In Vivo Diagnosis of Melanoma and Nonmelanoma Skin Cancer Using Oblique Incidence Diffuse Reflectance Spectrometry

Early detection and treatment of skin cancer can significantly improve patient outcome. However, present standards for diagnosis require biopsy and histopathologic examinations that are relatively invasive, expensive, and difficult for patients with many early-stage lesions. Here, we show an oblique incidence diffuse reflectance spectroscopic (OIDRS) system that can be used for rapid skin cancer detection in vivo. This system was tested under clinical conditions by obtaining spectra from pigmented and nonpigmented skin lesions, including melanomas, differently staged dysplastic nevi, and common nevi that were validated by standard pathohistologic criteria. For diagnosis of pigmented melanoma, the data obtained achieved 90% sensitivity and specificity for a blinded test set. In a second analysis, we showed that this spectroscopy system can also differentiate nonpigmented basal cell or squamous cell carcinomas from noncancerous skin abnormalities, such as actinic keratoses and seborrheic keratoses, achieving 92% sensitivity and specificity. Taken together, our findings establish how OIDRS can be used to more rapidly and easily diagnose skin cancer in an accurate and automated manner in the clinic

Caracterización limnológica y fauna de peces de la laguna La Helvecia (Córdoba, Argentina)

La laguna La Helvecia (33 ° 25'16'S, 62 ° 53'26'W, 90 ha) es uno de los pocos ambientes acuáticos permanentes que aún existen en los "Bañados del Saladillo" (Córdoba, Argentina). Durante noviembre de 2011 se realizó un estudio de caracterización de peces y limnología. Se utilizaron diferentes artes activos y pasivos y se midieron las variables de calidad del agua. Los valores promedio de pH, concentración de oxígeno, temperatura y transparencia del agua (disco Secchi) fueron 8.63, 9.05 mg/L, 23.8 °C y 39 cm respectivamente. La laguna fue clasificada como tipo "turbio". El agua era hipohalina (4,74 g/L), clorada sodica sulfatada y muy dura (298 ppm de CaCO3). La abundancia de macrozooplancton fue de 240,850 ind./m3. Se capturaron nueve especies de peces, pertenecientes a cinco órdenes y siete familias. Odontesthes bonariensis fue la especie más abundante (78.6%), mientras que Cyprinus carpio fue la especie con más biomasa (41.4%). El zooplancton (Cladocera y Copepdoda) fue el alimento principal de O. bonariensis. El principal hallazgo fue la presencia de Parapimelodus valenciennis. Los cambios graduales y permanentes que se han producido en el paisaje de la región, con mayores intensidades de uso del suelo, pueden haber sido las principales causas de la transformación de la laguna La Helvecia de claro a turbio, lo que favoreció la pesca recreativa.La Helvecia shallow lake (33°25’16’’S, 62°53’26’’W, 90 ha) is one of the few permanent aquatic environments that still exist in the “Bañados del Saladillo” (Córdoba, Argentina). During November 2011, a study of fish and limnological characterization was performed. Different active and passive gears were used and water quality variables were measured. Average values pH, oxygen concentration, temperature and water transparency (Secchi disk) were 8.63, 9.05 mg/L, 23.8 °C and 39 cm respectively. The shallow lake was classified as “turbid” type. The water was hypohaline (4.74 g/L), sulfated sodium chlorinated and very hard (298 ppm CaCO3). The macrozooplankton abundance was 240,850 org/m3. A total of nine species of fish, belonging to five orders and seven families were captured. Odontesthes bonariensis was the most abundant species (78.6%), while Cyprinus carpio was the species with most biomass (41.4%). Zooplankton (Cladocera and Copepdoda) was the main food of O. bonariensis. The principal finding was the presence of Parapimelodus valenciennis. The gradual and permanent changes that have occurred in the landscape of the region, with higher intensities of land use, may have been the main causes of the transformation of La Helvecia lake from clear to turbid, which favored the recreational fishery

Amelioration of Ischemic brain damage by peritoneal dialysis

Ischemic stroke is a devastating condition, for which there is still no effective therapy. Acute ischemic stroke is associated with high concentrations of glutamate in the blood and interstitial brain fluid. The inability of the tissue to retain glutamate within the cells of the brain ultimately provokes neuronal death. Increased concentrations of interstitial glutamate exert further excitotoxic effects on healthy tissue surrounding the infarct zone. We developed a strategy based on peritoneal dialysis to reduce blood glutamate levels, thereby accelerating brain-to-blood glutamate clearance. In a rat model of stroke, this simple procedure reduced the transient increase in glutamate, consequently decreasing the size of the infarct area. Functional magnetic resonance imaging demonstrated that the rescued brain tissue remained functional. Moreover, in patients with kidney failure, peritoneal dialysis significantly decreased glutamate concentrations. Our results suggest that peritoneal dialysis may represent a simple and effective intervention for human stroke patientsThis work was supported by grants from the Spanish MINECO to J. Sánchez-Prieto (BFU2010/16947), I. Lizasoain (SAF2011- 23354), and M.A. Moro (SAF2009-08145, SAF2012-33216, and CSD2010-00045); from Fondo Europeo de Desarrollo Regional (FEDER) “Instituto de Salud Carlos III” (RD06/0026, RD12/0014) to I. Lizasoain, M. Torres, J. Vivancos, and J. Sánchez-Prieto; from the “Comunidad de Madrid” (CAM-I2M2 2011-BMD-2349) to I. Lizasoain, M. Torres, J. Vivancos, and J. Sánchez-Prieto; and from NEUROSTEMCM to M.A. Moro (S2010/BMD-2336). Research in the laboratory of S. Canals and J. Lerma is supported by grants from the Spanish MINECO (BFU2009-09938, BFU2011-24084, and CSD2007-00023

In Vivo Diagnosis of Melanoma and Nonmelanoma Skin Cancer Using Oblique Incidence Diffuse Reflectance Spectrometry

Early detection and treatment of skin cancer can significantly improve patient outcome. However, present standards for diagnosis require biopsy and histopathologic examinations that are relatively invasive, expensive, and difficult for patients with many early-stage lesions. Here, we show an oblique incidence diffuse reflectance spectroscopic (OIDRS) system that can be used for rapid skin cancer detection in vivo. This system was tested under clinical conditions by obtaining spectra from pigmented and nonpigmented skin lesions, including melanomas, differently staged dysplastic nevi, and common nevi that were validated by standard pathohistologic criteria. For diagnosis of pigmented melanoma, the data obtained achieved 90% sensitivity and specificity for a blinded test set. In a second analysis, we showed that this spectroscopy system can also differentiate nonpigmented basal cell or squamous cell carcinomas from noncancerous skin abnormalities, such as actinic keratoses and seborrheic keratoses, achieving 92% sensitivity and specificity. Taken together, our findings establish how OIDRS can be used to more rapidly and easily diagnose skin cancer in an accurate and automated manner in the clinic

Geomicrobiological heterogeneity of lithic habitats in the extreme environment of Antarctic nunataks: a potential early Mars analog

Nunataks are permanent ice-free rocky peaks that project above ice caps in polar regions, thus being exposed to extreme climatic conditions throughout the year. They undergo extremely low temperatures and scarcity of liquid water in winter, while receiving high incident and reflected (albedo) UVA-B radiation in summer. Here, we investigate the geomicrobiology of the permanently exposed lithic substrates of nunataks from Livingston Island (South Shetlands, Antarctic Peninsula), with focus on prokaryotic community structure and their main metabolic traits. Contrarily to first hypothesis, an extensive sampling based on different gradients and multianalytical approaches demonstrated significant differences for most geomicrobiological parameters between the bedrock, soil, and loose rock substrates, which overlapped any other regional variation. Brevibacillus genus dominated on bedrock and soil substrates, while loose rocks contained a diverse microbial community, including Actinobacteria, Alphaproteobacteria and abundant Cyanobacteria inhabiting the milder and diverse microhabitats within. Archaea, a domain never described before in similar Antarctic environments, were also consistently found in the three substrates, but being more abundant and potentially more active in soils. Stable isotopic ratios of total carbon (δ 13C) and nitrogen (δ 15N), soluble anions concentrations, and the detection of proteins involved in key metabolisms via the Life Detector Chip (LDChip), suggest that microbial primary production has a pivotal role in nutrient cycling at these exposed areas with limited deposition of nutrients. Detection of stress-resistance proteins, such as molecular chaperons, suggests microbial molecular adaptation mechanisms to cope with these harsh conditions. Since early Mars may have encompassed analogous environmental conditions as the ones found in these Antarctic nunataks, our study also contributes to the understanding of the metabolic features and biomarker profiles of a potential Martian microbiota, as well as the use of LDChip in future life detection missions.This project has been funded by the Spanish Ministry of Science and Innovation (MICINN)/European Regional Development Fund (FEDER) project no. RTI2018-094368-B-I00; the European Research Council Consolidator grant no. 818602; and the Spanish State Research Agency (AEI) project no. MDM-2017-0737, Unidad de Excelencia “María de Maeztu” to Centro de Astrobiología

A Cautionary Tale: MARVELS Brown Dwarf Candidate Reveals Itself To Be A Very Long Period, Highly Eccentric Spectroscopic Stellar Binary

We report the discovery of a highly eccentric, double-lined spectroscopic binary star system (TYC 3010-1494-1), comprising two solar-type stars that we had initially identified as a single star with a brown dwarf companion. At the moderate resolving power of the MARVELS spectrograph and the spectrographs used for subsequent radial-velocity (RV) measurements (R ~ <30,000), this particular stellar binary mimics a single-lined binary with an RV signal that would be induced by a brown dwarf companion (Msin(i)~50 M_Jup) to a solar-type primary. At least three properties of this system allow it to masquerade as a single star with a very low-mass companion: its large eccentricity (e~0.8), its relatively long period (P~238 days), and the approximately perpendicular orientation of the semi-major axis with respect to the line of sight (omega~189 degrees). As a result of these properties, for ~95% of the orbit the two sets of stellar spectral lines are completely blended, and the RV measurements based on centroiding on the apparently single-lined spectrum is very well fit by an orbit solution indicative of a brown dwarf companion on a more circular orbit (e~0.3). Only during the ~5% of the orbit near periastron passage does the true, double-lined nature and large RV amplitude of ~15 km/s reveal itself. The discovery of this binary system is an important lesson for RV surveys searching for substellar companions; at a given resolution and observing cadence, a survey will be susceptible to these kinds of astrophysical false positives for a range of orbital parameters. Finally, for surveys like MARVELS that lack the resolution for a useful line bisector analysis, it is imperative to monitor the peak of the cross-correlation function for suspicious changes in width or shape, so that such false positives can be flagged during the candidate vetting process.Comment: 16 pages, 11 figures, 6 table

Immunohistochemical and Molecular Features of Melanomas Exhibiting Intratumor and Intertumor Histomorphologic Heterogeneity

Melanoma is a heterogeneous neoplasm at the histomorphologic, immunophenotypic, and molecular levels. Melanoma with extreme histomorphologic heterogeneity can pose a diagnostic challenge in which the diagnosis may predominantly rely on its immunophenotypic profile. However, tumor survival and response to therapy are linked to tumor genetic heterogeneity rather than tumor morphology. Therefore, understating the molecular characteristics of such melanomas become indispensable. In this study, DNA was extracted from 11 morphologically distinct regions in eight formalin-fixed, paraffin-embedded melanomas. In each region, mutations in 50 cancer-related genes were tested using next-generation sequencing (NGS). A tumor was considered genetically heterogeneous if at least one non-overlapping mutation was identified either between the histologically distinct regions of the same tumor (intratumor heterogeneity) or among the histologically distinct regions of the paired primary and metastatic tumors within the same patient (intertumor heterogeneity). Our results revealed that genetic heterogeneity existed in all tumors as non-overlapping mutations were detected in every tested tumor (n = 5, 100%; intratumor: n = 2, 40%; intertumor: n = 3, 60%). Conversely, overlapping mutations were also detected in all the tested regions (n = 11, 100%). Melanomas exhibiting histomorphologic heterogeneity are often associated with genetic heterogeneity, which might contribute to tumor survival and poor response to therapy

Multicenter phase II study of matured dendritic cells pulsed with melanoma cell line lysates in patients with advanced melanoma

<p>Abstract</p> <p>Background</p> <p>Several single center studies have provided evidence of immune activation and antitumor activity of therapeutic vaccination with dendritic cells (DC) in patients with metastatic melanoma. The efficacy of this approach in patients with favorable prognosis metastatic melanoma limited to the skin, subcutaneous tissues and lung (stages IIIc, M1a, M1b) was tested in a multicenter two stage phase 2 study with centralized DC manufacturing.</p> <p>Methods</p> <p>The vaccine (IDD-3) consisted 8 doses of autologous monocyte-derived matured DC generated in serum-free medium with granulocyte macrophage colony stimulating factor (GM-CSF) and interleukin-13 (IL-13), pulsed with lysates of three allogeneic melanoma cell lines, and matured with interferon gamma. The primary endpoint was antitumor activity.</p> <p>Results</p> <p>Among 33 patients who received IDD-3 there was one complete response (CR), two partial responses (PR), and six patients had stable disease (SD) lasting more than eight weeks. The overall prospectively defined tumor growth control rate was 27% (90% confidence interval of 13-46%). IDD-3 administration had minimal toxicity and it resulted in a high frequency of immune activation to immunizing melanoma antigens as assessed by <it>in vitro </it>immune monitoring assays.</p> <p>Conclusions</p> <p>The administration of matured DC loaded with tumor lysates has significant immunogenicity and antitumor activity in patients with limited metastatic melanoma.</p> <p>Clinical trial registration</p> <p>NCT00107159.</p

Prognostic model for patient survival in primary anorectal mucosal melanoma:stage at presentation determines relevance of histopathologic features

Pathological staging of primary anorectal mucosal melanoma is often performed according to the American Joint Commission on Cancer (AJCC) guidelines for cutaneous melanoma, as an anorectal melanoma-specific staging system does not exist. However, it remains unknown whether prognostic factors derived for cutaneous melanoma also stratify risk in anorectal melanoma. We retrospectively determined correlations between clinicopathological parameters and disease-specific survival in 160 patients. Patients were grouped by clinical stage at presentation (localized disease, regional or distant metastases). Cox proportional hazards regression models determined associations with disease-specific survival. We also summarized the somatic mutations identified in a subset of tumors analyzed for hotspot mutations in cancer-associated gene panels. Most of the patients were white (82%) and female (61%). The median age was 62 years. With a median follow-up of 1.63 years, median disease-specific survival was 1.75 years, and 121 patients (76%) died of anorectal melanoma. Patients presenting with regional (34%) or distant metastases (24%) had significantly shorter disease-specific survival compared to those with disease localized to the anorectum (42%). Of the 71 anorectal melanoma tumors analyzed for hotspot genetic alterations, somatic mutations involving the KIT gene (24%) were most common followed by NRAS (19%). Increasing primary tumor thickness, lymphovascular invasion, and absence of regression also correlated with shorter disease-specific survival. Primary tumor parameters correlated with shorter disease-specific survival in patients presenting with localized disease (tumor thickness) or regional metastases (tumor thickness, absence of regression, and lymphovascular invasion), but not in patients presenting with distant metastases. Grouping of patients according to a schema based on modifications of the 8th edition AJCC cutaneous melanoma staging system stratified survival in anorectal melanoma. Our findings support stage-specific associations between primary tumor parameters and disease-specific survival in anorectal melanoma. Moreover, the AJCC cutaneous melanoma staging system and minor modifications of it predicted survival among anorectal melanoma patients

Sleep Problems Are Related to a Worse Quality of Life and a Greater Non-Motor Symptoms Burden in Parkinson’s Disease

COPPADIS Study Group.[Introduction] The aim of the present study was to examine the frequency of self-reported sleep problems and their associated factors in a large cohort of PD patients.[Methods] PD patients and controls, recruited from 35 centers of Spain from the COPPADIS cohort were included in this cross-sectional study. Sleep problems were assessed by the Spanish version of the Parkinson’s disease Sleep Scale version 1 (PDSS-1). An overall score below 82 or a score below 5 on at least 1 item was defined as sleep problems.[Results] The frequency of sleep problems was nearly double in PD patients compared to controls: 65.8% (448/681) vs 33.5% (65/206) (p < 0.0001). Mean total PDSS score was lower in PD patients than controls: 114.9 ± 28.8 vs 132.8 ± 16.3 (p < 0.0001). Quality of life (QoL) was worse in PD patients with sleep problems compared to those without: PDQ-39SI, 19.3 ± 14 vs 13 ± 11.6 (p < 0.0001); EUROHIS-QoL8, 3.7 ± 0.5 vs 3.9 ± 0.5 (p < 0.0001). Non-motor symptoms burden (NMSS; OR = 1.029; 95%CI 1.015–1.043; p < 0.0001) and impulse control behaviors (QUIP-RS; OR = 1.054; 95%CI 1.009–1.101; p = 0.018) were associated with sleep problems after adjustment for age, gender, disease duration, daily equivalent levodopa dose, H&Y, UPDRS-III, UPDRS-IV, PD-CRS, BDI-II, NPI, VAS-Pain, VAFS, FOGQ, and total number of non-antiparkinsonian treatments.[Conclusion] Sleep problems were frequent in PD patients and were related to both a worse QoL and a greater non-motor symptoms burden in PD. These findings call for increased awareness of sleep problems in PD patients.Peer reviewe