The usefulness of c-Kit in the immunohistochemical assessment of melanocytic lesions

C-Kit (CD117), the receptor for the stem cell factor, a growth factor for melanocyte migra- tion and proliferation, has shown differential immunostaining in various benign and malig- nant melanocytic lesions. The purpose of this study is to compare c-Kit immunostaining in benign nevi and in primary and metastatic malignant melanomas, to determine whether c-Kit can aid in the differential diagnosis of these lesions. c-Kit immunostaining was per- formed in 60 cases of pigmented lesions, including 39 benign nevi (5 blue nevi, 5 intra- dermal nevi, 3 junctional nevi, 15 cases of pri- mary compound nevus, 11 cases of Spitz nevus), 18 cases of primary malignant melanoma and 3 cases of metastatic melanoma. The vast majority of nevi and melanomas examined in this study were posi- tive for c-Kit, with minimal differences between benign and malignant lesions. C-Kit cytoplasmatic immunoreactivity in the intraepidermal proliferating nevus cells, was detected in benign pigmented lesions as well as in malignant melanoma, increasing with the age of patients (P=0.007) in both groups. The patient’s age at presentation appeared to be the variable able to cluster benign and malignant pigmented lesions. The percentage of c-Kit positive intraepidermal nevus cells was better associated with age despite other vari- ables (P=0.014). The intensity and percentage of c-Kit positivity in the proliferating nevus cells in the dermis was significantly increased in malignant melanocytic lesions (P=0.015 and P=0.008) compared to benign lesions (compound melanocytic nevi, Spitz nevi, intradermal nevi, blue nevi). Immunostaning for c-Kit in metastatic melanomas was nega- tive. Interestingly in two cases of melanoma occurring on a pre-existent nevus, the melanoma tumor cells showed strong cytoplas- matic and membranous positivity for c-kit, in contrast with the absence of any immunoreac- tivity in pre-existent intradermal nevus cells. C-Kit does not appear to be a strong immuno- histochemical marker for distinguishing melanoma from melanocytic nevi, if we consid- er c-Kit expression in intraepidermal prolifer- ating cells. The c-Kit expression in proliferat- ing melanocytes in the dermis could help in the differential diagnosis between a superfi- cial spreading melanoma (with dermis inva- sion) and a compound nevus or an intradermal nevus. Finally, c-Kit could be a good diagnostic tool for distinguishing benign compound nevi from malignant melanocytic lesions with der- mis invasion and to differentiate metastatic melanoma from primary melanoma

The Response of Paroxysmal Supraventricular Tachycardia to Overdrive Atrial and Ventricular Pacing:

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75015/1/j.1540-8167.1993.tb01227.x.pd

Performance deficits of NK1 receptor knockout mice in the 5 choice serial reaction time task: effects of d Amphetamine, stress and time of day.

Background The neurochemical status and hyperactivity of mice lacking functional substance P-preferring NK1 receptors (NK1R-/-) resemble abnormalities in Attention Deficit Hyperactivity Disorder (ADHD). Here we tested whether NK1R-/- mice express other core features of ADHD (impulsivity and inattentiveness) and, if so, whether they are diminished by d-amphetamine, as in ADHD. Prompted by evidence that circadian rhythms are disrupted in ADHD, we also compared the performance of mice that were trained and tested in the morning or afternoon. Methods and Results The 5-Choice Serial Reaction-Time Task (5-CSRTT) was used to evaluate the cognitive performance of NK1R-/- mice and their wildtypes. After training, animals were tested using a long (LITI) and a variable (VITI) inter-trial interval: these tests were carried out with, and without, d-amphetamine pretreatment (0.3 or 1 mg/kg i.p.). NK1R-/- mice expressed greater omissions (inattentiveness), perseveration and premature responses (impulsivity) in the 5-CSRTT. In NK1R-/- mice, perseveration in the LITI was increased by injection-stress but reduced by d-amphetamine. Omissions by NK1R-/- mice in the VITI were unaffected by d-amphetamine, but premature responses were exacerbated by this psychostimulant. Omissions in the VITI were higher, overall, in the morning than the afternoon but, in the LITI, premature responses of NK1R-/- mice were higher in the afternoon than the morning. Conclusion In addition to locomotor hyperactivity, NK1R-/- mice express inattentiveness, perseveration and impulsivity in the 5-CSRTT, thereby matching core criteria for a model of ADHD. Because d-amphetamine reduced perseveration in NK1R-/- mice, this action does not require functional NK1R. However, the lack of any improvement of omissions and premature responses in NK1R-/- mice given d-amphetamine suggests that beneficial effects of this psychostimulant in other rodent models, and ADHD patients, need functional NK1R. Finally, our results reveal experimental variables (stimulus parameters, stress and time of day) that could influence translational studies

Academic stress in nursing undergraduates, a longitudinal cross-sectional study in covid-19 times

Introducción: el confinamiento vivido por el SARS-Cov2 ha modificado la forman en que el mundo funcionaba, sin embargo, el mayor impacto ha sido recibido en tres sectores, el sanitario, económico y educativo, siendo este último el punto de partida para la realización de la presente investigación. Objetivo: comparar la media de estrés académico en un grupo de alumnos de la licenciatura en enfermería en dos períodos durante la pandemia por Covid-19. Materiales y métodos: estudio cuantitativo, descriptivo, comparativo y longitudinal, aplicando el Inventario SISCO-24, con un muestreo no probabilístico consecutivo. Resultados y discusión: 75.0% de la población pertenece al sexo femenino, 38.8% estudia y trabajan simultáneamente, la edad promedio es de 19.72± DE 1.43, los dominios que resultaron más afectados son los síntomas físicos y psicológicos (ME: 14.63± DE 4.38; ME: 15.99± DE 4.44) y a través de la prueba t de Student para muestras relacionadas se identificó que no existen diferencias significativas entre las medias de estrés académico (t= 0.13; Sig. Bilateral: .990). Conclusión: los métodos de educación virtuales manifiestan una incompatibilidad con el proceso enseñanza-aprendizaje, señalando que el aumento de factores estresores académicos es persistente y mantiene niveles peligrosamente elevados que amenazan a la salud mentalIntroduction: the confinement experienced by SARS-Cov2 has modified the way in which the world functioned; however, the greatest impact has been received in three sectors, health, economic and educational, the latter being the starting point for this research. Objective: to compare the mean academic stress in a group of nursing students in two periods during the Covid-19 pandemic. Materials and methods: quantitative, descriptive, comparative, and longitudinal study, applying the SISCO-24 Inventory, with non-probabilistic consecutive sampling. Results and discussion: 75.0% of the population was female, 38.8% studied and worked simultaneously, the mean age was 19.72 SD 1.43, the most affected domains were physical and psychological symptoms (ME: 14.63 SD 4.38; ME: 15.99 SD 4.44) and through the student’s t-test for related samples it was identified that there were no significant differences between the means of academic stress (t= 0.13; Bilateral Sig.: .990). Conclusion: virtual education methods manifest an incompatibility with the teaching-learning process, indicating that the increase of academic stressors is persistent and maintains dangerously high levels that threaten mental healt

Why all the fuss about 2D semiconductors?

Graphene is no longer alone; a family of atomically thin 2D semiconductors has emerged. Optoelectronics and photonics applications are in their experimental infancy but the future holds much promise.Comment: Commentary article, 1 figure, 1 tabl

Association between footwear use and neglected tropical diseases: a systematic review and meta-analysis

BACKGROUND The control of neglected tropical diseases (NTDs) has primarily focused on preventive chemotherapy and case management. Less attention has been placed on the role of ensuring access to adequate water, sanitation, and hygiene and personal preventive measures in reducing exposure to infection. Our aim was to assess whether footwear use was associated with a lower risk of selected NTDs. METHODOLOGY We conducted a systematic review and meta-analysis to assess the association between footwear use and infection or disease for those NTDs for which the route of transmission or occurrence may be through the feet. We included Buruli ulcer, cutaneous larva migrans (CLM), leptospirosis, mycetoma, myiasis, podoconiosis, snakebite, tungiasis, and soil-transmitted helminth (STH) infections, particularly hookworm infection and strongyloidiasis. We searched Medline, Embase, Cochrane, Web of Science, CINAHL Plus, and Popline databases, contacted experts, and hand-searched reference lists for eligible studies. The search was conducted in English without language, publication status, or date restrictions up to January 2014. Studies were eligible for inclusion if they reported a measure of the association between footwear use and the risk of each NTD. Publication bias was assessed using funnel plots. Descriptive study characteristics and methodological quality of the included studies were summarized. For each study outcome, both outcome and exposure data were abstracted and crude and adjusted effect estimates presented. Individual and summary odds ratio (OR) estimates and corresponding 95% confidence intervals (CIs) were calculated as a measure of intervention effect, using random effects meta-analyses. PRINCIPAL FINDINGS Among the 427 studies screened, 53 met our inclusion criteria. Footwear use was significantly associated with a lower odds of infection of Buruli ulcer (OR=0.15; 95% CI: 0.08-0.29), CLM (OR=0.24; 95% CI: 0.06-0.96), tungiasis (OR=0.42; 95% CI: 0.26-0.70), hookworm infection (OR=0.48; 95% CI: 0.37-0.61), any STH infection (OR=0.57; 95% CI: 0.39-0.84), strongyloidiasis (OR=0.56; 95% CI: 0.38-0.83), and leptospirosis (OR=0.59; 95% CI: 0.37-0.94). No significant association between footwear use and podoconiosis (OR=0.63; 95% CI: 0.38-1.05) was found and no data were available for mycetoma, myiasis, and snakebite. The main limitations were evidence of heterogeneity and poor study quality inherent to the observational studies included. CONCLUSIONS/SIGNIFICANCE Our results show that footwear use was associated with a lower odds of several different NTDs. Access to footwear should be prioritized alongside existing NTD interventions to ensure a lasting reduction of multiple NTDs and to accelerate their control and elimination. PROTOCOL REGISTRATION PROSPERO International prospective register of systematic reviews CRD42012003338

Wet Granular Materials

Most studies on granular physics have focused on dry granular media, with no liquids between the grains. However, in geology and many real world applications (e.g., food processing, pharmaceuticals, ceramics, civil engineering, constructions, and many industrial applications), liquid is present between the grains. This produces inter-grain cohesion and drastically modifies the mechanical properties of the granular media (e.g., the surface angle can be larger than 90 degrees). Here we present a review of the mechanical properties of wet granular media, with particular emphasis on the effect of cohesion. We also list several open problems that might motivate future studies in this exciting but mostly unexplored field.Comment: review article, accepted for publication in Advances in Physics; tex-style change

A phase II trial of docetaxel and erlotinib as first-line therapy for elderly patients with androgen-independent prostate cancer

Background: Docetaxel is the standard first-line agent for the treatment of androgen-independent prostate cancer (AIPC). The combination of docetaxel with molecularly targeted therapies may offer the potential to increase the efficacy and decrease the toxicity of cytotoxic chemotherapy for prostate cancer. Previous studies demonstrate activation of the human epidermal growth factor receptor (EGFR) in prostate cancer. Erlotinib is a specific inhibitor of the tyrosine-kinase activity of EGFR. The goal of this study is to determine the anti-cancer activity docetaxel combined with erlotinib for the treatment of elderly subjects with AIPC. Methods: This is a multi-institutional Phase II study in patients with histologically confirmed adenocarcinoma of the prostate and age [greater than or equal to] 65 years. Patients were requred to have progressive disease despite androgen-deprivation therapy as determined by: (1) measurable lesions on cross-sectional imaging; (2) metastatic disease by radionucleotide bone imaging; or (3) elevated prostate specific antigen (PSA). Treatment cycles consisted of docetaxel 60 mg/m2 IV on day 1 and erlotinib 150 mg PO days 1-21. Patients with responding or stable disease after 9 cycles were eligible to continue on erlotinib alone as maintenance therapy. Results: Characteristics of 22 patients enrolled included: median age 73.5 years (range, 65-80); median Karnofsky Performance Status 90 (range 70-100); median hemoglobin 12.1 g/dl (range, 10.0-14.3); median PSA 218.3 ng/ml (range, 9-5754). A median of 6 treatment cycles were delivered per patient (range 1-17). No objective responses were observed in 8 patients with measurable lesions (0%, 95% CI 0-31%). Bone scan improvement and PSA decline was seen in 1 patient (5%, 95% CI 0.1-25%). Five of 22 patients experienced [greater than or equal to] 50% decline in PSA (23%, 95% CI 8-45%). Hematologic toxicity included grade 3 neutropenia in 9 patients and neutropenic fever in 2 patients. Common non-hematologic toxicities ([greater than or equal to] grade 3) included fatigue, anorexia, and diarrhea. Conclusion: Docetaxel/erlotinib can be delivered safely in elderly patients with AIPC. Anti-cancer disease activity appears generally comparable to docetaxel when used as monotherapy. Hematologic and nonhematologic toxicity may be increased over docetaxel monotherapy. Prospective randomized studies would be required to determine if the toxicity of docetaxel and erlotinib justifies its use in this setting.This study was supported by NIH Prostate SPORE P50 CA92131 to DBA. Phase One Foundation to MEG and DBA

Psychophysiological Markers of Vulnerability to Psychopathology in Men with an Extra X Chromosome (XXY)

Studying genetically defined syndromes associated with increased risk for psychopathology may help in understanding neurodevelopmental mechanisms related to risk for psychopathology. Klinefelter syndrome (47,XXY) is one of the most common sex chromosomal aneuploidies (1 in 650 male births) and associated with increased vulnerability for psychopathology, including psychotic symptoms. Yet, it remains unknown whether this increased risk is associated with underlying psychophysiological mechanisms that are typically deficient in individuals with psychotic disorders. The present study assessed three “classic” psychophysiological markers of psychosis in Klinefelter syndrome (KS): smooth pursuit eye movements (SPEM), prepulse inhibition (PPI) and P50 suppression. Fourteen adults with KS and 15 non-clinical adults participated in the study. Data on SPEM (reflecting visuo-motor control) as well as PPI and P50 suppression (reflecting sensory gating) were collected. Dysfunctions in SPEM were observed in individuals with KS, with less smooth pursuit as expressed in lower position gain. Also, reduced sensory gating in individuals with KS was suggested by significantly reduced prepulse inhibition of the startle response (PPI) (effect size 1.6). No abnormalities were found in suppression of the P50 (effect size 0.6). We speculate that impairments in these psychophysiological mechanisms may reflect core brain dysfunctions that may also mediate the described increased vulnerability for psychotic symptoms in KS. Although speculative, such deficit specific, rather than disorder specific, psychophysiological dysfunctions in KS might convey vulnerability to other types of psychopathology as well. As KS already can be diagnosed prenatally, the predictive value of childhood impairments in prepulse inhibition and smooth pursuit for development of psychopathology later in life could be assessed. In sum, studying individuals with KS may prove to be an avenue of research leading to new hypotheses and insights into “at risk” pathways to psychopathology

Falls and falls efficacy: the role of sustained attention in older adults

<p>Abstract</p> <p>Background</p> <p>Previous evidence indicates that older people allocate more of their attentional resources toward their gait and that the attention-related changes that occur during aging increase the risk of falls. The aim of this study was to investigate whether performance and variability in sustained attention is associated with falls and falls efficacy in older adults.</p> <p>Methods</p> <p>458 community-dwelling adults aged ≥ 60 years underwent a comprehensive geriatric assessment. Mean and variability of reaction time (RT), commission errors and omission errors were recorded during a fixed version of the Sustained Attention to Response Task (SART). RT variability was decomposed using the Fast Fourier Transform (FFT) procedure, to help characterise variability associated with the arousal and vigilance aspects of sustained attention.</p> <p>The number of self-reported falls in the previous twelve months, and falls efficacy (Modified Falls Efficacy Scale) were also recorded.</p> <p>Results</p> <p>Significant increases in the mean and variability of reaction time on the SART were significantly associated with both falls (p < 0.01) and reduced falls efficacy (p < 0.05) in older adults. An increase in omission errors was also associated with falls (p < 0.01) and reduced falls efficacy (p < 0.05). Upon controlling for age and gender affects, logistic regression modelling revealed that increasing variability associated with the vigilance (top-down) aspect of sustained attention was a retrospective predictor of falling (p < 0.01, OR = 1.14, 95% CI: 1.03 - 1.26) in the previous year and was weakly correlated with reduced falls efficacy in non-fallers (p = 0.07).</p> <p>Conclusions</p> <p>Greater variability in sustained attention is strongly correlated with retrospective falls and to a lesser degree with reduced falls efficacy. This cognitive measure may provide a novel and valuable biomarker for falls in older adults, potentially allowing for early detection and the implementation of preventative intervention strategies.</p