Repeated subcutaneous esketamine on treatment-resistant depression: An open-label dose titration study.

Background: Ketamine has gained prominence as one of the most effective therapeutic options in unipolar treatment-resistant depression (TRD). However, most studies related to the antidepressant action of ketamine used intravenous (IV) or intranasal (IN) administration. The subcutaneous (SC) route of administration is a promising alternative, as it results in plasma levels comparable to IV, causes fewer side effects, and is easier and cheaper to administer than both IV and/or IN routes.

The adipose tissue melanocortin 3 receptor is targeted by ghrelin and leptin and may be a therapeutic target in obesity.

Objective: Obesity is linked to perturbations in energy balance mechanisms, including ghrelin and leptin actions at the hypothalamic circuitry of neuropeptide Y (NPY) and melanocortin. However, information about the regulation of this system in the periphery is still scarce. Our objective was to study the regulation of the NPY/melanocortin system in the adipose tissue (AT) and evaluate its therapeutic potential for obesity and type 2 diabetes.

Immune Checkpoint Blockade Delays Cancer and Extends Survival in Murine DNA Polymerase Mutator Syndromes.

Unlabelled: Mutations in polymerases and exonuclease domains in humans are associated with increased cancer incidence, elevated tumor mutation burden (TMB) and response to immune checkpoint blockade (ICB). Although ICB is approved for treatment of several cancers, not all tumors with elevated TMB respond. Here we generated and proofreading mutator mice and show that ICB treatment of mice with high TMB tumors did not improve survival as only a subset of tumors responded.

RESPIRATION DEFECTS LIMIT SERINE SYNTHESIS REQUIRED FOR LUNG CANCER GROWTH AND SURVIVAL.

Unlabelled: Mitochondrial function is important for both energetic and anabolic metabolism. Pathogenic mitochondrial DNA (mtDNA) mutations directly impact these functions, resulting in the detrimental consequences seen in human mitochondrial diseases. The role of pathogenic mtDNA mutations in human cancers is less clear; while pathogenic mtDNA mutations are observed in some cancer types, they are almost absent in others.

Quality of eucalyptus wood chips for bioenergy as a function of drying time and horizontal chipper settings.

The increase in the use of energy from forest biomass has increased the demand for knowledge about tree-chipping operations. Therefore, this study aimed to evaluate the effect of different drying times of wood logs and various combinations of knife and anvil configurations in the horizontal chipper on the quality of chips produced for energy purposes. The study was conducted in a seven-year-old stand of .

G6PD Maintains Redox Homeostasis and Biosynthesis in LKB1-Deficient KRAS-Driven Lung Cancer.

Cancer cells depend on nicotinamide adenine dinucleotide phosphate (NADPH) to combat oxidative stress and support reductive biosynthesis. One major NAPDH production route is the oxidative pentose phosphate pathway (committed step: glucose-6-phosphate dehydrogenase, G6PD). Alternatives exist and can compensate in some tumors.

The Bidirectional Relationship of NPY and Mitochondria in Energy Balance Regulation.

Energy balance is regulated by several hormones and peptides, and neuropeptide Y is one of the most crucial in feeding and energy expenditure control. NPY is regulated by a series of peripheral nervous and humoral signals that are responsive to nutrient sensing, but its role in the energy balance is also intricately related to the energetic status, namely mitochondrial function. During fasting, mitochondrial dynamics and activity are activated in orexigenic neurons, increasing the levels of neuropeptide Y.

Inhibition of autophagy and MEK promotes ferroptosis in Lkb1-deficient Kras-driven lung tumors.

LKB1 and KRAS are the third most frequent co-mutations detected in non-small cell lung cancer (NSCLC) and cause aggressive tumor growth. Unfortunately, treatment with RAS-RAF-MEK-ERK pathway inhibitors has minimal therapeutic efficacy in LKB1-mutant KRAS-driven NSCLC. Autophagy, an intracellular nutrient scavenging pathway, compensates for Lkb1 loss to support Kras-driven lung tumor growth.

30-Day Morbidity and Mortality of Bariatric Surgery During the COVID-19 Pandemic: a Multinational Cohort Study of 7704 Patients from 42 Countries.

Background: There are data on the safety of cancer surgery and the efficacy of preventive strategies on the prevention of postoperative symptomatic COVID-19 in these patients. But there is little such data for any elective surgery. The main objectives of this study were to examine the safety of bariatric surgery (BS) during the coronavirus disease 2019 (COVID-19) pandemic and to determine the efficacy of perioperative COVID-19 protective strategies on postoperative symptomatic COVID-19 rates.

Modeling residual biomass from mechanized wood harvesting with data measured by forest harvester.

The lack of accurate models for estimating residual biomass in wood harvesting operations results in underutilization of this co-product by forestry companies. Due to the lack of this information, forestry operations planning, such as chipping and transport logistics, are influenced, with a consequent increase in costs. Thereby, the aim of this study was to propose and evaluate statistical models to estimate residual biomass of Eucalyptus sp.

Chlorophyll Oxidative Metabolism During the Phototrophic and Heterotrophic Growth of .

Different cultivation strategies have been developed with the aim of increasing the production rate of microalgal pigments. Specifically, biotechnological approaches are designed to increase antioxidant metabolites as chlorophyll and carotenoids. However, although significant advances have been built up, available information regarding both the chlorophyll metabolism and their oxidative reactions in photobioreactors is scarce.

Energy balance and CO2 emission in mechanized biomass harvesting in pine stands under thinning.

Biomass is an important component of the Brazilian energy matrix, with a potential contribution of co-products from thinned forests. The aim of this work was to evaluate the energy balance and CO2 potential emission in mechanized biomass harvesting operations in Pinus taeda stands at 9 and 10 years-old and under thinning, searching to support the use of co-product biomass from thinning as a renewable energy source. Thinning was carried out through cut-to-length harvesting method, in which large logs for sawmill and small logs for energy were produced.

The effect of enzymatic crosslinking on the viability of probiotic bacteria (Lactobacillus acidophilus) encapsulated by complex coacervation.

Lactobacillus acidophilus were encapsulated by complex coacervation followed by transglutaminase crosslinking, aiming to improve the resistance of the microcapsules and improve the protection for probiotics. Subsequently, microcapsules were dried by freeze drying. The encapsulation efficiency, morphology, thermal resistance, gastrointestinal simulation and storage stability were analysed for wet and dry forms.

Integrated Dynamic Characterization of Thermorheologically Simple Viscoelastic Materials Accounting for Frequency, Temperature, and Preload Effects.

In vibration insulation projects, a parameter affecting the dynamic properties of the viscoelastic materials is the previous static load acting on the supports, denominated here as the 'preload'. Most of the currently-used methodologies obtain the dynamic properties by considering only the effects of temperature and frequency. The additional effect of preload can be added to the usual methodologies by employing the hyperelastic theory developed by Mooney-Rivlin.

Knockdown of NF-κB1 by shRNA Inhibits the Growth of Renal Cell Carcinoma In Vitro and In Vivo.

Renal cell carcinoma (RCC) accounts for approximately 2%-3% of human malignancies and is the most aggressive among urologic tumors. Biological heterogeneity, drug resistance, and chemotherapy side effects are the biggest obstacles to the effective treatment of RCC. The NF-κB transcription factor is one of several molecules identified to be responsible for the aggressive phenotype of this tumor.

Rapid Chagas Disease Drug Target Discovery Using Directed Evolution in Drug-Sensitive Yeast.

Recent advances in cell-based, high-throughput phenotypic screening have identified new chemical compounds that are active against eukaryotic pathogens. A challenge to their future development lies in identifying these compounds' molecular targets and binding modes. In particular, subsequent structure-based chemical optimization and target-based screening require a detailed understanding of the binding event.

Telehealth solutions to enable global collaboration in rheumatic heart disease screening.

Background The global burden of rheumatic heart disease is nearly 33 million people. Telemedicine, using cloud-server technology, provides an ideal solution for sharing images performed by non-physicians with cardiologists who are experts in rheumatic heart disease. Objective We describe our experience in using telemedicine to support a large rheumatic heart disease outreach screening programme in the Brazilian state of Minas Gerais.

Echocardiographic prevalence of rheumatic heart disease in Brazilian schoolchildren: Data from the PROVAR study.

Background: Accurate estimates of Rheumatic Heart Disease (RHD) burden are needed to justify improved integration of RHD prevention and screening into the public health systems, but data from Latin America are still sparse.

Objective: To determine the prevalence of RHD among socioeconomically disadvantaged youth (5-18years) in Brazil and examine risk factors for the disease.

Methods: The PROVAR program utilizes non-expert screeners, telemedicine, and handheld and standard portable echocardiography to conduct echocardiographic screening in socioeconomically disadvantaged schools in Minas Gerais, Brazil.

Efficacy of a Standardized Computer-Based Training Curriculum to Teach Echocardiographic Identification of Rheumatic Heart Disease to Nonexpert Users.

The ability to integrate echocardiographic for rheumatic heart disease (RHD) into RHD prevention programs is limited because of lack of financial and expert human resources in endemic areas. Task shifting to nonexperts is promising; but investigations into workforce composition and training schemes are needed. The objective of this study was to test nonexperts' ability to interpret RHD screening echocardiograms after a brief, standardized, computer-based training course.

Rheumatic heart disease echocardiographic screening: approaching practical and affordable solutions.

Rheumatic heart disease (RHD) affects at least 32.9 million people worldwide and ranks as a leading cause of death and disability in low-income and middle-income countries (LMICs). Echocardiographic screening has been demonstrated to be a powerful tool for early RHD detection, and holds potential for global RHD control.

Trends in Procedure Type, Morbidity and In-Hospital Outcomes of Patients with Peripheral Artery Disease: Data from the Brazilian Public Health System.

Background: The prevalence of peripheral artery disease (PAD) is rising worldwide, with considerable impact on health care systems.

Methods: We aimed to characterize the trends in therapeutic procedures and outcomes of PAD in the Brazilian Public Health System Database (DataSUS) between 2008 and 2012.

Results: The number of hospitalizations remained stable from 2008 to 2012, although there was a significant change in the proportions of treatment modalities.