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BackgroundMitigation of climate change requires that new routes for the production of fuels and chemicals be as oil-independent as possible. The microbial conversion of lignocellulosic feedstocks into terpene-based biofuels and bioproducts represents one such route. This work builds upon previous demonstrations that the single-celled carotenogenic basidiomycete, Rhodosporidium toruloides, is a promising host for the production of terpenes from lignocellulosic hydrolysates.ResultsThis study focuses on the optimization of production of the monoterpene 1,8-cineole and the sesquiterpene α-bisabolene in R. toruloides. The α-bisabolene titer attained in R. toruloides was found to be proportional to the copy number of the bisabolene synthase (BIS) expression cassette, which in turn influenced the expression level of several native mevalonate pathway genes. The addition of more copies of BIS under a stronger promoter resulted in production of α-bisabolene at 2.2 g/L from lignocellulosic hydrolysate in a 2-L fermenter. Production of 1,8-cineole was found to be limited by availability of the precursor geranylgeranyl pyrophosphate (GPP) and expression of an appropriate GPP synthase increased the monoterpene titer fourfold to 143 mg/L at bench scale. Targeted mevalonate pathway metabolite analysis suggested that 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMGR), mevalonate kinase (MK) and phosphomevalonate kinase (PMK) may be pathway bottlenecks are were therefore selected as targets for overexpression. Expression of HMGR, MK, and PMK orthologs and growth in an optimized lignocellulosic hydrolysate medium increased the 1,8-cineole titer an additional tenfold to 1.4 g/L. Expression of the same mevalonate pathway genes did not have as large an impact on α-bisabolene production, although the final titer was higher at 2.6 g/L. Furthermore, mevalonate pathway intermediates accumulated in the mevalonate-engineered strains, suggesting room for further improvement.ConclusionsThis work brings R. toruloides closer to being able to make industrially relevant quantities of terpene from lignocellulosic biomass.

Obesity is a pandemic disease characterized by lipid accumulation, increased proinflammatory cytokines, and reactive oxygen species. It is associated with the development of comorbidities that lead to death. Additionally, drug treatments developed to control obesity are insufficient and have a variety of adverse effects. Thus, the search for new anti-obesity therapies is necessary. Campomanesia adamantium is a species from the Brazilian Cerrado that has the potential to treat obesity, as described by the antihyperlipidemic activity of its roots. Therefore, this study aimed to investigate the activity of the aqueous extract of C. adamantium leaves (AECa) on the control of reactive species in vitro, on lipid accumulation in adipocytes and Caenorhabditis elegans, and on the production of proinflammatory cytokines in adipocytes. The antioxidant capacity of AECa was observed by its action in scavenging DPPH• free radical, iron-reducing power, and inhibition of β-carotene bleaching. AECa reduced lipid accumulation in preadipocytes and in C. elegans. Moreover, AECa reduced the production of the proinflammatory cytokines MCP-1, TNF-α, and IL-6 in adipocytes. In summary, the antioxidant activity and the ability of AECa to reduce the accumulation of lipids and proinflammatory cytokines indicate, for the first time, the anti-obesity potential of C. adamantium leaves.

This paper analyzes, designs and implements a reconfigurable phase-shifted full-bridge (PSFB) converter. It adopts the topology of the traditional PSFB converter and incorporates clamping circuits to solve some fundamental problems of conventional topology. In addition, auxiliary switches are employed for output reconfiguration, which allows expanding the output voltage range without compromising the system efficiency. Single pole double throw (SPDT) mechanical switches are used to realize series and parallel connections. In this paper, the characterization of the PSFB converter with clamping circuit and its design considerations are discussed. A 10 kW prototype with a power density of 0.485 W/cm3, 900 V input voltage and 400/800 V nominal output voltage was manufactured. The experimental results validated the analysis and confirmed the high conversion efficiency for a wide load range; an efficiency of 96.69% was obtained for the full load condition.

Blueberries (Vaccinium corymbosum L.) are cultivated worldwide and are among the best dietary sources of bioactive compounds with beneficial health effects. This study aimed to investigate the components of Peruvian blueberry using high-performance liquid chromatography coupled to electrospray ionization and quadrupole time-of-flight mass spectrometry (HPLC–ESI–QTOF–MS/MS), identifying 11 compounds. Furthermore, we assessed in vitro the antioxidant activity and in vivo the antidepressant effect using a rat model and protective effect on lipid peroxidation (in the serum, brain, liver, and stomach). We also conducted molecular docking simulations with proteins involved in oxidative stress and depression for the identified compounds. Antioxidant activity was assessed by measuring total phenolic and flavonoid contents, as well as using 1,1-diphenyl-2-picrylhydrazin (DPPH), 2,2′-azino-bis-(3-ethylbenzothiazoline-6-sulfonic) acid (ABTS•+), and ferric-reducing antioxidant power (FRAP) assays. Peruvian blueberries demonstrated higher antioxidant activity than Vaccinium corymbosum fruits from Chile, Brazil, the United States, Turkey, Portugal, and China. The results showed that oral administration of Peruvian blueberries (10 and 20 mg/kg) for 28 days significantly (p < 0.001) increased swimming and reduced immobility in the forced swimming test (FST). Additionally, at doses of 40 and 80 mg/kg, oxidative stress was reduced in vivo (p < 0.001) by decreasing lipid peroxidation in brain, liver, stomach, and serum. Molecular docking and absorption, distribution, metabolism, excretion, and toxicity (ADMET) predictions were performed. In the molecular docking studies, quercitrin and 3,5-di-O-caffeoylquinic acid showed the best docking scores for nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, superoxide dismutase, and xanthine oxidase; while 3,5-dicaffeoylquinic acid methyl ester and caffeoyl coumaroylquinic acid had the best docking scores for monoamine oxidase and serotonin receptor 5-HT2. In summary, our results suggest that the antidepressant and protective effects against lipid peroxidation might be related to the antioxidant activity of Peruvian Vaccinium corymbosum L.

The demand for critical chemical elements applied in clean energy technologies is increasing and, although deep-sea mining feasibility still is an open question, it might be a pathway to overcome the problem. Among areas of interest for seabed mining, the Rio Grande Rise is an ocean ridge in the southwest Atlantic Ocean known for hosting a large polymetallic mineral deposit containing various critical elements at high concentrations. Therefore, this mineralogical and chemical study characterizes the Rio Grande Rise FeMn crusts and establishes features from a structural-chemical perspective that can guide further studies from various locations. Combining X-ray diffractometry, Raman spectroscopy, chemical analysis, and Scanning Electron Microscopy, it was found that samples are composed by manganese oxides, MnOx; ferryxite or goethite, FeOOH; magnesian calcite, Ca,Mg(CO3)2; and carbonate fluorapatite, Ca5(PO4,CO3)3F. The external portion of analyzed rocks consists of younger crust layers enriched in critical metals, such as cobalt (Co) and nickel (Ni), associated with MnOx – mainly vernadite and asbolane; titanium (Ti), associated with iron oxyhydroxides; and rare earth elements (REE), at distinct bearing minerals. Therefore, the data herein reported show that regions where the FeMn crusts have a thicker young layer host a higher content of critical elements. In addition, the information about the elemental distribution and mineral associations can guide further mineral and metallurgical processing steps.

Abstract Background & aims Apolipoproteins and lipoprotein(a) are associated with various cardiometabolic diseases, including insulin resistance, diabetes mellitus, hypertension, dyslipidemia, among others. This systematic review and meta-analysis was conducted to evaluate the association of these markers with metabolic syndrome (MetS). Methods We ran a systematic search through PubMed, Scopus, Embase, Ovid/Medline, and Web of Science on March 15, 2023. No language or date restrictions were applied. The only synthesised effect measure reported was the odds ratio (OR) with its corresponding 95% confidence interval (95% CI). We utilised the random-effects model for the quantitative synthesis. Results We analysed 50 studies (n = 150 519) with different definitions for MetS. Increased ApoB values were associated with MetS (OR = 2.8; 95% CI: 2.44–3.22; p

Resumen Objetivos: Determinar la predicción de las caídas y caídas recurrentes asociadas a factores de riesgo en el adulto mayor que vive en el domicilio. Metodología: Estudio cuantitativo y transversal realizado en La Libertad, Perú. La muestra fue de 1.110 adultos mayores que viven en el domicilio y se utilizó instrumentos como perfil social, enfermedades y medicamentos autorreferidos, caídas, estado cognitivo, síntomas depresivos, actividad básica e instrumental de la vida diaria, y equilibrio estático y dinámico. Se analizó con estadística descriptiva, curvas ROC y el área bajo la curva para evaluar los valores predictivos y la regresión logística. Resultados: La mayoría era mujer, de entre 60 y 79 años, con compañero, viven acompañados y trabajan. La prevalencia de caídas fue del 30,5% y de caídas recurrentes del 14%. Hubo predominio de aquellos sin déficit cognitivo, necesitaban ayuda para las actividades instrumentales e independientes para las básicas, sin síntomas depresivos y con equilibrio estático y dinámico preservado. En la regresión hubo relación entre caídas con ser mujer, vivir solo, número de enfermedades y medicamentos y dependencia para las actividades básicas. Para caídas recurrentes hubo asociación con vivir solo, uso de medicamentos y dependencia para las actividades instrumentales. Conclusiones: La caída está asociada a diferentes factores y su identificación precoz es importante para la creación de planes de cuidados por el equipo multiprofesional evitando problemas físicos y psicológicos en el adulto mayor.

En la capital de un país de América Latina y el Caribe, en una institución de salud muy prestigiosa, con investigadores acreditados, con comité de ética que revisa y aprueba o rechaza los protocolos, con innumerables documentos nacionales e internacionales, con la presencia de una autoridad regulatoria de las investigaciones; algo sucedió sin que nadie lo notara… hasta que una persona fue reclutada de modo solapado y sintió que no quería ser “un número y algo más”.

Abstract Evolution of complex communities of coexisting microbes remains poorly understood. The long-term evolution experiment on Escherichia coli (LTEE) revealed the spontaneous emergence of stable coexistence of multiple ecotypes, which persisted for more than 14,000 generations of continuous evolution. Here, using a combination of experiments and computer simulations, we show that the emergence and persistence of this phenomenon can be explained by the combination of two interacting trade-offs, rooted in biochemical constraints: First, faster growth is enabled by higher fermentation and obligate acetate excretion. Second, faster growth results in longer lag times when utilizing acetate after glucose is depleted. This combination creates an ecological niche for a slower-growing ecotype, specialized in switching to acetate. These findings demonstrate that trade-offs can give rise to surprisingly complex communities with evolutionarily stable coexistence of multiple variants in even the simplest environments.

Introduction: Organ transplantation is one of the most successful advances in modern medicine. However, a legal system is necessary for its practice to be free from ethical flaws and to respect donors, recipients, and family members. Objective: To map the global legislation regulating the donation, capture and distribution processes of organs and tissues from deceased donors for transplants. Method: A scoping review according to the Joanna Briggs Institute was conducted in the following databases: Medline, CINAHL, Virtual Health Library, SCOPUS, Web of Science, Science Direct, and EMBASE, as well as gray literature, and reported according to the PRISMA extension for scoping reviews. Results: We identified 3302 records, of which 77 were analyzed which enabled mapping the type of consent adopted and the existence of current legislation for harvesting organs and tissues after circulatory and brain death. Conclusion: Opt-out consent predominates in Europe, and there is harvesting after brain and circulatory death. Opt-out predominates in the Americas, while Opt-in and harvesting of organs and tissues after brain death predominate in Asia and Oceania. The procurement of organs and tissues from deceased donors is practically non-existent in Africa.

PURPOSEAs the fifth international consensus on advanced breast cancer (ABC5) established guidelines for the management of this disease, the aim of this article was to present the applicability of the consensus recommendations and to generate knowledge to improve access.METHODSSixty-one recommendation statements were selected and discussed by 15 breast cancer experts from Latin America (LA). After the discussion, the level of consensus was determined through a vote. In addition to this, the level of access to each of the recommendations presented, according to the country and health system, was exposed.RESULTSLatin American experts had a high level of agreement with the ABC5 consensus recommendations (range, 83%-100%). Twelve of 61 statements are not available for all patients in LA. Among the limitations to access, the following ones are described: limited access to certain technologies (stereotactic body radiotherapy, positron emission tomography-computed tomography), the high costs of drugs that limits access to treatment with CDK4/6 inhibitors, pertuzumab, or poly(ADP-ribose) polymerase inhibitors, and the lack of molecular tests for access to therapeutic targets, as well as the difficult geography and cultural diversity of our continent.CONCLUSIONDespite the great relevance of the recommendations of the ABC5 consensus guidelines, we highlight that we still need to improve access for all patients, regardless of the country or health system they are in, for which we call to action to policy makers and patient groups to improve clinical outcomes of patients with advanced breast cancer in our region.

El dengue es una infección viral transmitida a través del mosquito Aedes aegypti y presenta cuatro serotipos (DENV-1 a DENV-4). La enfermedad desencadena una variedad de manifestaciones clínicas, desde formas leves sin signos de alarma hasta formas graves, potencialmente mortales. Se presenta el caso de un niño de cinco años, procedente de la provincia del Callao, cuyos síntomas iniciales fueron fiebre, cefalea y malestar general. Al tercer día, el niño manifiestó dolor abdominal leve y vómitos escasos; posteriormente, distensión abdominal, ictericia y coluria. Fue hospitalizado en la unidad de cuidados intensivos pediátricos con deshidratación moderada, ictericia, edemas, abdomen distendido y doloroso, matidez desplazable, hígado a 2 cm debajo del reborde costal derecho y lúcido. Por exámenes complementarios, se evidenció falla hepática, hepatoesplenomegalia y derrame pleural en bases. Se diagnosticó dengue grave a través de una prueba de ELISA Ig M reactivo más sobreinfección por probable peritonitis bacteriana espontánea. Se inició el tratamiento con antibióticos, furosemida, plasma fresco congelado, crioprecipitado y metamizol. Al no observarse mejoría, se optimizó el diurético y se administró albúmina humana. Mostró mejoría con disminución de ascitis, edemas, ictericia y efusión pleural; también mejora del perfil hepático y de la coagulación, además de encontrarse afebril. Presentó inesperadamente dificultad respiratoria por insuficiencia cardiaca congestiva debido a miocardiopatía dilatada según ecocardiografía; se manejó con diuréticos. Fue dado de alta en estado afebril, sin edemas y con resolución de falla hepática y trastorno de coagulación.

BackgroundDengue has emerged as an unprecedented epidemic in Peru, and it is anticipated that this issue will escalate further owing to climate change. This study aimed to determine the risk factors associated with death from dengue in patients treated at Hospital II in Pucallpa, Peru.MethodologyThis retrospective cohort study collected information from the medical records of patients with a diagnosis of dengue treated at Hospital II Pucallpa-Peru between January 2019 and March 2023. The primary outcome was death, and the secondary outcome was death, development of severe dengue, or Intensive Care Unit (ICU) admission. Cox regression models were used to determine risk factors.FindingsThe clinical records of 152 patients were evaluated, with a median age of 27.5 years (interquartile range, 11-45). Among all patients, 29 (19.1%) developed severe dengue, 31 (20.4%) were admitted to the ICU, and 13 (8.6%) died during follow-up. In the survival analysis, bilirubin >1.2 mg/dL was associated with a higher risk of death aHR: 11.38 (95% CI: 1.2 106.8). Additionally, factors associated with poor prognosis included having 1 to 3 comorbidities aRR: 1.92 (1.2 to 3.2), AST ≥251 U/L aRR: 6.79 (2.2 to 21.4), history of previous dengue aRR: 1.84 (1.0 to 3.3), and fibrinogen ≥400 mg/dL aRR: 2.23 (1.2 to 4.1).SignificanceElevated bilirubin was associated with death from dengue, whereas an increase in comorbidities and a history of previous dengue were related to a poor prognosis of the disease. Early identification of severe dengue would be more feasible with improved access to laboratory testing, particularly in tropical areas with a high dengue incidence.

Actualmente el médico especialista tiene como parte del perfil de egreso la búsqueda, análisis y discusión de la información. La comprensión lectora se genera tras la relación del texto con el lector y se encarga de construir un conocimiento al relacionar lo leído y lo aprendido. Nos propusimos evaluar el nivel de competencia de lectura crítica en médicos residentes de medicina familiar (MF) de la Unidad de Medicina Familiar No. 24 (U.M.F. No.24), del Instituto Mexicano del Seguro Social (IMSS); para evaluar si cuentan con la competencia de lectura crítica se aplicó el instrumento de evaluación de lectura crítica (Campos A y cols. 2016). El 63% de los residentes de MF presento un nivel de comprensión lectora medio. No se encontró significancia estadística al correlacionar las variables comprensión lectora y sexo, y al correlacionar comprensión lectora y edad. Concluimos que la competencia de lectura crítica encontrada en los médicos residentes de la U.M.F. No. 24 es de nivel medio, siendo mayor que el nivel encontrado en otros estudios bajo condiciones similares. Es necesario establecer estrategias educativas que mejoren las capacidades de lectura crítica de artículos médicos.

BackgroundHuman milk contains a complex mixture of triacylglycerols (TAG), making it challenging to recreate using common ingredients.ObjectiveThe study aimed to develop an innovative fermentation technique to produce essential human milk TAG, effectively tackling a significant hurdle in infant nutrition.MethodAn in-depth analysis of the literature has been conducted to identify the specific TAG to be targeted. We used a microalgal oil production platform and a two-step procedure to modify its fatty acid and TAG composition. The palmitic acid (16:0) content has been increased by classical strain improvement techniques, followed by a step involving the expression of a lysophosphatidic acid acyltransferase (LPAAT) sequence capable of esterifying 16:0 specifically at the internal position (sn-2 palmitate) of TAG. Once the strain was stabilized, the fermentation was scaled up in a 50-L reactor to yield several kilograms of biomass. Subsequently, the oil was extracted and refined using standard oil processing conditions. Liquid chromatography-mass spectrometry was employed to monitor the TAG profile and the region specificity of 16:0 at the internal position (sn-2 palmitate) of TAG.ResultsThe initial strain had a 16:0 level of 25% of total fatty acids, which was increased to 30% by classical strain improvement. Simultaneously, the oleic acid level decreased from 61% to 57% of total fatty acids. Upon expression of an exogenous LPAAT gene, the level of the 16:0 esterified in the internal position of the TAG (sn-2 palmitate) increased by a factor of 10, to reach 73% of total palmitic acid. Consequently, the concentration of oleic acid in the internal position decreased from 81% to 22% of total fatty acids, with TAG analysis confirming that the primary TAG species in the oil was 1,3-dioleoyl-2-palmitoyl-glycerol (OPO). The 50-L-scale fermentation trial confirmed the strain's ability to produce oil with a yield of >150 g of oil per liter of fermentation broth in a timeframe of 5 days, rendering the process scalable for larger-scale industrialization.ConclusionWe have demonstrated the feasibility of producing a suitable TAG composition that can be effectively integrated into the formulations of infant nutrition in combination with other fats and oils to meet the infant feeding requirements.