Encorafenib and binimetinib followed by radiotherapy for patients with BRAFV600-mutant melanoma and brain metastases (E-BRAIN/GEM1802 phase II study).

BACKGROUND: Encorafenib plus binimetinib (EB) is a standard of care treatment for advanced BRAFV600-mutant melanoma. We assessed efficacy and safety of encorafenib plus binimetinib in patients with BRAFV600-mutant melanoma and brain metastasis (BM) and explored if radiotherapy improves the duration of response. METHODS: E-BRAIN/GEM1802 was a prospective, multicenter, single arm, phase II trial that enrolled patients with melanoma BRAFV600-mutant and BM. Patients received encorafenib 450 mg once daily plus binimetinib 45 mg BID, and those who achieved partial response or stable disease at first tumor assessment were offered radiotherapy. Treatment continued until progression.Primary endpoint was intracranial response rate (icRR) after 2 months of EB, establishing a futility threshold of 60%. RESULTS: The study included 25 patients with no BM symptoms and 23 patients with BM symptoms regardless of using corticosteroids. Among them, 31 patients (64.6%) received sequential radiotherapy. After two months, icRR was 70.8% (95% CI: 55.9-83.1); 10.4% complete response. Median intracranial PFS and OS were 8.5 (95% CI: 6.4-11.8) and 15.9 (95% CI: 10.7-21.4) months, respectively (8.3 months for icPFS and 13.9 months OS for patients receiving RDT). Most common grade 3-4 treatment-related adverse event was alanine aminotransferase (ALT) increased (10.4%). CONCLUSION: Encorafenib plus binimetinib showed promising clinical benefit in terms of icRR, and tolerable safety profile with low frequency of high grade TRAEs, in patients with BRAFV600-mutant melanoma and BM, including those with symptoms and need for steroids. Sequential radiotherapy is feasible but it does not seem to prolong response.

Identification of Arabidopsis thaliana small RNAs responsive to the fungal pathogen Botrytis cinerea at an early stage of interaction.

In plants, small RNAs (sRNAs), mainly microRNAs (miRNAs) and small interfering RNAs (siRNAs), have been described as key regulators of plant development, growth, and abiotic and biotic responses. Despite reports indicating the involvement of certain sRNAs in regulating the interaction between Botrytis cinerea (a major necrotrophic fungal phytopathogen) and host plants, there remains a lack of analysis regarding the potential regulatory roles of plant sRNAs during early stages of the interaction despite early immune responses observed then during infection. We present the first transcriptome-wide analysis of small RNA expression on the early interaction between the necrotrophic fungus Botrytis cinerea and the model plant Arabidopsis thaliana. We found that evolutionary conserved A. thaliana miRNAs were the sRNAs that accumulated the most in the presence of B. cinerea. The upregulation of miR167, miR159 and miR319 was of particular interest because these, together with their target transcripts, are involved in the fine regulation of the plant hormone signaling pathways. We also describe that miR173, which triggers the production of secondary siRNAs from TAS1 and TAS2 loci, as well as secondary siRNAs derived from these loci, is upregulated in response to B. cinerea. Thus, at an early stage of the interaction there are transcriptional changes of sRNA-guided silencing pathway genes and of a subset of sRNAs that targeted genes from the PPR gene superfamily, and these may be important mechanisms regulating the interaction between A. thaliana and B. cinerea. This work provides the basis for a better understanding of the regulation mediated by sRNAs during early B. cinerea-plant interaction and may help in the development of more effective strategies for its control.

Perioperative Nivolumab and Chemotherapy in Stage III Non-Small-Cell Lung Cancer.

BACKGROUND: Approximately 20% of patients with non-small-cell lung cancer (NSCLC) receive a diagnosis of stage III disease. There is no current consensus regarding the most appropriate treatment for these patients. METHODS: In this open-label, phase 2 trial, we randomly assigned patients with resectable stage IIIA or IIIB NSCLC to receive neoadjuvant nivolumab plus platinum-based chemotherapy (experimental group) or chemotherapy alone (control group), followed by surgery. Patients in the experimental group who had R0 resections received adjuvant treatment with nivolumab for 6 months. The primary end point was a pathological complete response (0% viable tumor in resected lung and lymph nodes). Secondary end points included progression-free survival and overall survival at 24 months and safety. RESULTS: A total of 86 patients underwent randomization; 57 were assigned to the experimental group and 29 were assigned to the control group. A pathological complete response occurred in 37% of the patients in the experimental group and in 7% in the control group (relative risk, 5.34; 95% confidence interval [CI], 1.34 to 21.23; P = 0.02). Surgery was performed in 93% of the patients in the experimental group and in 69% in the control group (relative risk, 1.35; 95% CI, 1.05 to 1.74). Kaplan-Meier estimates of progression-free survival at 24 months were 67.2% in the experimental group and 40.9% in the control group (hazard ratio for disease progression, disease recurrence, or death, 0.47; 95% CI, 0.25 to 0.88). Kaplan-Meier estimates of overall survival at 24 months were 85.0% in the experimental group and 63.6% in the control group (hazard ratio for death, 0.43; 95% CI, 0.19 to 0.98). Grade 3 or 4 adverse events occurred in 11 patients in the experimental group (19%; some patients had events of both grades) and 3 patients in the control group (10%). CONCLUSIONS: In patients with resectable stage IIIA or IIIB NSCLC, perioperative treatment with nivolumab plus chemotherapy resulted in a higher percentage of patients with a pathological complete response and longer survival than chemotherapy alone. (Funded by Bristol Myers Squibb and others; NADIM II ClinicalTrials.gov number, NCT03838159; EudraCT number, 2018-004515-45.).

Identification of ALK-positive patients with advanced NSCLC and real-world clinical experience with crizotinib in Spain (IDEALK study).

OBJECTIVES: To determine the incidence of ALK translocations in patients with advanced/metastatic NSCLC in Spain, to describe the clinical characteristics of these patients, and to evaluate the effectiveness and safety of treatment with crizotinib in a real-world setting. METHODS: This is an observational prospective and retrospective cohort study to determine the incidence of ALK translocations and to analyze the effectiveness and safety of crizotinib in a real-world setting. Patient characteristics, treatment patterns, time to best overall response, duration of treatment, objective response rates (ORR), rates of adverse events (AE), progression free survival (PFS) and overall survival (OS) were evaluated in the ALK study cohort of patients treated with crizotinib (prospective and retrospective). ALK incidence and quality of life (QoL) questionnaires were measured from patients included in the prospective cohort. RESULTS: The incidence of ALK translocations was 5.5 % (31 of 559 patients). Compared with ALK-negative patients, ALK-positive patients were significantly younger, predominantly female, and non-smokers. In the crizotinib effectiveness and safety study, 91 patients (42 prospective, 49 retrospective) with ALK-positive NSCLC (43.9 % in first-line, 56.1 % in second or more lines) were included. The ORR was 59.3 % and the median duration of response was 13.5 months (IQR, 5.3-26.2). The median PFS was 15.8 months (95 % CI, 11.8-22.3) and the median OS was 46.5 months, with 53 patients (58.2 %) still alive at data cut-off date. Frequently reported AEs included elevated transaminases, gastrointestinal disorders, and asthenia. Most patients (76.5 %) reported improved or stable scores for global QoL during treatment. CONCLUSIONS: The observed incidence of ALK translocations in NSCLC patients is aligned with published reports. This analysis of the real-world clinical experience in Spain confirms the therapeutic benefit and safety of crizotinib in advanced/metastatic ALK-positive NSCLC. CLINICALTRIALS: gov: NCT02679170.

Methylation of Subtelomeric Chromatin Modifies the Expression of the lncRNA TERRA, Disturbing Telomere Homeostasis.

The long noncoding RNA (lncRNA) telomeric repeat-containing RNA (TERRA) has been associated with telomeric homeostasis, telomerase recruitment, and the process of chromosome healing; nevertheless, the impact of this association has not been investigated during the carcinogenic process. Determining whether changes in TERRA expression are a cause or a consequence of cell transformation is a complex task because studies are usually carried out using either cancerous cells or tumor samples. To determine the role of this lncRNA in cellular aging and chromosome healing, we evaluated telomeric integrity and TERRA expression during the establishment of a clone of untransformed myeloid cells. We found that reduced expression of TERRA disturbed the telomeric homeostasis of certain loci, but the expression of the lncRNA was affected only when the methylation of subtelomeric bivalent chromatin domains was compromised. We conclude that the disruption in TERRA homeostasis is a consequence of cellular transformation and that changes in its expression profile can lead to telomeric and genomic instability.

Proteasome inhibition alters mitotic progression through the upregulation of centromeric α-Satellite RNAs.

Cell cycle progression requires control of the abundance of several proteins and RNAs over space and time to properly transit from one phase to the next and to ensure faithful genomic inheritance in daughter cells. The proteasome, the main protein degradation system of the cell, facilitates the establishment of a proteome specific to each phase of the cell cycle. Its activity also strongly influences transcription. Here, we detected the upregulation of repetitive RNAs upon proteasome inhibition in human cancer cells using RNA-seq. The effect of proteasome inhibition on centromeres was remarkable, especially on α-Satellite RNAs. We showed that α-Satellite RNAs fluctuate along the cell cycle and interact with members of the cohesin ring, suggesting that these transcripts may take part in the regulation of mitotic progression. Next, we forced exogenous overexpression and used gapmer oligonucleotide targeting to demonstrate that α-Sat RNAs have regulatory roles in mitosis. Finally, we explored the transcriptional regulation of α-Satellite DNA. Through in silico analyses, we detected the presence of CCAAT transcription factor-binding motifs within α-Satellite centromeric arrays. Using high-resolution three-dimensional immuno-FISH and ChIP-qPCR, we showed an association between the α-Satellite upregulation and the recruitment of the transcription factor NFY-A to the centromere upon MG132-induced proteasome inhibition. Together, our results show that the proteasome controls α-Satellite RNAs associated with the regulation of mitosis.

Are there differences by sex in lung cancer characteristics at diagnosis? -a nationwide study.

BACKGROUND: Lung cancer causes approximately 25% of all cancer deaths. Despite its relevance, few studies have analyzed differences by sex at the time of diagnosis in terms of symptoms, stage, age or smoking status. We aim to assess if there are differences between men and women on these characteristics at diagnosis. METHODS: We analyzed the Thoracic Tumour Registry (TTR), sponsored by the Spanish Lung Cancer Group using a case-series design. This is a nationwide registry of lung cancer cases which started recruitment in 2016. For each case included, clinicians fulfilled an electronic record registering demographic data, symptoms, exposure to lung cancer risk factors, and treatment received in detail. We compared men and women using descriptive statistics. RESULTS: A total of 13,590 participants took part in this study, 25.6% women. Women were 4 years younger than men (64 vs. 69), and men had smoked more frequently. Adenocarcinoma was the most frequent histological type in both sexes. Stage IV at diagnosis was 50.8% in women compared to 43.6% in men. Weight loss/anorexia/asthenia was the most frequent symptom in both sexes and there were no differences in the number of symptoms at diagnosis. There were no relevant differences in the frequency or number of symptoms by sex when non-small cell lung cancer (NSCLC) and small-cell lung cancer (SCLC) were analyzed separately. Smoking status did not appear to cause different lung cancer presentation in men compared to women. CONCLUSIONS: There seems to be no differences in lung cancer characteristics by sex at the time at diagnosis on stage, specific symptoms or number of symptoms.

Epidemiología y factores de riesgo para cuidados intensivos y mortalidad en pacientes hospitalizados por COVID-19 / Epidemiology and risk factors for intensive care and mortality in COVID-19 hospitalized patients

INTRODUCCIÓN: El Complejo Hospitalario Universitario Nuestra Señora de Candelaria (CHUNSC) ha sido el hospital con más ingresos COVID-19 de Canarias. OBJETIVO: determinar factores de riesgo de ingreso en Unidad de Cuidados Intensivos (UCI) y mortalidad. MATERIAL Y MÉTODOS: Estudio observacional analítico retrospectivo de pacientes con COVID-19 confirmado, ingresados entre 25 febrero y 31 mayo 2020 en el CHUNSC. RESULTADOS: Ingresaron 264 pacientes, 56,8% hombres, edad media 65,3 años. Tasa de letalidad 15,2%. Factores de riesgo asociados con ingreso en UCI: neumonía (OR 2,22, IC 95% 1,08-4,55, p = 0,029) y síndrome de distrés respiratorio agudo (SDRA) (OR 4,94, IC 95% 1,46-16,68; p = 0,010). Factores asociados con mortalidad: edad ≥ 60 años (OR 3,94, IC 95% 1,21-12,82, p = 0,023), neumonía (OR 3,38, IC 95% 1,35-8,47, p = 0,009), SDRA (OR 5,84, IC 95% 1,60-21,24, p = 0,007) y enfermedad renal crónica (ERC) (OR 3,74, IC 95% 1,40-9,98, p = 0,009). CONCLUSIONES: Neumonía y SDRA se asociaron con ingreso en UCI. Neumonía, SDRA, edad ≥ 60 años y ERC se asociaron con mayor riesgo de mortalidad

INTRODUCTION: Complejo Hospitalario Universitario Nuestra Señora de Candelaria (CHUNSC) had the highest number of COVID-19 admissions in the Canary Islands. Aim of the study was to determine the risk factors for admission to the Intensive Care Unit (ICU) and mortality. METHODS: Retrospective analytical longitudinal study of patients with confirmed COVID-19, hospitalized between February 25 and May 31, 2020, at CHUNSC. RESULTS: In the study period, 264 patients were admitted, 56.8% men, mean age 65.3 years. Most frequent symptoms: cough (67%) and fever (59.8%), most frequent comorbidities: cardiovascular disease (60.6%) and diabetes (26.5%). Global Case Fatality Rate (CFR) 15.2%. Risk factors associated with ICU admission: Pneumonia (OR 2.22, 95%CI 1.08-4.55, p = 0.029) and Acute Respiratory Distress Syndrome (ARDS) (OR 4.94, 95%CI 1.46-16.68; p = 0.010). Risk factors associated with mortality: age ≥ 60 years (OR 3.94, 95%CI 1.21-12.82, p = 0.023), pneumonia (OR 3.38, 95%CI 1.35-8.47, p = 0.009), ARDS (OR 5.84, 95%CI 1.60-21.24, p = 0.007) and chronic kidney disease (CKD) (OR 3.74, 95%CI 1.40-9.98, p = 0.009). CONCLUSION: Pneumonia and ARDS were associated with ICU admission. Pneumonia, ARDS, age ≥ 60 years and CKD were associated with mortality

Lung cancer symptoms at diagnosis: results of a nationwide registry study.

BACKGROUND: Lung cancer is currently the leading cause of cancer death. Despite its high incidence and mortality, there are few studies describing its symptoms at diagnosis broken down by tumour stage and tobacco use. Accordingly, this study was proposed to describe the frequency of the most common symptoms of non-small cell lung cancer and small cell lung cancer (SCLC) at diagnosis, with a breakdown by stage and tobacco use. PATIENTS AND METHODS: Cases were collected from the Spanish Thoracic Tumour Registry, a nationwide registry sponsored by the Spanish Lung Cancer Group. More than 50 hospitals recruited histologically confirmed lung cancer cases and information was gathered through personal interview plus data contained in the electronic clinical record. There were no data available on the lag between the appearance of the first symptoms and diagnosis of lung cancer. RESULTS: A total of 9876 patients (74% male, median age 64 years) were recruited from 2016 to 2019. Of these, 12.5% presented with SCLC. Stage IV was the most frequent stage at diagnosis (46.6%), and the most frequent symptom was cough (33.9%), followed by dyspnoea (26.7%). No symptom was present in 59% of patients diagnosed in stage I; 40% of stage I patients presented with at least one symptom, while 27.7% of patients in stage IV had no symptoms at diagnosis. Cough was the most frequent symptom in SCLC (40.6%), followed by dyspnoea (34.3%). The number of symptoms was similar across the respective smoking categories in SCLC, and differences between the symptoms analysed did not exceed 7% in any case. CONCLUSION: The absence of the most frequent symptoms (ie, cough, pain, dyspnoea) should not lead to a decision to rule out the presence of lung cancer. A relevant percentage of stage IV patients displayed no symptoms at diagnosis.

Origin and Evolutionary Dynamics of the miR2119 and ADH1 Regulatory Module in Legumes.

MicroRNAs are important regulators of gene expression in eukaryotes. Previously, we reported that in Phaseolus vulgaris, the precursor for miR2119 is located in the same gene as miR398a, conceiving a dicistronic MIR gene. Both miRNA precursors are transcribed and processed from a single transcript resulting in two mature microRNAs that regulate the mRNAs encoding ALCOHOL DEHYDROGENASE 1 (ADH1) and COPPER-ZINC SUPEROXIDE DISMUTASE 1 (CSD1). Genes for miR398 are distributed throughout the spermatophytes; however, miR2119 is only found in Leguminosae species, indicating its recent emergence. Here, we used public databases to explore the presence of the miR2119 sequence in several plant species. We found that miR2119 is present only in specific clades within the Papilionoideae subfamily, including important crops used for human consumption and forage. Within this subfamily, MIR2119 and MIR398a are found together as a single gene in the genomes of the Millettioids and Hologalegina. In contrast, in the Dalbergioids MIR2119 is located in a different locus from MIR398a, suggesting this as the ancestral genomic organization. To our knowledge, this is a unique example where two separate MIRNA genes have merged to generate a single polycistronic gene. Phylogenetic analysis of ADH1 gene sequences in the Papilionoideae subfamily revealed duplication events resulting in up to four ADH1 genes in certain species. Notably, the presence of MIR2119 correlates with the conservation of target sites in particular ADH1 genes in each clade. Our results suggest that post-transcriptional regulation of ADH1 genes by miR2119 has contributed to shaping the expansion and divergence of this gene family in the Papilionoideae. Future experimental work on ADH1 regulation by miR2119 in more legume species will help to further understand the evolutionary history of the ADH1 gene family and the relevance of miRNA regulation in this process.

Rehabilitación del Atrapamiento Femoroacetabular tras Artroscopia (RAFA): revisión sistemática y propuesta de programa contextualizado / Rehabilitation after Arthroscopy for FemoroAcetabular impingement: a systematic review and proposal of a contextualised protocol / Reabilitação do aprisionamento femoroacetabular após artroscopia: revisão sistemática e proposta de um programa contextualizado

La artroscopia de cadera para el atrapamiento femoroacetabular es un procedimiento reciente. Se ha estudiado la etiología, diagnóstico y tratamiento artroscópico del atrapamiento femoroacetabular, no así la rehabilitación postoperatoria. Hemos examinado los estudios de la última década sobre estructura y contenidos de los programas de rehabilitación del atrapamiento femoroacetabular tras artroscopia. Se realizó una revisión sistemática de acuerdo a la declaración PRISMA, las bases de datos seleccionadas fueron Scopus, Web of Science, PubMed, Dialnet y Cochrane Library Plus, evaluándose la calidad metodológica de los trabajos mediante la escala de Coleman modificada. Se analizaron los programas de los estudios incluidos, hallándose fases, contenidos y criterios comunes, mostrando escasa evidencia y heterogeneidad metodológica, que no permite estandarizar los protocolos de rehabilitación. En conclusión, con toda la información se ha diseñado un protocolo integral dirigido al paciente para ser aplicado y medir sus resultados en el contexto socioeconómico de la población española

Hip arthroscopy to manage femoroacetabular impingement is a recent procedure. Etiology, diagnosis and arthroscopy treatment of femoroacetabular impingement has been deeply studied, but postoperative rehabilitation not. We reviewed studies from the past decade regarding structure and contents of rehabilitation programs after hip arthroscopy for femoracetabular impingement. A systematic search according to PRISMA statement was conducted. "Scopus", "Web of Science", "PubMed", "Dialnet" and "Cochrane Library Plus" were the selected databases. Study methodological quality was evaluated using the modified Coleman methodology score. Protocols of included studies were analysed and common phases, contents and criteria were extracted. Literature analysis shows a lack of evidence and methodological heterogeneity and this does not allow the rehabilitation protocols to be standardised. All the existing information has been integrated for the design of a contextualised comprehensive patient-centered protocol, for application and outcome measurement in the socio-economic context of Spanish population

A artroscopia do quadril para o impacto femoroacetabular é um procedimento recentemente expandido. A etiologia, o diagnóstico e o tratamento artroscópico do impacto femoroacetabular foram estudados, mas não a reabilitação pós-operatória. Nós examinamos os estudos da última década sobre a estrutura e os conteúdos dos programas de reabilitação para o impacto femoroacetabular após a artroscopia. Uma revisão sistemática foi realizada de acordo com a declaração PRISMA, os bancos de dados selecionados foram Scopus, Web of Science, PubMed, Dialnet e Cochrane Library Plus, avaliando a qualidade metodológica dos trabalhos utilizando a escala de Coleman modificada. Os programas dos estudos incluídos foram analisados, encontrando fases, conteúdos e critérios comuns, mostrando pouca evidência e heterogeneidade metodológica, o que não permite padronizar os protocolos de reabilitação. Em conclusão, com todas as informações, foi elaborado um protocolo integral para que o paciente seja aplicado e mensure seus resultados no contexto socioeconômico da população espanhola

Northern Blot Analysis of microRNAs and Other Small RNAs in Plants.

The study of regulatory small RNAs, such as siRNAs and microRNAs in plants, has necessitated methods tailored to their unique features. Their analysis demands the use of sensitive and quantitative methods for their detection. The use of Northern blot hybridization offers an attractive alternative to address qualitative as well as quantitative features. We highlight the advantages and shortcomings of this method and offer a detailed description of the techniques that best work in our hands, considering their use for the study of several small RNAs in multiple samples. We enumerate relevant details as well as cautionary comments in cases where we have detected potential difficulties.

A dicistronic precursor encoding miR398 and the legume-specific miR2119 coregulates CSD1 and ADH1 mRNAs in response to water deficit.

Plant microRNAs are commonly encoded in transcripts containing a single microRNA precursor. Processing by DICER-LIKE 1 and associated factors results in the production of a small RNA, followed by its incorporation into an AGO-containing protein complex to guide silencing of an mRNA possessing a complementary target sequence. Certain microRNA loci contain more than one precursor stem-loop structure, thus encoding more than one microRNA in the same transcript. Here, we describe a unique case where the evolutionary conserved miR398a is encoded in the same transcript as the legume-specific miR2119. The dicistronic arrangement found in common bean was also observed in other legumes. In Phaseolus vulgaris, mature miR398 and miR2119 are repressed in response to water deficit, and we demonstrate that both are functional as they target the mRNAs for CSD1 and ADH1, respectively. Our results indicate that the repression of miR398 and miR2119 leads to coordinated up-regulation of CSD1 and ADH1 mRNAs in response to water deficit in common bean and possibly in other legumes. Furthermore, we show that miRNA directed CSD1 and ADH1 mRNAs up-regulation also occurs when common bean plants are exposed to flooding, suggesting that plant redox status and fermentation metabolism must be closely coordinated under different adverse conditions.

Efficacy and learning curve of a hand-held echocardiography device in an oncology outpatient clinic: Expanding the use of echoscopic heart examination beyond cardiology.

Certain chemotherapy drugs for breast cancer may induce cardiotoxicity and these patients should be echocardiographically monitored. The performance of a focused echocardiographic evaluation (echoscopy) at the patient's location by a non-cardiologist appears to be feasible. The aim of the present study was to assess the accuracy of echoscopy performed by medical oncologists in an outpatient clinic using hand-held echocardiography devices. The study cohort comprised consecutive unselected patients who attended an oncology outpatient clinic. Two medical oncologists attended a one-week training period, which included theoretical and practical teaching by an expert cardiologist. Every subject underwent two echo examinations. The first examination was performed by an oncologist using a hand-held echo device and the second was performed by a cardiologist using a 'premium' device. Out of the 101 enrolled patients, 32 were men (31.7%) and the mean age was 56.03±16.88 years. There was a good global agreement [intra-class correlation coefficient (ICC): 0.65 for left ventricular ejection fraction (LVEF)]. When the results were analyzed depending on the period of time when the echo studies were performed, a clear and short learning curve was observed: LVEF started at ICC=0.58 and increased to 0.66 and 0.77 in the second and third period, respectively. There were extremely few clinically significant differences and a learning curve was also evident. In conclusion, cardiac echoscopy performed by an oncologist with a hand-held device may lead to a similar clinical management as a study performed by an expert cardiologist with a 'premium' system in patients under chemotherapy following a short training period.

Pancreatic acinar cell carcinoma with bilateral ovarian metastases, panniculitis and polyarthritis treated with FOLFIRINOX chemotherapy regimen. A case report and review of the literature.

Pancreatic acinar cell carcinoma (PACC) is a rare pancreatic tumor, with an estimated frequency of less than 1% of pancreatic malignancies. There are no prospective studies to guide diagnostic or therapeutic algorithms. We report the case of a 36 year-old woman, diagnosed of a pancreatic tumor with liver and peritoneal metastases that was initially managed as a neuroendocrine tumor with temozolomide and capecitabine. After two cycles a severely painful arthritis developed in her left ankle with panniculitis and extensive fat necrosis, and CT scan demonstrated progressive disease. Pathology of the primary was reassessed establishing the diagnosis of PACC. The patient started treatment with FOLFIRINOX regimen, achieving clinical benefit and disease stabilization. We also briefly reviewed the literature on this rare subtype of pancreatic tumor.

A new species of Erythrodiplax breeding in bromeliads in Costa Rica (Odonata: Libellulidae).

We describe a new species, Erythrodiplax laselva (Libellulidae), that breeds in bromeliads and Cochliostema (Commelinaceae) in the eastern lowlands of Costa Rica. The closest known relative is thought to be E. castanea, widespread in Central and South America, and not E. bromeliicola, which is known to breed in bromeliads in Cuba and Jamaica. The male, female, genitalia, and larva are described and illustrated.

Thermal gelation of aqueous hydroxypropylmethylcellulose solutions with SDS and hydrophobic drug particles.

The thermal gelation of hydroxypropylmethylcellulose (HPMC) solutions has been studied as a function of sodium dodecyl sulfate (SDS) concentration with and without griseofulvin, a model particulate BCS Class II drug by rheological measurements of gelation temperature (Tgel), steady-state viscosity (η) at 25 °C, and ζ-potential. Polymer adsorption on the drug was demonstrated by a decrease in η and potential in the absence of SDS. Griseofulvin had a synergistic effect on gelation which was attributed to an effective spanning of associated hydrophobic polymeric regions through interactions with the adsorbed polymer. Adding SDS offsets this effect on Tgel shielding hydrophobic interactions. Higher SDS concentrations had no effect on the particles surface as evidenced by constant ζ-potential and Tgel. Yet, polymeric chains are saturated and larger surfactant aggregates account for the increase in viscosity. Understanding the gelation mechanism and complex interactions of HPMC with surfactants and drugs is necessary for the design of pharmaceutical products and optimization of their performance properties.

Comparación de ecuaciones antropométricas para evaluar la masa muscular en jugadores de badminton / Comparison of anthropometric equations for estimation muscle mass in badminton player

Actualmente la cuantificación de la masa muscular es un área de estudio que ocupa distintas disciplinas científicas tanto de la salud como de las ciencias del deporte por ser un componente de la masa corporal que está en íntima relación con aspectos de la salud y del rendimiento deportivo. Existe una gran variedad de métodos y ecuaciones para su estimación pero la aplicación de las mismas no siempre resulta la más adecuada. El propósito de nuestro estudio es determinar la masa muscular en 37 jugadores de bádminton españoles, a través de técnicas antropométricas y hallar la fórmula más apropiada para dicha población. Fueron evaluadas 55 variables antropométricas: peso, estatura. perímetros, diámetros, longitudes, alturas y pliegues cutáneos. La composición corporal estimada de los jugadores de bádminton fue de 44 por ciento para la masa muscular y de 13 por ciento para la masa grasa. Los resultados indican que la táctica de fraccionamiento tetracompartimental que mejor se ajusta y concuerda con el peso real estimado con balanza es la siguiente: Masa Residual (Wurch), Masa Ósea (Rocha), Masa Grasa (Faulkner) y Masa Muscular (Drinkwater o Kerr).

The quantification of muscle mass is an area of study that addresses various scientific disciplines from health and sport science as a component of body mass that is in close connection with aspects of health and athletic performance. A variety of methods and equations for their estimation, but implementing them is not always the most appropriate. The purpose of our study is to determine the muscle mass of 37 badminton players of Spain, through anthropometric techniques and finding the most appropriate for this population. We studied 37 badminton players follow the protocol ISAK. Anthropometric variables were evaluated: weight, height, girth, breadth, lengths, heights and skin fold. For the fractionation of body composition in four components were combined different formulas to find the strategy that best fits and matches the estimated weight scale. We used the Wurch’s formula for residual mass, Rochas for bone mass, Brozek’s fat mass and to the muscle mass was concluded that the most appropriate for this population with those of Kerr’s. Body composition was estimated for our population: 10.8 percent bone mass, 15.3 percent residual mass, 13.2 percent fat mass and 44.9 percent muscle mass.

Aplicación de un modelo matemático al taper en jóvenes nadadores / Applying a mathematical model to taper in young swimmers

Ante una competición importante, la dosis de entrenamiento debe reducirse con la intención de mejorar el rendimiento. El presente estudio tiene por objetivo determinar los efectos de la aplicación de un modelo matemático durante la reducción progresiva no lineal de la carga de entrenamientoo taper en jóvenes nadadores. Diez nadadores fueron testados antes y después del taper. Las variables utilizadas para el control fueron el volumen de entrenamiento, la relación entre volumen e intensidad media de entrenamiento en una temporada (MITS) y la frecuencia de entrenamiento. La disminución del volumen de entrenamiento tras aplicar el modelo matemático resultó en la primera semana del 30,9%, y en la segunda semana del 71,2%. La disminución de los MITS tras aplicar el modelo matemático tuvo un resultado en la primera semana del 30,8%, y en la segunda semana del 71,1%. La frecuencia de entrenamiento se disminuyó un 10% en la primera semana, y hasta el 40% en la segunda semana. Las marcas obtenidas entre el primer y el segundo tests fueron significativamente mejores para el segundo (p < 0,05). El lactato máximo también se modificó de manera significativa (p < 0,05), a diferencia del lactato mínimo, en el que no se detectaron diferencias. La correlación entre lactato máximo y la marca obtenida resultó significativa (p < 0,05). El valor de la percepción subjetivo del esfuerzo (RPE), tras aplicar el modelo matemático, disminuyó, aunque no significativamente(p > 0,05). Estos datos indican que el taper propuesto no provoca pérdidas de sensaciones ni de entrenamiento, pues las marcas obtenidas mejoraron de forma significativa, al igual que lo hizo el lactato máximo, lo que demuestra una clara correlación entre lactato máximo y marca (AU)

Before an important competition, the training dose should be reduced with the intention of improving the performance. This study aims to determine the impact of the implementation of a mathematical model during the non-linear, progressive reduction of the training load or taper in young swimmers. Ten swimmers were tested before and after the taper. The control variables measured during the training were the volume, the relationship between the volume and the mean intensity of training season (MITS) and the frequency of training. The decrease in the volume of training after applying the mathematical model was of 30.9% in the first week, and of 71.2% in the second week. The decrease in MITS after applying the mathematical model was of 30.8% in the first week, and of 71.1% in the second week. The training frequency was decreased by 10% in the first week, and up to 40% in the second week. The records obtained between the first and the second tests were significantly better (p < 0.05). The maximum lactate production also increased significantly (p < 0.05), unlike the speed of lactate clarifying that it did not. The correlation between lactate and the maximum mark obtained was significant (p < 0.05). The value SPE (subjective perception of effort)after applying the mathematical model decreased, but not significantly (p > 0.05). These data indicate that the taper proposed does not cause loss of sensation or training, since the records improved significantly, as did the maximum production of lactate, showing a high correlation between maximum lactate and record (AU)

Conserved and novel miRNAs in the legume Phaseolus vulgaris in response to stress.

MicroRNAs (miRNAs) are small RNA molecules recognized as important regulators of gene expression. Although plant miRNAs have been extensively studied in model systems, less is known in other plants with limited genome sequence data. We are interested in the identification of miRNAs in Phaseolus vulgaris (common bean) to uncover different plant strategies to cope with adverse conditions and because of its relevance as a crop in developing countries. Here we present the identification of conserved and candidate novel miRNAs in P. vulgaris present in different organs and growth conditions, including drought, abscisic acid treatment, and Rhizobium infection. We also identified cDNA sequences in public databases that represent the corresponding miRNA precursors. In addition, we predicted and validated target mRNAs amongst reported EST and cDNAs for P. vulgaris. We propose that the novel miRNAs present in common bean and other legumes, are involved in regulation of legume-specific processes including adaptation to diverse external cues.