Tomato miR156-targeted SlSBP15 represses shoot branching by modulating hormone dynamics and interacting with GOBLET and BRANCHED1b.

The miRNA156 (miR156)/SQUAMOSA PROMOTER-BINDING PROTEIN-LIKE (SPL/SBP) regulatory hub is highly conserved among phylogenetically distinct species, but how it interconnects multiple pathways to converge to common integrators controlling shoot architecture is still unclear. Here, we demonstrated that the miR156/SlSBP15 node modulates tomato shoot branching by connecting multiple phytohormones with classical genetic pathways regulating both axillary bud development and outgrowth. miR156-overexpressing plants (156-OE) displayed high shoot branching, whereas plants overexpressing a miR156-resistant SlSBP15 allele (rSBP15) showed arrested shoot branching. Importantly, the rSBP15 allele was able to partially restore the wild-type shoot branching phenotype in the 156-OE background. rSBP15 plants have tiny axillary buds, and their activation is dependent on shoot apex-derived auxin transport inhibition. Hormonal measurements revealed that indole-3-acetic acid (IAA) and abscisic acid (ABA) concentrations were lower in 156-OE and higher in rSBP15 axillary buds, respectively. Genetic and molecular data indicated that SlSBP15 regulates axillary bud development and outgrowth by inhibiting auxin transport and GOBLET (GOB) activity, and by interacting with tomato BRANCHED1b (SlBRC1b) to control ABA levels within axillary buds. Collectively, our data provide a new mechanism by which the miR156/SPL/SBP hub regulates shoot branching, and suggest that modulating SlSBP15 activity might have potential applications in shaping tomato shoot architecture.

Brazilian cardio-oncology: the 10-year experience of the Instituto do Cancer do Estado de Sao Paulo.

BACKGROUND: In recent years, the field of cardio-oncology has grown worldwide, bringing benefits to cancer patients in terms of survival and quality of life. This study reports the experience of a pioneer cardio-oncology programme at University Cancer Hospital in Brazil over a period of 10 years, describing the clinical profile of patients and the clinical outcomes. METHODS: A retrospective study was conducted on a cohort of patients treated at the cardio-oncology programme from April 2009 to February 2019. We analysed the characteristics of patients and outcomes, including mortality, according to the type of clinical indication for outpatient care (general cardiology, perioperative evaluation and follow-up and treatment cardiotoxicity). RESULTS: From a total of 26,435 medical consultations, we obtained the data of 4535 individuals among the medical care outpatients. When we analysed the clinical characteristics of patients considering the clinical indication - general cardiology, perioperative evaluation and cardiotoxicity outpatient clinics, differences were observed with respect to age (59 [48-66], 66 [58-74] and 69 [62-76], p < 0.001), diabetes (67 [15%], 635 [22.6%] and 379 [29.8%]; p < 0.001), hypertension (196 [43.8%], 1649 [58.7%] and 890 [70.1%], p < 0.001) and dyslipidaemia (87 [19.7%), 735 [26.2%] and 459 [36.2%], p < 0.001). A similar overall mortality rate was observed in the groups (47.5% vs. 45.7% vs. 44.9% [p = 0.650]). CONCLUSION: The number of oncologic patients in the Cardio-Oncology Programme has grown in the last decade. A well-structured cardio-oncology programme is the key to achieving the true essence of this area, namely, ongoing care for cancer patients throughout the disease treatment process, optimizing their cardiovascular status to ensure they can receive the best therapy against cancer.

Low root PIP1-1 and PIP2 aquaporins expression could be related to reduced hydration in 'Rangpur' lime plants exposed to aluminium.

In acidic soils, aluminium (Al) occurs as Al3+, which is phytotoxic. One of the most conspicuous symptoms of Al toxicity is the root growth inhibition, which can lead to low water uptake and consequent reduction in leaf hydration and gas exchange. However, fibrous xylem vessels have been observed in roots of 'Rangpur' lime plants (Citrus limonia L.) when exposed to Al, which could affect the functioning of aquaporins, ultimately reducing their expression. We confirmed a decrease of CO2 assimilation (A), stomatal conductance (gs), transpiration (E) and relative leaf water content (RWC) in 3-month-old C. limonia plants exposed to 1480 µM Al in nutrient solution for 90 days. The estimated hydraulic conductivity from soil to the leaf (KL) and leaf water potential (Ψw) also showed low values, although not consistently reduced over time of Al exposure. The relative expression of aquaporin genes belonging to PIP family (PIP1-1, PIP1-2 and PIP2) showed downregulation for ClPIP1-1 and ClPIP2 and upregulation for ClPIP1-2 in plants exposed to Al. Furthermore, ClPIP1-1 was positively correlated with A and gs in plants exposed to Al. Therefore, downregulation of ClPIP1-1 and ClPIP2 in roots of 'Rangpur' lime plants could be associated with the low leaf hydration of this species when exposed to Al.

Association between muscle function and body composition, vitamin D status, and blood glucose in postmenopausal women with type 2 diabetes.

AIMS: The aim of this study was to examine the association between muscle function, and body composition, vitamin D status, and blood glucose in post-menopausal women with type 2 diabetes (T2D). METHODS: Forty post-menopausal women (62.48±7.67years; 154.6±5.11cm; 73.93±15.43kg; 31.13±5.82 BMI kg/m2) with a diagnosis of T2D participated in this cross-sectional study. The patients performed fasting blood sample exams, anthropometrics assessments, body composition, and clinical exams. Subjects performed physical tests including handgrip, timed up and go, 30-s chair stand, arm curl, and sit-to-stand. The correlation between the parameters of physical tests, age, body composition, vitamin D, and blood glucose was assessed by Pearson correlation. RESULTS: The results showed there were significant correlations between blood glucose and relative strength (R=-0.398, p=0.011), arm curl test (R=-0.367 and p=0.020), and hip flexion (R=0.427, p=0.006). CONCLUSIONS: These findings are important because they highlight the importance of resistance training in individuals with T2D and the relationship with a fat increase during a dicrease process. Furthermore, the concentration of serum glucose might be associated with decreases in muscle strength and muscle function in older adults. Thus, T2D patients should be involved with strength training to improve the strength and the muscle hypertrophy.

Neonatal Candidemia Caused by Candida haemulonii: Case Report and Review of Literature.

Candidemia is a frequent condition in Neonatal Intensive Care Units (NICU) and usually complicates the newborns clinical course. Several factors are responsible for candidiasis, such as prematurity and use of broad-spectrum antibiotics, and in these cases, there are the involvement of various Candida species, as C. albicans, and C. parapsilosis. However, other species as C. haemulonii has been rarely described in candidemia cases, being considered an emergent pathogen. Thus, we report a case of neonatal candidemia by C. haemulonii and a review of literature of fungemia by this yeast. The patient was a neonate with gestational age of 26 weeks and birth weight of 660 g hospitalized in a NICU from a Brazilian hospital. The identification of the etiological agent was performed by phenotypic methods, scanning electron microscopy, sequencing of the ITS region of rDNA, and mass spectrometry. Antifungal susceptibility testing was carried out according to the Clinical Laboratories and Standards Institute guidelines. The newborn was diagnosed with candidemia by C. haemulonii resistant to amphotericin B with minimal inhibitory concentration (MIC) of 8 µg/mL, sensitive to fluconazole (MIC: 8 µg/mL) and voriconazole (MIC: 0.12 µg/mL). The treatment with fluconazole (12 mg/kg/day) was established with good outcome. Candidemia by C. haemulonii is still being limited to a few sporadic cases in adults with endemic and restricted occurrences in neonates. Usually, the therapy with amphotericin B is ineffective against this species. Our results showed the importance of the mycological diagnosis associated to antifungigrama for the successful clinical management followed by important epidemiological data.

Phosphorylated AKT preserves stallion sperm viability and motility by inhibiting caspases 3 and 7.

AKT, also referred to as protein kinase B (PKB or RAC), plays a critical role in controlling cell survival and apoptosis. To gain insights into the mechanisms regulating sperm survival after ejaculation, the role of AKT was investigated in stallion spermatozoa using a specific inhibitor and a phosphoflow approach. Stallion spermatozoa were washed and incubated in Biggers-Whitten-Whittingham medium, supplemented with 1% polyvinyl alcohol (PVA) in the presence of 0 (vehicle), 10, 20 or 30 µM SH5, an AKT inhibitor. SH5 treatment reduced the percentage of sperm displaying AKT phosphorylation, with inhibition reaching a maximum after 1 h of incubation. This decrease in phosphorylation was attributable to either dephosphorylation or suppression of the active phosphorylation pathway. Stallion spermatozoa spontaneously dephosphorylated during in vitro incubation, resulting in a lack of a difference in AKT phosphorylation between the SH5-treated sperm and the control after 4 h of incubation. AKT inhibition decreased the proportion of motile spermatozoa (total and progressive) and the sperm velocity. Similarly, AKT inhibition reduced membrane integrity, leading to increased membrane permeability and reduced the mitochondrial membrane potential concomitantly with activation of caspases 3 and 7. However, the percentage of spermatozoa exhibiting oxidative stress, the production of mitochondrial superoxide radicals, DNA oxidation and DNA fragmentation were not affected by AKT inhibition. It is concluded that AKT maintains the membrane integrity of ejaculated stallion spermatozoa, presumably by inhibiting caspases 3 and 7, which prevents the progression of spermatozoa to an incomplete form of apoptosis.

Blood transfusion in cardiac surgery is a risk factor for increased hospital length of stay in adult patients.

BACKGROUND: Allogeneic red blood cell (RBC) transfusion has been proposed as a negative indicator of quality in cardiac surgery. Hospital length of stay (LOS) may be a surrogate of poor outcome in transfused patients. METHODS: Data from 502 patients included in Transfusion Requirements After Cardiac Surgery (TRACS) study were analyzed to assess the relationship between RBC transfusion and hospital LOS in patients undergoing cardiac surgery and enrolled in the TRACS study. RESULTS: According to the status of RBC transfusion, patients were categorized into the following three groups: 1) 199 patients (40%) who did not receive RBC, 2) 241 patients (48%) who received 3 RBC units or fewer (low transfusion requirement group), and 3) 62 patients (12%) who received more than 3 RBC units (high transfusion requirement group). In a multivariable Cox proportional hazards model, the following factors were predictive of a prolonged hospital length of stay: age higher than 65 years, EuroSCORE, valvular surgery, combined procedure, LVEF lower than 40% and RBC transfusion of > 3 units. CONCLUSION: RBC transfusion is an independent risk factor for increased LOS in patients undergoing cardiac surgery. This finding highlights the adequacy of a restrictive transfusion therapy in patients undergoing cardiac surgery. TRIAL REGISTRATION: Clinicaltrials.gov identifier: http://NCT01021631.

Autophagy and apoptosis have a role in the survival or death of stallion spermatozoa during conservation in refrigeration.

Apoptosis has been recognized as a cause of sperm death during cryopreservation and a cause of infertility in humans, however there is no data on its role in sperm death during conservation in refrigeration; autophagy has not been described to date in mature sperm. We investigated the role of apoptosis and autophagy during cooled storage of stallion spermatozoa. Samples from seven stallions were split; half of the ejaculate was processed by single layer centrifugation, while the other half was extended unprocessed, and stored at 5°C for five days. During the time of storage, sperm motility (CASA, daily) and membrane integrity (flow cytometry, daily) were evaluated. Apoptosis was evaluated on days 1, 3 and 5 (active caspase 3, increase in membrane permeability, phosphatidylserine translocation and mitochondrial membrane potential) using flow cytometry. Furthermore, LC3B processing was investigated by western blotting at the beginning and at the end of the period of storage. The decrease in sperm quality over the period of storage was to a large extent due to apoptosis; single layer centrifugation selected non-apoptotic spermatozoa, but there were no differences in sperm motility between selected and unselected sperm. A high percentage of spermatozoa showed active caspase 3 upon ejaculation, and during the period of storage there was an increase of apoptotic spermatozoa but no changes in the percentage of live sperm, revealed by the SYBR-14/PI assay, were observed. LC3B was differentially processed in sperm after single layer centrifugation compared with native sperm. In processed sperm more LC3B-II was present than in non-processed samples; furthermore, in non-processed sperm there was an increase in LC3B-II after five days of cooled storage. These results indicate that apoptosis plays a major role in the sperm death during storage in refrigeration and that autophagy plays a role in the survival of spermatozoa representing a new pro-survival mechanism in spermatozoa not previously described.

Development and characterization of microsatellite markers for Hebanthe eriantha (Amaranthaceae).

PREMISE OF THE STUDY: Hebanthe eriantha (Amaranthaceae) is extensively collected and used in folk medicine. Microsatellite markers were developed and characterized to investigate the genetic structure and diversity of germplasm collections of this species. METHODS AND RESULTS: Eleven highly polymorphic microsatellite markers were developed. The number of alleles observed for each locus ranged from two to eight. The observed and expected heterozygosities ranged from 0.000 to 0.808 and 0.455 to 0.851, respectively. CONCLUSIONS: These results show the utility of microsatellite loci for studies of population genetics in H. eriantha, which are important for the future conservation and cultivation of this medicinal species.

Melatonin reduces lipid peroxidation and apoptotic-like changes in stallion spermatozoa.

Lipid peroxidation (LPO) has been claimed as a major factor involved in stallion damage during storage or cryopreservation. Because melatonin is a well-known potent antioxidant, the aim of the present study was to investigate the effect of melatonin during in vitro incubation. Furthermore, we investigated the presence of specific melatonin receptors (MT1 and MT2) using specific polyclonal antibodies and western blotting. Stallion spermatozoa were incubated up to 3 hr at 37°C in the presence of different concentrations of melatonin (0, 50 pm, 100 pm, 200 pm, or 1 µm). At the beginning and at the end of the incubation period, sperm motility (using computer-assisted sperm analysis), membrane integrity and permeability, fluidity of the sperm membrane, LPO, and mitochondrial membrane potential (Δψm) were flow cytometrically evaluated. Melatonin reduced changes in the spermatozoa related to apoptosis (increased sperm membrane permeability and lowered Δψm) (P < 0.05). Furthermore, LPO was dramatically reduced (P < 0.01) while no effect was observed on sperm motility or kinematics. Interestingly, melatonin helped maintain a more fluid sperm plasmalemma (P < 0.05). Our results clearly show the absence of MT1 and MT2 receptors in the stallion spermatozoa. It is concluded that melatonin is a useful tool to improve the quality of stored stallion sperm, increasing their life span and reducing premature aging, this likely relates to melatonin's antioxidant properties.

Transfusion requirements after cardiac surgery: the TRACS randomized controlled trial.

CONTEXT: Perioperative red blood cell transfusion is commonly used to address anemia, an independent risk factor for morbidity and mortality after cardiac operations; however, evidence regarding optimal blood transfusion practice in patients undergoing cardiac surgery is lacking. OBJECTIVE: To define whether a restrictive perioperative red blood cell transfusion strategy is as safe as a liberal strategy in patients undergoing elective cardiac surgery. DESIGN, SETTING, AND PATIENTS: The Transfusion Requirements After Cardiac Surgery (TRACS) study, a prospective, randomized, controlled clinical noninferiority trial conducted between February 2009 and February 2010 in an intensive care unit at a university hospital cardiac surgery referral center in Brazil. Consecutive adult patients (n = 502) who underwent cardiac surgery with cardiopulmonary bypass were eligible; analysis was by intention-to-treat. INTERVENTION: Patients were randomly assigned to a liberal strategy of blood transfusion (to maintain a hematocrit ≥30%) or to a restrictive strategy (hematocrit ≥24%). MAIN OUTCOME MEASURE: Composite end point of 30-day all-cause mortality and severe morbidity (cardiogenic shock, acute respiratory distress syndrome, or acute renal injury requiring dialysis or hemofiltration) occurring during the hospital stay. The noninferiority margin was predefined at -8% (ie, 8% minimal clinically important increase in occurrence of the composite end point). RESULTS: Hemoglobin concentrations were maintained at a mean of 10.5 g/dL (95% confidence interval [CI], 10.4-10.6) in the liberal-strategy group and 9.1 g/dL (95% CI, 9.0-9.2) in the restrictive-strategy group (P < .001). A total of 198 of 253 patients (78%) in the liberal-strategy group and 118 of 249 (47%) in the restrictive-strategy group received a blood transfusion (P < .001). Occurrence of the primary end point was similar between groups (10% liberal vs 11% restrictive; between-group difference, 1% [95% CI, -6% to 4%]; P = .85). Independent of transfusion strategy, the number of transfused red blood cell units was an independent risk factor for clinical complications or death at 30 days (hazard ratio for each additional unit transfused, 1.2 [95% CI, 1.1-1.4]; P = .002). CONCLUSION: Among patients undergoing cardiac surgery, the use of a restrictive perioperative transfusion strategy compared with a more liberal strategy resulted in noninferior rates of the combined outcome of 30-day all-cause mortality and severe morbidity. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01021631.

Spontaneous Bacterial Pericarditis and Coronary Sinus Endocarditis Caused by Oxacillin-Susceptible Staphylococcus aureus.

This paper describes a case of a 44-year-old male patient previously healthy admitted with an unusual spontaneous acute bacterial pericarditis associated with coronary sinus mass. Two-dimensional echocardiography showed large loculated pericardial effusion with signs of diastolic restriction and an image suggesting vegetation in topography of the right atrium coronary sinus. Pericardial drainage, coronary sinus vegetation resection, and antibiotic therapy with Oxacillin were performed due to Oxacillin-susceptible Staphylococcus aureus identified on the pericardial effusion and blood culture. This is a rare condition and a unique combination of a spontaneous acute bacterial pericarditis with coronary sinus endocarditis without cardiac valve compromise.

Endomyocardial fibrosis as a cause of Budd-Chiari syndrome and fatal pulmonary embolism.

A 24-year-old-man had right-sided heart failure of 3 months' duration. A Doppler echocardiogram revealed atrium and right ventricular enlargement, obliteration of the right ventricular apex, and a mass with an echolucent center measuring 20x21 mm in the right ventricular outlet. He died of pulmonary embolism. At autopsy, a huge organized thrombus obliterating the right ventricular apex passing through the tricuspid valve to the right atrium and then extending to the inferior vena cava up to the suprahepatic veins was seen. Histologically, an intense fibrotic thickening of the endomyocardium extending into the myocardium was observed. Cardiac thrombosis associated with endomyocardial fibrosis should be added to the list of causes of Budd-Chiari syndrome.