Evaluation of the optimal dose of gibberellic acid (Full gib) in the induction of sprouting of yungay potato variety tuber (Solanum tuberosum L.)

This research was carried out in the district of Luya, province of Chachapoyas, Amazonas, with the objective of evaluating the optimal dose of gibberellic acid (Full Gib) in the induction of sprouting of potato tubers (Solanum tuberosum L.) Yungay variety. A Completely Randomized Design (CRD) with two factors three replications and seven treatments was used. Minitat 17 statistical software, ANOVA, and the Tukey mean comparison test at 5% were used for data analysis. The treatments were: Nothing was applied (T1), 7.5 mL of Full Gib in 20 L of water, for 15 min (T2), 7.5 mL of Full Gib in 20 L of water, for 20 min (T3), 10 mL of full Gib in 20 L of water, for 15 min (T4), 10 mL of full Gib in 20 L of water, for 20 min (T5), 12. 5 mL of full Gib in 20 L of water, for 15 min (T6), 12.5 mL of full Gib in 20 L of water, for 20 min (T7). The variables evaluated were: Sprouting percentage, number of sprouts, sprout length, and sprout diameter per tuber. According to the results obtained, it can be observed that treatments 5 and 3 obtained the highest germination percentages with 86.17 and 85.67%, respectively, surpassing the other treatments; there were no significant differences between treatments in the number of sprouts per tuber. Treatments 5, 3, and 4 were better, with results of 8.93, 8.83, and 8.68, respectively; on the other hand, the variable shoot length obtained the best results in treatments 5 and 3 with 7.69 and 7.50 cm, respectively. Similarly, the shoot diameter variable had positive results in treatments 3 and 5 with 6.0 and 5.9 mm, respectively

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

Concurrent overexpression of serum p53 mutation related with Helicobacter pylori infection

Abstract Background & Aims In the province of Cadiz (Spain), the adjusted mortality rate for gastric cancer in the coastal town of Barbate is 10/100.000 inhabitants, whereas in the inland town of Ubrique, the rate is twice as high. The rate of Helicobacter pylori (H. pylori) infection (H. pylori antibodies) in the normal population was 54% in Ubrique, but only 32% in Barbate. In the two decades since its original discovery, p53 has found a singularly prominent place in our understanding of human gastric cancer and H. pylori cause accumulation of reactive oxygen species in the mucosa compartment. This study was designed to compare serum levels of p53 in a population characterized by high mortality due to stomach cancer and a high prevalence of H. pylori infection and another population in which mortality from this cause and the prevalence of H. pylori infection are low. Materials and methods 319 subjects from the low mortality population and 308 from the high mortality population were studied, as were 71 patients with stomach cancer. We measured serum immunoglobulin G antibody to H. pylori and serum mutant p53 protein and ceruloplasmin. Results The difference between the two populations in the prevalence of H. pylori infection was significant (p Conclusions There is a significant association between infection with H. pylori, elevated titers of H. pylori antibodies, and positivity for serum mutant p53 protein. Such information can significantly increase our basic knowledge in molecular pathology of gastric cancer and protection against H. pylori infection.</p

Therapeutic Drug Monitoring of Antifungal Agents in Critically Ill Patients: Is There a Need for Dose Optimisation?

Invasive fungal infections are an important cause of morbidity and mortality, especially in critically ill patients. Increasing resistance rates and inadequate antifungal exposure have been documented in these patients, due to clinically relevant pharmacokinetic (PK) and pharmacodynamic (PD) alterations, leading to treatment failure. Physiological changes such as third spacing (movement of fluid from the intravascular compartment to the interstitial space), hypoalbuminemia, renal failure and hepatic failure, as well as common interventions in the intensive care unit, such as renal replacement therapy and extracorporeal membrane oxygenation, can lead to these PK and PD alterations. Consequently, a therapeutic target concentration that may be useful for one patient may not be appropriate for another. Regular doses do not take into account the important PK variations in the critically ill, and the need to select an effective dose while minimising toxicity advocates for the use of therapeutic drug monitoring (TDM). This review aims to describe the current evidence regarding optimal PK/PD indices associated with the clinical efficacy of the most commonly used antifungal agents in critically ill patients (azoles, echinocandins, lipid complexes of amphotericin B, and flucytosine), provide a comprehensive understanding of the factors affecting the PK of each agent, document the PK parameters of critically ill patients compared to healthy volunteers, and, finally, make recommendations for therapeutic drug monitoring (TDM) of antifungals in critically ill patients

Therapeutic Drug Monitoring of Antifungal Agents in Critically Ill Patients: Is There a Need for Dose Optimisation?

Invasive fungal infections are an important cause of morbidity and mortality, especially in critically ill patients. Increasing resistance rates and inadequate antifungal exposure have been documented in these patients, due to clinically relevant pharmacokinetic (PK) and pharmacodynamic (PD) alterations, leading to treatment failure. Physiological changes such as third spacing (movement of fluid from the intravascular compartment to the interstitial space), hypoalbuminemia, renal failure and hepatic failure, as well as common interventions in the intensive care unit, such as renal replacement therapy and extracorporeal membrane oxygenation, can lead to these PK and PD alterations. Consequently, a therapeutic target concentration that may be useful for one patient may not be appropriate for another. Regular doses do not take into account the important PK variations in the critically ill, and the need to select an effective dose while minimising toxicity advocates for the use of therapeutic drug monitoring (TDM). This review aims to describe the current evidence regarding optimal PK/PD indices associated with the clinical efficacy of the most commonly used antifungal agents in critically ill patients (azoles, echinocandins, lipid complexes of amphotericin B, and flucytosine), provide a comprehensive understanding of the factors affecting the PK of each agent, document the PK parameters of critically ill patients compared to healthy volunteers, and, finally, make recommendations for therapeutic drug monitoring (TDM) of antifungals in critically ill patients.</jats:p

Therapeutic Drug Monitoring of Antifungal Agents in Critically Ill Patients: Is There a Need for Dose Optimisation?

Las infecciones fúngicas invasivas son una causa importante de morbilidad y mortalidad, especialmente en pacientes críticos. Se ha documentado un aumento en las tasas de resistencia y una exposición antifúngica inadecuada en estos pacientes, debido a alteraciones farmacocinéticas (FC) y farmacodinámicas (FD) clínicamente relevantes, que conducen al fracaso del tratamiento. Cambios fisiológicos como el tercer espacio (movimiento de líquido del compartimento intravascular al espacio intersticial), hipoalbuminemia, insuficiencia renal e insuficiencia hepática, así como intervenciones comunes en la unidad de cuidados intensivos, como la terapia de reemplazo renal y la oxigenación por membrana extracorpórea, pueden provocar estas alteraciones FC y FD. En consecuencia, una concentración terapéutica objetivo que puede ser útil para un paciente puede no ser apropiada para otro. Las dosis habituales no tienen en cuenta las importantes variaciones farmacocinéticas en pacientes críticos, y la necesidad de seleccionar una dosis eficaz minimizando la toxicidad justifica el uso de la monitorización terapéutica de fármacos (MTF). Esta revisión tiene como objetivo describir la evidencia actual sobre los índices farmacocinéticos/farmacodinámicos óptimos asociados a la eficacia clínica de los antifúngicos más utilizados en pacientes críticos (azoles, equinocandinas, complejos lipídicos de anfotericina B y flucitosina), proporcionar una comprensión integral de los factores que afectan la farmacocinética de cada fármaco, documentar los parámetros farmacocinéticos de pacientes críticos en comparación con voluntarios sanos y, finalmente, formular recomendaciones para la monitorización terapéutica de fármacos (MTF) de antifúngicos en pacientes críticos.Invasive fungal infections are an important cause of morbidity and mortality, especially in critically ill patients. Increasing resistance rates and inadequate antifungal exposure have been documented in these patients, due to clinically relevant pharmacokinetic (PK) and pharmacodynamic (PD) alterations, leading to treatment failure. Physiological changes such as third spacing (movement of fluid from the intravascular compartment to the interstitial space), hypoalbuminemia, renal failure and hepatic failure, as well as common interventions in the intensive care unit, such as renal replacement therapy and extracorporeal membrane oxygenation, can lead to these PK and PD alterations. Consequently, a therapeutic target concentration that may be useful for one patient may not be appropriate for another. Regular doses do not take into account the important PK variations in the critically ill, and the need to select an effective dose while minimising toxicity advocates for the use of therapeutic drug monitoring (TDM). This review aims to describe the current evidence regarding optimal PK/PD indices associated with the clinical efficacy of the most commonly used antifungal agents in critically ill patients (azoles, echinocandins, lipid complexes of amphotericin B, and flucytosine), provide a comprehensive understanding of the factors affecting the PK of each agent, document the PK parameters of critically ill patients compared to healthy volunteers, and, finally, make recommendations for therapeutic drug monitoring (TDM) of antifungals in critically ill patients