Analyses and Insights into Genetic Reassortment and Natural Selection as Key Drivers of Piscine orthoreovirus Evolution.

Piscine orthoreovirus (PRV) is a pathogen that causes heart and skeletal muscle inflammation in Salmo salar and has also been linked to circulatory disorders in other farmed salmonids, such as Oncorhynchus kisutch and Oncorhynchus mykiss. The virus has a segmented, double-stranded RNA genome, which makes it possible to undergo genetic reassortment and increase its genomic diversity through point mutations. In this study, genetic reassortment in PRV was assessed using the full genome sequences available in public databases. This study used full genome sequences that were concatenated and genome-wide reassortment events, and phylogenetic analyses were performed using the recombination/reassortment detection program version 5 (RDP5 V 5.5) software. Additionally, each segment was aligned codon by codon, and overall mean distance and selection was tested using the Molecular Evolutionary Genetics Analysis X software, version 10.2 (MEGA X version 10.2). The results showed that there were 17 significant reassortment events in 12 reassortant sequences, involving genome exchange between low and highly virulent genotypes. PRV sequences from different salmonid host species did not appear to limit the reassortment. This study found that PRV frequently undergoes reassortment events to increase the diversity of its segmented genome, leading to antigenic variation and increased virulence. This study also noted that to date, no reassortment events have been described between PRV-1 and PRV-3 genotypes. However, the number of complete genomic sequences within each genotype is uneven. This is important because PRV-3 induces cross-protection against PRV-1, making it a potential vaccine candidate.

Whipple's cephalic pancreaticoduodenectomy versus pyloric-preserving pancreaticoduodenectomy. Retrospective study.

INTRODUCTION: Controversy exists in the literature as to the best technique for pancreaticoduodenectomy (PD), whether pyloric preservation (PP-CPD) or Whipple's technique (with antrectomy [W-CPD]), the former being associated with a higher frequency of delayed gastric emptying (DGE). METHODS: Retrospective and comparative study between PP-CPD technique (n = 124 patients) and W-CPD technique (n = 126 patients), in patients who were operated for tumors of the pancreatic head and periampullary region between the period 2012 and 2023. RESULTS: Surgical time was longer, although not significant, with the W-CPD technique. Pancreatic and peripancreatic tumor invasion (p = 0.031) and number of lymph nodes resected (p < 0.0001) reached statistical significance in W-CPD, although there was no significant difference between the groups in terms of lymph node tumor invasion. Regarding postoperative morbimortality (medical complications, postoperative pancreatic fistula [POPF], hemorrhage, RVG, re-interventions, in-hospital mortality, Clavien-Dindo complications), ICU and hospital stay, no statistically significant differences were observed between the groups. During follow-up, no significant differences were observed between the groups for morbidity and mortality at 90 days and survival at 1, 3 and 5 years. Binary logistic regression analysis for DGE showed that binary relevant POPF grade B/C was a significant risk factor for DGE. CONCLUSIONS: Postoperative morbidity and mortality and long-term survival were not significantly different with PP-CPD and W-CPD, but POPF grade B/C was a risk factor for DGE grade C.

Buccopharyngeal route administered high polyphenolic olive oil and COVID-19: A pilot clinical trial.

INTRODUCTION: Waning immunity after vaccination justifies the need for additional effective COVID-19 treatments. Immunomodulation of local immune response at the oropharyngeal mucosa could hypothetically activate mucosal immunity, which can prevent SARS-CoV-2 main immune evasion mechanisms in early stages of the disease and send an effective warning to other components of immune system. Olive polyphenols are biologically active compounds with immunomodulatory activity. There are previous studies based on immunomodulation with olive polyphenols and respiratory infections using an enteral route, which point to potential effects on time to resolution of symptoms. The investigators sought to determine whether participants following immunomodulation with tiny quantities of high polyphenolic olive oil administered through an oromucosal route could have a better outcome in COVID-19. SUMMARY: This pilot clinical trial investigated the effect of buccopharyngeal administered high polyphenolic olive oil on COVID-19 incidence, duration, and severity. IMPORTANCE: Waning immunity after vaccination justifies the need of further research for additional effective treatments for COVID-19. OBJECTIVE: Immunomodulation of local immune response at the buccopharyngeal mucosa could hypothetically activate mucosal immunity, which would in turn difficult SARS-CoV-2 immune evasion mechanisms in early stages of the disease and send an effective warning to other components of immune system. Olive polyphenols are biologically active compounds with immunomodulatory activity. There are previous studies based on immunomodulation with olive polyphenols and respiratory infections, using an enteral route, which suggest potential shortening of time to resolution of symptoms. The investigators sought to determine whether participants following immunomodulation with tiny quantities of high polyphenolic olive oil administered through an oromucosal route could have a better outcome in COVID-19. DESIGN, SETTING, AND PARTICIPANTS: Double blind, randomized pilot clinical trial conducted at a single site, Talavera de la Reina, Spain. Potential study participants were identified by simple random sampling from the epidemiological database of contact patients recently diagnosed of COVID-19 during the study period. A total of 88 adult participants were enrolled and 84 completed the 3-month study, conducted between July 1, 2021 and August 31, 2022. INTERVENTION: Participants were randomized to receive oromucosal administered high polyphenolic olive oil, 2 mL twice a day for 3 months or no treatment. MAIN OUTCOME AND MEASURES: Primary outcomes were incidence, duration, and severity of COVID-19 after intervention. RESULTS: There were no differences in incidence between both groups but there were significant differences in duration, the median time to resolution of symptoms was 3 days in the high polyphenolic olive oil group compared with 7 days in the no-treatment group. Although time to resolution is directly related to severity, this study did not find any differences in severity. CONCLUSION AND RELEVANCE: Among full-vaccinated adults recent infected with COVID-19, a daily intake of tiny quantities of oromucosal administered high polyphenolic olive oil before infection significantly improved the time to symptom resolution. This finding strongly support the appropriateness of further deep research on the use of oromucosal administered high polyphenolic olive oil as an effective immune strategy against COVID-19.

Duodenopancreatectomía cefálica en pacientes octogenarios con tumores de páncreas / Cephalic duodenopancreatectomy in octogenarium patients with pancreatic tumors

Introducción: Según estudios previos, la duodenopancreatectomía cefálica (DPC) por cáncer de páncreas (CP) se asocia a un incremento de la supervivencia mediana tanto en pacientes octogenarios como en pacientes de menor edad. Métodos: Estudio retrospectivo y comparativo de la DPC realizada en 30 pacientes≥80 años con CP y en 159 pacientes<80 años. Resultados: Los pacientes octogenarios presentaban una tasa significativamente mayor de morbilidad cardiovascular preoperatoria y un comportamiento tumoral más agresivo (mayor anemia, ictericia y CA 19-9 preoperatorios, invasión vascular y neural y menor frecuencia de resección R0 a pesar de utilizar la misma técnica quirúrgica). No hubo diferencias significativas en cuanto a complicaciones postoperatorias. La mortalidad postoperatoria fue similar en ambos grupos (3,3% en octogenarios versus 3,1% en <80 años). Las causas de mortalidad durante el seguimiento fueron fundamentalmente por recidiva tumoral, complicaciones cardiovasculares y COVID-19 (2 octogenarios). La supervivencia actuarial a 1, 3 y 5 años fue significativamente mayor en pacientes <80 años que en octogenarios (el 85,9%, el 61,1% y el 39,2% versus el 72,7%, el 28,9% y el 9,6%, respectivamente; p=0,001). En el estudio multivariable, la presencia de una fístula pancreática y la no utilización de tutor externo del Wirsung influyeron de forma estadísticamente significativa sobre la mortalidad a 90 días post-DPC. Conclusiones: La morbimortalidad post-DPC es similar en octogenarios y <80 años, aunque la supervivencia a largo plazo es menor por la agresividad tumoral y comorbilidad asociada a la edad avanzada. (AU)

Introduction: Current literature supports the claim that performing a cephalic pancreaticoduodenectomy (CPD) as treatment for pancreatic cancer (PC) is associated with an increase in median survival, both in octogenarian (≥80 years) patients as well as younger patients. Methods: This is a retrospective and comparative trial, comparing results for CPD performed on 30 patients ≥80 years with PC and 159 patients <80 years. Results: The patients in the octogenarian group showed a significantly higher rate of preoperative cardiovascular morbidity and a more aggressive tumoral behaviour, including more significant preoperative anemia, jaundice and levels of CA 19-9, higher vascular and neural invasion, and a lower rate of R0 resection despite using the same surgical technique. There were no significant differences in terms of postoperative complications. Postoperative mortality was similar in both groups (3.3% in octogenarians vs. 3.1% in patients <80 years). Mortality during follow-up was mainly due to tumour recurrence, cardiovascular complications and COVID-19 in 2elderly patients. Actuarial survival at 1, 3 and 5 years was significantly larger for patients <80 years old, as compared to octogenarians (85.9%, 61.1% and 39.2% versus 72.7%, 28.9% and 9.6%, respectively; P=0.001). The presence of a pancreatic fistula and not using external Wirsung stenting were significantly associated with 90-day postoperative mortality after a CPD. Conclusions: Morbidity and mortality post-CPD is similar in octogenarians and patients younger than 80, although long-term survival is shorter due to more aggressive tumours and comorbidities associated with older age. (AU)

Cephalic pancreatoduodenectomy in octogenarian patients with pancreatic tumors.

INTRODUCTION: Current literature supports the claim that performing a cephalic pancreaticoduodenectomy (CPD) as treatment for pancreatic cancer (PC) is associated with an increase in median survival, both in octogenarian (≥80 years) patients as well as younger patients. METHODS: This is a retrospective and comparative trial, comparing results for CPD performed on 30 patients ≥80 years with PC and 159 patients <80 years. RESULTS: The patients in the octogenarian group showed a significantly higher rate of preoperative cardiovascular morbidity and a more aggressive tumoral behaviour, including more significant preoperative anemia, jaundice and levels of CA 19-9, higher vascular and neural invasion, and a lower rate of R0 resection despite using the same surgical technique. There were no significant differences in terms of postoperative complications. Postoperative mortality was similar in both groups (3.3% in octogenarians vs 3.1% in patients <80 years). Mortality during follow-up was mainly due to tumour recurrence, cardiovascular complications and COVID-19 in 2 elderly patients. Actuarial survival at 1, 3 and 5 years was significantly larger for patients <80 years old, as compared to octogenarians (85.9%, 61.1% and 39.2% versus 72.7%, 28.9% and 9.6%, respectively; P = 0.001). The presence of a pancreatic fistula and not using external Wirsung stenting were significantly associated with 90-day postoperative mortality after a CPD. CONCLUSIONS: Morbidity and mortality post-CPD is similar in octogenarians and patients younger than 80, although long-term survival is shorter due to more aggressive tumours and comorbidities associated with older age.

An update on neurobiological mechanisms involved in the development of chemotherapy-induced cognitive impairment (CICI).

Cancer is the second leading cause of death worldwide despite efforts in early diagnosis of the disease and advances in treatment. The use of drugs that exert toxic effects on tumor cells or chemotherapy is one of the most widely used treatments against cancer. However, its low toxic selectivity affects both healthy cells and cancer cells. It has been reported that chemotherapeutic drugs may generate neurotoxicity that induces deleterious effects of chemotherapy in the central nervous system. In this sense, patients report decreased cognitive abilities, such as memory, learning, and some executive functions after chemotherapy. This chemotherapy-induced cognitive impairment (CICI) develops during treatment and persists even after chemotherapy. Here we present a review of the literature on the main neurobiological mechanisms involved in CICI using a Boolean formula following the steps of the PRISMA guidelines that were used to perform statements searches in various databases. The main mechanisms described in the literature to explain CRCI include direct and indirect mechanisms that induce neurotoxicity by chemotherapeutic agents. Therefore, this review provides a general understanding of the neurobiological mechanisms of CICI and the possible therapeutic targets to prevent it..

Colocolic intussusception by lipoma in transverse colon. A cause of intestinal obstruction.

Lipomas in the colon usually present as sessile polypoid masses, rarely pedunculated, with variable dimensions. They are generally asymptomatic and diagnosed incidentally although occasionally they may debut with symptoms. We present the case of a 48-year-old male with intestinal obstruction secondary to colonic lipoma causing invagination at the level of the transverse colon.

CCNE1 and PLK1 Mediate Resistance to Palbociclib in HR+/HER2- Metastatic Breast Cancer.

PURPOSE: In hormone receptor-positive (HR+)/HER2- metastatic breast cancer (MBC), it is imperative to identify patients who respond poorly to cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) and to discover therapeutic targets to reverse this resistance. Non-luminal breast cancer subtype and high levels of CCNE1 are candidate biomarkers in this setting, but further validation is needed. EXPERIMENTAL DESIGN: We performed mRNA gene expression profiling and correlation with progression-free survival (PFS) on 455 tumor samples included in the phase III PEARL study, which assigned patients with HR+/HER2- MBC to receive palbociclib+endocrine therapy (ET) versus capecitabine. Estrogen receptor-positive (ER+)/HER2- breast cancer cell lines were used to generate and characterize resistance to palbociclib+ET. RESULTS: Non-luminal subtype was more prevalent in metastatic (14%) than in primary tumor samples (4%). Patients with non-luminal tumors had median PFS of 2.4 months with palbociclib+ET and 9.3 months with capecitabine; HR 4.16, adjusted P value < 0.0001. Tumors with high CCNE1 expression (above median) also had worse median PFS with palbociclib+ET (6.2 months) than with capecitabine (9.3 months); HR 1.55, adjusted P value = 0.0036. In patients refractory to palbociclib+ET (PFS in the lower quartile), we found higher levels of Polo-like kinase 1 (PLK1). In an independent data set (PALOMA3), tumors with high PLK1 show worse median PFS than those with low PLK1 expression under palbociclib+ET treatment. In ER+/HER2- cell line models, we show that PLK1 inhibition reverses resistance to palbociclib+ET. CONCLUSIONS: We confirm the association of non-luminal subtype and CCNE1 with resistance to CDK4/6i+ET in HR+ MBC. High levels of PLK1 mRNA identify patients with poor response to palbociclib, suggesting PLK1 could also play a role in the setting of resistance to CDK4/6i.

Trophic ecology of juvenile bull sharks (Carcharhinus leucas) in the Coyote estuary, Costa Rica.

Bull shark (Carcharhinus leucas) is a near-threatened elasmobranch species capable of moving between the fresh and salty waters of tropical and subtropical coastal areas, for which we still lack important ecological information. During their first years of life, bull sharks use estuarine systems as nursery areas, making them highly susceptible to environmental and anthropogenic pressures. We studied the trophic ecology of juveniles found in the Coyote estuary, a potential nursery area in Costa Rica, to understand the potential impact of further bull shark declines and gain knowledge that could aid in their conservation. We analysed the trophic ecology of juvenile bull sharks [81-103 cm total length (TL)] in the Coyote estuary, Costa Rica, using stable isotopes of δ15 N and δ13 C. Since one problem using this technique in juveniles is the confounding effect of the maternal signature, we sampled different tissues (muscle and plasma), verified the status of the shark's umbilical scar and identified the size at which the isotope signature is a result of the animal's current diet. The isotopic values of the muscle tissue reflected the maternal isotopic signature. In contrast, plasma values reflected the diet of juvenile bull sharks >95 cm TL and with a closed umbilical scar. Juvenile bull sharks fed primarily on teleost fishes of the order Anguilliformes and Siluriformes, and have a high trophic position (≥4.0) in the Coyote estuary. Our findings suggest that this estuary is an important feeding site for juvenile bull sharks of the Pacific of Costa Rica. Thus, the protection of essential habitats such as the Coyote estuary will benefit not only bull shark conservation, but also the conservation of an array of fish species that also use this habitat as a rookery, many of which are of commercial interest.

Overall survival with palbociclib plus endocrine therapy versus capecitabine in postmenopausal patients with hormone receptor-positive, HER2-negative metastatic breast cancer in the PEARL study.

BACKGROUND: An earlier analysis of the PEARL phase III study showed that palbociclib plus endocrine therapy (ET) does not improve progression-free survival (PFS) over capecitabine in aromatase inhibitor-resistant, hormone receptor-positive/human epidermal growth factor receptor 2-negative metastatic breast cancer (MBC) patients. Here, we report the final overall survival (OS) analysis. METHODS: Postmenopausal patients (N = 601) were randomized 1:1 to capecitabine or palbociclib plus ET (exemestane, Cohort 1; fulvestrant, Cohort 2). OS was analysed in Cohort 2, the wild-type ESR1 population and the overall population. Additionally, we analysed subsequent systemic therapies and explored PFS2 (time from randomization to the end of the first subsequent therapy/death). RESULTS: OS was 31.1 months for palbociclib plus fulvestrant and 32.8 months for capecitabine (adjusted hazard ratio [aHR] 1.10, 95% confidence interval [CI] 0.81-1.50, P = 0.550). In the wild-type ESR1 population, OS was 37.2 months for palbociclib plus ET and 34.8 months for capecitabine (aHR 1.06, 95% CI 0.81-1.37, P = 0.683). In OS analyses, no subgroup showed superiority for palbociclib plus ET over capecitabine. OS in the overall population was 32.6 months for palbociclib plus ET and 30.9 months for capecitabine (P = 0.995). Subsequent systemic therapy was given to 79.8% and 82.9% of patients with palbociclib plus ET and capecitabine, respectively. Median PFS2 was similar between study arms (Cohort 2, P = 0.941; wild-type ESR1 population, P = 0.827). No new safety findings were observed. CONCLUSIONS: Palbociclib plus ET did not show a statistically superior OS compared to capecitabine in MBC patients progressing on aromatase inhibitors. TRIAL REGISTRATION: NCT02028507 (ClinTrials.gov), 2013-003170-27 (EudraCT).

Health-related quality of life with palbociclib plus endocrine therapy versus capecitabine in postmenopausal patients with hormone receptor-positive metastatic breast cancer: Patient-reported outcomes in the PEARL study.

BACKGROUND: The PEARL study showed that palbociclib plus endocrine therapy (palbociclib/ET) was not superior to capecitabine in improving progression-free survival in postmenopausal patients with metastatic breast cancer resistant to aromatase inhibitors, but was better tolerated. This analysis compared patient-reported outcomes. PATIENTS AND METHODS: The PEARL quality of life (QoL) population comprised 537 patients, 268 randomised to palbociclib/ET (exemestane or fulvestrant) and 269 to capecitabine. Patients completed the European Organisation for Research and Treatment of Cancer QLQ-C30 and QLQ-BR23 and EQ-5D-3L questionnaires. Changes from the baseline and time to deterioration (TTD) were analysed using linear mixed-effect and stratified Cox regression models, respectively. RESULTS: Questionnaire completion rate was high and similar between treatment arms. Significant differences were observed in the mean change in global health status (GHS)/QoL scores from the baseline to cycle 3 (2.9 for palbociclib/ET vs. -2.1 for capecitabine (95% confidence interval [CI], 1.4-8.6; P = 0.007). The median TTD in GHS/QoL was 8.3 months for palbociclib/ET versus 5.3 months for capecitabine (adjusted hazard ratio, 0.70; 95% CI, 0.55-0.89; P = 0.003). Similar improvements for palbociclib/ET were also seen for other scales as physical, role, cognitive, social functioning, fatigue, nausea/vomiting and appetite loss. No differences were observed between the treatment arms in change from the baseline in any item of the EQ-5D-L3 questionnaire as per the overall index score and visual analogue scale. CONCLUSION: Patients receiving palbociclib/ET experienced a significant delay in deterioration of GHS/QoL and several functional and symptom scales compared with capecitabine, providing additional evidence that palbociclib/ET is better tolerated. TRIAL REGISTRATION NUMBER: NCT02028507 (ClinTrials.gov). EUDRACT STUDY NUMBER: 2013-003170-27.

Duodenopancreatectomía cefálica y tutorización externa del conducto de Wirsung. Resultados de una serie de 80 casos consecutivos / Pancreaticoduodenectomy and external Wirsung stenting: our outcomes in 80 cases

Introducción: Existe controversia respecto a la técnica ideal de reconstrucción pancreático-yeyunal posresección duodeno-pancreática. La tutorización externa del Wirsung se ha considerado por muchos autores como una técnica con menor incidencia de fístulas y morbimortalidad. Analizamos nuestra experiencia con esta técnica. Pacientes y métodos: Análisis retrospectivo de la morbimortalidad, de una serie de 80 pacientes consecutivos intervenidos, durante 6,5 años, por tumores pancreáticos cefálicos o periampulares realizando resección y pancreático-yeyunostomía con tutorización externa del Wirsung. Resultados: La edad media de los pacientes fue 68,3 ± 9 años y la tasa de resecabilidad del 78%. La consistencia del páncreas era blanda en 51,2% de pacientes y dura en 48,8%. Se preservó el píloro en 43,8%. El tumor más frecuente fue el adenocarcinoma (68,8%) y se consiguió un R0 en 70%. La fístula bioquímica se presentó en 11,2%, la fístula pancreática grado B en 12,5% y la C en 2,5%, mientras que la tasa de reintervención abdominal fue del 10%. La mediana de estancia hospitalaria fue de 16 días y la mortalidad postoperatoria y a 90 días fue del 2,5%. La tasa de retraso del vaciamiento gástrico fue del 36,3%, diabetes de novo del 12,5% e insuficiencia exocrina del 30%. La supervivencia a uno, tres y cinco años fue 80,2, 53,6 y 19,2%. Conclusiones: Aunque nuestras tasas de morbimortalidad con la tutorización externa del Wirsung son bajas, coincidiendo con series más amplias recientemente publicadas, se precisa un análisis comparativo con otras técnicas reconstructivas, con más casos, para elegir la mejor opción después de una duodenopancreatectomía cefálica. (AU)

Introduction: There is controversy regarding the ideal pancreaticojejunostomy technique after pancreaticoduodenectomy. Many authors consider the external Wirsung stenting technique to be associated with a low incidence of fistula, morbidity and mortality. We analyse our experience with this technique. Patients and methods: A retrospective analysis of the morbidity and mortality of a series of 80 consecutive patients who had been treated surgically over a 6.5-year period for pancreatic head or periampullary tumors, performing pancreaticoduodenectomy and pancreaticojejunostomy with external Wirsung duct stenting. Results: Mean patient age was 68.3 ± 9 years, and the resectability rate was 78%. The texture of the pancreas was soft in 51.2% of patients and hard in 48.8%. Pylorus-preserving resection was performed in 43.8%. Adenocarcinoma was the most frequent tumor (68.8%), and R0 was confirmed in 70% of patients. Biochemical fistula was observed in 11.2%, pancreatic fistula grade B in 12.5% and C in 2.5%, whereas the abdominal reoperation rate was 10%. Median postoperative hospital stay was 16 days, and postoperative and 90-day mortality was 2.5%. Delayed gastric emptying was observed in 36.3% of patients, de novo diabetes in 12.5%, and exocrine insufficiency in 3. Patient survival rates after 1, 3 and 5 years were 80.2, 53.6 and 19.2%, respectively. Conclusions: Although our low rates of postoperative complications and mortality using external Wirsung duct stenting coincides with other more numerous recent series, it is necessary to perform a comparative analysis with other techniques, including more cases, to choose the best reconstruction technique after pancreaticoduodenectomy. (AU)

Pancreaticoduodenectomy and external Wirsung stenting: Our outcomes in 80 cases.

INTRODUCTION: There is controversy regarding the ideal pancreaticojejunostomy technique after pancreaticoduodenectomy. Many authors consider the external Wirsung stenting technique to be associated with a low incidence of fistula, morbidity and mortality. We analyse our experience with this technique. PATIENTS AND METHODS: A retrospective analysis of the morbidity and mortality of a series of 80 consecutive patients who had been treated surgically over a 6.5-year period for pancreatic head or periampullary tumors, performing pancreaticoduodenectomy and pancreaticojejunostomy with external Wirsung duct stenting. RESULTS: Mean patient age was 68.3 ± 9 years, and the resectability rate was 78%. The texture of the pancreas was soft in 51.2% of patients and hard in 48.8%. Pylorus-preserving resection was performed in 43.8%. Adenocarcinoma was the most frequent tumor (68.8%), and R0 was confirmed in 70% of patients. Biochemical fistula was observed in 11.2%, pancreatic fistula grade B in 12.5% and C in 2.5%, whereas the abdominal reoperation rate was 10%. Median postoperative hospital stay was 16 days, and postoperative and 90-day mortality was 2.5%. Delayed gastric emptying was observed in 36.3% of patients, de novo diabetes in 12.5%, and exocrine insufficiency in 3. Patient survival rates after 1, 3 and 5 years were 80.2%, 53.6% and 19.2%, respectively. CONCLUSIONS: Although our low rates of postoperative complications and mortality using external Wirsung duct stenting coincides with other more numerous recent series, it is necessary to perform a comparative analysis with other techniques, including more cases, to choose the best reconstruction technique after pancreaticoduodenectomy.

Is acute lymphoblastic leukemia with mature B-cell phenotype and KMT2A rearrangements a new entity? A systematic review and meta-analysis.

The association between mature B-cell phenotype and KMT2A rearrangements in acute lymphoblastic leukemia is a very rare finding. It identifies a group of patients with similar clinical and biological characteristics that clearly differs from the entity B-cell lymphoblastic leukemia/lymphoma with t(v;11q23)/KMT2A-rearranged, which typically presents an immature pro B-cell phenotype. We describe the clinical-biological characteristics and disease outcome of three pediatric ALL patients with these features treated at our institution, and review 28 cases described in the literature. Most cases occur in children under 2 years-old, presenting a mature B-cell phenotype that uniformly expresses cytoplasmic and surface IgM with lambda light chain restriction, with heterogeneous co-expression of immaturity antigens. Patients do not have MYC rearrangements and all show KMT2A abnormalities, with 76% presenting t(9;11)(p21;q23)/MLLT3-KMT2A. These patients have an unfavorable clinical outcome and a 48% relapse rate. In-depth knowledge of this disease entity is needed to improve outcome.

Analysis of Nostoc muscorum biomass production in a hydroponic system / Análisis de la producción de biomasa de Nostoc muscorum en sistema hidropónico / Análise da produção de biomassa de Nostoc muscorum num sistema hidropônico

Abstract Nostoc is a genus of filamentous cyanobacteria with biotechnological applications in human nutrition, biomedicine, biofertilization and commercial production of biofuels. However, the low growth rate in liquid medium due to its periphytic nature and its tendency to form biofilms, limits its large-scale production. Therefore, the aim of this study was to evaluate the biomass production of Nostoc muscorum in a modified hydroponic system. Cultures of N. muscorum were made by triplicate, in a hydroponic system under semicontrolled conditions of temperature (29 ± 13 °C), light intensity (32 ± 54 µmol/m2/s) and photoperiod (12 hours), for a total of 23 days inside a greenhouse. Temperature, pH, conductivity and dry biomass production were monitored on alternating days. The results showed that the maximum dry biomass production was 0.2276 ± 0.0114 g/m2/day, and the average productivity was 0.4149 ± 0.0207 g/m2/day. The maximum biomass production of N. muscorum was achieved on day thirteen with 0.3185 ± 0.0159 g/m2/day. The correlation statistical analysis of environmental variables did not show significant differences; thus, temperature, pH and electrical conductivity did not affect the biomass production of N. muscorum. Consequently, the algal growth was influenced by the species physiology only. The support used in the hydroponic system allowed the adhesion and development of the algae mucilaginous layer without requiring drying periods as in conventional crops. The hydroponic system provided a continuous flow of nutrients hat could prevent the attack of opportunistic bacteria and fungi, generating a high growth rate of N. muscorum. The hydroponic system represents a viable alternative for the production of N. muscorum biomass under greenhouse conditions at large scale.

Resumen Nostoc es un género de cianobacterias filamentosas con aplicaciones biotecnológicas en nutrición humana, biomedicina, biofertilización y producción comercial de biocombustibles. Sin embargo, su baja tasa de crecimiento en medio líquido por su naturaleza perifítica y su tendencia a formar biofilms, limita su producción a gran escala. Por lo tanto, el objetivo de este estudio fue analizar la producción de biomasa de Nostoc muscorum en un sistema hidropónico modificado. Para ello, se realizaron cultivos de N. muscorum por triplicado, en un sistema hidropónico bajo condiciones semicontroladas de temperatura (29 ± 13°C), intensidad lumínica (32 ± 54 µmol/m2/s) y fotoperiodo (12 horas), durante 23 días en un invernadero. La temperatura, el pH, la conductividad eléctrica y la producción de biomasa seca, fueron monitoreados en días alternados. Los resultados arrojaron que la producción máxima de biomasa seca fue de 0.2276 ± 0.0114 g/m2/día, y la productividad promedio fue de 0.4149 ± 0.0207 g/m2/día. A su vez, la producción máxima de biomasa de N. muscorum se obtuvo el día trece con 0.3185 ± 0.0159 g/m2/día. El análisis estadístico de correlación de variables ambientales no arrojó diferencias significativas, por lo que la temperatura, el pH y la conductividad eléctrica no afectaron la producción de biomasa de N. muscorum. Consecuentemente, el crecimiento algal fue influenciado por la fisiología de la especie. El soporte empleado en el sistema hidropónico permitió la adherencia y el desarrollo de la capa mucilaginosa de la cianobacteria sin requerir períodos de desecación como en los cultivos convencionales. El sistema hidropónico proporcionó un flujo continuo de nutrientes que podría prevenir el ataque de bacterias y hongos oportunistas, generando una alta tasa de crecimiento. De este modo, este sistema hidropónico representa una alternativa viable para la producción de biomasa de N. muscorum en condiciones de invernadero a gran escala.

Resumo Nostoc é um gênero de cianobactérias filamentosas com aplicações biotecnológicas em nutrição humana, biomedicina, biofertilização e produção comercial de biocombustíveis. Entretanto, sua baixa taxa de crescimento em meio líquido, devido à sua natureza perifítica e sua tendência a formar biofilmes, limita sua produção em larga escala. Portanto, o objetivo deste estudo foi analisar a produção de biomassa de Nostoc muscorum num sistema hidropônico modificado. Para isso, foram realizadas culturas de N. muscorum em triplicata num sistema hidropônico sob temperatura (29 ± 13°C) e intensidade da luz (32 ± 54 µmol/m2 /s) semicontroladas com fotoperíodo de 12 horas durante 23 dias numa estufa. A temperatura, o pH, a condutividade elétrica e a biomassa seca foram monitorados em dias alternados. Os resultados mostraram que a produção máxima de biomassa seca foi de 0,2276 ± 0,0114 g/m2 /dia e a produtividade média foi de 0,4149 ± 0,0207 g/ m2 /dia. No entanto, a produção máxima de biomassa de N. muscorum foi obtida no dia treze com 0,3185 ± 0,0159 g/m / dia. A análise estatística da correlação de variáveis ambientais não mostrou nenhuma diferença significativa, de modo que a temperatura, o pH e a condutividade eléctrica não afetaram a produção de biomassa de N. muscorum e o crescimento foi influenciado pela fisiologia da espécie. O suporte utilizado permitiu a adesão e desenvolvimento da camada mucilaginosa das algas sem a necessidade de períodos de secagem como nas culturas convencionais. O sistema hidropônico proporcionou um fluxo contínuo de nutrientes que impede o ataque de bactérias e fungos oportunistas, gerando uma alta taxa de crescimento. Portanto, este sistema hidropônico representa uma alternativa viável para a produção de biomassa de N. muscorum em larga escala sob condições de estufa.

Role of Connexins 30, 36, and 43 in Brain Tumors, Neurodegenerative Diseases, and Neuroprotection.

Gap junction (GJ) channels and their connexins (Cxs) are complex proteins that have essential functions in cell communication processes in the central nervous system (CNS). Neurons, astrocytes, oligodendrocytes, and microglial cells express an extraordinary repertory of Cxs that are important for cell to cell communication and diffusion of metabolites, ions, neurotransmitters, and gliotransmitters. GJs and Cxs not only contribute to the normal function of the CNS but also the pathological progress of several diseases, such as cancer and neurodegenerative diseases. Besides, they have important roles in mediating neuroprotection by internal or external molecules. However, regulation of Cx expression by epigenetic mechanisms has not been fully elucidated. In this review, we provide an overview of the known mechanisms that regulate the expression of the most abundant Cxs in the central nervous system, Cx30, Cx36, and Cx43, and their role in brain cancer, CNS disorders, and neuroprotection. Initially, we focus on describing the Cx gene structure and how this is regulated by epigenetic mechanisms. Then, the posttranslational modifications that mediate the activity and stability of Cxs are reviewed. Finally, the role of GJs and Cxs in glioblastoma, Alzheimer's, Parkinson's, and Huntington's diseases, and neuroprotection are analyzed with the aim of shedding light in the possibility of using Cx regulators as potential therapeutic molecules.

Chlorella, ¿un potencial biofertilizante? / Chlorella, a potential biofertilizer? / Chlorella, um potencial biofertilizante?

Resumen Las microalgas son organismos fotoautótrofos con un rápido crecimiento y la habilidad de adaptarse a diversos ambientes. Convierten el dióxido de carbono en biomasa y debido a esto, se considera que tienen gran potencial biotecnológico. La biomasa algal puede usarse en la industria alimenticia y de compuestos bioactivos, en la producción de biocombustibles, en la bioremediación y biofertilización. Como biofertilizantes, las microalgas clorofitas y cianofitas, producen polisacáridos (mucílago) que pueden evitar la erosión, mejorar la estructura y el contenido de material orgánica de los suelos, y aumentar la concentración de iones en los cultivos. Reduciendo de esta forma la necesidad de fertilizantes químicos convencionales. El uso de estas microalgas como biofertilizantes se denomina algalización. Durante este proceso se usan principalmente clorofitas por su alta tasa de crecimiento, la facilidad de su cultivo a gran escala, y su adaptación a las condiciones del suelo. El género Chlorella es de gran interés porque diversos estudios han mostrado que puede ayudar en la fijación del nitrógeno, mejorar las propiedades físicas y químicas del suelo, y producir sustancias que promueven el desarrollo de la planta y el control de infecciones. Por esta razón, las microalgas del género Chlorella representan una alternativa viable para la biofertilización, generando beneficios no solo para la producción agrícola sino también para el medio ambiente.

Abstract Microalgae are photoautotrophic organisms with fast growth and the ability to adapt to different environments. They convert carbon dioxide into biomass and are considered to have great biotechnological potential because of it. Algal biomass can be used in food and bioactive compounds industry, in biofuels production, in bioremediation and biofertilization. As biofertilizers, chlorophytes and cyanophytes microalgae produce polysaccharides (mucilage) that can avoid erosion, improve the structure and organic matter content in the soil, and increase the ions concentration for crop plants. Thus, reducing the need for conventional crop chemical fertilizers. The use of this microalgae as biofertilizers is called algalization. Algalization uses mainly chlorophytes due to their high growth rate, their simple large scale cultivation, and their adaptation to soil conditions. Chlorella genus is of special interest because research has shown that it can help with nitrogen fixation, improve physical and chemical properties of the soil, and produce substances that can promote plant development and infections control. Therefore, microalgae from Chlorella genus are a viable alternative for biofertilization, generating benefits for agricultural production and the environment.

Resumo As microalgas são organismos fotoautotróficos com crescimento rápido e capacidade de adaptação a diferentes ambientes. Eles convertem dióxido de carbono em biomassa e, por isso, são considerados com um grande potencial biotecnológico. A biomassa de algas pode ser usada na indústria alimentar e de compostos bioactivos, na produção de biocombustíveis, na biorremediação e biofertilização. Como biofertilizantes, as microalgas clorófitas e cianófitas produzem polissacarídeos (mucilagem) que podem evitar a erosão, melhorar a estrutura e o conteúdo de matéria orgânica do solo, e aumentar a concentração de iões nas culturas, reduzindo assim a necessidade de fertilizantes químicos convencionais. O uso dessas microalgas como biofertilizantes é chamado de algalização. Durante este processo, usam-se eles ​​principalmente clorofíceas por sua alta taxa de crescimento, facilidade de cultura em larga escala, e sua adaptação às condições do solo. A Chlorella é de grande interesse porque vários estudos têm mostrado que pode auxiliar na fixação do nitrogênio, melhorar as propriedades físicas e químicas do solo, e produzir substâncias que promovem o crescimento das plantas e o controle de infecções. Por esta razão, as microalgas do gênero Chlorella representam uma alternativa viável para a biofertilização, gerando benefícios não só para a produção agrícola, mas também para o meio ambiente.

Oral metronomic vinorelbine combined with endocrine therapy in hormone receptor-positive HER2-negative breast cancer: SOLTI-1501 VENTANA window of opportunity trial.

BACKGROUND: The biological effect of oral metronomic vinorelbine (mVNB) alone or in combination with endocrine therapy in patients with hormone receptor-positive (HR+)/HER2-negative breast cancer has been scarcely addressed. METHODS: Postmenopausal women with untreated stage I-III HR+/HER2-negative breast cancer were randomized (1:1:1) to receive 3 weeks of letrozole (LTZ) 2.5 mg/day, oral mVNB 50 mg 3 days/week, or the combination. The primary objective was to evaluate, within PAM50 Luminal A/B disease, if the anti-proliferative effect of LTZ+mVNB was superior to monotherapy. An anti-proliferative effect was defined as the mean relative decrease of the PAM50 11-gene proliferation score in combination arm vs. both monotherapy arms. Secondary objectives included the evaluation of a comprehensive panel of breast cancer-related genes and safety. An unplanned analysis of stromal tumor-infiltrating lymphocytes (sTILs) was also performed. PAM50 analyses were performed using the nCounter®-based Breast Cancer 360™ gene panel, which includes 752 genes and 32 signatures. RESULTS: Sixty-one patients were randomized, and 54 paired samples (89%) were analyzed. The main patient characteristics were mean age of 67, mean tumor size of 1.7 cm, mean Ki67 of 14.3%, stage I (55.7%), and grades 1-2 (90%). Most baseline samples were PAM50 Luminal A (74.1%) or B (22.2%). The anti-proliferative effect of 3 weeks of LTZ+mVNB (- 73.2%) was superior to both monotherapy arms combined (- 49.9%; p = 0.001) and mVNB (- 19.1%; p < 0.001). The anti-proliferative effect of LTZ+mVNB (- 73.2%) was numerically higher compared to LTZ (- 65.7%) but did not reach statistical significance (p = 0.328). LTZ+mVNB induced high expression of immune-related genes and gene signatures, including CD8 T cell signature and PDL1 gene and low expression of ER-regulated genes (e.g., progesterone receptor) and cell cycle-related and DNA repair genes. In tumors with ≤ 10% sTILs at baseline, a statistically significant increase in sTILs was observed following LTZ (paired analysis p = 0.049) and LTZ+mVNB (p = 0.012). Grade 3 adverse events occurred in 3.4% of the cases. CONCLUSIONS: Short-term mVNB is well-tolerated and presents anti-proliferative activity alone and in combination with LTZ. The high expression of immune-related biological processes and sTILs observed with the combination opens the possibility of studying this combination with immunotherapy. Further investigation comparing these biological results with other metronomic schedules or drug combinations is warranted. TRIAL REGISTRATION: NCT02802748 , registered 16 June 2016.