Evolving patterns and clinical outcome of genetic studies performed at diagnosis in acute myeloid leukemia patients: Real life data from the PETHEMA Registry.

BACKGROUND: There are no studies assessing the evolution and patterns of genetic studies performed at diagnosis in acute myeloid leukemia (AML) patients. Such studies could help to identify potential gaps in our present diagnostic practices, especially in the context of increasingly complex procedures and classifications. METHODS: The REALMOL study (NCT05541224) evaluated the evolution, patterns, and clinical impact of performing main genetic and molecular studies performed at diagnosis in 7285 adult AML patients included in the PETHEMA AML registry (NCT02607059) between 2000 and 2021. RESULTS: Screening rates increased for all tests across different time periods (2000-2007, 2008-2016, and 2017-2021) and was the most influential factor for NPM1, FLT3-ITD, and next-generation sequencing (NGS) determinations: NPM1 testing increased from 28.9% to 72.8% and 95.2% (p < .001), whereas FLT3-ITD testing increased from 38.1% to 74.1% and 95.9% (p < .0001). NGS testing was not performed between 2000-2007 and only reached 3.5% in 2008-2016, but significantly increased to 72% in 2017-2021 (p < .001). Treatment decision was the most influential factor to perform karyotype (odds ratio [OR], 6.057; 95% confidence interval [CI], 4.702-7.802), and fluorescence in situ hybridation (OR, 2.273; 95% CI, 1.901-2.719) studies. Patients ≥70 years old or with an Eastern Cooperative Oncology Group ≥2 were less likely to undergo these diagnostic procedures. Performing genetic studies were associated with a favorable impact on overall survival, especially in patients who received intensive chemotherapy. CONCLUSIONS: This unique study provides relevant information about the evolving landscape of genetic and molecular diagnosis for adult AML patients in real-world setting, highlighting the increased complexity of genetic diagnosis over the past 2 decades.

Cumulative Impact of Serial Partial Nephrectomy for the Treatment of Recurrent Renal Masses.

PURPOSE: Reoperative partial nephrectomy (RePN) offers several advantages for the treatment of recurrent, multifocal renal masses. RePN has been previously demonstrated to be technical feasibility and delay the need for renal replacement therapy. However, there is still inherent complexity and known risks to reoperative nephrectomy. We studied the largest population of reoperative partial nephrectomies to characterize renal functional outcomes and the likelihood of intra- and post-operative complications. MATERIALS AND METHODS: Query of an institutional surgical registry was conducted. Demographic data, serum creatinine (SCr) for eGFR and protein dipstick results were assessed within 1 week prior to surgery, and postoperative function assessments were studied within a year of surgery. RePN was defined as serial surgical resection of the ipsilateral renal unit. RESULTS: A total of 1131 PNs performed on 663 patients at a single center were retrospectively evaluated. In reoperative cases, median number of operations per renal unit was 2 (range: 2-6). There was a stepwise decline in eGFR with an average decline of 6.1 with each RePN. With each subsequent nephrectomy, surgical duration, estimated blood loss, and incidence of preoperative anemia increased. Postoperative eGFR showed a significant positive association with preoperative eGFR, while negative associations were found with age, number of previous ipsilateral partial nephrectomies, number of tumors, and largest tumor size. High-grade complications were associated with the number of ipsilateral partial nephrectomies, tumors count, and tumor size. Robotic or laparoscopic procedures exhibited a likelihood of Grade 3 or greater complications compared to open surgery. CONCLUSION: RePN contributes to renal dysfunction and an increased risk of surgical complications. Intraoperative blood loss and surgical duration increase with subsequent nephrectomy. Such risks are dependent on the number of prior operative interventions on the kidney, suggesting a stepwise progression of surgical morbidity.

The effect of successful educational actions in transition from primary to secondary school.

While data show improvement in terms of educational access, dropout rates are significant in many countries. In Spain, 28% of students drop out of school without finishing secondary school, more than double the EU average. Thus, extensive research has shown the consequences of the dropout phenomenon, including negative effects on employment, welfare dependency, as well as health and emotional problems. The transition from primary to secondary education is a critical turning point. This situation worsens in the case of refugee and migrant minors who are refugees or with migrant backgrounds. Although there is strong evidence revealing the potential of SEAs to advance educational success for all in different contexts, no research has yet explored the effect of SEAs on enabling a successful transition from primary to secondary education, which could considerably impact decreasing dropout rates. Drawing on a qualitative case study of a secondary educational centre in Spain, this study analyses the impact of the implementation of three SEAs in key aspects related to primary-secondary transitions. Findings show how the systematic implementation of SEAs impacts the ease of the primary-secondary transition: positive relationships between the educational community are promoted, school connectedness across transition is strengthened, and academic support networks are enhanced. The study therefore suggests the benefits of SEAs as strategies that can enhance positive primary-secondary school transitions in terms of students' perception of belongingness, and academic performance.

Renal cell carcinoma and risk of second primary cancer: A Danish nationwide cohort study.

AIM: To examine the risk of second primary cancer in patients with incident renal cell carcinoma (RCC). METHODS: We identified all patients diagnosed with incident RCC during 1995-2019, using population-based Danish medical registries. Patients were followed from the date of RCC diagnosis until any second primary cancer diagnosis, death, emigration, or December 31, 2019, whichever came first. We computed the absolute risk, standardized incidence ratio (SIR), and excess absolute risk of second primary cancer, with 95% confidence intervals (CIs), among patients with RCC compared to the general population. RESULTS: The absolute 1- and 20-year risks of any second primary cancer were 2.8% and 17.8%, respectively. Within 1 year after RCC diagnosis, we detected 20 excess cancer cases per 1000 person-years (PY) (SIR, 2.3; 95% CI: 2.1-2.6). Moreover, we detected an additional four excess cancer cases per 1000 PY during 1 to <5 years of follow-up (SIR, 1.3; 95% CI: 1.2-1.4), and 6 per 1000 PY beyond 5 years of follow-up (SIR, 1.4; 95% CI: 1.3-1.5). The sustained elevated cancer risk beyond 1 year of follow-up was mainly attributed to excess risk of lung and bladder cancer. The risk of second primary cancer was higher in 2006-2019 than in 1995-2005, but only during the first year of follow-up. CONCLUSION: Patients with incident RCC have a sustained 40% elevated long-term risk of second primary cancer, compared with the general population. This increased risk is mainly attributed to lung and bladder cancer.

Therapeutic hypothermia: A descriptive, cohort study conducted over 10 years at a tertiary care public hospital. / Hipotermia terapéutica: estudio descriptivo de una cohorte de 10 años en un hospital público de alta complejidad.

Introduction. Therapeutic hypothermia (TH) reduces the risk of death or disability in children with moderate to severe hypoxic ischemic encephalopathy (HIE). Objective. To describe a population of patients with HIE that required TH and their course until discharge. Population and methods. Retrospective, descriptive, cohort study. All patients admitted to TH between 2013 and 2022 were studied. Epidemiological, clinical, monitoring, and treatment data were assessed, together with supplementary tests and condition at discharge. Risk factors were compared between deceased patients and survivors; and, among the latter, those requiring special healthcare needs (SHCN) at discharge. Results. A total of 247 patients were included. Mortality: 11%. Most common sentinel event: prolonged second stage of labor (39%). Treatment initiation: median of 5 hours of life. Seizures: 57%. Intravenous erythropoietin: 66.7%. Abnormal pattern in brain function monitoring: 52%. Normalization of monitoring: median of 24 hours. Pathological magnetic resonance imaging: 42%. Predictor variables of mortality: severe Sarnat and Sarnat staging and pathological ultrasound upon admission. Conclusion. The overall mortality rate was 11%. Referrals increased more markedly since 2018. The time of TH initiation was later than in previous reports. Severe neurological signs as per the Sarnat and Sarnat staging and a pathological baseline cranial ultrasound were independent predictors of mortality at discharge. Patients with SHCN at discharge showed a normalized tracing in the amplitude-integrated electroencephalography performed later. The most common finding in the magnetic resonance imaging was basal ganglia involvement. No statistically significant differences were observed in terms of clinical characteristics or complications among patients who received erythropoietin.

Introducción. La hipotermia terapéutica (HT) reduce el riesgo de muerte o discapacidad en niños con encefalopatía hipóxico-isquémica (EHI) moderada-grave. Objetivo. Describir una población de pacientes con EHI que requirió HT y su evolución hasta el alta hospitalaria. Población y métodos. Estudio descriptivo de cohorte retrospectivo. Se analizaron todos los pacientes que ingresaron a HT entre 2013 y 2022. Se evaluaron datos epidemiológicos, clínicos, de monitoreo, tratamiento, estudios complementarios y condición al alta. Se compararon los factores de riesgo entre pacientes fallecidos y sobrevivientes, y de estos, los que requirieron necesidades especiales al alta (NEAS). Resultados. Se incluyeron 247 pacientes. Mortalidad: 11 %. Evento centinela más frecuente: período expulsivo prolongado (39 %). Inicio del tratamiento: mediana 5 horas de vida. Convulsiones: 57 %. Eritropoyetina intravenosa: 66,7 %. Patrón anormal de monitoreo de función cerebral: 52 %. Normalización del monitoreo: mediana 24 horas. Resonancia magnética patológica: 42 %. Variables predictoras de mortalidad: Sarnat y Sarnat grave, y ecografía patológica al ingreso. Conclusión. La mortalidad global fue del 11 %. Las derivaciones aumentaron en forma más evidente a partir del año 2018. El horario de inicio de HT fue más tardío que en reportes anteriores. Los signos neurológicos de gravedad según la escala de Sarnat y Sarnat y la ecografía cerebral basal patológica fueron predictores independientes de mortalidad al alta. Los pacientes con NEAS presentaron normalización del trazado del electroencefalograma de amplitud integrada más tardío. El hallazgo más frecuente en la resonancia fue la afectación de los ganglios basales. No se encontraron diferencias clínicas ni de complicaciones estadísticamente significativas entre los pacientes que recibieron eritropoyetina.

Loss of the ability to regenerate body appendages in vertebrates: from side effects of evolutionary innovations to gene loss.

The ability to regenerate large body appendages is an ancestral trait of vertebrates, which varies across different animal groups. While anamniotes (fish and amphibians) commonly possess this ability, it is notably restricted in amniotes (reptiles, birds, and mammals). In this review, we explore the factors contributing to the loss of regenerative capabilities in amniotes. First, we analyse the potential negative impacts on appendage regeneration caused by four evolutionary innovations: advanced immunity, skin keratinization, whole-body endothermy, and increased body size. These innovations emerged as amniotes transitioned to terrestrial habitats and were correlated with a decline in regeneration capability. Second, we examine the role played by the loss of regeneration-related enhancers and genes initiated by these innovations in the fixation of an inability to regenerate body appendages at the genomic level. We propose that following the cessation of regenerative capacity, the loss of highly specific regeneration enhancers could represent an evolutionarily neutral event. Consequently, the loss of such enhancers might promptly follow the suppression of regeneration as a side effect of evolutionary innovations. By contrast, the loss of regeneration-related genes, due to their pleiotropic functions, would only take place if such loss was accompanied by additional evolutionary innovations that compensated for the loss of pleiotropic functions unrelated to regeneration, which would remain even after participation of these genes in regeneration was lost. Through a review of the literature, we provide evidence that, in many cases, the loss in amniotes of genes associated with body appendage regeneration in anamniotes was significantly delayed relative to the time when regenerative capability was lost. We hypothesise that this delay may be attributed to the necessity for evolutionary restructuring of developmental mechanisms to create conditions where the loss of these genes was a beneficial innovation for the organism. Experimental investigation of the downregulation of genes involved in the regeneration of body appendages in anamniotes but absent in amniotes offers a promising avenue to uncover evolutionary innovations that emerged from the loss of these genes. We propose that the vast majority of regeneration-related genes lost in amniotes (about 150 in humans) may be involved in regulating the early stages of limb and tail regeneration in anamniotes. Disruption of this stage, rather than the late stage, may not interfere with the mechanisms of limb and tail bud development during embryogenesis, as these mechanisms share similarities with those operating in the late stage of regeneration. Consequently, the most promising approach to restoring regeneration in humans may involve creating analogs of embryonic limb buds using stem cell-based tissue-engineering methods, followed by their transfer to the amputation stump. Due to the loss of many genes required specifically during the early stage of regeneration, this approach may be more effective than attempting to induce both early and late stages of regeneration directly in the stump itself.

Home-visiting Parenting Programs to Improve Mother-Infant Interactions at Early Ages: A Systematic Review.

Objective: To systematically review studies examining the effects of home-visiting preventive parenting programs (HV-PPs) on improving the quality of mother-child interactions in early childhood. Method: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses protocol, we identified 3,586 studies published between 2018 and 2022 by searching the following databases: PubMed, Web of Science, BVS/LILACS, SciELO, and PsycNET/PsycINFO. After applying the eligibility criteria, 17 articles were selected for review. Results: Most studies were conducted in high-income countries (53%) and the remainder were conducted in upper-middle-income countries, predominantly using a randomized controlled trial design and with strong methodological quality. The 17 studies applied 13 different HV-PPs, predominantly using video feedback, based on various dosages and schedules. Most studies (77%) showed significant positive effects on mother-child interactions by improving mainly positive maternal behaviors (e.g., sensitivity and responsiveness). Positive effects occurred independent of the study design, sample characteristics, measures, and constructs assessed. However, the findings suggest that the combination of fewer than six sessions, durations shorter than three months, and a very early start did not impact mother-child interactions, as expected. Few studies have explored negative maternal behaviors, children's behaviors, and dyadic interactions such as mutuality and synchrony. Conclusions: HV-PPs positively impacted mother-child interactions in early childhood despite the large heterogeneity across program designs, outcome measures, and overlapping constructs. Based on the results, we discuss the practical and economic implications of using parenting programs as a preventive approach.

Increased Natural Killer (NK)-cell cytotoxicity and Trypanosoma cruzi-specific memory B cells in subjects with discordant serology for Chagas disease.

The presence of memory T cell specific for Trypanosoma cruzi in subjects with discordant serology for Chagas disease supports a cleared infection in these subjects. Using high-dimensional flow cytometry, ELISPOT assays and quantitative PCR, antibody-secreting cells and memory B cells specific for T. cruzi, total B-cell phenotypes, innate immune responses and parasite DNA were evaluated in serodiscordant, seropositive and seronegative subjects for T. cruzi infection. T. cruzi-specific memory B cells but no antibody-secreting cells specific for T. cruzi, increased proportion of nonclassical monocytes and increased levels of polyfunctional NK cells were found in serodiscordant compared with seropositive subjects. None of the serodiscordant subjects evaluated showed detectable parasite DNA, most of them did not show cardiac abnormalities and a group of them had had confirmed positive serology for Chagas disease. The unique immune profiles in serodiscordant subjects support that T. cruzi infection was cleared or profoundly controlled in these subjects.

Supplementing narasin or monensin to control coccidiosis in naturally infected calves.

This experiment compared narasin and monensin as anticoccidials for calves naturally infected with Eimeria spp. Twenty-four weaned, non-castrated male calves (Bos indicus × B. taurus cross) were assigned to this experiment (days -8 to 42). All calves were infected by Eimeria spp. according to oocyst count per gram (OPG) from fecal samples collected on days -8 and -7 (average 1,059 ±â€…101 oocysts/g). Calves were housed in individual pens, received corn silage, mineral mix, and water for ad libitum consumption, in addition to a grain-based supplement at 200 g/head daily. Fecal samples were collected on days -2 and -1 for OPG, and results averaged as initial OPG value. Calves were blocked according to initial OPG into eight blocks of three calves each, ranked within each block according to body weight (BW) recorded on day -1, and assigned to receive narasin (NAR; 0.8 mg/kg of BW), monensin (MON; 1 mg/kg of BW), or no ionophore (CON; negative control). Ionophores were added to the grain-based supplement, and offered from days 0 to 42 of the experiment. Calf BW was recorded on days 7, 14, 21, 28, 35, and 42. Fecal samples were collected on days 6 and 7, 13 and 14, 20 and 21, 26 and 27, 34 and 35, and 41 and 42 for OPG analysis, and results from samples collected on consecutive days were averaged. Aliquoted fecal samples were also pooled across calves from the same treatment and collection days, and used to determine the prevalence of individual species of Eimeria. No treatment effects were detected (P ≥ 0.51) for calf BW or growth rate. A treatment × day interaction was detected (P < 0.01) for OPG, as NAR and MON calves had less (P < 0.01) OPG compared with CON calves beginning on day 7. The OPG was also less (P ≤ 0.03) in MON compared with NAR calves on days 7, 14, and 28, but did not differ (P ≥ 0.48) on days 21, 35, and 42. The anticoccidial efficacy of NAR and MON did not differ (P ≥ 0.16) when calculated across all Eimeria spp., or according to prevalence of E. bovis and E. alabamensins. A treatment × day interaction was detected (P = 0.04) for anticoccidial efficacy to E. alabamensis, which was greater (P < 0.01) in MON calves on days 7 and 14 and did not differ (P ≥ 0.40) afterward. Collectively, both ionophores were similarly effective in controlling coccidiosis upon completion of the 42-d study, although the anticoccidial effects of monensin were noted earlier in the experiment. Nonetheless, these results corroborate narasin as an efficient anticoccidial ionophore for naturally infected calves.

Effect of Smoking on Longitudinal Interferon-ϒ Release Assay Results among Close Contacts of People with Pulmonary Tuberculosis.

Diagnosis of M. tuberculosis (Mtb) infection in close contacts is critical for TB control. Smoking is a risk factor for Mtb infection and TB disease but its effect on longitudinal interferon-gamma release assay (IGRA) results remains unknown. We conducted a multi-site prospective study in Brazil between 2015-2019, among close contacts of adults with culture-confirmed pulmonary TB. IGRA was performed at baseline, month 6 if negative at baseline, and month 24-30 after enrollment. IGRA results were categorized as IGRA-positive (maintained from baseline to last visit), IGRA-conversion (from negative to positive at any time), IGRA-reversion (from positive to negative at any time), and IGRA-negative (maintained from baseline to last visit). Associations between IGRA results and smoking status at baseline (current/former vs never) in contacts were evaluated using propensity score-adjusted logistic regression models. Estimated propensity score was used as a covariate in models, which regressed the outcome (IGRA-positive, IGRA-conversion, IGRA-reversion) on smoking status. Of 430 close contacts, 89 (21%) were IGRA-positive, 30 (7%) were converters, 30 (7%) were reverters and 22 were indeterminate. Smoking frequency was 26 (29%) among IGRA-positive contacts, 7 (23%) in converters, and 3 (10%) in reverters. Smoking in contacts was associated with lower odds of IGRA-reversion (adjusted odds ratio = 0.16; 95% confidence interval = [0.03-0.70]). We did not detect associations between smoking and IGRA-positive or IGRA-conversion. Our findings highlight the importance of smoking on longitudinal IGRA results. This has implications for clinical care and clinical trials in which IGRA status is monitored or used as an outcome.

An unusual case of gallstone ileus 35 years post-cholecystectomy masked by an incisional hernia.

Gallstone ileus is an uncommon cause of mechanical bowel obstruction in patients with cholecystitis and gallstones who develop a fistula over time. In the post-cholecystectomy patient, the presence of gallstone ileus is extremely rare; these patients have different pathophysiological pathways, such as a spilled gallstone that subsequently erodes into the bowel, subtotal cholecystectomies, and diverticulae that can hold a gallstone for hidden several years. In these patients, the clinical presentations are unique because of their rarity and because the gallbladder had been previously removed. A high index of suspicion by the medical team is needed for diagnosis. We present the case of an 85-year-old male who had a history of cholecystectomy 35 years ago. He presented to the emergency department with intestinal obstruction. Since he had a hernia, it was thought to be the cause of the obstruction; however, during surgery, we were surprised to find a gallstone ileus. After surgery, he fully recovered.

Peer support as a potential tool to promote pharmacists' wellbeing.

Discussion regarding burnout in health professionals, including community pharmacists, has grown substantially since the arrival of the COVID-19 pandemic. Rapid legislative and societal behavioural changes led to significant global disruption of physical and emotional wellbeing during the pandemic as pharmacists continued to provide care while under unprecedented levels of stress. Community pharmacists have had an essential role in maintaining face-to-face care as the number of COVID-19 diagnoses and deaths rose. Communications emerged from the World Health Organisation which implored long-term changes to healthcare workplaces, including increased access to psychosocial support for employees. Peer support is a unique initiative in that it is low-cost and accessible across many platforms. Its main purpose is to bring people together with shared experiences and can often include people in the same career field or workplace. The feasibility and efficacy of peer support programs have been studied in other professional groups such as nurses and physicians, and also in undergraduate medical students. The conclusions drawn from these studies suggest that involvement in peer support reduced the risk of burnout and increased workplace engagement. In contrast to many other healthcare professionals, community pharmacists often work in relative isolation. Research has shown that younger pharmacists, and those in the earlier stages of their careers, reported feeling stressed, undervalued and supported. They also mentioned a desire for access to a mentoring or coaching program. Following the success of peer support in other cohorts, research is needed to verify if this intervention will similarly benefit early career community pharmacists.

Exploring the molecular landscape of cancer of unknown primary: A comparative analysis with other metastatic cancers.

Cancer of unknown primary (CUP) tumors are biologically very heterogeneous, which complicates stratification of patients for treatment. Consequently, these patients face limited treatment options and a poor prognosis. With this study, we aim to expand on the current knowledge of CUP biology by analyzing two cohorts: a well-characterized cohort of 44 CUP patients, and 213 metastatic patients with known primary. These cohorts were treated at the same institution and characterized by identical molecular assessments. Through comparative analysis of genomic and transcriptomic data, we found that CUP tumors were characterized by high expression of immune-related genes and pathways compared to other metastatic tumors. Moreover, CUP tumors uniformly demonstrated high levels of tumor-infiltrating leukocytes and circulating T cells, indicating a strong immune response. Finally, the genetic landscape of CUP tumors resembled that of other metastatic cancers and demonstrated mutations in established cancer genes. In conclusion, CUP tumors possess a distinct immunophenotype that distinguishes them from other metastatic cancers. These results may suggest an immune response in CUP that facilitates metastatic tumor growth while limiting growth of the primary tumor.

Effects of a lower versus a higher oxygenation target in intensive care unit patients with chronic obstructive pulmonary disease and acute hypoxaemic respiratory failure: a subgroup analysis of a randomised clinical trial.

Background: Oxygen supplementation is ubiquitous in intensive care unit (ICU) patients with chronic obstructive pulmonary disease (COPD) and acute hypoxaemia, but the optimal oxygenation target has not been established. Methods: This was a pre-planned subgroup analysis of the Handling Oxygenation Targets in the ICU (HOT-ICU) trial, which allocated patients with acute hypoxaemia to a lower oxygenation target (partial pressure of arterial oxygen [Pao2] of 8 kPa) vs a higher target (Pao2 of 12 kPa) during ICU admission, for up to 90 days; the allocation was stratified for presence or absence of COPD. Here, we report key outcomes for patients with COPD. Results: The HOT-ICU trial enrolled 2928 patients of whom 563 had COPD; 277 were allocated to the lower and 286 to the higher oxygenation group. After allocation, the median Pao2 was 9.1 kPa (inter-quartile range 8.7-9.9) in the lower group vs 12.1 kPa (11.2-12.9) in the higher group. Data for arterial carbon dioxide (Paco2) were available for 497 patients (88%) with no between-group difference in time-weighted average; median Paco2 6.0 kPa (5.2-7.2) in the lower group vs 6.2 kPa (5.4-7.3) in the higher group. At 90 days, 122/277 patients (44%) in the lower oxygenation group had died vs 132/285 patients (46%) in the higher (relative risk 0.98; 95% confidence interval 0.82-1.17; P=0.67). No statistically significant differences were found in any secondary outcome. Conclusions: In ICU patients with COPD and acute hypoxaemia, a lower vs a higher oxygenation target did not reduce mortality. There were no between-group differences in Paco2 or in secondary outcomes. Clinical trial registration: NCT03174002, EudraCT number 2017-000632-34.

Circulating angiotensin-(1-7) is decreased in patients with isolated nocturnal hypertension.

Isolated nocturnal hypertension (INHT), defined as nighttime elevated blood pressure (BP) with normal daytime BP assessed by ambulatory BP monitoring, is associated with higher cardiovascular morbidity and mortality. We hypothesized that an alteration in the circulating renin-angiotensin system (RAS) contributes to INHT development. We examined circulating levels of angiotensin (Ang) (1-7) and Ang II and ACE2 activity in 26 patients that met the INHT criteria, out of 50 that were referred for BP evaluation (62% women, 45 ±â€Š16 years old). Those with INHT were older, had a higher BMI, lower circulating Ang-(1-7) (P = 0.002) and Ang II levels (P = 0.02) and no change in ACE2 activity compared to those normotensives. Nighttime DBP was significantly correlated with Ang-(1-7) and Ang II levels. Logistic regression showed significant association in Ang-(1-7) and Ang II levels with INHT. Our study reveals differences in circulating RAS in individuals with INHT.

Citrus psorosis virus 24K protein inhibits the processing of miRNA precursors by interacting with components of the biogenesis machinery.

Sweet orange (Citrus sinensis) is one of the most important fruit crops worldwide. Virus infections in this crop can interfere with cellular processes, causing dramatic economic losses. By performing RT-qPCR analyses, we demonstrated that citrus psorosis virus (CPsV)-infected orange plants exhibited higher levels of unprocessed microRNA (miRNA) precursors than healthy plants. This result correlated with the reported reduction of mature miRNAs species. The protein 24K, the CPsV suppressor of RNA silencing (VSR), interacts with miRNA precursors in vivo. Thus, this protein becomes a candidate responsible for the increased accumulation of unprocessed miRNAs. We analyzed 24K RNA-binding and protein-protein interaction domains and described patterns of its subcellular localization. We also showed that 24K colocalizes within nuclear D-bodies with the miRNA biogenesis proteins DICER-LIKE 1 (DCL1), HYPONASTIC LEAVES 1 (HYL1), and SERRATE (SE). According to the results of bimolecular fluorescence complementation and co-immunoprecipitation assays, the 24K protein interacts with HYL1 and SE. Thus, 24K may inhibit miRNA processing in CPsV-infected citrus plants by direct interaction with the miRNA processing complex. This work contributes to the understanding of how a virus can alter the regulatory mechanisms of the host, particularly miRNA biogenesis and function.IMPORTANCESweet oranges can suffer from disease symptoms induced by virus infections, thus resulting in drastic economic losses. In sweet orange plants, CPsV alters the accumulation of some precursors from the regulatory molecules called miRNAs. This alteration leads to a decreased level of mature miRNA species. This misregulation may be due to a direct association of one of the viral proteins (24K) with miRNA precursors. On the other hand, 24K may act with components of the cell miRNA processing machinery through a series of predicted RNA-binding and protein-protein interaction domains.

Use of Ozone as a Substrate Treatment for the Control of Trichoderma in the Production of Pleurotus ostreatus.

Pleurotus ostreatus is one of the most widely cultivated species in the world. It can be produced in many lignocellulosic substrates after carrying out a treatment to eliminate competing microorganisms. The most commonly used is pasteurization by steam or by immersion in hot water. The aim of this work is to evaluate if ozone can be employed as treatment for decontamination of the substrate used for the production of the edible mushroom P. ostreatus to control of green mold Trichoderma. Wheat straw was employed as a substrate. We used two different methodologies: bubbling ozone into a tank with water and the substrate, and injecting ozone into a closed tank with the substrate inside. Ten treatments were carried out including two treatments with inoculation by a spray of conidia of Trichoderma. The effect of ozone on the conidia was also evaluated. We found that the treatment of the substrate with ozone in immersed water resulted more effective (lower growth of Trichoderma) than injecting ozone into a closed tank. Anyway, we found that the contaminant fungi could grow on the substrate in both treatments with ozone. We observed that although ozone affected the conidia when it was bubbled into water, some of them still managed to survive and could germinate 72 h later. P. ostreatus could grow and produce fruiting bodies on a substrate that was previously treated with ozone and yields were not affected. Based on the results obtained, we conclude that ozone may not be an effective agent to control Trichoderma in highly contaminated substrates, at least in the experimental conditions that we used, for the production of P. ostreatus.