Removal of redox-sensitive Rubisco Activase does not alter Rubisco regulation in soybean.

Rubisco activase (Rca) facilitates the catalytic repair of Rubisco, the CO2-fixing enzyme of photosynthesis, following periods of darkness, low to high light transitions or stress. Removal of the redox-regulated isoform of Rubisco activase, Rca-α, enhances photosynthetic induction in Arabidopsis and has been suggested as a strategy for the improvement of crops, which may experience frequent light transitions in the field; however, this has never been tested in a crop species. Therefore, we used RNAi to reduce the Rca-α content of soybean (Glycine max cv. Williams 82) below detectable levels and then characterized the growth, photosynthesis, and Rubisco activity of the resulting transgenics, in both growth chamber and field conditions. Under a 16 h sine wave photoperiod, the reduction of Rca-α contents had no impact on morphological characteristics, leaf expansion rate, or total biomass. Photosynthetic induction rates were unaltered in both chamber-grown and field-grown plants. Plants with reduced Rca-α content maintained the ability to regulate Rubisco activity in low light just as in control plants. This result suggests that in soybean, Rca-α is not as centrally involved in the regulation of Rca oligomer activity as it is in Arabidopsis. The isoform stoichiometry supports this conclusion, as Rca-α comprises only ~ 10% of the Rubisco activase content of soybean, compared to ~ 50% in Arabidopsis. This is likely to hold true in other species that contain a low ratio of Rca-α to Rca-ß isoforms.

The relative abundance of wheat Rubisco activase isoforms is post-transcriptionally regulated.

Diurnal rhythms and light availability affect transcription-translation feedback loops that regulate the synthesis of photosynthetic proteins. The CO2-fixing enzyme Rubisco is the most abundant protein in the leaves of major crop species and its activity depends on interaction with the molecular chaperone Rubisco activase (Rca). In Triticum aestivum L. (wheat), three Rca isoforms are present that differ in their regulatory properties. Here, we tested the hypothesis that the relative abundance of the redox-sensitive and redox-insensitive Rca isoforms could be differentially regulated throughout light-dark diel cycle in wheat. While TaRca1-ß expression was consistently negligible throughout the day, transcript levels of both TaRca2-ß and TaRca2-α were higher and increased at the start of the day, with peak levels occurring at the middle of the photoperiod. Abundance of TaRca-ß protein was maximal 1.5 h after the peak in TaRca2-ß expression, but the abundance of TaRca-α remained constant during the entire photoperiod. The redox-sensitive TaRca-α isoform was less abundant, representing 85% of the redox-insensitive TaRca-ß at the transcript level and 12.5% at the protein level. Expression of Rubisco large and small subunit genes did not show a consistent pattern throughout the diel cycle, but the abundance of Rubisco decreased by up to 20% during the dark period in fully expanded wheat leaves. These results, combined with a lack of correlation between transcript and protein abundance for both Rca isoforms and Rubisco throughout the entire diel cycle, suggest that the abundance of these photosynthetic enzymes is post-transcriptionally regulated.

Apoptosis Pathways Triggered by a Potent Antiproliferative Hybrid Chalcone on Human Melanoma Cells.

The World Health Organization reported that approximately 324,000 new cases of melanoma skin cancer were diagnosed worldwide in 2020. The incidence of melanoma has been increasing over the past decades. Targeting apoptotic pathways is a potential therapeutic strategy in the transition to preclinical models and clinical trials. Some naturally occurring products and synthetic derivatives are apoptosis inducers and may represent a realistic option in the fight against the disease. Thus, chalcones have received considerable attention due to their potential cytotoxicity against cancer cells. We have previously reported a chalcone containing an indole and a pyridine heterocyclic rings and an α-bromoacryloylamido radical which displays potent antiproliferative activity against several tumor cell lines. In this study, we report that this chalcone is a potent apoptotic inducer for human melanoma cell lines SK-MEL-1 and MEL-HO. Cell death was associated with mitochondrial cytochrome c release and poly(ADP-ribose) polymerase cleavage and was prevented by a non-specific caspase inhibitor. Using SK-MEL-1 as a model, we found that the mechanism of cell death involves (i) the generation of reactive oxygen species, (ii) activation of the extrinsic and intrinsic apoptotic and mitogen-activated protein kinase pathways, (iii) upregulation of TRAIL, DR4 and DR5, (iv) downregulation of p21Cip1/WAF1 and, inhibition of the NF-κB pathway.

Rubisco activation by wheat Rubisco activase isoform 2ß is insensitive to inhibition by ADP.

Rubisco activase (Rca) is a catalytic chaperone that remodels the active site, promotes the release of inhibitors and restores catalytic competence to Rubisco. Rca activity and its consequent effect on Rubisco activation and photosynthesis are modulated by changes to the chloroplast environment induced by fluctuations in light levels that reach the leaf, including redox status and adenosine diphosphate (ADP)/adenosine triphosphate (ATP) ratio. The Triticum aestivum (wheat) genome encodes for three Rca protein isoforms: 1ß (42.7 kDa), 2ß (42.2 kDa) and 2α (46.0 kDa). The regulatory properties of these isoforms were characterised by measuring rates of Rubisco activation and ATP hydrolysis by purified recombinant Rca proteins in the presence of physiological ADP/ATP ratios. ATP hydrolysis by all three isoforms was sensitive to inhibition by increasing amounts of ADP in the assay. In contrast, Rubisco activation activity of Rca 2ß was insensitive to ADP inhibition, while Rca 1ß and 2α were inhibited. Two double and one quadruple site-directed mutants were designed to elucidate if differences in the amino acid sequences between Rca 1ß and 2ß could explain the differences in ADP sensitivity. Changing two amino acids in Rca 2ß to the corresponding residues in 1ß (T358K & Q362E) resulted in significant inhibition of Rubisco activation in presence of ADP. The results show that the wheat Rca isoforms differ in their regulatory properties and that amino acid changes in the C domain influence ADP sensitivity. Advances in the understanding of Rubisco regulation will aid efforts to improve the efficiency of photosynthetic CO2 assimilation.

Melatonin Induces Melanogenesis in Human SK-MEL-1 Melanoma Cells Involving Glycogen Synthase Kinase-3 and Reactive Oxygen Species.

Melatonin is present in all living organisms where it displays a diversity of physiological functions. Attenuation of melanogenesis by melatonin has been reported in some mammals and also in rodent melanoma cells. However, melatonin may also stimulate melanogenesis in human melanoma cells through mechanisms that have not yet been revealed. Using the human melanoma cells SK-MEL-1 as a model, an increase in both tyrosinase activity and melanin was already observed at 24 h after melatonin treatment with maximal levels of both being detected at 72 h. This effect was associated with the induction in the expression of the enzymes involved in the synthesis of melanin. In this scenario, glycogen synthase kinase-3ß seems to play a significant function since melatonin decreased its phosphorylation and preincubation with specific inhibitors of this protein kinase (lithium or BIO) reduced the expression and activity of tyrosinase. Blocking of PI3K/AKT pathway stimulated melanogenesis and the effect was suppressed by the inhibitors of glycogen synthase kinase-3ß. Although melatonin is a recognized antioxidant, we found that it stimulates reactive oxygen species generation in SK-MEL-1 cells. These chemical species seem to be an important signal in activating the melanogenic process since the antioxidants N-acetyl-l-cysteine and glutathione decreased both the level and activity of tyrosinase stimulated by melatonin. Our results support the view that regulation of melanogenesis involves a cross-talk between several signaling pathways.

Melatonin enhances hyperthermia-induced apoptotic cell death in human leukemia cells.

Melatonin is an endogenous indoleamine with a wide range of biological functions. In addition to modulating circadian rhythms, it plays important roles in the health as an antioxidant. Melatonin has also the ability to induce apoptosis in cancer cells and to enhance the antitumoral activity of chemotherapeutic agents. In this study, the effect of melatonin on hyperthermia-induced apoptosis was explored using human leukemia cells. The results demonstrate that melatonin greatly improved the cytotoxicity of hyperthermia in U937 cells. The potentiation of cell death was achieved with 1 mmol/L concentrations of the indoleamine but not with concentrations close to physiological levels in blood (1 nmol/L). This effect was associated to an enhancement of the apoptotic response, revealed by an increase in cells with hypodiploid DNA content and activation of multiple caspases (caspase-2, caspase-3, caspase-8, and caspase-9). Melatonin also increased hyperthermia-induced Bid activation as well as translocation of Bax from the cytosol to mitochondria and cytochrome c release. Hyperthermia-provoked apoptosis and potentiation by melatonin were abrogated by a broad-spectrum caspase inhibitor (z-VAD-fmk) as well as by specific inhibitors against caspase-8 or caspase-3. In contrast, blocking of the mitochondrial pathway of apoptosis either with a caspase-9 inhibitor or overexpressing the anti-apoptotic protein Bcl-2 (U937/Bcl-2) reduced the number of apoptotic cells in response to hyperthermia but it was unable to suppress melatonin enhancement. Melatonin appears to modulate the apoptotic response triggered by hyperthermia in a cell type-specific manner as similar results were observed in HL-60 but not in K562 or MOLT-3 cells.

Temperature dependence of in vitro Rubisco kinetics in species of Flaveria with different photosynthetic mechanisms.

There is general consensus in the literature that plants with different photosynthetic mechanisms (i.e. C3 vs. C4) have Rubiscos characterised by different kinetic performances. However, potential differences in the temperature dependencies of Rubisco kinetic parameters between C3 and C4 plants are uncertain. Accordingly, six species of Flaveria with contrasting photosynthetic mechanisms (C3, C3/C4 and C4) were selected and their Rubisco Michaelis-Menten constants for CO2 and RuBP (K c and K RuBP), carboxylase catalytic turnover rate ([Formula: see text]) and CO2/O2 specificity factor (S c/o) were measured between 10 and 40 °C. The results confirmed different Rubisco characteristics between C3 and C4 plants. Rubisco from the C3 species had higher E a for K c and [Formula: see text] than that from C4 species, which were translated into differences in the temperature response of the carboxylase catalytic efficiency ([Formula: see text]/K c). However, E a did not differ for S c/o or K RuBP. Although a mechanism remains uncertain, it appears that the Asp/Glu-149-Ala and Met-309-Ile substitutions lead to differences in the temperature responses of catalysis between C3 and C4 Rubiscos in Flaveria. Therefore, the above observations are consistent with the fact that C3 species have a higher photosynthetic efficiency and ecological dominance in cool environments, with respect to C4 species in temperate environments.

Effects of long-term individual and combined water and temperature stress on the growth of rice, wheat and maize: relationship with morphological and physiological acclimation.

This study evaluates the long-term individual and combined effects of high temperature (HT) and water deficit (WD) stress on plant growth, leaf gas-exchange and water use efficiency in cultivars of the three most important crops worldwide, rice, wheat and maize. Total plant biomass (Bt ) accumulation decreased under all treatments, being the combined HT-WD treatment the most detrimental in all three species. Although decreases in Bt correlated with adjustments in biomass allocation patterns (i.e. the leaf area ratio), most of the variation observed in Bt was explained by changes in leaf gas exchange parameters. Thus, integrated values of leaf carbon balance obtained from daily course measurements of photosynthesis and respiration were better predictors of plant growth than the instantaneous measurements of leaf gas exchange. Leaf water use efficiency, assessed both by gas exchange and carbon isotope measurements, was negatively correlated with Bt under WD, but not under the combined WD and HT treatment. A comparative analysis of the negative effects of single and combined stresses on the main parameters showed an additive component for WD and HT in rice and maize, in contrast to wheat. Overall, the results of the specific cultivars included in the study suggest that the species native climate plays a role shaping the species acclimation potential to the applied stresses. In this regard, wheat, originated in a cold climate, was the most affected species, which foretells a higher affectation of this crop due to climate change.

[Diagnostic yield and postoperative management of patients submitted to brain biopsy in a university hospital]. / Eficacia diagnóstica y manejo posoperatorio de los pacientes sometidos a biopsia cerebral en un hospital universitario.

OBJECTIVE: To assess the diagnostic yield and the incidence of perioperative complications in patients undergoing an open or closed cerebral biopsy and to determine the length of intensive care monitoring, for early diagnosis and fast management of perioperative complications. MATERIAL AND METHOD: This was a retrospective analysis of all the patients that underwent brain biopsy between January 2006 and July 2012. We recorded demographic data, comorbidities, modality of biopsy, intraoperative clinical data, histological results, computed tomography scanning findings and occurrence, and type of perioperative complications and moment of appearance. RESULTS: Seventy-six brain biopsies in 75 consecutive patients (51 closed and 25 open) were analysed. Diagnostic yield was 98% for closed biopsies and 96% for open biopsies. Mortality related to the procedures was 3.9 and 4%, respectively. The incidence of major complications was 3.9% for closed biopsies and 8% for open biopsies; half of these appeared within the first 24 postoperative hours, during patient stay in the Intensive Care Unit. Age was the only risk factor for complications (P=.04) in our study. No differences in morbimortality were found between the studied groups. CONCLUSIONS: Diagnostic yield was very high in our series. Because the importance of early diagnosis of complications for preventing long-term sequelae, we recommend overnight hospital stay for observation after open or closed brain biopsy.

Cardiorespiratory impact of transesophageal endoscopic mediastinoscopy compared with cervical mediastinoscopy: a randomized experimental study.

BACKGROUND: Transesophageal natural-orifice transluminal endoscopic surgery (NOTES) mediastinoscopy has been described as a feasible, less-invasive alternative to video-assisted mediastinoscopy (VAM). We aimed to investigate hemodynamic and respiratory effects during transesophageal NOTES mediastinoscopy compared with VAM. PATIENTS AND METHODS: This was a short-survival experiment in 20 female pigs randomized to NOTES (n = 10) or VAM (n = 10) mediastinoscopy. In the NOTES group, an endoscopist accessed the mediastinum through a 5-cm submucosal tunnel in the esophageal wall, and CO2 was used to create the pneumomediastinum. Conventional VAM was carried out by thoracic surgeons. A 30-minute systematic exploration of the mediastinum was then performed, including invasive monitoring for hemodynamic and respiratory data. Blood samples were drawn for gas analyses. RESULTS: All experiments except 2 in the NOTES group (one because of technical difficulties, the other because of thoracic lymphatic duct lesion) were completed as planned, and animals survived 24 hours. Also, 3 animals in the NOTES group presented a tension pneumothorax that was immediately recognized and percutaneously drained. VAM and NOTES animals showed similar pulmonary and systemic hemodynamic behavior during mediastinoscopy. Pulmonary gas exchange pattern was mildly impaired during the NOTES procedure, showing lower partial arterial oxygen pressure associated with higher airway pressures (more important in animals that presented with pneumothorax). CONCLUSIONS: NOTES mediastinoscopy induces minimal deleterious respiratory effects and hemodynamic changes similar to conventional cervical VAM and could be feasible when performed under strict hemodynamic and respiratory surveillance. Notably, serious complications caused by the injury of pleura are more frequent in NOTES, which mandates an improvement in technique and suitable equipment.

Down-regulation of wheat Rubisco activase isoforms expression by virus-induced gene silencing.

Rubisco activase (Rca) is an essential photosynthetic enzyme that removes inhibitors from the catalytic sites of the carboxylating enzyme Rubisco. In wheat, Rca is composed of one longer 46 kDa α-isoform and two shorter 42 kDa ß-isoforms encoded by the genes TaRca1 and TaRca2. TaRca1 produces a single transcript from which a short 1ß-isoform is expressed, whereas two alternative transcripts are generated from TaRca2 directing expression of either a long 2α-isoform or a short 2ß-isoform. The 2ß isoform is similar but not identical to 1ß. Here, virus-induced gene silencing (VIGS) was used to silence the different TaRca transcripts. Abundance of the transcripts and the respective protein isoforms was then evaluated in the VIGS-treated and control plants. Remarkably, treatment with the construct specifically targeting TaRca1 efficiently decreased expression not only of TaRca1 but also of the two alternative TaRca2 transcripts. Similarly, specific targeting of the TaRca2 transcript encoding a long isoform TaRca2α resulted in silencing of both TaRca2 alternative transcripts. The corresponding protein isoforms decreased in abundance. These findings indicate concomitant down-regulation of TaRca1 and TaRca2 at both transcript and protein levels and may impact the feasibility of altering the relative abundance of Rca isoforms in wheat.

Can primary health care mitigate the effects of economic crises on child health in Latin America? An integrated multicountry evaluation and forecasting analysis.

BACKGROUND: Latin American and Caribbean countries are dealing with the combined challenges of pandemic-induced socicoeconomic stress and increasing public debt, potentially leading to reductions in welfare and health-care services, including primary care. We aimed to evaluate the impact of primary health-care coverage on child mortality in Latin America over the past two decades and to forecast the potential effects of primary health-care mitigation during the current economic crisis. METHODS: This multicountry study integrated retrospective impact evaluations in Brazil, Colombia, Ecuador, and Mexico from 2000 to 2019 with forecasting models covering up to 2030. We estimated the impact of coverage of primary health care on mortality rates in children younger than 5 years (hereafter referred to as under-5 mortality) across different age groups and causes of death, adjusting for all relevant demographic, socioeconomic, and health-care factors, with fixed-effects multivariable negative binomial models in 5647 municipalities with an adequate quality of vital statistics. We also performed several sensitivity and triangulation analyses. We integrated previous longitudinal datasets with validated dynamic microsimulation models and projected trends in under-5 mortality rates under alternative policy response scenarios until 2030. FINDINGS: High primary health-care coverage was associated with substantial reductions in post-neonatal mortality rates (rate ratio [RR] 0·72, 95% CI 0·71-0·74), toddler (ie, aged between 1 year and <5 years) mortality rates (0·75, 0·73-0·76), and under-5 mortality rates (0·81, 0·80-0·82), preventing 305 890 (95% CI 251 826-360 517) deaths of children younger than 5 years over the period 2000-19. High primary health-care coverage was also associated with lower under-5 mortality rates from nutritional deficiencies (RR 0·55, 95% CI 0·52-0·58), anaemia (0·64, 0·57-0·72), vaccine-preventable and vaccine-sensitive conditions (0·70, 0·68-0·72), and infectious gastroenteritis (0·78, 0·73-0·84). Considering a scenario of moderate economic crisis, a mitigation response strategy implemented in the period 2020-30 that increases primary health-care coverage could reduce the under-5 mortality rate by up to 23% (RR 0·77, 95% CI 0·72-0·84) when compared with a fiscal austerity response, and this strategy would avoid 142 285 (95% CI 120 217-164 378) child deaths by 2030 in Brazil, Colombia, Ecuador, and Mexico. INTERPRETATION: The improvement in primary health-care coverage in Brazil, Colombia, Ecuador, and Mexico over the past two decades has substantially contributed to improving child survival. Expansion of primary health-care coverage should be considered an effective strategy to mitigate the health effects of the current economic crisis and to achieve Sustainable Development Goals related to child health. FUNDING: UK Medical Research Council. TRANSLATIONS: For the Spanish and Portuguese translations of the abstract see Supplementary Materials section.

Photosynthetic characterization of Rubisco transplantomic lines reveals alterations on photochemistry and mesophyll conductance.

Improving Rubisco catalysis is considered a promising way to enhance C3-photosynthesis and photosynthetic water use efficiency (WUE) provided the introduced changes have little or no impact on other processes affecting photosynthesis such as leaf photochemistry or leaf CO2 diffusion conductances. However, the extent to which the factors affecting photosynthetic capacity are co-regulated is unclear. The aim of the present study was to characterize the photochemistry and CO2 transport processes in the leaves of three transplantomic tobacco genotypes expressing hybrid Rubisco isoforms comprising different Flaveria L-subunits that show variations in catalysis and differing trade-offs between the amount of Rubisco and its activation state. Stomatal conductance (g s) in each transplantomic tobacco line matched wild-type, while their photochemistry showed co-regulation with the variations in Rubisco catalysis. A tight co-regulation was observed between Rubisco activity and mesophyll conductance (g m) that was independent of g s thus producing plants with varying g m/g s ratios. Since the g m/g s ratio has been shown to positively correlate with intrinsic WUE, the present results suggest that altering photosynthesis by modifying Rubisco catalysis may also be useful for targeting WUE.

Comparative study of NOTES alone versus NOTES guided by a new image registration system for navigation in the mediastinum: a study in a porcine model.

BACKGROUND: Natural orifice transluminal endoscopic surgery (NOTES) mediastinoscopy (MED) through the esophagus has proved to be feasible in the animal model. However, injury of the adjacent pleura and pneumothorax has been reported as a frequent adverse event when using a blind access. OBJECTIVE: To assess the utility and safety of a CT-based image registration system (IRS) for navigation in the mediastinum. DESIGN: Prospective, randomized, controlled trial in 30 Yorkshire pigs. Thirty-minute MEDs were performed: 15 MEDs were performed with IRS guidance (MED-IRS), and 15 MEDs were performed with a blind access. SETTING: Animal research laboratory. INTERVENTIONS: In both groups, the mediastinum was accessed through a 10-cm submucosal tunnel in the esophageal wall. Timed exploration was performed with identification of 8 mediastinal structures. MAIN OUTCOME MEASUREMENTS: Technical feasibility, adverse events, and the number of mediastinal structures identified. RESULTS: Thirty animals weighing 31.5 ± 3.5 kg were included in this study. MED was not possible in 2 animals in the "MED with blind access" group but was possible in all MEDs performed with IRS. The mean number of identified organs was slightly higher in "with IRS-MED" (6.13 ± 1.3) than with MED with blind access (4.7 ± 2.3; P = .066). Moreover, the right atrium and vena cava were identified in more cases with IRS-MED than in MED with blind access (13 vs 3 and 15 vs 11, P = .000 and P = .03, respectively). There were 3 (23%) adverse events with IRS-MED and 4 (27%) with "MED with blind access" (P = not significant), with pneumothorax being the most frequent (2 and 3, respectively). LIMITATIONS: Nonsurvival animal study. CONCLUSIONS: This study demonstrates that the IRS system appears feasible in natural orifice transluminal endoscopic surgery MED and suggests that IRS guidance might be useful for selected procedures.

Melatonin induces apoptosis through a caspase-dependent but reactive oxygen species-independent mechanism in human leukemia Molt-3 cells.

Melatonin is a naturally occurring indoleamine synthesized in the pineal gland that exhibits an extensive repertoire of biological activities. An increasing number of studies indicate that melatonin protects normal cells, while it reducing cancer cell proliferation. In this study, we investigated the effect of melatonin on the growth of the human leukemia cells and found that it efficiently reduced the number of cells in a concentration- and time-dependent manner. Thus, incubation with the indoleamine increased the percentage of cells with a hypodiploid DNA content, augmented the number of annexin V-positive cells, and also provoked ultrastructural changes that are features of apoptotic cell death. Evaluation of caspases revealed that caspase-3, caspase-6, caspase-7, and caspase-9, but not caspase-8 and caspase-2, were quickly activated (3-6 hr). The increase in the activity of these proteases was associated with up-regulation of the pro-apoptotic factor Bax and also with the release of cytochrome c from mitochondria. Pretreatment of the cells with the general caspase inhibitor z-VAD-fmk, reduced melatonin-induced apoptosis, but it did not block cell death suggesting that melatonin activates an alternative cell death modality in the absence of caspase activity. Thus, the activation of caspases was preceded by a fast (<30 min) increase in reactive oxygen species (ROS). Rotenone and antimycin A reduced the levels of ROS stimulated by melatonin, indicating that the complex I and the complex III of the mitochondrial electron transport chain are important sources of these chemical species. However, the role of ROS in melatonin-induced cell death remains elusive because anti-oxidants that were shown to decrease ROS levels (glutathione, N-acetyl-l-cysteine and Trolox) were unable to abrogate melatonin-induced cell death.

Construction and Evaluation of a Realistic Low-Cost Model for Training in Chest-Tube Insertion.

INTRODUCTION: Emergency thoracostomy is applied in life-threatening situations. Simulation plays a pivotal role in training in invasive techniques used mainly in stressful situations. Currently available commercial simulation models for thoracostomy have various drawbacks. METHODS: We designed a thoracostomy phantom from discarded hospital materials and pigskin with underlying flesh. The phantom can be used alone for developing technical skills or mounted on an actor in simulation scenarios. Medical students, intensive care unit (ICU) and emergency department teams, and thoracostomy experts evaluated its technical fidelity and usefulness for achieving learning objectives in workshops. RESULTS: The materials used to construct the phantom cost €47. A total of 12 experts in chest-tube placement and 73 workshop participants (12 ICU physicians and nurses, 20 emergency physicians and nurses, and 41 fourth-year medical students) evaluated the model. All groups rated the model's usefulness and the sensation of perforating the pleura highly. Experts rated the air release after pleura perforation lower than other groups. Lung reexpansion was the lowest rated item in all groups. Ratings of the appearance and feel of the model correlated strongly among all groups and experts. The ICU professionals rated the resistance encountered in introducing the chest drain lower than the other groups. CONCLUSIONS: This low-cost, reusable, transportable, and highly realistic model is an attractive alternative to commercial models for training in chest-tube insertion skills.

Preintervention imaging and intraoperative management care of the hypertrophic obstructive cardiomyopathy patient.

With an estimated overall mortality of less than 1 percent per year, hypertrophic cardiomyopathy, is the most common genetic cardiomyopathy. Intraoperative transesophageal echocardiography is the standard of care for assessing patients with hypertrophic obstructive cardiomyopathy undergoing surgical septal myectomy, allowing surgical planning, intraoperative hemodynamic monitoring, and postprocedural assessment of the repair, including detection of immediate complications. At various phases during surgical septal myectomy, the changing hemodynamic conditions may lead to worsening or improvement in left ventricle outflow tract obstruction by change in preload or afterload, systolic anterior motion of the mitral valve, or sympathetic stimulation. These characteristics represent unique challenges in the management of these patients, requiring a comprehensive understanding of the management of all the conditions required to decrease the left ventricle outflow tract gradient avoiding obstruction, which include the maintenance of sinus rhythm, adequate rate avoiding tachycardia and bradycardia, and avoidance of systemic hypotension preserving preload and afterload, with adequate vasoactive agents. The aim of this review is to summarize the perioperative assessment and management of patients undergoing hypertrophic obstructive myopathy surgery.

Feasibility of a Multimodal Prehabilitation Programme in Patients Undergoing Cytoreductive Surgery for Advanced Ovarian Cancer: A Pilot Study.

INTRODUCTION: Treatment for advanced ovarian cancer (AOC) comprises cytoreductive surgery combined with chemotherapy. Multimodal prehabilitation programmes before surgery have demonstrated efficacy in postoperative outcomes in non-gynaecological surgeries. However, the viability and effects of these programmes on patients with AOC are unknown. We aimed to evaluate the feasibility and postoperative impact of a multimodal prehabilitation programme in AOC patients undergoing surgery. METHODS: This single-centre, before-and-after intervention pilot study included 34 patients in two cohorts: the prehabilitation cohort prospectively included 15 patients receiving supervised exercise, nutritional optimisation, and psychological preparation from December 2019 to January 2021; the control cohort included 19 consecutive patients between January 2018 and November 2019. Enhanced Recovery After Surgery guidelines were followed. RESULTS: The overall adherence to the multimodal prehabilitation programme was 80%, with 86.7% adherence to exercise training, 100% adherence to nutritional optimisation, and 80% adherence to psychological preparation. The median hospital stay was shorter in the prehabilitation cohort (5 (IQR, 4-6) vs. 7 days (IQR, 5-9) in the control cohort, p = 0.04). Differences in postoperative complications using the comprehensive complication index (CCI) were not significant (CCI score: 9.3 (SD 12.12) in the prehabilitation cohort vs. 16.61 (SD 16.89) in the control cohort, p = 0.08). The median time to starting chemotherapy was shorter in the prehabilitation cohort (25 (IQR, 23-25) vs. 35 days (IQR, 28-45) in the control cohort, p = 0.03). CONCLUSIONS: A multimodal prehabilitation programme before cytoreductive surgery is feasible in AOC patients with no major adverse effects, and results in significantly shorter hospital stays and time to starting chemotherapy.

Physiological and morphological adaptations in relation to water use efficiency in Mediterranean accessions of Solanum lycopersicum.

The physiological traits underlying the apparent drought resistance of 'Tomàtiga de Ramellet' (TR) cultivars, a population of Mediterranean tomato cultivars with delayed fruit deterioration (DFD) phenotype and typically grown under non-irrigation conditions, are evaluated. Eight different tomato accessions were selected and included six TR accessions, one Mediterranean non-TR accession (NTR(M)) and a processing cultivar (NTR(O)). Among the TR accessions two leaf morphology types, normal divided leaves and potato-leaf, were selected. Plants were field grown under well-watered (WW) and water-stressed (WS) treatments, with 30 and 10% of soil water capacity, respectively. Accessions were clustered according to the leaf type and TR phenotype under WW and WS, respectively. Correlation among parameters under the different water treatments suggested that potential improvements in the intrinsic water-use efficiency (A(N)/g(s)) are possible without negative impacts on yield. Under WS TR accessions displayed higher A(N)/g(s), which was not due to differences in Rubisco-related parameters, but correlated with the ratio between the leaf mesophyll and stomatal conductances (g(m)/g(s)). The results confirm the existence of differential traits in the response to drought stress in Mediterranean accessions of tomato, and demonstrate that increases in the g(m)/g(s) ratio would allow improvements in A(N)/g(s) in horticultural crops.

The pharmacogenetics of treatment with olanzapine.

Genetic polymorphism in olanzapine-metabolizing enzymes, transporters and drug targets is associated with alterations in safety and efficacy. The aim of this systematic review is to describe all clinically relevant pharmacogenetic information on olanzapine and to propose clinically actionable variants. Two hundred and eighty-four studies were screened; 76 complied with the inclusion criteria and presented significant associations. DRD2 Taq1A (rs1800497) *A1, LEP -2548 (rs7799039) G and CYP1A2*1F alleles were related to olanzapine effectiveness and safety variability in several studies, with a high level of evidence. DRD2 -141 (rs1799732) Ins, A-241G (rs1799978) G, DRD3 Ser9Gly (rs6280) Gly, HTR2A rs7997012 A, ABCB1 C3435T (rs1045642) T and G2677T/A (rs2032582) T and UGT1A4*3 alleles were related to safety, effectiveness and/or pharmacokinetic variability with moderated level of evidence.