Biometrical Analysis of the Anterior Communicating Artery and the Anterior Cerebral Artery in the Precommunicating Segment of the Cerebral Arterial Circle

Indexación: ScieloLa conformación del círculo arterial cerebral tiene relevancia en la clínica neuroquirúrgica por la relación compleja que presentan las arterias que lo originan y su gran variabilidad. Debido a la alta frecuencia con que se observan aneurismas en las arteria comunicante anterior y en el segmento precomunicante (A1) de la arteria cerebral anterior se efectuó un análisis biométrico de ellas. El trabajo se realizó en 36 cerebros frescos procedentes de especímenes cuyos datos bioantropológicos estaban registrados. El calibre de la arteria comunicante anterior fue de 1.68 mm y la longitud, en promedio, de 2.50 mm. En el lado derecho el segmento A1 de la arteria cerebral anterior tenía una longitud de 12.91mm y un calibre de 2.39 mm. En el lado izquierdo, la longitud de este segmento fue de 12.77 mm y presentó un calibre de 2.46mm. En un 29% de las muestras analizadas, se presentaron arterias comunicantes dobles, con una longitud de 2.92 mm y un calibre de 0.95 mm. Se observó variabilidad en los componentes que constituyen el círculo arterial cerebral, cuando se consideran variables como lado, sexo e índice cefálico. PALABRAS CLAVE: Arteria comunicante anterior; Arteria cerebral anterior; Círculo arterial del cerebro; Índice cefálico.SUMMARY: The conformation of the cerebral arterial circle has relevance in the clinical neurosurgery for the complex relate that present the arteries that originate it and its great variability. Due to the high frequency with that aneurysms are observed in the anterior communicant artery and the anterior cerebral artery in the precommunicating segment (A1), we have decided to make an analysis biometrical in them. The work had done in 36 available fresh brains in the laboratories and they come from specimens whose data bioanthropological were registered. The caliber of the anterior communicating artery corresponds to 1.68 mm and the longitude to 2.50 mm. The segment A1 of the anterior cerebral artery it corresponds to a longitude of 12.91mm and it presents a caliber of 2.39 mm in the right side. In the left side the longitude of this segment is of 12.77 mm and it presents a caliber of 2.46. In 29% of the analyzed samples, they register double communicating arteries, with a longitude of 2.92 mm and a caliber of 0.95 mm. Variability of the components is observed that they constitute the cerebral arterial circle when is considered: side, sex and cephalic index KEY WORDS: Anterior communicating artery; Anterior cerebral artery; Cerebral arterial circle; Cephalix index

Phospho-kinase profile of triple negative breast cancer and androgen receptor signaling

BACKGROUND: The androgen receptor (AR) plays a central role in the oncogenesis of different tumors, as is the case in prostate cancer. In triple negative breast cancer (TNBC) a gene expression classification has described different subgroups including a luminal androgen subtype. The AR can be controlled by several mechanisms like the activation of membrane tyrosine kinases and downstream signaling pathways. However little is known in TNBC about how the AR is modulated by these mechanisms and the potential therapeutic strategists to inhibit its expression. METHODS: We used human samples to evaluate the expression of AR by western-blot and phospho-proteomic kinase arrays that recognize membrane tyrosine kinase receptors and downstream mediators. Western-blots in human cell lines were carried out to analyze the expression and activation of individual proteins. Drugs against these kinases in different conditions were used to measure the expression of the androgen receptor. PCR experiments were performed to assess changes in the AR gene after therapeutic modulation of these pathways. RESULTS: AR is present in a subset of TNBC and its expression correlates with activated membrane receptor kinases-EGFR and PDGFRβ in human samples and cell lines. Inhibition of the PI3K/mTOR pathway in TNBC cell lines decreased notably the expression of the AR. Concomitant administration of the anti-androgen bicalutamide with the EGFR, PDGFRβ and Erk1/2 inhibitors, decreased the amount of AR compared to each agent given alone, and had an additive anti-proliferative effect. Administration of dihydrotestosterone augmented the expression of AR that was not modified by the inhibition of the PI3K/mTOR or Erk1/2 pathways. AR expression was posttranscriptionally regulated by PI3K or Erk1/2 inhibition. CONCLUSION: Our results describe the expression of the AR in TNBC as a druggable target and further suggest the combination of bicalutamide with inhibitors of EGFR, PDGFRβ or Erk1/2 for future development

Antitumor activity of the novel multi-kinase inhibitor EC-70124 in triple negative breast cancer

This is an open-access article distributed under the terms of the Creative Commons Attribution License.-- et al.Disseminated triple negative breast cancer (TNBC) is an incurable disease with limited therapeutic options beyond chemotherapy. Therefore, identification of druggable vulnerabilities is an important aim. Protein kinases play a central role in cancer and particularly in TNBC. They are involved in many oncogenic functions including migration, proliferation, genetic stability or maintenance of stem-cell like properties. In this article we describe a novel multi-kinase inhibitor with antitumor activity in this cancer subtype. EC-70124 is a hybrid indolocarbazole analog obtained by combinatorial biosynthesis of Rebeccamycin and Staurosporine genes that showed antiproliferative effect and in vivo antitumoral activity. Biochemical experiments demonstrated the inhibition of the PI3K/mTOR and JAK/STAT pathways. EC-70124 mediated DNA damage leading to cell cycle arrest at the G2/M phase. Pathway analyses identified several deregulated functions including cell proliferation, migration, DNA damage, regulation of stem cell differentiation and reversion of the epithelial-mesenchymal transition (EMT) phenotype, among others. Combination studies showed a synergistic interaction of EC-70124 with docetaxel, and an enhanced activity in vivo. Furthermore, EC-70124 had a good pharmacokinetic profile. In conclusion these experiments demonstrate the antitumor activity of EC-70124 in TNBC paving the way for the future clinical development of this drug alone or in combination with chemotherapy.Ministry of Economy and Competitiveness of Spain (BFU2012-39151 and RD12/0036/0003 to AP), and the AECC (to AP). Instituto de Salud Carlos III (PI13/01444) ACEPAIN and CRIS Cancer Foundation (to AO). JCM is a recipient of a Miguel Servet fellowship program (CP12/03073).Peer Reviewe

Florecimientos de dinoflagelados nocivos en la costa Pacífica de Costa Rica

Since 1979 has been reported harmful microalgae blooms (HAB) on the Pacific coast of Costa Rica, it was identified until 2005 at least 13 taxa of dinoflagellates. In recent years these phenomena have intensified both spatially and temporarily, discolorations occur almost uninterrupted; they are distributed for months and which extend along the coast causing death fish and smelly in the water. Such massive FAN started with Pyrodinium bahamense, whose discoloration in 2000 lasted for more than one year and in which morphotypes were observed the two varieties of the species, coexisting alongside with Gymnodinium catenatum and causing serious cases of paralytic shellfish poisoning by seafood consumption (PSP). Later, from September 2003 until June 2004, Cochlodinium cf. polykrikoides produced discolorations in the entire Pacific coast followed by extensive stains of Akasiwo sanguinea and Gymnodinium instriatum. The latest event was observed in June 2005 when Alexandrium monilatum produced extensive discolorations with chains formed by more than 100 cells. The HAB of dinoflagellates are now common along the coasts of Costa Rica, possibly as a result of the current environmental conditions that favor the massive proliferation of invasive species (aggressive), which can even affect other sites in the American Pacific as the case of P. bahamense var. compressum which can be moved towards Mexico along the Central Pacific Coast through the Costa Rica Current Flow and Mexican Western Current.Desde 1979 se han reportado florecimientos de especies de microalgas nocivas (FAN) en la costa Pacífica de Costa Rica, reconociéndose hasta el 2005 al menos 13 taxa de dinoflagelados. En años recientes estos fenómenos se han intensificado tanto espacial como temporalmente, produciéndose discoloraciones casi ininterrumpidas que se extienden por toda la costa produciendo mortalidad de peces y fetidez en el agua. Tales FAN masivos se iniciaron con Pyrodinium bahamense en el 2000, quien perduró por más de un año y en el cual se observaron morfotipos correspondientes a las dos variedades de la especie, coexistiendo junto a Gymnodinium catenatum y ocasionando serios casos de Intoxicación Paralizante por Consumo de Mariscos (IPM). Posteriormente, de septiembre del 2003 hasta junio del 2004, Cochlodinium cf. polykrikoides produjo discoloraciones en toda la costa Pacífica, seguidas por manchas extensas de Akasiwo sanguinea y Gymnodinium instriatum. El evento más reciente se observó en junio del 2005 cuando Alexandrium monilatum produjo extensas discoloraciones con cadenas formadas por más de 100 células. Los FAN de dinoflagelados ahora son comunes en las costas de Costa Rica, posiblemente como resultado de las condiciones ambientales actuales que favorecen la proliferación masiva de especies invasivas (agresivas), las cuales incluso pueden afectar otros sitios del Pacífico americano como es el caso de P. bahamense var. compressum que puede desplazarse hasta México, a lo largo de la costa del Pacífico centroamericano a través de la Corriente Costera de Costa Rica y la Corriente Occidental Mexicana

Adaptation of the Bergen Social Media Addiction Scale (BSMAS) in Spanish

The impact of social networks on people's daily lives is worrisome, particularly in adolescents and young people, who seem to exceed the limits of normal use. Constant excessive use can lead to pathological behaviors linked to social media addiction (SMA). Our objectives were to 1) adapt the Bergen Social Media Addiction Scale (BSMAS) to Spanish and 2) evaluate its psychometric properties in a young population. The BSMAS was adapted to Spanish, involving experts on social media addiction and people from the target population during the adaptation process. For the psychometric evaluation, 650 Peruvian college students responded to the Spanish version (53.5 % women aged 18 to 40, M = 21.5 SD = 2.7). The one-dimensional measurement model proposed for the original BSMAS was confirmed for our version (X2(9) = 23.9315, CFI = 0.994, TLI = 0.990, SRMR = 0.032, RMSEA = 0.061). The reliability was good (α = 0.863; 95 % CI: 0.848–0.870; ω = 0.864; 95 % CI: 0.846–0.844), and the measurement invariance was confirmed for sex and age by fitting models. The concurrent validity with external social media addiction and mental health indicators was also confirmed. This study provides new and relevant information on the BSMAS validity and allows its application to Spanish-speaker college students from Peru and similar countries.info:eu-repo/semantics/publishedVersio

The effect of early treatment with ivermectin on viral load, symptoms and humoral response in patients with non-severe COVID-19: A pilot, double-blind, placebo-controlled, randomized clinical trial.

Background Ivermectin inhibits the replication of SARS-CoV-2 in vitro at concentrations not readily achievable with currently approved doses. There is limited evidence to support its clinical use in COVID-19 patients. We conducted a Pilot, randomized, double-blind, placebo-controlled trial to evaluate the efficacy of a single dose of ivermectin reduce the transmission of SARS-CoV-2 when administered early after disease onset. Methods Consecutive patients with non-severe COVID-19 and no risk factors for complicated disease attending the emergency room of the Clínica Universidad de Navarra between July 31, 2020 and September 11, 2020 were enrolled. All enrollments occurred within 72 h of onset of fever or cough. Patients were randomized 1:1 to receive ivermectin, 400 mcg/kg, single dose (n = 12) or placebo (n = 12). The primary outcome measure was the proportion of patients with detectable SARS-CoV-2 RNA by PCR from nasopharyngeal swab at day 7 post-treatment. The primary outcome was supported by determination of the viral load and infectivity of each sample. The differences between ivermectin and placebo were calculated using Fisher's exact test and presented as a relative risk ratio. This study is registered at ClinicalTrials.gov: NCT04390022. Findings All patients recruited completed the trial (median age, 26 [IQR 19-36 in the ivermectin and 21-44 in the controls] years; 12 [50%] women; 100% had symptoms at recruitment, 70% reported headache, 62% reported fever, 50% reported general malaise and 25% reported cough). At day 7, there was no difference in the proportion of PCR positive patients (RR 0·92, 95% CI: 0·77-1·09, p = 1·0). The ivermectin group had non-statistically significant lower viral loads at day 4 (p = 0·24 for gene E; p = 0·18 for gene N) and day 7 (p = 0·16 for gene E; p = 0·18 for gene N) post treatment as well as lower IgG titers at day 21 post treatment (p = 0·24). Patients in the ivermectin group recovered earlier from hyposmia/anosmia (76 vs 158 patient-days; p < 0.001). Interpretation Among patients with non-severe COVID-19 and no risk factors for severe disease receiving a single 400 mcg/kg dose of ivermectin within 72 h of fever or cough onset there was no difference in the proportion of PCR positives. There was however a marked reduction of self-reported anosmia/hyposmia, a reduction of cough and a tendency to lower viral loads and lower IgG titers which warrants assessment in larger trials. Funding ISGlobal, Barcelona Institute for Global Health and Clínica Universidad de Navarra

B-cell regeneration profile and minimal residual disease status in bone marrow of treated multiple myeloma patients

© 2021 by the authors.B-cell regeneration during therapy has been considered as a strong prognostic factor in multiple myeloma (MM). However, the effects of therapy and hemodilution in bone marrow (BM) B-cell recovery have not been systematically evaluated during follow-up. MM (n = 177) and adult (≥50y) healthy donor (HD; n = 14) BM samples were studied by next-generation flow (NGF) to simultaneously assess measurable residual disease (MRD) and residual normal B-cell populations. BM hemodilution was detected in 41 out of 177 (23%) patient samples, leading to lower total B-cell, B-cell precursor (BCP) and normal plasma cell (nPC) counts. Among MM BM, decreased percentages (vs. HD) of BCP, transitional/naïve B-cell (TBC/NBC) and nPC populations were observed at diagnosis. BM BCP increased after induction therapy, whereas TBC/NBC counts remained abnormally low. At day+100 postautologous stem cell transplantation, a greater increase in BCP with recovered TBC/NBC cell numbers but persistently low memory B-cell and nPC counts were found. At the end of therapy, complete response (CR) BM samples showed higher CD19− nPC counts vs. non-CR specimens. MRD positivity was associated with higher BCP and nPC percentages. Hemodilution showed a negative impact on BM B-cell distribution. Different BM B-cell regeneration profiles are present in MM at diagnosis and after therapy with no significant association with patient outcome.This work has been supported by the International Myeloma Foundation-Black Swan Research Initiative, the EuroFlow Consortium (grant LSHB-CT-2006-018708); Centro de Investigación Biomédica en Red de Cáncer (CIBER-ONC; Instituto de Salud Carlos III, Ministerio de Economía y Competitividad, Madrid, Spain and FONDOS FEDER), numbers: CB16/12/00400, CB16/12/00233, CB16/12/00369, CB16/12/00489 and CB16/12/00480; grant from Bilateral Cooperation Program between Coordenação de Aperfeiçoamento de Pessoal de Nível Superior-CAPES (Brasília/Brazil) and Dirección General de Políticas Universitárias (DGPU)-Ministério de Educación, Cultura y Deportes (Madrid/Spain) number DGPU 311/15; Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro of Brazil (FAPERJ) numbers: E26/110.105/2014 and E26/102.191/2013; grant from Conselho Nacional de Desenvolvimento Científico e Tecnológico of Brazil (CNPQ), number: 400194/2014-7. R.M.d.P. was supported by a grant from Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES/DGPU), number: 000281/2016-06 and CAPES/PROEX 641/2018, Brazil; Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro of Brazil (FAPERJ) number: E01/200/537/2018

A deletion at Adamts9-magi1 Locus is associated with psoriatic arthritis risk

Objective: Copy number variants (CNVs) have been associated with the risk to develop multiple autoimmune diseases. Our objective was to identify CNVs associated with the risk to develop psoriatic arthritis (PsA) using a genome-wide analysis approach. Methods: A total of 835 patients with PsA and 1498 healthy controls were genotyped for CNVs using the Illumina HumanHap610 BeadChip genotyping platform. Genomic CNVs were characterised using CNstream analysis software and analysed for association using the χ2 test. The most significant genomic CNV associations with PsA risk were independently tested in a validation sample of 1133 patients with PsA and 1831 healthy controls. In order to test for the specificity of the variants with PsA aetiology, we also analysed the association to a cohort of 822 patients with purely cutaneous psoriasis (PsC). Results: A total of 165 common CNVs were identified in the genome-wide analysis. We found a highly significant association of an intergenic deletion between ADAMTS9 and MAGI1 genes on chromosome 3p14.1 (p=0.00014). Using the independent patient and control cohort, we validated the association between ADAMTS9-MAGI1 deletion and PsA risk (p=0.032). Using next-generation sequencing, we characterised the 26 kb associated deletion. Finally, analysing the PsC cohort we found a lower frequency of the deletion compared with the PsA cohort (p=0.0088) and a similar frequency to that of healthy controls (p>0.3). Conclusions: The present genome-wide scan for CNVs associated with PsA risk has identified a new deletion associated with disease risk and which is also differential from PsC risk

Rarity of monodominance in hyperdiverse Amazonian forests.

Tropical forests are known for their high diversity. Yet, forest patches do occur in the tropics where a single tree species is dominant. Such "monodominant" forests are known from all of the main tropical regions. For Amazonia, we sampled the occurrence of monodominance in a massive, basin-wide database of forest-inventory plots from the Amazon Tree Diversity Network (ATDN). Utilizing a simple defining metric of at least half of the trees ≥ 10 cm diameter belonging to one species, we found only a few occurrences of monodominance in Amazonia, and the phenomenon was not significantly linked to previously hypothesized life history traits such wood density, seed mass, ectomycorrhizal associations, or Rhizobium nodulation. In our analysis, coppicing (the formation of sprouts at the base of the tree or on roots) was the only trait significantly linked to monodominance. While at specific locales coppicing or ectomycorrhizal associations may confer a considerable advantage to a tree species and lead to its monodominance, very few species have these traits. Mining of the ATDN dataset suggests that monodominance is quite rare in Amazonia, and may be linked primarily to edaphic factors

Influence of hypothermia on right atrial cardiomyocyte apoptosis in patients undergoing aortic valve replacement

BACKGROUND: There is increasing evidence that programmed cell death can be triggered during cardiopulmonary bypass (CPB) and may be involved in postoperative complications. The purpose of this study was to investigate whether apoptosis occurs during aortic valve surgery and whether modifying temperature during CPB has any influence on cardiomyocyte apoptotic death rate. METHODS: 20 patients undergoing elective aortic valve replacement for aortic stenosis were randomly assigned to either moderate hypothermic (ModHT group, n = 10, 28°C) or mild hypothermic (MiHT group, n = 10, 34°C) CPB. Myocardial samples were obtained from the right atrium before and after weaning from CPB. Specimens were examined for apoptosis by flow cytometry analysis of annexin V-propidium iodide (PI) and Fas death receptor staining. RESULTS: In the ModHT group, non apoptotic non necrotic cells (annexin negative, PI negative) decreased after CPB, while early apoptotic (annexin positive, PI negative) and late apoptotic or necrotic (PI positive) cells increased. In contrast, no change in the different cell populations was observed over time in the MiHT group. Fas expression rose after reperfusion in the ModHT group but not in MiHT patients, in which there was even a trend for a lower Fas staining after CPB (p = 0.08). In ModHT patients, a prolonged ischemic time tended to induce a higher increase of Fas (p = 0.061). CONCLUSION: Our data suggest that apoptosis signal cascade is activated at early stages during aortic valve replacement under ModHT CPB. This apoptosis induction can effectively be attenuated by a more normothermic procedure