Pediatric Dermatology, EarlyView.
Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00306932607174,00302841026182,alsfakia@gmail.com
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Τετάρτη 2 Μαΐου 2018
Texting atopic dermatitis patients to optimize learning and eczema area and severity index scores: A pilot randomized control trial
The Association of Dietary Intakes of Total Polyphenol and Its Subclasses with the Risk of Metabolic Syndrome: Tehran Lipid and Glucose Study
Metabolic Syndrome and Related Disorders, Ahead of Print.
Genetic and Environmental Influences on the Associations Between Uric Acid Levels and Metabolic Syndrome Over Time
Metabolic Syndrome and Related Disorders, Ahead of Print.
Clinical and Body Compositional Factors Associated with Metabolic Syndrome in Obese Koreans: A Cross-Sectional Study
Metabolic Syndrome and Related Disorders, Ahead of Print.
Relationship of Selected Adipokines with Markers of Vascular Damage in Patients with Type 2 Diabetes
Metabolic Syndrome and Related Disorders, Ahead of Print.
Vertical shift in ciliate body-size spectrum and its environmental drivers in western Arctic pelagic ecosystems
Abstract
As an inherent functional trait, body-size spectrum is widely used as an informative indicator to summarize community structures in taxon-free space. The vertical shift in the body-size spectrum of pelagic ciliates and its environmental drivers were explored at eight depth layers from the water surface to a depth of 100 m in western Arctic pelagic ecosystems. A total of 85 samples were collected at 23 sampling stations during the summer sea-ice reduction period from August 5 to August 24, 2016. Based on equivalent spherical diameter (ESD), six body-size ranks were identified, of which ranks S2 (15–25 μm), S3 (26–38 μm), S4 (39–60 μm), and S6 (79–91 μm) were the top four levels in frequency of occurrence and ranks S2 and S3 were the dominant levels in abundance. The body-size spectrum of the ciliates showed a clear vertical shift, with a significant succession among the dominant body-size units from the water surface to deeper layers in the water column. Multivariate analysis demonstrated a significant vertical variation in the body-size spectrum of the ciliates among the eight depths, which was significantly correlated with nutrients (phosphate and nitrite + nitrate) and chlorophyll a (Chl a), alone or in combination with dissolved oxygen. Four body-size diversity/distinctness indices were significantly correlated with the levels of phosphate, nitrite + nitrate, ammonium, and Chl a. Our results demonstrated that the body-size spectrum of pelagic ciliates can be shifted by environmental drivers (mainly nutrients and Chl a); thus, we suggest that it may be used to indicate water quality status on a vertical scale in the water column in deep seas.
A tricky case of hair loss in a child: Trichoscopy saves the day
Indian Dermatology Online Journal 2018 9(3):203-204
Dermoscopy of cutaneous mastocytoma
Indian Dermatology Online Journal 2018 9(3):218-219
Intense pulsed light therapy for acne-induced post-inflammatory erythema
Indian Dermatology Online Journal 2018 9(3):159-164
Background: Intense pulsed light (IPL) is a comparatively new system of practice in treating acne-induced post inflammatory erythema (PIE) which is a difficult condition to treat, and variations exist in the results from published studies with insufficient or limited scientific evidence of IPL on Indian skin. Aim: To study the efficacy of IPL in the treatment of acne-induced PIE and to document adverse effects of the procedure. Settings and Design: A hospital-based retrospective observational study on 33 patients with acne-induced PIE who completed treatment with IPL during the time period of July 2015 to June 2017. Patients and Methods: All 33 patients were treated with vascular mode of IPL using 560-nm filter every 3 weeks for three to six sessions. Grading of PIE was done by Clinician Erythema Severity Score, and the objective parameters were assessed statistically for improvement using photographs. Adverse effects were noted and followed up. Statistical Analysis: Wilcoxon sign rank test and Pearson's correlation. Results: There was statistically significant reduction in mean erythema score from 2.57 ± 0.66 to 1.21 ± 0.48 following IPL (Z = −5.295, P < 0.001—Wilcoxon sign rank test). Excellent improvement was noted in 11 (33.33%), good in 15 (45.45%), fair in 4 (12.12%), and poor in 3 (9.09%), and the results were consistent on follow-up. Adverse effects included erythema, hyperpigmentation, and hypopigmentation which were all transient and resolved completely in all patients on follow-up. Conclusion: IPL is an effective and safe alternative to otherwise difficult-to-treat acne-induced PIE.
Congenital insensitivity to pain and anhydrosis syndrome
Indian Dermatology Online Journal 2018 9(3):211-212
Correlation between disease severity, family income, and quality of life in psoriasis: A study from South India
Indian Dermatology Online Journal 2018 9(3):165-169
Background: Psoriasis is a common, chronic inflammatory disorder of skin characterized by a long clinical course with exacerbations, remissions, and relapses. The cost of therapy and psychological burden of the disease depends on disease severity. The objective of this study was to assess the quality of life and financial status and to correlate the financial burden of the disease with the severity of psoriasis and quality of life. Materials and Methods: A total of 102 psoriasis patients attending the dermatology outpatient department in our hospital were enrolled in this study. A detailed history and complete physical examination, including, Psoriasis Area and Severity Index (PASI), was done. Their family income was calculated. Quality of life was measured using the dermatology life quality index (DLQI) proposed by Finlay et al. Multiple linear regression was done to identify the predictor variables of quality of life (DLQI). P < 0.05 was considered statistically significant. Results: Among the 102 psoriasis patients 78 were men(76.5%) and 24 were women(23.5%). The mean PASI score was 8.20 ± 6.18 the mean DLQI was 13.01 ± 6.95, and mean family income was INR 15570.10 ± INR 10081.82 per month. There was a significant positive correlation between disease severity and DLQI, and a significant negative correlation between family income and PASI as well as DLQI. Conclusion: The quality of life in psoriasis is affected by both the disease severity and financial status of the patient. The chronic course of psoriasis along with disease severity, in a background of low financial status, impairs the quality of life.
Newer topical treatments in skin and nail dermatophyte infections
Indian Dermatology Online Journal 2018 9(3):149-158
Dermatophytes are amongst the most common causative agents of fungal infections worldwide and widespread in the developing countries. Various studies have found the significantly rising trend of this infection in India especially in last 4-5 years. The growing epidemic of recurrent/chronic dermatophytosis has led to the need for newer antifungal agents and/or preparations. Furthermore, resistance to commonly used topical and oral antifungals has increased alarmingly. Significantly increasing resistance has led to state of anxiety in physicians and significant distress to the patients socially, emotionally, and financially. Newer formulations or newer derivatives of existing drug classes and few newer drug classes are being developed to tackle this menace. Other forms of local therapies including lasers and photodynamic therapy are still in developmental phase and still need to be optimized in terms of dosing schedule, frequency of use and duration of therapy. Moreover, cost of these therapies remained most important obstacle in developing countries like India. We are hereby reviewing the newer formulations of topical therapies and drugs/interventions in experimental phase.
Serum levels of 25-hydroxyvitamin D in chronic urticaria and its association with disease activity: A case control study
Indian Dermatology Online Journal 2018 9(3):170-174
Aim: To evaluate the relationship between vitamin D levels and chronic spontaneous urticaria (CSU) and compare with healthy age and sex matched controls. Material and Methods: This was a hospital-based cross-sectional study conducted over a period of 1 year, in which 110 patients with CSU were recruited along with an equal number of sex and age-matched healthy controls. For each patient, urticaria activity score (UAS) was calculated and autologous serum skin test (ASST) was performed. Plasma 25-hydroxyvitamin D [25-(OH)D] was analyzed by chemiluminescence method. A deficiency in vitamin D was defined as serum 25-(OH)D concentrations <30 ng/mL. The statistical analysis was carried out by using appropriate statistical tests. Results: The mean serum 25-(OH)D levels of CSU patients was 19.6 ± 6.9 ng/mL, whereas in control group, the mean level was 38.5 ± 6.7, the difference being statistically significant (P < 0.001). A significant negative correlation was found between vitamin D levels and UAS. (P < 0.001). The number of patients with ASST positivity was 44 (40%). Conclusion: The patients with CSU had reduced levels of vitamin D when compared to healthy controls. Furthermore, there was a significant negative correlation between the levels of serum vitamin D and severity of CSU.
Cytomorphological diagnosis of isolated cutaneous aspergillosis in an immunocompetent host
Indian Dermatology Online Journal 2018 9(3):206-208
SkinIndia Quiz 45: Asymptomatic nodular lesion over the neck in an old woman
Indian Dermatology Online Journal 2018 9(3):214-215
Metastatic angiosarcoma of lower extremity
Indian Dermatology Online Journal 2018 9(3):177-181
Angiosarcoma (AS) is an uncommon malignant neoplasm characterized by rapidly proliferating, extensively infiltrating anaplastic cells derived from blood vessels. These are aggressive tumors and tend to recur locally, spread widely with high rate of lymph node and systemic metastases. They are more frequent in skin and soft tissue, head and neck being the most common sites. Here we report a case of metastatic AS affecting lower extremity in an elderly patient on a background of chronic lymphedema due to filariasis (Stewart–Treves syndrome).
Dermoscopy of trichoepithelioma: A clue to diagnosis
Indian Dermatology Online Journal 2018 9(3):222-223
Pachydermoperiostosis mimicking acromegaly: A case report
Indian Dermatology Online Journal 2018 9(3):182-184
Pachydermoperiostosis is a rare, hereditary disease commonly presenting with digital clubbing, pachyderma, and periosteal hypertrophy. Coarsening of facial features and spade-like enlargement of hands and feet may give rise to a diagnostic dilemma between pachydermoperiostosis and acromegaly. This report highlights a case of a 36-year-old man who presented with broadening of hands and feet, facial skin thickening, and edematous and drooping eyelids for the last 10 years.There was no history of similar presentation in his family. Such clinical presentation in corroboration with normal growth hormone level and prominent radiological abnormalities prompted us to make a diagnosis of pachydermoperiostosis.
Unsuspected amelanotic melanoma in an elephantiasis foot
Indian Dermatology Online Journal 2018 9(3):202-203
Erasmus syndrome: Association of silicosis and systemic sclerosis
Indian Dermatology Online Journal 2018 9(3):185-187
Silicosis is an inflammatory disease of the lung characterized by irreversible lung fibrosis which develops from prolonged pulmonary inhalation and retention of crystalline silica and immune reaction. It mainly appears as an occupational hazard in persons involved in stone-quarrying, mining, and sand blasting. Crystalline silica is not only known to be responsible for silicosis but also for other autoimmune diseases including systemic lupus erythematosus (SLE), rheumatoid arthritis (RA)-Caplan syndrome, systemic sclerosis (SSc), and antineutrophil cytoplasmic antibody (ANCA)-related vasculitis. Erasmus syndrome is the association of silica exposure and subsequent development of SSc. The limited numbers of cases reported in the literature were miners and only sporadically involved in other professionals. Here, we report a case of a 52 -year-old stone cutter who developed silicosis and SSc after 25 years of exposure.
Bacillary angiomatosis in an immunocompetent individual
Indian Dermatology Online Journal 2018 9(3):205-206
Congenital eccrine angiomatous hamartoma: A rare entity revisited
Indian Dermatology Online Journal 2018 9(3):188-190
Eccrine angiomatous hamartoma (EAH) is a rare benign malformation characterized by eccrine and vascular components. It usually presents at birth or during early infancy or childhood on lower extremities as a nodule or plaque. We report a case of asymptomatic tumoral swelling over the left leg in a 5-month-old Indian infant since birth. This was diagnosed as EAH on histopathology and confirmed on immunohistochemistry.
Extensive mucocutaneous papillomas in a case of focal dermal hypoplasia
Indian Dermatology Online Journal 2018 9(3):208-210
Rhinoscleroma: An unusual presentation
Indian Dermatology Online Journal 2018 9(3):191-193
Rhinoscleroma is a chronic granulomatous disease caused by Klebsiella rhinoscleromatis. It commonly affects the nasal cavity and nasopharynx, but it can also involve the larynx, trachea, bronchi, middle ear, and orbit. We are reporting a rare presentation of rhinoscleroma in a middle-aged female patient involving the lips and gums.
Herpes zoster: Hand dominance the missing link to unilaterality?
Indian Dermatology Online Journal 2018 9(3):212-213
A 5-year follow-up study of 633 cutaneous SCC excisions: rates of local recurrence and lymph node metastasis
A 5-year follow-up study of 633 cutaneous squamous cell cancer (SCC) excisions was performed collecting data on rates of local recurrence and nodal metastasis.
Effects of the chloro-s-triazine herbicide terbuthylazine on DNA integrity in human and mouse cells
Abstract
Terbuthylazine belongs to the chloro-s-triazine group of herbicides and acts primarily as a photosynthesis inhibitor. The mechanisms of action related to its exposure, relevant both in animals and humans, are still insufficiently investigated. This comprehensive study focused on the outcomes of terbuthylazine exposure at cell level in vitro, and a mice model in vivo. Experiments in vitro were conducted on whole human peripheral blood, isolated lymphocytes, and HepG2 cells exposed for 4 h to terbuthylazine at 8.00, 0.80, and 0.58 ng/mL, which is comparable with current reference values set by the European Commission in 2011. Terbuthylazine cytotoxicity was evaluated using dual fluorescent staining with ethidium bromide and acridine orange on lymphocytes, and CCK-8 colorimetric assay on HepG2 cells. The levels of DNA damage were measured using alkaline and hOGG1-modified comet assays. The potency of terbuthlyazine regarding induction of oxidative stress in vitro was studied using a battery of standard oxidative stress biomarkers. The in vivo experiment was conducted on Swiss albino mice exposed to terbuthlyazine in the form of an active substance and its formulated commercial product Radazin TZ-50 at a daily dose of 0.0035 mg/kg bw for 14 days. Following exposure, the DNA damage levels in leukocytes, bone marrow, liver, and kidney cells of the treated mice were measured using an alkaline comet assay. In vitro results suggested low terbuthylazine cytotoxicity in non-target cells. The highest tested concentration (8.00 ng/mL) reduced lymphocyte viability by 15%, mostly due to apoptosis, while cytotoxic effects in HepG2 cells at the same concentration were negligible. Acute in vitro exposure of human lymphocytes and HepG2 cells to terbuthylazine resulted in low-level DNA instability, as detected by the alkaline comet assay. Further characterization of the mechanisms behind the DNA damage obtained using the hOGG1-modified comet assay indicated that oxidative DNA damage did not prevail in the overall damage. This was further confirmed by the measured levels of oxidative stress markers, which were mostly comparable to control. Results obtained in mice indicate that both the active substance and formulated commercial product of terbuthylazine produced DNA instability in all of the studied cell types. We found that DNA in liver and kidney cells was more prone to direct toxic effects of the parent compound and its metabolites than DNA in leukocytes and bone marrow cells. The overall findings suggest the formation of reactive terbuthylazine metabolites capable of inducing DNA cross-links, which hinder DNA migration. These effects were most pronounced in liver cells in vivo and HepG2 cells in vitro. To provide a more accurate explanation of the observed effects, additional research is needed. Nevertheless, the present study provides evidence that terbuthylazine at concentrations comparable with current reference values possesses toxicological risk because it caused low-level DNA instability, both at cellular and animal organism level, which should be further established in forthcoming studies.
A review on the engine performance and exhaust emission characteristics of diesel engines fueled with biodiesel blends
Abstract
Biodiesels have gained much popularity because they are cleaner alternative fuels and they can be used directly in diesel engines without modifications. In this paper, a brief review of the key studies pertaining to the engine performance and exhaust emission characteristics of diesel engines fueled with biodiesel blends, exhaust aftertreatment systems, and low-temperature combustion technology is presented. In general, most biodiesel blends result in a significant decrease in carbon monoxide and total unburned hydrocarbon emissions. There is also a decrease in carbon monoxide, nitrogen oxide, and total unburned hydrocarbon emissions while the engine performance increases for diesel engines fueled with biodiesels blended with nano-additives. The development of automotive technologies, such as exhaust gas recirculation systems and low-temperature combustion technology, also improves the thermal efficiency of diesel engines and reduces nitrogen oxide and particulate matter emissions.
Removal of nickel from aqueous solution using supported zeolite-Y hollow fiber membranes
Abstract
This work describes the development of supported zeolite-Y membranes, prepared using the hydrothermal method, for the removal of nickel from an aqueous solution. Alumina hollow fibers prepared using the phase inversion and sintering technique were used as an inert support. The supported zeolite-Y membranes were characterized using the field emission scanning electron microscope (FESEM), X-ray diffraction (XRD), and the water permeation and rejection test. The performance of the supported zeolite-Y membranes for heavy metal removal using batch adsorption and filtration test was studied using the atomic absorption spectroscopy (AAS). The adsorption study shows that the removal of nickel was pH-dependent but affected by the presence of α-alumina. The seeded zeolite-Y membrane gave the highest adsorption capacity which was 126.2 mg g−1. This enabled the membrane to remove 63% of nickel ions from the aqueous solution within 180 min of contact time. The adsorption mechanism of nickel onto the zeolite-Y membrane was best fitted to the Freundlich isotherm. The kinetic study concluded that the adsorption was best fitted to pseudo-second-order model with higher correlation coefficient (R2 = 0.9996). The filtration study proved that the zeolite-Y membrane enabled to reduce the concentration of heavy metal at parts per billion level.
TOPSIS-based parametric optimization of compression ignition engine performance and emission behavior with bael oil blends for different EGR and charge inlet temperature
Abstract
The demand for higher fuel energy and lesser exhaust emissions of diesel engines can be achieved by fuel being used and engine operating parameters. In the present work, effects of engine speed (RPM), injection timing (IT), injection pressure (IP), and compression ratio (CR) on performance and emission characteristics of a compression ignition (CI) engine were investigated. The ternary test fuel of 65% diesel + 25% bael oil + 10% diethyl ether (DEE) was used in this work and test was conducted at different charge inlet temperature (CIT) and exhaust gas recirculation (EGR). All the experiments are conducted at the tradeoff engine load that is 75% engine load. When operating the diesel engine with 320 K CIT, brake thermal efficiency (BTE) is improved to 28.6%, and carbon monoxide (CO) and hydrocarbon (HC) emissions have been reduced to 0.025% and 12.5 ppm at 18 CR. The oxide of nitrogen (NOx) has been reduced to 240 ppm at 1500 rpm for 30% EGR mode. Technique for Order of Preference by Similarity to Ideal Solution (TOPSIS) method is frequently used in multi-factor selection and gray correlation analysis method is used to study uncertain of the systems.
A 5-year follow-up study of 633 cutaneous SCC excisions: rates of local recurrence and lymph node metastasis
Publication date: Available online 2 May 2018
Source:Journal of Plastic, Reconstructive & Aesthetic Surgery
Author(s): K. Khan, R. Mykula, R. Kerstein, N. Rabey, T. Bragg, A. Crick, S. Heppell, P. Budny, M. Potter
BackgroundA 5-year follow-up study of 633 cutaneous squamous cell cancer (SCC) excisions was performed collecting data on rates of local recurrence and nodal metastasis.MethodsA retrospective analysis of patients was performed across 4 regional plastic surgery centres (Stoke Mandeville Hospital, Aylesbury, John Radcliffe Hospital, Oxford, Salisbury District Hospital, Salisbury, and Queen Alexandra Hospital, Portsmouth) assessing rates of local recurrence and nodal metastasis.ResultsWe report 5-year outcomes from 598 SCCs (95% follow-up rate). The total recurrence rate (local recurrence and nodal metastasis) was 6.7% (n = 40) at 5 years, with 96% of these occurring within 2 years. Median time to local recurrence was 9 months (1-57), with 76.9% (n = 20) undergoing further wide local excision. Median time to lymph node metastasis was 5.5 months (1-18 months). There were two cases of disease-related death. Only 15% (n = 6) of incomplete excisions recurred. Interestingly, 19.1% (n=9) of 47 SCCs with perineural invasion on original histopathology recurred versus only 5.6% (n=31) of the 551 SCCs without perineural invasion (p = 0.005).ConclusionsThis study is one of the largest studies to date following up 598 SCC excisions at 5-years with total recurrence rates comparable to current published literature. We report perineural invasion as a significant predictor of recurrence and that 96% of total recurrence occurred within 2 years. This is in contrast to current U.K. guidelines (75% at 2 years, 95% at 5 years) suggesting shorter length of hospital follow-up may be reasonable.
Detection of Borrelia in Ixodes scapularis ticks by silver stain, immunohistochemical and direct immunofluorescent methods
Journal of Cutaneous Pathology, EarlyView.
Mirror Neuron Populations Represent Sequences of Behavioral Epochs During Both Execution and Observation
Mirror neurons (MNs) have the distinguishing characteristic of modulating during both execution and observation of an action. Although most studies of MNs have focused on various features of the observed movement, MNs also may monitor the behavioral circumstances in which the movement is embedded, including time periods preceding and following the observed movement. Here, we recorded multiple MNs simultaneously from implanted electrode arrays as two male monkeys executed and observed a reach, grasp, and manipulate task involving different target objects. MNs were recorded from premotor cortex (PM-MNs) and primary motor cortex (M1-MNs). During execution trials, hidden Markov models (HMMs) applied to the activity of either PM-MN or M1-MN populations most often detected sequences of four hidden states, which we named according to the behavioral epoch during which each state began: initial, reaction, movement, and final. The hidden states of MN populations thus reflected not only the movement, but also three behavioral epochs during which no movement occurred. HMMs trained on execution trials could decode similar sequences of hidden states in observation trials, with complete hidden state sequences decoded more frequently from PM-MN populations than from M1-MN populations. Moreover, population trajectories projected in a 2D plane defined by execution trials were preserved in observation trials more for PM-MN than for M1-MN populations. These results suggest that MN populations represent entire behavioral sequences, including both movement and non-movement. PM-MN populations showed greater similarity than M1-MN populations in their representation of behavioral sequences during execution versus observation.
SIGNIFICANCE STATEMENT Mirror neurons (MNs) are thought to provide a neural mechanism for understanding the actions of others. However, for an action to be understood, both the movement per se and the non-movement context before and after the movement need to be represented. We found that simultaneously recorded MN populations encoded sequential hidden neural states corresponding approximately to sequential behavioral epochs of a reach, grasp, and manipulate task. During observation trials, hidden state sequences were similar to those identified in execution trials. Hidden state similarity was stronger for MN populations in premotor cortex than for those in primary motor cortex. Execution/observation similarity of hidden state sequences may contribute to understanding the actions of others without actually performing the action oneself.
On the Flexibility of Basic Risk Attitudes in Monkeys
Monkeys and other animals appear to share with humans two risk attitudes predicted by prospect theory: an inverse-S-shaped probability-weighting (PW) function and a steeper utility curve for losses than for gains. These findings suggest that such preferences are stable traits with common neural substrates. We hypothesized instead that animals tailor their preferences to subtle changes in task contexts, making risk attitudes flexible. Previous studies used a limited number of outcomes, trial types, and contexts. To gain a broader perspective, we examined two large datasets of male macaques' risky choices: one from a task with real (juice) gains and another from a token task with gains and losses. In contrast to previous findings, monkeys were risk seeking for both gains and losses (i.e., lacked a reflection effect) and showed steeper gain than loss curves (loss seeking). Utility curves for gains were substantially different in the two tasks. Monkeys showed nearly linear PWs in one task and S-shaped ones in the other; neither task produced a consistent inverse-S-shaped curve. To account for these observations, we developed and tested various computational models of the processes involved in the construction of reward value. We found that adaptive differential weighting of prospective gamble outcomes could partially account for the observed differences in the utility functions across the two experiments and thus provide a plausible mechanism underlying flexible risk attitudes. Together, our results support the idea that risky choices are constructed flexibly at the time of elicitation and place important constraints on neural models of economic choice.
SIGNIFICANCE STATEMENT We respond in reliable ways to risk, but are our risk preferences stable traits or ephemeral states? Using various computational models, we examined two large datasets of macaque risky choices in two different tasks. We observed several deviations from "classic" risk preferences seen in humans and monkeys: no reflection effect, loss seeking as opposed to loss aversion, and linear and S-shaped, as opposed to inverse-S-shaped, probability distortion. These results challenge the idea that our risk attitudes are evolved traits shared with the last common ancestor of macaques and humans, suggesting instead that behavioral flexibility is the hallmark of risky choice in primates. We show how this flexibility can emerge partly as a result of interactions between attentional and reward systems.
Functional Organization of the Temporal-Parietal Junction for Theory of Mind in Preverbal Infants: A Near-Infrared Spectroscopy Study
Successful human social life requires imagining what others believe or think to understand and predict behavior. This ability, often referred to as theory of mind (ToM), reliably engages a specialized network of temporal and prefrontal brain regions in older children and adults, including selective recruitment of the temporal–parietal junction (TPJ). To date, how and when this specialized brain organization for ToM arises is unknown due to limitations in functional neuroimaging at younger ages. Here, we used the emerging technique of functional near-infrared spectroscopy to measure the functional brain response across parietal, temporal, and prefrontal regions in 7-month-old male and female infants as they viewed different video scenarios of a person searching for a hidden object. Over different conditions, we manipulated whether the person held an accurate (true) or inaccurate (false) belief about the location of the hidden object in the videos. In two separate experiments, we observed that activity from the TPJ, but not other temporal and prefrontal regions, spontaneously tracked with the beliefs of the other person, responding more during scenarios when the other person's belief regarding the location of the object was false compared with scenarios when her belief was true. These results mirror those obtained with adults to show that the TPJ already shows some functional organization relevant to high-level social cognition by around 7 months of age. Furthermore, these results suggest that infants may draw on similar core mechanisms to implicitly track beliefs, as adults do when reasoning explicitly about them.
SIGNIFICANCE STATEMENT Humans selectively engage a network of brain regions, including the temporal–parietal junction (TPJ), to track what others think, an ability referred to as theory of mind. How and when this specialized brain organization for high-level social cognition arises is unknown. Using the emerging technique of near-infrared spectroscopy with 7-month-old infants, we observed that activity of the TPJ, but not other temporal and frontal regions, distinguished between scenarios when another person's belief about the location of the object was false compared with scenarios when the belief was true. These results suggest that a basic neural architecture to understand and predict the actions of others based on their beliefs may be present from the first year of life.
Parietal-Occipital Interactions Underlying Control- and Representation-Related Processes in Working Memory for Nonspatial Visual Features
Although the manipulation of load is popular in visual working memory research, many studies confound general attentional demands with context binding by drawing memoranda from the same stimulus category. In this fMRI study of human observers (both sexes), we created high- versus low-binding conditions, while holding load constant, by comparing trials requiring memory for the direction of motion of one random dot kinematogram (RDK; 1M trials) versus for three RDKs (3M), or versus one RDK and two color patches (1M2C). Memory precision was highest for 1M trials and comparable for 3M and 1M2C trials. And although delay-period activity in occipital cortex did not differ between the three conditions, returning to baseline for all three, multivariate pattern analysis decoding of a remembered RDK from occipital cortex was also highest for 1M trials and comparable for 3M and 1M2C trials. Delay-period activity in intraparietal sulcus (IPS), although elevated for all three conditions, displayed more sensitivity to demands on context binding than to load per se. The 1M-to-3M increase in IPS signal predicted the 1M-to-3M declines in both behavioral and neural estimates of working memory precision. These effects strengthened along a caudal-to-rostral gradient, from IPS0 to IPS5. Context binding-independent load sensitivity was observed when analyses were lateralized and extended into PFC, with trend-level effects evident in left IPS and strong effects in left lateral PFC. These findings illustrate how visual working memory capacity limitations arise from multiple factors that each recruit dissociable brain systems.
SIGNIFICANCE STATEMENT Visual working memory capacity predicts performance on a wide array of cognitive and real-world outcomes. At least two theoretically distinct factors are proposed to influence visual working memory capacity limitations: an amodal attentional resource that must be shared across remembered items; and the demands on context binding. We unconfounded these two factors by varying load with items drawn from the same stimulus category ("high demands on context binding") versus items drawn from different stimulus categories ("low demands on context binding"). The results provide evidence for the dissociability, and the neural bases, of these two theorized factors, and they specify that the functions of intraparietal sulcus may relate more strongly to the control of representations than to the general allocation of attention.
Sustained Expression of Negative Regulators of Myelination Protects Schwann Cells from Dysmyelination in a Charcot-Marie-Tooth 1B Mouse Model
Schwann cell differentiation and myelination in the PNS are the result of fine-tuning of positive and negative transcriptional regulators. As myelination starts, negative regulators are downregulated, whereas positive ones are upregulated. Fully differentiated Schwann cells maintain an extraordinary plasticity and can transdifferentiate into "repair" Schwann cells after nerve injury. Reactivation of negative regulators of myelination is essential to generate repair Schwann cells. Negative regulators have also been implicated in demyelinating neuropathies, although their role in disease remains elusive. Here, we used a mouse model of Charcot–Marie–Tooth neuropathy type 1B (CMT1B), the P0S63del mouse characterized by ER stress and the activation of the unfolded protein response, to show that adult Schwann cells are in a partial differentiation state because they overexpress transcription factors that are normally expressed only before myelination. We provide evidence that two of these factors, Sox2 and Id2, act as negative regulators of myelination in vivo. However, their sustained expression in neuropathy is protective because ablation of Sox2 or/and Id2 from S63del mice of both sexes results in worsening of the dysmyelinating phenotype. This is accompanied by increased levels of mutant P0 expression and exacerbation of ER stress, suggesting that limited differentiation may represent a novel adaptive mechanism through which Schwann cells counter the toxic effect of a mutant terminal differentiation protein.
SIGNIFICANCE STATEMENT In many neuropathies, Schwann cells express high levels of early differentiation genes, but the significance of these altered expression remained unclear. Because many of these factors may act as negative regulators of myelination, it was suggested that their misexpression could contribute to dysmyelination. Here, we show that the transcription factors Sox2 and Id2 act as negative regulators of myelination in vivo, but that their sustained expression in Charcot–Marie–Tooth type 1B (CMT1B) represents an adaptive response activated by the Schwann cells to reduce mutant protein toxicity and prevent demyelination.
Alpha Oscillations Are Causally Linked to Inhibitory Abilities in Ageing
Aging adults typically show reduced ability to ignore task-irrelevant information, an essential skill for optimal performance in many cognitive operations, including those requiring working memory (WM) resources. In a first experiment, young and elderly human participants of both genders performed an established WM paradigm probing inhibitory abilities by means of valid, invalid, and neutral retro-cues. Elderly participants showed an overall cost, especially in performing invalid trials, whereas younger participants' general performance was comparatively higher, as expected.
Inhibitory abilities have been linked to alpha brain oscillations but it is yet unknown whether in aging these oscillations (also typically impoverished) and inhibitory abilities are causally linked. To probe this possible causal link in aging, we compared in a second experiment parietal alpha-transcranial alternating current stimulation (tACS) with either no stimulation (Sham) or with two control stimulation frequencies (theta- and gamma-tACS) in the elderly group while performing the same WM paradigm. Alpha- (but not theta- or gamma-) tACS selectively and significantly improved performance (now comparable to younger adults' performance in the first experiment), particularly for invalid cues where initially elderly showed the highest costs. Alpha oscillations are therefore causally linked to inhibitory abilities and frequency-tuned alpha-tACS interventions can selectively change these abilities in the elderly.
SIGNIFICANCE STATEMENT Ignoring task-irrelevant information, an ability associated to rhythmic brain activity in the alpha frequency band, is fundamental for optimal performance. Indeed, impoverished inhibitory abilities contribute to age-related decline in cognitive functions like working memory (WM), the capacity to briefly hold information in mind. Whether in aging adults alpha oscillations and inhibitory abilities are causally linked is yet unknown. We experimentally manipulated frequency-tuned brain activity using transcranial alternating current stimulation (tACS), combined with a retro-cue paradigm assessing WM and inhibition. We found that alpha-tACS induced a significant improvement in target responses and misbinding errors, two indexes of inhibition. We concluded that in aging alpha oscillations are causally linked to inhibitory abilities, and that despite being impoverished, these abilities are still malleable.
BACE1 Mediates HIV-Associated and Excitotoxic Neuronal Damage Through an APP-Dependent Mechanism
HIV-associated neurocognitive disorders (HANDs) share common symptoms with Alzheimer's disease (AD), which is characterized by amyloid-β (Aβ) plaques. Plaques are formed by aggregation of Aβ oligomers, which may be the toxic species in AD pathogenesis, and oligomers are generated by cleavage of amyloid precursor protein (APP) by β-site amyloid precursor protein cleaving enzyme 1 (BACE1). BACE1 inhibitors reverse neuronal loss and cognitive decline in animal models of AD. Although studies have also found evidence of altered APP processing in HIV+ patients, it is unknown whether increased BACE1 expression or Aβ oligomer production is a common neuropathological feature of HAND. Moreover, it is unknown whether BACE1 or APP is involved in the excitotoxic, NMDAR-dependent component of HIV-associated neurotoxicity in vitro. Herein, we hypothesize that HIV-associated neurotoxicity is mediated by NMDAR-dependent elevation of BACE1 and subsequent altered processing of APP. Supporting this, we observed elevated levels of BACE1 and Aβ oligomers in CNS of male and female HIV+ patients. In a model of HIV-associated neurotoxicity in which rat neurons are treated with supernatants from HIV-infected human monocyte-derived macrophages, we observed NMDAR-dependent elevation of BACE1 protein. NMDA treatment also increased BACE1 and both pharmacological BACE1 inhibition and genetic loss of APP were partially neuroprotective. Moreover, in APP knock-out (APP–/–) mouse neurons, NMDA-induced toxicity was BACE1 independent, indicating that cytotoxicity of BACE1 is dependent upon APP cleavage. Our findings suggest that increased BACE1 and the resultant Aβ oligomer production may contribute to HIV-associated neuropathogenesis and inhibition of BACE1 could have therapeutic potential in HANDs.
SIGNIFICANCE STATEMENT HIV-associated neurocognitive disorders (HANDs) represent a range of cognitive impairments affecting ~50% of HIV+ individuals. The specific causes of HAND are unknown, but evidence suggests that HIV-infected macrophage infiltration into the brain may cause neuronal damage. Herein, we show that neurons treated with conditioned media from HIV-infected macrophages have increased expression of β-site amyloid precursor protein cleaving enzyme 1 (BACE1), a protein implicated in Alzheimer's disease pathogenesis. Moreover, inhibition of BACE1 prevented neuronal loss after conditioned media exposure, but had no effect on HIV-associated neurotoxicity in neurons lacking its cleavage target amyloid precursor protein. We also observed increased BACE1 expression in HIV+ patient brain tissue, confirming the potential relevance of BACE1 as a therapeutic target in HANDs.
Matrix Metalloproteinase-Mediated Blood-Brain Barrier Dysfunction in Epilepsy
The blood-brain barrier is dysfunctional in epilepsy, thereby contributing to seizure genesis and resistance to antiseizure drugs. Previously, several groups reported that seizures increase brain glutamate levels, which leads to barrier dysfunction. One critical component of barrier dysfunction is brain capillary leakage. Based on our preliminary data, we hypothesized that glutamate released during seizures mediates an increase in matrix-metalloproteinase (MMP) expression and activity levels, thereby contributing to barrier leakage. To test this hypothesis, we exposed isolated brain capillaries from male Sprague Dawley rats to glutamate ex vivo and used an in vivo/ex vivo approach of isolated brain capillaries from female Wistar rats that experienced status epilepticus as an acute seizure model. We found that exposing isolated rat brain capillaries to glutamate increased MMP-2 and MMP-9 protein and activity levels, and decreased tight junction protein levels, which resulted in barrier leakage. We confirmed these findings in vivo in rats after status epilepticus and in brain capillaries from male mice lacking cytosolic phospholipase A2. Together, our data support the hypothesis that glutamate released during seizures signals an increase in MMP-2 and MMP-9 protein expression and activity levels, resulting in blood-brain barrier leakage.
SIGNIFICANCE STATEMENT The mechanism leading to seizure-mediated blood-brain barrier dysfunction in epilepsy is poorly understood. In the present study, we focused on defining this mechanism in the brain capillary endothelium. We demonstrate that seizures trigger a pathway that involves glutamate signaling through cytosolic phospholipase A2, which increases MMP levels and decreases tight junction protein expression levels, resulting in barrier leakage. These findings may provide potential therapeutic avenues within the blood-brain barrier to limit barrier dysfunction in epilepsy and decrease seizure burden.
Active Braking of Whole-Arm Reaching Movements Provides Single-Trial Neuromuscular Measures of Movement Cancellation
Movement inhibition is an aspect of executive control that can be studied using the countermanding paradigm, wherein subjects try to cancel an impending movement following presentation of a stop signal. This paradigm permits estimation of the stop-signal reaction time or the time needed to respond to the stop signal. Numerous countermanding studies have examined fast, ballistic movements, such as saccades, even though many movements in daily life are not ballistic and can be stopped at any point during their trajectory. A benefit of studying the control of nonballistic movements is that antagonist muscle recruitment, which serves to actively brake a movement, presumably arises in response to the stop signal. Here, nine human participants (2 female) performed a center-out whole-arm reaching task with a countermanding component, while we recorded the activity of upper-limb muscles contributing to movement generation and braking. The data show a clear response on antagonist muscles to a stop signal, even for movements that have barely begun. As predicted, the timing of such antagonist recruitment relative to the stop signal covaried with conventional estimates of the stop-signal reaction time, both within and across subjects. The timing of antagonist muscle recruitment also attested to a rapid reprioritization of movement inhibition, with antagonist latencies decreasing across sequences consisting of repeated stop trials; such reprioritization also scaled with error magnitude. We conclude that antagonist muscle recruitment arises as a manifestation of a stopping process, providing a novel, accessible, and within-trial measure of the stop-signal reaction time.
SIGNIFICANCE STATEMENT The countermanding or stop-signal paradigm permits estimation of how quickly subjects cancel an impending movement. Traditionally, this paradigm has been studied using simple movements, such as saccadic eye movements or button presses. Here, by measuring upper limb muscle activity while human subjects countermand whole-arm reaching movements, we show that movement cancellation often involves prominent recruitment of antagonist muscles that serves to actively brake the movement, even on movements that have barely begun. The timing of antagonist muscle recruitment correlates with traditional estimates of movement cancellation. Because they can be detected on a single-trial basis, muscle-based measures may provide a new way of characterizing movement cancellation at an unprecedented within-trial resolution.
Cascades of Homeostatic Dysregulation Promote Incubation of Cocaine Craving
In human drug users, cue-induced drug craving progressively intensifies after drug abstinence, promoting drug relapse. This time-dependent progression of drug craving is recapitulated in rodent models, in which rats exhibit progressive intensification of cue-induced drug seeking after withdrawal from drug self-administration, a phenomenon termed incubation of drug craving. Although recent results suggest that functional alterations of the nucleus accumbens (NAc) contribute to incubation of drug craving, it remains poorly understood how NAc function evolves after drug withdrawal to progressively intensify drug seeking. The functional output of NAc relies on how the membrane excitability of its principal medium spiny neurons (MSNs) translates excitatory synaptic inputs into action potential firing. Here, we report a synapse-membrane homeostatic crosstalk (SMHC) in male rats, through which an increase or decrease in the excitatory synaptic strength induces a homeostatic decrease or increase in the intrinsic membrane excitability of NAc MSNs, and vice versa. After short-term withdrawal from cocaine self-administration, despite no actual change in the AMPA receptor-mediated excitatory synaptic strength, GluN2B NMDA receptors, the SMHC sensors of synaptic strength, are upregulated. This may create false SMHC signals, leading to a decrease in the membrane excitability of NAc MSNs. The decreased membrane excitability subsequently induces another round of SMHC, leading to synaptic accumulation of calcium-permeable AMPA receptors and upregulation of excitatory synaptic strength after long-term withdrawal from cocaine. Disrupting SMHC-based dysregulation cascades after cocaine exposure prevents incubation of cocaine craving. Thus, cocaine triggers cascades of SMHC-based dysregulation in NAc MSNs, promoting incubated cocaine seeking after drug withdrawal.
SIGNIFICANCE STATEMENT Here, we report a bidirectional homeostatic plasticity between the excitatory synaptic input and membrane excitability of nucleus accumbens (NAc) medium spiny neurons (MSNs), through which an increase or decrease in the excitatory synaptic strength induces a homeostatic decrease or increase in the membrane excitability, and vice versa. Cocaine self-administration creates a false homeostatic signal that engages this synapse-membrane homeostatic crosstalk mechanism, and produces cascades of alterations in excitatory synapses and membrane properties of NAc MSNs after withdrawal from cocaine. Experimentally preventing this homeostatic dysregulation cascade prevents the progressive intensification of cocaine seeking after drug withdrawal. These results provide a novel mechanism through which drug-induced homeostatic dysregulation cascades progressively alter the functional output of NAc MSNs and promote drug relapse.
The Magnitude, But Not the Sign, of MT Single-Trial Spike-Time Correlations Predicts Motion Detection Performance
Spike-time correlations capture the short timescale covariance between the activity of neurons on a single trial. These correlations can significantly vary in magnitude and sign from trial to trial, and have been proposed to contribute to information encoding in visual cortex. While monkeys performed a motion-pulse detection task, we examined the behavioral impact of both the magnitude and sign of single-trial spike-time correlations between two nonoverlapping pools of middle temporal (MT) neurons. We applied three single-trial measures of spike-time correlation between our multiunit MT spike trains (Pearson's, absolute value of Pearson's, and mutual information), and examined the degree to which they predicted a subject's performance on a trial-by-trial basis. We found that on each trial, positive and negative spike-time correlations were almost equally likely, and, once the correlational sign was accounted for, all three measures were similarly predictive of behavior. Importantly, just before the behaviorally relevant motion pulse occurred, single-trial spike-time correlations were as predictive of the performance of the animal as single-trial firing rates. While firing rates were positively associated with behavioral outcomes, the presence of either strong positive or negative correlations had a detrimental effect on behavior. These correlations occurred on short timescales, and the strongest positive and negative correlations modulated behavioral performance by ~9%, compared with trials with no correlations. We suggest a model where spike-time correlations are associated with a common noise source for the two MT pools, which in turn decreases the signal-to-noise ratio of the integrated signals that drive motion detection.
SIGNIFICANCE STATEMENT Previous work has shown that spike-time correlations occurring on short timescales can affect the encoding of visual inputs. Although spike-time correlations significantly vary in both magnitude and sign across trials, their impact on trial-by-trial behavior is not fully understood. Using neural recordings from area MT (middle temporal) in monkeys performing a motion-detection task using a brief stimulus, we found that both positive and negative spike-time correlations predicted behavioral responses as well as firing rate on a trial-by-trial basis. We propose that strong positive and negative spike-time correlations decreased behavioral performance by reducing the signal-to-noise ratio of integrated MT neural signals.
GABAergic Local Interneurons Shape Female Fruit Fly Response to Mating Songs
Many animals use acoustic signals to attract a potential mating partner. In fruit flies (Drosophila melanogaster), the courtship pulse song has a species-specific interpulse interval (IPI) that activates mating. Although a series of auditory neurons in the fly brain exhibit different tuning patterns to IPIs, it is unclear how the response of each neuron is tuned. Here, we studied the neural circuitry regulating the activity of antennal mechanosensory and motor center (AMMC)-B1 neurons, key secondary auditory neurons in the excitatory neural pathway that relay song information. By performing Ca2+ imaging in female flies, we found that the IPI selectivity observed in AMMC-B1 neurons differs from that of upstream auditory sensory neurons [Johnston's organ (JO)-B]. Selective knock-down of a GABAA receptor subunit in AMMC-B1 neurons increased their response to short IPIs, suggesting that GABA suppresses AMMC-B1 activity at these IPIs. Connection mapping identified two GABAergic local interneurons that synapse with AMMC-B1 and JO-B. Ca2+ imaging combined with neuronal silencing revealed that these local interneurons, AMMC-LN and AMMC-B2, shape the response pattern of AMMC-B1 neurons at a 15 ms IPI. Neuronal silencing studies further suggested that both GABAergic local interneurons suppress the behavioral response to artificial pulse songs in flies, particularly those with a 15 ms IPI. Altogether, we identified a circuit containing two GABAergic local interneurons that affects the temporal tuning of AMMC-B1 neurons in the song relay pathway and the behavioral response to the courtship song. Our findings suggest that feedforward inhibitory pathways adjust the behavioral response to courtship pulse songs in female flies.
SIGNIFICANCE STATEMENT To understand how the brain detects time intervals between sound elements, we studied the neural pathway that relays species-specific courtship song information in female Drosophila melanogaster. We demonstrate that the signal transmission from auditory sensory neurons to key secondary auditory neurons antennal mechanosensory and motor center (AMMC)-B1 is the first-step to generate time interval selectivity of neurons in the song relay pathway. Two GABAergic local interneurons are suggested to shape the interval selectivity of AMMC-B1 neurons by receiving auditory inputs and in turn providing feedforward inhibition onto AMMC-B1 neurons. Furthermore, these GABAergic local interneurons suppress the song response behavior in an interval-dependent manner. Our results provide new insights into the neural circuit basis to adjust neuronal and behavioral responses to a species-specific communication sound.
Control of Excitation/Inhibition Balance in a Hippocampal Circuit by Calcium Sensor Protein Regulation of Presynaptic Calcium Channels
Activity-dependent regulation controls the balance of synaptic excitation to inhibition in neural circuits, and disruption of this regulation impairs learning and memory and causes many neurological disorders. The molecular mechanisms underlying short-term synaptic plasticity are incompletely understood, and their role in inhibitory synapses remains uncertain. Here we show that regulation of voltage-gated calcium (Ca2+) channel type 2.1 (CaV2.1) by neuronal Ca2+ sensor (CaS) proteins controls synaptic plasticity and excitation/inhibition balance in a hippocampal circuit. Prevention of CaS protein regulation by introducing the IM-AA mutation in CaV2.1 channels in male and female mice impairs short-term synaptic facilitation at excitatory synapses of CA3 pyramidal neurons onto parvalbumin (PV)-expressing basket cells. In sharp contrast, the IM-AA mutation abolishes rapid synaptic depression in the inhibitory synapses of PV basket cells onto CA1 pyramidal neurons. These results show that CaS protein regulation of facilitation and inactivation of CaV2.1 channels controls the direction of short-term plasticity at these two synapses. Deletion of the CaS protein CaBP1/caldendrin also blocks rapid depression at PV-CA1 synapses, implicating its upregulation of inactivation of CaV2.1 channels in control of short-term synaptic plasticity at this inhibitory synapse. Studies of local-circuit function revealed reduced inhibition of CA1 pyramidal neurons by the disynaptic pathway from CA3 pyramidal cells via PV basket cells and greatly increased excitation/inhibition ratio of the direct excitatory input versus indirect inhibitory input from CA3 pyramidal neurons to CA1 pyramidal neurons. This striking defect in local-circuit function may contribute to the dramatic impairment of spatial learning and memory in IM-AA mice.
SIGNIFICANCE STATEMENT Many forms of short-term synaptic plasticity in neuronal circuits rely on regulation of presynaptic voltage-gated Ca2+ (CaV) channels. Regulation of CaV2.1 channels by neuronal calcium sensor (CaS) proteins controls short-term synaptic plasticity. Here we demonstrate a direct link between regulation of CaV2.1 channels and short-term synaptic plasticity in native hippocampal excitatory and inhibitory synapses. We also identify CaBP1/caldendrin as the calcium sensor interacting with CaV2.1 channels to mediate rapid synaptic depression in the inhibitory hippocampal synapses of parvalbumin-expressing basket cells to CA1 pyramidal cells. Disruption of this regulation causes altered short-term plasticity and impaired balance of hippocampal excitatory to inhibitory circuits.
Time Course of Brain Network Reconfiguration Supporting Inhibitory Control
Hemodynamic research has recently clarified key nodes and links in brain networks implementing inhibitory control. Although fMRI methods are optimized for identifying the structure of brain networks, the relatively slow temporal course of fMRI limits the ability to characterize network operation. The latter is crucial for developing a mechanistic understanding of how brain networks shift dynamically to support inhibitory control. To address this critical gap, we applied spectrally resolved Granger causality (GC) and random forest machine learning tools to human EEG data in two large samples of adults (test sample n = 96, replication sample n = 237, total N = 333, both sexes) who performed a color–word Stroop task. Time–frequency analysis confirmed that recruitment of inhibitory control accompanied by slower behavioral responses was related to changes in theta and alpha/beta power. GC analyses revealed directionally asymmetric exchanges within frontal and between frontal and parietal brain areas: top-down influence of superior frontal gyrus (SFG) over both dorsal ACC (dACC) and inferior frontal gyrus (IFG), dACC control over middle frontal gyrus (MFG), and frontal–parietal exchanges (IFG, precuneus, MFG). Predictive analytics confirmed a combination of behavioral and brain-derived variables as the best set of predictors of inhibitory control demands, with SFG theta bearing higher classification importance than dACC theta and posterior beta tracking the onset of behavioral response. The present results provide mechanistic insight into the biological implementation of a psychological phenomenon: inhibitory control is implemented by dynamic routing processes during which the target response is upregulated via theta-mediated effective connectivity within key PFC nodes and via beta-mediated motor preparation.
SIGNIFICANCE STATEMENT Hemodynamic neuroimaging research has recently clarified regional structures in brain networks supporting inhibitory control. However, due to inherent methodological constraints, much of this research has been unable to characterize the temporal dynamics of such networks (e.g., direction of information flow between nodes). Guided by fMRI research identifying the structure of brain networks supporting inhibitory control, results of EEG source analysis in a test sample (n = 96) and replication sample (n = 237) using effective connectivity and predictive analytics strategies advance a model of inhibitory control by characterizing the precise temporal dynamics by which this network operates and exemplify an approach by which mechanistic models can be developed for other key psychological processes.
Alpha‐1 antitrypsin deficiency panniculitis: clinical and pathologic characteristics of 10 cases
International Journal of Dermatology, EarlyView.
Epitope spread in chronic mucosal GVHD: mucous membrane pemphigoid resolution with rituximab
International Journal of Dermatology, EarlyView.
Wells syndrome: a case of successful treatment with omalizumab
International Journal of Dermatology, EarlyView.
Comorbidities of Japanese patients with palmoplantar pustulosis: a report from a single center
International Journal of Dermatology, EarlyView.
Cellular transplantation procedures in vitiligo: what is in a name?
International Journal of Dermatology, EarlyView.
Subungual exostosis and subungual osteochondromas: a description of 25 cases
International Journal of Dermatology, EarlyView.
Clinical and molecular characterization and response to Acitretin in three Families with Sjögren‐Larsson Syndrome
International Journal of Dermatology, EarlyView.
Chronic oral lichenoid erosions revealing haematological malignancies
Journal of the European Academy of Dermatology and Venereology, EarlyView.
Bedside reasoning on causes and mechanisms of diseases in the era of precision medicine: a timeless story?
Journal of the European Academy of Dermatology and Venereology, EarlyView.
Positive Jacquet's sign in traction alopecia
Journal of the European Academy of Dermatology and Venereology, EarlyView.
Association of serious infections with pemphigus and pemphigoid: analysis of the Nationwide Inpatient Sample
Journal of the European Academy of Dermatology and Venereology, EarlyView.
Candida induces the expression of IL‐36γ in human keratinocytes: implications for a pathogen‐driven exacerbation of psoriasis?
Journal of the European Academy of Dermatology and Venereology, EarlyView.
Various cold plasma devices for the treatment of actinic keratosis
Journal of the European Academy of Dermatology and Venereology, EarlyView.
Anti‐inflammatory therapy with tumour necrosis factor inhibitors is associated with reduced risk of major adverse cardiovascular events in psoriasis
Journal of the European Academy of Dermatology and Venereology, EarlyView.
Medically unexplained dermatologic symptoms and psychodermatology
Journal of the European Academy of Dermatology and Venereology, EarlyView.
A case of hereditary fibrosing poikiloderma with tendon contractures, myopathy and pulmonary fibrosis (POIKTMP) with the emphasis on cutaneous histopathological findings
Journal of the European Academy of Dermatology and Venereology, EarlyView.
Both children and adult patients with difficult‐to‐treat atopic dermatitis have high prevalences of concomitant allergic contact dermatitis and are frequently polysensitized
Journal of the European Academy of Dermatology and Venereology, EarlyView.
Deoxycholic Acid for Fibrofatty Residua of Infantile Hemangiomas
Autoimmune Diseases in Patients With Cutaneous Lupus Erythematosus
Knowledge Removes Discomfort
Knowledge Removes Discomfort—Reply
Association of Nodal Metastasis With Vermilion Lip Location in Cutaneous SCC of the Lip
Association of subchondral bone texture on magnetic resonance imaging with radiographic knee osteoarthritis progression: data from the Osteoarthritis Initiative Bone Ancillary Study
Abstract
Objectives
To assess whether initial or 12–18-month change in magnetic resonance imaging (MRI) subchondral bone texture is predictive of radiographic knee osteoarthritis (OA) progression over 36 months.
Methods
This was a nested case-control study including 122 knees/122 participants in the Osteoarthritis Initiative (OAI) Bone Ancillary Study, who underwent MRI optimised for subchondral bone assessment at either the 30- or 36-month and 48-month OAI visits. Case knees (n = 61) had radiographic OA progression between the 36- and 72-month OAI visits, defined as ≥ 0.7 mm minimum medial tibiofemoral radiographic joint space (minJSW) loss. Control knees (n = 61) without radiographic OA progression were matched (1:1) to cases for age, sex, body mass index and initial medial minJSW. Texture analysis was performed on the medial femoral and tibial subchondral bone. We assessed the association of texture features with radiographic progression by creating a composite texture score using penalised logistic regression and calculating odds ratios. We evaluated the predictive performance of texture features for predicting radiographic progression using c-statistics.
Results
Initial (odds ratio [95% confidence interval] = 2.13 [1.41–3.40]) and 12– 18-month change (3.76 [2.04–7.82]) texture scores were significantly associated with radiographic OA progression. Combinations of texture features were significant predictors of radiographic progression using initial (c-statistic [95% confidence interval] = 0.65 [0.64–0.65], p = 0.003) and 12–18-month change (0.68 [0.68-0.68], p < 0.001) data.
Conclusions
Initial and 12–18-month changes in MRI subchondral bone texture score were significantly associated with radiographic progression at 36 months, with better predictive performance for 12–18-month change in texture. These results suggest that texture analysis may be a useful biomarker of subchondral bone in OA.
Key Points
• Subchondral bone MRI texture analysis is a promising knee osteoarthritis imaging biomarker.
• In this study, subchondral bone texture was associated with knee osteoarthritis progression.
• This demonstrates predictive and concurrent validity of MRI subchondral bone texture analysis.
• This method may be useful in clinical trials with interventions targeting bone.
Stylus/tablet user input device for MRI heart wall segmentation: efficiency and ease of use
Abstract
Objectives
To determine whether use of a stylus user input device (UID) would be superior to a mouse for CMR segmentation.
Methods
Twenty-five consecutive clinical cardiac magnetic resonance (CMR) examinations were selected. Image analysis was independently performed by four observers. Manual tracing of left (LV) and right (RV) ventricular endocardial contours was performed twice in 10 randomly assigned sessions, each session using only one UID. Segmentation time and the ventricular function variables were recorded. The mean segmentation time and time reduction were calculated for each method. Intraclass correlation coefficients (ICC) and Bland-Altman plots of function variables were used to assess intra- and interobserver variability and agreement between methods. Observers completed a Likert-type questionnaire.
Results
The mean segmentation time (in seconds) was significantly less with the stylus compared to the mouse, averaging 206±108 versus 308±125 (p<0.001) and 225±140 versus 353±162 (p<0.001) for LV and RV segmentation, respectively. The intra- and interobserver agreement rates were excellent (ICC≥0.75) regardless of the UID. There was an excellent agreement between measurements derived from manual segmentation using different UIDs (ICC≥0.75), with few exceptions. Observers preferred the stylus.
Conclusion
The study shows a significant reduction in segmentation time using the stylus, a subjective preference, and excellent agreement between the methods.
Key Points
• Using a stylus for MRI ventricular segmentation is faster compared to mouse
• A stylus is easier to use and results in less fatigue
• There is excellent agreement between stylus and mouse UIDs
How many versus how much: comprehensive haemodynamic evaluation of partial anomalous pulmonary venous connection by cardiac MRI
Abstract
Objectives
The objective of this study was to investigate the effect of location and number of anomalously connected pulmonary veins and any associated atrial septal defect (ASD) on the magnitude of left-to-right shunting in patients with partial anomalous pulmonary venous connection (PAPVC), and how that influences right ventricular volume loading.
Methods and results
The cardiac magnetic resonance (CMR) and echocardiography examinations of 26 paediatric patients (mean age, 11.2 ± 5.1 years) with unrepaired PAPVC were analysed. Fourteen patients had right-sided, 11 left-sided and 1 patient bilateral PAPVC. An ASD was present in 11 patients, of which none had a Qp/Qs < 1.5 and 8 had a Qp/Qs≥ 2.0. No patient with isolated left upper PAPVC experienced a Qp/Qs ≥ 2.0 compared to 9/12 patients with right upper PAPVC. Qp/Qs correlated with indexed right ventricle (RV) end-diastolic volume (RVEDVi, r = 0.59, p = 0.002) by CMR and with echocardiographic right ventricular end-diastolic dimension (RVED) z-score (r = 0.68, p = 0.003). A RVEDVi >124 ml/m2 by CMR and a RVED z-score >2.2 by echocardiography identified patients with a Qp/Qs ≥1.5 with good sensitivity and specificity.
Conclusions
An asymptomatic patient with a single anomalously connected left upper pulmonary vein and without an ASD is unlikely to have a significant left-to-right shunt. On the other hand, right-sided PAPVC is frequently associated with a significant left-to-right shunt, especially when an ASD is present.
Key Points
• Patients with PAPVC and ASD routinely have a significant left-to-right shunt.
• Patients with right PAPVC are likely to have a significant left-to-right shunt.
• Patients with left PAPVC are unlikely to have a significant left-to-right shunt.
• CMR is helpful in decision-making for patients with PAPVC.
Quantitative correlation between uptake of Gd-BOPTA on hepatobiliary phase and tumor molecular features in patients with benign hepatocellular lesions
Abstract
Purpose
The purpose of our study was to correlate the quantitative analysis of benign hepatocellular tumor uptake on delayed hepatobiliary phase (HBP) imaging with the quantitative level of OATP expression.
Methods
This single-center retrospective study, which took place between September 2009 and March 2015, included 20 consecutive patients with a proven pathologic and immunohistochemical (IHC) diagnosis of FNH or HCA, including quantification of the OATP expression. The patients underwent Gd-BOPTA-enhancement MRI, including an HBP. The analysis of HBP uptake was performed using the liver-to-lesion contrast enhancement ratio (LLCER). Mean LLCER and OATP expressions were compared between FNH and HCA, and the expression of OATP was correlated with the LLCER value.
Results
Of the 23 benign hepatocellular tumors, 9 (39%) were FNH and 14 (61%) were HCA, including 6 inflammatory, 2 HNF1a inactivated, 3 β-catenin-mutated and 3 unclassified HCAs. On HBP, 100% of the FNH appeared hyper- or isointense, and 79% of the adenomas appeared hypointense. The mean OATP expression of FNH (46.67 ± 26.58%) was significantly higher than that of HCA (22.14 ± 30.74%) (p = 0.0273), and the mean LLCER of FNH (10.66 ± 7.403%) was significantly higher than that of HCA (-13.5 ± 12.25%) (p < 0.0001). The mean LLCER of β-catenin-mutated HCA was significantly higher than that of other HCAs (p = 0.011). Significant correlation was found between the OATP expression and LLCER values (r = 0.661; p = 0.001).
Conclusion
In benign hepatocellular tumors, the quantitative analysis of hepatobiliary contrast agent uptake on HBP is correlated with the level of OATP expression and could be used as an imaging biomarker of the molecular background of HCA and FNH.
Key Points
• Gd-BOPTA uptake on HBP correlates with the OATP level in benign hepatocellular tumors
• FNH and β-catenin-mutated HCA showed an increased lesion-to-liver contrast enhancement ratio (LLCER)
• Increased LLCER may be explained by activation of the Wnt β-catenin pathway
Radiogenomics correlation between MR imaging features and major genetic profiles in glioblastoma
Abstract
Objectives
To assess the association between MR imaging features and major genomic profiles in glioblastoma.
Methods
Qualitative and quantitative imaging features such as volumetrics and histogram analysis from normalised CBV (nCBV) and ADC (nADC) were evaluated based on both T2WI and CET1WI. The imaging parameters of different genetic profile groups were compared and regression analyses were used for identifying imaging-molecular associations. Progression-free survival (PFS) was analysed by a Kaplan-Meier test and Cox proportional hazards model.
Results
An IDH mutation was observed in 18/176 patients, and ATRX loss was positive in 17/158 of the IDH-wt cases. The IDH-mut group showed a larger volume on T2WI and a higher volume ratio between T2WI and CET1WI than the IDH-wt group (p < 0.05). In the IDH-mut group, higher mean nADC values were observed compared with the IDH-wt tumours (p < 0.05). Among the IDH-wt tumours, IDH-wt, ATRX-loss tumours revealed higher 5th percentile nADC values than the IDH-wt, ATRX-noloss tumours (p = 0.03). PFS was the longest in the IDH-mut group, followed by the IDH-wt, ATRX-loss groups and the IDH-wt, ATRX-noloss groups, consecutively (p < 0.05). We found significant associations of PFS with the genetic profiles and imaging parameters.
Conclusion
Major genetic profiles of glioblastoma showed a significant association with MR imaging features, along with some genetic profiles, which are independent prognostic parameters for GBM.
Key Points
• Significant correlation exists between radiological parameters such as volumetric and ADC values and major genomic profiles such as IDH mutation and ATRX loss status
• Radiological parameters such as the ADC value were feasible predictors of glioblastoma patients' prognosis
• Imaging features can predict major genomic profiles of the tumours and the prognosis of glioblastoma patients
Saying and believing: the norm commonality assumption
Abstract
One very popular assumption in the epistemological literature is that belief and assertion are governed by one and the same epistemic norm. This paper challenges this claim. Extant arguments in defence of the view are scrutinized and found to rest on value-theoretic inaccuracies. First, the belief-assertion parallel is shown to lack the needed normative strength. Second, I argue that the claim that assertion inherits the norm of belief in virtue of being an expression thereof rests on a failed instance of deontic transmission. Third, the inheritance argument from the norm for action is proven guilty of deontic equivocation. Last but not least, it is argued that, on a functionalist normative picture, assertion and belief are governed by different epistemic norms, in virtue of serving different epistemic functions.
Assessment of the direct effects of DDAH I on tumour angiogenesis in vivo
Abstract
Nitric oxide (NO) has been strongly implicated in glioma progression and angiogenesis. The endogenous inhibitors of NO synthesis, asymmetric dimethylarginine (ADMA) and N-monomethyl-l-arginine (l-NMMA), are metabolized by dimethylarginine dimethylaminohydrolase (DDAH), and hence, DDAH is an intracellular factor that regulates NO. However, DDAH may also have an NO-independent action. We aimed to investigate whether DDAH I has any direct role in tumour vascular development and growth independent of its NO-mediated effects, in order to establish the future potential of DDAH inhibition as an anti-angiogenic treatment strategy. A clone of rat C6 glioma cells deficient in NO production expressing a pTet Off regulatable element was identified and engineered to overexpress DDAH I in the absence of doxycycline. Xenografts derived from these cells were propagated in the presence or absence of doxycycline and susceptibility magnetic resonance imaging used to assess functional vasculature in vivo. Pathological correlates of tumour vascular density, maturation and function were also sought. In the absence of doxycycline, tumours exhibited high DDAH I expression and activity, which was suppressed in its presence. However, overexpression of DDAH I had no measurable effect on tumour growth, vessel density, function or maturation. These data suggest that in C6 gliomas DDAH has no NO-independent effects on tumour growth and angiogenesis, and that the therapeutic potential of targeting DDAH in gliomas should only be considered in the context of NO regulation.
Reactive oxygen species, antioxidant enzyme activity, and gene expression patterns in a pair of nearly isogenic lines of nicosulfuron-exposed waxy maize ( Zea mays L.)
Abstract
Nicosulfuron is a post-emergence herbicide used for weed control in maize fields (Zea mays L.). Here, the pair of nearly isogenic inbred lines SN509-R (nicosulfuron resistant) and SN509-S (nicosulfuron sensitive) was used to study the effect of nicosulfuron on growth, oxidative stress, and the activity and gene expression of antioxidant enzymes in waxy maize seedlings. Nicosulfuron treatment was applied at the five-leaf stage and water treatment was used as control. After nicosulfuron treatment, the death of SN509-S might be associated with increased oxidative stress. Compared with SN509-R, higher O2·- and H2O2 accumulations were observed in SN509-S, which can severely damage lipids and proteins, thus reducing membrane stability. The effects were exacerbated with extended exposure time. Both O2·- and H2O2 detoxification is regulated by enzymes. After nicosulfuron treatment, superoxide dismutase (SOD), catalase, ascorbate peroxidase (APX), monodehydroascorbate reductase (MDHAR), dehydroascorbate reductase (DHAR), glutathione reductase (GR), and glutathione-S-transferase (GST) of SN509-S were significantly lower than those of SN509-R. Compared to SN509-R, ascorbate content (AA), glutathione (GSH) content, GSH to glutathione disulfide ratios, and AA to dehydroascorbate ratios significantly declined with increasing exposure time in SN509-S. Compared to SN509-S, nicosulfuron treatment increased the transcript levels of most of the APX genes except for APX1, and in contrast to Gst1, upregulated the transcription of sod9, MDHAR, DHAR, and GR genes in SN509-R. These results suggest that on a transcription level and in accordance with their responses, detoxifying enzymes play a vital role in the O2·- and H2O2 detoxification of maize seedlings under nicosulfuron exposure.
Analysis of short-term and sub-chronic effects of ambient air pollution on preterm birth in central China
Abstract
Recently, an increasing number of studies have reported the possible linkage between maternal exposure to ambient air pollution and adverse birth outcomes. This retrospective cohort study aimed to evaluate the effect of short-term and sub-chronic exposure to air pollutants on preterm birth occurred in Shiyan and Jingzhou, Hubei province, China from 2014 to 2016. General additive models (GAM) were performed to examine the impact of the daily and cumulative weekly air pollutants exposure. The non-linear patterns between adverse birth outcomes and weather condition were assessed by including penalized smoothing splines in the model. The demographic characteristics of pregnant women were also included in the model as covariates. A total of 16,035 cases were analyzed. Significant short-term effects of air pollution exposure at lag 1 day on preterm birth were observed. In adjusted single-pollutant city-specific model, the association between acute air pollutant exposure and preterm birth was significant in Shiyan (PM2.5: OR = 1.066, 95% CI 1.027, 1.106; PM10: OR = 1.048, 95% CI 1.022, 1.076; O3: OR = 1.029, 95% CI 1.004, 1.056) and Jingzhou (PM2.5: OR = 1.037, 95% CI 1.008, 1.068; PM10: OR = 1.025, 95% CI 1.007, 1.043; SO2: OR = 1.082, 95% CI 1.023, 1.144; NO2: OR = 1.211, 95% CI 1.098, 1.335) per 10 μg/m3 increment. Also, weekly average cumulative air pollution exposure was significantly associated with preterm birth in both areas.
Saving which differences? Creeping minimalism and disagreement
Abstract
Much thought has been devoted to how metaethical disagreement between moral realism and expressivism can be saved once minimalism starts creeping. Very little thought has been given to how creeping minimalism affects error-theories' disagreement with their metaethical competitors. The reason for this omission, I suspect, is found in the belief that whilst locating distinctive moral realist and expressivist positions within a minimalist landscape poses a severe challenge, no such difficulties are encountered when differentiating error-theories from moral realism and expressivism. In the first part of this paper, I show that this belief is mistaken: Insofar as moral realists and error-theorists are still taken to disagree, creeping minimalism renders their disagreement moral, but makes these positions metaethically indistinguishable. In the second part of the paper, I present a modified inferentialist solution to the problem of creeping minimalism which seeks to put error-theories back on the metaethical map. Yet, this too comes at a cost, in that it significantly modifies our interpretation of error-theories. Whichever way we turn, then, creeping minimalism not only forces us to re-phrase metaethical positions in a way that is compatible with minimalism, but also requires us to change our very understanding of these positions.
Efficient removal of cadmium from soil-washing effluents by garlic peel biosorbent
Abstract
Paddy field soil contaminated by cadmium may produce cadmium-contained corns causing Itai-itai disease, and in situ washing of soil with the organic acid is a good technical choice due to its convenience and cost-effectiveness. While the bottleneck of this technique is how to recycle the huge volume of washing effluent in an efficient and economical way. Biosorption of cadmium on the garlic peel was attempted in present study and it was found quite satisfactorily effective to remove all cadmium from the real soil leaching effluent after three-time sequential adsorption. The systematical investigation on the effect of various parameters on the adsorption of cadmium on garlic peel in the existence of tartaric ligand was performed and it was found that tartrate could change Cd2+ into Cd(tar)0 species whose electrical charge state would restrain its approach to the adsorbent particles. The porous microstructure in the transversal surface of garlic peel and the abundant groups of −COOH are the main factors affecting the adsorption capability. A demonstrative flowsheet of soil remediation by chemical washing coupled with biosorption was proposed correspondingly, in which the cadmium could be recovered from the soil washing effluent, and the recovered effluent was reused for next soil washing, and recovered garlic peel was reused for cadmium adsorption from the effluents again, showing a great prospect in the remediation of paddy field soil contaminated by cadmium.
Combined effects of phosphate-solubilizing bacterium XMT-5 ( Rhizobium sp.) and submerged macrophyte Ceratophyllum demersum on phosphorus release in eutrophic lake sediments
Abstract
Simulation experiments were conducted using sediments collected from the Taihu Lake to determine the combined effects of submerged macrophytes Ceratophyllum demersum and phosphate-solubilizing bacteria (PSB) strain XMT-5 (Rhizobium sp.) on phosphorus (P) concentrations in overlying waters and sediments. After 30 days of experimental incubation, the total phosphorus (TP) and dissolved total phosphorus (DTP) concentrations of the overlying water subjected to AMB and AHMB treatments (both with the combined effects of PSB cells and submerged macrophytes) were generally lower than those of the AM (with individual effects of inoculated C. demersum) and AB (with individual effects of a smaller amount of inoculated PSB cells) control treatments but higher than that of the A (with no effects of inoculated PSB cells or C. demersum) and AHB (with individual effects of a larger amount of inoculated PSB) control treatments. The TP contents of the sediment in the AMB and AHMB treatments were significantly lower than those of the other control treatments. The TP contents of the C. demersum cocultured with the PSB strain XMT-5 cells in the AMB and AHMB treatments were all significantly higher than that of the AM treatment, indicating the enhancement of P uptake by submerged plants inoculated with PSB. The bacterial diversity structures of the rhizosphere sediment subjected to different treatments were also analyzed by the high-throughput sequencing method. According to the ACE and Chao 1 indices, the bacterial diversity in the AMB and AHMB treatments were the highest. Although many sources contributed to the decrease in the nutrient loads of the lake sediment, harvesting macrophytes inoculated with PSB cells prior to their senescence might constitute a significant in-lake measure for reducing internal P load.
Groundwater vulnerability assessment in karstic aquifers using COP method
Abstract
Access to safe and reliable drinking water is amongst the important indicators of development in each society, and water scarcity is one of the challenges and limitations affecting development at national and regional levels and social life and economic activity areas. Generally, there are two types of drinking water sources: the first type is surface waters, including lakes, rivers, and streams and the second type is groundwaters existing in aquifers. Amongst aquifers, karst aquifers play an important role in supplying water sources of the world. Therefore, protecting these aquifers from pollution sources is of paramount importance. COP method is amongst the methods to investigate the intrinsic vulnerability of this type of aquifers, so that areas susceptible to contamination can be determined before being contaminated and these sources can be protected. In the present study, COP method was employed in order to spot the regions that are prone to contamination in the region. This method uses the properties of overlying geological layers above the water table (O factor), the concentration of flow (C factor), and precipitation (P factor) over the aquifer, as the parameters to assess the intrinsic vulnerability of groundwater resources. In this regard, geographical information system (GIS) and remote sensing (RS) were utilized to prepare the mentioned factors and the intrinsic vulnerability map was obtained. The results of COP method indicated that the northwest and the west of the region are highly and very vulnerable. This study indicated that regions with low vulnerability were observed in eastern areas, which accounted for 15.6% of the area. Moderate vulnerability was 40% and related to the northeast and southeast of the area. High vulnerability was 38.2% and related to western and southwestern regions. Very high vulnerability was 6.2% and related to the northwest of the area. By means of the analysis of sensitivity of the model, it was determined that the focus factor of the flow has the greatest impact on the creation of vulnerability in the region. Also, these results were validated through electrical conductivity and discharge time series of the regional springs that are located in the vulnerable zones.
Efficient removal of benzene in air at atmospheric pressure using a side-on type 172 nm Xe 2 excimer lamp
Abstract
The photochemical removal of benzene was studied in air at atmospheric pressure using a side-on type 172 nm Xe2 excimer lamp with a wide irradiation area. After 1.5 min photoirradiation, C6H6 (1000 ppm) in air was completely converted to HCOOH, CO, and CO2 at a total flow rate of 1000 mL/min. The initial decomposition rate of C6H6 was determined to be 1.18 min−1. By using a flow system, C6H6 (200 ppm) was completely removed at a total flow rate of 250 mL/min. The conversion of C6H6 and the energy efficiency in the removal of C6H6 changed in the 31−100% and 0.48−1.2 g/kWh range, respectively, depending on the flow rate, the O2 concentration, and the chamber volume. On the basis of kinetic model simulation, dominant reaction pathways were discussed. Results show that the O(3P) + C6H6 reaction plays a significant role in the initial stage of the C6H6 decomposition. Important experimental parameters required for further improvement of the C6H6 removal apparatus using a 172 excimer lamp were discussed based on model calculations.
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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