). However, we also found a tolerant attitude, mainly among our middle-aged participants, toward withholding and withdrawing (treatment) based on theological, eschatological, financial and quality of life arguments. Our study reveals that religious beliefs and worldviews have a great impact on the ethical attitudes toward end-of-life issues. We found divergent positions toward withholding and withdrawing life-sustaining treatments, reflecting the lines of reasoning found in normative Islamic literature. In our interviews, theological and eschatological notions emerged as well as financial and quality of life arguments.
Why ‘believes’ is not a vague predicate
Abstract
According to what I call the 'Vagueness Thesis' ('VT') about belief, 'believes' is a vague predicate. On this view, our concept of belief admits of borderline cases: one can 'half-believe' something (Price in Belief, George Allen & Unwin, London, 1969) or be 'in-between believing' it (Schwitzgebel in Philos Q 51:76–82, 2001, Noûs 36:249–275, 2002, Pac Philos Q 91:531–553, 2010). In this article, I argue that VT is false and present an alternative picture of belief. I begin by considering a case—held up as a central example of vague belief—in which someone sincerely claims something to be true and yet behaves in a variety of other ways as if she believes that it is not. I argue that, even from the third-person perspective prioritised by proponents of VT, the case does not motivate VT. I present an alternative understanding of the case according to which the person in question believes as they say they do yet also has a belief-discordant implicit attitude otherwise. Moreover, I argue that, independently of the interpretation of any particular case, VT fails to accommodate the first-person perspective on belief. Belief is not only an item of one's psychology that helps explain one's behaviour; it is what one takes to be true. This fact about belief manifests itself in the nature of deliberation concerning whether to believe something and that of introspection regarding whether one believes something. Attending to these phenomena reveals that VT is not merely unmotivated, but untenable.
Calcipotriene/betamethasone dipropionate for the treatment of psoriasis vulgaris: an evidence-based review.
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Calcipotriene/betamethasone dipropionate for the treatment of psoriasis vulgaris: an evidence-based review.
Clin Cosmet Investig Dermatol. 2017;10:385-391
Authors: Patel NU, Felix K, Reimer D, Feldman SR
Abstract
While topical medications remain the cornerstone of the psoriasis treatment paradigm, they also come with the risk of multiple side effects. An alternative topical treatment option, calcipotriene or calcipotriol, is a vitamin D derivative that is thought to work by inhibiting keratinocyte proliferation and enhancing keratinocyte differentiation. Multiple studies have demonstrated its efficacy and safety in improving psoriasis when used in combination with topical corticosteroids. Given the effectiveness and side effect profile seen with this combination of topical steroid and calcipotriene, the US Food and Drug Administration approved a calcipotriene/betamethasone dipropionate product for use in psoriasis patients over the age of 12 in 2006. Our paper seeks to review clinical trial evidence of this combination medication and its use in the treatment of psoriasis vulgaris. While assessment of available evidence indicates that the topical medication is both safe and effective for the treatment of psoriasis vulgaris, addressing limitations of what is known, such as tolerability, adherence, and patient preference, of this combination drug in future high-impact studies is needed.
PMID: 29033598 [PubMed]
Prevalence and clinical significance of focal incidental 18 F-FDG uptake in different organs: an evidence-based summary
Abstract
Purpose
Several meta-analyses and systematic reviews have reported data about the prevalence and the malignancy risk of focal incidental uptake detected by 18F-FDG PET (FIU). This review aims to summarize the published evidence-based data about the most common sites, prevalence and malignancy risk of FIU, to derive schematic estimates in this setting.
Methods
A comprehensive computer literature search of meta-analyses or systematic reviews regarding FIU and published in PubMed/MEDLINE and/or Cochrane library database through June 2017 was carried out.
Results
Twelve articles were discussed in our summary and different organs were evaluated. The pooled prevalence of FIU ranged, respectively, from 1.6 to 3.6% for colon–rectum, from 1 to 2.46% for thyroid, being 0.4% for breast, 1.8% for prostate and 0.6% for parotid. Despite that, the pooled risk of malignancy considering histology as reference standard was quite high in all organs evaluated in the summary, except for parotid gland. In fact, it ranged from 61.5 to 76% for FIU in the colon–rectum (including both premalignant and malignant lesions), from 33.2 to 37% for FIU in the thyroid gland, and it was 60 and 62%, respectively, for breast and prostate FIU. For parotid FIU pathologically proven the pooled risk of malignancy was only 20.4%.
Conclusions
Our summary showed that the most frequent sites of FIUs are colon and thyroid according to literature data. The risk of malignancy is quite high for FIU in colon-rectum, thyroid, breast and prostate especially when histologically analyzed. Beyond the localization, when FIU are detected further investigation is warranted.
Photocatalytic decomposition of methanol over La/TiO 2 materials
Abstract
Lanthanum-modified TiO2 photocatalysts (0.2–1.5 wt% La) were investigated in the methanol decomposition in an aqueous solution. The photocatalysts were prepared by the common sol-gel method followed by calcination. The structural (X-ray diffraction, Raman, X-ray photoelectron spectroscopy), textural (N2 physisorption), and optical properties (diffuse reflectance spectroscopy, photoelectrochemical measurements) of all synthetized nanomaterials were correlated with photocatalytic activity. Both pure TiO2 and La-doped TiO2 photocatalysts proved higher yields of hydrogen in comparison to photolysis. The photocatalyst with optimal amount of lanthanum (0.2 wt% La) showed almost two times higher amount of hydrogen produced at the same time as in the presence of pure TiO2. The photocatalytic activity increased with both increasing photocurrent response and decreasing amount of lattice and surface O species. It has been shown that both direct and indirect mechanisms of methanol photocatalytic oxidation participate in the production of hydrogen. Both direct and indirect mechanisms take part in the formation of hydrogen.
Biologics for Itch: IL-4/IL-13, IL-31, IL-17, and IL-23 Antagonists
Abstract
Purpose of Review
The purpose of this review is to provide the current knowledge on antipruritic properties of IL-4/IL-13, IL-31, IL-17, and IL-23 antagonists in selected chronic skin conditions.
Recent Findings
Since pruritus is regarded as one of the most bothersome and unpleasant symptoms accompanying numerous inflammatory skin disorders, efforts are ongoing in the development of new treatment strategies capable of reducing its intensity thus improving the patients' quality of life. Recent discoveries in targeted therapies and studies on pruritus have established that blockade of certain cytokines and/or pathways not only reduces the severity of skin involvement, but also shows a potent antipruritic activity.
Summary
Considering a favorable safety profile of biologic drugs, their antipruritic properties are very promising and give a new hope for clinicians and the patients suffering from a number of itchy dermatoses. These recent findings clearly show that certain cytokines and their receptors may represent potential targets for innovative antipruritic drugs. Newer insights into the underlying pathogenesis of itch and identification of novel molecular pathways will undoubtedly promote the progress in the field of pruritus management.
Emerging treatment paradigms in brain metastasis in non-small cell lung cancer: an overview of the current landscape and challenges ahead.
Abstract
Advances in the last decade in genomic profiling and the identification of druggable targets amenable to biological agents, has transformed the management and survival of a subgroup of patients with brain metastasis in non-small cell lung cancer. In parallel, clinicians have re-evaluated the role of whole brain radiotherapy in selected patients with brain metastases to reduce neurocognitive toxicity. Continual progress in this understudied field is required: optimisation of the sequence of schedules for therapies in patients with brain metastases of differing genomic profiles, focusing on new strategies to overcome mechanisms of biological resistance and increasing drug penetrability into the central nervous system. This review summarises the field to date and possible treatment strategies based on current evidence.Phase II Trial of Pembrolizumab in Patients with Platinum Refractory Germ Cell Tumors: A Hoosier Cancer Research Network Study GU14-206
Background
Despite remarkable results with salvage standard-dose or high-dose chemotherapy about 15% of patients with relapsed germ-cell tumors (GCT) are incurable. Immune checkpoint inhibitors have produced significant remission in multiple tumor types. We report the first study of immunotherapy in patients with GCT. Patients and Methods
Single arm phase 2 trial investigating pembrolizumab 200mg IV Q3weeks until disease progression in patients with relapsed GCT and no curable options. Patients age≥18 with GCT who progressed after first-line cisplatin-based chemotherapy and after at-least 1 salvage regimen (high-dose or standard-dose chemotherapy) were eligible. Centrally assessed programmed death-ligand 1 (PD-L1) on tumor and infiltrating immune cells was scored. Primary endpoint was overall response rate (ORR) using immune-related response criteria. Simon two-stage design with type I error 20% and power 80% was utilized. Results
12 male patients were enrolled. Median age 38. All patients had non-seminoma. Primary site was testis (11) or mediastinum (1). Median AFP 615 (range,1-32,760) and hCG 4 (range,0.6-37,096). 6 patients had late relapse (>2years). Median number of previous chemotherapy regimens was 3. 6 patients received prior high-dose chemotherapy. 2 patients had positive PD-L1 staining (H-score 90 and 170). Median number of pembrolizumab doses was 2 (range,1-8). There were 6 grade 3 adverse events. No immune-related adverse events were reported. No partial or complete responses were observed. 2 patients achieved radiographic stable disease for 28 and 19 weeks, respectively; both had continued rising AFP level despite radiographic stability and had negative PD-L1 staining. Conclusion
This is the first reported trial evaluating immune checkpoint inhibitors in GCT. Pembrolizumab is well tolerated but does not appear to have clinically meaningful single-agent activity in refractory GCT.Clinical trial information:NCT02499952.Sticky fingers at work: palmitoylation-dependent MC1R activation
Abstract
The melanocortin-1 receptor (MC1R) is a G protein-coupled receptor (GPCR) positively coupled to the cAMP pathway. MC1R is expressed in melanocytes, where it is critically involved in the cutaneous responses to solar ultraviolet radiation (UVR). The current paradigm posits that UVR-induced DNA damage in skin keratinocytes activates expression of the POMC gene encoding for the precursor of α-melanocyte-stimulating hormone (αMSH). The resulting paracrine release of αMSH activates MC1R in melanocytes and switches the production of melanin pigments from basal pheomelanogenesis to synthesis of eumelanins.
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Photodynamic therapy inhibits melanogenesis through paracrine effects by keratinocytes and fibroblasts
Summary
Photodynamic therapy (PDT) is a treatment option for skin cancer and premalignant skin diseases and exhibits rejuvenation effects, including reducing fine wrinkles and whitening, on aged skin. In the present study, we investigated the mechanism underlying the whitening effects of PDT on melanocytes in vitro and in vivo. Exposure of melanocytes to PDT in vitro reduced their melanin content and tyrosinase activity without, however, affecting cell survival. Interestingly, melanogenesis was also inhibited by exposing melanocytes to conditioned media of PDT-treated keratinocytes or dermal fibroblasts. This paracrine effect was likely due to a decreased release of melanocyte-stimulating cytokines such as Kit ligand and hepatocyte growth factor from these cells. Furthermore, we observed that PDT reduced mottled hyperpigmentation of photoaged patient skin in vivo, highlighting the clinical importance of skin whitening by PDT.
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Suppression of MAPK signaling in BRAF-activated PTEN-deficient melanoma by blocking β-catenin signaling in cancer-associated fibroblasts
Summary
Cancer-associated fibroblasts (CAFs) in the tumor microenvironment have been associated with formation of a dynamic and optimized niche for tumor cells to grow and evade cell death induced by therapeutic agents. We recently reported that ablation of β-catenin expression in stromal fibroblasts and CAFs disrupted their biological activities in in vitro studies and in an in vivo B16F10 mouse melanoma model. Here, we show that the development of a BRAF-activated PTEN-deficient mouse melanoma was significantly suppressed in vivo after blocking β-catenin signaling in CAFs. Further analysis revealed that expression of phospho-Erk1/2 and phospho-Akt were greatly reduced, effectively abrogating the activating effects and abnormal cell cycle progression induced by Braf and Pten mutations. In addition, the epithelial-mesenchymal transition (EMT) -like process was also suppressed in melanoma cells. Taken together, our data highlight an important crosstalk between CAFs and the RAF-MEK-ERK signaling cascade in BRAF-activated melanoma, and may offer a new approach to abrogate host-dependent drug resistance in targeted therapy.
This article is protected by copyright. All rights reserved.
Wound care evidence, knowledge and education amongst nurses: a semi-systematic literature review
Abstract
The aims of this study were to determine the knowledge and skills of nurses involved in wound care, to provide a critical overview of the current evidence base underpinning wound care and to determine the extent of utilisation of existing evidence by nurses involved in the management of wounds in practice.
A semi-systematic review of the literature was undertaken on Cinahl, Medline Science Direct and Cochrane using the search terms: wound, tissue viability, education, nurse, with limitations set for dates between 2009 and 2017 and English language.
Shortfalls were found in the evidence base underpinning wound care and in links between evidence and practice, prevalence of ritualistic practice and in structured education at pre- and post-registration levels.
The evidence underpinning wound care practice should be further developed, including the conduction of independent studies and research of qualitative design to obtain rich data on both patient and clinician experiences of all aspects of wound management. More structured wound care education programmes, both at pre-registration/undergraduate and professional development levels, should be established.
Skin tears and risk factors assessment: a systematic review on evidence-based medicine
Abstract
Skin tears represent a common condition of traumatic wounds, which may be encountered in some categories of individuals at the extremes of age, such as infants and the elderly. Despite the high prevalence and cost of these lesions, there has been little investigation into the risk factors that lead to this condition. The aim of this review was to systematically evaluate the main risk factors involved in development of skin tears. We planned to include all the studies dealing with risk factors related to skin tears. Only publications in English were considered. We excluded all the studies that did not properly fit our research question and those with insufficient data. Of the 166 records found, 24 matched our inclusion criteria. After reading the full-text articles, we decided to exclude seven articles because of the following reasons: (1) not responding properly to our research questions and (2) insufficient data; the final set included 17 articles. From a literature search, we found the following main issues related to risk factors, which have been described in detail in this section: age-related skin changes, dehydration, malnutrition, sensory changes, mobility impairment, pharmacological therapies and mechanical factors related to skin care practices. Our findings clearly show that in frail populations (especially infant and elderly), the stratification risk, as a primary prevention strategy, is an effective tool in avoiding the development of chronic wounds. The development and the implementation of prevention strategies based on appropriate knowledge of the risk factors involved and the adoption of correct techniques during skin care practices could reduce or even avoid the onset of skin tears.
Determination of the human cytochrome P450 monooxygenase catalyzing the enantioselective oxidation of 2,2′,3,5′,6-pentachlorobiphenyl (PCB 95) and 2,2′,3,4,4′,5′,6-heptachlorobiphenyl (PCB 183)
Abstract
2,2′,3,5′,6-Pentachlorobiphenyl (PCB 95) and 2,2′,3,4,4′,5′,6-heptachlorobiphenyl (PCB 183) possess axial chirality and form the aS and aR enantiomers. The enantiomers of these congeners have been reported to accumulate in the human body enantioselectively via unknown mechanisms. In this study, we determined the cytochrome P450 (CYP) monooxygenase responsible for the enantioselective oxidization of PCB 95 and PCB 183, using a recombinant human CYP monooxygenase. We evaluated 13 CYP monooxygenases, namely CYP1A1, CYP1A2, CYP1B1, CYP2A6, CYP2B6, CYP2C8, CYP2C19, CYP2E1, CYP2J2, CYP3A4, CYP3A5, CYP4F2, and aromatase (CYP19), and revealed that CYP2A6 preferably oxidizes aS-PCB 95 enantioselectively; however, it did not oxidize PCB 183. The enantiomer composition was elevated from 0.5 (racemate) to 0.54. In addition, following incubation with CYP2A6, the enantiomer fraction (EF) of PCB 95 demonstrated a time-dependent increase.
Evaluation of leafy vegetables as bioindicators of gaseous mercury pollution in sewage-irrigated areas
Abstract
Mercury (Hg) can evaporate and enter the plants through the stomata of plant leaves, which will cause a serious threat to local food safety and human health. For the risk assessment, this study aimed to investigate the concentration and accumulation of total gaseous mercury (TGM) in five typical leafy vegetables (Chinese chives (Allium tuberosum Rottler), amaranth (Amaranthus mangostanus L.), rape (Brassica campestris L.), lettuce (Lactuca sativa L.), and spinach (Spinacia oleracea L.)) grown on sewage-irrigated areas in Tianjin, China. The following three sites were chosen to biomonitor Hg pollution: a paddy field receiving sewage irrigation (industrial and urban sewage effluents) for the last 30 years, a vegetable field receiving sewage irrigation for 15 years, and a grass field which did not receive sewage irrigation in history. Results showed that the total Hg levels in the paddy (0.65 mg kg−1) and vegetation fields (0.42 mg kg−1) were significantly higher than the local background level (0.073 mg kg−1) and the China national soil environment quality standard for Hg in grade I (0.30 mg kg−1). The TGM levels in ambient air were significantly higher in the paddy (71.3 ng m−3) and vegetable fields (39.2 ng m−3) relative to the control (9.4 ng m−3) and previously reported levels (1.45 ng m−3), indicating severe Hg pollution in the atmospheric environment of the sewage-irrigated areas. Furthermore, gaseous mercury was the dominant form of Hg uptake in the leaves or irreversibly bound to leaves. The comparison of Hg uptake levels among the five vegetables showed that the gradient of Hg accumulation followed the order spinach > red amaranth > Chinese chives > rape > lettuce. These results suggest that gaseous Hg exposure in the sewage-irrigated areas is a dominant Hg uptake route in leafy vegetables and may pose a potential threat to agricultural food safety and human health.
Contact dermatitis caused by a new rubber compound detected in canvas shoes
Summary
Background
In 2015 and 2016, female patients in Flanders consulted a dermatologist because they developed skin lesions after wearing a specific brand of canvas shoes.
Objectives
To identify the culprit allergen in the shoes.
Methods
Eighteen young females aged 14–22 years presented with itching and erythematous to purple-coloured eczematous lesions on both feet. They were patch tested by 10 dermatologists with the European baseline series. Some patients underwent testing with additional series. Pieces of the shoe fabrics were tested in 11 of 18 patients. Chemical analysis of the shoe materials was performed. Finally, patients were tested with a thin-layer chromatogram of the shoe extracts and dilutions of the suspected rubber compound.
Results
All 18 patients showed positive reactions to thiuram mix. Ten of 11 patients reacted to a piece of shoe fabric. Chemical analysis showed the presence of dimethylthiocarbamylbenzothiazole sulfide (DMTBS). No thiurams were detected. Four patients tested with the chromatogram developed positive reactions to DMTBS. Positive reactions to low concentrations were observed in the 4 patients tested with a DMTBS dilution series; one patient reacted to 0.00001% in acetone.
Conclusions
DMTBS, the culprit allergen, is a component formed during rubber vulcanization that probably cross-reacts with the thiuram mix.
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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
