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Abstract Biodiversity and ecosystem functions are highly threatened by global change. It has been proposed that geodiversity can be used as an easy-to-measure surrogate of biodiversity to guide conservation management. However, so far, there is mixed evidence to what extent geodiversity can predict biodiversity and ecosystem functions at the regional scale relevant for conservation planning. Here, we analyse how geodiversity computed as a compound index is suited to predict the diversity of four taxa and associated ecosystem functions in a tropical mountain hotspot of biodiversity and compare the results with the predictive power of environmental conditions and resources (climate, habitat, soil). We show that combinations of these environmental variables better explain species diversity and ecosystem functions than a geodiversity index and identified climate variables as more important predictors than habitat and soil variables, although the best predictors differ between taxa and functions. We conclude that a compound geodiversity index cannot be used as a single surrogate predictor for species diversity and ecosystem functions in tropical mountain rain forest ecosystems and is thus little suited to facilitate conservation management at the regional scale. Instead, both the selection and the combination of environmental variables are essential to guide conservation efforts to safeguard biodiversity and ecosystem functions.

The COVID-19 pandemic, and the associated confinement, imposed a novel personal and social context for university students; nevertheless, few studies have addressed the effects of this on distance university students. Indeed, defining the needs of these students under such unique circumstances will allow them to receive the support necessary to effectively reduce their perceived stress and improve their academic achievement. A predictive model was designed to examine the direct effects of the variables' age and perceived study time on stress and academic achievement in students in an online learning context, as well as to assess the indirect effects through the mediating role of academic self-efficacy. Using path analysis, the model was tested on a sample of 1030 undergraduate students between 18 and 60 years old enrolled on a psychology degree course at the UNED (National Distance Learning University of Spain). The model provides a good fit to the data, confirming the mediating role of academic self-efficacy. Perceived study time is a factor negatively associated with stress and positively with academic achievement. However, it appeared that age was not related to academic achievement, indicating that academic self-efficacy had no mediating effect on these two variables. Academic self-efficacy is a mediator and protective factor in challenging times like the COVID-19 pandemic. These results may contribute to the design of educational and clinical interventions for students at an online learning university over an extended age range.

Abstract This study investigated the impact of drying temperature on the physicochemical and mechanical properties of banana pseudostem fibers sourced from the Cordoba region in Colombia. Banana fibers (BFs) were extracted through mechanical decortication from the banana pseudostem (BP) of the plant and subsequently oven-dried at temperatures of 40 °C and 90 °C. Six mathematical models were employed to analyze the drying behavior of the fibers. The density of the BFs was determined using the apparent density method, and their chemical composition was evaluated via bromatological analysis. Fiber diameter was measured using optical microscopy (OM). The BF samples were characterized by scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TG), contact angle measurements, and tensile testing. The results indicated that noncellulosic materials were removed from the fibers when dried at 90 °C, as evidenced by alterations in thermal degradation and fiber surface morphology observed through TG and SEM, suggesting a reduction in lignin content. While drying temperature did not affect fiber stiffness or ductility, a correlation with fiber diameter was noted. Thinner fibers, ranging from 148 to 250 μm, exhibited increased tensile strength and Young’s modulus, attributed to a more compact microfibril arrangement.

Abstract A lactate/albumin ratio (LAR) greater than 0.5 measured early in the course of pediatric critical illness is associated with greater mortality. Whether the elevated LAR can be explained by microcirculation disorders in children with sepsis is not known. In this longitudinal retrospective study (January 2021-January 2024), serum albumin and lactate were measured on admission to the pediatric intensive care unit (PICU), with sublingual video microscopy performed simultaneously to measure microcirculation. A total of 178 children were included, 37% of whom had septic shock measured with the Phoenix Sepsis Score. Patients with remote sepsis had greater odds of an elevated LAR (aOR 6.87: 95% CI 1.98–23.73; p

The phenomenon of disinformation raises serious questions for society, affecting public trust and democratic stability. In this context, an attempt is made to configure a profile of the practices of identification and fight against disinformation, assess the incidence of social networks, and identify citizens’ perceptions of media literacy in Ecuador. The methodology used is quantitative and qualitative, with a descriptive approach, using a survey, interviews with experts, and focus groups. The converging points between experts and citizens are the need to develop media literacy processes that begin in basic education and the institutionalisation of the fight against disinformation, which should be assumed through an articulation between citizens and schools. On the other hand, training to identify fake news is directly related to information verification practices. Likewise, statistical evidence shows that Ecuadorians who verify information perceive themselves as fully informed citizens.

La granulomatosis con poliangitis (GPA) es una vasculitis de pequeño vaso, está asociada a anticuerpos anticitoplasma de neutrófilos (ANCA), compromete principalmente el tracto respiratorio superior y el compromiso gastrointestinal está presente de un 4-20 %. Sin embargo, la isquemia mesentérica es una de las asociaciones más inusuales. Se reporta un caso de un hombre de 64 años con síntomas rinosinusales crónicos, quien consulta por dolor abdominal asociado a lesiones purpúricas palpables; después, con clínica de abdomen agudo que requirió laparotomía exploratoria de urgencias en donde se evidenció isquemia mesentérica. Se realizó el diferencial de causas tromboembólicas sistémicas, se descartaron causas comunes y durante el ejercicio diagnóstico se documentó, por medio de criterios clínicos, paraclínicos e histopatológicos, una GPA ANCA proteinasa 3 (PR3) positivo, se inició tratamiento con ciclofosfamida y corticoides, hubo mejoría significativa de las manifestaciones clínicas iniciales.

Abstract We study the non-equilibrium dynamics of two coupled SYK models, conjectured to be holographically dual to an eternal traversable wormhole in AdS2. We consider different periodic drivings of the parameters of the system. We analyze the energy flows in the wormhole and black hole phases of the model as a function of the driving frequency. Our numerical results show a series of resonant frequencies in which the energy absorption and heating are enhanced significantly and the transmission coefficients drop, signalling a closure of the wormhole. These frequencies correspond to part of the conformal tower of states and to the boundary graviton of the dual gravitational theory. Furthermore, we provide evidence supporting the existence of a hot wormhole phase between the black hole and wormhole phases. When driving the strength of the separate SYK terms we find that the transmission can be enhanced by suitably tuning the driving.

La obesidad es un problema multifactorial con fenotipo de riesgo cardiometabólico que requiere un estilo de vida saludable con intervenciones dietéticas como pilar del tratamiento. El auge en la investigación de componentes bioactivos de la dieta permite conocer su regulación en la expresión de genes y en la patogénesis de obesidad. Los polifenoles son compuestos variables y abundantes en alimentos de origen vegetal en la dieta de nuestra población. La adherencia a patrones dietéticos ricos en polifenoles confiere beneficios en la progresión de obesidad, función inmunomoduladora con regulación a la baja de vías de señalización proinflamatorias y disminución del estrés oxidativo, mejora la homeostasis de glucosa, regula la diferenciación de adipocitos, la oxidación de ácidos grasos y modula el microbioma intestinal. La evidencia en los beneficios que otorgan los polifenoles está bien establecida a nivel preclínico; sin embargo, la traslación al entorno clínico en las intervenciones dietéticas sigue siendo compleja debido a la variabilidad en la dosis efectiva, la biodisponibilidad y la falta de estandarización. Promover la investigación clínica activa con intervenciones dietéticas que incluyan estos componentes, así como promover la alimentación de la población basada en estos nutrimentos, contribuye al control de la transición exponencial de la obesidad.

ABSTRACT The presence of arbuscular mycorrhizal fungi (AMF) is essential for the survival and establishment of most plant species in nature. The reproductive success of invasive plant species in a particular habitat could also depend on these AM fungi. Cinchona pubescens, commonly known as quinine, is highly invasive on Santa Cruz Island, Galápagos, but at the same time severely endangered in its native range on mainland Ecuador due to overexploitation in the past. In this study, we aim at determining the AMF communities associated with C. pubescens at both locations to investigate whether the successful invasion of C. pubescens on Santa Cruz is related to its association with a particular community of AMF. For this, roots of C. pubescens trees were sampled at three sites, one site on Santa Cruz and two sites in the province of Loja, on mainland Ecuador. Communities of AM fungi were determined through the molecular cloning and sequencing of the 18S nrDNA gene and through the delimitation of Operational Taxonomic Units (OTUs), associated with the plant roots. We found 36 AMF OTUs associated with C. pubescens, most of them belonging to the genus Glomus. The highest richness of AMF OTUs was detected in samples from sites located on mainland Ecuador. The AMF communities between Santa Cruz and mainland Ecuador were significantly different, and only five OTUs were shared between both locations. Two dominant OTUs in C. pubescens from Santa Cruz were detected but no dominant OTUs from mainland Ecuador. Almost two thirds of the OTUs associated with C. pubescens had a wide global distribution. Our results suggest that the successful invasion of C. pubescens on Santa Cruz could have been facilitated by local generalist AMF and not by particular AMF. The observed generalist AMF from both locations could be important for conservation plans of restoring the endangered C. pubescens in the native forests on mainland Ecuador.

This paper proposes a research agenda to study cultural networks that assumes their role both in making meaning and as adaptative tools for humans and their communities. First, the agenda grounds the study of cultural networks in Whitehead’s (1861–1947) metaphysics of process, posing that cultural networks emerge during human’s production of relations with the world of phenomena. Then, the paper identifies two approaches to studying cultural networks, reassembling them or generating them. Thirdly, it contextualizes the importance of understanding cultural networks vis a vis the consolidation of the digital humanities in the academic domain, and the productivity of networks as tools to explore the cultural in networked domains of human experience. The final remarks locate the proposed research agenda within the context of multidisciplinary research on cultural analytics.

Introducción. El reflejo nauseoso es un mecanismo de protección que impide que alimentos y agentes no deseados penetren en la vía aérea inferior. Usualmente, hace parte del examen físico de la deglución para detectar la disfagia orofaríngea, pero es un signo potencialmente ambiguo. Objetivo. Evaluar el valor diagnóstico del reflejo nauseoso en pacientes con disfagia orofaríngea neurogénica y en pacientes sin ella. Materiales y métodos. Se trata de un estudio observacional, analítico, en pacientes con disfagia orofaríngea neurogénica (casos) y en personas sin disfagia (controles), en el cual se evaluó por visualización directa la ausencia o la presencia del reflejo nauseoso de forma bilateral. Este resultado se ajustó por sexo, edad y otras variables de interacción. Resultados. Se evaluaron 86 pacientes con disfagia orofaríngea neurogénica y 80 personas sin ella. En el examen físico de la deglución, la presencia del reflejo mostró una relación positiva con los pacientes (lado derecho: OR = 3,97; IC95%: 2,01-7,84; lado izquierdo: OR = 4,84; IC95%: 2,41-9,72), pero una asociación negativa con los controles. En ambos grupos, ni el sexo ni la edad, ni otras variables de interacción modificaron el reflejo nauseoso. Conclusiones. La ausencia o la presencia del reflejo nauseoso no confirma ni excluye la existencia de una disfagia orofaríngea por causas neurológicas o neuromusculares; por lo tanto, no es recomendable que los profesionales de la salud se fíen del resultado de este reflejo. Los médicos tratantes deben ir más allá de una simple revisión del reflejo nauseoso, incluso en pacientes neurológicos en quienes se supone que debería estar ausente.

The present work analyzes the use of hybrid joints for the construction of yachts with the purpose of reducing the structural weight. By means of the elaboration of specimens made of tubular steel and fiberglass (GFRP). This is to significantly reduce the weight of the superstructure, allowing the yacht to be lighter. At the same time this reduces the fuel consumption, being environmentally friendly. Several test tubes were built with different layers of fiberglass covering the tubular structure in the form of a crosshead, to give it greater strength. To test the forces supported by this composite material, half of the specimens were tested in flexure and the other half in traction. On the other hand, the deformation of the material was analyzed by means of extensometers to observe the moment of failure in the hybrid joint. After the tests, it was determined that the flexural specimens present three important phases, the first is linear (elastic zone), the second phase showed cracks and a parabolic curve was formed (plastic zone) and finally the rupture. The same occurred with the tensile specimens, with the difference that the hybrid joint is the last to fail, withstanding a considerable force before reaching the plastic zone. Finally, the deformations were checked by means of a mathematical model, both in bending and in traction. All the experiments carried out both in bending and in tension were checked with a mathematical model made in ACP Ansys giving reliable results. The modeling program is very successful for future structural analysis, especially with composite laminations.

BackgroundSome clinical dyslipidemia cases do not respond to statins, known as statin-resistant familial hypercholesterolemia (SR-FH), in which patients are under a high cardiovascular risk despite statin therapy. Therefore, novel therapeutic alternatives are required. Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) reduce cholesterol levels and cardiovascular disease risk, particularly in patients with SR-FH, where PCSK9i may differentially affect pro- and anti-inflammatory mediators depending on the clinical setting.AimTo evaluate the effect of PCSK9i treatment on pro- and anti-inflammatory cytokines in patients with SR-FH.MethodsBefore–after comparison, quasi-experimental, single-center study in patients with SR-FH. Blood samples were processed to obtain complete blood counts of glycated hemoglobin and serum lipid levels. Flow cytometry was performed to characterize baseline circulating M1- and M2-macrophages and monocytes. Multiplexing of plasma samples was used to compare plasma fraktaline, interleukins (ILs), monocyte chemoattractant protein-1 (MCP-1), and tumor necrosis factor (TNF)-alpha. The endpoints were lower serum lipid levels and pro-inflammatory mediator modification.ResultsTwenty patients with SR-FH, aged 58 years and most of them males, were included, with a mean body–mass index of 26.4 and showing ischemic heart disease and similar values of baseline M1- and M2-macrophages and monocytes. Six-month iPSCK-9 therapy considerably reduced LDLc, increased anti-inflammatory cytokine (IL-4), and modified pro-inflammatory cytokine (TNF-alpha and MCP-1) levels. No notable effects were observed for the other markers.ConclusionPCSK9i therapy exerted subclinical anti-inflammatory and anti-atherogenic effects, indicating potential benefits for clinical outcomes.

A network of agronomists, researchers, and practitioners associated with cacao farming provided open access to their independent field trials across Latin America and the Caribbean (LAC). A centralized dataset was assembled using qualitative and quantitative data from 25 experimental field trials (hereafter referred to as “CacaoFIT”) spanning several LAC agroecosystems. This dataset was used to document the main traits and agroclimatic attributes of the cacao cultivation model being tested within the CacaoFIT network. By synthesizing data from an entire network of cacao trials, this study aimed to highlight specific design features and management practices that may contribute to better cacao farming sustainability. The CacaoFIT network comprises 200 ha of field trials testing over 150 cacao genotypes and set up under different shade canopy design, management, and research goals. Small-sized trials were common across Mesoamerica, whereas medium to large-size trials were distinct to South America. Cacao trials were 15 years old (on average) and ranged from 3 to 25 years of establishment. Most cacao trials were managed conventionally (i.e., 55%), while 20% were under organic practices, and the remaining 25% presented both conventional and organic management approaches. Most field trials (ca. 60%) planted an average of 10 international clones or national cultivars at high (1,230–1,500 plants ha−1) and medium density (833–1,111 plants ha−1). Mixed shade canopies were the dominant agroforestry model, while timber vs. leguminous shade canopies were also common. The diversity and depth of research domains examined across the CacaoFIT network varied widely. Agronomy and agroforestry topics dominated the research agenda across all trials, followed by environmental services domains. Cacao physiology and financial performance were researched to a lesser extent within the network. Five featured field trials from CacaoFIT offered technical guidelines to inform cacao farming within similar contexts. This collaborative work is a scaffold to encourage public–private partnerships, capacity building, and data sharing amongst cacao researchers across the tropics.

Microfluidic systems offer controlled microenvironments for cell-to-cell and cell-to-stroma interactions, which have precise physiological, biochemical, and mechanical features. The optimization of their conditions to best resemble tumor microenvironments constitutes an experimental modeling challenge, particularly regarding carcinogenesis in the central nervous system (CNS), given the specific features of the blood–brain barrier (BBB). Gel-free 3D microfluidic cell culture systems (gel-free 3D-mFCCSs), including features such as self-production of extracellular matrices, provide significant benefits, including promoting cell–cell communication, interaction, and cell polarity. The proposed microfluidic system consisted of a gel-free culture device inoculated with human brain microvascular endothelial cells (HBEC5i), glioblastoma multiforme cells (U87MG), and astrocytes (ScienCell 1800). The gel-free 3D-mFCCS showed a diffusion coefficient of 4.06 × 10−9 m2·s−1, and it reconstructed several features and functional properties that occur at the BBB, such as the vasculogenic ability of HBEC5i and the high duplication rate of U87MG. The optimized conditions of the gel-free 3D-mFCCS allowed for the determination of cellular proliferation, invasion, and migration, with evidence of both physical and biochemical cellular interactions, as well as the production of pro-inflammatory cytokines. In conclusion, the proposed gel-free 3D-mFCCSs represent a versatile and suitable alternative to microfluidic systems, replicating several features that occur within tumor microenvironments in the CNS. This research contributes to the characterization of microfluidic approaches and could lead to a better understanding of tumor biology and the eventual development of personalized therapies.

Purpose:To describe and compare a peritoneal closure technique using cyanoacrylate glue (Glubran 2®, GEM, Cardiolink SL) with a microdroplet device (Glutack®, GEM, Cardiolink SL) in laparoscopic transabdominal preperitoneal repair (TAPP) of inguinal hernia with the routinely used barbed suture peritoneal closure (V-Lock 3.0, Covidien France).Materials and methods:From January to August 2022, 60 patients undergoing TAPP repair for uni- or bilateral inguinal hernia were randomized into one of two groups. One using as mesh fixation and peritoneal closure the Glutack® device with Glubran 2® cyanoacrylate glue (Glu-close group) and the other using mesh fixation with cyanoacrylate and peritoneal closure with V-lock 3.0 (Sut-close group), with a follow-up of 12 months. Demographic variables, operative time, peritoneal closure time, main surgical findings and main intra- and postoperative complications were analyzed prospectively.Results:63 patients were included with no losses to follow-up. The mean operative time was 34 min (range 58.25) for the glu-close group and 40 (range 64.25) for the sut-close group, with no conversion (0%) for either group. The mean flap closure time was 1.18 min (SD 24 0.19) for the glu-close group and 3.24 min (SD 0.78) for the sut-close group, with statistically significant differences (p < 0.001). The intraoperative complication rate was 0 for the glu-close group and 0 for the sut-close group, with no significant difference. The median hospital stay was 0.8 days (range, 0–1) for both groups. The median duration of follow-up was 12 months and none had hernia recurrence. The postoperative VAS score at the first and second check-up at 1 month and 3 months was 2.83 (SD 1.341) and 0.60 (SD 0.621) in the sut-close group and 1.03 (0.984) and 0.24 (SD 0.435) in the glue-close group, with significant differences (p < 0.001 and p < 0.012).Conclusion:The data demonstrated by the study are that the glue can be used safely to close the peritoneum and that the method provides a small, statistically significant but not clinically relevant reduction in the time to close the peritoneal flap, as well as in postoperative pain after surgery in short and medium term.

Glucose transporter (GLUT4), discovered in 1988, is primarily located in adipocytes and muscle cells. Its unique transport mechanism is characterized by a 10-fold increase in exocytosis rate, which is dependent on insulin. GLUT4’s storage vesicles and recycling pathways, as well as its role in plasma glucose homeostasis and glucose clearance, particularly in the postprandial period, present intriguing lines of research. This transporter has been associated with several metabolic disturbances and components of metabolic syndrome and cardiovascular risks, including type 2 diabetes, hypertension, and dyslipidemia, where insulin resistance plays a major role. At present, there are various methods available to study this phenomenon, but the question remains as to whether these models truly represent the in vivo processes.

Hepatocyte growth factor (HGF) exhibits potent growth-inducing properties across various tissues, while epidermal growth factor (EGF) acts as a molecular integration point for diverse stimuli. HGF plays a crucial role in hepatic metabolism, tissue repair, and offers protective effects on epithelial and non-epithelial organs, in addition to its involvement in reducing apoptosis and inflammation, underscoring its anti-inflammatory capabilities. The HGF-Met system is instrumental in hepatic metabolism and enhancing insulin sensitivity in animal diabetes models. Similarly, the EGF and its receptor tyrosine kinase family (EGFR) are critical in regulating cell growth, proliferation, migration, and differentiation in both healthy and diseased states, with EGF also contributing to insulin sensitivity. In this observational study, we aimed to identify correlations between serum levels of HGF and EGF, insulin, glucagon, glucose, and primary serum lipids in patients with type 2 diabetes mellitus (DM), taking into account the impact of gender. We noted differences in the management of glucose, insulin, and glucagon between healthy men and women, potentially due to the distinct influences of sexual hormones on the development of type 2 DM. Additionally, metabolites such as glucose, albumin, direct bilirubin, nitrites, and ammonia might influence serum levels of growth factors and hormones. In summary, our results highlight the regulatory role of insulin and glucagon in serum glucose and lipids, along with variations in HGF and EGF levels, which are affected by gender. This link is especially significant in DM, where impaired cell proliferation or repair mechanisms lead to metabolic changes. The gender-based differences in growth factors point to their involvement in the pathophysiology of the disease.

Mutations in the lipoyltransferase 1 (LIPT1) gene are rare inborn errors of metabolism leading to a fatal condition characterized by lipoylation defects of the 2-ketoacid dehydrogenase complexes causing early-onset seizures, psychomotor retardation, abnormal muscle tone, severe lactic acidosis, and increased urine lactate, ketoglutarate, and 2-oxoacid levels. In this article, we characterized the disease pathophysiology using fibroblasts and induced neurons derived from a patient bearing a compound heterozygous mutation in LIPT1. A Western blot analysis revealed a reduced expression of LIPT1 and absent expression of lipoylated pyruvate dehydrogenase E2 (PDH E2) and alpha-ketoglutarate dehydrogenase E2 (α-KGDH E2) subunits. Accordingly, activities of PDH and α-KGDH were markedly reduced, associated with cell bioenergetics failure, iron accumulation, and lipid peroxidation. In addition, using a pharmacological screening, we identified a cocktail of antioxidants and mitochondrial boosting agents consisting of pantothenate, nicotinamide, vitamin E, thiamine, biotin, and α-lipoic acid, which is capable of rescuing LIPT1 pathophysiology, increasing the LIPT1 expression and lipoylation of mitochondrial proteins, improving cell bioenergetics, and eliminating iron overload and lipid peroxidation. Furthermore, our data suggest that the beneficial effect of the treatment is mainly mediated by SIRT3 activation. In conclusion, we have identified a promising therapeutic approach for correcting LIPT1 mutations.

Objetivo: como parte de la elaboración de una guía de práctica clínica (GPC) para el cuidado de personas con baja visión en Colombia, se recomienda incluir la participación de pacientes. El objetivo fue identificar los aspectos de la vida cotidiana que se ven más afectados por la baja visión, los cuales se deben trabajar en un proceso de rehabilitación de la visión y así reconocer las barreras para acceder a ese proceso. Además, se pretende calificar la importancia de los desenlaces para los pacientes y sus cuidadores. Metodología: pacientes con baja visión y sus familiares fueron invitados a participar en un grupo focal que indagó por sus percepciones sobre los aspectos más afectados por la baja visión, los elementos más importantes de los procesos de rehabilitación de la visión y sus barreras más frecuentes. Resultados: se reportaron dificultades en la realización de las actividades instrumentales, como el uso del computador o celular, el uso del transporte público, el manejo del dinero, ir de compras, la movilidad y la orientación. La rehabilitación de la visión exitosa fue definida como aquella que les permite recuperar la independencia y ganar confianza en sí mismos. Las intervenciones de rehabilitación que mejoren las capacidades de orientación y movilidad, que incluyan acompañamiento psicológico para el paciente y la familia y que cuenten con enfoques grupales fueron altamente apreciadas. Las barreras administrativas fueron las más mencionadas. Conclusión: estos resultados apoyaron la toma de decisiones en el desarrollo de las recomendaciones de la GPC para personas con baja visión en Colombia.

Properly designed agroforestry systems (AFS) can generate optimal cocoa bean (BC) yields, produce co-products and provide ecosystem services. This study analyzes the interactions between climate, AFS structure and BC yield in six climatic zones across three natural regions of Colombia. A total of 305 plots of 1,000 m2 each were established in 132 farms where the cocoa-AFS structure, BC yield and climatic variables were determined. Five typologies of cocoa-AFS were obtained based on the characteristics of the shade canopy and the abundance of cocoa trees: “Highly diversified multistratum with high biomass” (HDMHB), “Diversified multistratum with high shade and abundance of Musaceae (DMHSM),” “Diversified multistratum with high abundance of cocoa trees (DMHDC),” “Diversified monostratum with low shade (DMLS)” and “monostratum with minimal shade (MMS).” In the departments of Huila and Caquetá, Andean and Amazonia regions, respectively, the HDMHB typology predominated, while in Meta, the Orinoquia region, it was MMS. In the temperate-humid zone, the DMHDC and DMHSM typologies were not found. A high floristic diversity of the shade canopy was found: 229 species; Caquetá registered the highest number (152). The most frequent canopy companion species were Musa paradisiaca, Cariniana pyriformis, Cedrela odorata, Psidium guajava, Musa sapientum, and Cordia alliodora. The highest abundance of cocoa trees occurs in areas with lower temperature and relative humidity and in AFS with lower abundance of fruit and timber trees. Zones with higher temperature and lower precipitation had higher abundance of timber species (r = 0.23). The BC yield is higher in areas with higher precipitation and is related to the lower abundance of individuals of timber and fruit species, and to the higher abundance of Fabaceae. The BC yield depends on the typology (p

ABSTRACTLivestock production in the Colombian Amazonia is typically dual-purpose (meat and milk) based on silvopastoral systems. We aimed to assess how the ecological condition of these systems correspond to the ecosystem services they generate based on an assessment of farmers’ knowledge of the tree species. We evaluated 159 paddocks. We recorded 143 tree species from 37 families, with 22 species being most common (relative occurrence frequency = 57%). Based on tree species composition, we characterized four states of silvopastoral condition (hereon ‘paddock condition types’) using clustering techniques: (i) High structural complexity and highest tree species richness (HSCR); (ii) High species diversity and tall trees (HDTT); (iii) High species diversity and medium-sized trees (HDMT); (iv) Structurally simple with lowest species richness (SSLR). Tree species richness was significantly higher in HSCR (11.70 ± 1.47 per paddock), than in SSLR (2.86 ± 0.80). HDTT and HDMT had similar richness, with intermediate values (5.55 ± 0.82 and 6.38 ± 0.51, respectively). Farmers appreciate a number of ecosystem services provided by the silvopastoral system, but a limited number of tree species are valued. This indicates the need for additional biodiversity conservation measures in these landscapes, including measures to improve knowledge about the value of tree species with few occurrences or low densities.

Abstract Background Patients with COVID-19 have a high incidence of acute kidney injury (AKI), which is associated with mortality. The objective of the study was to determine the factors associated with AKI in patients with COVID-19. Methodology A retrospective cohort was established in two university hospitals in Bogotá, Colombia. Adults hospitalized for more than 48 h from March 6, 2020, to March 31, 2021, with confirmed COVID-19 were included. The main outcome was to determine the factors associated with AKI in patients with COVID-19 and the secondary outcome was estimate the incidence of AKI during the 28 days following hospital admission. Results A total of 1584 patients were included: 60.4% were men, 738 (46.5%) developed AKI, 23.6% were classified as KDIGO 3, and 11.1% had renal replacement therapy. The risk factors for developing AKI during hospitalization were male sex (OR 2.28, 95% CI 1.73–2.99), age (OR 1.02, 95% CI 1.01–1.03), history of chronic kidney disease (CKD) (OR 3.61, 95% CI 2.03–6.42), High Blood Pressure (HBP) (OR 6.51, 95% CI 2.10–20.2), higher qSOFA score to the admission (OR 1.4, 95% CI 1.14–1.71), the use of vancomycin (OR 1.57, 95% CI 1.05–2.37), piperacillin/tazobactam (OR 1.67, 95% CI 1.2–2.31), and vasopressor support (CI 2.39, 95% CI 1.53–3.74). The gross hospital mortality for AKI was 45.5% versus 11.7% without AKI. Conclusions This cohort showed that male sex, age, history of HBP and CKD, presentation with elevated qSOFA, in-hospital use of nephrotoxic drugs and the requirement for vasopressor support were the main risk factors for developing AKI in patients hospitalized for COVID-19.

Objetivo. Analizar cómo asumieron la educación en casa 63 docentes de la educación primaria que han trabajado el proceso de inclusión con estudiantes que presentan retos educativos en lo visual (procesamiento a través de imágenes), cognitivo (procesamiento en acciones concretas) y comunicativo (procesamiento viso-gestual para personas usuarias de lengua de señas colombiana-LSC) en la ciudad de Medellín durante la pandemia 2020-2021. Método. Este trabajo de investigación cualitativa con enfoque interpretativo utilizó la técnica de grupo focal, organizando al personal docente en tres grupos por colectivo de estudiantes con retos educativos: visual, cognitivo y comunicativo, el análisis se centró en la forma como asumieron la educación en casa, estrategias utilizadas y toma de decisiones para la orientación del aprendizaje en consideración a los desafíos que implica este colectivo de personas en sus formas de aprender. Los datos se analizaron mediante la codificación abierta selectiva y axial. Resultados. Los resultados se agrupan en seis momentos de la educación en casa por la que ha transitado el personal docente, referidos a: la desorientación, el aterrizaje forzoso, la adaptación, la cooperación, la expansión y el retorno, cada espacio tiene sus características, aciertos y desaciertos durante el tiempo de la experiencia. Conclusiones. Lo más cercano a la realidad vivida durante la pandemia por el personal docente corresponde a la educación remota y no a educación en casa, caracterizada en desaciertos durante el tiempo de pandemia influenciada en el bajo conocimiento en accesibilidad cognitiva y en uso de las TIC en plataformas, orientación a familias carentes o con baja accesibilidad en conectividad, y aciertos en el trabajo colaborativo en red entre docentes, comunidad académica para discutir las prácticas de enseñanza y evaluación en la educación inclusiva. Los hallazgos en cada momento experimentado por el profesorado durante la pandemia fueron aprovechados para proyectar los desafíos en la educación con el estudiantado. Estos hallazgos se centran a nivel socioemocional, en el aprendizaje, la enseñanza, el apoyo familiar y la formación docente en el retorno a la presencialidad.

Abstract Background Neurodegeneration with brain iron accumulation (NBIA) disorders are a group of neurodegenerative diseases that have in common the accumulation of iron in the basal nuclei of the brain which are essential components of the extrapyramidal system. Frequent symptoms are progressive spasticity, dystonia, muscle rigidity, neuropsychiatric symptoms, and retinal degeneration or optic nerve atrophy. One of the most prevalent subtypes of NBIA is Pantothenate kinase-associated neurodegeneration (PKAN). It is caused by pathogenic variants in the gene of pantothenate kinase 2 (PANK2) which encodes the enzyme responsible for the first reaction on the coenzyme A (CoA) biosynthesis pathway. Thus, deficient PANK2 activity induces CoA deficiency as well as low expression levels of 4′-phosphopantetheinyl proteins which are essential for mitochondrial metabolism. Methods This study is aimed at evaluating the role of alpha-lipoic acid (α-LA) in reversing the pathological alterations in fibroblasts and induced neurons derived from PKAN patients. Iron accumulation, lipid peroxidation, transcript and protein expression levels of PANK2, mitochondrial ACP (mtACP), 4′′-phosphopantetheinyl and lipoylated proteins, as well as pyruvate dehydrogenase (PDH) and Complex I activity were examined. Results Treatment with α-LA was able to correct all pathological alterations in responsive mutant fibroblasts with residual PANK2 enzyme expression. However, α-LA had no effect on mutant fibroblasts with truncated/incomplete protein expression. The positive effect of α-LA in particular pathogenic variants was also confirmed in induced neurons derived from mutant fibroblasts. Conclusions Our results suggest that α-LA treatment can increase the expression levels of PANK2 and reverse the mutant phenotype in PANK2 responsive pathogenic variants. The existence of residual enzyme expression in some affected individuals raises the possibility of treatment using high dose of α-LA.

Abstract Background Proportional assist ventilation with load-adjustable gain factors (PAV+) is a mechanical ventilation mode that delivers assistance to breathe in proportion to the patient’s effort. The proportional assistance, called the gain, can be adjusted by the clinician to maintain the patient’s respiratory effort or workload within a normal range. Short-term and physiological benefits of this mode compared to pressure support ventilation (PSV) include better patient-ventilator synchrony and a more physiological response to changes in ventilatory demand. Methods The objective of this multi-centre randomized controlled trial (RCT) is to determine if, for patients with acute respiratory failure, ventilation with PAV+ will result in a shorter time to successful extubation than with PSV. This multi-centre open-label clinical trial plans to involve approximately 20 sites in several continents. Once eligibility is determined, patients must tolerate a short-term PSV trial and either (1) not meet general weaning criteria or (2) fail a 2-min Zero Continuous Positive Airway Pressure (CPAP) Trial using the rapid shallow breathing index, or (3) fail a spontaneous breathing trial (SBT), in this sequence. Then, participants in this study will be randomized to either PSV or PAV+ in a 1:1 ratio. PAV+ will be set according to a target of muscular pressure. The weaning process will be identical in the two arms. Time to liberation will be the primary outcome; ventilator-free days and other outcomes will be measured. Discussion Meta-analyses comparing PAV+ to PSV suggest PAV+ may benefit patients and decrease healthcare costs but no powered study to date has targeted the difficult to wean patient population most likely to benefit from the intervention, or used consistent timing for the implementation of PAV+. Our enrolment strategy, primary outcome measure, and liberation approaches may be useful for studying mechanical ventilation and weaning and can offer important results for patients. Trial registration ClinicalTrials.gov NCT02447692 . Prospectively registered on May 19, 2015.

Primary mitochondrial diseases result from mutations in nuclear DNA (nDNA) or mitochondrial DNA (mtDNA) genes, encoding proteins crucial for mitochondrial structure or function. Given that few disease-specific therapies are available for mitochondrial diseases, novel treatments to reverse mitochondrial dysfunction are necessary. In this work, we explored new therapeutic options in mitochondrial diseases using fibroblasts and induced neurons derived from patients with mutations in the GFM1 gene. This gene encodes the essential mitochondrial translation elongation factor G1 involved in mitochondrial protein synthesis. Due to the severe mitochondrial defect, mutant GFM1 fibroblasts cannot survive in galactose medium, making them an ideal screening model to test the effectiveness of pharmacological compounds. We found that the combination of polydatin and nicotinamide enabled the survival of mutant GFM1 fibroblasts in stress medium. We also demonstrated that polydatin and nicotinamide upregulated the mitochondrial Unfolded Protein Response (mtUPR), especially the SIRT3 pathway. Activation of mtUPR partially restored mitochondrial protein synthesis and expression, as well as improved cellular bioenergetics. Furthermore, we confirmed the positive effect of the treatment in GFM1 mutant induced neurons obtained by direct reprogramming from patient fibroblasts. Overall, we provide compelling evidence that mtUPR activation is a promising therapeutic strategy for GFM1 mutations.

Los fenotipos de obesidad se presentan en individuos con igual índice de masa corporal que tienen diferentes perfiles metabólicos y pronósticos de salud. Su presencia desde etapas tempranas de la vida hace que incremente la probabilidad de que una mujer arribe al embarazo con estas características, por lo que es necesario promover un posicionamiento conceptual para su identificación. En gestantes normopeso, se sugiere identificar el fenotipo normopeso obeso cuando presenta valor igual o superior al 30 % de la grasa corporal o al 90 percentil de la suma de pliegues cutáneos tricipital y subescapular. De ellas, las que tengan valores iguales o superiores al 75 percentil del índice de adiposidad visceral y del producto de acumulación de los lípidos, se consideran normopeso metabólicamente obesas. En las obesas se propone el uso de los criterios que definen al síndrome metabólico en mujeres, con valores ajustados para gestantes, para identificar la salud metabólica. Los argumentos expuestos demuestran lo idóneo de estratificar el riesgo metabólico al inicio de la gestación al clasificarlas en fenotipos de obesidad, mediante indicadores antropométricos, bioquímicos y clínicos que identifican al síndrome metabólico.

Contexto: la diabetes mellitus tipo 2 (DM2) es una enfermedad prevalente que puede comprometer cualquier órgano. La enfermedad renal diabética (ERD) es una de las complicaciones de la DM2. Objetivo: conocer las características sociodemográficas, clínicas, de laboratorio clínico y biomarcadores interleucina (IL)-17 e IL-33 en plasma y orina de nuestra población con DM2 y ERD, y encontrar si hay diferencias al comparar con pacientes sin ERD y sin DM2. Metodología: en este estudio de corte transversal los datos se obtuvieron de las historias clínicas. Se midieron las IL-17 e IL-33 en plasma y orina mediante kits comerciales de ensayo de inmunoabsorción ligado a enzimas. Resultados: se incluyeron 62 pacientes con DM2, 23 pacientes con ERD, 39 pacientes sin ERD y 29 pacientes sin DM2. Aquellos con DM2 tienen mayores niveles en orina de IL-17 comparado con los que no tienen DM2 (p

IntroductionLoneliness is a distressful feeling that can affect mental and physical health, particularly among older adults. Cortisol, the primary hormone of the Hypothalamic-Pituitary-Adrenal axis (HPA-axis), may act as a biological transducer through which loneliness affects health. While most previous studies have evaluated the association between loneliness, as a unidimensional construct, and diurnal cortisol pattern, no research has examined this relationship discriminating between social and emotional loneliness in older adults. As sex differences in the negative mental health outcomes of loneliness have been reported, we also investigated whether diurnal cortisol indices and loneliness associations occur in a sex-specific manner.MethodsWe analyzed the diurnal cortisol- pattern in 142 community-dwelling, non-depressed, Caucasian older adults (55,6% female) aged 60-90. Social and emotional (family and romantic) loneliness scores were assessed using the Spanish version of the Social and Emotional Loneliness Scale for Adults (SELSA). Five salivary cortisol samples were used to capture key features of the diurnal cortisol pattern, including: awakening and bedtime cortisol levels, awakening response (CAR), post-awakening cortisol output (post-awakening cortisol [i.e., the area under the curve with reference to the ground: AUCG]), total diurnal cortisol release (AUCG), and diurnal cortisol slope (DCS).ResultsAfter controlling for sociodemographic variables, the hierarchical linear multiple regression analyses revealed that in male older adults, higher scores on social and family loneliness were associated with elevated awakening cortisol levels, total diurnal cortisol output, and a steeper diurnal cortisol slope (DCS). However, these associations were not observed in female older adults. In addition, feelings of romantic loneliness were positively associated with bedtime cortisol levels and AUCG in older males. Multilevel growth curve modeling showed that experiencing more social and emotional loneliness predicted higher diurnal cortisol output throughout the day in older male adults.DiscussionThe presence of sex differences in the relationship between cortisol indices and loneliness among older adults holds particular significance for diagnostic and screening procedures. Combining loneliness scales as screening tools with diurnal cortisol measures has the potential to be an effective and cost-efficient approach in identifying higher-risk individuals at early stages.

Abstract Background Artisanal and small-scale gold mining activities are producing contamination with heavy metals and metalloids (HMM) into soils and water worldwide. The HMM are considered as one of the major abiotic stresses due to their long-term persistence in soil. In this context, arbuscular mycorrhizal fungi (AMF) confer resistance to a variety of abiotic plant stressors including HMM. However, little is known regarding the diversity and composition of AMF communities in heavy metal polluted sites in Ecuador. Methods In order to investigate the AMF diversity, root samples and associated soil of six plant species were collected from two sites polluted by heavy metals, located in Zamora-Chinchipe province, Ecuador. The AMF 18S nrDNA genetic region was analyzed and sequenced, and fungal OTUs were defined based on 99% sequence similarity. Results were contrasted with AMF communities from a natural forest and from reforestation sites located in the same province and with available sequences in GenBank. Results The main pollutants in soils were Pb, Zn, Hg, Cd and Cu with concentrations exceeding the soil reference value for agricultural use. Molecular phylogeny and OTU delimitation showed 19 OTUs, the family Glomeraceae was the most OTU-rich followed by Archaeosporaceae, Acaulosporaceae, Ambisporaceae and Paraglomeraceae. Most of the OTUs (11 of 19) have been found at other locations worldwide, 14 OTUs were proven from nearby non-contaminated sites in Zamora-Chinchipe. Conclusion Our study showed that there are no specialized OTUs at the studied HMM polluted sites, but rather generalists adapted to a wide variety of habitats. Their potential role in phytoremediation approaches remains to be investigated.

Abstract Aim The aim of this study was to determine the prevalence of feelings of being a second victim among midwives and obstetricians in Spain and to explore possible differences between the two professions. Design Cross‐sectional descriptive‐analytical observational study. Methods An online survey collecting several variables was administered throughout the Spanish territory. Spanish version of the Second Victim Experience and Support Tool (SVEST) was used. The data collection period was from May to December 2020. Results A total sample of 719 obstetricians and midwives were studied. There were significant differences between the two groups with respect to seven dimensions of SVEST: greater feelings of being a second victim among obstetricians in the dimensions physical distress/p ≤ .001, non‐work‐related support/p ≤ .001 and absenteeism/p ≤ .001 and greater feelings of being a second victim among midwives in the dimensions psychological distress/p ≤ .001, supervisor support/p = .011, professional self‐efficacy/p ≤ .001 and intention to change jobs/p ≤ .001.

Introducción. El ataque cerebrovascular (ACV) es una entidad nosológica, que además de producir diferentes déficits funcionales y estructurales, origina diversos tipos de limitaciones funcionales y restricción en la participación social. Objetivo. Describir las características clínicas, los aspectos sociales, laborales y la percepción funcional individual en pacientes con ACV, atendidos en una institución neurológica de Colombia. Materiales y Métodos. Estudio descriptivo en 81 pacientes, con tiempo de egreso hospitalario entre seis meses y dos años. Retrospectivamente se recolectaron datos de historia clínica, referente a signos y síntomas, y territorio vascular comprometido. Posteriormente se aplicó una encuesta de 19 preguntas abiertas sobre percepción, evolución y estado actual de discapacidad secundaria al evento. Resultados. Se evaluaron 71,6% pacientes con ACV isquémico, 19.8% hemorrágico y 8,6% lacunar. El territorio más afectado fue cerebral media (58%). Los síntomas más frecuentes al ingreso fueron disartria y trastorno motor en extremidades. El 65,3% refirió mejoría subjetiva de la deficiencia motora. El 64,3% de los pacientes eran laboralmente activos antes del ACV, solo 10,7% continúan en su oficio previo. Conclusión. El tipo isquémico es la principal causa de ataque cerebrovascular agudo en esta institución. Las manifestaciones clínicas dadas por lateraciones motoras y del habla están acordes al teritorio vascular afectado. A pesar de la autopercepción de mejoría existe un impacto considerable en el ámbito laboral de esta población.

La epilepsia es un trastorno neurológico crónico que afecta cerca de 45 millones de personas y responde por el 1% de la carga global de enfermedad. Entre 20 y 40% de todos los casos son epilepsia fármaco resistente, cuya opción de manejo es generalmente quirúrgica. La ocurrencia de déficit neurológico secundario a cirugía por epilepsia fármaco resistente es menor al 6%. Puede presentarse un déficit motor en cirugía de epilepsia fármaco resistente por fenómenos vasculares en el posoperatorio, a pesar de preservar la corteza motora; o secundario a resección de la zona epileptogénica, cuando está ubicada sobre el área M1-S1 o en la corteza de asociación motora. Se presentan dos pacientes con cirugía para epilepsia fármaco resistente, la evaluación, el seguimiento y la rehabilitación controlada de la función motora voluntaria, por neurorehabilitación.

INTRODUCCIÓN: la epilepsia es una entidad común en el mundo. El 80% se controla con medicación, pero el 20 a 40% de los casos, corresponde a epilepsia fármaco resistente. El 40% de estos casos, tienen origen en el lóbulo temporal y 20% en el lóbulo frontal. La etiología más frecuente en lóbulo temporal, de epilepsia fármaco resistente, es la esclerosis mesial temporal y la cirugía es una alternativa de tratamiento. OBJETIVO: describir las características clínicas y cambios en las pruebas neuropsicológicas previas y posteriores a la intervención quirúrgica de epilepsia fármaco resistente. MATERIALES y MÉTODOS: estudio de tipo descriptivo en una serie de 38 pacientes con dos evaluaciones neu-ropsicológicas y clínicas (previas y posteriores), a la intervención quirúrgica. RESULTADOS: el 73.7% (28/38) tuvo diagnóstico de esclerosis mesial temporal definida y 13.2% signos de esclerosis mesial temporal, ambos por reporte de resonancia magnética. La zona epileptogénica más común fue temporal (97.3%), ubicándose en el 37.8% al lado derecho, 32.4% bitemporal y 29.7% al lado izquierdo. Se observó un mantenimiento de la función cognitiva antes y después de la intervención quirúrgica. CONCLUSIÓN: la cirugía de epilepsia fármaco resistente constituye en sí una técnica de neuro rehabilitación, que reseca puntualmente el déficit estructural o funcional cerebral y otorga una respuesta eficaz a síndromes epilépticos remediables, en la cual la preservación de las funciones cognitivas deben ser meta y resultado.

Se revisó desde una perspectiva biológica y clínica el compromiso del olfato por déficit neurológico pos traumatismo encéfalo craneano (TEC), para concientizar a la comunidad científica sobre la importancia de la relación de este déficit y su impacto en la vida diaria. Se hizo una revisión narrativa de tema sobre las bases biológicas, fisiológicas y clínicas, y el impacto en la vida diaria del olfato. Se revisó la literatura sobre el estado del arte actual. El sistema olfativo es una parte esencial de la fisiología humana y juega un papel crítico en la salud y el comportamiento, por ello su alteración conlleva a la afectación en la calidad de vida de los pacientes, que implica consecuencias físicas y/o psicológicas. Las opciones de rehabilitación del olfato son escazas o nulas, y existe poca literatura a nivel clínico, derivado del subdiagnóstico; además, la complejidad biológica para la evaluación, diagnóstico y rehabilitación del olfato posterior a lesión neurológica y/o otorrinolaringológica dificulta las estrategias de manejo. Los procesos de rehabilitación neurológica del olfato son un tema de potencial desarrollo que requiere del trabajo conjunto entre las neurociencias básicas y clínicas.

There is currently no consensus or homogeneous recommendation about the role of the laparoscopic approach in emergent inguinal hernia surgery. The aim of this manuscript is showing our experience and results of laparoscopic approach for emergent groin hernia repair comparing with open approach. A retrospective review of a prospectively maintained database between January 2011 and December 2021 of acute incarcerated groin hernia that were operated at Virgen del Rocio University Hospital. In this period, they were identified 463 patients with groin hernia that required an emergency repair. 454 patients underwent open surgery (group 1) and 36 patients underwent laparoscopic approach (TAPP procedure) (group 2). Median length stay was 1 day in lap group and 2 days in open approach. Reintervention was necessary in 20 cases (4.40%) from group 1 and one (2.27%) from group 2. In laparoscopic approach, no mortality was described but in open approach, 10 patients (2.20%) died. Globally, 58 cases (12.77%) from group 1 and six patients (16.66%) from group 2 presented any complication. Wound infection was higher in group of open repairs (5.94% vs. 2.77%). Non-surgical complications were higher in open approach (19 vs. 0). There is no statistical significance in any of these items. Laparoscopic approach is a safe, feasible and effective therapeutic option for the treatment of incarcerated groin hernia that require emergency surgery, but prospective and randomized comparative studies are needed to establish the best approach.

One of the strategies to combat micronutrient malnutrition is by developing biofortified common bean lines (Phaseolus vulgaris L.) capable of tolerating different stress conditions. In this study, the adaptive responses of different biofortified bean lines grown under combined stress of acidic soil and high-temperatures were evaluated in the Colombian Amazon. A total of 247 common bean lines from the Mesoamerican gene pool were used to determine the adaptive response in terms of phenological, physiological, and agronomic behavior under combined stress conditions. The lines tested were obtained from different single crosses, double crosses, and backcrosses between different bean materials, of which 146 were obtained from F4 families with high iron (Fe) content in seed and 99 common bean lines from F5 families. Different bean lines had grain yields (GY) higher than 1400 kg ha−1 from the F5 (lines: 859, 805, 865, and 657) and F4 (lines: 2853 and 2796) families. The superior performance of these lines was related to a higher photosynthate partitioning that has allowed an increase in pod formation (pod partitioning index, PPI) from the canopy biomass (CB) and grain filling (pod harvest index, PHI; harvest index, HI), resulting in higher values of GY. Values of GY were correlated with CB (r = 0.36), PPI (r = 0.6), PHI (r = 0.68), and HI (r = 0.8, p < 0.001). This increase in agronomic performance is due to a greater allocation of energy to the photosynthetic machinery (ΦII) and its dissipation in the form of heat (ΦNPQ), with increases in the leaf temperature difference (LTD). Based on the results obtained, six biofortified lines of common bean (lines F5: 859, 805, 865, and 657; lines F4: 2853 and 2796) showed traits of tolerance to combined stress and can serve as progenitors to increase Fe and Zn concentration in the seeds of lines that tolerate the combined stress from acidic soil and high temperature in the Colombian Amazon region.

Abstract Background Neurodegeneration with brain iron accumulation (NBIA) is a group of rare neurogenetic disorders frequently associated with iron accumulation in the basal nuclei of the brain characterized by progressive spasticity, dystonia, muscle rigidity, neuropsychiatric symptoms, and retinal degeneration or optic nerve atrophy. Pantothenate kinase-associated neurodegeneration (PKAN) is one of the most widespread NBIA subtypes. It is caused by mutations in the gene of pantothenate kinase 2 (PANK2) that result in dysfunction in PANK2 enzyme activity, with consequent deficiency of coenzyme A (CoA) biosynthesis, as well as low levels of essential metabolic intermediates such as 4′-phosphopantetheine, a necessary cofactor for essential cytosolic and mitochondrial proteins. Methods In this manuscript, we examined the therapeutic effectiveness of pantothenate, panthetine, antioxidants (vitamin E and omega 3) and mitochondrial function boosting supplements (L-carnitine and thiamine) in mutant PANK2 cells with residual expression levels. Results Commercial supplements, pantothenate, pantethine, vitamin E, omega 3, carnitine and thiamine were able to eliminate iron accumulation, increase PANK2, mtACP, and NFS1 expression levels and improve pathological alterations in mutant cells with residual PANK2 expression levels. Conclusion Our results suggest that several commercial compounds are indeed able to significantly correct the mutant phenotype in cellular models of PKAN. These compounds alone or in combinations are of common use in clinical practice and may be useful for the treatment of PKAN patients with residual enzyme expression levels.

This work presents the modelling, design, construction, and control of an exoskeleton for ankle joint flexion/extension rehabilitation. The dynamic model of the ankle flexion/extension is obtained through Euler-Lagrange formulation and is built in Simulink of MATLAB using the non-linear differential equation derived from the dynamic analysis. An angular displacement feedback PID controller, representing the human neuromusculoskeletal control, is implemented in the dynamic model to estimate the joint torque required during ankle movements. Simulations are carried out in the model for the ankle flexion/extension range of motion (ROM), and the results are used to select the most suitable actuators for the exoskeleton. The ankle rehabilitation exoskeleton is designed in SolidWorks CAD software, built through 3D printing in polylactic acid (PLA), powered by two on-board servomotors that deliver together a maximum continuous torque of 22 [kg cm], and controlled by an Arduino board that establishes Bluetooth communication with a mobile app developed in MIT App Inventor for programming the parameters of the rehabilitation therapies. The result of this work is a lightweight ankle exoskeleton, with a total mass of 0.85 [kg] including actuators (servomotors) and electronics (microcontroller and batteries), which can be used in telerehabilitation practices guaranteeing angular displacement tracking errors under 10%.

Abstract Background Mitochondrial diseases represent one of the most common groups of genetic diseases. With a prevalence greater than 1 in 5000 adults, such diseases still lack effective treatment. Current therapies are purely palliative and, in most cases, insufficient. Novel approaches to compensate and, if possible, revert mitochondrial dysfunction must be developed. Results In this study, we tackled the issue using as a model fibroblasts from a patient bearing a mutation in the GFM1 gene, which is involved in mitochondrial protein synthesis. Mutant GFM1 fibroblasts could not survive in galactose restrictive medium for more than 3 days, making them the perfect screening platform to test several compounds. Tetracycline enabled mutant GFM1 fibroblasts survival under nutritional stress. Here we demonstrate that tetracycline upregulates the mitochondrial Unfolded Protein Response (UPRmt), a compensatory pathway regulating mitochondrial proteostasis. We additionally report that activation of UPRmt improves mutant GFM1 cellular bioenergetics and partially restores mitochondrial protein expression. Conclusions Overall, we provide compelling evidence to propose the activation of intrinsic cellular compensatory mechanisms as promising therapeutic strategy for mitochondrial diseases.