Background: Harvesting an optimally thinned anterolateral thigh flaps (ALTFs) is a challenge in overweight individuals and in the Western population. Here, we describe a novel honeycomb technique to achieve a superthin ALTF in overweight patients. Methods: Forty patients with a body mass index(BMI) >25 kg/m2 who required a thinned ALTF for reconstruction were randomly assigned to a honeycomb technique (HCT) group or a microdissection technique (MDT) group. Patients in the HCT group received cavitron ultrasonic surgical aspiration (CUSA) to thin the flaps, and flap thinning was performed with a conventional MDT in the MDT group. The perfusion of all flaps was measured by indocyanine green fluorescence (ICG) angiography before and after thinning. Hypoperfusion was defined as 30 percent. Results: The mean BMI was 28.6±2.0 and 27.3±1.9 in the HCT group and the MDT group, respectively. The flap size, perforator, type of dissection and the initial perfusion were comparable between the two groups. However, significantly more patients (9/21) experienced final hypoperfusion in the MDT group than in the HCT group (2/19) (p=0.034). In addition, blood loss and final flap thickness were significantly lower in the HCT group (p
Τετάρτη 9 Μαΐου 2018
An innovative approach to attached cultivation of Chlorella vulgaris using different materials
Abstract
This article investigates the innovative attached cultivation of Chlorella vulgaris (C. vulgaris) using different materials as an alternative to high capital techniques of harvesting such as centrifugation, flocculation, and filtration. A simple attached algal cultivation system was proposed that was equipped by 10 submerged supporting materials which can harvest algal cells, efficiently. The effect of operational parameters such as light intensity, the rate of aeration, and auto-harvesting time was investigated. A chip, durable, and abundant cellulosic material (Kaldnes carriers covered by kenafs, KCCKs) was proposed for auto-harvesting C. vulgaris cells. The results revealed that optimum aeration rate, light intensity, and auto-harvesting of microalgal cells were 3.6 vvm, 10,548 W/m2, and 12 days, respectively. Six of these KCCKs had the highest biofilm formation percent up to 33%. In this condition, the rate of cell growth increased to 0.6 mg/cm2. Therefore, this system can be used for appropriate auto-harvesting of microalgae in the attached growth systems. C. vulgaris biomass composition is valuable for biodiesel, bioethanol, and animal protein production.
Metal contamination in quail meat: residues, sources, molecular biomarkers, and human health risk assessment
Abstract
Quail meat is an emerging source of high-quality animal protein. Quails are exposed to a wide range of xenobiotics such as heavy metals. In this study, residual concentrations of four toxic metals, of significant public health importance, including cadmium (Cd), lead (Pb), arsenic (As), and nickel (Ni), were determined in edible tissues of quails. In addition, metal loads were measured in water, feed, and litter samples collected from same quail farms as possible sources for quail exposure to heavy metals. The possible use of metallothionein (MT) and heat shock protein 70 (Hsp70) as molecular biomarkers of exposure to heavy metals was further investigated. Furthermore, the dietary intake and the potential risk assessment of the examined heavy metals among children and adults were calculated. The edible tissues of quails contained high concentrations of four heavy metals (contents (ppm/ww) ranging from 0.02 to 0.32 in Cd, 0.05 to 1.96 in Pb, 0.002 to 0.32 in As, and 1.17 to 3.94 in Ni), which corresponded to the high contents of these metals in the feeds, water, and litter. MT and Hsp70 mRNA expressions showed positive correlations with the concentrations of heavy metals in tissues indicating the possibility to use these proteins as biomarkers for quail's exposure to toxic metals. Dietary intake of quail meat and risk assessment revealed potential risks especially for children after prolonged exposure to the examined metals. Thus, legislations should be established and continuous screening of metal residues should be adopted in order to reduce the toxic metal concentrations in feeds and drinking water for quails. Reduction of exposure to heavy metals subsequently would lead to minimization of exposure of such toxicants through consumption of quail meat.
Systematic review of the efficacy of fat grafting and platelet‐rich plasma for wound healing
International Wound Journal, EarlyView.
Role of lncRNAs as prognostic markers of hepatic cancer and potential therapeutic targeting by S-adenosylmethionine via inhibiting PI3K/Akt signaling pathways
Abstract
Hepatic cancer (HCC) is a well-identified dilemma throughout the world, and hence, the molecular mechanisms and strategy for preventive protection against this malignancy are critical. S-adenosylmethionine (SAM) is a unique methyl granter in vast reactions, including DNA methylation, and secures the genome against hypomethylation, which is a hallmark of tumors. Consequently, SAM may control the rate of gene expression. The objective of this investigation was to evaluate the expression of long noncoding RNAs (lncRNAs) transcript involved in hepatic tumorigenesis, including additional coding CEBPA (ecCEBPA) and urothelial carcinoma related 1 (UCA1), antioxidant enzymes transcripts, and relevant signaling pathway in diethylnitrosamine (DEN)-prompted HCC along with their conceivable targeting by SAM at different stages of HCC in rats. Our outcomes revealed that SAM particularly when given at the starting phase downregulates ecCEBPA and UCA1 gene transcripts and ameliorate histopathological alterations in DEN-initiated HCC. Interestingly, SAM attenuates DEN-induced upregulation of PI3K/Akt protein expression. However, SAM upregulates the antioxidant enzymes mRNA transcripts and effectively diminishing DNA oxidation. The results of a DNA fragmentation assay further support the capacity of SAM to ameliorate DEN-induced hepatic malignancy. These results revealed the role of ecCEBPA and UCA1 in HCC and suggest that these lncRNAs may be helpful as prognostic and analytical biomarkers of HCC. Curiously, SAM readily targets the studied genes via inhibiting PI3K/Akt signaling pathway, which should make SAM an appealing agent for both chemoprevention and treatment of HCC.
Effect of sulfonated graphene on uptake, translocation, and metabolism of 2,4,4′-trichlorobiphenyl in maize seedlings
Abstract
Graphene may affect fate of organic contaminants due to its strong adsorption properties, which is very crucial for accurately assessing ecological risk of graphene and concurrent contaminants, while the current information remains largely unknown. Here, we firstly explored the adsorption characteristics of sulfonated graphene (SG) for a widespread polychlorinated biphenyl 2,4,4′-trichlorobiphenyl (PCB28) (0.5–100 μg L−1). Subsequently, the influence of SG on the uptake, translocation, and metabolism of PCB28 in maize seedlings was investigated through hydroponic exposure experiment. Adsorption isotherm of PCB28 to SG fitted best with the Langmuir model and the Polanyi-Dubinin-Manes (PDM) model, with the maximum adsorption capacity (Qmax) calculated as around 530 mg kg−1. The presence of SG significantly promoted the maximum accumulation amount of PCB28 in roots by 112%, whereas reduced that in stems and leaves by 32 and 39%, respectively. The translocation factor (TFs) of PCB28 from roots to stems was 26–70% lower for SG exposed seedlings than nonexposed seedlings when the exposure time was longer than 24 h, demonstrating an obvious suppression of SG in the transportation of PCB28 from roots to stems. PCB28 could be metabolized to PCB8 and PCB18 through dechlorination and rearrangement in different parts of maize seedlings. SG significantly increased the accumulation of PCB8 and PCB18 in roots, but decreased that in stems and leaves. These findings might provide new implications for the risk assessment of SG and PCBs in the environment.
Electrochemical treatment of humic acid using particle electrodes ensembled by ordered mesoporous carbon
Abstract
In order to degrade the macromolecular pollutant of humic acid, the powder ordered mesoporous carbon (POMC, average pore diameter 4.29 nm) was first applied for preparing the granular OMC (GOMC, Φ × H = 4 × 3–6 mm) as electrodes in a continuous three-dimensional (3D) electrochemical system. The POMC was synthesized by hard-templating method and characterized using scanning electron microscopy (SEM), transmission electron microscopy (TEM), particle size distribution, N2 adsorption/desorption technology, and Fourier-transform infrared (FT-IR). The effects of electrochemical degradation parameters, such as current and hydraulic retention time (HRT), were investigated, and the degradation mechanism of HA was explored as well. The results indicated that the degradation efficiency of HA, chemical oxygen demand (COD), and total organic carbon (TOC) reached 95.3, 86.2, and 62.7%, respectively, under initial HA of 100 mg/L, current of 0.2 A, and HRT of 130 min. The detection of electron paramagnetic resonance (EPR) showed that plenty of ˙OH was generated on GOMC electrodes, which made the 3D system more effective than the conventional two-dimensional (2D) system. The cyclic voltammetry curves indicated that the reactions of HA on the OMC materials surface included both direct oxidation and direct reduction.
Controlling factors of soil selenium distribution in a watershed in Se-enriched and longevity region of South China
Abstract
Selenium (Se) is an essential nutritional element for human beings. Many studies have been conducted on concentration and distribution patterns of soil Se in low Se, Se-enriched, and selenosis areas; however, soil Se has not been systematically studied in a watershed, especially in Se-enriched longevity region and karst area in South China. This study is carried out to explore the controlling factors of Se-enriched soils in Baishou river tributary watershed, where soils are Se-enriched, and local people have the phenomenon of longevity. The area-weighted average rock Se concentration in the watershed is 0.054 mg/kg, and there are no significant differences in rock Se concentration between different strata and between different lithological rocks. The area-weighted average concentration of Se in soils (0–20 cm) is 0.80 mg/kg, and the soil Se concentration is of high level in the watershed. Soil Se concentration decreases from upstream to downstream in the watershed, and significantly correlated with elevation. Climate is the main factor causing high content of soil Se in the watershed which lacks black rock series. The difference of clastic and carbonate parent materials in soil forming process and the physical and chemical properties (pH, OM, etc.) are the main reasons for the spatial variation of Se distribution in the watershed. The research will be beneficial to the development and utilization of Se-enriched soil in Se-enriched area.
Adsorption of platinum ion from “aged” aqueous solution: application and comparative study between purified MWCNTs and triphenylphosphine MWCNTs
Abstract
This study entails adsorption attempt of platinum ion from "aged" aqueous solution with purified multiwalled carbon nanotubes and tryphenylphosphine-linked multiwalled carbon nanotubes (1) and (2) (Tpp-MWCNTs (1) and Tpp-MWCNTs (2)). The aims were to produce and use purified MWCNTs, Tpp-MWCNTs (1) and (2) and compare their adsorption capacity. These adsorbents were characterised with SEM, FTIR, XPS, BET and zeta potential. Tpp-MWCNTs (1) and (2) differ by their atomic percentage content of phosphorus which is 0.7 and 2.6%, respectively. A commercial stock solution (1000 mg/L) of platinum was used for the batch adsorption experiments. The data revealed that the adsorption was dependent on the following parameters: pH, contact time and initial concentration. The adsorbents attained higher adsorption capacity at pH 2 with an initial concentration of 7.9 mg/L, adsorbent dose of 0.8 g/L, contact time of 60 min at room temperature (RT), whereas 48.25, 40.06 and 41.31 mg/g were adsorbed from 20 mg/L by purified MWCNTs, Tpp-MWCNTs (1) and (2), respectively. The results are quite interesting and show that purified MWCNTs are better than Tpp-MWCNTs under the experimental conditions. The data was best described by the Langmuir model and the adsorption process occurs on the surface monolayer of the adsorbents. The isotherm studies confirmed that the adsorption of platinum ion is favourable. The findings indicate that the practical adsorption of platinum ion using the adsorbents investigated is useful.
Time in the Theory of Relativity: Inertial Time, Light Clocks, and Proper Time
Abstract
In a way similar to classical mechanics where we have the concept of inertial time as expressed in the motions of bodies, in the (special) theory of relativity we can regard the inertial time as the only notion of time at play. The inertial time is expressed also in the propagation of light. This gives rise to a notion of clock—the light clock, which we can regard as a notion derived from the inertial time. The light clock can be seen as a solution of the theory, which complies with the requirement that a clock to be so must have a rate that is independent from its past history. Contrary to Einstein's view, we do not need the concept of "clock" as an independent concept. This implies, in particular, that we do not need to rely on the notions of atomic clock or atomic time in the theory of relativity.
Heavy metal bioaccumulation by Miscanthus sacchariflorus and its potential for removing metals from the Dongting Lake wetlands, China
Abstract
Bioaccumulation of five heavy metals (Cd, Cu, Mn, Pb, and Zn) in six plant organs (panicle, leaf, stem, root, rhizome, and bud) of the emergent and perennial plant species, Miscanthus sacchariflorus, were investigated to estimate the plant's potential for accumulating heavy metals in the wetlands of Dongting Lake. We found the highest Cd concentrations in the panicles and leaves; while the highest Cu and Mn were observed in the roots, the highest Pb in the panicles, and the highest Zn in the panicles and buds. In contrast, the lowest Cd concentrations were detected in the stem, roots, and buds; the lowest Cu concentrations in the leaves and stems; the lowest Mn concentrations in the panicles, rhizomes, and buds; the lowest Pb concentrations in the stems; and the lowest Zn concentrations in the leaves, stems, and rhizomes. Mean Cu concentration in the plant showed a positive regression coefficient with plot elevation, soil organic matter content, and soil Cu concentration, whereas it showed a negative regression coefficient with soil moisture and electrolyte leakage. Mean Mn concentration showed positive and negative regression coefficients with soil organic matter and soil moisture, respectively. Mean Pb concentration exhibited positive regression coefficient with plot elevation and soil total P concentration, and Zn concentration showed a positive regression coefficient with soil available P and total P concentrations. However, there was no significant regression coefficient between mean Cd concentration in the plant and the investigated environmental parameters. Stems and roots were the main organs involved in heavy metal accumulation from the environment. The mean quantities of heavy metals accumulated in the plant tissues were 2.2 mg Cd, 86.7 mg Cu, 290.3 mg Mn, 15.9 mg Pb, and 307 mg Zn per square meter. In the Dongting Lake wetlands, 0.7 × 103 kg Cd, 22.9 × 103 kg Cu, 77.5 × 103 kg Mn, 3.1 × 103 kg Pb, and 95.9 × 103 kg Zn per year were accumulated by aboveground organs and removed from the lake through harvesting for paper manufacture.
Dramatic source-sink transition of N 2 O in the water level fluctuation zone of the Three Gorges Reservoir during flooding-drying processes
Abstract
Biogeochemical cycling of nitrous oxide (N2O), a significant greenhouse gas (GHG), can influence global climate change. The production and emission of N2O mediated by hydrological regimes is particularly active in water level fluctuation zones (WLFZs). However, the hydrological mechanisms affecting N2O transformation and production across the water-sediment micro-interface remain unclear. In this study, intact sediment cores from the WLFZs of the Three Gorges Reservoir (TGR) were incubated for 24 days in a laboratory microcosm to identify the effects of the flooding-drying processes on the yield and emission of N2O. Results showed a source-sink transition of N2O in the first 1.5 days during the flooding period, with the water column subsequently acting as a sink relative to the atmosphere in the following experimental period. The source-sink transition was ascribed to changes in oxygen concentration in the water column and sediment regulation of NO3−-N transformation, resulting in denitrification and N2O production. Preliminary estimates on the mass budget of N2O in a typical WLFZs of the TGR showed slight emission fluxes, ranging from 13.08 to 43.08 μmol m−2 from flooding period to drying process. Although these N2O emissions were relatively low, the emission peak detected during the initial period (first 1.5 days) of the flooding phase provides important knowledge on the mitigation of GHG emissions from hydropower sources, which should be incorporated into future reservoir operations.
Tracking metal ions with polypyrrole thin films adhesively bonded to diazonium-modified flexible ITO electrodes
Abstract
Adhesively bonded polypyrrole thin films doped with benzene sulfonic acid (BSA) were electrodeposited on aminobenzenediazonium-modified flexible ITO electrodes and further employed for the detection of Pb2+, Cu2+, and Cd2+ metal ions in aqueous medium. The aminophenyl (AP) adhesive layer was grafted to ITO by electroreduction of the in situ generated parent diazonium compound. Polypyrrole (PPy) thin films exhibited remarkable adhesion to aminophenyl (ITO-AP). The strongly adherent polypyrrole films exhibited excellent electroactivity in the doped state with BSA which itself served to chelate the metal ions in aqueous medium. The surface of the resulting, modified flexible electrode was characterized by XPS, SEM, and electrochemical methods. The ITO-AP-PPy electrodes were then used for the simultaneous detection of Cu2+, Cd2+, and Pb2+ by differential pulse voltammetry (DPV). The detection limits were 11.1, 8.95, and 0.99 nM for Cu2+, Cd2+, and Pb2+, respectively. In addition, the modified electrodes displayed a good reproducibility, making them suitable for the determination of heavy metals in real wastewater samples.
Horseradish peroxidase-mediated decolourization of Orange II: modelling hydrogen peroxide utilization efficiency at different pH values
Abstract
Enzymatic decolourization of azo-dyes could be a cost-competitive alternative compared to physicochemical or microbiological methods. Stoichiometric and kinetic features of peroxidase-mediated decolourization of azo-dyes by hydrogen peroxide (P) are central for designing purposes. In this work, a modified version of the Dunford mechanism of peroxidases was developed. The proposed model takes into account the inhibition of peroxidases by high concentrations of P, the substrate-dependant catalatic activity of peroxidases (e.g. the decomposition of P to water and oxygen), the generation of oxidation products (OP) and the effect of pH on the decolourization kinetics of the azo-dye Orange II (OII). To obtain the parameters of the proposed model, two series of experiments were performed. In the first set, the effects of initial P concentration (0.01–0.12 mM) and pH (5–10) on the decolourization degree were studied at a constant initial OII concentration (0.045 mM). Obtained results showed that at pH 9–10 and low initial P concentrations, the consumption of P was mainly to oxidize OII. From the proposed model, an expression for the decolourization degree was obtained. In the second set of experiments, the effect of the initial concentrations of OII (0.023–0.090 mM), P (0.02–4.7 mM), HRP (34–136 mg/L) and pH (5–10) on the initial specific decolourization rate (q0) was studied. As a general rule, a noticeable increase in q0 was observed for pHs higher than 7. For a given pH, q0 increased as a function of the initial OII concentration. Besides, there was an inhibitory effect of high P concentrations on q0. To asses the possibility of reusing the enzyme, repeated additions of OII and P were performed. Results showed that the enzyme remained active after six reuse cycles. A satisfactory accordance between the change of the absorbance during these experiments and absorbances calculated using the proposed model was obtained. Considering that this set of data was not used during the fitting procedure of the model, the agreement between predicted and experimental absorbances provides a powerful validation of the model developed in the present work.
Psoriatic patients with chronic viral hepatitis do not have an increased risk of liver cirrhosis despite long-term methotrexate use: real-world data from a nationwide cohort study in Taiwan.
Prior studies have shown that methotrexate may lead to liver cirrhosis in psoriatic patients. Real-world data show that long-term methotrexate use is not associated with an increased risk of liver cirrhosis among psoriatic patients with chronic viral hepatitis. Methotrexate may be a treatment option in psoriatic patients with chronic viral hepatitis.
Histomorphologic spectrum of germline-related and sporadic BAP-1 Inactivated Melanocytic Tumors
The histomorphology of BAP-1 inactivated melanocytic tumors (BIMTs) includes cases with spitzoid cytomorphology and cases with smaller epithelioid cells without spitzoid features. Approximately 12% of patients with BIMTs have germline BAP-1 mutations. BIMT patients with extensive junctional involvement of BAP-1 inactivated melanocytes, prior melanoma or BIMT may be considered for germline testing.
Poly-γ-glutamic acid, a bio-chelator, alleviates the toxicity of Cd and Pb in the soil and promotes the establishment of healthy Cucumis sativus L . seedling
Abstract
Poly-γ-glutamic acid (γ-PGA) can be used as a chemical stabilizer to chelate heavy metals in polluted soils. We investigated the effects of γ-PGA on cucumber seedlings under Cd and Pb stresses. γ-PGA effectively reduced the growth inhibitory effects of Cd and Pb on cucumber seedlings. Cd and Pb absorption in cucumber seedlings was also decreased. Further, γ-PGA decreased the malondialdehyde content, and increased the proline content and the total antioxidant capacity of cucumber seedlings in a dose-dependent manner. Infrared spectral characterization of γ-PGA-Cd and γ-PGA-Pb showed that Cd2+ and Pb2+ bind to free carboxyl groups on γ-PGA. Furthermore, γ-PGA-Cd and γ-PGA-Pb were degraded by 22.02 and 24.68%, respectively, within 28 weeks. The chelating rate of γ-PGA-Pb and γ-PGA-Cd reached 27.26 and 14.28%, respectively. Further, γ-PGA alleviated the negative effects of Cd and Pb on soil microorganisms. Thus, γ-PGA can effectively reduce the accumulation of heavy metals in crops caused by heavy metal pollution of farmland, and has significant application value.
Utility of Baseline Transaminase Monitoring During Systemic Terbinafine Therapy for Pediatric Onychomycosis
To the Editor We applaud the important research findings by Patel et al regarding pediatric onychomycosis. In this study, the authors appropriately conclude that routine laboratory monitoring of children during treatment with terbinafine may be unnecessary, considering (1) the low incidence of clinically significant adverse effects; (2) the costs of laboratory tests; (3) workup of spurious laboratory abnormalities; and (4) patient discomfort.
Hair Loss Associated With Cucurbit Poisoning
This case report describes a patient experiencing hair loss following cucurbit poisoning.
Catalyzing Future Drug, Device, and Information Technology Breakthroughs in Dermatology
This Viewpoint announces the creation of the Advancing Innovation in Dermatology Accelerator Fund and describes its aims.
Paraffin Prosthesis
To remedy the inevitable changes that accompany the aging body, fillers have been used since the early 19th century in efforts to enhance appearance. With goals of rejuvenating and restructuring both real and perceived bodily imperfections, the development of fillers was not without its share of blunders. The story of fillers begins with the discovery of paraffin in 1830 by a German chemist named Baron Karl Ludwig von Reichenbach. He was able to create the material through the dry distillation of beechwood tar. Noting that the substance was extremely unreactive, he thought paraffin could be used as a lubricant or perhaps as a replacement for beeswax in candles. The name paraffin comes from the Latin words parum and affinis, meaning barely and affinity, respectively. In the years to follow, paraffin would take the medical community by storm.
The Potential of Behavioral Counseling to Prevent Skin Cancer
Skin cancers, ie, melanoma and keratinocyte skin cancer, are the most common cancers. The number of melanomas is expected to nearly double by 2030, tripling annual treatment costs in the United States. Because skin cancer is strongly associated with UV radiation (UVR) exposure, the Centers for Disease Control and Prevention recommend reducing unprotected exposure to UVR. The US Surgeon General issued a Call to Action to Prevent Skin Cancer, appealing for efforts to identify effective skin cancer prevention interventions.
Chronic Urticaria Associated With Methylisothiazolinone Type IV Hypersensitivity
This case report describes a patient with chronic urticaria associated with methylisothiazolinone type IV hypersensitivity.
Indoor Tanners as a Priority Population for Skin Cancer Screening
The study by Heckman et al published in this issue of JAMA Dermatology makes a significant contribution to our understanding of skin cancer screening for indoor tanners. The literature contains only a handful of studies that examined skin screening prevalence and factors that may be associated with this practice among indoor tanners. The National Health Interview Survey (NHIS), a national probability survey of the US adult population, collects data on skin screening and indoor tanning and provides a valuable opportunity to examine potential factors associated with these practices in a large sample. Results of previous studies of skin screening and indoor tanning using NHIS data have been mixed, possibly because of differences in methods and sampling. One study of 2010 NHIS data found a positive association between indoor tanning in the past year and ever having had a skin examination, whereas another study of a subsample of the 2015 NHIS data found no association.
Thyroid Function Screening in Children With Alopecia Areata
To the Editor In their recent article in JAMA Dermatology, Patel et al describe the prevalence of thyroid disorders among subgroups of children with alopecia areata (eg, those with Down syndrome), and interpret the findings as justification for screening such children. Unfortunately, the authors did not attempt to exclude children presenting with symptoms of thyroid dysfunction (eg, heat or cold intolerance, fatigue, growth abnormalities). Indeed, a category of thyroid dysfunction among the 59 patients with abnormal results was "subclinical thyroid dysfunction," implying that the other patients may have had clinical signs or symptoms of thyroid disease. Since screening, by definition, is conducted among asymptomatic individuals, the results reported by Patel et al cannot be interpreted to support or refute screening guidelines. Children with symptoms of thyroid dysfunction are more likely to receive thyroid function tests and are also more likely to have thyroid dysfunction; therefore, the true prevalence of thyroid disorders among asymptomatic children with alopecia areata who receive thyroid screening is expected to be lower than the estimates in this study. Whether the true prevalence is high enough in certain subgroups to justify screening cannot be determined from the data presented.
Inpatient Dermatologists—Crucial for the Management of Skin Diseases in Hospitalized Patients
Inpatient dermatology is an emerging subspecialty focused on the care of skin diseases in hospitalized patients. Inpatient dermatologists provide expertise that the primary team and other consultative services lack. The cases encountered in hospital dermatology are often different from those seen in the traditional dermatology outpatient clinic and therefore require dermatologists with specific expertise.
The Effect of Dermatology Consultation on Outcomes of Patients With Presumed Cellulitis
This randomized clinical trial examines the association of dermatologic consultation with duration of hospital stay and intravenous antibiotic treatment in patients with suspected cellulitis.
Facial Neutrophilic Dermatosis Mimicking Iododerma Associated With IBD
This case report describes a patient with facial neutrophilic dermatosis mimicking iododerma and associated with inflammatory bowel disease.
Outcomes of Early Dermatology Consultation for Inpatients Diagnosed With Cellulitis
This cohort study examines the effects of dermatology consultation on misdiagnosis of cellulitis in patients admitted to emergency departments.
Death by Gun Violence—Guns Are Not the Problem
To the Editor I read with interest the editorial by Bauchner et al regarding gun violence and wish to offer a different opinion. My family and I live on a farm in a rural area near Nashville, Tennessee. Crime, including violent crime, is essentially unheard of in our part of the county. I believe that this stems, in part, from the well-known fact that those of us living here are armed. We have rifles and shotguns in our homes and pistols in our vehicles and/or on our persons.
Skin Examination Patterns and Thinner Nodular vs Superficial Spreading Melanoma at Diagnosis
This cross-sectional pooled analysis analyzes the association between skin examination practices and diagnosis with thin nodular or superficial spreading melanoma.
Task Shifting in Dermatology—A Call to Action
To the Editor In response to the Evidence Synopsis by Brown et al on the practice of task shifting, we would like to highlight how task shifting is currently being successfully implemented in health programs in India, with emphasis on National Leprosy Eradication Program.
Skin Cancer Screening Among Indoor Tanners and Nontanners
This survey study of 30 352 participants investigates the association between indoor tanning and skin cancer screening.
Depression Screening in Dermatology—Think Isotretinoin
To the Editor We applaud McDonald et al for publishing "The PHQ-2 in Dermatology—Standardized Screening for Depression and Suicidal Ideation." The importance of this work cannot be overemphasized. We agree that dermatologists are uniquely situated to identify psychiatric concerns related to skin disease, and the PHQ-2 (Patient Health Questionnaire-2) is a great screening tool for this. Since we published on the use of the PHQ-2 in the context of isotretinoin, we have had positive feedback on its use and wish to reemphasize the importance in association with the article by McDonald et al. Additionally, we believe that their algorithmic approach warrants an expansion.
Sun Protection Use and Sunburn Among US Adults
This cross-sectional study using National Health Interview Survey data examined the prevalence of sun protection use and sunburn and the association between sunburn and demographic characteristics and health behaviors in the US population.
Haldi Ceremony—Historical Use of Turmeric
Long before golden lattes and turmeric face creams became popular in the West, ancient South Asian civilizations were using the native golden root as a panacea to treat everything from arthritis to indigestion to various skin conditions. Its active ingredient, curcumin, has been shown to have anti-inflammatory, antioxidant, and wound-healing properties and also influences multiple downstream signaling pathways. In addition to medicinal uses, turmeric has played an important role in South Asian cuisine and cultural practices.
Interest and Uptake of MC1R Testing for Melanoma Risk in a Diverse Primary Care Population
This randomized clinical trial examines the prevalence of interest in and uptake of MC1R testing in the general population and examines patterns across demographic and skin cancer risk factors.
Demographic, Academic, and Publication Factors Associated With Academic Dermatology Career Selection
This cohort study examines associations between demographic, academic, and publication factors and dermatology trainees' initial choice of academic vs private practice careers.
Recurrent Unilateral Periorbital Edema Associated With Subcutaneous Cysticercosis
This case report describes a patient with recurrent unilateral periorbital edema caused by subcutaneous cysticercosis.
Cost-effectiveness of Skin Cancer Referral and Consultation Using Teledermoscopy in Australia
This study uses a decision-analytic model to assess the cost-effectiveness of teledermoscopy as a referral mechanism for skin cancer diagnosis and management in Australia.
Firm Papules and Nodules on Face, Neck, and Thorax
A man in his early 40s who had been injured in a land mine explosion 15 years earlier presents with a 6-month history of asymptomatic, erythematous nodules. What is your diagnosis?
Macrophage Depletion Ameliorates Peripheral Neuropathy in Aging Mice
Aging is known as a major risk factor for the structure and function of the nervous system. There is urgent need to overcome such deleterious effects of age-related neurodegeneration. Here we show that peripheral nerves of 24-month-old aging C57BL/6 mice of either sex show similar pathological alterations as nerves from aging human individuals, whereas 12-month-old adult mice lack such alterations. Specifically, nerve fibers showed demyelination, remyelination and axonal lesion. Moreover, in the aging mice, neuromuscular junctions showed features typical for dying-back neuropathies, as revealed by a decline of presynaptic markers, associated with α-bungarotoxin-positive postsynapses. In line with these observations were reduced muscle strengths. These alterations were accompanied by elevated numbers of endoneurial macrophages, partially comprising the features of phagocytosing macrophages. Comparable profiles of macrophages could be identified in peripheral nerve biopsies of aging persons. To determine the pathological impact of macrophages in aging mice, we selectively targeted the cells by applying an orally administered CSF-1R specific kinase (c-FMS) inhibitor. The 6-month-lasting treatment started before development of degenerative changes at 18 months and reduced macrophage numbers in mice by ~70%, without side effects. Strikingly, nerve structure was ameliorated and muscle strength preserved. We show, for the first time, that age-related degenerative changes in peripheral nerves are driven by macrophages. These findings may pave the way for treating degeneration in the aging peripheral nervous system by targeting macrophages, leading to reduced weakness, improved mobility, and eventually increased quality of life in the elderly.
SIGNIFICANCE STATEMENT Aging is a major risk factor for the structure and function of the nervous system. Here we show that peripheral nerves of 24-month-old aging mice show similar degenerative alterations as nerves from aging human individuals. Both in mice and humans, these alterations were accompanied by endoneurial macrophages. To determine the pathological impact of macrophages in aging mice, we selectively targeted the cells by blocking a cytokine receptor, essential for macrophage survival. The treatment strongly reduced macrophage numbers and substantially improved nerve structure and muscle strength. We show, for the first time, that age-related degenerative changes in peripheral nerves are driven by macrophages. These findings may be helpful for treatment weakness and reduced mobility in the elderly.
Pallidal Deep-Brain Stimulation Disrupts Pallidal Beta Oscillations and Coherence with Primary Motor Cortex in Parkinson's Disease
In Parkinson's disease (PD), subthalamic nucleus beta band oscillations are decreased by therapeutic deep-brain stimulation (DBS) and this has been proposed as important to the mechanism of therapy. The globus pallidus is a common alternative target for PD with similar motor benefits as subthalamic DBS, but effects of pallidal stimulation in PD are not well studied, and effects of pallidal DBS on cortical function in PD are unknown. Here, in 20 PD and 14 isolated dystonia human patients of both genders undergoing pallidal DBS lead implantation, we recorded local field potentials from the globus pallidus and in a subset of these, recorded simultaneous sensorimotor cortex ECoG potentials. PD patients had elevated resting pallidal low beta band (13–20 Hz) power compared with dystonia patients, whereas dystonia patients had elevated resting pallidal theta band (4–8 Hz) power compared with PD. We show that this results in disease-specific patterns of interaction between the pallidum and motor cortex: PD patients demonstrated relatively elevated phase coherence with the motor cortex in the beta band and this was reduced by therapeutic pallidal DBS. Dystonia patients had greater theta band phase coherence. Our results support the hypothesis that specific motor phenomenology observed in movement disorders are associated with elevated network oscillations in specific frequency bands, and that DBS in movement disorders acts in general by disrupting elevated synchronization between basal ganglia output and motor cortex.
SIGNIFICANCE STATEMENT Perturbations in synchronized oscillatory activity in brain networks are increasingly recognized as important features in movement disorders. The globus pallidus is a commonly used target for deep-brain stimulation (DBS) in Parkinson's disease (PD), however, the effects of pallidal DBS on basal ganglia and cortical oscillations are unknown. Using invasive intraoperative recordings in patients with PD and isolated dystonia, we found disease-specific patterns of elevated oscillatory synchronization within the pallidum and in coherence between pallidum and motor cortex. Therapeutic pallidal DBS in PD suppresses these elevated synchronizations, reducing the influence of diseased basal ganglia on cortical physiology. We propose a general mechanism for DBS therapy in movement disorders: functional disconnection of basal ganglia output and motor cortex by coherence suppression.
Refinement of Spatial Receptive Fields in the Developing Mouse Lateral Geniculate Nucleus Is Coordinated with Excitatory and Inhibitory Remodeling
Receptive field properties of individual visual neurons are dictated by the precise patterns of synaptic connections they receive, including the arrangement of inputs in visual space and features such as polarity (On vs Off). The inputs from the retina to the lateral geniculate nucleus (LGN) in the mouse undergo significant refinement during development. However, it is unknown how this refinement corresponds to the establishment of functional visual response properties. Here we conducted in vivo and in vitro recordings in the mouse LGN, beginning just after natural eye opening, to determine how receptive fields develop as excitatory and feedforward inhibitory retinal afferents refine. Experiments used both male and female subjects. For in vivo assessment of receptive fields, we performed multisite extracellular recordings in awake mice. Spatial receptive fields at eye-opening were >2 times larger than in adulthood, and decreased in size over the subsequent week. This topographic refinement was accompanied by other spatial changes, such as a decrease in spot size preference and an increase in surround suppression. Notably, the degree of specificity in terms of On/Off and sustained/transient responses appeared to be established already at eye opening and did not change. We performed in vitro recordings of the synaptic responses evoked by optic tract stimulation across the same time period. These recordings revealed a pairing of decreased excitatory and increased feedforward inhibitory convergence, providing a potential mechanism to explain the spatial receptive field refinement.
SIGNIFICANCE STATEMENT The development of precise patterns of retinogeniculate connectivity has been a powerful model system for understanding the mechanisms underlying the activity-dependent refinement of sensory systems. Here we link the maturation of spatial receptive field properties in the lateral geniculate nucleus (LGN) to the remodeling of retinal and inhibitory feedforward convergence onto LGN neurons. These findings should thus provide a starting point for testing the cell type-specific plasticity mechanisms that lead to refinement of different excitatory and inhibitory inputs, and for determining the effect of these mechanisms on the establishment of mature receptive fields in the LGN.
Long-Term Depression Is Independent of GluN2 Subunit Composition
NMDA receptors (NMDARs) mediate both long-term potentiation and long-term depression (LTD) and understanding how a single receptor can initiate both phenomena remains a major question in neuroscience. A prominent hypothesis implicates the NMDAR subunit composition, specifically GluN2A and GluN2B, in dictating the rules of synaptic plasticity. However, studies testing this hypothesis have yielded inconsistent and often contradictory results, especially for LTD. These inconsistent results may be due to challenges in the interpretation of subunit-selective pharmacology and in dissecting out the contributions of differential channel properties versus the interacting proteins unique to GluN2A or GluN2B. In this study, we address the pharmacological and biochemical challenges by using a single-neuron genetic approach to delete NMDAR subunits in conditional knock-out mice. In addition, the recently discovered non-ionotropic nature of NMDAR-dependent LTD allowed the rigorous assessment of unique subunit contributions to NMDAR-dependent LTD while eliminating the variable of differential charge transfer. Here we find that neither the GluN2A nor the GluN2B subunit is strictly necessary for either non-ionotropic or ionotropic LTD.
SIGNIFICANCE STATEMENT NMDA receptors are key regulators of bidirectional synaptic plasticity. Understanding the mechanisms regulating bidirectional plasticity will guide development of therapeutic strategies to treat the dysfunctional synaptic plasticity in multiple neuropsychiatric disorders. Because of the unique properties of the NMDA receptor GluN2 subunits, they have been postulated to differentially affect synaptic plasticity. However, there has been significant controversy regarding the roles of the GluN2 subunits in synaptic long term depression (LTD). Using single-neuron knock-out of the GluN2 subunits, we show that LTD requires neither GluN2A nor GluN2B.
Neural Activity in Ventral Medial Prefrontal Cortex Is Modulated More Before Approach Than Avoidance During Reinforced and Extinction Trial Blocks
Ventromedial prefrontal cortex (vmPFC) is thought to provide regulatory control over Pavlovian fear responses and has recently been implicated in appetitive approach behavior, but much less is known about its role in contexts in which appetitive and aversive outcomes can be obtained and avoided, respectively. To address this issue, we recorded from single neurons in vmPFC while male rats performed our combined approach and avoidance task under reinforced and non-reinforced (extinction) conditions. Surprisingly, we found that cues predicting reward modulated cell firing in vmPFC more often and more robustly than cues preceding avoidable shock; in addition, firing of vmPFC neurons was both response (press or no-press) and outcome (reinforced or extinction) selective. These results suggest a complex role for vmPFC in regulating behavior and support its role in appetitive contexts during both reinforced and non-reinforced conditions.
SIGNIFICANCE STATEMENT Selecting context-appropriate behaviors to gain reward or avoid punishment is critical for survival. Although the role of ventromedial prefrontal cortex (vmPFC) in mediating fear responses is well established, vmPFC has also been implicated in the regulation of reward-guided approach and extinction. Many studies have used indirect methods and simple behavioral procedures to study vmPFC, which leaves the literature incomplete. We recorded vmFPC neural activity during a complex cue-driven combined approach and avoidance task and during extinction. Surprisingly, we found very little vmPFC modulation to cues predicting avoidable shock, whereas cues predicting reward approach robustly modulated vmPFC firing in a response- and outcome-selective manner. This suggests a more complex role for vmPFC than current theories suggest, specifically regarding context-specific behavioral optimization.
Electrical Stimulation in Hippocampus and Entorhinal Cortex Impairs Spatial and Temporal Memory
The medial temporal lobe (MTL) is widely implicated in supporting episodic memory and navigation, but its precise functional role in organizing memory across time and space remains elusive. Here we examine the specific cognitive processes implemented by MTL structures (hippocampus and entorhinal cortex) to organize memory by using electrical brain stimulation, leveraging its ability to establish causal links between brain regions and features of behavior. We studied neurosurgical patients of both sexes who performed spatial-navigation and verbal-episodic memory tasks while brain stimulation was applied in various regions during learning. During the verbal memory task, stimulation in the MTL disrupted the temporal organization of encoded memories such that items learned with stimulation tended to be recalled in a more randomized order. During the spatial task, MTL stimulation impaired subjects' abilities to remember items located far away from boundaries. These stimulation effects were specific to the MTL. Our findings thus provide the first causal demonstration in humans of the specific memory processes that are performed by the MTL to encode when and where events occurred.
SIGNIFICANCE STATEMENT Numerous studies have implicated the medial temporal lobe (MTL) in encoding spatial and temporal memories, but they have not been able to causally demonstrate the nature of the cognitive processes by which this occurs in real-time. Electrical brain stimulation is able to demonstrate causal links between a brain region and a given function with high temporal precision. By examining behavior in a memory task as subjects received MTL stimulation, we provide the first causal evidence demonstrating the role of the MTL in organizing the spatial and temporal aspects of episodic memory.
Subthreshold Amyloid Predicts Tau Deposition in Aging
Current approaches to the early detection of Alzheimer's disease (AD) rely upon classifying individuals as "positive" or "negative" for biomarkers related to the core pathology of β-amyloid (Aβ). However, the accumulation of Aβ begins slowly, years before biomarkers become abnormal. We used longitudinal [11C] Pittsburgh Compound B PET scanning and neuropsychological assessment to investigate the earliest changes in AD pathology and how it affects memory in cognitively normal older humans (N = 71; mean age 75 years; 35% male). We used [18F] AV-1451 PET scanning at the end of the observation period to measure subsequent tau deposition in a subset of our sample (N = 37). We found evidence for an inverted-U relationship between baseline Aβ levels and Aβ slope in asymptomatic older adults, suggesting a slowing of Aβ accumulation even in cognitively normal adults. In participants who were nominally amyloid negative, both the rate of amyloid accumulation and the baseline levels of Aβ predicted early tau deposition in cortical Braak regions associated with AD. Amyloid measures were only sensitive to memory decline as baseline levels of Aβ increased, suggesting that pathological accumulation occurs before impacting memory. These findings support the necessity of early intervention with amyloid-lowering therapies even in those who are amyloid negative.
SIGNIFICANCE STATEMENT The progressive nature of Alzheimer's disease (AD) necessitates the earliest possible detection of pathological or cognitive change if disease progression is to be slowed. We examined cognitively normal older adults in whom AD pathology is starting to develop, with the goal of early detection of AD pathology or cognitive changes. We found amyloid measures to be sensitive early on in predicting subsequent early tau deposition. Further, it appears that rates of amyloid accumulation already begin to slow in preclinical AD, suggesting that it is a relatively late stage of AD progression. Thus, it is crucial to examine older adults early, before amyloid levels have saturated, to intervene to slow disease progression.
Fear Memory Recall Potentiates Opiate Reward Sensitivity through Dissociable Dopamine D1 versus D4 Receptor-Dependent Memory Mechanisms in the Prefrontal Cortex
Disturbances in prefrontal cortical (PFC) dopamine (DA) transmission are well established features of psychiatric disorders involving pathological memory processing, such as post-traumatic stress disorder and opioid addiction. Transmission through PFC DA D4 receptors (D4Rs) has been shown to potentiate the emotional salience of normally nonsalient emotional memories, whereas transmission through PFC DA D1 receptors (D1Rs) has been demonstrated to selectively block recall of reward- or aversion-related associative memories. In the present study, using a combination of fear conditioning and opiate reward conditioning in male rats, we examined the role of PFC D4/D1R signaling during the processing of fear-related memory acquisition and recall and subsequent sensitivity to opiate reward memory formation. We report that PFC D4R activation potentiates the salience of normally subthreshold fear conditioning memory cues and simultaneously potentiates the rewarding effects of systemic or intra-ventral tegmental area (VTA) morphine conditioning cues. In contrast, blocking the recall of salient fear memories with intra-PFC D1R activation, blocks the ability of fear memory recall to potentiate systemic or intra-VTA morphine place preference. These effects were dependent upon dissociable PFC phosphorylation states involving calcium-calmodulin-kinase II or extracellular signal-related kinase 1–2, following intra-PFC D4 or D1R activation, respectively. Together, these findings reveal new insights into how aberrant PFC DAergic transmission and associated downstream molecular signaling pathways may modulate fear-related emotional memory processing and concomitantly increase opioid addiction vulnerability.
SIGNIFICANCE STATEMENT Post-traumatic stress disorder is highly comorbid with addiction. In this study, we use a translational model of fear memory conditioning to examine how transmission through dopamine D1 or D4 receptors, in the prefrontal cortex (PFC), may differentially control acquisition or recall of fear memories and how these mechanisms might regulate sensitivity to the rewarding effects of opioids. We demonstrate that PFC D4 activation not only controls the salience of fear memory acquisition, but potentiates the rewarding effects of opioids. In contrast, PFC D1 receptor activation blocks recall of fear memories and prevents potentiation of opioid reward effects. Together, these findings demonstrate novel PFC mechanisms that may account for how emotional memory disturbances might increase the addictive liability of opioid-class drugs.
Cell-Type-Specific Contributions of Medial Prefrontal Neurons to Flexible Behaviors
Behavioral flexibility and impulse control are necessary for successful execution of adaptive behavior. They are impaired in patients with damage to the prefrontal cortex (PFC) and in some clinically important conditions, such as obsessive-compulsive disorder. Although the medial prefrontal cortex (mPFC) has been investigated as a critical structure for behavioral flexibility and impulse control, the contribution of the underlying pyramidal neuron cell types in the mPFC remained to be understood. Here we show that interneuron-mediated local inactivation of pyramidal neurons in the mPFC of male and female mice induces both premature responses and choice bias, and establish that these impulsive and compulsive responses are modulated independently. Cell-type-specific photoinhibition of pyramidal deep layer corticostriatal or corticothalamic neurons reduces behavioral flexibility without inducing premature responses. Together, our data confirm the role of corticostriatal neurons in behavioral flexibility and demonstrate that flexible behaviors are also modulated by direct projections from deep layer corticothalamic neurons in the mPFC to midline thalamic nuclei.
SIGNIFICANCE STATEMENT Behavioral flexibility and impulse control are indispensable for animals to adapt to changes in the environment and often affected in patients with PFC damage and obsessive-compulsive disorder. We used a probabilistic reversal task to dissect the underlying neural circuitry in the mPFC. Through characterization of the three major pyramidal cell types in the mPFC with optogenetic silencing, we demonstrated that corticostriatal and corticothalamic but not corticocortical pyramidal neurons are temporally recruited for behavioral flexibility. Together, our findings confirm the role of corticostriatal projections in cognitive flexibility and identify corticothalamic neurons as equally important for behavioral flexibility.
Restoring Tip60 HAT/HDAC2 Balance in the Neurodegenerative Brain Relieves Epigenetic Transcriptional Repression and Reinstates Cognition
Cognitive decline is a debilitating hallmark during preclinical stages of Alzheimer's disease (AD), yet the causes remain unclear. Because histone acetylation homeostasis is critical for mediating epigenetic gene control throughout neuronal development, we postulated that its misregulation contributes to cognitive impairment preceding AD pathology. Here, we show that disruption of Tip60 histone acetlytransferase (HAT)/histone deacetylase 2 (HDAC2) homeostasis occurs early in the brain of an AD-associated amyloid precursor protein (APP) Drosophila model and triggers epigenetic repression of neuroplasticity genes well before Aβ plaques form in male and female larvae. Repressed genes display enhanced HDAC2 binding and reduced Tip60 and histone acetylation enrichment. Increasing Tip60 in the AD-associated APP brain restores Tip60 HAT/HDAC2 balance by decreasing HDAC2 levels, reverses neuroepigenetic alterations to activate synaptic plasticity genes, and reinstates brain morphology and cognition. Such Drosophila neuroplasticity gene epigenetic signatures are conserved in male and female mouse hippocampus and their expression and Tip60 function is compromised in hippocampus from AD patients. We suggest that Tip60 HAT/HDAC2-mediated epigenetic gene disruption is a critical initial step in AD that is reversed by restoring Tip60 in the brain.
SIGNIFICANCE STATEMENT Mild cognitive impairment is a debilitating hallmark during preclinical stages of Alzheimer's disease (AD), yet its causes remain unclear. Although recent findings support elevated histone deacetylase 2 (HDAC2) as a cause for epigenetic repression of synaptic genes that contribute to cognitive deficits, whether alterations in histone acetlytransferase (HAT) levels that counterbalance HDAC2 repressor action occur and the identity of these HATs remain unknown. We demonstrate that disruption of Tip60 HAT/HDAC2 homeostasis occurs early in the AD Drosophila brain and triggers epigenetic repression of neuroplasticity genes before Aβ plaques form. Increasing Tip60 in the AD brain restores Tip60 HAT/HDAC2 balance, reverses neuroepigenetic alterations to activate synaptic genes, and reinstates brain morphology and cognition. Our data suggest that disruption of the Tip60 HAT/HDAC2 balance is a critical initial step in AD.
NPY Induces Stress Resilience via Downregulation of Ih in Principal Neurons of Rat Basolateral Amygdala
Neuropeptide Y (NPY) expression is tightly linked with the development of stress resilience in rodents and humans. Local NPY injections targeting the basolateral amygdala (BLA) produce long-term behavioral stress resilience in male rats via an unknown mechanism. Previously, we showed that activation of NPY Y1 receptors hyperpolarizes BLA principal neurons (PNs) through inhibition of the hyperpolarization-activated, depolarizing H-current, Ih. The present studies tested whether NPY treatment induces stress resilience by modulating Ih. NPY (10 pmol) was delivered daily for 5 d bilaterally into the BLA to induce resilience; thereafter, the electrophysiological properties of PNs and the expression of Ih in the BLA were characterized. As reported previously, increases in social interaction (SI) times persisted weeks after completion of NPY administration. In vitro intracellular recordings showed that repeated intra-BLA NPY injections resulted in hyperpolarization of BLA PNs at 2 weeks (2W) and 4 weeks (4W) after NPY treatment. At 2W, spontaneous IPSC frequencies were increased, whereas at 4W, resting Ih was markedly reduced and accompanied by decreased levels of HCN1 mRNA and protein expression in BLA. Knock-down of HCN1 channels in the BLA with targeted delivery of lentivirus containing HCN1-shRNA increased SI beginning 2W after injection and induced stress resilience. NPY treatment induced sequential, complementary changes in the inputs to BLA PNs and their postsynaptic properties that reduce excitability, a mechanism that contributes to less anxious behavior. Furthermore, HCN1 knock-down mimicked the increases in SI and stress resilience observed with NPY, indicating the importance of Ih in stress-related behavior.
SIGNIFICANCE STATEMENT Resilience improves mental health outcomes in response to adverse situations. Neuropeptide Y (NPY) is associated with decreased stress responses and the expression of resilience in rodents and humans. Single or repeated injections of NPY into the basolateral amygdala (BLA) buffer negative behavioral effects of stress and induce resilience in rats, respectively. Here, we demonstrate that repeated administration of NPY into the BLA unfolds several cellular mechanisms that decrease the activity of pyramidal output neurons. One key mechanism is a reduction in levels of the excitatory ion channel HCN1. Moreover, shRNA knock-down of HCN1 expression in BLA recapitulates some of the actions of NPY and causes potent resilience to stress, indicating that this channel may be a possible target for therapy.
Detachment of Chain-Forming Neuroblasts by Fyn-Mediated Control of cell-cell Adhesion in the Postnatal Brain
In the rodent olfactory system, neuroblasts produced in the ventricular-subventricular zone of the postnatal brain migrate tangentially in chain-like cell aggregates toward the olfactory bulb (OB) through the rostral migratory stream (RMS). After reaching the OB, the chains are dissociated and the neuroblasts migrate individually and radially toward their final destination. The cellular and molecular mechanisms controlling cell–cell adhesion during this detachment remain unclear. Here we report that Fyn, a nonreceptor tyrosine kinase, regulates the detachment of neuroblasts from chains in the male and female mouse OB. By performing chemical screening and in vivo loss-of-function and gain-of-function experiments, we found that Fyn promotes somal disengagement from the chains and is involved in neuronal migration from the RMS into the granule cell layer of the OB. Fyn knockdown or Dab1 (disabled-1) deficiency caused p120-catenin to accumulate and adherens junction-like structures to be sustained at the contact sites between neuroblasts. Moreover, a Fyn and N-cadherin double-knockdown experiment indicated that Fyn regulates the N-cadherin-mediated cell adhesion between neuroblasts. These results suggest that the Fyn-mediated control of cell–cell adhesion is critical for the detachment of chain-forming neuroblasts in the postnatal OB.
SIGNIFICANCE STATEMENT In the postnatal brain, newly born neurons (neuroblasts) migrate in chain-like cell aggregates toward their destination, where they are dissociated into individual cells and mature. The cellular and molecular mechanisms controlling the detachment of neuroblasts from chains are not understood. Here we show that Fyn, a nonreceptor tyrosine kinase, promotes the somal detachment of neuroblasts from chains, and that this regulation is critical for the efficient migration of neuroblasts to their destination. We further show that Fyn and Dab1 (disabled-1) decrease the cell–cell adhesion between chain-forming neuroblasts, which involves adherens junction-like structures. Our results suggest that Fyn-mediated regulation of the cell–cell adhesion of neuroblasts is critical for their detachment from chains in the postnatal brain.
Credit Assignment in a Motor Decision Making Task Is Influenced by Agency and Not Sensory Prediction Errors
Failures to obtain reward can occur from errors in action selection or action execution. Recently, we observed marked differences in choice behavior when the failure to obtain a reward was attributed to errors in action execution compared with errors in action selection (McDougle et al., 2016). Specifically, participants appeared to solve this credit assignment problem by discounting outcomes in which the absence of reward was attributed to errors in action execution. Building on recent evidence indicating relatively direct communication between the cerebellum and basal ganglia, we hypothesized that cerebellar-dependent sensory prediction errors (SPEs), a signal indicating execution failure, could attenuate value updating within a basal ganglia-dependent reinforcement learning system. Here we compared the SPE hypothesis to an alternative, "top-down" hypothesis in which changes in choice behavior reflect participants' sense of agency. In two experiments with male and female human participants, we manipulated the strength of SPEs, along with the participants' sense of agency in the second experiment. The results showed that, whereas the strength of SPE had no effect on choice behavior, participants were much more likely to discount the absence of rewards under conditions in which they believed the reward outcome depended on their ability to produce accurate movements. These results provide strong evidence that SPEs do not directly influence reinforcement learning. Instead, a participant's sense of agency appears to play a significant role in modulating choice behavior when unexpected outcomes can arise from errors in action execution.
SIGNIFICANCE STATEMENT When learning from the outcome of actions, the brain faces a credit assignment problem: Failures of reward can be attributed to poor choice selection or poor action execution. Here, we test a specific hypothesis that execution errors are implicitly signaled by cerebellar-based sensory prediction errors. We evaluate this hypothesis and compare it with a more "top-down" hypothesis in which the modulation of choice behavior from execution errors reflects participants' sense of agency. We find that sensory prediction errors have no significant effect on reinforcement learning. Instead, instructions influencing participants' belief of causal outcomes appear to be the main factor influencing their choice behavior.
Determination of nine pharmaceutical active compounds in surface waters from Paraopeba River Basin in Brazil by LTPE-HPLC-ESI-MS/MS
Abstract
A simple, inexpensive, versatile, and environment-friendly extraction method, using low-temperature partitioning extraction (LTPE), was validated to quantify pharmaceutical-active compounds (PhACs) in surface water samples by high-performance liquid chromatography coupled to electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS). The PhACs analyzed were acetaminophen, bezafibrate, diclofenac, diltiazem, fluconazole, linezolid, miconazole, ondansetron hydrochloride, and trimethoprim. The detection and quantification limits ranged from 0.15 to 12.30 ng L−1 and 0.43 to 40.60 ng L−1, respectively. Recovery rates ranged from 46 to 135%, and relative standard deviation (RSD%) varied between 0.49 and 6.13%. This method was applied to monitor water contamination by PhACs in the Paraopeba River Basin (PRB), Minas Gerais state, Brazil. All PhACs, except linezolid which was not detected, were found in PRB water samples in concentrations that ranged from 2.6 ng L−1 to 2.62 μg L−1.
Photooxidation of Octahydro Tetramethyl Naphthalenylethanone in Perfumes and Aftershaves
Photochemistry and Photobiology, EarlyView.
Solvent-Extracted Wool Wax: Thermotropic Properties and Skin Efficacy
Background/Aims: Wool wax is a soft, yellow, waxy substance that is secreted by the sebaceous glands of sheep. The purpose of wool wax is to waterproof and protect the wool. Chemically, wool wax is a complex mixture of esters, fatty acids, and alcohols. Wool waxes with different properties can be obtained by following different extraction methodologies. Methods: Two differently extracted wool waxes are compared in this study. Their effectiveness in mimicking the properties of skin lipids is evaluated. In addition, the lipid compositions and thermotropic behaviours of the 2 differently extracted wool waxes were evaluated. Results: The solvent-extracted wool wax was found to have a significantly higher polar lipid content than that of the water-extracted wool wax. This increase in the polar character of the solvent-extracted wool wax was also demonstrated by increased values of transition and degradation temperatures in the differential scanning calorimetry and thermogravimetric analyses, respectively. In addition, solvent-extracted wool wax demonstrated the ability to reinforce stratum corneum lipids, which led to improved skin barrier function. Conclusions: The suitability of the solvent-extracted wool wax for application in the preparation of cosmetics and dermatological products was demonstrated.
Skin Pharmacol Physiol 2018;31:198–205
Skin Pharmacol Physiol 2018;31:198–205
Against reductive ethical naturalism
Abstract
This paper raises an objection to two important arguments for reductive ethical naturalism. Reductive ethical naturalism is the view that ethical properties reduce to the properties countenanced by the natural and social sciences. The main arguments for reductionism in the literature hold that ethical properties reduce to natural properties by supervening on them, either because supervenience is alleged to guarantee identity via mutual entailment, or because non-reductive supervenience relations render the supervenient properties superfluous. After carefully characterizing naturalism and reductionism, we will present, explain, and raise objections against each of the main reductionist arguments: (a) that supervenience does not support the claim that ethical properties and their subvenient natural properties are mutually entailing; (b) that reductive views undermine the claim that ethical properties yield resemblance; and (c) that supervenience does not entail that non-descriptive ethical properties are superfluous in the most fundamental sense.
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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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https://www.youtube.com/watch?v=DFOhpBjLqN4&t=1s , Η ΘΕΡΑΠΕΙΑ ΓΙΑ ΟΛΕΣ ΤΙΣ ΑΣΘΕΝΕΙΕΣ 1 Περιεχόμενα Σύντομο βιογραφικό Πρόλογος μεταφραστ...
